2004 Abstracts - American Association of Clinical Endocrinologists

Transcription

Endocrine
Practice
Volume 10 (Suppl 1), March/April 2004
Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
www.aace.com
ABSTRACTS
for the
AMERICAN ASSOCIATION OF
CLINICAL ENDOCRINOLOGISTS
13TH ANNUAL MEETING
& CLINICAL CONGRESS
APRIL 28 – MAY 2, 2004
Boston, Massachusetts
Endocrine Practice
(ISSN 1530-891X)
1000 Riverside Avenue
Suite 205
Jacksonville, Florida 32204
ABSTRACTS
Note: Included are only abstract numbers that were accepted for Poster Presentations at the 2004 AACE Annual Meeting
Abstract #4
Abstract #5
Diabetes Mellitus and Impaired Glucose Tolerance
Prevalence in Population of the Republic of Uzbekistan
Gestational Diabetes Mellitus Presenting With
Unprovoked Diabetic Ketoacidosis
B.A. Sultanov, MD, F.A. Khaidarova, and S.I. Ismailov
Hylton V. Joffe, MD, and
Karen C. McCowen, MD, MRCPI
Introduction: Diabetes mellitus (DM) is one of
the most common chronic diseases, frequently resulting
in severe complications, invalidism and early mortality.
Worldwide, about 100 million people have diabetes, a
number expected to increase to 215 million by 2010.
An epidemiologic study in the Republic of Uzbekistan
was begun in 1978 as part of the “Diabetes Mellitus
Epidemiology in the USSR” program. Dr. T.K. Ibragimov
conducted the study, finishing it in 1992.
Objective: In view of the above, work was initiated
to study DM and IGT prevalence in various climaticgeographical zones of the Republic.
Methods: To diagnose DM and IGT, the methods
recommended by the WHO (1999) were used. Random
sampling was used for selection of units for follow-up. The
selective totality of the representative group of patients for
this epidemiological study was calculated according to a
formula offered by R.M. Biryukova.
Results: We examined 2927 persons in three regions
(response 97.5%), 1,073 males and 1,854 females among
them. DM and IGT prevalence in population of the Republic
of Uzbekistan Age groups Tashkent Karshi Nukus
30-40 years
41-50 years
51-60 years
61-69 years
Total
DM
IGT
DM I
GT
DM
IGT
0%
0.2%
1.2%
2%
1.2%
1.6%
2.1%
2.5%
0.97%
0.8%
1%
0.2%
0.7%
0.9%
1%
0.5%
0.9%
0.9%
0.8%
0.4%
1.1%
1.1%
1.6%
0.2%
3.4%
7.4%
2.7%
1.9%
3%
4%
Conclusion: DM and IGT prevalence in the examined
population in the Republic of Uzbekistan are 3.3% (n=98)
and 5.6% (n=164), respectively. The highest rate of DM
and IGT prevalence (2% and 2.5%, respectively) was
observed among female residents of Tashkent of age group
of 61-69 years.
© 2004 AACE
Objective: To describe a rare form of gestational
diabetes mellitus (GDM) characterized by abrupt,
unprovoked diabetic ketoacidosis (DKA).
Methods: Case report with literature review.
Results: A 31-year-old pregnant, overweight (pregravid body mass index 27 kg/m2) African-American
woman with sickle cell trait and acanthosis nigricans but no
known history of diabetes mellitus presented at 23 weeks
gestation with a 1-week history of polyuria and polydipsia.
Routine urinalysis 13 days prior showed no glycosuria
or ketonuria. Her father and several uncles have type 2
diabetes mellitus. In the emergency department, plasma
glucose was 643 mg/dL, sodium 125 mmol/L, potassium
4.5 mmol/L, creatinine 1.4 mg/dL, CO2 13 mmol/L, anion
gap 21 mmol/L, arterial pH 7.36, and HbA1c 8.5%. There
was no evidence of infection. She was diagnosed with
DKA, treated acutely with intravenous fluids and insulin,
then transitioned to twice daily NPH and pre-meal lispro
insulins, which maintained tight glycemic control (total
daily insulin dose ~60 units). At delivery, islet cell and
glutamic acid decarboxylase (GAD) antibodies were
negative and HbA1c level was 5.9%. All postpartum
finger stick glucose recordings were <120 mg/dL without
insulin. Eight weeks later, her fasting and 2-hour blood
glucose measurements during an oral glucose tolerance
test were 89 mg/dL and 67 mg/dL, respectively. She
remains normoglycemic 8 months postpartum. Reports in
the literature of DKA during pregnancy usually represent
new-onset type 1 diabetes mellitus or GDM complicated
by severe infection or glucocorticoid treatment for preterm
labor.
Conclusion: Since pregnancy is a state of accelerated
ketosis, DKA may be more easily precipitated by
intercurrent illness than in non-pregnant states. However,
clear documentation of unprovoked DKA in cases of true
GDM is extremely rare.
ENDOCRINE PRACTICE Vol 10 (Suppl 1) March/April 2004 1
2 Abstracts, Endocr Pract. 2004;10(Suppl 1)
Abstract #7
Evaluation of Serum Lipid Levels and Their
Correlation with HbA1c as a Metabolic Control Index
in Children and Adolescents with Type 1 Diabetes
Nosrat Ghaemi, MD, Ali Heidari, MD, and
Rahim Vakili, MD
Background: Type 1 diabetes mellitus is the most
common endocrine disorder of childhood. It is associated
with various physiological consequences, of which
cardiovascular diseases are the most significant cause of
morbidity, due largely to atherosclerosis and dyslipidemia,
which play important roles as risk factors.
Objective: This study explores the need for early
dyslipidemia screening of patients with type 1 diabetes.
Methods: In a descriptive, cross-sectional study,
we determined lipoprotein and HbA1c levels in a sample
of randomly selected patients with type 1 diabetes who
were referred to a center of diabetes research. Data were
statistically analyzed by SPSS.
Results: 51 patients (30 boys, 21 girls) with a mean
age of 13.47 +/- 3.6 years, an age range of 5 to 19 years,
and a disease duration of 3.9 +/-3, were evaluated. Mean
levels of TG, TC, LDL, HDL and HbA1c were 97+/-55.4,
180.8+/-44.1, 113.3+/-32.6, 48.4+/-10.8 mg/dL and 8.1+/1.8%, respectively. In the group under poor glycemic
control (HbA1c >9), mean levels of TG, TC, LDL, HDL
were 123.6+/-75.8, 199.4+/-61.8, 129.2+/-44.7 and 50.9+/9.6; in the second group (HbA1c <9), mean levels were
85.9+/-40.6, 173.0+/-32.3, 106.6 +/-23.7 and 47.3+/-11.2
mg/dL, respectively.
Conclusion: Mean lipid values of these patients
compared to those blood lipid treatment goals (TG<150,
TC<170, LDL<100, HDL>40) confirmed that only TC and
LDL were higher than optimal levels. The group under poor
glycemic control had significantly higher TG (P = 0.02),
TC (P = 0.05) and LDL levels (P = 0.02) compared with
subjects under better control. Findings were comparable
between groups, however, in the case of HDL. We suggest
screening of patients with type 1 diabetes for dyslipidemia
as soon as possible regardless of diabetic disease duration.
Abstract #8
Administration of Recombinant Human TSH
(Thyrogen) as a Coadjuvant in Treatment of Papillary
Thyroid Carcinoma: A Case Report
Sigfirdo Miracle-Lopez, MD, and Marco A. Segovia
Objective: To report a case of papillary thyroid
carcinoma in which recombinant human TSH (thyrogen)
was used as a coadjuvant to treatment.
Summary: Four years prior to her clinical
presentation a 67- year-old woman noted the presence
of a solid, rounded, hard, fixed mass in the right lateral
side of her neck. This mass was 0.5 cm in diameter upon
her initial clinical presentation, but grew over time to 3
cm in diameter. Upon physical examination, her thyroid
was nontender to palpation, and a rounded mass of 0.5
cm in diameter was noted on the right lobe. Ultrasound
of the neck identified a calcified lymph node on the right
lateral side of her neck. A thyroid scan detected a defect
in radioiodine uptake of 1.2 cm in the right thyroid lobule.
Fine needle aspiration biopsy (FNAB) was performed on
the lateral mass, with histopathologic findings of papillary
carcinoma. The patient was admitted to the hospital for
surgical exploration of her neck, which revealed a lymph
node conglomerate on the right side of her neck with
metastasis to the escaleno muscle and the base of the skull.
The surgical team was unable after 12 hours of surgery to
perform a total thyroidectomy, so only a modified right
hemithyroidectomy was performed. The histopathologic
report confirmed the diagnosis of papillary carcinoma
of the thyroid with regional lymph node metastasis and
metastasis to the escaleno muscle and the base of the skull.
The patient was left without thyroid hormone replacement
therapy pending elevation of her TSH to administer I131.
Thyroid function tests performed 4 weeks later revealed
a TSH of 7.04, so the decision was made to administer
recombinant human TSH (Thyrogen) at a dose of 0.9 mg
subcutaneously on two consecutive days. Serum TSH and
Tg measures were performed with the following results:
06-I-03 09:00 hrs (pre-Thyrogen) TSH 7.40, Tg 135;
06-I-03 14:00 hrs (5 hours post 0.9 mg Thyrogen) TSH
48; 07-I-03 09:00 hrs (24 hours post 0.9 mg Thyrogen)
TSH 98; 07-I-03 14:00 hrs (5 hours post 2 hr dose of 0.9
mg Thyrogen) TSH 116, Tg 235. 200 mCi of I131 were
administered on the 7th of January. The patient presented
with mild inflammation of the salivary glands, mild
nausea and vomiting on one occasion 28 hours after the
administration of the I131. Her free T4 (FT4) never exceeded
the maximum normal levels for the assay (reference values
0.8 to 2.0). She presented with tachycardia of 120 bpm on
two occasions without need of medication and without
hemodynamic repercussion tachycardia (both instances
self-resolved in less than 5 minutes). The patient was
discharged from the hospital on January 10th. On January
13th a whole body scan (WBS) was performed, revealing
a thyroid remnant of approximately 3 by 5 cm in the left
lobule, without any sign of distant metastasis. The patient
was begun on 50 ìg levothyroxine (Eutirox), then tritated
to a dose of 100 ìg to keep TSH values under 0.1. Four
months later, after withdrawing levothyroxine for 3 weeks,
a follow up WBS was performed (with a TSH of 47 and
a Tg of 214), first with Tc99 (May 8th 2003), which was
negative, and afterwards with I131, which showed a remnant
Abstracts, Endocr Pract. 2004;10(Suppl 1) 3
1 cm in diameter on the left thyroid bed. The patient was
readmitted to the hospital to receive 150 mCi of I131 on May
9, 2003 (accumulated dose 350 mCi). Levothyroxine was
restarted 1 week later. On June 7, 2003, new tests were
performed with a resultant TSH of 22 and a Tg of 1.21, so
levothyroxine was increased to 150 ìg per day. The patient
is currently asymptomatic awaiting a new WBS and thyroid
ultrasound.
Conclusion: Administration of recombinant human
TSH (Thyrogen) 48 hours prior to the administration of
I131is a safe and efficacious way to increase TSH values
over 30 in patients in whom total thyroidectomy cannot be
performed.
Successful Outcome after 23 Years of Diabetes
Insipidus with Absence of Thirst: A Case Report
fully alert and actively involved in community activities,
and manages the financial arrangements of several local
volunteer organizations.
Discussion: Long-term survival of patients with
adipsic diabetes insipidus is limited not only by the
underlying pathology but by marked fluctuations in
electrolyte levels that eventually cause severe neurological
problems. A review of the literature and expert opinion
regarding this disorder failed to identify any other patients
who have survived adipsic DI as long as this patient has.
Conclusion: This 46-year-old male with adipsic
diabetes insipidus of 23 years duration has achieved the
longest survival with this condition that has so far been
reported in the literature. An interesting and important
development is that he is now able to carefully maintain
normal or near normal serum sodium levels with little
difficulty due to his ability to detect subtle changes in
personality that indicate his need to change fluid intake.
Jyoti Bhattarai, MD, and Arnold M. Moses, MD
Abstract #10
Objective: To describe a case of adipsic diabetes
insipidus of 23 years duration.
Summary: The 46-year-old male patient was first
hospitalized at age 22, following a motor vehicle accident
in which he sustained multiple skull fractures and was
unconscious. When he regained consciousness, loss of
vision in one eye was reported. He developed polyuria
and was found to have the following laboratory values:
serum sodium162 meq/L, chloride 121meq/L, bicarbonate
34 meq/L, serum osmolality 356 mOsm/kg, and urine
osmolality 120 mOsm/kg. This patient was not thirsty while
hypernatremic. Diabetes insipidus (DI) was diagnosed on
the basis of his elevated serum sodium level associated
with dilute urine. While in the hospital, his adipsic DI
was managed with desmopressin and close monitoring of
fluid intake, urine output, and weight along with vital signs
and frequent serum electrolytes levels. He was sent home
after about 2 months with no apparent cognitive deficits,
but still adipsic. His DI was well managed at home with
close supervision by his mother and extended family. He
followed a consistent regimen of desmopressin nasal spray
and was instructed to drink 200 ml of fluid more than
his urine output in the previous 4 hours. On this closely
monitored regimen, the patient’s serum sodium remained
within or close to normal range for the next 12 years. Both
he and his mother noted that when he fell behind on his
fluid intake and his serum sodium became elevated, his
personality changed so that he became angry and agitated.
In contrast, when his serum sodium fell below normal, he
became sleepy. Recognizing these changes in mood, he
was eventually able to maintain his serum sodium within
or close to normal range with less intensive monitoring of
his fluid intake, output, weight, and vital signs. He remains
Metformin and B12 Deficiency with Myelopathy
Abstract #9
Ronnie Mohammed, MD, and Michael Eufemio, MD
Objective: To present a first report of metformin
associated B12 deficiency with myelopathy.
Methods: The patient’s medical records and pertinent
literature were reviewed.
Results: A 68-year-old male with type 2 diabetes
mellitus of 13 years duration had been treated with
glyburide. Metformin was added, and the dose was
gradually increased up to 2000 mg/day. He remained
on this combination, maintaining good glycemic control
(mean HbA1c 6.2%). Three years later, he was admitted
to hospital after experiencing weakness of his lower
extremities with frequent falls and difficulty walking.
Physical examination revealed a moderate paraparesis,
brisk reflexes, bilateral ankle clonus, and a left Babinski
sign. MRI of the spine revealed atrophy of the cervical and
thoracic cord. Laboratory data were as follows: B12 88
pg/mL [179-1132], folate 8.8 ng/mL [3.1-12.4], WBC 4.3
k/ul [4.8-10], Hg 15.2 g/dL [14-16.5], MCV 99 fl [80-94],
platelets 200 k/µL [150-350}and TSH 1.55 µIU/mL. Parietal
cell and intrinsic factor blocking antibodies assays revealed
negative results. Intramuscular injections of B12 were
started and continued on a monthly basis. He subsequently
exhibited significant improvement in his neurological
symptoms. After 4 months, he regained normal strength
in his lower extremities and clonus disappeared, but he
remained mildly unsteady with a persistent left Babinski
sign. Despite regular injections over a 30-month period
his B12 level rose to a mean of only 374 ng/L [200-1100].
His metformin dose of 2000 mg/day remained unchanged
during this period. He subsequently developed a stroke and
required a period of rehabilitation during which he lost
weight. His oral hypoglycemic agents were discontinued,
as he maintained adequate glycemic control on diet alone.
His B12 levels then steadily increased, peaking at 1882
ng/L with an eventual plateau at approximately 950 ng/L.
Currently, his B12 levels remain at this level 12 months
after B12 injections were discontinued.
Conclusion: This report provides evidence for a
causal relationship between metformin and B12 deficiency.
Metformin is known to lower B12 levels in 10-30% of
patients by inhibiting absorption. In the case of this patient,
metformin may be also enhancing metabolism of B12, as
serum levels failed to rise significantly despite parenteral
therapy. The potential for serious neurological sequelae
may provide impetus to recommend screening patients
on metformin for B12 deficiency, especially if other risk
factors for this deficiency are present (e.g., history of
gastrointestinal surgery or vegetarian diet).
Abstract #12
Chordoma: a Rare Cause of a Sellar Mass
Masquerading as a Pituitary Adenoma with Invasion
of the Sphenoid and Nasal Cavities
Irma L. Antonio, MD, and
Laura Acampado, MD, FPCP, FPSEM
Objective: To report a case of chordoma as a rare
cause of a sellar mass resembling a pituitary adenoma with
invasion of the sphenoid and nasal cavities.
Summary: A 49-year-old woman was admitted for
severe headache of 10 years duration. She developed
bilateral visual loss, diplopia, and numbness of the
face. Later, she reported bilateral nasal obstruction,
anosmia, rhinorrhea, and facial pain. There were no
symptoms suggestive of a hyperfunctioning tumor. Neuroophthalmologic examination revealed sensory deficit of
cranial nerve V, papilledema, and no light perception in
both eyes. Hormonal evaluation was normal except for a
slightly elevated prolactin level. Computed tomographic
scan of the head revealed a large sellar-suprasellar mass
with bony destruction, calcification, and extension to
the sphenoid sinus. Soft tissue masses were noted on
the posterior area of the nasal septum. Intranasal biopsy
revealed the presence of pituitary adenoma, and the
patient underwent transphenoidal excision of the tumor.
Final histopathologic evaluation revealed the presence of
chordoma. Postoperatively, the patient’s nasal obstruction
improved, but she remained blind. She declined radiation
therapy. Invasive chordoma involving the sellar region is
rare. It can mimic clinical features of the more commonly
encountered pituitary adenoma. For this reason, this tumor
is easily misdiagnosed, so timely identification requires a
high index of suspicion. Presence of cranial neuropathy,
visual field loss, and nasal obstruction should direct
clinicians to consider nonpituitary causes of sellar mass.
Abstract #13
Hospital Malnutrition: An Assessment of the Nutritional
Status, Adequacy of Nutrient Delivery Among Intubated
Patients, and Nutritional Support Practices of
Physicians in the Philippine General Hospital
Irma L. Antonio, MD, Elizabeth Limos, RND, Gabriel
Jasul, MD, Gerardine Fernandez, MD, and
Laura Acampado, MD
Objective: This investigation explored the
following questions: (1) what is the nutritional status of
intubated patients on admission and on discharge? (2) what
are the reasons physicians report for discontinuing patient
feedings, leading to inadequate nutrient intake? (3) Does
inadequate nutrition leads to increased risk of mortality?
Methods: In this cross-sectional, prospective
cohort study, anthropometric measurements, albumin,
and total lymphocyte count were measured upon hospital
admission and discharge in 190 intubated patients in
medical wards and the intensive care unit. Descriptive
statistics, paired t-tests, and estimation of relative risk were
calculated.
Results: A majority of patients had triceps skinfold
thickness <25th percentile, midupper arm circumference
of <80th percentile, arm muscle area of <5th percentile
(revealing muscle wasting), moderate hypoalbuminemia,
and normal total lymphocyte counts. Common physician
reasons for discontinuing feeding were concerns about
airway management, extubation/weaning, and diagnostic
procedures. Comparison of patient anthropometric values
and albumin levels upon admission and discharge demonstrated significant deterioration in these values during hospitalization. Among patients with inadequate caloric intake,
the risk of mortality is 8.9 times (95% confidence interval
3.44,23) that of patients with adequate caloric intake.
Abstract #14
Increased Incidence of Insulin Resistance in Men with
Erectile Dysfunction Causes Increased Cardiac Risk
Tina Bansal, MD, Andre Guay, MD,
Bartholomew Woods, MD, Jerilynn Jacobson, MA, and
Richard Nesto, MD
Objective: To study the incidence of insulin resistance
(IR) in men with erectile dysfunction (ED) as our prior
studies show that 90% of men with ED have increased
cardiovascular risk.
Methods: The severity of ED in the 154 men was
evaluated by the Sex Health Inventory for Men (SHIM).
IR was calculated using the Quantitative Insulin Sensitivity
Check Index (QUICKI), which has a higher correlation
than HOMA with euglycemic clamp studies.
Results: IR occurred in 79.2% of our ED population
(n = 154), versus 25% in the general population, and in
73.3% of our non-T2DM group (n = 120). IR and FBS
correlated with increasing severity of ED (P = 0.01 in both
cases).
Conclusion: The incidence of IR among patients with
ED is three times higher than that occurring in the general
population. ED should, therefore, should be considered a
possible risk factor for cardiovascular disease.
Abstract #15
The Combination of Testosterone-Gel 1% (Androgel)
and Sildenafil for Treatment of Erectile Dysfunction:
Safety Assessment in Hypogonadal Non-Responders to
Sildenafil Monotherapy
Zurab Bebia, MD, PhD, MS, Barbara A. Block, BA,
Cindy Lane, BS, John J. Brennan, PhD, Lisa M. Zipfel, MS,
and Sherwin L. Schwartz, MD
Background: The erectile pathway is testosterone
dependent, and hypogonadism decreases a response to
phosphodiesterase-5 inhibitors. Androgen replacement has
been reported as effective concomitant therapy to sildenafil
in hypogonadal men with erectile dysfunction (ED) who do
not benefit from sildenafil alone.
Objective: To evaluate safety of testosterone gel 1%
(AndroGel, Solvay Pharmaceuticals Inc.) in combination
with sildenafil (Viagra, Pfizer) in treatment of ED in
hypogonadal men who do not benefit from sildenafil
alone.
Methods: We present data from a randomized,
placebo-controlled, double-blind, parallel-group, multicenter study in 75 hypogonadal men (age range 8-80 years)
treated for ED with confirmed lack of response to sildenafil
alone.
Results: During the 12-week treatment phase, 16
subjects (41%) in the AndroGel group and 11 subjects
(31%) in the placebo group experienced adverse events.
Treatment-emergent adverse events reported by more than
one subject included angina pectoris (AndroGel group: 2
subjects, 5%; placebo: no subjects) and vascular disorders
(AndroGel group: 2 subjects, 5%; placebo: 1 subject, 3%).
No clinically meaningful changes or group differences
were reported regarding vital signs, physical examination,
urinanalysis, hematology, or any biochemistry parameter.
Subgroup analysis in hypertensive, hyperlipidemic, and
diabetic subjects revealed no significant deterioration
in clinical or laboratory parameters. Four subjects in
AndroGel group experienced a serious adverse event
(angina pectoris, upper respiratory tract infection, arthritis,
and renal cell carcinoma), none of which was believed
related to the study medication.
Conclusion: These results demonstrate that
combination of AndroGel and sildenafil is safe and
well-tolerated in the treatment of erectile dysfunction in
hypogonadal men.
(This study was supported by Unimed Pharmaceuticals,
Inc. a subsidiary of Solvay Pharmaceuticals, Inc.)
Abstract #16
Resolution of Biochemical Hyperthyroidism in a
Patient with Graves’ Disease and Stiff-Man Syndrome
Treated with Prednisone and Imuran.
Israel Orija, MD, and Robert S. Zimmerman, MD
Objective: Report an unusual presentation and
response to therapy in Graves’ disease.
Methods: A 51-year-old Caucasian female with a history of lumbar spondylosis presented with low backache,
stiffness, muscle spasms, and difficulty walking. She also
had diaphoresis, heat intolerance, palpitations, and dyspnea.
Physical examination revealed emotional lability, tremors,
anxiety, lid lag, hyperreflexia, and the absence of goiter. Her
paraspinal and abdominal muscles were tense, and her gait
was narrow and spastic with a stooped forward motion. TSH
was < 0.005 µU/mL (0.4-5.5), T4 11.1 µg/dL (5-11), FTI
10.7 µg/dL (6-11), T3 170 ng/dL (94-170). Thyroid stimulating immunoglobulin (TSI) was 1986% (70-150%) and
thyroid blocking immunoglobulin (TBI) was 82.5 U/L (<
5). Radioactive iodine uptake was 15.8% at 4 hr (estimated
33% at 24 hr). Pulmonary function testing demonstrated
restrictive physiology. An assay for antiGAD antibodies
revealed positive results. An EMG Identified abnormalities in the voluntary deactivating motor units of paraspinal muscles consistent with stiff-man syndrome (SMS).
Propranolol relieved the patient’s hyperthyroid symptoms.
She required hospitalization for gait difficulties and severe
dyspnea and was treated with clonazepam and intravenous
immunoglobulin (IVIG) with marked improvement in her
muscular symptoms. Two months after hospitalization she
deteriorated, and was treated with a second course of IVIG
to which she had no response. She responded to intravenous
methylprednisolone 1 gm daily for 5 days, prednisone 60 mg
a day, and imuran 150 mg daily for control of her muscular
symptoms. Muscle aches, stiffness, and gait subsequently
improved markedly. The patient is now clinically euthyroid
with a TSH level of 0.54 µU/mL and FTI 5.0 µg/dL.
Conclusion: SMS is associated with autoimmune
disorders. The natural history of the relationship between
Graves’ disease and SMS has not been clearly elucidated.
Graves’ disease is in remission in this patient following
immunosuppressive therapy for SMS.
Abstract #17
Severe Rhabdomyolysis in a Patient with
Diabetic Ketoacidosis
Hylton V. Joffe, MD, and Martin J. Abrahamson, MD
Objective: To describe a case of severe rhabdomyolysis
associated with diabetic ketoacidosis (DKA).
Results: A healthy, thin 26-year-old Cantonese woman
presented with 6 days’ history of nausea, vomiting, and
non-specific abdominal pain that progressed to myalgias,
polyuria, polydipsia, and delirium. She was asleep in bed
for many hours preceding admission. Her only medication
was an oral contraceptive, and she did not use herbal
medications or alcohol. Her father has been diagnosed
with type 2 diabetes mellitus. In the emergency room, the
patient’s urine was tea-colored with 4+ glucose, ketones,
and the presence of blood without erythrocytes apparent
upon urinalysis. Toxicologic analysis of her blood revealed
negative results. Her plasma glucose level was 809 mg/dL,
betahydroxybutyrate 6.9 mmol/L, lactate 3.2 mmol/L,
sodium 126 mmol/L, potassium 4.9 mmol/L, creatinine
2.2 mg/dL, bicarbonate 9 mmol/L, leukocytes 24,800/
ìL, arterial pH 7.06, and creatine phosphokinase (CK)
46,305 IU/L. Testing for Islet cell, insulin, and glutamic
acid decarboxylase (GAD) antibodies revealed negative
results. HbA1c was 6.7%. This patient was diagnosed
with DKA and rhabdomyolysis, and treated aggressively
with intravenous insulin, fluids, and bicarbonate. Within
18 hours, she was alert and oriented, and the observed
metabolic abnormalities had been corrected. She was
then transitioned to glargine with premeal administration
of lispro. CK levels peaked at 51,330 IU/L, but serum
creatinine levels normalized without dialysis. Blood and
urine cultures, and serology for acute cytomegalovirus and
Epstein-Barr virus infections were negative. Case series
suggest that subclinical rhabdomyolysis may occur in as
many as one half of all patients presenting with DKA.
However, severe rhabdomyolysis is very unusual among
patients with DKA and has been associated with high
mortality rates.
Conclusion: DKA seldom presents concomitantly
with severe rhabdomyolysis. With prompt treatment, these
patients do not necessarily have poor outcomes.
Abstract #18
Effect of Hospital-Wide Insulin Protocols on Glycemic
Control and Length of Stay in a Community Hospital
Renu Joshi, MD, and Amy Helmuth
Objective: To assess glycemic control and length of
stay (LOS) prior to and 1 year following implementation
of hospital-wide intravenous and subcutaneous insulin
regimen protocols using preprinted physician order sheets.
Methods: Implementation of customized insulin
protocols based on patient specific variables. Initial data
collection was retrospective, followed by prospective data
collection from computerized systems and random chart
review.
Results: The average LOS was 2.6 days higher
among diabetic versus nondiabetic patients prior to
implementation. One year after implementation, blood
glucose values for all patients decreased from 196 mg/dL to
182 mg/dL (P<0.05). LOS decreased from 4.7 days to 3.9
days among patients with primary diagnoses of diabetes (P
= 0.02), from 6.2 to 5.8 days among patients with secondary
diagnosis of diabetes (P = 0.001), and from 6.9 to 6.0 days
among surgical patients (P = 0.00006). No differences in
LOS for were observed among non-diabetic patients.
Conclusions: Statistically significant improvements
were noted in overall glycemic control and LOS
among hospitalized patients with diabetes 1 year after
implementation of preprinted insulin protocols.
Abstract #19
Dexamethasone-Suppressible Androgens and
Insulin Resistance
E.Russell Weidman, MD, FACE,
Kenneth D. Smith, MD, FACE,
Luis J. Rodriguez-Rigau, MD, FACE, and
Steven M. Petak, MD, JD, FACE
Objective: To study the relationship between
insulin resistance and androgen levels before and after
dexamethasone suppression.
Background: Insulin resistance has been associated
with excess androgen secretion by the ovaries but its effect
on the adrenal glands is less clear.
Methods: Fifty-nine women between the ages of 14
and 48 years who were evaluated for hyperandrogenism
underwent a standard 75 gm, 2-hour glucose tolerance
test with insulin measurements as well as a 2-day low
dose dexamethasone suppression test. Insulin sensitivity
index (ISI) was calculated for each patient and compared
to DHEA-sulfate and testosterone levels measured before
(pre-DS, pre-T) and after (post-DS, post-T) dexamethasone
suppression testing. The difference between the pre- and
post- values was defined as the suppressible fraction (supDS, sup-T).
Results: Significant inverse correlations were found
between the ISI, the pre-T (P<0.025), and the post-T
(P<0.001), but not between the ISI and the sup-T. No
correlation was found between the ISI and any of the DS
measurements.
Conclusion: The presence of dexamethasonesuppressible androgens did not correlate with insulin
resistance. This finding suggests that insulin resistance
primarily affects ovarian androgen production.
Abstract #20
Effects of Exenatide (Synthetic Exendin-4) on Glucose
Control and Safety in Patients with Type 2 Diabetes
Treated with Metformin, a Sulfonylurea, or Both:
An Ongoing, Open-Label Phase 3 Trial
Terri Poon, MD, Kristin Taylor, PhD,
Loretta Nielsen, PhD, Sarah Boies,
Dongliang Zhuang, PhD, Amanda Varns,
Jay Zhou, Dennis Kim, MD, Alain Baron, MD,
Mark Fineman, and Orville Kolterman, MD
Objective: To report preliminary results from an
ongoing open-label phase III trial demonstrating that
exenatide treatment is associated with improved glycemic
control in patients with type 2 diabetes.
Background: Exenatide is an incretin mimetic with
glucoregulatory activity in patients with type 2 diabetes.
Methods: Subjects with type 2 diabetes treated with
metformin (MET), a sulfonylurea (SFU), or both were
enrolled in this open-label phase III trial. Exenatide was
administered subcutaneously, twice daily (BID) before
morning and evening meals, and oral antidiabetic agents
were continued. Exenatide was initiated at 5 µg BID (Wks
0-4), then escalated to 10 µg BID. One hundred-twenty
subjects (53 men, 67 women; 17 MET, 33 SFU, 70 MET/
SFU; mean age 59±9y; mean BMI 31.7±4.8kg/m2 [±SD])
were followed for 24 weeks.
Results: Baseline HbA1c was 8.6±0.1% (±SE). The
dropout rate was <15%, with less than one third of these
subjects withdrawing due to nausea. Subjects showed
progressive reductions in HbA1c, with no apparent waning
of effect over time. The HbA1c change from baseline was
-1.3±0.1% at Wk 24, and 44% achieved HbA1c values
less than or equal to 7%. Antiexenatide antibodies were
observed in some subjects, however there was no apparent
relationship between antibody emergence and glycemic
changes. In general, exenatide was well tolerated. Nausea
was the most frequent adverse event.
Conclusion: Preliminary results from this ongoing
open-label trial support previous observations that
exenatide treatment is associated with improved glycemic
control in patients with type 2 diabetes.
Abstract #21
A Case of Primary Adrenal Insufficiency:
Autoimmune or Chemical Mediated?
Krishna R. Bhaghayath, MD, and
Debra L. Simmons, MD, FACE
Objective: To present a case study and review
the literature regarding etiology of primary adrenal
insufficiency.
Results: A 26-year-old man presented with weight
loss, nausea, vomiting, fatigue, constipation, and
orthostatic dizziness. Cosyntropin stimulation revealed the
following: basal cortisol level 0.2 µ/dL, 30 minutes 0.3µ/
dL, 60 minutes 0.2µ/dL. Antiadrenal antibody evaluation
revealed a ratio of 1:20 (normal <1:10), and an ACTH level
of 638 pg/mL. PPD was negative, and adrenal computer
tomography scan results were unremarkable. Social history
was significant for exposure to a chemical agent resistant
coating (CARC) paint containing multiple chemical agents.
A literature review revealed that autoimmunity is the most
common cause replacing tuberculosis. CARC exposure
is reported to cause pulmonary symptoms but has not
previously been associated with endocrine pathology.
Conclusion: Although a literature review did not
reveal any prior reports of a relationship between adrenal
insufficiency and exposure to CARC, the reported findings
may reflect an important new association.
Abstract #22
Primary Hyperaldosteronism in a Patient with Adrenal
Insufficiency
Francisco Puentes, MD, Carlos Isales, MD, FACE, and
Thomas Jackson, MD
Objective: We report a case of a patient with primary
hyperaldosteronism and concurrent adrenal insufficiency.
Methods: A 73-year-old man with longstanding primary hyperaldosteronism developed adrenal insufficiency
after rupture of an abdominal aortic aneurysm and a prolonged hypotensive episode.
Results: Our patient was evaluated for hypokalemia
and orthostatic hypotension. A cortrosyn stimulation test
demonstrated a blunted cortisol response with suppressed
plasma renin activity and an elevated plasma aldosterone
value. The patient was diagnosed with Addinson`s
syndrome and primary hyperaldosteronism, and treated
with prednisone and spironolactone with subsequent
improvement in his symptoms.
Conclusion: Aldosterone secretion is generally better
conserved than is cortisol secretion in patients with hypoxic
injury, possible related to the fact that the glomerulosa layer
is only a few cells thick. In this case, the patient continued
to demonstrate elevated aldosterone secretion despite
depressed cortisol secretion. Clinicians should maintain a
high index of clinical suspicion and not rule out adrenal
insufficiency in patients presenting with hypokalemia.
Abstract #23
Unusual Presentation of Adrenal Insufficiency
Sabyasachi Sen, MD, MRCP, and George Tully, III, MD
Objective: To describe a case of adrenal insufficiency
in a male patient treated with intravenous fluids
intermittently for 18 years.
Methods: We present clinical and laboratory findings
in this case, and discuss features of chronic primary adrenal
insufficiency.
Results: A 51-year-old gentleman presented clinically
in 1984 with features of gastroenteritis, hyponatremia,
borderline hyperkalemia, tiredness, weight loss, and
dehydration. He was treated on that and several subsequent
similar occasions with intravenous normal saline and 5%
dextrose both in and out of the hospital, with the help of
his wife, a registered nurse. In 1999, he was diagnosed with
autoimmune hypothyroidism and started on L-thyroxine
therapy. In 2002, this patient exhibited weight loss, marked
tiredness, apathy, and a random cortisol level of >0.2mg/
dL, and was referred at that time to our endocrine clinic.
Conclusion: Though this patient did not have all
the features of chronic adrenal insufficiency, clinical and
laboratory findings satisfied most criteria for this diagnosis.
Fortunately, he did not have acute symptomatic episodes
and managed to function well physically for 18 years
without cortisol replacement, though he did demonstrate
some psychological changes. His symptoms improved
significantly after cortisol replacement, when he began to
gain weight, reported improved mood, and resumed his
sporting activities. In cases of chronic adrenal insufficiency
it is important to suspect the abnormality early. Effective
treatment is rewarding for the patient, both physically and
mentally.
Abstract #24
Dual Effect of Ocreotide on Du-145 Prostate
Carcinoma Cell Line: From Growth Proliferation to
Reversal of Chemoresistance
Bulent Karabulut, MD, Nur Selvi, MSc,
Ege Tavmergen Goker, MD, and Erdem Goker, MD
Objective: To explore the effect of ocreotide on the
Du-145 prostate carcinoma (PC) cell line.
Background: The PC cell line is known to be
hormone independent and chemoresistant. Ocreotide is
cytostatic and induces topoisomerase II.
Method: Effects of ocreotide on the PC cell line
were evaluated alone and in the presence of topoisomerase
II inhibitors (VP-16 and doxorubicin). A Western blot
analysis was performed to demonstrate the induction of the
topoisomerase II enzyme.
Results: Ocreotide increases the growth of tumor
cells resistant to VP-16 and doxorubicin. Concomitant
use of ocreotide and chemotherapeutics demonstrated
no advantage over a single agent. Sequential ocreotide
followed by VP-16 or doxorubicin resulted in a prominent
synergy.
Conclusion: These preliminary results are very
encouraging regarding the sequential use of ocreotide
followed by topoisomerase inhibitors. These in vitro results
are warranted to clinical study using sequential ocreotide
and VP-16 or doxorubicin.
Abstract #25
Platelet Dysfunction in Lean Women with Polycystic
Ovary Syndrome and Association with Insulin
Sensitivity
Ege Tavmergen Göker, MD, Cande Y. lmaz, MD,
Didem Dereli, MD, Erol Tavmergen, MD, and
Rafael Levi, MD
Objective: Platelet dysfunctions were evaluated
among women with polycystic ovary syndrome (PCOS)
before and after treatment with metformin.
Background: Increased fibrinogen and plasminogen
activator inhibitor (PAI) levels and platelet dysfunctions
are detected among women with PCOS.
Methods: 20 women with PCOS received metformin
850 mg BID over a period of 6 months. Metabolic
parameters and platelet levels were evaluated at baseline
and after 3 and 6 months of therapy. Resulting data were
compared to those from 20 normal ovulating women.
Results: Women with PCOS demonstrated significantly higher levels of adenosine diphosphate (ADP; 77,4003,3
vs. 67,3002,8), collagen (79,7001,8 vs. 69,1003,9), and
epinephine (84,7002,6 vs. 67,8003,8) induced platelet aggregations. At the end of the 6th month treatment period,
significant reductions in ADP, collagen, and epinephrine
levels were noted among women with PCOS who were
treated with metformin.
Conclusion: Metformin treatment results in significant improvements in platelet dysfunction among women
with PCOS.
Abstract #26
Does an Absent Pituitary Stalk and Hypopituitarism
Always Present in Infancy?
Mariam Daniel, MD, Douglas Rogers, MD,
Charles Faiman, MD, and Amir Hamrahian, MD
Objective: To describe a case of absent pituitary stalk
and hypopituitarism in late childhood.
Methods: A 14-year-old girl was evaluated for
acquired growth hormone (GH) deficiency as part of
multiple pituitary hormone deficiency.
Results: This patient presented clinically with primary amenorrhea and absence of secondary sexual characteristics. Her height was at the 35th percentile for age, and her
weight at the 75th percentile. As an infant she was delivered
by cesarean section for breech presentation and subsequently suffered two skull fractures in infancy. Laboratory
analysis revealed anterior pituitary insufficiency reflected
in abnormalities of GH, FSH, LH, ACTH, and possibly
TSH production. MRI scanning at the time of this evaluation demonstrated an absent infundibulum, hypoplastic
adenohypophysis, and an ectopic neurohypophysis at the
infundibular recess of the third ventricle. Pathogenic theories for this instance of absent infundibula include defective embryonal development, perinatal asphyxia, and stalk
transection during breech delivery. Other midline CNS
defects can be associated with this condition, though our
patient displayed none of these. It is unclear whether cranial trauma contributed to the pituitary anomalies observed
in this patient.
Conclusion: The documented anterior pituitary
insufficiency was likely of late onset given her normal
height. This clinical picture serves as sharp contrast to
the usual presentation of absent pituitary stalk and panhypopituitarism in infancy.
Abstract #27
BMD Increases Over 3 Years Explain Only a Small
Proportion of Vertebral Fracture Risk Reduction
Nelson Watts, MD, FACE, Ian Barton, PhD,
Jonathon Adachi, MD, and Robert Lindsay, MD, PhD
Objective: To determine the contribution of bone
mineral density (BMD) to reduction of risk of new vertebral
fractures on risedronate over a 3-year period.
Background: BMD is widely used as a surrogate
measure of fracture risk. Disagreement exists about
whether treatment-associated increases in BMD accurately
predict decreases in fracture risk of similar magnitude.
Methods: We evaluated patients from the three pivotal
risedronate fracture endpoint trials (VERT-NA, VERT-MN
and HIP) in postmenopausal women with osteoporosis.
Women received risedronate (2.5 mg or 5mg daily) or
placebo daily for up to 3 years. All patients additionally
received calcium 1000 mg/day, and if baseline vitamin D
levels were low, up to 500 IU of vitamin D supplementation
daily.
A method based on the Cox regression model proposed
by Li et al (Statistics in Medicine, 2001) was used to
estimate the overall treatment effect in reducing the risk of
incident new vertebral fracture and the effect explained by
BMD within a single model. Patients with a post-baseline
BMD measurement and a known vertebral fracture status
during years 0-3 were included in the analysis (N=3224 for
lumbar spine; N=3533 for femoral neck).
Results: The proportion of vertebral fracture risk
reduction explained by BMD increases over the observed
3 year period was estimated at only 18% (95% CI: 10%,
26%; P<0.001) for lumbar spine and 11% (95% CI: 7%,
15%; P<0.001) for femoral neck.
Conclusion: Only a small proportion of vertebral
fracture risk reduction is explained by the increase in BMD
at either the lumbar spine or femoral neck.
Abstract #28
If Left Untreated, One-third of Osteoporotic Women
Without Fractures Will Experience Vertebral
Fractures after 5 Years
Zhengqing Li, PhD, Robert Lindsay, MD, PhD, and
Simon Pack, PhD
Objective: Approximately 1 in 5 postmenopausal
women who experience a vertebral fracture will suffer
another vertebral fracture within just one year. Our
objective was to complement this analysis by investigating
longitudinal changes in a population of osteoporotic
women who were initially fracture-free, modeling fracture
prevalence over time.
Methods: We estimated the 1-year risk of patients
having increased future vertebral fractures in the case
of different numbers of existing fractures. Women with
prevalent vertebral fractures or lumbar spine or femoral
neck BMD T-score <-2.5 were selected from the placebo
arms (calcium and vitamin-D) of the risedronate fracture
trials (VERT-MN, VERT-NA, HIP). Using 1-year risk
estimates, we used a simple Markov model to predict
fracture risk in a hypothetical population of osteoporotic
women, initially without vertebral fractures, over time.
Results: After 1 year, 8% of a population meeting
the selection criteria were predicted to sustain one or more
vertebral fractures if left untreated (i.e., receiving only
calcium and vitamin-D), a 1-in-13 risk. After 5 years, 33%
would sustain vertebral fractures, with 11% sustaining
two or more. Sensitivity analysis revealed that each 1%
reduction in absolute risk translates to an approximately
4% reduction in 5-year prevalence of subsequent fractures.
Correspondingly, a therapeutic agent reducing the 1-year
relative risk by 75% would cut the 5-year prevalence of
future fractures to 10%.
Conclusion: The prevalence of fracture and multiple
fractures increases rapidly over time if an osteoporotic
population is untreated. Treatment to prevent the first
fracture significantly reduces the future burden of the
disease.
Abstract #29
Back Pain is Associated with Reduced Health-related
Quality of Life Among Postmenopausal Women
With Osteoporosis
Rachel Wagman, MD, John Krege, MD, Peiqi Chen, PhD,
Stuart Silverman, MD, and Veronica Piziak, MD, PhD
Objective: To evaluate the association between back
pain and health-related quality of life (HRQoL) among
postmenopausal women with osteoporosis.
Background: Postmenopausal women with osteoporosis may present with back pain. It is therefore of interest
to study the impact of back pain on incremental decreases
in HRQoL.
Methods: The association between back pain and
HRQoL was assessed in a subset of women enrolled
in the Fracture Prevention Trial (Neer, 2001) using the
Osteoporosis Assessment Questionnaire (OPAQ). The
OPAQ is a validated, self-administered instrument of 14
domains reflected in 4 composite dimensions. A twosample t-test was used to compare HRQoL between
participants with or without baseline back pain.
Results: Participants with back pain (172/471) reported significantly (P<0.05) lower domain scores (body image, dressing/reaching, fear of falling, fatigue, household/
self-care, independence, level of tension, social activity,
standing/sitting, transfers, usual work, walking/bending).
These differences in domain scores were reflected in
significantly (P<0.01) lower dimension scores (physical
function, emotional status, symptoms, social interaction),
reflecting lower HRQoL.
Conclusion: Back pain was associated with a significant reductions in HRQoL among these trial participants.
Abstract #30
Duration of Teriparatide Treatment Corresponds
With Back Pain Reduction in Postmenopausal
Women With Osteoporosis
Rachel Wagman, MD, Clifford J Rosen, MD,
John Krege, MD, Peiqi Chen, PhD, and
Richard Wasnich, MD
Objective: To evaluate the effect of duration of
teriparatide treatment on back pain in postmenopausal
women with osteoporosis.
Methods: In a placebo-controlled, double-blind study
of 1637 postmenopausal women with osteoporosis (Neer,
2001), women were randomized to treatment with rhPTH
(1-34) (teriparatide, TPTD) 20 or 40 µg/day, for a median
of 19 months. A Cox regression model, treating time as
a continuous covariate, evaluated outcome differences
between groups treated with TPTD 20 µg/day versus 40
µg/day.
Results: Women receiving treatment with TPTD
incurred lower risk for new or worsening back pain. Cox
regression analysis showed no significant difference per
month of therapy between the TPTD 20 µg/day and 40 µg/
day doses. Compared to placebo, TPTD treatment reduced
hazard ratios of overall and severe back pain by 10% and
11% for each additional month of therapy (hazard ratios
0.902 and 0.886, P<0.0001).
Conclusion: Mechanisms for added clinical benefit
with continued TPTD therapy may include fewer fractures
and/or fewer severe fractures.
Abstract #31
Early Effects of Teriparatide in Postmenopausal
Women with Osteoporosis
Rachel Wagman, MD, Derek Misurski, PhD,
Grattan Woodson, MD, Maria Greenwald, MD,
Peiqi Chen, PhD, and William Shergy, MD
Objective: To explore early effects of teriparatide in
fracture prevention among postmenopausal women with
osteoporosis.
Background: In the Fracture Prevention Trial, treatment with rhPTH (1-34) (teriparatide, TPTD) for a median
of 19 months decreased the risk of vertebral and non-vertebral fractures among postmenopausal women with
osteoporosis (Neer, 2001). Early evidence of bone formation with TPTD has been demonstrated, with statistically
significant increases in serum levels of procollagen type I
of carboxy-terminal propeptide (PICP) and lumbar spine
BMD occurring one and three months, respectively, after
TPTD initiation (Heathman, 2000; Marcus, 2003). These
were the earliest time points at which these two parameters
have been measured.
Methods: An analysis was performed on time to first
fracture at six non-vertebral sites (hip, distal forearm, humerus, clavicle, pelvis, leg).
Results: Participants who received TPTD20
demonstrated a reduced incidence of non-vertebral fragility
fracture at 18 months compared to those receiving placebo
(P=0.0067). The difference in cumulative percentage of
events between the treated and non-treated groups diverged
after four months of treatment and the divergence continued
to increase for the duration of the trial.
Conclusion: We conclude that there is continued
evidence demonstrating the early effectiveness of TPTD
therapy.
Abstract #32
Significant Osteomalacia, Cortical Porosity and
Decreased Trabecular Bone Volume Associated with
Jejunoileal Bypass Surgery in a Unique Patient 32
Years after Surgery
Dhiren M. Haria, MD, and Harris C. Taylor, MD
Objective: To identify for the first time bone
histomorphometry and micro CT in a patient 32 years after
jejunoileal bypass (JIB).
Background: Estimates suggest that at least 25,000
JIB surgeries have been performed in the US, of which
approximately one-third may have been reversed. This
leaves a large number of patients at continuing risk for
metabolic bone disease.
Case report: A 64-year-old Caucasian woman with
a history of chronic lymphedema, recurrent cellulitis,
CHF, CVA, sleep apnea, and JIB surgery for obesity 32
years previously, was admitted for treatment of chronic
lymphedema. She reported no bone pain at the time of
admission, lived alone at home, ambulated with a walker,
did not smoke, and drank alcohol only occasionally. Routine
medications included metalozone, calcium carbonate+D,
furosemide, alendronate, diltiazem, lansoprazole, and
aspirin. During her JIB surgery, 20 inches of jejunum
was anastomosed end-to-side to 4 inches of ileum. Initial
physical examination revealed bilateral lung crackles,
massive bilateral lymphedema, and a small ulcer on the
posterior aspect of her right leg.
Methods: 1) Chemical assessment of calcium-PTHvitamin D axis. 2) Undecalcified tetracycline-labeled bone
biopsy with histomorphometric and micro CT evaluation of
micro and macro bone architecture, respectively.
Results: Serum calcium: 6.2 mg/dL (normal range
8.8-10.5 mg/dL); ionized calcium: 0.87 mmol/L (1.151.35 mmol/L), creatinine: 1.3 mg/dL (0.6-1.0 mg/dL);
albumin-2 gm/dL (3.0-5.0 gm/dL), magnesium: 1.0 mg/dL
(1.5-2.1 mg/dL ); phosphorus: 3.1 mg/dL (2.2-4.6 mg/
dL); potassium: 3.6 mmol/L (3.5-5.1 mmol/L); alkaline
phosphatase: 204 U/L (50-136 U/L ); bicarbonate: 35
mmol/L (23-33 mmol/L); PTH: 213 pg/mL (10-60 pg/mL);
25 OH-vit D <7 ng/mL (10-68 ng/mL); 1,25(OH)2 vit D: 37
pg/mL (15-60 pg/mL); and spot urine calcium <5.0mg/dL.
Bone biopsy demonstrated significant osteomalacia with
increased osteoid surface of 59.4 % (normal mean value
7.84%); increased mineralization lag time of 90.1 days
(normal mean 21.3 days); decreased adjusted apposition
rate of 0.05 mm3/mm2/y (normal value 0.23 mm3/mm2/y)
but increased volume based bone formation rate of 0.715
mm3/mm2/y (normal value 0.235 mm3/mm2/y). Increased
cortical porosity, but no evidence of significant marrow
fibrosis, was noted while cancellous bone volume was
decreased to 15.2% (normal value 21.5%). Micro CT of
the bone biopsy confirmed both increased cortical porosity
and decreased cancellous bone volume. The patient was
started on 50,000 units of vitamin D twice a week, which
was increased in 6 weeks to thrice a week with concurrent
calcium carbonate supplementation of 500 mg QID.
Conclusion: Significant osteomalacia and decreased
cortical and trabecular bone may remain a potential
problem among patients with unreversed JIB surgery after
more than 3 decades.
Abstract #33
Surgical Patients With Diabetes Have a Longer
Hospital Length of Stay
Vera Fajtova, MD, Rita McCarthy, RNP,
Monte Brown, MD, Tom Gakis, Michael Gustafson, MD,
MBA, Marc Laufgraben, and Ronald Arky, MD
Objective: To identify areas to target regarding cost
savings related to care of surgical patients with diabetes
who have longer hospital lengths of stay.
Background: In the U.S., the cost of hospitalization
accounts for nearly 45% of the direct cost of caring for
patients with diabetes.
Methods: To identify areas to target regarding cost
savings, we analyzed the patient population admitted to
Brigham and Women’s Hospital, Boston, Massachusetts.
Patients with diabetes were identified by primary and
secondary diagnostic codes and/or use of antidiabetic
medication. Patients identified with diabetes accounted for
10-12% of our total number of discharged patients.
Results: The average length of stay (LOS) for patients
with diabetes was 1.3 to 1.6 days longer than that noted
among patients without diabetes. The average charge for
patients with diabetes was 42% greater than among those
without diabetes. The greatest differential in both cost and
LOS occurred regarding surgical services.
Conclusion: Findings of this study were used
to justify creation of a program designed to improve
the quality of care and reduce increased inpatient cost
associated with diabetes.
Abstract #34
Can a Small Pituitary Tumor Cause a
“Splitting” Headache?
Cynthia Abacan, MD, Amir Hamrahian, MD,
Charles Faiman, MD and Marc Mayberg, MD
Objective: To present a case of a young man with
debilitating headaches that resolved after resection of a
pituitary microprolactinoma.
Methods: The clinical presentation, laboratory and
radiological data are presented below.
Results: A 17-year-old male presented with sharp,
stabbing headaches associated with nausea, photophobia
and dizziness. He had previously lost consciousness and
was debilitated. Examination showed an obese, fullyandrogenized male with a testicular size of 15 cc bilaterally.
Laboratory results are shown below.
PRE-OP
TSH
Free T4
Prolactin
Testosterone
FSH
IGF-1
3.1
0.9
46.2
67
10
188
POSTOP
5.4
253
11
356
REFERENCE
RANGES
0.4 - 5.5 μU/mL
0.7 - 1.8 ng/dL
2.0 - 14.0 ng/mL
220 - 1000 ng/dL
1 - 10 mU/mL
182 - 780 ng/mL
Results of a standard Cortrosyn test were in the
borderline low range (17.9 µg/dL at 30 minutes). Results
of an arginine/GHRH stimulation test were subnormal
(peak: 4.5 ng/mL). MRI revealed a 1.0 cm pituitary lesion
with a fluid level suggestive of a Rathke’s cleft cyst or
hemorrhage. Transsphenoidal resection was performed,
and tumor tissue immunostained positively for the presence
of prolactin. The patient’s headaches resolved immediately
after surgery, and he demonstrated rapid normalization of
prolactin levels and recovery of the HPG axis.
Conclusion: This case is remarkable due to the
magnitude of the patient’s headaches relative to the
relatively small size of the pituitary lesion, coupled with
the dramatic resolution of the headaches postoperatively.
Abstract #35
Polycystic Ovarian Syndrome Presenting as
Primary Amenorrhea
Berhane Seyoum, MD, Nnemka Ekwueme-Sturdivant, MD,
and Cristina B. Guzman, MD, FACE
Objective: Presentation of a case of polycystic ovarian
syndrome presenting as primary amenorrhea.
Background: Polycystic ovary syndrome (PCOS)
is classically defined by chronic anovulation, infertility,
and hyperandrogenism. The menstrual pattern may be
oligomenorrhea or amenorrhea and typically begins in the
peripubertal period. Although delayed menarche may be an
initial presentation, primary amenorrhea is unusual.
Case presentation: We present a case of a 19-yearold female patient with primary amenorrhea and signs of
hyperandrogenism. She had no family history of menstrual
irregularities or diabetes. Her past medical history was
unremarkable except for amenorrhea and increased facial
hair growth. She had a progesterone challenge test at age
age 15, to which she had a normal response, and after
which she was started on oral contraceptive (OC) pills
. She maintained regular menses during three years of
OC therapy, but each time discontinuation of OCs was
attempted she failed to resume spontaneous menstruation.
Physical exam revealed a BMI of 26 kg/m2. She
had facial acne along with terminal hair growth over the
chin and upper lip area. Ferriman-Gallway score was 13.
Pelvic examination revealed no clitoromegaly. Laboratory
assessment during follicular phase revealed the following
values: testosterone 69 ng/dL; estradiol 22 pg/mL; DHEAS
327 µg/dL; FSH 4.4 mIU/mL; LH 7.4 mIU/mL; insulin
17 IU/mL; glucose 75 mg/dL. After dexamethasone 1 mg
suppression test the patient’s cortisol level was 1.2 µg /dL.
Baseline 17-OH progesterone was 185 ng/dL with a 60
minutes post-ACTH response of 380 ng/dL. Chromosomal
testing revealed 46, XX. A transvaginal pelvic ultrasound
of the ovaries revealed multiple cysts bilaterally.
Conclusion: The four most common causes of
primary amenorrhea are ovarian failure (48.5%), congenital
absence of the uterus and vagina (16.2%), GnRH deficiency
(8.3%), and constitutional delay of puberty (6.0%). PCOS,
a common disorder, is a rare cause of primary amenorrhea,
but should be considered in the differential diagnosis of this
condition.
Abstract #36
Anaplastic Thyroid Carcinoma: A Case Report of 12
Year Survival without Surgery
Maryann Mugo, MD, and
Romayne Kurukulasuriya, MD, FACE
Objective: Presentation of a case of long-term survival
of anaplastic thyroid carcinoma without surgical excision.
Case Report: A 62-year-old man presented to our
endocrinology service with a longstanding history of
“thyroid cancer.” Twelve years previously he noticed a
left-sided lump in his neck that grew rapidly over several
days. An initial fine needle aspiration of the mass revealed
inconclusive results. A computerized tomography scan
of the neck revealed a 6 cm x 3 cm mass on the left
lobe of the thyroid gland. The patient then underwent
open biopsy of the mass without thyroidectomy or neck
dissection. Pathologic evaluation of the biopsied tissue
revealed anaplastic thyroid carcinoma. No local or distant
metastases were identified at diagnosis. Treatment included
tracheostomy, radiotherapy and chemotherapy followed by
thyroid hormone replacement. Re-evaluation of histologic
slides 12 years later confirmed the diagnosis of anaplastic
thyroid carcinoma.
Conclusion: This case represents an extremely
rare example of survival of anaplastic thyroid carcinoma
of more than 5 years. Interestingly, this patient survived
for this extended period of time without neck dissection,
which is considered an integral part of therapy for this rare,
aggressive cancer.
Abstract #37
Metformin-associated Lactic Acidosis
Maria Paliou, MD, Emilia Liao, MD,
Jonathan Schlosser, DO, and Leonid Poretsky, MD
Objective: To present a case of severe lactic acidosis
in a postoperative diabetic patient on metformin, and to
discuss the implications of metformin in the development
of lactic acidosis.
Methods: Clinical and laboratory data are presented
for a case of severe lactic acidosis.
Results: A 70-year-old woman with a history of
diabetes mellitus type 2 treated with metformin developed
fever, diarrhea, and lethargy one day after outpatient
surgery. She had taken her usual metformin dose the day of
surgery. Arterial blood gas pH was 7.15, with a lactic acid
level of 17.1 mEq/L was noted. Exploratory laparotomy
revealed only a grossly cirrhotic liver. Blood cultures
revealed the presence of Escherichia coli infection. Her
serum metformin level was 0.98 mg/dL (therapeutic levels
1-2 mg/dL). The patient subsequently developed renal
and hepatic failure, and hemodialysis was initiated. The
patient died despite all resuscitative measures, and autopsy
revealed no additional significant findings.
Conclusion: We conclude that metformin, despite
normal blood levels, may have exacerbated the degree of
hypoxic lactic acidosis and further impaired lactic acid
clearance by the diseased liver. Great caution should
therefore be exercised in administering metformin during
the early postoperative period to patients in whom infection
risk is high.
Abstract #38
Treating PCOS: Hepatic Adenomas Revisited
Stephanie T. Page, MD, PhD, and
Dace Trence, MD, FACE
Objective: Women with polycystic ovary syndrome
(PCOS) on oral contraceptive (OC) therapy may be at
increased risk for development of hepatic adenomas. We
report the case of a patient with PCOS who developed
multiple hepatic adenomas after 8 years of OC therapy.
Background: OCs are indicated in the treatment
of PCOS. A rare side effect of this therapy is hepatic
adenomas.
Case report: A 22-year-old woman with PCOS treated
with ethinyl estradiol 30 mcg/norgestrel 0.3 mg for 8 years
presented with nausea, diarrhea, and anorexia. Metformin
therapy had been recently discontinued. Physical examina-
tion revealed tenderness at the patient’s hepatic margin,
prompting ultrasound evaluation. Subsequent computerized tomographic (CT) scanning revealed multiple hypervascular hepatic lesions, the largest of which measured 4.1
cm x 4.6 cm. Liver biopsy was consistent with hepatic adenoma. OC therapy was discontinued, and subsequent CT
scans demonstrated reduction in adenoma size.
Conclusion: Hepatic adenomas are associated with
the use of OCs and anabolic androgens. PCOS is typically
treated with OCs, but patients also have inherently high
levels of androgen. Review of literature revealed only
one previously reported case of multiple adenoma with
OC therapy in a patient with PCOS. We recommend
an elevated n index of suspicion for hepatic adenoma
development in women with PCOS undergoing long-term
therapy with OCs.
Abstract #39
“Routine” Pan-hypopituitarism Following Surgery/
Radiation--Fact or Fallacy?
Stephanie T. Page, MD, PhD, and
Dace Trence, MD, FACE
Objective: To report a case of pituitary hormone
recovery after surgery and radiation and review the
literature regarding this outcome.
Background: Panhypopituitarism is a recognized
complication of surgery and radiation for pituitary
adenomas.
Case report: A 32-year-old man with acromegaly
was treated by transsphenoidal resection plus external
beam radiation for a 1.8 cm left pituitary mass 10.5 years
prior to his presentation as a new patient at our clinic.
Current medications included thyroxine, testosterone,
and hydrocortisone, and his medical records revealed
recent normal IGF-1 levels and follow-up MRI scans
with no residual tumor apparent. Testosterone withdrawal
attempted several years ago indicated a need to resume
replacement. On further inquiry, this patient revealed that
he had run out of medications 2-3 months prior to our
evaluation. Laboratory assessment at that time revealed
normal pituitary function including thyroid, testosterone,
and cortisol levels.
Conclusion: Spontaneous recovery of pituitary
function can occur in patients who have undergone
transphenoidal resection and radiation. Our review of the
literature suggests that this may occur in up to 35% of
patients even in the setting of macroadenomas. Periodic
noncortisol hormone withdrawal should be considered to
evaluate the pituitary axis in such patients, even years after
initial tumor treatment.
Abstract #40
HIV-associated Hypercalcemia and Osteoporosis
Maria Paliou, MD, Jonathan Schlosser, DO, and
Emilia Liao, MD
Objective: To report a case of osteoporosis, hypercalcemia and nephrolithiasis in an HIV-positive patient.
Methods: Clinical and laboratory data are presented
followed by a review of the literature.
Case report: A 54-year-old woman with a history
of positive HIV status and HAART presented with
hypercalcemia and calcium oxalate kidney stones. Her
serum calcium level was 12.2 mg/dL with completely
suppressed PTH production. Urinary calcium and oxalate
levels were elevated at 292.5 mg/24h and 45.6 mg/24h,
respectively. Urinary and serum Ntx were elevated at
45 nmol BCE/mmol Cr and 13.9 nmol BCE/mmol Cr.
Vitamin D 25-OH and 1-25 OH, PTH-rP, SPEP, UPEP,
magnesium, phosphate, alkaline phosphatase, creatinine,
and ACE levels were normal, as were chest radiograph, CT,
bone scan, and mammogram results. Bone densitometry
revealed osteoporosis of the lumbar spine. Alendronate
was initiated and calcium improved, though the patient
developed recurrent kidney stones.
Conclusion: HIV infection and HAART can precipitate osteoporosis. Hypercalcemia is present in 2.9% of
HIV-positive patients, and is due to medications or caused
by granulomatous or neoplastic processes. In the case of
our patient, we conclude that HAART, HIV, or both caused
increased osteoclastic activity leading to hypercalcemia,
hypercalciuria and osteoporosis.
Abstract #41
Systemic Lupus Erythematosus and Graves’ Disease
Miguel E. Pinto, MD, Jaime E. Villena, MD, and
Sandro M. Corigliano, MD
Objective: To report a case of a woman with a history
of systemic lupus erythematosus (SLE) who developed
worsening nephrotic syndrome after receiving methimazole for treatment of associated Graves’ disease.
Methods: We reviewed and abstracted the patient’s
medical records and conducted a review of the pertinent
medical literature.
Case report: A 26-year-old woman with a 4-year
history of SLE and nephrotic syndrome secondary to glomerulonephritis was referred to our unit for treatment of
previously untreated hyperthyroidism. Current medications
included prednisone 60 mg daily and high-dose intrave-
nous pulse cyclophosphamide bimonthly. She had recently
sought treatment at another hospital because she noted
tremor, heat intolerance, increased perspiration, palpitations, and hyperdefecation. Physical examination revealed
exophtalmos, diffuse enlargement of the thyroid gland, and
hyperreflexia. Family history was significant for diagnosis
of Graves’ disease in an aunt. Laboratory values were as
follows: thyrotropin 0.42 µIU/dL (normal range: 0.3 to
5.0 µIU/dL), free thyroxine 6.85 ng/dL (0.8 o 2.0 ng/dL),
triiodothyronine 415 ng/dL (86 to 190 ng/dL). A screen for
antithyroid peroxidase antibodies (TPO Ab) yielded positive results. 131I uptake was 60% at 24 hours (normal, 1535%). Therapy was begun with methimazole 40 mg given
once daily and propanolol 40 mg three times daily. A few
days later, the patient developed severe edema, arthralgias,
fatigue, and malaise. Her proteinuria worsened and treatment was suspended. In our unit she received propanolol 40
mg three times a day and 12 mCi 131I with resultant clinical
improvement. She remained euthyroid for the next eight
months, then developed hypothyroidism and required treatment with 50 µmg levothyroxine once daily.
Conclusion: Autoinmune thyroid disease has been
associated with a number of nonorgan-specific rheumatological disorders. SLE patients demonstrate increased prevalence of thyroid disorders, mainly hypothyroidism, though
there is no reported associated increase in hyperthyroidism
among these patients. Patients with SLE also demonstrate a
higher prevalence of TPO Ab than does the general population. Thyroid function and TPO Ab tests should therefore
be performed in all patients with SLE.
Abstract #42
Pan-hypopituitarism in a Patient with Metastatic
Breast Cancer, and Review of Literature Regarding
Pituitary Metastasis
Garumuni A. DeSilva, MD, MS,
Rennert, MD, FACE, FACP, and Samuel Engel, MD
Objective: To report a case of pan-hypopituitarism in
a patient with metastatic breast cancer.
Case report: A 73-year-old woman with a history of
metastatic breast cancer was admitted to the hospital with
dehydration and psychosis. Laboratory evaluation revealed
TSH 0.04 µU/mL; free T4 0.79 ng/dL; prolactin 56.8 ng/
mL; ACTH 12 pmol/L; morning random cortisol 0.8; FSH3.7 mU/mL; and LH <0.5. Initial MRI of the brain reported
an enlarged pituitary with a possible adenoma. There was
no evidence of chiasmal compression. MRI evaluation of
the pituitary confirmed the presence of an asymmetrically
enlarged gland. This patient was treated with steroids
and thyroid replacement therapy with resolution of her
psychosis. She subsequently received chemotherapy for
breast cancer with adriamycin. Repeat MRI of the brain 5
months later revealed a decrease in the size of the pituitary
lesion.
Discussion: We propose that this patient developed
pan-hypopituitarism secondary to pituitary metastasis of
breast cancer. Literature review revealed that 3-5% of
patients with any carcinoma have manifestations secondary
to pituitary metastasis. In one autopsy series, up to 27%
of patients developed micrometastases to the pituitary. In
a study of hypophysectomy specimens of patients with
breast cancer, 5.5 to 25% demonstrated occult metastasis to
the pituitary. Breast cancer is the most common source of
symptomatic metastasis. Among women with symptomatic
pituitary metastases, up to 70% are related to primary breast
cancer. Further details including clinical manifestations,
diagnosis, treatment and prognosis of pituitary metastasis
will be discussed.
Abstract #43
Prevalence of Comorbid Metabolic Abnormalities in
Non-Diabetic Overweight or Obese Adults
Steven Weinstein, MD, PhD, Barbara Tardiff, MD,
Catherine Vicary, BS, Marshall Block, MD, and
Sherwyn Schwartz, MD
Objective: To describe the prevalence of dyslipidemia, impaired fasting glucose, metabolic syndrome, and
hypertension in a sample of overweight/ or obese non-diabetic patients presenting in 2001 for medical weight loss
treatment.
Methods: Prospective data from 1,968 adult non-diabetic subjects enrolled in a U.S. multicenter (65 sites) trial
of an investigational drug (Axokine) for medical weight
loss treatment.
Results (mean [SD] or %): Demography and anthropometry: gender, 88.6% female; age, 44.1 [10.9] years;
race, 81.7% white, non-Hispanic; weight, 106.8 [20.1] kg;
BMI, 38.8 [6.0] kg/m2; waist circumference, 114.8 [14.8]
cm. Comorbidity prevalence: dyslipidemia, 77.2%; impaired fasting glucose (110-125 mg/dL), 8.3%; metabolic
syndrome, 45.7%; hypertension, 27.2%.
Conclusion: Even among patients without type
2 diabetes mellitus, the prevalence of obesity-related
comorbid risk factors is high in overweight or obese adult
patients presenting for medical weight loss treatment.
Abstract #44
Abstract #45
Preoperative Neck Ultrasound is a Costeffective Approach in Treating Patients with
Hyperparathyroidism and Coexisting Thyroid Disease
Primary Hyperparathyroidism and
Subclinical Hypothyroidism
Angela Mensah, MS, Mira Milas, MD, Eren Berber, MD,
Antonia Stephen, MD, and Allan Siperstein, MD
Objective: To evaluate the impact of neck ultrasound
performed for preoperative parathyroid localization in
patients with hyperparathyroidism (HPT) on identification
and treatment of coexisting thyroid disease.
Background: Thyroid disease has high prevalence in
the general population and thyroid tumors are thought to
be even more common among patients with HPT. Finding
unexpected thyroid pathology at the time of parathyroid
surgery adds unplanned surgical interventions, operative
time, and cost.
Methods: We reviewed records of 250 consecutive
patients with primary HPT due to single adenomas
who underwent surgeon-performed preoperative neck
ultrasound (U/S) in clinic. Cost analysis based on Medicare
reimbursement was calculated for this cohort, comparing
management strategy with and without routine U/S.
Results: Forty percent (101/250) of HPT patients had
coexisting thyroid disease, presenting as benign colloid
nodules/goiter (n = 56), cysts (n = 20), thyroiditis (n = 13),
follicular adenomas (n = 11), and papillary cancer (n = 1).
Only 6% of patients with HPT had known thyroid disease
prior to this evaluation. U/S-detected nodular thyroid disease
led to fine needle biopsy in 20% (20/101) and concomitant
thyroidectomy in 14% (14/101). Thyroid pathology did not
reduce the sensitivity (84%) and specificity (87%) of U/S
in localizing parathyroid adenomas. Calculated hospital
costs for clinical treatments and out-of-pocket patient costs
were not statistically different between an U/S-guided and
non-U/S management approaches. Costs incurred by U/S
and biopsy were offset by those related to thyroid surgery
that would have been required by the nature of thyroid
abnormalities found in 31% (31/101) of patients at time of
parathyroidectomy.
Conclusion: Routine use of U/S in HPT patients identifies a high prevalence of predominantly benign thyroid
conditions. Vigilant recognition of coexisting thyroid disease is crucial for avoiding delayed diagnosis and planning
for possible simultaneous parathyroid-thyroid surgery. U/S
is a valuable tool for minimizing thyroidectomy in patients
with subclinical thyroid disease.
Sandro M. Corigliano, MD
Objective: To report a case of a woman with a history of
osteoporosis who developed primary hyperparathyroidism
and subclinical hypothyroidism.
medical records and conducted a review of pertinent
medical literature.
Results: A 68-year-old woman with a personal history
of nephrolithiasis, osteoporosis, and osteoarthritis of the
knees came to our unit with a 2-week history of bone pain,
constipation, and fatigue. She had in the past undergone
hysterectomy and bilateral salpingo-oophorectomy due to
uterine leiomyoma. Physical examination revealed central
obesity, dry skin, and enlargement of the left side of the
thyroid gland. Her serum calcium level was 10.7 mg/dL
(normal, 8.5 to 10.5 mg/dL), phosphorus was 2.7 mg/dL (
2.5 to 4.5 mg/dL), alkaline phosphatase was 433 U/L (41 to
133 U/L), albumin was 4 g/dL (3.4 to 4.7 g/dL), thyrotropin
was 8.45 µIU/dL (0.3 to 5.0 µIU/dL), free thyroxine was
1.69 ng/dL (0.8 to 2.0 ng/dL), and iPTH was 221 (10 to 60
pg/mL). Her urine calcium level in 24 hours was 476 mg
(60 to 200 mg) and phosphorus was 994 mg (400 to 700 mg
). Thyroid ultrasonography revealed a parathyroid adenoma
behind the left lobe of the gland that was confirmed with
Tc-99m MIBI scintigraphy. The patient subsequently
underwent hemithyroidectomy and parathyroidectomy.
Currently, she is asymptomatic, and is treated with
levothyroxine 50 µg daily, alendronate 70 mg weekly and
calcium supplementation. Her last serum calcium level and
thyroid function tests were normal.
Conclusion: Primary hyperparathyroidism and
thyroid disease are both relatively common diseases,
and can coexist in the same patient. In some cases, prior
exposure to radiation may play a role in this association.
Both conditions are common among postmenopausal
women. This is probably the major factor that accounts for
the coexistence of these two pathologies.
Abstract #46
Parathyroid Carcinoma: A Diagnostic Dilemma
Stefanie Addington, MD
Objective: To describe a case of parathyroid carcinoma
and difficulty with diagnosis/management.
Methods: We present clinical, laboratory, and
pathologic data in our patient. Pertinent literature is also
reviewed.
Results: A 50-year-old man presented to our VA
endocrine clinic with hypercalcemia. He had GERD but
no history of nephrolithiasis, renal disease, polyuria,
constipation, depression, or hypertension. He was found
to have hypercalcemia (serum calcium concentration 12.7
mg/dL), a normal phosphorus level, and an elevated intact
parathyroid hormone level (243.4 pg/mL). Results of a
sestamibi scan were consistent with a large left parathyroid
adenoma or carcinoma. Pathology revealed parathyroid
tissue with capsular invasion. Hypercalcemia resolved
post-operatively.
Conclusion: Parathyroid carcinoma is rare. Diagnosis
and treatment of parathyroid carcinoma are challenging.
Given its poor prognosis, however, a high level of suspicion
should exist for this condition preoperatively in order to
assure the best possible outcome.
Abstract #47
Hypercalcemic Crisis Precipitated By
Elective Termination Of Pregnancy
Shalini Bhat MD, and Alan Farwell MD
Objective: To describe a case of hypercalcemic crisis
due to primary hyperparathyroidism (PHP) precipitated by
elective termination of pregnancy (ETP) in a previously
asymptomatic patient.
Methods: A case report is presented and relevant
medical literature is reviewed.
Results: A 20-year-old woman underwent an ETP
at 12 weeks gestation. She then developed increasing
abdominal pain and was admitted to the hospital one week
later. A Dilation and curettage was performed, but her
abdominal pain persisted and eventually localized to the
epigastric region. Laboratory evaluation revealed elevated
serum calcium (12.1 mg/dL), serum parathyroid hormone
(PTH) (558 pg/mL), and serum amylase (285 U/L) levels.
An abdominal CT scan revealed pancreatitis, and a Tc-99
sestamibi scan was suspicious for a left-sided parathyroid
adenoma. Review of systems revealed no symptoms of
hypercalcemia prior to the ETP. The patient underwent
excision of a solitary parathyroid adenoma that was
associated with a fall in intraoperative serum PTH to 60.3
pg/mL. The patient’s abdominal pain resolved completely
postoperatively, and her serum calcium retuned to normal
range, at 9.7 mg/dL. Review of the literature reveals that
the placenta actively transports calcium to the fetus to
protect maternal bone stores and that up to 80% of pregnant
patients with PHP are asymptomatic, suggesting that the
disease may be ameliorated by the placental transport of
calcium. A single case report has described hypercalcemic
crisis after full-term delivery. This is the first case report
describing hypercalcemic crisis after an ETP.
Conclusion: This case suggests that active placental
transport may be protective in primary hyperparathyroidism
and that hypercalcemic crisis may result after the loss of the
placenta in ETP in patients with PHP.
Abstract #48
Risedronate and Alendronate Pharmacokinetics:
A Head-to-Head Comparison at Clinical Doses
David Burgio, PhD, C. Christiansen, MD,
Darrell Russell, BS, Lu Sun, MD,
Robert Lindsay, MD, PhD, and Roger Phipps, PhD
Objective: The objective of this study is to make
a head-to-head comparison of the pharmacokinetics of
risedronate and alendronate after single intravenous doses
at clinical dosage levels.
Methods: In a 52-week, open label, randomized study
of postmenopausal women with osteopenia or osteoporosis
(age range 43-73 years), subjects were administered
single intravenous doses of 14C-risedronate sodium (230
µg; 2.9 µCi) or 14C-alendronic acid (450 µg; 3.2 µCi),
each approximately equivalent to an oral weekly dose,
followed by weekly oral doses of unlabeled Actonel (35
mg) or Fosamax (70 mg), respectively. Concentrations of
14
C-risedronate and 14C-alendronate in serum and urine
are measured over the 52-week study period by liquid
scintillation counting as long as the samples contained
adequate radioactivity, and thereafter by accelerator mass
spectrometry (AMS). Use of AMS allows measurement of
these compounds at concentrations of 10 pg/mL and lower.
The study in-life is ongoing; presented here are urinary
excretion results from the first 27days (the primary endpoint).
Results/Conclusion: The cumulative urinary excretion
of risedronate (66%) was significantly higher than that
of alendronate (55%) over the first 27 days of treatment.
This resulted in one-third more drug retained on bone for
alendronate compared with risedronate (34% risedronate;
45% alendronate). The absolute amount of drug retained
from the initial dose at 27 days was 78 µg risedronate
sodium and 202 µg alendronic acid. This difference (2.5-
fold at 27 days) is estimated to increase disproportionately
with repeated dosing (to >2.8-fold at 6 months). This
suggests a smaller skeletal burden is associated with
long-term risedronate use, and indicates the potential for
improved control of therapy for risedronate compared to
alendronate.
Percent of Dose Excreted in Urine (Median)
Interval
Risedronate
Alendronate
P value*
(n = 15)
(n = 17)
0-24 hours
0-72 hours
0-336 hours
0-648 hours
49.0
54.5
63.5
66.2
44.5
48.2
52.6
55.1
0.0966
0.0235
0.0025
0.0020
*Wilcoxon Rank Sum test
Abstract #49
Metabolic Syndrome in Patients with Conventional
Risk Factors for Coronary Disease
Vishal C. Mehra, MD
Objective: The purpose of the study was to establish
that there exists a significant association between metabolic
syndrome (MS) and coronary microangiopathy (CM).
Methods: A retrospective review of cardiac catheterization records was performed in symptomatic patients who
demonstrated positive stress tests and had post-catheterization diagnoses of “normal’ coronaries from July 1999 to
May 2002. An overall descriptive analysis of this cohort
was undertaken with special emphasis on the presence of
ATP III clinical criteria for MS.
Results: The overall prevalence of MS in this
predominantly black cohort was found to be 62%, of which
75% were women (P = 0.0139). By age group, the trend in
prevalence of MS in this cohort paralleled the NHANES
database, with a peak in the 60- to 70-year-old age group,
though the absolute prevalence was much higher than that
detected in NHANES, at 72%. Of all the five criteria for
metabolic syndrome, hypertension (100%) and obesity
(96%) were most often met in the patients who did have
MS.
Conclusion: We were able to show that a majority
of patients with CM at an inner-city university center had
MS. These results underscore the pathophysiological role
of insulin resistance at the core of this coronary vascular
dysfunction. Implications of establishing this association
are in promoting nonpharmacological approaches or insulin-sensitizing agents to treat this endothelial dysfunction,
irrespective of the presence of overt diabetes.
Abstract #50
Back Pain in Women With Postmenopausal
Osteoporosis Treated With Teriparatide 40 μg/day
(TPTD40) or With Alendronate 10 mg/day (ALN10)
P.D. Miller, W.J. Shergy, Peiqi Chen,
Mark Rohe, J.H. Krege
Objective: To explore incidence of back pain among
women with postmenopausal osteoporosis treated with
teriparatide versus alendronate.
Methods: This report includes back pain findings collected during adverse event monitoring of a double-blind
randomized trial of oral ALN10 (n = 73) plus placebo
injection, versus oral placebo plus TPTD40 injection (n =
73). Patients received study drug for a median period of
14 months during the trial and then were followed for 30
months of additional observation.
Results: Compared to ALN10, significantly (P≤0.016)
fewer women treated with TPTD40 reported back pain
(19.2% vs. 5.5%) and moderate or severe back pain (13.7%
vs. 2.7%) during the trial period. During the trial and the
first 18 months of follow-up, differences in the incidence
of back pain (28.3% vs. 9.6%) and moderate or severe
back pain (18.9% vs. 3.9%) remained significant between
groups (P<0.016). During the trial and 30 months of follow-up, differences in the incidence of moderate or severe
back pain (18.9% vs. 5.8%) remained significant between
groups (P=0.04).
Conclusion: In this study, significantly fewer patients
randomized to treatment with TPTD40 reported back pain
than patients randomized to treatment with ALN10.
Abstract #51
Non-autoimmune Thyroiditis in a Patient Receiving
Peginterferon Alfa-2a and Ribavirin for Chronic
Hepatitis C Virus Infection
Michael D. Goldberg, MD, and
Yaron Tomer, MD, FACP, FACE
Objective: To describe an uncommon form of interferon (IFN)-related thyrotoxicosis in a patient treated for
chronic hepatitis C virus (HCV) infection. Similar cases
described in the literature are critically reviewed.
Background: The development of autoimmune thyroid disease in HCV-infected patients treated with IFN is
a well-described phenomenon, and most common cause
of thyrotoxicosis is Graves’ disease. There are, however,
reports in the literature of IFN-induced thyrotoxicosis with
negative antibodies and very low radioactive iodine uptake
(RAIU). The clinical course in these cases resembles nonautoimmune subacute thyroiditis. There is no consensus
regarding discontinuation of IFN therapy, and very little
experience with rechallenging with a second course of
IFN.
Methods: A clinical case report and literature review.
Case report: A 26-year-old Egyptian female with no
significant medical history and normal thyroid function was
treated with peginterferon alfa-2a and ribavirin for chronic
HCV infection. Virologic response to combination therapy
was excellent. During the twelfth week of treatment she
presented with fatigue, weight loss, anxiety, and tremor;
there was no neck pain, fever, goiter, or signs of ophthalmopathy. Laboratory investigation revealed thyrotoxicosis
with weakly positive assay results for anti-Tg antibodies
and negative results for anti-TPO and TSH-receptor antibodies. RAIU was 0.1% at 24 hours. Propranolol was initiated and antiviral therapy was discontinued. After several
weeks the patient’s thyroid function normalized, but she
subsequently developed hypothyroidism and required levothyroxine therapy.
Conclusion: Transient thyroiditis, though unusual,
should be considered in patients who develop thyrotoxicosis during IFN therapy for chronic HCV infection. While
the etiology of IFN-related autoimmune thyroid disease is
generally thought to involve mechanisms such as stimulation of Th1 polarization of T cells, induction of thyroiditis
without the development of autoantibodies raises the possibility of a direct effect of IFN on the thyroid, distinct from
autoimmune mechanisms.
Abstract #52
Quantitative Measurement of Diabetic
Peripheral Neuropathy
David Oyer, MD, and David Saxon
Objective: A technique to evaluate peripheral neuropathy is presented.
Summary: Patients lie supine with bare feet, and the
C128 tuning fork is struck so that the ends just strike each
other. The stem is held with two fingers. After demonstrating the vibration sensation, strike again, hold the stem
against the dorsal surface of the large toe, and have the
patient say when they no longer feel the vibration. The
number of seconds elapsed is measured on both toes. In
30 random diabetic patients, the right foot averaged 10.9
+/- 6.7 seconds compared to 9.7 +/- 7.1 seconds on the left.
The Pearson correlation coefficient comparing the right to
the left readings on the same patient was 0.947. Normal is
18 seconds. When vibration is not perceived at all, many
patients still report detectable sensation on monofilament
testing. Of patients with scores of 6 seconds or less, 3 of 12
had diabetic foot ulcers, compared to no ulcers among 50
patients with scores of 6 or more.
Conclusion: Quantitative tuning fork evaluation
identifies early neuropathy in diabetics.
Abstract #53
Evaluation of Echocardiographic Parameters
in Patients With Mild Heart Failure Receiving
Pioglitazone or Glyburide
Alfonso Perez, MD, Mehmood Khan, MD,
Patrick Gallagher, and Yinzhong Chen
Objective: Evaluate the cardiovascular effects of
treatment with pioglitazone versus glyburide in patients
with type 2 diabetes and mild cardiac disease.
Methods: Three hundred subjects were enrolled in
a 52-week randomized, multi-center, double-blind study.
Patients received pioglitazone (n = 151; 15 to 45 mg daily)
or glyburide (n = 149; 2.5 to 15 mg daily).
Results: Mean changes (± SD) from baseline are
shown in the table below.
Pioglitazone
Glyburide
P
value
Left ventricular mass (g)
-6.57 ± 30.37
-3.98 ± 26.60
0.373
Cardiac index (LPM/m2)
0.28 ± 1.67
0.02 ± 0.66
0.166
Fractional shortening (%)
-0.09 ± 6.98
0.14 ± 6.90
0.996
Left ventricular ejection
fraction (LVEF)
4.06 ± 9.85
4.07 ± 10.17
0.374
Conclusion: There were no significant differences
between treatment groups in change from baseline with
regard to left ventricular mass, cardiac index, fractional
shortening, or left ventricular ejection fraction. These
changes indicate an overall improvement from baseline
among patients in both treatment groups.
Abstract #54
Pioglitazone Combination Therapy with Sulfonylurea,
Metformin, or Insulin is Associated with Improvements
in Components of Diabetic Dyslipidemia
Alfonso Perez, MD, Mahinda Karunaratne,
Mehmood Khan, MD, and Todd Johnson
Objective: To explore the effects of treatment with
pioglitazone (PIO) in combination with sulfonylurea (SU),
metformin (MET), or insulin (INS) on major components
of diabetic dyslipidemia in patients with type 2 diabetes
mellitus.
Methods: Three independent multicenter, doubleblind, 24-week randomized trials compared the effects of
30 mg and 45 mg dosages of PIO daily plus either SU,
MET, or INS.
Results: Combination treatment with PIO resulted in
statistically significant improvements from baseline with
regard to triglyceride decreases, HDL increases, average
and peak LDL particle size increases, and the overall shift
in LDL subparticles from small to large. HDL subfractions
were similarly affected after combination treatment with
PIO.
Conclusion: The findings from these trials suggest that
treatment with PIO may contribute positively to improving
lipid profiles of patients with diabetic dyslipidemia.
Abstract #55
Using Inhaled Insulin
Victor L. Roberts, MD, and Barbara Lake, ARNP-C, CDE
Objective: To describe key issues regarding inhaled
insulin and related patient education.
Background: Insulin, an integral part of diabetes
mellitus treatment, has been the target of ongoing developments intended to enhance efficacy, safety, and convenience of use by persons with diabetes. One of the most
recent of these developments is inhaled insulin.
Summary: Recent research demonstrates sufficient
permeability of lung tissue to insulin that an aerosol delivery system may be practical and useful in treating patients
with diabetes. Several pharmaceutical companies are conducting clinical trials of inhaled insulin, and preliminary
data demonstrate safety and efficacy among patients with
type 1 and type 2 diabetes. Patient education must be an
integral part of initiating treatment with inhaled insulin.
As with all insulin compounds, patients must be increasingly vigilant in their blood glucose self-monitoring during
treatment with inhaled insulin to prevent hypoglycemic
episodes (HE) as blood glucose levels normalize. Patients
must learn to administer inhaled insulin using a hand-held
device, and to properly care for this device. They must
also learn to calculate their insulin doses based upon
self-monitored blood glucose values and the amount of
carbohydrates to be consumed. Patients must also identify
and appropriately treat HE. Diabetic education should be
completed and reinforced to assure efficacious use of this
new insulin delivery system.
Abstract #56
Specialized Diabetes Care Achieves Tighter Glycemic
Control Than Does Standard Medical Care in
Treatment of High Risk Patients
Serena Cardillo, MD, Nayyar Iqbal, MD, and
Prakash Seshadri, MD
Objective: To explore the impact of patient care in
a multidisciplinary diabetes clinic setting compared to
standard care, regarding diabetes control among patients at
high risk for developing complications.
Methods: A retrospective cohort study was performed
at the Philadelphia VA Medical Center (PVAMC) among
patients with type 2 diabetes and HbA1c values >9%. Three
cohorts of patients were examined: 1) diabetes clinic patients (N = 40) seen in a multidisciplinary clinic, 2) medical
clinic patients (N = 40) cared for in a general medicine clinic, and 3) diabetes clinic patients (N = 40) seen 12 months
prior to specialist intervention (historical controls). Main
outcome measures included baseline and 4-month followup HbA1c values, BMI, and medication profile. Data were
obtained by chart review.
Results: Diabetes clinic patients experienced a significantly greater decline in HbA1c concentration (-2.19%)
compared to medical clinic patients (-1.0%, P = 0.02) and
historical controls (-0.03%, P<0.001). Changes in insulin
and metformin dosages were significantly greater among
diabetes clinic patients (+16 units and +396 mg, respectively) compared to medical clinic patients (+4.52 units
[P=0.01] and 0 mg [P = 0.003]) and historical controls (+4
units [P = 0.01] and +76 mg [P = 0.03]). Medical visits
were more frequent among diabetes clinic patients (3.12)
compared to medical clinic patients (1.97 [P = 0.00]) and
historical controls (2.20 [P = 0.004] during the study period. No difference in BMI was noted among the cohorts.
Conclusion: Specialized multidisciplinary care
significantly improves glycemic control in patients with
poorly controlled type 2 diabetes. Our findings suggest
that more frequent medical visits and aggressive titration of
medication doses are valuable in achieving treatment goals.
While the locus of diabetes care has shifted to primary care
centers, patients at high risk for developing complications
may benefit from a transition in care that includes dedicated
diabetes management.
Abstract #57
Oxidative Stress in Diabetic Cardiomyopathy
Firoozeh Farahmand, MD
Objective: To describe a model of oxidative stress
as a possible mechanism of diabetes-induced myocardial
dysfunction.
Background: The burden of cardiovascular disease
related to diabetes will increase substantially in coming
decades. Myocardial dysfunction occurs even in the case of
adequate insulin therapy and normal blood glucose levels,
though the precise mechanism by which diabetes induces
myocardial dysfunction is not fully understood.
Summary: When the equilibrium between free
radical production and cellular antioxidant defenses is
disturbed in favor of the creation of more free radicals,
this situation creates oxidative stress that promotes cellular
injury. Convincing experimental and clinical evidence
exist to suggest that oxidative stress is increased in
diabetes. Cardiac dysfunction is clearly associated with
reduced antioxidant reserves and increased oxidative
stress in animals with streptozotocin-induced diabetes,
and antioxidant treatment with probucol modifies these
changes. The observed beneficial effect of probucol
may have been caused under these circumstances by an
increase in myocardial antioxidant enzyme production
and a corresponding decrease in lipid peroxidation. These
findings suggest that diabetic cardiomyopathy is associated
with an antioxidant deficit, though beneficial effects of
probucol may also be related to an improvements in plasma
insulin levels.
Conclusion: This new concept of oxidative stress as
an important trigger in onset and progression of diabetes and
its complications may inspire new and unique therapeutic
options for treatment of diabetes and its complications.
Abstract #58
Synergistic Effects of Simvastatin and Pioglitazone on
Inflammatory Cytokines Interferon-gamma, Tumor
Necrosis Factor-alpha, Interleukin-6 and C-reactive
Protein in Diabetic Patients With Hyperlipidemia and
Coronary Artery Disease
Stanley A. Tan, MD, PhD, and Linda G. Tan, MD
Objective: To evaluate synergistic effects of simvastatin and pioglitazone on inflammatory cytokine levels in
diabetic patients with hyperlipidemia and coronary artery
disease.
Background: Interferon-gamma (IFN-γ), tumor
necrosis factor-alpha (TNF-γ), interleukin-6 (IL-6) and C-
reactive protein (CRP) aggravate atherosclerosis. Diabetics
typically have increased cytokine levels and are at increased
risk for coronary artery disease (CAD). Simvastatin and
pioglitazone decrease CRP levels.
Methods: In this study we compared the combined
effects of simvastatin and pioglitazone on cytokine levels
in diabetic patients with hyperlipidemia and CAD. Group
S: 16 diabetics with hyperlipidemia and CAD who were on
simvastatin 40 mg/d were started on pioglitazone 15 mg/d.
Group P: 12 diabetics who were on pioglitazone 15 mg/d
were started on simvastatin 40 mg/d. Lipid profiles and cytokine levels were evaluated bimonthly.
Results: Cytokine levels were above normal in all
subjects prior to starting simvastatin or pioglitazone.
Simvastatin treatment decreased LDL cholesterol, increased HDL, and decreased IFN-γ, TNF-γ. IL-6, and CRP.
Protocol P decreased IFN-γ, TNF-γ, IL-6, and CRP levels
and slightly but significantly decreased LDL levels. When
pioglitazone was added to treatment of patients receiving
simvastatin, cytokine level decreases greater than the sum
of individual group occurred. Simvastatin lowered LDL
and increased HDL when added to treatment of patients
receiving pioglitazone, and cytokine level decreases were
also synergistic, comparable to those observed among patients receiving simvastatin.
Conclusion: Simvastatin plus pioglitazone lowers cytokine levels synergistically, and optimizes patients’ lipid
profiles. Thus, simvastatin plus pioglitazone offers beneficial treatment for diabetics with hyperlipidemia and CAD.
Abstract #59
Achieving Target HbA1c Levels in Studies with
Inhaled Insulin (Exubera) in Type 2 Diabetes
Richard Bergenstal, MD
Objective: The present analysis describes the effectiveness of inhaled insulin (Exubera) in achieving HbA1c
<6.5% in three recent Phase III studies.
Background: The American Association of Clinical
Endocrinologists currently recommends that people with
type 2 diabetes mellitus strive for an HbA1c goal of 6.5%
or less.
Method: Data are from three open-label, randomized,
parallel-group, multicenter trials involving patients with
type 2 diabetes. Study 1 compared treatment with premeal
inhaled insulin plus a bedtime dose of Ultralente insulin (n
= 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150) over 24 weeks in
patients previously treated with insulin. Study 2 compared
premeal inhaled insulin monotherapy (n = 105), inhaled insulin in addition to existing oral agent therapy (n = 102), or
continued oral agent therapy alone (n = 102) over 12 weeks
in patients failing combination oral agents (HbA1c ≥8%).
Study 3 compared premeal inhaled insulin monotherapy (n
= 76) with rosiglitazone 4 mg BID (n = 69) over 12 weeks
in patients failing diet and exercise alone.
Results: In each of the three studies, treatment groups
demonstrated comparable HbA1c values at baseline. Only
patients with HbA1c values ≤6.5% at baseline were in
Study 1, and made up 7.7% and 3.5% of patients in the
inhaled and subcutaneous groups, respectively). However,
by study end, more patients achieved HbA1c ≤6.5% with
inhaled insulin therapy compared to other regimens in all
three studies. Study 1: inhaled insulin 28.7% versus subcutaneous insulin 17.2%. Study 2: inhaled insulin 12.2%
(in combination with oral agents) or 7.8% (monotherapy)
versus continued oral therapy 0%. Study 3: inhaled insulin
28.0% versus rosiglitazone 7.5%. Similar differences in
favor of inhaled insulin were observed using the American
Diabetes Association criterion of HbA1c <7%. In all three
studies, inhaled insulin was well tolerated and associated
with high levels of patient satisfaction.
Conclusion: Results from these three studies suggest
that inhaled insulin may be a valuable tool in helping a
wide variety of patients with type 2 diabetes reach recommended goals for glycemic control irrespective of their
current therapy. This includes patients failing to achieve
adequate control with lifestyle modification, combination
oral agents, or subcutaneous insulin therapy.
Abstract #60
Pituitary Teratoma Presenting with Diabetes Insipidus
Carolyn Narvacan-Montano, MD, and
Thelma D. Crisostomo, MD
Objective: The authors describe a case of pituitary
teratoma initially presenting with diabetes insipidus.
Background: Pituitary teratoma usually affects patients in childhood. Patients may present with diabetes
insipidus at the time of diagnosis.
Method: Case presentation.
Case report: A 22-year-old man was diagnosed with
pituitary germinoma 7 years ago, when he underwent a
33-day session of LINAC and craniotomy with tumor excision followed 6 months later by stereotactic surgery and
etoposide chemotherapy. He was readmitted two years after
chemotherapy due to diabetes insipidus, and underwent additional craniotomy with tumor excision. Biopsy revealed
malignant teratoma. The patient’s diabetes insipidus resolved following therapy with DDAVP.
Conclusion: Malignant pituitary teratoma is a rare
disease and may present with diabetes insipidus. Treatment
includes radiotherapy and surgery.
Abstract #62
Bilateral Pleural Effusions in a Patient on
Infertility Treatment
Chitra Varadachari, MD, and Dinae Dean, MD
Objective: To present a case of a patient with ovarian hyperstimulation syndrome (OHSS) who initially presented with shortness of breath and bilateral hemorrhagic
pleural effusions. A review of pertinent medical literature
is presented.
Background: OHSS is an iatrogenic complication of
infertility treatment.
Case report: A 30-year-old African-American woman
presented to the emergency department with a 1-week history of fever with chills, worsening cough with sputum
production, chest tightness with deep inspiration, and
worsening dyspnea on exertion. She was taking infertility treatment with Lo/Ovral, medroxyprogesterone acetate
and gonadotropins. Her physical exam was remarkable
for hypoxia, dullness at lung bases bilaterally (right more
than left), and the absence of ascites. Laboratory studies
revealed WBC 13,000 mm3, HgB 10.2 g/dL, and platelet
count 333,000 mm3. Her serum chemistries were unremarkable. A chest radiograph revealed bilateral pleural effusions (right more than left) that were confirmed by chest
CT scan. A urine pregnancy test revealed negative results.
Thoracentesis revealed hemorrhagic pleural effusions
bilaterally. Pleural fluid analysis revealed frankly bloody
aspirate, RBC count 45,250, WBC count 750 with N 65%,
L 33%, LDH 278, and total protein 4.1. Serum estradiol
upon admission was 3000 pg/mL. Abdominal ultrasound
ruled out ascites, and pulmonary embolism was ruled out
by pulmonary angiography. Therapy was initiated by discontinuing hormonal treatment and beginning antibiotic
treatment for community acquired pneumonia. The patient
continued to improve symptomatically and was discharged
on the 5th day of her hospitalization.
Discussion: OHSS occurs during the luteal phase or
pregnancy. It has a complex pathogenesis and can present
with various clinical manifestations secondary to changes
in hemodynamics. The spectrum of clinical symptoms of
OHSS includes ascites, hydrothorax, renal insufficiency,
and thrombotic complications. Our patient presented with
isolated pleural effusion but did not have ascites. Her case
is unique because she had bilateral, hemorrhagic pleural
effusions. Pathogenesis of this condition entails a complex
pathway involving various cytokines. Several theories have
been proposed, with the leading idea involving acute release
of VGEF and IL-6 that leads to autocrine-paracrine action
increasing vascular permeability, resulting in the observed
symptoms. Other theories involve the renin-angiotensin
system, which is evidenced by increases in renin concentrations in plasma and intrathoracic fluid. The proposed
mechanism of the associated isolated hydrothorax is development of positive intra-abdominal pressure with negative
intrathoracic pressure and diaphragmatic defects allowing
passage of fluid from the abdomen to the thorax. Patients
with isolated hydrothorax seem to have a better prognosis,
and symptoms of this condition resolve with supportive
care alone. Our patient’s symptoms improved significantly
with supportive care, as a follow-up chest radiograph 3
months later revealed resolution of hydrothorax.
Conclusion: OHSS should be in the differential
diagnosis of patients on infertility therapy who present
with isolated pulmonary symptoms. Pulmonary embolism
should be ruled out, as there is a high associated risk for
this condition among these patients. The spectrum of manifestations in OHSS is not clearly defined, and is secondary to the complex pathogenic cascade involved. Timely
management of OHSS and aggressive hemodynamic support decrease significant morbidities associated with this
condition.
Abstract #64
A Comparative Pharmacokinetic Study of Metformin
Hydrochloride Oral Solution (100 mg/mL) in Healthy
Adult Male Patients Under Fasting, Low-Fat, and
High-fat Meal Conditions
Kiran Marthak, MD
Objective: To compare single-dose oral bioavailability of metformin oral solution (100 mg/mL) (MOS) under
fasting and fed states.
Methods: This open-label, randomized, three-treatment, three-period, six-sequence, single-dose, crossover
pharmacokinetic study assessed the comparative effect of
(A) fasting, (B) a low-fat meal, and (C) a high-fat meal
on MOS bioavailability in healthy men. A single 10-mL
MOS dose given with 240 mL water was administered after
overnight fasting (≥10 hours), and 30 minutes after a lowor high-fat breakfast. Serial blood samples were collected
up to 24 hours after a single MOS dose. A 7-day washout
period was implemented between each period. Plasma
metformin concentrations were determined by a validated
high-pressure liquid chromatography method.
Results: Thirty-four men (age 19-39 years old; weight
42-75 kg) were enrolled, 33 of whom completed the study.
Ratio of least square means for Cmax, AUC0-t and AUC0-inf
were 94.6%, 116.0%, and 115.6% respectively for B versus
A; 89.4%, 112.6%, and 112.6% respectively for C versus A;
105.9%, 103.0%, and 102.7%, respectively for B versus C.
Conclusion: In the fasting and fed states, oral bioavailability of MOS was within the 80-125% FDA-ac-
ceptance criterion. The implication of these findings is that
bioavailability of MOS is unaffected by fasting versus fed
conditions.
Abstract #65
Purpura Fulminans Secondary to Propylthiouracil
Jayanthi Suppiah, MD, Aisha Nauman, MD,
Carmel Fratianni, MD, Ketan Goswami, MD, and
Romesh Khardori, MD
Objective: To report a case of purpura fulminans secondary to propylthiouracil therapy.
Background: Purpura fulminans is a severe form of
hemorrhagic infarction with skin necrosis, and is often a
fatal disease. It is commonly associated with bacterial/viral
infections and drugs, particularly treatment with propylthiouracil. Nearly forty cases of propylthiouracil-induced
vasculitis have been reported in the English literature,
though very few of these involved purpura fulminans.
Methods: Case presentation and literature review.
Case report: We describe a 23-year-old woman with
Graves’ disease diagnosed 4 yrs ago previously. This patient presenting at 15 weeks gestation, with previous treatment with methimazole changed to propylthiouracil during
her pregnancy. She presented with painful purpuric lesions
over her face, upper, and lower extremities. On admission, laboratory evaluation demonstrated pancytopenia,
elevated liver enzymes, and prolonged prothrombin time.
Laboratory values were consistent with disseminated intravascular coagulation. Cryoglobulins were not detected.
Investigation of electrolyte levels and renal function revealed normal results. A thyroid profile revealed TSH 0.13
mIU/mL, total T4 13.4μg/dL, and total T3 131 ng/dL. An
antineutrophil cytoplasmic antibody assay by immunofluorescence revealed positive results. Skin biopsy revealed
noninflammatory thrombosis of the microvasculature of the
dermis, with focal neutrophilic necrotizing vasculitis of the
small vessels at the dermosubcutaneous junction. Staining
for all immunoglobulins and complement components
revealed negative results. All blood and tissue cultures
and viral serologies likewise revealed negative findings.
Treatment of purpura fulminans consisted of anticoagulation therapy with heparin, replacement of deficient clotting
factors, and multiple skin grafting procedures. In view of
untreated hyperthyroidism posing a threat to her fetus, the
patient underwent total thyroidectomy during her second
trimester of pregnancy.
Conclusion: Striking features of this patient’s presentation include severity and rapidity of symptom onset, as
well as their temporal relationship with her hyperthyroid
state and the reintroduction of propylthiouracil. It is unclear
whether antineutrophil cytoplasmic antibody has a direct
role in the pathophysiology of propylthiouracil-induced
vasculitis and, more importantly, its role in purpura fulminans.
Abstract #67
A Patient with Graves’ Disease, Hypercalcemia and
Thymic Hyperplasia
Irma Gazeroglu, MD, Ira Katz, MD, and
Maria P. Solano, MD
Objective: To report a case of a patient with Graves’
disease, hypercalcemia and thymic hyperplasia.
Background: Hyperthyroidism can cause mild
hypercalcemia.
Method: Case report and literature review.
Case report: We report a case of a woman who
presented to the emergency room with complaints of dyspnea, fatigue, generalized weakness, and constipation of 5
months’ duration associated with weight loss of 40 pounds
and severe hypercalcemia (calcium level 15.0 mg/dL corrected for albumin). She was diagnosed with Graves’ disease and a 3.5 cm x 2.5 cm x 3 cm soft tissue mass in the
anterior mediastinum consistent with thymic hyperplasia.
Thymic hyperplasia has been associated with Graves’ disease, and hypercalcemia has been reported in association
with thymic hyperplasia as a result of increased PTH-rP.
Our patient had a low PTH-rP level, however, suggesting another mechanism for her hypercalcemia. After her
thymus was removed, her serum calcium levels remained
elevated and normalized only after RAI treatment for
Graves’ thyrotoxicosis.
Abstract #70
Osteogenesis Imperfecta in the Adult
Regina Dodis, DO, Keith Swan, MD, and
Nancy Rennert, MD
Objective: To describe a case of osteogenis imperfecta in adulthood.
Background: Bone fragility has long been an
expected part of the aging process, however, it is important
to differentiate osteopenia of aging from pathologic osteopenia. Although not routinely a part of the differential diagnosis for bone fracture in the adult, osteogenesis imperfecta
(OI) can on rare occasions be the source of dysfunction. OI
is usually inherited as an autosomal dominant trait, but can
appear as a new sporadic mutation. A diagnostic problem
lies in the differentiation of these individuals from those
with adult idiopathic osteoporosis.
Methods: Case report and literature review.
Results: We report a case of a 50-year-old Caucasian
woman with pathologic bone fractures and a medical
history significant for cervical cancer treated with total
hysterectomy at age 30. She had never been on hormone
replacement therapy and probably still produced estrogen
at the time of this evaluation. She had no family history of
known bone disease or frequent fractures. The patient first
presented clinically 21⁄2 years ago complaining of severe
leg, back, and rib pain without history of trauma. During
several ER visits for hip pain, radiological studies revealed
multiple fractures of the bilateral ribs and iliac wings as
well as the right superior and inferior pubic rami, left pubic
symphysis, and right scapula and acromion, all without
antecedent trauma. DEXA scanning revealed severe osteoporosis with spinal and femoral bone mineral densities
(BMD) T-scores of -3.8 and -3.3 SD, respectively. Physical
examination was remarkable for kyphosis, scoliosis, and
difficulty in ambulation due to pain and deformity. Her hair
was thinning, her sclera had a grey-blue hue, the gingiva
were hypertrophic with poor dentition (she lost her teeth at
age 30). No gross hearing deficits were noted. She reported
multiple points of bony tenderness over her rib cage, spine,
and pelvis, and her range of motion was limited in her hips
and shoulder secondary to pain. Laboratory evaluation was
significant for normal CBC and blood chemistry findings
(including calcium and phosphorus), and normal liver function tests, thyroid function tests, PTH level, and 24 hours
urinary calcium determination. Her alkaline phosphatase
level was modestly elevated. The patient was started on
weekly Fosamax treatment and referred for an audiogram
and physiatric evaluation. Repeat BMD determinations
were planned in 9 months.
Conclusion: An extensive literature search revealed
no similar cases of severe OI in adult patients. Recent reports in children suggest that intravenous bisphosphonates
(pamidronate) may be more effective than oral bisphosphonates in slowing progression of OI and decreasing fractures. However, hypocalcemia has emerged as a significant
side effect of bisphosphonate therapy in patients with OI
and the long term consequences of osteoclastic inhibition and low bone turnover are unknown. Cases of use of
intravenous pamidronate in adult patients similar to ours
have not been reported, and at this time, no specific recommendations have been made in the literature regarding
care of OI in adulthood. Pending results of a repeat clinical evaluation and BMD determination we may consider
therapeutic use of intravenous pamidronate in this patient.
As our patient represents an index case of OI, her family
will be screened and counseled.
Abstract #73
Parathyroid Lipoadenoma: Clinical Characteristics
and Review of 25 Cases
Lisa Chow, MD, Haitham Abu-Lebdeh, MD, and
Robert Wermers, MD
Objective: To describe the clinical and pathological
features of parathyroid lipoadenoma (PL), a rare histological variant of parathyroid adenoma.
Methods: Retrospective review of cases seen at our
institution since 1955.
Results: This case series involved 17 women (median
age 65.6) and 8 men (median age 48.3). The men were
more symptomatic and were diagnosed earlier (P = 0.05).
Twenty-one cases (84%) had hypercalcemia (mean calcium
10.7 mg/dL) but only six patients (38%) demonstrated hypercalcemia-related symptoms. Preoperative localization
with neck ultrasound and nuclear imaging demonstrated
comparable sensitivity (50%). Twenty-two patients (88%)
underwent surgery. Average weight of the tumor was 1041
grams (SD = 2083 grams). Only one (4%) adenoma was
located ectopically. Five patients (20%) had additional
foci of parathyroid pathology. Correlations between PL
weight, PTH levels, and calcium levels were not statistically significant.
Conclusion: This is the largest case review describing
clinical characteristics of parathyroid PL. Given the high
incidence (20%) of coexisting parathyroid pathology and
poor imaging results, parathyroid PL may be difficult to
diagnose and treat.
Abstract #74
Pituitary Carcinoma: Long-term Remission
with Chemotherapy
Anne M. Rosenberg, MD, William F. Young, Jr., MD,
Ronald L. Richardson, MD, and
Bernd W. Scheithauer, MD
Objective: To compare outcomes of patients treated
with traditional therapies to the outcomes of patients treated with the chemotherapeutic regimen cyclophosphamide,
vincristine, and dacarbazine (CVD).
Background: Pituitary carcinoma is a rare adenohypophysial tumor with a poor prognosis. Traditional
therapies, such as surgical resection, radiation therapy and
dopamine agonists are generally palliative in nature. The
use of the CVD has not been described previously in the
literature.
Methods: A chart and literature review was performed.
Results: The fifteen patients previously reported in
the literature were treated most commonly with surgical
resection followed by radiation therapy and dopamine agonists. Over 60% of these patients died of metastatic disease
within one year of diagnosis. The first patient treated with
CVD therapy presented with an ACTH-producing pituitary
tumor metastatic to the liver. She underwent resection of
the liver lesions followed by CVD. In the subsequent 5
years, her serum ACTH concentration has remained within
normal range, the liver metastasis has not recurred, and the
pituitary lesion has been stable in size. The second patient
treated with CVD presented with a gonadotropin-producing tumor and skeletal metastasis. Fifteen months after
completing her final cycle of chemotherapy, no new metastatic lesions have appeared.
Conclusion: CVD chemotherapy is the first treatment
modality that has had a significant antitumor effect in patients with pituitary carcinoma.
Abstract #75
Pseudohypoparathyroidism Type 1b During Pregnancy
Daniel K. Short, MD, PhD, and Bart L. Clarke, MD
Objective: To educate clinicians on management of
pseudohypoparathyroidism type 1b during pregnancy.
Methods: Case presentation and literature review.
Results: A 27-year-old woman presented for management of pseudohypoparathyroidism type 1b early in pregnancy. Her prepregnancy ergocalciferol treatment (50,000
IU/week) was stopped as it is contraindicated in pregnancy.
Prenatal multivitamin therapy was begun, and her prior
calcium supplement was continued. She subsequently delivered a fullterm healthy infant without complications. Her
serum PTH level decreased significantly during pregnancy,
and after delivery, her PTH level increased to her prepregnancy value despite continued use of her prenatal vitamin.
Conclusion: Previously published case reports have
shown both worsening and improvement of pseudohypoparathyroidism during pregnancy. Patients with this condition should be monitored closely for hypocalcemia during
pregnancy.
Abstract #76
Comparison of the Ability of New and the Older
Criteria for Impaired Fasting Glucose to Predict
Coronary Disease or Coronary Events
Jeannemarie D. Hinkle, MD, and William B. Kruyer, MD
Background: The new ADA criteria for impaired
fasting glucose (IFG) defines this term to include patients
with fasting glucose of 100-110 mg/dL. Previous studies
have shown that impaired fasting glucose is predictive of
cardiovascular disease and events. It is not known whether
the new criterion for IFG is equally predictive.
Objective: To determine whether fasting glucose levels of 100-110 mg/dL are predictive of coronary anatomy
and events.
Methods: A database of 1487 nondiabetic asymptomatic male military aviators with occupational coronary
angiography and long-term follow-up (mean follow-up
14.2 years) was queried for fasting glucose level at the
time of angiography. Subjects were divided into 3 groups:
(A) those with fasting blood glucose <100mg/dL, (B) those
with fasting blood glucose ≥100 and ≤110mg/dL, and (C)
those with fasting blood glucose >110mg/dL. Coronary
disease (CAD) was defined as coronary artery stenosis of
20% or greater. Cardiac events included cardiac death, nonfatal myocardial infarction, and coronary revascularization
or angina.
Results: Fasting glucose data was available for 1439/
1487 (97%) of subjects. There were 687 subjects in group
A, 567 in group B, and 183 in group C. The prevalence of
CAD was 21% higher in group B compared to group A (P
<0.05), but 12.5% lower than group C (P <0.05). No difference was noted in the frequency of cardiac events over
follow-up between groups A and B, but those with fasting
glucose >110mg/dL exhibited a higher frequency of cardiac
events (P <0.05), and almost double the rate of all-cause
mortality (P <0.005%), compared to the other groups.
Conclusion: In an asymptomatic population undergoing occupational angiography, impaired fasting glucose of
100-110mg/dL identified a group with increased prevalence
of coronary disease, but no higher rate of cardiac events or
death compared to individuals with normal fasting glucose
levels.
serum glucose levels was lower and nadir serum glucose
levels were higher when acarbose was administered premeal. Long-term follow-up confirms sustained resolution
of symptoms on a maintenance regimen of acarbose.
Conclusion: Acarbose, an agent that delays dietary
carbohydrate absorption, offers effective treatment for patients with severe alimentary hypoglycemia.
Abstract #77
Two Tumors Equals A Triad: A Case of Carney’s Triad
Acarbose Ameliorates Alimentary Hypoglycemia:
Case Report and Literature Review
Cacia V. Soares-Welch, MD, Geoffrey B. Thompson, MD,
J. Aidan Carney, MD, PhD, and William F. Young, MD
Candi Nobles-James, MD, Anjanette Tan, MD, and
Stephen A. Brietzke, MD
Objective: To alert clinicians to the possibility of the
presence of a rare syndrome when a patient presents clinically with paraganglioma, gastric stromal tumor, or pulmonary chondroma.
Methods: Case presentation and review of the
literature.
Results: A 23-year-old woman was evaluated for recurrent nausea and vomiting. Multiple pulmonary lesions
and polyploid gastric masses were identified. Invasive diagnostic procedures concluded that these were pulmonary
chondromas and gastric stromal tumors, respectively. Tests
for paraganglioma were negative, and the patient was diagnosed with incomplete expression of Carney’s triad. She
Objective: To examine the efficacy of a well-tolerated
treatment for severe alimentary hypoglycemia.
Methods: An 83-year-old man presented with severe
neuroglycopenic postprandial hypoglycemia, in the context
of end stage renal disease and remote partial gastrectomy.
Three-hour mixed meal tolerance test measuring serum
glucose, insulin, and C-peptide was accomplished on
separate days with (Day 1) or without (Day 2) preprandial
acarbose administration.
Results: The area under the curve for insulin and peak
Abstract #78
Late Recurrence of Painless Sporadic Subacute
Thyroiditis after Discontinuation of Levothyroxine
Anjanette S. Tan, MD
Objective: To describe a case of recurrent thyrotoxic
subacute thyroiditis (SAT) after discontinuation of chronic
levothyroxine therapy
Methods: A 47-year-old university professor was
treated for painless SAT five years previously. He took levothyroxine (LT4) for nearly five years, until stopping it on
his own. He felt entirely well until five weeks later, when
he developed diaphoresis, palpitations, tremor, and reduced
stamina. Proptosis, goiter, and thyroidal tenderness were
absent. Serum TSH was suppressed, free T4 was elevated,
antithyroid peroxidase and thyroid stimulating antibody
titers were normal, and radioiodine uptake was low.
Results: Thyrotoxicosis resolved after six weeks, and
LT4 therapy was resumed when hypothyroidism was biochemically confirmed.
Conclusion: Thyrotoxic painless SAT can be triggered (rarely) by discontinuation of maintenance levothyroxine therapy, through a yet unknown mechanism.
Abstract #79
is currently under surveillance for recurrence of the gastric
stromal tumor and development of paraganglioma.
Conclusion: The triad of gastric stromal tumor,
pulmonary chondroma, and paraganglioma, known as
Carney’s triad, must be considered in a patient who presents with any of these tumors. The triad is a chronic, persistent, indolent disease, the main threat of which comes from
metastatic gastric sarcomas and, occasionally, malignant
paraganglioma. Patients benefit from early identification
and treatment of tumors in this disorder.
Abstract #80
Occult Medullary Carcinoma Presenting with a
Large Mediastinal Mass
Leena Singh, MD, PhD, Ashraf Khan, MD,
Neil Aronin, MD, FACP, FACE, Nilima Patwardhan, MD,
and Francis Podbielski, MD
Objective: To describe a case of occult medullary thyroid carcinoma (MTC) presenting with a large mediastinal
mass.
Methods: We present a case report describing clinical, laboratory, and radiologic assessment of a male patient
with occult MTC and a large mediastinal mass.
Results: A 67-year-old man, noted during rotator cuff
surgery to have an enlarged anterior cervical lymph node,
underwent neck and chest CT scans which revealed multiple
enlarged cervical lymph nodes and a mediastinal mass. An
excisional biopsy of the lymph node was positive for MTC
and immunostained positively for the presence of amyloid,
chromogranin and calcitonin. The patient underwent 24-hr
urine collection, which revealed normal catecholamine,
VMA, and metanephrine levels. He also demonstrated normal calcium, phosphorus, and iPTH levels and a calcitonin
level of 23,390 pg/mL. He underwent total thyroidectomy,
sternotomy for resection of the mediastinal mass, and bilateral lymph node dissection. Pathologic evaluation revealed
a 1-2 mm foci of MTC in the right lobe and microscopic
foci of MTC in the left lobe of the thyroid. This assessment
also revealed a 11 cm x 9.5 cm x 4 cm mediastinal mass that
was positive for the presence of MTC, with MTC involvement of 3 of 11 evaluated lymph nodes.
Conclusion: Previous reports exist of lymph node
metastases in patients with micro-MTC. This is an interesting case of occult MTC in an asymptomatic man presenting
with lymphadenopathy and a large mediastinal metastasis.
Abstract #81
Osteoporosis Screening by Primary Care Physicians in
an Inner City Teaching Hospital in Brooklyn
Vaidehi Kaza, MD, Eric A. Jaffe, MD,
Gerald Posner, MD, Maria Ferandez-Renedo, MD, and
Zewge S. Deribe, MD
Objective: To determine whether women in an inner
city area over the age of 65 years (W>65 yrs) are appropriately counseled and screened for osteoporosis (OP) per
the U.S. Preventive Services Task Force (USPSTF) guidelines.
Background: OP is a major public health threat
for more than 28 million Americans, 80% of whom are
women. However, it is estimated that OP is under-reported
by 60% among White women aged more than 80 years,
and 66% among elderly African American Women (AAW).
AAW may have different predisposing factors for OP,
and are more likely than white women to die following a
hip fracture. Diseases such as sickle cell anemia and systemic lupus erythematosus are more prevalent among the
African-American population, and are linked to development of OP.
Methods: During a two-month period, (August and
September 2003) women over 65 years of age coming to an
inner city primary care medical clinic were given a questionnaire that based on USPSTF recommendations. The
survey was given to them in the waiting area and primary
care physicians (PCPs) did not know about the survey.
Results: Responses of 149 women were evaluated.
The sample consisted of minority women, predominantly
AAW. The mean age of the group was 74.9 years with a
standard deviation of 7.7 years. Of the 149 women, 90
(60.4%) were educated about OP screening and prevention; 85 women (57%) were asked about history of fractures in the past; and only 70 (47%) were offered bone
densitometry.
Yes (%)
No (%)
Educated by PCP about OP
Hx of fracture questioned
DEXA offered
90(60.4%)
85(57%)
70(47%)
59(39.7%)
64(43%)
79(53%)
Conclusion: Our data show that the level of OP
education and screening by primary care physicians in
an inner city area is inadequate. It is increasingly necessary to promote awareness among PCPs about the USPTF
and National Osteoporosis Foundation recommendations.
Larger studies should be done to assess the level of compliance of PCPs with national osteoporoisis prevention guidelines to effectively screen for OP and to prevent its serious
consequences by timely treatment.
Abstract #82
Over-the-Counter Induced Hypoglycemia
Antoine Makdissi, MD, and Jennifer Wojtowicz, DO
Objective: To present a case of hypoglycemia induced
by an over-the-counter menopause preparation containing
chromium.
Methods: Clinical case presentation and literature
review.
Results: A 55-year-old white female presented with
episodes of mild confusion, hunger, and paresthesiae that
resolved after eating. These episodes occurred mainly
mid- to late-morning. The patient underwent a 100 gm oral
glucose tolerance test that revealed fasting blood glucose
of 70 mg/dL, one-hour blood glucose of 95 mg/dL, and
three-hour blood glucose of 33 mg/dL. The patient then experienced symptoms similar to her episodes at home. It was
recommended that the patient make dietary changes. She
began to eat small, frequent meals that included protein and
avoided simple sugars. Her symptoms improved slightly,
though hypoglycemic symptoms still occurred mid- to latemorning almost daily. Upon further review it was discovered that this patient was taking 2 to 3 pills every morning
of an over-the-counter menopause supplement containing
chromium 200 μg, and had taken the preparation the morning of her oral glucose test. She was instructed to stop the
supplement, and reported no further symptoms.
Conclusion: Chromium has been shown in several
studies to lower postprandial blood glucose. This case illustrates the importance of inquiring about all over-thecounter medications patients are taking, and determining
their composition.
Abstract #83
Hypercalcemia Unresponsive to Intravenous
Bisphosphonates: More than One Cause?
Anuj Bhargava, MD
An 87-year-old woman with a 10-year history of
chronic lymphocytic leukemia (CLL) was admitted to hospital because of weakness and worsening hypercalcemia.
Her calcium levels ranged between 11.2 and 11.4 mg/dL for
4 years, but had increased further 3 months previously. Her
blood calcium levels did not diminish on various regimens
of intravenous bisphosphonates given empirically by her
internist as frequently as every 7 days. In hospital, intact
PTH was elevated at 245 pg/mL, with serum calcium of
13.1. Biopsy of enlarged axillary lymph nodes revealed
large cell lymphoma, suggesting Richter’s transformation
of CLL. The patient’s 25-hydroxyvitamin D level was sup-
pressed at 7 ng/mL (normal range 20-57 ng/mL), while
her 1,25-dihydroxyvitamin D level was elevated at 126
pg/mol (15-75 pg/mol). Her blood calcium level normalized after parathyroidectomy but increased again to 12.3
mg/dL shortly afterward. On the fourth postoperative day
her 1,25-dihydroxyvitamin D level remained high at 92
pg/mol. CHOP chemotherapy, pamidronate, and high dose
prednisone finally led to normalization of her calcium
levels.
Discussion: This patient likely had hypercalcemia due
to longstanding hyperparathyroidism that worsened after
Richter’s transformation of CLL. Adequate and longlasting treatment required definitive treatment of both causes.
To the author’s knowledge, this is the first reported case of
hyperparathyroidism complicated by Richter’s transformation, presenting as severe unresponsive hypercalcemia.
Conclusion: Failure of multiple doses of bisphosphonates to correct hypercalcemia should heighten suspicion
for more than one cause of hypercalcemia.
Abstract #84
Depression and a History of Excessive Alcohol Intake
Are Main Determinants for Poor Adherence to
Treatment in Mexican Type 2 Diabetic Patients
Israel Lerman, MD, Enrique Caballero, MD,
Francisco Gómez-Pérez, Sergio Hernández, MD,
Liliana Lozano, MD, and Antonio Villa, MD
Objective: To examine the relationship between demographic, clinical, and psychosocial variables and diabetes selfcare management among Mexican type 2 diabetic
patients.
Methods: Cross sectional study of 176 consecutive
type 2 diabetic patients aged 30 to 75 years attending a tertiary healthcare center in Mexico City. A brief medical history was obtained and clinically validated questionnaires
were completed.
Results: Most patients were women (63%), with a
mean age ± SD of 55 ± 11 years, a mean duration of diabetes of 12 ± 8 years and a mean HbA1c level of 9.0 ± 2.0%.
Adherence to the three main recommendations (meal plan,
exercise, and medication) was observed in 26% of patients.
Poor adherence to at least 2 or 3 of the main recommendations of diabetes treatment was associated with a depressive
state (OR 2.38, 95% CI 1.1-4.9, P <0.01) a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03)
and not monitoring blood glucose levels (OR 2.94, 95% CI
1.3-6.1, P = 0.008).
Conclusion: Lack of adherence to diabetes care recommendations is frequently observed in Mexican type 2 diabetic patients. It is vitally important that depression be identified and treated effectively among people with diabetes.
Abstract #85
Abstract #86
Ultrasound-guided Laser Thermal Ablation of
Parathyroid Adenomas
Gatifloxacin-induced Hypoglycemia
Roberto Valcavi, MD, Andrea Frasoldati, MD, PhD,
Angelo Bertani, MD, and Marialaura Pesenti, MD
Sendil Krishnan, MD, Hank Freedy, PharmD,
Jann Johnston, MD, Melissa Ray, PharmD, and
Raymond Eder, PharmD
Objectives and Background: Parathyroidectomy is
commonly considered the only curative treatment for primary hyperparathyroidism (pHPT). This excludes hyperparathyroid patients at high surgical risk from a definitive
cure for this condition. We tested laser thermal ablation
(LTA) in three hyperparathyroid patients considered unsuitable for surgery. LTA causes coagulative tissue necrosis
leading to eventual fibrosis (liver, thyroid).
Methods: In all patients, parathyroid (PT) adenomas were localized by neck US and sestamibi scinti scan.
Localization was confirmed by ultrasound (US)-guided
fine needle aspiration biopsy findings of PTH levels ≥ 1000
pg/mL in the needle washouts. Parathyroid volume (mean
± SD) was 0.67 ± 0.28 mL. LTA was performed under US
guidance using as a laser source a Nd-YAG operating at
1064 μm (DEKA-MELA; Florence, Italy). Serum PTH
and calcium measurements and US examinations were performed at baseline and 1, 3, and 6 months after LTA. In case
of an insufficient (<50%) decrease of the lesion volume or
persistent pHPT, LTA treatment was repeated.
Results: 5 LTA treatment sessions were performed
(output power = 2 W, mean energy delivered = 2668 J).
After 6 months, a 71.4% mean decrease of parathyroid
volume was observed (final volume = 0.17 ± 0.04 mL). US
pattern of parathyroid adenomas changed from hypoechoic
to inhomogeneous/hyperechoic due to necrosis and fibrosis. After treatment, mean serum calcium and PTH levels
dropped (see Table). LTA treatment was well tolerated.
Patient number 1 developed transitory dysphonia not associated with permanent vocal cord damage.
Objective: To identify the incidence of hypoglycemia
among patients receiving gatifloxacin.
Methods: A retrospective review of 152 episodes
of hypoglycemia between July 2002 and February 2003
among patients over sixty years of age, occurring within 24
hours after receiving gatifloxacin.
Results: Our analysis identified at least 24 potential
instances of gatifloxicin-associated hypoglycemia, an incidence of 15% (12% in diabetics). Fifty percent of the 24
cases identified occurred among type 2 diabetics treated
with oral agents only. Twenty-five percent of cases were
among type 2 diabetics treated with insulin +/- an oral
agent (an insulin sensitizer or sulfonylurea). An additional
twenty-five percent of subjects had no history of diabetes.
In this last group, the average creatinine clearance was 24
mL/minute, and average BMI was 19. In less than one-third
of cases identified the observed hypoglycemia was attributed to the effects of gatifloxacin.
Conclusion: Studies by the manufacturer show the
occurrence of hypoglycemia-induced gatifloxacin at 0.1%.
Previous reports are isolated, but our review of the last
nine months alone suggests a much higher incidence of
this side effect. Patients with type 2 diabetes appear to be
particularly at risk, though cases do occur among nondiabetic patients. Advanced age, poor nutrition, and decreased
creatinine clearance may pose additional risk of hypoglycemia in these patients. As more physicians become informed
of these risks, increased surveillance of gatifloxacin will
likely lead to decreased episodes of hypoglycemia among
susceptible patients.
Time
interval
Baseline
Calcium
(mg/dL)
1-month
Calcium
(mg/dL)
12.7
PTH
(pg/
mL)
310
Patient 2
11.5
Patient 3*
10.9
Patient 1
3-months
Calcium
(mg/dL)
11.2
PTH
(pg/
mL)
270
212
9.8
115
9.9
6-months
Calcium
(mg/dL)
10.0
PTH
(pg/
mol)
115
10.5
PTH
(pg/
mL)
115
115
9.2
95
9.6
63
80
9.4
52
9.6
58
*Number of LTA sessions; normal serum PTH: 8 - 75 pg/mL; normal serum
calcium: 8.5 - 10.5 mg/dL
Conclusion: LTA is a promising technique for treatment of primary hyperparathyroidism. Technical details
(e.g. number of fibers used, amount of energy delivered
per LTA session) are currently under study to optimize efficacy of this technique. If LTA proves curative and safe in
wider studies it may offer an alternative option to surgery
in patients with pHPT.
Abstract #87
Long-Term Survival in a Patient with MEN2B and
Metastatic Medullary Thyroid Carcinoma
Claudia Panzer, MD, Robert Beazley, Stuart Chipkin, and
Susanne Ebner
Objective: To describe the prolonged survival of a patient with multiple endocrine neoplasia type 2B (MEN2B),
hepatic metastases from thyroid medullary carcinoma, and
recurrence of pheochromocytoma.
Methods: We review the clinical findings, laboratory data and results of imaging studies in our patient over
the course of 12 years. In addition, we summarize previ-
ously reported cases of prolonged survival among MEN2B
patients.
Results: In 1992, a 25-year-old Puerto Rican woman
presented to the emergency department with a 10-year
history of chronic constipation. Her physical exam was
remarkable for marfanoid body habitus, neuromas of the
tongue and conjunctiva, and bilateral thyroid nodules. An
abdominal radiograph revealed megacolon, and further
workup revealed medullary thyroid carcinoma with esophageal and tracheal invasion, hepatic metastatic lesions, and
bilateral pheochromocytomas. The patient was subsequently treated by modified radical neck dissection and bilateral
adrenalectomy. She did well over the next 10 years and
even became pregnant (amniocentesis was negative for the
RET mutation). She continued to have stable, but elevated
levels of CEA and calcitonin with unchanged hepatic metastases. Ten years after her initial presentation the patient
became symptomatic with frequent palpitations, and urine
and plasma levels of metanephrines were elevated. Abdominal MRI remained negative, but MIBG revealed recurrent
pheochromocytoma in the left adrenal bed.
Conclusion: This case report does not only present a
classic case of MEN2B, but also adds to the evidence that
the natural course of medullary thyroid cancer in MEN2B
may not be as aggressive as previously thought. It also
underscores the importance of long-term monitoring for
recurrent pheochromocytoma in all patients.
Abstract #88
temperature of 37.2 °C. There were no significant eye, skin,
hair, or nail findings. She had no enlargement of the thyroid
gland, and reported pain upon abdominal palpation. A fine
tremor was noted in her hands, and her reflexes were symmetric and brisk. She was medicated with ranitidine and
dimenhydrinate with no effect. Results of abdominal ultrasound and endoscopy were normal, as were serum levels of
glucose, creatinine, amylase, electrolytes, and aminotransferases. Her thyrotropin level was 0.002 μIU/dL (normal
range 0.3 to 5.0 μIU/dL), free thyroxine was 4.75 ng/dL
(0.8 to 2.0 ng/dL), and triiodothyronine was 516 ng/dL
(86 to 190ng/dL). Radionuclide imaging showed a diffuse
hyperfunctioning thyroid gland. Therapy was begun with
methimazole 40 mg once daily and propanolol 40 mg three
times daily, which decreased her clinical symptoms. She
was dismissed from the hospital ten days later without any
complaints, and was subsequently lost to follow up.
Conclusion: Severe vomiting can be the initial symptom of hyperthyroidism and disappears after successful
treatment with methimazole. Vomiting in thyrotoxicosis
is a well recognized but unusual phenomenon, and it has
been postulated that this is due to direct action of thyroid
hormone on the chemoreceptor trigger zone.
Abstract #89
Exogenous Hypertestosteronemia from Multiple
Sources in a Woman
Geoffrey Redmond, MD
Thyrotoxic Vomiting: An Unrecognized
Symptom of Thyrotoxicosis
Sandro Corigliano, MD
Objective: To describe intractable vomiting and abdominal pain as initial complaints in a patient with hyperthyroidism.
medical records and conducted a review of the pertinent
medical literature.
Results: A 59-year-old woman came to the emergency department complaining of a 3-week history of weight
loss (about ten kilograms in the last month), epigastric
pain, nausea, and severe vomiting. Her personal history
was unremarkable, and she had no family history of hyperthyroidism. Physical examination revealed blood pressure
of 100/60 mmHg, heart rate of 102 beats/minute, and body
Objective: To report female hyperandrogenism from
exogenous sources. Use of testosterone by women has been
advocated for enhancement of libido. Adverse effects include seborrhea, acne, hirsutism, and androgenic alopecia.
Methods: Laboratory assay of testosterone.
Results: This 54-year-old Caucasian woman presented for evaluation of alopecia that had existed for the
previous 6 years. She had been using oral DHEA and a
compounded cream containing testosterone. Endocrine
evaluation revealed a total testosterone (TT) level of 249
ng/dL (normal adult female range 12-72 ng/dL). She discontinued the cream and DHEA, but TT remained elevated
at 124 ng/dL. Further history revealed that her husband had
been using testosterone gel for hypogonadism. Upon her
husband’s discontinuation of the gel, the patient’s testosterone level fell to 38 ng/dL.
Conclusion: A variety of sources can cause exogenous hypertestosteronemia in women.
Abstract #90
Epinephrine-Secreting Pheochromocytoma
Presenting with Near-syncope and Hypotension
Evans R. Fernández, MD, Aaron Chidakel, MD,
Nicholas V. Papapietro, MD, and
Adrienne M. Fleckman, MD
Objective: To describe a patient presenting with nearsyncope and hypotension (HTN) in the setting of an adrenal
epinephrine-producing pheochromocytoma.
Methods: We present a case report with surgical and
pathologic findings, and review medical literature regarding epinephrine-secreting pheochromocytoma associated
with hypotension.
Results: A 64-year-old woman had multiple nearsyncopal attacks unrelated to postural change, for over a
year. Results of echocardiography, exercise stress testing,
passive upright tilt testing, and Holter monitoring were all
unremarkable. Her clinical course was complicated by a
myocardial infarction. While in cardiac rehabilitation, she
experienced a near-syncopal episode associated with severe
HTN. She was hospitalized as a consequence, and during
hospitalization experienced a documented episode of HTN
without orthostasis. Additional evaluation established a
diagnosis of an epinephrine-secreting pheochromocytoma.
She subsequently underwent laparoscopic removal of the
tumor, which led to resolution of all symptoms.
Conclusion: Manifestations of pheochromocytoma
may mimic many conditions, resulting in misdiagnoses and
improper treatment. Epinephrine-secreting pheochromocytoma is a rare but important underlying etiology of nonorthostatic HTN manifestation. Finally, this report suggests
that syncope may be secondary to isolated HTN caused by
high epinephrine levels triggering vasodilation via effects
on peripheral β-2-receptors.
Abstract #91
Comparison of Cord Blood Insulin in Large-forGestational-Age Infants and Appropriate-for-Age
Filipino Infants of Nondiabetic Mothers: A Pilot Study
Florence M. Amorado-Santos, MD,
Maria Honolina S. Gomez, MD, FACE,
Maria Victoria R. Olivares, MD, and
Zayda N. Gamilla, MD, FPOGS
Objectives: (A) To compare the demographic profile
of Filipino mothers with large-for-gestational-age (LGA)
and average-for-gestational-age (AGA) babies following
nondiabetic pregnancies; (B) to compare cord blood insulin levels in LGA and AGA Filipino infants of nondiabetic
mothers, and (C) to evaluate the association between hyperinsulinemia and macrosomia among Filipino infants.
Background: The Pederson hypothesis states that
excessive fetal growth is a result of maternal hyperglycemia leading to excessive fetal hyperinsulinism as the
mechanism responsible for the birth of LGA and macrosomic babies in diabetic pregnancies. There are, however,
LGA babies born of mothers without hyperglycemia or
diabetes mellitus. This study explores hyperinsulinism in
LGA babies whose mothers are nondiabetic, and evaluates
related factors contributing to the birth of large babies in
the Filipino population.
Methods: Subjects comprised consecutive infants of
term gestation (37-42 completed weeks) who satisfy criteria for LGA (study group) and AGA (control group), whose
mothers had regular prenatal checkups and did not develop
gestational diabetes. Mixed arteriovenous blood was obtained from the triple-clamped umbilical cord at delivery
and quantitatively assayed for insulin. Descriptive analysis
used mean values (standard deviation) and proportion to
analyze demographic data and baseline characteristics of
LGA and AGA babies. Student’s t test was used to compare
mean values of cord blood insulin. Odds ratio were calculated to evaluate the association between body size and
hyperinsulinism.
Results: Ten LGA babies and 12 AGA babies were
identified as subjects. Maternal height and birth length and
head circumference of the babies were significantly different between AGA and LGA infants. Four LGA infants were
hyperinsulinemic at birth. Mean cord blood insulin levels
among LGA babies were higher than those noted among
AGA babies, though this difference did not reach statistical
significance. Odds ratio calculations demonstrated a 7.33
chance of LGA babies having hyperinsulinemia.
Conclusion: A subset of LGA babies from nondiabetic
pregnancies have hyperinsulinemia. Maternal height and
infant birth length and head circumference are statistically
significant indicators of increased size in this population of
infants.
Abstract #92
True Hermaphroditism: An Intersex Infant’s
Journey to Adulthood
Proceso Marc F. Udarbe, MD, and
Maria Honolina S. Gomez, MD, FACE
Objective: Presenting a case report of a 21-year-old
true hermaphrodite Filipino man with feminization as a
consequence of subtherapeutic management.
Methods: Clinical case presentation.
Results: A 21-year-old Filipino man with gynecomastia, tall stature, and a moderately feminized and eunuchoid
appearance was referred for evaluation and continuous
care. The patient was born with ambiguous genitalia and
had been reared as a male. Karyotypic analysis revealed
46 XY chromosomes. No medical or surgical intervention was done until age 13, when he underwent surgery.
Intraoperative findings at that time included a uterus, two
fallopian tubes, and bilateral cryptorchidism. Hysterectomy
was performed along with bilateral oophorectomy and repair of cryptorchidism and hypospadia. Pathologic evaluation revealed atrophic changes, testicular, epididymal, and
fallopian tissue, weakly proliferative endometrium, and
chronic endocervicitis, findings consistent with a diagnosis
of true hermaphroditism. This patient was then started on
testosterone undecanoate orally. Secondary sexual characteristics failed to develop, and the patient developed gynecomastia and tall stature. He subsequently experienced
feminization and questioned his masculine gender identity.
Physical examination revealed a tall phenotypic man, 1.88
meters (> +2SD) in height, weighing 94 kg, BMI 26.5,
with Tanner stage II breast development, micropenis, impalpable testis, sparse pubic hair, and absent axillary hair.
Laboratory evaluation revealed hypergonadotropic hypogonadism, osteopenia, and open epiphyseal lines. Pelvic
ultrasound revealed a cervix. He was treated with testosterone 200 mg IM once monthly. After 6 months of treatment,
the patient noted increased penis size, increased pubic and
body hair, presence of erectile and ejaculatory capabilities,
and a decrease in breast size.
Conclusion: A 21-year-old Filipino man, a true hermaphrodite, presented with gynecomastia and tall stature
due to inadequate testosterone replacement, preventing
normal sexual differentiation. He was successfully treated
with intramuscular testosterone.
Abstract #93
A Case of Tall Stature and Gonadal Dysgenesis:
Rare Jeopardy in an Adult
Mary Flor R. Gafate, MD, and
Maria Honolina S. Gomez, MD, FACE
Objective: To report a rare case of 46XX pure gonadal dysgenesis diagnosed in adulthood in a 21-year-old
Filipina with tall stature, primary amenorrhea, and sexual
infantilism.
Methods: A case report of 46XX pure gonadal
dysgenesis is presented, and related medical literature is
reviewed.
Results: A Filipino woman was born full term to
healthy, nonconsanguineous parents after an uncomplicated pregnancy. Birth size was reportedly normal, and her developmental course was unremarkable until age 13, when
she became noticeably tall for her age, measuring 175 cm
(> +2SD based on the International Reference Standard for
Filipinos). She subsequently exhibited persistent amenorrhea and sexual infantilism, and sought endocrinologic consult at age 21. Physical examination revealed delayed puberty (breast Tanner stage 2; pubic hair Tanner stage 2) with
a height of 187 cm. Her familial target height was 165 cm
(mother’s height was 167 cm while the father’s height was
172 cm), and heights of her two siblings were appropriate
for age. Endocrine studies revealed elevated gonadotropin
levels (FSH 29 IU/L and LH 21 IU/L). Growth hormone,
thyroid function test, prolactin, and cortisol evaluations
were within normal limits. A cranial CT scan revealed a
normal sella turcica with calcification of the pineal gland.
Findings of an MRI of the brain were normal. Karyotyping
and chromosomal analysis were consistent with 46XX, and
transvaginal ultrasonography revealed absence of ovaries.
Radiograph of the wrist identified epiphyseal fusion. She
was treated with hormone replacement therapy with estradiol-norethisterone.
Conclusion: Gonadal estrogens exert a maturational
effect on skeletal tissues. Tall stature in this patient was
secondary to estrogen deficiency due to gonadal dysgenesis
that became obvious during puberty. As this patient’s condition was not diagnosed early, there was sustained growth
despite tall stature. Patients with this rare condition benefit
from early recognition and treatment.
Abstract #94
Sporadic Medullary Thyroid Carcinoma:
Waterloo for the Unsuspecting Clinician
Mary Flor R. Gafate, MD, Edgardo G. Cabrera, MD, FPCS,
and Maria Honolina S. Gomez, MD, FACE
Objective: To report a case of sporadic medullary thyroid carcinoma in a 28-year-old Filipina.
Methods: We present a case report of a young Filipina
with sporadic medullary thyroid cancer (MTC). Reported
cases in medical literature were reviewed.
Results: A 28-year-old Filipina noted a right thyroid
nodule three years prior to consultation but demonstrated
with no symptoms of thyrotoxicosis during this time.
Thyroid function tests were normal and thyroid ultrasound
revealed a hypoechoic nodule, 2.3 cm x 1.4 cm x 1.4 cm,
in the upper pole of the right lobe of the thyroid gland.
Fine needle aspiration was performed with cytopathologic
confirmation of a toxic nodule versus a follicular tumor. A
subsequent thyroid scan revealed a hypofunctional nodule
on the right lobe of the thyroid. The patient was treated
with levothyroxine 150 μg/day, and experienced no changes until two years later when further enlargement of her
thyroid nodule was noted. She then underwent near-total
thyroidectomy. Rush frozen section cytopathologic evalu-
ation revealed a malignant tumor, with diagnosis favoring
poorly differentiated follicular carcinoma versus MTC.
Immunohistochemistry of tumor tissue was performed
upon endocrinologic referral, and calcitonin immunostaining revealed tumor cells with diffuse cytoplasmic positivity
for calcitonin. Thyroglobulin immunostaining and evaluation for multiple endocrine neoplasia were performed.
Laboratory analyses revealed normal levels of urine
metanephrines, ionized calcium, and parathyroid hormone.
Serum calcitonin and CEA levels were elevated postoperatively at 594 ng/mL and 184.0 ng/mL, respectively.
The patient subsequently underwent radical neck dissection for a palpable cervical lymph node, with subsequent
histopathologic confirmation of metastatic MTC involving
8 of 21 lymph nodes. The sternocleidomastoid muscle, external jugular vein, nerve, and parotid gland were free of
metastatic involvement. CT scan of the neck, chest, and abdomen were unremarkable. The patient was subsequently
maintained on levothyroxine 300 μg/day. Genetic testing
of her parents and siblings revealed no mutations in exons
609, 611, 618, 620, and 634 of the RET protooncogene.
Three years later, her CEA level was normal, though her
serum calcitonin level remained slightly elevated.
Conclusion: MTC accounts for 3.5-10% of thyroid
malignancies, of which approximately 75% are sporadic.
Because of variations in histopathologic features of MTC,
a high index of suspicion is necessary for early detection of
this thyroid malignancy.
Abstract #95
Diabetes Mellitus Remission after Multiple Tumor
Resection in Pheochromocytoma
Simona Fica, Ana Maria Stefanescu, Carmen Barbu,
Dana Terzea, M. Coculescu, and T. Ciprut
Objective: To describe a case of remission of diabetes
mellitus after multiple tumor resection in a patient with
pheochromocytoma.
Background: Decreased insulin sensitivity is the main
cause for pheochromocytoma-associated diabetes mellitus,
and insulin-dependent diabetes mellitus may be completely
reversed by appropriate treatment of pheochromocytoma.
Case report: A 2-year history of adult-onset diabetes
mellitus (maximum blood glucose level of 360 mg/dL), occurred in a patient with hypertension of 5 years’ duration.
High urinary normetanephrine levels of 3000 µg/24 h were
noted (urinary metanephrine = 163 µg/24 h), and a CT scan
revealed a left adrenal mass of 0.8 cm x 0.6 cm. Findings
of a chest radiography were negative. Removal and cyto-
histopathologic analysis of this tumor revealed medullary
hyperplasia but resulted in no significant effect on the
patient’s diabetes mellitus or urinary metanephrine levels
(urinary normetanephrine = 3770 μg/24 h, metanephrine
= 84 μg/24 h). Compare these and above values to those
in orig ms one year later, a chest radiography and CT scan
revealed a tumor in the posterior mediastinum. Surgical
removal of the tumor was followed by normalization of
the patient’s blood pressure and remission of her diabetes
mellitus. Urinary metanephrine levels also normalized
(normetanephrine = 254 μg/24 h, metanephrine = 82 μg/24
h. Histologic examination identified chromaphyn tissue
– pheocromocytoma.
Conclusion: Our case report provides evidence that
endogenous catecholamine excess in patients with pheochromocytoma can induce insulin resistance in patients
with normal glucose tolerance. Moreover, remission of
the cathecholamine-induced diabetes mellitus may provide
evidence for complete cure of pheochromocytoma.
Abstract #96
Girls with Hypothyroidism in South India:
A Ten-Year Analysis
G.R. Sridhar, MD, DM, and G. Nagamani, MD, DGO
Objectives: To profile 111 girls aged less than 15 years
diagnosed with hypothyroidism at a single clinical facility
in South India between 1992 and 2003.
Methods: Retrospective analysis of electronic medical records between December 1992 and June 2003.
Results: Ages of girls diagnosed with hypothyroidism
at our clinical facility between 1992 and 2003 ranged from
10 months to 14 years (10.75 +/- 2.62 years). Each year,
between seven and 16 girls presented with hypothyroidism
(16 in 1999 and 7 in 1997), with cases appearing throughout the year without clustering in any season (March to
June: 38, 34.2%; July to August: 40, 36.0%; November
to February: 33, 29.7%). Serum thyroxine values for the
girls (n = 32) ranged from 0.01-4.8 μg/dL (2.39 μg/dL +/1.54 μg/dL), and thyrotropin from 10-370 μIU/mL (66.03
μIU/mL +/- 57.37 μIU/mL). Within this group, one girl
presented with each of the following concurrent pathologies or abnormalities: lingual thyroid, thyroglossal cyst,
precocious puberty, Turner syndrome, Down syndrome,
amaurosis, and vitiligo. Two sisters were twins.
Conclusion: Between seven and 16 girls with hypothyroidism came to our clinical facility every year over the
index time frame, without apparent seasonal variation.
Abstract #97
Abstract #98
Efficacy of Risedronate in Reducing Nonvertebral
Fracture Risk is Greater than That of Nasal Calcitonin
and Alendronate in an Observational Setting
Evaluation of Serum Insulin and Demographic
Profile of Childhood Obesity in Central India
Nelson Watts, MD, MACE, Joe Doyle, PhD,
Karen Worely, PhD, Michael Steinbuch, PhD, and
Richard Sheer, BS
Objective: The aim of this study was to compare
antifracture efficacy of risedronate with other osteoporosis
therapies in an observational setting.
Methods: From an administrative claims database,
we included patients age 45 years and older treated with
risedronate, alendronate, or nasal calcitonin therapy (93%
women, mean age 69 years). The risk of nonvertebral fractures (clavicle, humerus, wrist, pelvis, hip, and leg) was
compared after adjusting for age, sex, estrogen use, prior
fragility fractures, and a general morbidity indicator (number of concomitant medications). Results for the following
two time periods were evaluated: six-month fracture assessment in 7081 individuals with a new “index” prescription for risedronate (5 mg/day or 30 mg/wk), alendronate
(5/10 mg/day, 35/70 mg/wk) or nasal calcitonin between
July 2000 and December 2001, and 12-month fracture incidence in a subset of 5024 patients with an index prescription between July 2000 and June 2001.
Results: Compared with patients receiving nasal calcitonin, those receiving risedronate demonstrated statistically
significant reductions in risk of nonvertebral fractures after
6 months (RR=0.31; P = 0.02) and 12 months (RR=0.25,
P<0.01) of therapy. Compared with patients receiving
alendronate, risedronate-treated patients exhibited a lower
risk of nonvertebral fractures at 6 months that attained borderline statistical significance (RR=0.46, P = 0.07), and a
statistically significant reduction in nonvertebral fractures
at 12 months (RR=0.41, P = 0.04).
Conclusion: Patients treated with risedronate have a
significantly lower risk of nonvertebral fractures compared
with those treated with alendronate or nasal calcitonin during the first 12 months of therapy. This study demonstrates
substantial and rapid antifracture efficacy of risedronate
compared to alendronate or nasal calcitonin in an observational setting.
Muktanshu P. Patil, MBBS, MD (AM), CCH,
Satish B. Deopujari, MD, DNB, and
Shailesh U. Pitale, MD, DNB, DAB, FACE
Objectives: To evaluate the demographic profile of
obese children and to explore the prevalence of hyperinsulinemia in childhood obesity.
Methods: Ongoing cross sectional evaluation of
childhood obesity cases. Thorough clinical evaluation was
performed in each case, followed by thyroid function tests,
and fasting blood sugar, and serum insulin determinations.
Results: Twenty-three of 75 children screened were
included in this analysis. Mean age of children included
in the study was 10.8 + 2.08 years. Mean birth weight was
2.8 + 0.51 kg. Birth weight more than 3.5 kg was noted
in 7 of 23 subjects (30%). Mean BMI was 24.95 + 4.33
kg/m2 and 9 of 23 subjects (39%) had BMI >28 kg/m2.
Acanthosis nigricans was noted in 14 of 23 (61%), and 13
of 23 subjects (57%) reported a history of diabetes among
their parents. Glucose insulin ratio of <4 was noted in 16 of
23 subjects (70%). The mean serum insulin level was 32.04
mIU/mL. Only 1 of 23 subjects (4.35%) had hypothyroidism. Sedentary activities were preferred over physical play
by 18 of 23 (78%) of the subjects.
Conclusion: High birth weight and sedentary lifestyle
are the major contributors of childhood obesity. There is a
high prevalence of hyperinsulinemia among Indian children
with obesity compared to that reported in Western populations, which may predispose Indian children to higher rates
of metabolic syndrome and type 2 diabetes mellitus.
Abstract #99
Comparing Efficacy and Tolerability of Metformin XT
Given Daily to Immediate-Release Metformin Given
Twice Daily in Patients with Type 2 Diabetes
Robert M. Niecestro, PhD, and Mark Kipnes, MD
Objective: To evaluate efficacy and tolerability of
metformin XT (XT) given once daily compared to that of
immediate-release metformin (IRM) given twice daily.
Background: XT demonstrates a dose-associated increase in metformin exposure following oral administration
of 1000 to 2500 mg.
Methods: This double blind, multicenter, randomized
study evaluated efficacy and tolerability of XT daily versus
IRM twice daily in 115 patients (24 receiving XT 2000 mg,
32 receiving XT 2500 mg, 33 receiving IRM 2000 mg, and
26 receiving IRM 2500 mg). All patients were treated for 6
months. The primary efficacy variable was mean change in
HbA1c levels between baseline and endpoint.
Results: The mean change in HbA1c was 0.19%
(P = 0.3027) for patients treated with XT and 0.33% for
those treated with IRM (P = 0.00218). In the 2500 mg dose
groups, the observed change in HbA1c was –0.02% for the
XT group and 0.61% for the IRM group. Both treatments
were well tolerated.
Conclusion: Increasing the dose of XT from 2000 mg
to 2500 mg improved glycemic control in this population
of patients.
Abstract #100
of the importance and complexity of diabetes prevention. Despite recent data showing the benefits of lifestyle
change, the utility and practicality of implementing these
changes remain a significant clinical challenge.
Methods: We evaluated the effectiveness and cost of
establishing a multidisciplinary, office-based, weight loss
clinic supervised by clinical endocrinologists.
Results: Within the past year, individuals enrolling
in our clinic lost over 4,400 pounds. This enabled them to
discontinue 70 medications and reduce insulin use by 590
units. Diet-induced weight loss among individuals with
IRS produced dramatic improvements on the defining components of the IRS (P values versus to baseline). HDL-C
levels did not change statistically from baseline.
Comparison of Extended-Release Metformin and
Immediate-release Metformin
Mark Kipnes, MD, and Robert M. Niecestro, PhD
Objective: To compare the tolerability, pharmacokinetics, and pharmacodynamics of extended-release metformin (ERM) to immediate-release metformin (IRM).
Methods: In this Phase II, single-center, two-way
crossover study involving two- and four-week treatment
periods, patients were randomized to receive 2000 mg
ERM administered at 6:00 pm with dinner, or 1000 mg
IRM administered at 8:00 am with breakfast and 1000 mg
IRM at 6:00 pm with dinner. Subjects were then switched
to the other treatment after a washout period.
Results and Conclusion: The AUC0-24h for metformin
was 26811 ± 7055 ng-hr/mol for ERM and 27371 ± 5781
for IRM (mean ± SD). No significant differences were noted between ERM and IRM cohorts with regard to HbA1c
values. Patients treated with ERM exhibited significantly
lower plasma insulin levels (P<0.05) and maintained lower
plasma glucose levels between 6:00 pm and 6:00 am compared to those treated with IRM over a comparable time
frame. ERM administered at dinner reduced insulin levels.
Abstract #101
Effectiveness and Cost of Establishing a Weight
Loss Clinic for the Treatment of Insulin Resistance
Syndrome by Clinical Endocrinologists
Christopher Case, MD, Alan Rauba, MD, and
Lisa Williams, RD
Introduction: The number of individuals with obesity and insulin resistance syndrome (IRS) are increasing
to pandemic proportions. The American Association of
Clinical Endocrinologists suggests that clinicians should
lead the multidisciplinary treatment approach because
Systolic BP (mmHg)
Diastolic BP (mmHg)
Glucose (mg/dL)
Triglycerides (mg/dL)
Cholesterol (mg/dL)
Baseline
After
Weight Loss
P
value
133
78
123
186
197
120
73
90
99
158
<0.001
<0.001
<0.001
<0.001
<0.001
Our center offers several levels of programs with
physician supervision utilizing dietitians, behaviorists, and
exercise specialists. Education is emphasized in weekly
individual or group classes, typically in the evening to
maximize office space and personnel. Within one year, the
center was cost efficient, self-sustaining, and expanding.
Conclusion: These results suggest a model for clinical endocrinologists to effectively incorporate evidencebased medicine in the treatment of obesity and IRS into
routine daily practice.
Abstract #102
Treatment Of Hyperglycemia Following
Severe Head Injury
Denise Teves, MD
Objective: To identify hyperglycemia as a marker of
systemic stress response after severe head injury, and its
relationship to neurologic outcome.
Background: Severe head injury is in the acute stage
followed by an intense sympathoadrenal response. Lesions
of the hypothalamus and lower brain stem and cerebral
ischemia cause catecholamines (CAT) release. The increase in circulating CAT levels causes a hyperdynamic
cardiovascular response and a rise in blood glucose. CAT
release also increases glycogen breakdown and inhibits insulin secretion after injury. Increased anaerobic glucolysis
and lactate accumulation might lead to secondary neuronal
damage. Results of previous studies suggest that hyper-
glycemia may be associated with increased mortality after
brain injury.
Methods: This is a report of a man with marked hyperglycemia after severe head injury, with discussion of
treatment considerations and neurological outcome.
Results: A 29-year-old man was admitted to the ICU
following an assault with subsequent subdural hematoma
and cerebral edema and a Glasgow Coma Score (GCS)
of 3. The patient had no prior medical problems and was
taking no medications. Family history was significant for
diabetes in his mother and maternal aunt. Upon physical
examination he was hypertensive and had swelling of the
right orbit with right subconjunctival hemorrhage. He was
intubated and unconscious and had acanthosis nigricans in
axillary areas. On admission his blood glucose levels (BG)
increased to 178 and on day 8 and were as high as 270 with
poor response to insulin drip at 14 units per hour. Mannitol
was used, but steroid therapy was not implemented. His
HbA1c level was normal, as were his electrolyte levels. He
required treatment with crystalloid fluids and antihypertensive medications and was on tube feedings. Insulin glargine
was begun and the insulin drip was discontinued on day
11. His neurological status improved and he could follow
simple commands. Dosages of insulin glargine and lispro
were drastically reduced at that point and the patient was
discharged on day 16 to a rehabilitation center (BG=96).
Conclusion: Adequate insulin treatment of hyperglycemia after brain injury can minimize the damage induced
by glucose at the site of cerebral lesions and may improve
neurologic outcome.
Abstract #103
Rare Presentation of Multiple Autoimmune
Disorders in Graves’ Disease
Grishma Parikh, MD, Allen Sapadin, MD,
David Reich, MD, Isaac Sachmechi, MD, FACE, FACP
Objective: To describe a case of multiple autoimmune
disorders in a patient with Graves’ disease.
Background: Antithyroid drugs like propylthiouracil
and methimazole may induce skin eruptions similar to lupus.
Case report: A 32-year-old African American woman
with a history of Graves’ disease, myasthenia gravis, and
pancytopenia was admitted to the hospital after a suicide
attempt. Physical examination was remarkable for a pulse
rate of 140 bpm, diffuse goiter with bruit, exophthalmos,
and perioral and intraoral vesicular blisters. Treatment
with propranolol and propylthiouracil was initiated. Due
to worsening leukopenia and obstructive symptoms manifested by dysphagia, total thyroidectomy was performed.
Laboratory evaluation was significant for pancytopenia
with white cell count of 3700/mm3 (normal 4.5-11×1000/
mm3), platelets 72000/mm3 (130-400×1000/mm3), thyroid
stimulating hormone (TSH) level <0.06 mIU/mL (0.2-6
mIU/mL), thyroxin (T4) >24 µg/dL (4.5-12 µg/dL), triiodothyronine (T3) 516 ng/dL (45-150 ng/dL), and free T4>6
ng/dL (0.71-1.85 ng/dL), erythrocyte sedimentation rate 40
mm/hr, complements C3 58 mg/dL (104-187 mg/dL), and
C4 12 mg/dL (21-87 mg/dL). The patient was ribonucleoprotein-negative, Smith antibody-negative, Sjogrens/Ro
antibody-positive, and antihistone antibody-positive. Skin
biopsy results were consistent with bullous lupus. After
treatment with isotretinoin and dapsone orally, new blister
formation ceased. After surgery the patient eventually became hypothyroid, requiring replacement with synthyroid.
Conclusion: Cases such as this are usually characterized by a positive antihistone antibody, while other lupus
related serologic tests are negative. This case is novel
because skin manifestations were not drug induced. It
was unclear whether pancytopenia was true autoimmune
pancytopenia secondary to Graves’ disease, or secondary to
lupus. To the best of our knowledge, this is the first reported
case of Graves’ disease associated with myasthenia gravis
and bullous lupus.
Abstract #104
A Real Estate Agent With Episodes of
Confusion: A Case of Malignant Insulinoma
Nikheel S. Kolatkar, MD, Gail Adler, MD, PhD, and
Mark Hermann, MD
Objective: To describe a case of malignant insulinoma
presenting initially as mental confusion.
Case report: A 43-year-old woman with no significant prior medical history was seen for suspected hypoglycemia. Six months previously she experienced diaphoresis
and weakness lasting 15-30 minutes once weekly after
morning exercise. Episodes increased in frequency and began to be associated with mental confusion. A 72-hour fast
protocol subsequently demonstrated biochemical evidence
for insulinoma. Chromogranin, pancreatic polypeptide,
VIP, and gastrin levels were normal. An abdominal CT scan
revealed a 2-cm mass in the pancreatic tail with enlarged
local nodes and hepatic lesions. Results of an octreotide
scan were negative. PET scanning demonstrated active
uptake in the hepatic lesions. Surgical resection of the pancreatic mass, regional nodes, spleen, and gallbladder were
performed along with RF ablation of the major hepatic lesions. Pathologic evaluation of tumor tissue confirmed the
presence of malignant insulinoma. Treatment with adjuvant
diazoxide stabilized the patient’s blood glucose levels.
Abstract #105
Abstract #107
Cowden Syndrome Associated With Galactorrhea
Meeting the Challenge of Diabetes Care at a
Resident-Run Community Health Center
Mouhammed Amir Habra, MD, Camilo Jimenez, MD, and
Rena Vassilopoulou-Sellin, MD
Objective: To describe a case of Cowden syndrome
(CS) associated with galactorrhea.
Background: CS is an autosomal dominant disease related to PTEN gene mutation. CS predisposes patients to benign
and malignant tumors of the thyroid, breast, and endometrium.
Case report: A 38-year-old black woman presented
with goiter after subtotal thyroidectomy at the age of 12
and 34 years for multinodular goiter. She met diagnostic
criteria for CS by having a gastric lipoma, colonic polyps, a
right cerebellar gangliocytoma, and multiple facial and oral
papillomas. She reported a 3-year history of galactorrhea
but was otherwise without significant symptoms. Her only
medication was levothyroxine 125 μg/day. Her prolactin
level was 71 ng/mL with normal thyroid function test results. MRI of the sella revealed a normal pituitary gland.
Conclusion: This is the first reported case of galactorrhea associated with CS. Careful evaluation is required in
CS as the condition carries significant risk for tumors of
multiple organs.
Abstract #106
Spurious Hypocalcemia After
Gadolinium Administration
Sandra F. Williams, MD, and Thomas J. Moraghan, MD
Objective: To report a case of spurious hypocalcemia
following gadolinium administration.
Background: Despite prior descriptions of the potential interference of some gadolinium chelates with colorimetric assays for serum calcium, clinical awareness of this
phenomenon is low.
Case report: An asymptomatic 78-year-old man was
determined to have critically low serum calcium levels
of 5.8 mg/dL (normal: 8.9-10.1 mg/dL) measured via the
standard colorimetric assay following contrasted magnetic
resonance angiography with gadolinium enhancement.
Reanalysis of the same serum sample using absorption
spectroscopy revealed normal calcium values (9.7 mg/dL),
confirming the diagnosis of spurious hypocalcemia.
Conclusion: Our case illustrates a clinical example of
confirmed spurious hypocalcemia secondary to gadolinium
use. Reports of cases such as this will increase clinician
awareness of this phenomenon and subsequently prevent
inappropriate evaluations and potentially dangerous and
inappropriate interventions.
Nancy J. Rennert, MD, FACE, FACP, and
Sandra Mini, MD
Objective: We describe how quality care can be provided in community health centers (CHC) despite many
barriers.
Background: CHC often fail to meet standards of
care for patients with diabetes.
Summary and conclusion: The Norwalk Community
Health Center (NCHC) is a federally qualified CHC where
diabetes care is provided by internal medicine residents
supervised by an attending endocrinologist. Patients are
of minority ethnic backgrounds, primarily Hispanic (60%),
medically underserved, and economically disadvantaged.
We evaluated the quality of our diabetes program at
NCHC by applying for a nationally recognized benchmark
– certification under the NCQA/ADA Diabetes Physician
Recognition Program (DPRP). As part of this process,
clinical guidelines for outpatient management of diabetes
were distributed to all residents and attending physicians.
One year later, using the NCQA/ADA DPRP application
criteria, a representative random sample (n = 35) of patients
seen in our diabetes clinic was selected for further evaluation. Charts were reviewed to assess 12 key measures
shown to improve patient outcome. NCQA/ADA Physician
Recognition was achieved for the diabetes program at
NCHC and is valid for 3 years. Our data and national data
will be shown and described in detail. Demographic data
will be discussed comparing our patient population to that
of other US physician applicants to the NCQA/ADA DPRP
indicating the uniqueness of this achievement. Improving
the quality of care provided at NCHC required a multifactor approach including emphasis on culturally sensitive patient education and training of physicians and other health
care providers.
Abstract #108
A Case of Type B Insulin Resistance
Lisa C. Moore, MD, Archana Sadhu, MD,
Dorothy Martinez, MD, and Robin Kate Kelley, MD
Objective: To describe a severe case of type B insulin
resistance.
Methods: Case report and literature review.
Case report: A 66-year-old woman requiring approximately 400 units of insulin daily presented for glycemia
management. Diabetic ketoacidosis was diagnosed, man-
aged with continuous insulin infusion, and resolved within
24 hours. The patient required approximately 700 to 36,000
units of insulin daily, maintaining average blood sugars
between 300 and 700 with ketosis but no acidosis. Serum
samples were evaluated for insulin receptor antibody, and
the patient was sequentially started on treatment with
cellcept, solumedrol, intravenous immunoglobulin, plasmapheresis, and cytoxan. Ultimately, her insulin drip was
replaced by subcutaneous insulin, with no ketosis. Insulin
receptor antibody titer was positive, and management required immunosuppression in addition to insulin.
Abstract #109
MEN 1 Causing Headaches in a Pregnant Woman
Pierre Theuma, MD
Objective: To describe a case of MEN 1 precipitating
headaches in a pregnant woman.
Case report: A 31-year-old woman presented at 26
weeks of gestation complaining of progressively worsening headaches, nausea, vomiting, and constipation. She described a past medical history of pituitary macroprolactinoma for which she was treated with cabergoline, which was
discontinued when her pregnancy was confirmed. A 14-mm
pituitary macroadenoma was noted upon non-contrast MRI.
There was no associated compression of the optic chiasm,
and formal visual field testing was normal. Laboratory results included serum calcium of 12.5 mg/dL (normal value
8.5-10.5 mg/dL). Further evaluation confirmed primary hyperparathyroidism with an intact parathormone (PTH) level
of 165 pg/mL. The patient was hospitalized for aggressive
hydration and loop-diuretic therapy but her hypercalcemia
persisted, and parathyroidectomy was performed at 28
weeks of gestation, with successful removal of an 18 g left
superior parathyroid adenoma.
Conclusion: Primary hyperparathyroidism during
pregnancy poses significant risks to both mother and fetus.
Controversies regarding management of this problem during gestation will be discussed and the available literature
reviewed.
Abstract #110
Inhaled Fluticasone and Cushing’s Syndrome
Nadia Yaqub, MD, and John William Leidy, MD
Objective: To describe a case of Cushing’s syndrome
related to use of inhaled fluticasone.
Background: An association between Cushing’s
syndrome and inhaled fluticasone is rarely reported in
literature.
Case report: A male patient with severe persistent
asthma was treated with high dose inhaled fluticasone
propionate over a 6-year period. He developed features of
Cushing’s syndrome, including central obesity, thin skin,
dorsocervical fat pad, violaceous striae, muscle wasting,
and severe osteopenia, and the patient demonstrated biochemical evidence of adrenal suppression. His other medications included diltiazem and zafirlukast. These drugs
inhibit action of the CYP3A4 enzyme, which metabolizes
inhaled fluticasone. This patient reported clinical improvement of the above symptoms after switching to alternative
drugs including a less potent budesonide inhaler.
Conclusion: This case illustrates the potential for
clinically relevant adverse effects of inhaled corticosteroids
even when given at indicated doses, due to the action of potentially interfering drugs. Under conditions of polypharmacy, drug-drug interactions involving cytochrome enzymatic metabolic pathways should never be overlooked.
Abstract #112
Diagnosis of Insulinoma Utilizing a Continuous
Glucose Monitoring System in a Patient with
Diabetes Mellitus
Paraskevi Sapountzi, MD, Gerald Charnogursky, MD,
Fadi Nabhan, MD, Donna Murphy, CDE, RN, and
Maryann Emanuele, MD, FACP
Objective: To present a case of a young patient with
type 2 diabetes mellitus (DM) in whom a continuous glucose monitoring system (CGMS) significantly helped in the
diagnosis of insulinoma.
Methods: A 20-year-old woman with a history of
diet-controlled DM diagnosed by a positive oral glucose
tolerance test presented to our clinic with a history of
documented hypoglycemia with symptoms suggestive of
neuroglycopenia. She reported gaining 25 pounds in the
previous year, and denied ingestion of any diabetic medications, alcohol or illicit drugs. A neurological evaluation,
which included a head CT and EEG, revealed no significant
findings. A CGMS was ordered to document her hypoglycemic episodes.
Results: The CGMS revealed frequent, severe episodes of nocturnal hypoglycemia. The patient was admitted
to the hospital and within an hour experienced a profound
hypoglycemic episode with elevated C-peptide, insulin,
and proinsulin levels consistent with insulinoma. An MRI
of the abdomen subsequently demonstrated a 1.2-cm lesion
in the tail of the pancreas. The patient underwent successful
enucleation of the tumor, and cytohistologic evaluation of
tumor revealed insulinoma.
Conclusion: Insulinoma should be considered in the
differential diagnosis in young patients with unexplained
symptomatic hypoglycemia and DM. A CGMS may, in
addition, play a crucial role in the evaluation of such
patients.
Abstract #113
Demonstration of Parathyroid Hormone by
Immunostaining in Small Cell Lung Cancer
Fadi Nabhan, MD, Jason Castator, MD,
Adam Quinn, DO, Mary Ann Emanuele, MD, and
Nasrin Azad, MD
Objective: We report a case of a patient demonstrating
positive immunostaining for the presence of adrenocorticotropic hormone (ACTH) and parathyroid hormone (PTH)
in small cell lung cancer tissue.
Background: Ectopic production of PTH is extremely rare.
Case report: An 81-year-old male presented with
mental changes and weight loss. In laboratory analysis, a
24-hour urine collection revealed a urine cortisol level of
5975 μg/g creatinine (normal 8-77 μg/g creatinine), a serum ACTH concentration 1185 pg/dL (5-52 pg/dL), serum
calcium 5.6 mg/dL (8.5-10.5 mg/dL), 25-OH Vitamin D 6
ng/mL (10-68 ng/mL), intact PTH level 398 pg/mL (10-65
pg/mL) and normal test values regarding renal function.
24-hour urine collection also revealed calcium 600 mg/24
hours (50-300 mg/24 hours), and phosphorus 2.6 gms.
Patient subsequently suffered deterioration of his condition
with multiple organ failure and death. Autopsy revealed
atrophic parathyroid glands in the neck with no parathyroid
adenoma seen elsewhere. Histology of lung tumor tissue
confirmed the presence of small cell lung cancer (SCLC).
On immunohistochemical evaluation the tumor tissue
stained positive for the presence of ACTH and PTH.
Conclusion: The presence of atrophic parathyroid
glands and the absence of an ectopic parathyroid adenoma
suggest that the observed elevated serum PTH level may be
related to tumor production, especially in association with
ectopic ACTH synthesis. Although we have not performed
arteriovenous gradient determination of PTH levels in lung
tumor tissue in this patient, positive immunostaining for
the presence of ACTH and PTH indirectly suggests that
the tumor may be a source for the elevated levels of serum
PTH. Additional studies involving mRNA demonstrations
for PTH in SCLC tissues would aid in confirming these
findings.
Abstract #114
Adrenal Insufficiency and Amyloidosis,
Diagnostic Questions: A Case Report and Discussion
Fadi Nabhan, MD, and Nicholas Emanuele, MD, FACP
Objective: To present and discuss a case of adrenal
insufficiency and amyloidosis.
Background: Amyloidosis is characterized by the
presence of fibrillar proteins, which may infiltrate any organ. Existing autopsy studies reveal an involvement rate of
the adrenal glands of 47-96%. Most studies used abnormal
cosyntropin stimulation test results as proof of the clinical
significance of this involvement.
Case report: An 81-year-old man presented with a
3-day history of weakness, lethargy, and nausea. He had a
history of systemic amyloidosis and was taking low dose
prednisone for neuropathy. Six months earlier a cosyntropin stimulation test was done to evaluate similar complaints
at that time. Findings of this test demonstrated a high baseline ACTH concentration and a normal cortisol level. At
the current presentation, a cosyntropin stimulation test was
again performed, and revealed an elevated ACTH level
and cortisol values consistent with adrenal insufficiency
(see Table below). It was concluded that the deteriorating
cortisol response was due to progressive amyloid involvement of the adrenal glands. His steroid dose was increased
to standard replacement therapy with modest clinical response. He was admitted to the hospital a few days later
with pneumonia and was treated with stress dose steroids
but progressed to multiple organ failure and death. An autopsy showed normal adrenal glands.
Conclusion: In amyloidosis, adrenal insufficiency,
proven by an abnormal cosyntropin stimulation test, does
not prove amyloidosis involvement of the adrenal glands.
Table. Cosyntropin Stimulation Test Values
Cortisol
baseline
Cortisol 60
minutes after
cosyntropin
stimulation
ACTH (normal:
10-46 pg/ mL)
First
stimulation
test
21 μg/dL
26 μg/dL
142 pg/mL
Second
stimulation
test
11 μg/dL
14 μg/dL
109 pg/mL
Abstract #115
Comparison of Alendronate and Raloxifene Across
Age Subgroups: Results From the Effect Study
P Miller, S Bonnick, E Chen, R Petruschke,
J Palmisano, and A de Papp, MD
Objective: To evaluate the consistency of effect of
alendronate (ALN) and raloxifene (RLX) across two age
subgroups (<65 vs. >65).
Methods: Patients were treated with ALN 70 mg
once-weekly or RLX 60 mg daily for 1 year. Prespecified
age subgroup (<65 and ≥65) analyses were performed on
percent change in lumbar spine (LS) BMD and urinary
N-telopeptide (NTx). Post-hoc evaluation of the percent of
patients with ≥0% increase in LSBMD was included.
Results:
Subgroup
ALN
RLX
Difference
(95% CI)
<65 (n = 243)
1) % Change LS BMD
2) % ≥0% Change LS BMD
3) % Change in NTX
4.1
91.7
-59.0
1.3
69.5
-21.5
2.8 (1.9, 3.7)
22.2 (12.0, 32.4)
-47.8 (-55.4, -39.0)
≥65 (n = 208)
1) % Change LS BMD
2) % ≥0% Change LS BMD
3) % Change in NTX
4.5
95.6
-60.9
2.6
81.2
-34.4
2.0 (1.1, 2.9)
14.4 (5.6, 23.1)
-40.5 (-49.7, -29.6)
Conclusion: Treatment with ALN 70 mg once-weekly is associated with greater increases in BMD, greater
reduction in resorption markers, and a greater percentage
of responders than is treatment with RLX, regardless of
patient age.
Abstract #116
Profile Of Diabetics With Tuberculosis Under
the Directly Observed Treatment Strategy (DOTS) of
the University of Santo Tomas Hospital
E. Cunanan, MD, B. Matawaran, MD, H. Gomez, MD,
and R. Reyes, MD
Objective: This descriptive cross-sectional study aims
to review the presentation and treatment outcome of tuberculosis (TB) among diabetics under the University of Santo
Tomas Hospital Directly Observed Treatment Strategy
(USTH-DOTS) clinic and to compare the findings with
their nondiabetic counterparts.
Background: One effective TB case-holding strategy currently implemented in the Philippines to improve
TB treatment compliance is DOTS, wherein health care
workers watch and make sure that each patient takes the
correct antiTB medications during the course of therapy.
Methods: A review of the medical records of diabetics
with tuberculosis enrolled at the USTH-DOTS clinic was
done. All diabetics with tuberculosis were defined based on
demographic, clinical, and radiologic data and microbiologic profile. Results were compared with their nondiabetic
counterparts.
Results: Among the 299 enrollees, twenty-four (8%)
had diabetes mellitus. Sixteen were known diabetics prior
to TB diagnosis, while 8 were found to be diabetic on workup during the course of therapy. Ages ranged from 31 to
71 years (mean 50.6 years). There were 13 females and 11
males with a ratio of 1.2:1. Cough, fever, weight loss, and
anorexia were the most common presenting features in both
groups. Fifty-four percent of diabetics had previous intake
of antiTB drugs in contrast to 13.8% of nondiabetics. Fiftyeight percent of diabetics versus 34.2% of nondiabetics had
positive AFB smear, 29.2% of diabetics versus 21.5% of
nondiabetics had positive sputum MTB culture. 16.7% of
diabetics versus 12.7% of nondiabetics had in vitro first line
antiTB drug resistance. 12.5% of diabetics versus 4% of
nondiabetics had in vitro multidrug-resistant tuberculosis.
12.5% of diabetics versus 3.27% of nondiabetics had in
vitro resistance to ciprofloxacin. Fifty percent of diabetics
versus 60% of nondiabetics had purely apical involvement
while 37.5% of diabetics versus 19.6% of nondiabetics
presented with multilobar lesions. One of the 24 diabetics
presented solely with middle lobe involvement. Fifty percent of diabetics and 29.5% of nondiabetics had pulmonary
cavities apparent on chest radiograph. Completion rate for
diabetics was at 87.5%, while nondiabetics had an 82.9%
completion rate.
Conclusion: Though external validity of these study
findings is limited by its small subject population size
and by retrospective data collection, some differences in
the pattern of clinical presentation of tuberculosis among
diabetics are worth noting, such as the relatively higher
rate of multidrug resistance, ciprofloxacin resistance, and
treatment failure rates.
Abstract #117
Comparision of Homeostasis Model Assessment
(HOMA) and Insulin Sensitivity Index (ISI0-120)
Method for Study of Insulin Resistance
M.K. Bhatnagar, MD, FICP, Vinyas Singh, MD,
Jayashree Bhattacharjee, MD, and
S.K. Jain, MD, DM, FACE
Objective: To compare insulin sensitivity determination by the Homeostasis Model Assessment (HOMA)
and the Insulin Sensitivity Index (ISI0-120) methods, and
to suggest a simple, reliable method of evaluating insulin
resistance.
Background: Insulin sensitivity is ideally measured
by the euglycaemic hyperinsulinemic clamp method. This
method is not practical in clinical practice, as it is invasive,
expensive, and cumbersome. Many practical methods
were suggested by various investigators, including HOMA
(Mathews et al, 1985), a simple and relatively established
method. More recently, the ISI0-120 method has been suggested by Gutt et al (2).
Methods: Forty subjects with two or more clinical
features of insulin resistance syndrome and 30 age- and
sex-matched control subjects were evaluated fo
r insulin resistance. All case and control subjects
underwent complete clinical and biochemical evaluation.
A standard oral glucose tolerance test was performed and
plasma glucose and serum insulin levels were estimated at
baseline and 2 hours later using glucose oxidase and ELISA
principles, respectively. Insulin resistance was calculated
by HOMA and ISI0-120 formulae (1,2).
Results: The mean fasting serum insulin (±SD) in
cases was 19.4 ± 8.6 mu/L and in control was 11.8 ± 2.6
mu/L. The levels were significantly different (P≤0.001).
The 2 hrs post-glucose serum insulin in case subjects was
46.38 ± 32.1 mu/L and among control subjects was 65.8 ±
5.9mu/L which was also significantly different (P ≤0.001).
Insulin resistance as calculated by the HOMA method was
significantly higher among case versus control subjects
(6.8 ± 7.8 vs. 2.44 ± 0.6; P <0.001) and insulin sensitivity
calculated by ISI0-120 was also significantly higher among
case versus control subjects (238.3 ± 111.0 vs. 196.5 ±
33.1; P <0.033). Comparison of both methods by Pearson’s
Coefficient revealed a significant, moderate negative correlation (r = -0.497, P ≤0.001).
Conclusion: HOMA and ISI0-120 both are simple,
practical methods for estimating insulin resistance. The
ISI0-120 method considers both fasting and post-2-hour glucose and insulin values for calculation of insulin sensitivity,
while the HOMA method requires only fasting values. The
HOMA method latter is therefore much simpler to perform
and is as reliable as the ISI0-120 method.
REFERENCES
1.
2.
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis
model assessment insulin resistance and β-cell function from
fasting plasma glucose and insulin concentrations in man.
Diabetologia. 1985;28:412-419.
Gutt M, Davis CL, Spitzer SB, et al. Validation of the insulin sensitivity index (ISI0-120): comparison with other measures. Diabetes Research and Clinical Practice. 2000;47:
177-184.
Abstract #118
Primary Bilateral Adrenal Lymphoma:
A Rare But Distinct Clinical Entity
Philip E. Knapp, MD and Stephanie L. Lee, MD, PhD
Objective: To discuss bilateral adrenal lymphoma
(BAL) as a cause of adrenal insufficiency.
Methods: Case report and review of the literature.
Results: A 68-year-old woman presented with weight
loss, fatigue, and low grade fever. Her past medical history was significant for exposure to tuberculosis. Physical
examination revealed adrenal insufficiency and dramatic,
homogenous, bilateral adrenal enlargement. Refractory
thrombocytopenia precluded adrenal biopsy. A definitive
diagnosis made after autopsy revealed B-cell lymphoma
involving both adrenal glands.
Conclusion: BAL is a rare but well-described clinical
entity with over 70 cases reported in the literature. It is often limited to the adrenal glands, suggesting a primary adrenal origin. Differential diagnosis of adrenal insufficiency
with bilateral adrenal enlargement includes tuberculosis,
histoplasmosis, and metastatic malignancy. Primary BAL
should be considered in the differential diagnosis of adrenal
insufficiency with bilateral adrenal enlargement.
Abstract #119
Cut-Off Levels for Anthropometric Indices to Diagnose
Obesity in Asian Indians
Sachin K. Jain, MD, DM, FACE, Ritesh Panwar, and
Siddharth Mukerjee
Objective: To establish appropriate cut-off levels
of body mass index (BMI), waist-hip ratio (WHR), and
waist circumference (WC) for diagnosing obesity in Asian
Indians, defining >30% body fat (BF) in females and >25%
BF in males as obesity.
Background: Asian Indians are at a high risk for
developing premature atherosclerosis, possibly related to
increased insulin resistance and unfavorable body fat distribution in spite of having lower BMI compared to Western
populations. Metabolic consequences of obesity tend to occur at lower BMI, and smaller WHR and WC among Asian
Indians compared to Western populations.
Methods: One hundred four healthy volunteers (56
males and 48 females) without family history of diabetes
mellitus (DM) and hypertension (HT) participated in the
study. Detailed clinical examination and anthropometric
measurements were performed and percent BF was calculated by measuring skin fold thickness at triceps, biceps,
suprailiac, and subscapular sites, using equations of Durnin
and Womersley (1). Correlation between percent BF calculations determined by this method and by densitometry
range from 0.7 to 0.9 in different age groups (1).
Results: Mean ± SD age was 34.2 ± 8.4 years among
men and 36.1 ±7.8 years among women. Among men, BMI,
WHR, WC and% BF were 23.0 ± 4.0 kg/m2, 0.9 ± 0.1, 84.5
± 12.6 cm, and 23.6 ± 7.2%, respectively. Comparable values among women subjects were 23.5 ± 5.0 kg/m2, 0.8 ±
0.1, 76.1 ± 11.8 cm and 33.1 ± 6.2%, respectively. Based
on receiver operating characteristic curves, a cut-off value
defining obesity based upon BMI among men was 23 kg/m2
(sensitivity [sens] = 91.3%; specificity [sp] = 81.8%). For
WHR a comparable cut-off value was 0.9 (sens = 87.0%;
sp = 84.8%), and for WC, 86.1 cm (sens = 91.3%; sp =
84.8%), taking >25% BF as standard for obesity. A cut-off
value defining obesity among women subjects based on
BMI was 20 kg/m2 (sens = 93.9%; sp = 93.3%). For WHR
a comparable cut-off variable was 0.78 (sens = 72.7%; sp
= 66.7), and for WC it was 68.0 cm (sens = 90.9%; sp =
93.3%), assuming >30% BF as standard for obesity.
Conclusion: In Asian Indian populations, cut-off levels of anthropometric indices BMI, WHR, and WC should
be lowered to accurately define obesity and predict related
risks. Among men, BMI, WHR, and WC should be >23kg/
m2, >0.92, and >86.0 cm, and among women, comparable
vales should be >20.0 kg/m2, >0.78, and >68cm respectively. This is a preliminary study only. Confirmation of
these findings in a large group of subjects will help define
cut-off levels of anthropometric indices more appropriately
for the population.
REFERENCES
1.
Durnin JV, Womersley J. Body fat assessed from total
body density and its estimation from skinfold thickness;
measurements from 481 men and women aged 16-72 years.
British Journal of Nutrition 1974;32:77-97.
Abstract #120
“Pseudo” Hungry Bone Syndrome After
Parathyroidectomy for Tertiary Hyperparathyroidism
Richard Pinsker, MD , Nikhil Siony, MD, J. Leibowitz, MD,
Urvashi Mehta, MD, Devashish Ray, MD,
Thomas Santucci, Jr., MD, and Himanshu Pandya, MD
Objective: To report a case of “pseudo” hungry bone
syndrome following parathyroidectomy for tertiary hyperparathyroidism.
Care report: A 27-year-old woman came to the emergency department complaining of tingling and numbness
over her entire body. She had five-year history of end stage
renal failure treated by hemodialysis, and had undergone
subtotal parathyroidectomy 10 days previously, at a tertiary
care center. Despite optimal medical management, she
subsequently developed severe renal osteodystrophy with
marked elevation of her serum calcium and PTH levels.
She was determined to have “tertiary” hyperparathyroidism
and was sent to surgery, and suffered severely hypocalcemia immediately afterward. She was discharged nine days
later, but returned to our emergency department the next
day, when laboratory evaluation revealed an initial calcium
level of 7.6 mg/dL (normal 8.5-10.5 mg/dL), phosphorus
of 1.3 mg/dL (2.3-4.3 mg/dL), albumin of 4.2 g/dL (3.5-5.0
g/dL), and alkaline phosphatase of 742 U/L (39-117 U/L).
After five days of intravenous calcium, a switch to oral
medication resulted in lower extremity cramps and weakness. High dose intravenous calcium and calcitriol were
needed for 20 days before stabilization. Initial impression
was “hungry bone syndrome.” The lengthy recovery time
and the low phosphorous level favored this diagnosis,
though the patient’s PTH values did not, as intact PTH levels were barely detectable in this patient. Eventually, she
was referred for reimplantation of parathyroid tissue.
Conclusion: We concluded that this patient had
underlying postoperative hypoparathyroidism and severe
metabolic calcium bone deficit. Osteomalacia may have
been a contributing factor.
Abstract #122
MilkAlkali Syndrome in Pregnancy
Michalis K. Picolos, MD, Charles R. Sims, MD,
Linda Fonseca, MD, Mary A. Carroll, MD, and
Victor Lavis, MD.
Objective: To report a case of milk-alkali syndrome
in pregnancy.
Background: Severe hypercalcemia, a potentially life
threatening medical emergency, is rare in pregnancy.
Methods: We present the clinical and laboratory data
on our patient and review related medical literature.
Results: A 32-year-old woman presented in the early
second trimester of pregnancy with hyperemesis and altered mentation. Laboratory evaluation revealed severe
hypercalcemia (calcium 22mg/dL; normal value 8.5-10.5
mg/dL), alkalosis and acute renal insufficiency with appropriately suppressed serum levels of parathyroid hormone
(PTH), PTH-related peptide, 25-hydroxyvitamin D, and
1,25-dihydroxyvitamin D. Chest radiograph and mammography revealed normal findings. Upon further evaluation it
was determined that her metabolic and clinical picture resulted from excessive ingestion of calcium carbonate-containing antacid for gastroesophageal reflux. The patient was
treated with aggressive hydration and furosemide therapy,
and received one dose of intravenous etidronate, leading to
short-term symptomatic hypocalcemia. To our knowledge,
this is the third reported case of milk-alkali syndrome in
pregnancy.
Conclusion: Milkalkali syndrome seems to be an
uncommon but important cause of severe hypercalcemia in
pregnancy. Treatment with etidronate may carry a significant risk of hypocalcemia. Given its unknown effect on the
fetus, etidronate should probably be reserved for patients
unresponsive to aggressive hydration and diuretic therapy.
Abstract #123
A Case of Adrenal Insufficiency Secondary to
Allgrove Syndrome (“4A” Syndrome)
A. Vijay Rathinam, MD; Elias S. Siraj, MD
Introduction: We describe a case of a patient who
presented with adrenal insufficiency, and was finally diagnosed with Allgrove syndrome.
Background: Allgrove syndrome (“4A” syndrome)
is an autosomal recessive condition defined by alacrima,
achalasia, adrenocortical insufficiency and, often, additional features such as autonomic dysfunction (4A).
Case Report: A 48-year-old African American man
presented for management of adrenal insufficiency. His
past medical history was significant for a spastic neurologic condition and achalasia since birth, alacrima, and
a history of “autonomic dysfunction” manifesting as orthostatic symptoms, inappropriate sweating, and erectile
dysfunction. About 6 to 7 years prior to presentation he
was diagnosed with adrenal insufficiency and treated with
hydrocortisone replacement. His history is also remarkable
for short stature, vocal cord paralysis, intermittent xerostomia, history of esophageal candidiasis, and episodes of
hypoglycemia. Physical examination revealed short stature,
spastic gait, orthostatic drop in blood pressure, nasal twang
in voice, diminished gag response on left, anisocoria, hyperpigmentation of skin, palmar and solar hyperkeratosis,
increased muscle tone, exaggerated reflexes, and clonus.
Laboratory evaluation confirmed adrenal insufficiency but
revealed no evidence of thyroid, parathyroid, or pituitary
disease. Serum levels of very-long chain fatty acids and
immunoglobulin fractions were normal.
Conclusion: This case depicts a relatively common
condition (adrenal insufficiency) caused by a rare disease
(Allgrove syndrome). Differential diagnoses including
autoimmune polyendocrinopathies and X-linked adrenomyloneuropathy were ruled out. We suggest that the possibility of Allgrove syndrome be considered in patients with
adrenal insufficiency presenting with some of the unusual
features mentioned above.
Abstract #124
Successful In Vitro Fertilization After Treatment
With Propylthiouracil in a Woman With Infertility
and Subclinical Hyperthryoidism
Adriana Ioachimescu, MD, Elias S. Siraj, MD
Introduction: Though various thyroid diseases have
been associated with impaired fertility, subclinical hyperthyroidism has not been. In addition, whether treating subclinical hyperthyroidism restores fertility remains an open
question. We are reporting here a case in which treatment of
subclinical hyperthyroidism resulted in successful in vitro
fertilization (IVF) after 3 failed attempts.
Case Report: A 32-year-old woman presented to our
clinic for evaluation of whether her thyroid abnormality
contributed to her infertility and failed prior IVF attempts.
The patient had a history of primary infertility for three
years prior to this presentation. Despite undergoing pelvic
surgery for endometriosis, she was unable to conceive, and
it was concluded that she has tubal infertility. IVF was attempted three times without success. For previous 3 years,
the patient was known to have low TSH in the range of
0.2-0.4 mU/L (normal: 0.4-5.5 mU/L) with normal T4 and
T3. Physical examination revealed a 3-cm left thyroid nodule, which was found to be benign colloid nodule upon fine
needle aspiration. Thyroid-associated autoantibodies were
absent. After discussion with the patient, a decision was
made to treat her with propylthiouracil (PTU) in an attempt
to normalize her TSH levels. After 6 months of therapy and
adjustment of her PTU dose, her TSH level was 0.95 mU/L,
with normal T4 and T3 while on PTU 50 mg TID. IVF was
subsequently performed successfully, and resulted in a twin
pregnancy. The PTU was continued and adjusted throughout her pregnancy, which culminated in the term delivery of
healthy fraternal twins.
Conclusion: This is the first case report suggesting
that reversal of subclinical hyperthyroidism possibly contributed to restoration of fertility.
Abstract #126
Salsalate, A Novel Treatment for Type 2 Diabetes
Robert J. Silver, MD. Waleed Aldhahi, MD, FRCPC,
Steven E. Shoelson, MD, PhD, and
Allison B. Goldfine, MD
Objectives: In this investigation we sought to determine whether targeted IKKβ/NF-κB inhibition with
salsalate offers effective treatment of type 2 diabetes
(T2D).
Background: The serine kinase IKKβ is a downstream mediator of insulin resistance through inhibition
of the insulin receptor substrate and activation of inflammation via NF-κB. High doses of salicylates (aspirin)
inhibit IKKβ in rodents and improve glucose metabolism
in patients with T2D. In contrast to aspirin, salsalate is an
equipotent inhibitor of NF-κB but is not associated with
increased risk of bleeding.
Methods: Six subjects with T2D were administered
salsalate (~3 g/day) for two weeks. Misoprostol 200 µg
QID was also given throughout the study. Patients underwent euglycemic hyperinsulinemic clamp procedures
before and after therapy.
Results: Salsalate therapy was associated with significant decreases in fasting glucose (P = 0.03), triglycerides
(P = 0.005), diastolic blood pressure (P = 0.002), and glucose disposal rate during euglycemic clamp procedures (P
= 0.01). Weight, systolic blood pressure, hepatic, and renal
function were not significantly affected.
Conclusion: These data support the hypothesis that
inhibition of IKKβ/NF-κB activity is a potential novel target for treatment of insulin resistance in patients with T2D
and that salsalate may be a safe, effective treatment for this
common disease.
Abstract #127
Patients With Type 1 Diabetes: Perceptions
Associated With Pramlintide as an Adjunctive
Treatment To Insulin
David Marrero, PhD, Davida Kruger, MSN,
Terrie Burrell, PhD, Maurice Gloster, MD,
John Crean, PhD, Kathrin Herrmann, PhD, and
Orville Kolterman, MD
Objective and Methods: Pramlintide (PRAM) is an
amylin analog was studied as an adjunct to insulin treatment in patients with diabetes. In a 29-week, randomized,
triple-blind, placebo (PBO)-controlled trial in patients
with type 1 diabetes, treatment satisfaction associated
with PRAM was assessed in a study-specific, prospective,
non–validated 14-item satisfaction survey using a 6-point
Likert scale (“strongly disagree” [1] to “strongly agree”
[6]) at study exit.
Results: Of 296 patients randomized to treatment,
266 patients who received PRAM 30 or 60 µg TID/QID
in addition to insulin (CSII or MDI) completed the survey
(age 41 + 13 years, HbA1C 8.1 + 0.8%, BMI 28 + 5kg/m2).
PRAM-treated subjects perceived greater beneficial effects
with regard to blood glucose levels, weight, and appetite
control (P<0.001), irrespective of CSII or MDI regimen.
These subjects also reported significant improvements in
their ability to function at home, work, and school, regard-
ing how they felt overall, in their confidence regarding
self management of their diabetes (P<0.001 all measures),
and in reduction of “some worries” about having diabetes
(P = 0.003). PRAM-treated subjects, however, reported
more side effects (P = 0.002), but their overall satisfaction scores were relatively low (2.3 + 1.6 [PRAM] vs. 1.7
+1.3 [PBO]). Subjects perceived, however, that benefits of
PRAM outweighed the inconvenience of additional injections (P<0.001). Analyses of variance identified limited
interaction between treatment and other covariates (age,
gender, duration of diabetes, HbA1C level, and BMI) in
the survey outcome, though subjects on CSII reacted more
negatively to PBO treatment than those on MDI. Factor
analysis revealed that quality of life had an eigenvalue of
7.6 (54.5% of variance), and future use had an eigenvalue
of 1.6 (11.4% of variance). The consistency of the survey
as assessed by Cronbach’s alpha was 0.9 for the scale as a
whole, 0.9 for quality of life factor, and 0.7 for future use
factor.
Conclusion: In summary, these findings from a prospective, non-validated survey indicate favorable overall
patient satisfaction with PRAM treatment and warrant
further evaluation.
Abstract #128
Effects of Pramlintide on Postprandial Glucose
Excursions and Measures of Oxidative Stress in
Patients With Type 1 Diabetes
J. Frias , MD, FACE, A. Ceriello, MD, Y. Wang, PhD,
J.A. Ruggles, PhD, O.G. Kolterman, MD, L. Piconi, PhD,
D.G. Magg, MD, and C Weyer, MD
Objective: This study assessed the effects of pramlintide (PRAM), an analog of the naturally occurring -cell
hormone amylin, on markers of oxidative stress (OS) in the
postprandial (PP) period.
Background: OS is increased in the PP period among
patients with diabetes (DM), and has been implicated in the
pathogenesis of micro- and macrovascular complications.
Methods: In a randomized, single-blind, placebo-controlled, crossover study, 18 subjects with type 1 DM (age 38
± 15 years, duration of DM 22 ± 12 years, HbA1C level 9.4
± 1.7% [mean ± SD]) underwent two standardized breakfast meal tests, t = 0 minutes. In addition to PP injection of
regular insulin (mean ± SE: 7.2 ± 0.9 and 7.5 ± 1.0 U at t =
-30 minutes for PRAM and placebo [PBO], respectively),
subjects received subcutaneous injection of either PRAM
(60 g at t = 0 minutes) or PBO (at t = -15 minutes).
Results: The plasma concentrations of glucose and
markers of OS (nitrotyrosine [NT], oxidized LDL cholesterol [oxLDL-C], and total-trapping antioxidant parameter
[TRAP]) were assessed at baseline and during the 4hour
PP period. Compared with PBO, PRAM significantly reduced PP excursions of glucose (>100%), NT (>100%) and
oxLDL-C (>100%), and protected TRAP from consumption (>100% increase).
Postprandial
excursions
(incremental AUC0-4h)
Glucose (mmol/L·h)
NT (μmol/L·h)
OxLDL-C (U/L·h)
TRAP (μmol/L·h)
Results: Plasma PRAM concentrations were measured for 4 hours after injection and the area under the
curve (AUC0-4h [pmol·h/L]) was calculated.
Table. Relative PRAM Bioavailability to Reference (abdomen 12.7-mm)
[Least squares (LS) mean ratio AUC0-4h and 95% Confidence Interval (CI)]
PRAMP
-0.6 ± 2.5
0.07 ± 1.4
-4.3 ± 3.4
-0.79 ± 73.3
BO
+11.0 ± 2.9
5.3 ± 2.2
19.4 ± 6.0
-200 ± 89.4
P value
0.001
0.014
0.002
0.021
Type 1 NonObese (n = 18)
Type 1 Obese
(n = 15)
Type 2 NonObese (n = 16)
Type 2 Obese
(n = 18)
LS
mean
ratio
(SE)
95%
CI
LS
mean
ratio
(SE)
95%
CI
LS
mean
ratio
(SE)
95%
CI
LS
mean
ratio
(SE)
95%
CI
Abdomen
6.0-mm
0.92
(0.10)
0.74,
1.13
1.03
(0.11)
0.83,
1.28
0.81
(0.10)
0.64,
1.03
1.06
(0.10)
0.87,
1.28
Mean ± SE, P values based on mixed-effects models.
Arm
12.7-mm
1.09
(0.11)
0.88,
1.35
1.36
(0.15)
1.09,
1.69
1.03
(0.12)
0.81,
1.31
1.20
(0.11)
1.00,
1.45
Correlation analyses adjusted for treatment revealed a significant association between change in glucose level and
change in each measure of OS (P<0.001 for all correlations). The most frequent adverse events noted were mild
to moderate hypoglycemia and mild nausea.
Conclusion: In summary, the reduction in PP glucose
excursions achieved with addition of PRAM to short-acting
insulin regimens in patients with type 1 DM was associated
with a significant reduction in PP oxidative stress.
Thigh
12.7-mm
1.02
(0.11)
0.83,
1.27
1.06
(0.11)
0.85,
1.32
0.91
(0.11)
0.72,
1.16
0.99
(0.09)
0.82,
1.20
Abstract #129
Pramlintide Pharmacokinetics in Type 1 and Type 2
Diabetes: Effects of Injection Site, Needle Length
and Body Size
Although there was some variability across the various
subgroups, there were no clearly discernible, clinically
significant effects of injection site, needle length, or BMI
on relative PRAM bioavailability in either the T1DM or
T2DM groups. Nausea was the most common adverse
event reported, occurring more frequently among T1DM
than T2DM subjects.
Conclusion: Generally, results of this study indicate
that PRAM can be administered at different injection sites,
with two needle lengths, and at a fixed dose irrespective of
body size.
Abstract #130
C. Weyer. MD, Y. Wang, PhD, C. Schnabel, PhD,
E. Zabala BS, K. Lutz PhD, M. Fineman BS, and
O. Kolterman, MD
Profile of an Endocrine Clinic in Jamaica
Objective: To evaluate the effects of injection site,
needle length, and body size on the pharmacokinetic (PK)
of subcutaneous (SC) pramlintide (PRAM).
Background: In clinical studies, the amylin analog
PRAM reduces HbA1c levels without weight gain in patients with type 1 (T1DM) and insulin-using patients with
type 2 (T2DM) diabetes mellitus. Unlike insulin, the PK
profile of PRAM allows routine treatment with a fixed-dose
regimen.
Methods: This randomized, open-label, domiciled, 5way crossover study assessed the effects of injection site,
needle length and body size on the PK of subcutaneous
(SC) PRAM in 67 insulin-using patients with T1DM or
T2DM who were either nonobese (body mass index [BMI]
27 kg/m2) or obese (BMI 30 to 45 kg/m2). On 4 consecutive days, subjects received a single SC injection of PRAM
(60 g in T1DM, 120 g in T2DM) using 3 different injection
sites (2 needle lengths, 6.0-mm and 12.7-mm) in the abdomenal site.
Objective: To determine the type and frequency of
diseases in the clinic and determine the future growth and
development.
Methods: This was a retrospective review of appointments and final diagnosis of all patients attending our clinic
between October 1992 and May 1999.
Results: There were 263 clinic days and 6314 patient
visits made by 1503 patients. The commonest organ affected was the thyroid (83.2 %) and the anterior pituitary
gland (7.4%). The commonest thyroid diseases seen were
hyperthyroidism (54.7 %) and hypothyroidism (18.5%).
Two cases of carcinoid syndrome were noted.
Conclusion: Further development of our endocrine
clinic might involve creating a separate thyroid clinic.
R. Wright-Pascoe, MD
Abstract #131
Secondary or Tertiary Hyperparathyroidism in
Tumor Induced Osteomalacia
Naifa L. Busaidy, MD, Camilo Jimenez, MD,
Mouhammed Amir Habra, MD, and Robert F. Gagel, MD
Objective: We report two cases of tumor-induced
osteomalacia (TIO) who developed primary or secondary
hyperparathyroidism.
Background: TIO is a rare form of (usually acquired)
hypophosphatemic osteomalacia. It is most commonly associated with benign mesenchymal tumor of bone, although
it may occur in patients with several different malignancies,
including prostate and lung cancer. Recent studies indicate
that increased production of the newly-discovered hormone
fibroblast growth factor 23 (FGF23) causes the renal phosphate-wasting characteristic of this syndrome. Effective
management of TIO includes treatment with phosphate or
vitamin D, or surgical excision of the tumor.
Case report: The first case (JCEM 85:549, 2000)
presented with a long-term history of acquired hypophosphatemic osteomalacia. Following 10 years of phosphate
and vitamin D therapy the patient developed primary hyperparathyroidism. The second patient presented with TIO
with hypophosphatemia and a hip fracture with a hemangiopericytoma but was not curative. Subsequent treatment
phosphate and vitamin D 50,000 units daily improved his
clinical status, but led to development of secondary hyperparathyroidism with intact parathyroid hormone values of
100 pg/mL (normal 10-65 pg/mL) and a low ionized calcium level. Doubling of his vitamin D and calcium normalized his PTH levels.
Conclusion: These two cases emphasize the importance of monitoring serum ionized calcium and intact PTH
levels in patients with TIO.
Abstract #132
Inadequate Iodine Supplementation in
American Multivitamins
Stephanie L, Lee, MD, PhD, FACE, and Jatin Roper, BS
Objective: To determine the iodine content of daily
multiple vitamins to help patients maintain an adequate iodine daily intake, especially during pregnancy and lactation.
Background: The iodine requirement for normal thyroid physiology in nonpregnant adults is 150 μg/day and
between 200-290 μg/day in pregnant and lactating women.
The U.S. National Health and Nutrition Examination
Survey (NHANES III) conducted from 1988 to 1994
demonstrated a decrease in the average urinary iodine con-
centration to 124.6 μg/g creatinine compared to the 293.3
g/g creatinine noted in the NHANES I survey performed
between 1971 and 1974. In particular, the risk for insufficient dietary iodine intake among women of childbearing
age (15-44 years) increased 380%.
Methods: We searched retail pharmacies, online
pharmacies, corporate websites, the PDR for Nutritional
Supplements (1997), and Facts and Comparisons (Wolters
Kluwer Health, 2003) to obtain names and reported iodine
contents of multivitamins. Our survey included overthe-counter and prescription vitamins, but not parenteral
products. Twelve pediatric- and adult-strength multiple
vitamins were evaluated for iodine content.
Results: The majority of multivitamins (268 of 560;
52%) do not contain iodine. One hundred ninety-seven of
390 (51%) adult multivitamins, 44 of 69 (64%) prenatal
multivitamins, 27 of 62 (45%) children’s multivitamins,
and 0 of 39 (0%) infant liquid multivitamins contain iodine.
Most adult multivitamins that list iodine contain the RDA
of 150 μg per daily dose. Although the majority of prenatal
vitamins contain some iodine, only 10 of 69 (14.5%) contain more than 150 μg per daily dose. Six pediatric and six
adult multivitamin formulations were analyzed spectrophotometrically for iodine, revealing analyzed contents similar
to those stated on the multivitamin label.
Conclusion: These results are notable for the often
inadequate iodine content of multivitamins. The majority
of multivitamins do not contain iodine, and of those that
do, most contain 150 g per daily dose. Notably, only 10 of
69 (14.5%) prenatal multivitamins contain more than 150
g per daily dose, despite international agreement that pregnant and lactating women require at least 200-290 g per
day of dietary iodine. Only eight of 101 (8%) of children’s
and infant’s multivitamins contain at least the RDA. Of
significance, none of the liquid children’s/infant’s multivitamin formulations contain iodine. Mild iodine deficiency
(<50 μg/day) is associated with goiter formation and may
have implications for normal fetal and infant growth and
development. It is important that populations that avoid
food containing iodine such as iodized salt, eggs, and milk
receive a multivitamin supplement that contains adequate
levels of iodine. A list of multivitamins and the labeled
content of iodine is available on the American Thyroid
Association website, www.thyroid.org.
Abstract #134
Metabolic Syndrome Diagnosis and Management in
Continuity Care
S. Dipp, MD, P. Charney, MD, and N. Rennert, MD
Objective: To explore the diagnosis and management
of metabolic syndrome among patients in continuity care.
Background: Physicians often do not have a high index of suspicion for the presence of metabolic syndrome.
Methods: Norwalk Hospital Internal Medicine residents provide all medical care at a local community health
center under supervision of attending physicians. Review
of over 400 charts of continuity patients was completed
between Sept 2002 and March 2003 with attention to components of metabolic syndrome.
Results: Chart review revealed that blood pressure
was documented in 97% of cases, but weight was noted less
often (63%), as were height (19%), BMI (4%), and physical inactivity (0%). Diagnoses noted were obesity (14%),
hypertension (62%), tobacco use (45%), abnormal lipid
profile (31%), and diabetes (30%). Management included
exercise (21%), diet (26%), tobacco cessation (14%), and
nutrition referral (1.4%).
Conclusion: Metabolic syndrome diagnosis and management should become a greater focus among physicians.
We have developed a pilot program for identification and
treatment of this condition.
Abstract #135
Pan Hypopituitarism in a Patient With
Metastatic Breast Cancer and Literature
Review of Pituitary Metastasis
G.A. DeSilva MD, Samuel S. Engel, MD
Objective: To describe a case of pan hypopituitarism
in a patient with metastatic breast cancer.
Method: Case presentation and review of related
literature.
Case report: A 73-year-old woman with a history of
metastatic breast cancer, was admitted to the hospital with
dehydration and psychosis. Laboratory evaluation revealed
a TSH level of 0.04 mIU/mL (normal 0.2-6 mIU/mL),
free T4 of 0.79 ng/dL (0.71-1.85 ng/dL), prolactin of 56.8,
ACTH of 12 pg/dL (5-52 pg/dL), morning random cortisol
of 0.8 μg/dL (7-25 μg/dL), FSH of 3.7 IU/L (<200 IU/L),
and LH <0.5 IU/L (15-70 IU/L). Initial MRI of the brain revealed an enlarged pituitary gland with a possible adenoma
without evidence of chiasmal compression. MRI of the
pituitary confirmed the presence of an asymmetrically enlarged gland. The patient was treated with steroids and thyroid replacement therapy with resolution of her psychosis,
and subsequently received chemotherapy with adriamycin
for breast cancer. Repeat MRI of the brain 5 months later
revealed a decrease in the size of the pituitary lesion.
Discussion: We propose that this patient developed
panhypopituitarism secondary to pituitary metastasis of
breast cancer. Literature review reveals that 3 to 5% of
patients with any carcinoma have manifestations secondary
to pituitary metastasis. In one autopsy series, up to 27%
patients had micrometastases to the pituitary. In one study
of hypophysectomy specimens of patients with breast cancer, 5.5-25% had occult metastasis to the pituitary gland.
Breast cancer is the most common source of symptomatic
metastasis. Among women with symptomatic pituitary metastases, up to 70% are due to breast cancer. Further details
including clinical manifestations, diagnosis, treatment and
prognosis of pituitary metastasis will be discussed.
Abstract #138
Thyroid Function and Outcomes in
Chronic Critical Illness
Michael Goldberg, MD,
Jeffrey I. Mechanick, MD, FACP, FACN, FACE, and
David M. Nierman, MD
Objective: We defined thyroid status in patients with
chronic critical illness (CCI) and examined its relationship
with outcomes.
Background: Disturbances in thyroid function may
alter ventilatory drive, but their effect on liberation from
prolonged mechanical ventilation is unknown.
Methods: CCI patients were managed in a dedicated
respiratory care unit (RCU). Thyroid function tests (TSH
and free T4) were routinely performed at RCU admission.
We retrospectively screened a computer database covering
24 months for associations between thyroid function and
the following important clinical outcomes: liberation from
mechanical ventilation, survival to hospital discharge, and
RCU and hospital lengths of stay.
Results: Of 185 patients who were studied, 81% had
normal TSH values (0.35-5.50 μIU/mL). There were no
associations between categorical TSH values and outcome
variables. Mean TSH did not differ significantly between
patients who were successfully liberated from mechanical
ventilation (5.55 μIU/mL) and those who were not (3.10
μIU/mL) (P = 0.09), nor between those patients who survived to discharge (4.58 μIU/mL) and those who did not
(4.17 μIU/mL) (P = 0.80). Patients with hypothyroidism
were treated with levothyroxine and monitored according
to published guidelines; 88% were successfully weaned
and survived to discharge.
Conclusion: There is no evidence that thyroid status is related to liberation from mechanical ventilation or
survival or CCI patients. A small percentage of patients
with CCI have primary hypothyroidism, which should be
identified by routine screening and managed as in other
populations.
Abstract #139
Abstract #140
Differences in HbA1c Levels Between Insulin
Glargine and NPH Insulin at Equivalent Incidences of
Hypoglycemia in Patients With Type 2 Diabetes
Long-Term Efficacy and Safety of Pegvisomant:
Results From an Extension Phase of a Multicenter
Open-Label Trial in Patients With Acromegaly
Converting From Long-Acting Octreotide
Matthew Riddle, MD, Christophe Arbet-Engels, MD,
Ha H. Nguyen, MD
Objective: To explore differences in HbA1c levels
among patients with type 2 diabetes treated with insulin
glargine and NPH insulin given equivalent incidences of
hypoglycemia.
Background: Fear of hypoglycemia remains a barrier
to achieving HbA1c levels ≤7%. The Treat-to-Target Trial
demonstrated that systematic titration of bedtime NPH insulin or glargine added to 1 or 2 antihyperglycemic agents
can reach this target in almost 60% of insulin naïve patients
with type 2 diabetes mellitus but with more hypoglycemia
occurring when NPH is used versus glargine (Diabetes
Care 2003;26:3080-6).
Methods: Analysis of data from 721 subjects completing 24 weeks of treatment, using a Poisson regression
model, further examined the relationship between hypoglycemia and HbA1c levels achieved with each type of
insulin.
Results: Baseline characteristics for 347 subjects
taking glargine and 374 taking NPH were similar: 55%
versus 56% male, mean age 55 versus 56 years, duration of
diabetes 8.5 versus 8.9 years, BMI 32.5 versus 32.2 kg/m2,
baseline HbA1c level 8.61% versus 8.56%, respectively.
Of subjects with HbA1c levels ≤8.5% at baseline, 74%
versus 75% reached the HbA1c target level, compared with
48% versus 45% for those starting above 8.5%. Of those
with baseline HbA1c levels ≤8.5%, 54% had no nocturnal hypoglycemia documented ≤69 mg/dL with glargine
versus 49% with NPH; those starting above 8.5% experienced such events in 38% versus 45% of cases. Within
the range of HbA1c 5.6% to 7.8%, statistically lower rates
of nocturnal and all hypoglycemic events occurred with
glargine treatment (P<0.05). At given rates of hypoglycemia, clinically significant differences of HbA1c levels were
predicted by the model.
Conclusion: As the following figure shows, under the
conditions of this trial, at a rate of 3 events per patient-year
(one every 4 mo) patients are predicted to achieve HbA1c
levels of 6.5% with glargine versus 7.5% with NPH.
David M. Cook, MD
Objective and background: Patients with acromegaly
who received long-acting octreotide (LAR) for ≥3 months
were enrolled in a 32-week, open-label trial of pegvisomant. These results were reported at the 2003 Endocrine
Society meeting. Here, we report the results of a 12-week
extension phase of that study.
Methods: At the end of the open-label, 32-week
pegvisomant conversion trial, patients who were on a
stable dose of pegvisomant qualified to continue in a 12week extension phase. In the conversion trial, pegvisomant
10 mg/d was initiated 4 weeks after the last dose of LAR
(week 0), and the dose was adjusted at weeks 12, 20, and 28
with the aim of normalizing serum IGF-I concentrations.
During the extension phase, patients continued to receive
the same dose of pegvisomant they received at the end of
the initial trial. The mean dose at week 32 was 16 mg/d
(range, 5–40 mg/d).
Results: Fifty-two patients were enrolled in the initial
trial; 31 patients continued in the extension phase. During
the course of the extension period, median IGF-I concentrations were not significantly changed from week 32 to
week 44 (226 μg/mL [range, 103–514 μg/mL] versus 192
g/mL [range, 93–456 g/mL], respectively). With continued
treatment, the percentage of patients with IGF-I concentrations within the age-adjusted normal range increased from
84% (26/31) at week 32 to 97% (28/29) at week 44 (vs.
46% with LAR at week 0). Pegvisomant was generally
well tolerated throughout the entire treatment period, with
little difference in the types and incidence of adverse events
between the initial 32-week study period and the extension
period.
Conclusion: By the end of the study, normalization
of IGF-I concentrations was achieved in almost all patients
treated with pegvisomant.
Abstract #141
Congenital Adrenal Hyperplasia Associated
With Ovarian Adrenal-Like Tissue
I. Cruz-Bautista, A. Reza-Albarrán, B. Loredo,
S. Hernández-Jiménez, A. Gamboa, A. Angeles,
Paz Francisco, M.L. Robles, F.J. Gómez-Pérez, and
J.A. Rull
Objective: We report the case of a girl with nonclassic heterozygous 21-hydroxylase deficiency and ovarian
adrenal-like tissue.
Background: More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency. Many tumors like adenoma, myelolipoma, adrenal
hemangyoma, incidentalomas, or testes adrenal-like tissue
have previously been associated with congenital adrenal
hyperplasia (CAH). These testicular lesions are commonly
bilateral but ovarian adrenal rests are not frequent.
Case report: A 20-year-old woman with a family
history of diabetes and hypertension developed hirsutism,
acne, irregular menses, and overweight at the age of 14
years, and complained of recent worsening of hirsutism
and deep voice. Physical examination revealed increased
muscle mass, acantosis nigricans in cervical, axillar, and
inguinal regions, and mild clitoromegaly. Laboratory
evaluation on follicular phase revealed testosterone 1.6
and 4.9 ng/mL (normal 0.2-0.8 ng/mL), FSH 4.95 mU/mL
(4-12 mU/mL), LH 2.4 mU/mL (2-10 mU/mL), estradiol
43.97 pg/mL (24.5-195 pg/mL), 17--hydroxyprogesterone
(17OHP) 7.1 ng/mL (0.3-2.2 ng/mL), prolactin 12 ng/mL
(3.9-29.5 ng/mL), cortisol AM 137 ng/mL (70-250 ng/mL),
ACTH 24 pg/mL (10-100 pg/mL), DHEA 7.7 ng/mL (0.72.2 ng/mL), androstenedione D4 286 pg/mL (700-2000
pg/mL), DHEA-S 119 g/dL (35-430 g/dL), glucose 65
mg/dL and insulin 17.4 U/mL, HOMA 2.7, Ca-125 antigen
10.7 U/mL (0.0-35 U/mL), α-fetoprotein 0.5 ng/mL (0.110 ng/mL), and carcinoembriyonic antigen 2.2 ng/mL (0-5
ng/mL). Ultrasonography and CT scanning revealed an
enlarged right ovary due to a 4-cm mixed tumor; adrenal
glands appeared normal. ACTH-stimulated 17--hydroxylase confirmed the diagnosis of CAH. Unilateral salpingooophorectomy was performed. Histological examination of
the tumor (4.1 cm x 3.2cm) revealed polygonal cells with
abundant cytoplasm and compact nuclei, and histological
diagnosis was tumor of steroid cells with typical characteristics of adrenal tissue. The patient was treated with metformin 500 mg and cyproterone acetate. Three months later,
the patient’s testosterone levels fell to 1 ng/mL (0.2-0.8
ng/mL) and there was improvement of clinical features and
regular menses. Nowadays her testosterone and 17OHP
levels are 0.3 and 0.69 ng/mL, respectively.
Conclusion: In this case, presence of tumor was
investigated because of this patient’s high levels of testosterone. This search revealed adrenal rests in ovarian tissue. Although there was a fall in the androgen levels after
resection of the tumor, control of the overproduction of
androgens continued to be necessary due to the underlying
adrenal enzyme deficiency.
Abstract #142
Metastatic Enlarging ACTH-Producing
Pituitary Carcinoma
Loredo Beatriz, I. Cruz-Bautista, A. Reza-Albarrán,
A. Angeles, Paz Francisco, F. Gómez Perez, J.A Rull
Objective: We report the case of a 35-year-old man
with a silent corticothrop metastatic carcinoma.
Background: The pathogenic mechanisms underlying pituitary tumorigenesis are largely unknown. Previous
reports suggest that aggressive pituitary adenomas and/or
carcinomas may be associated with genetic alterations
distinct from those responsible for more common and
less aggressive pituitary adenomas. Pituitary carcinoma is
extremely rare, representing less than 1% or all pituitary
tumors. The latency period between resection of the primary lesion and presentation with metastases range from 3
to 180 months. Some series found an association between
p53 expression and tumor behavior and the loss of Rb gene
expression and development of some pituitary carcinomas,
but results are variable.
Case report: A 19-year-old young man presented to
our practice complaining of loss of libido. Ophthalmologic
examination revealed central visual field alterations that
progressed to bilateral amaurosis. Computed tomography
(CT) scanning of the head revealed a pituitary-dependent
mass. Trans-sphenoidal surgery was performed with resection of a nonproducing pituitary adenoma. His visual fields
returned to normal and no replacement therapy was given
postoperatively. One year later, the patient returned to our
office complaining of continuous headache. Follow-up CT
of the head revealed a remaining pituitary mass, larger
in size than the previous one. Conventional radiotherapy
(total dose of 5500cGy) was administered. At the age of
24, four years later, visual alterations appeared, and preoperative neuroimaging revealed local sellar recurrence.
Subfrontal craniotomy was performed, and pathological
diagnosis was ACTH-secretory pituitary chromophobe
adenoma. Complete visual field recovery did not occur.
Hypopituitarism developed postoperatively and replacement therapy with T4, glucocorticoid and testosterone was
initiated. In 1997, nine years after the beginning of the
disease, clinical symptoms of Cushing syndrome appeared.
Overnight 1- and 8-mg dexamethasone suppression tests
indicated a diagnosis of adrenocorticotropin-dependent
Cushing’s syndrome. IRM revealed three masses (about
2 inches each) in the right temporal and sphenoidal areas
and near the cavernous sinus. Transfrontal craniotomy was
performed. Histological examination of tumor tissue revealed pituitary tissue, and immunohistochemical analysis
revealed positive staining for ACTH, establishing that the
tumor was of pituitary origin. Months later IRM showed
more pituitary masses and in 1998 this patient underwent
a trans-sphenoidal resection to place a brachytherapy sensor and received eight sessions. He was free of symptoms
and signs of hypercortisolism for two years. In May 2002
he again developed clinical and biochemical features of
hypercortisolism with the plasma ACTH remaining at high
levels. IRM revealed an increase of size of a metastatic pituitary tumor with left cavernous sinus infiltration.
Comment: We present the case of a young man with
a nonfunctioning carcinoma that evolved over 9 years to a
metastatic ACTH-secretory pituitary carcinoma.
In the beginning the tumor exhibited features of silent
corticotroph carcinomas, aggressive tumors with recurrence rates higher than 50%.
A minority of previously described ACTH-secreting carcinomas exhibit only mass effects at presentation.
Some patients develop Cushing’s disease at the time of
local recurrence or with metastatic disease, as did our
patient. Whether these tumors were truly nonfunctioning
or produced a subclinical Cushing’s disease is not clear.
Generally they undergo repeated resections of metastases,
and radiation therapy has only a palliative effect. Mean
overall survival from time of diagnosis of Cushing’s disease to death among published cases is 10 years.
Abstract #143
The Prevalence of the Components of Metabolic
Syndrome Among Patients Infected With HIV
Mehta Roopa, Loredo Beatriz, Sañudo Maria- Elena,
Hernández Sergio, C.A. Aguilar-Salinas, F.J. GómezPérez, J.A Rull-Rodrigo
Objective: To investigate the prevalence of the components of metabolic syndrome among patients infected
with HIV.
Background: Persons infected with HIV develop
metabolic abnormalities in relation to antiretroviral medications and because of the infection itself. These alterations
include dyslipidemia, morphological changes (accumulation of fat and lipoatrophy) and disorders of carbohydrate
metabolism. The metabolic abnormalities are similar to
those encountered in metabolic syndrome. There is no data
regarding the prevalence of these abnormalities in Mexico.
Method: In this retrospective, cross-sectional study,
records of 468 patients with HIV who attended at least one
appointment in the hospital were reviewed. The prevalence
of dyslipidemia, arterial hypertension, diabetes, and family
history of these conditions were noted. Two hundred ninety-seven patients (77.3%) had never received antiretroviral
treatment; those remaining were on one or more antiretroviral drugs. The NCEP-ATP III criteria were employed for
diagnosis of the components of metabolic syndrome.
Results: The majority of the patients were men
(88.5%). More than a third had a first degree relative with
diabetes. Family history of coronary heart disease (20.6%)
and dyslipidemia (7.8%) was also present. Among patients
naive to antiretroviral treatment, the following prevalences
were found: hypertriglyceridemia 35.1%, HDL-C <35 mg/
dL 37.9%, systolic hypertension 7.3%, diastolic hypertension 1.0%, and diabetes 2.7%. 19.2% of these patients had a
BMI <20, and 22.4% were overweight or obese. The group
on antiretroviral treatment had the following results: hypertriglyceridemia 53.6%, low HDL-C 44.4%, systolic hypertension 2.7%, diastolic hypertension 1.4%, and diabetes
3.6%. Seventeen percent had a BMI <20, and 26.7% were
overweight or obese. On comparing the two groups, only
prevalence of hypertriglyceridemia was significantly different (P<0.001). With regard to medications, nucleoside
reverse transcriptase inhibitors were most frequent (67.1%)
followed by protease inhibitors (PI) (29.7%). Indinavir was
the PI most commonly used (14.7%). Prevalence of the
metabolic syndrome was 9.4% among those patients naive
to antiretroviral therapy and 6.7% among those on therapy.
Hypertriglyceridemia was predominantly noted among
patients naive to treatment who had a BMI < 25 (70.5%).
In contrast, among treated patients, hypertriglyceridemia
was found frequently in individuals with BMI >25 (50%)
(P=0.01). A similar pattern was noted with respect to hypercholesterolemia, but was not statistically significant.
Conclusion: These results demonstrate that risk
factors (e.g. family history) that predispose HIV patients
to metabolic complications associated with the pharmacological treatment of HIV are prevalent in the Mexican
population. Before the initiation of treatment, there is
a high prevalence of hypertriglyceridemia and/or low
HDL-C; predominantly among subjects with BMI <25. In
subjects on therapy the prevalence of hypertriglyceridemia
is higher still, generally observed in those with BMI >25.
These findings suggest that causal mechanisms for hypertriglyceridemia are distinct in this population. Among those
on therapy, nutritional recuperation and adverse effects of
medications may explain the results, while among those
naive to therapy, wasting and opportunistic infections may
be responsible.
Abstract #145
Osteoporosis in a Young Man
R. Mehta, L. Robles, A.E. Yépez, A. Reza,
F. Gómez-Pérez, and J.A. Rull
Objective: To describe diagnosis and therapy of idiopathic osteoporosis in a young man.
Case report: This is the case of a 32-year-old man who
presented with left hip pain and back pain at the age of 25. A
year later he noted a reduction in his height and that gradually
the pain had worsened, preventing him from climbing stairs.
He received analgesics and calcium but did not improve
significantly. His spinal radiographs revealed generalized
osteopenia with fractures and degeneration of the vertebral
bodies. The serum levels of parathyroid hormone, calcium,
and phosphorus were normal. In addition he reported a history of multiple fractures of the left shoulder and left hip.
The patient was first seen in February 2002 and mentioned
weight loss of 10 kg in the previous 5 years, a reduction in
height from 1.64 m to 1.46 m and reported pain in his chest,
back, and left hip. Protein electrophoresis and bone marrow
aspiration revealed normal findings, and findings of Bence
Jones analysis were negative. Radiological studies revealed
severe reduction in bone density and biconcave deformation of all the lumbar vertebral bodies, plus salt-and-pepper
changes in the cranial bones and lytic lesions in the ribs.
Densitometry results were as follows: right hip T = -5.1; vertebral column T = -6.4; left radius T = -3.6. This patient was
diagnosed with idiopathic osteoporosis of the young adult,
high turnover type, and began on treatment with alendronate
70 mg/week and 600 mg elemental calcium and vitamin
D. In April 2002, bone turnover markers improved to the
following values: osteocalcin 48.6; hidroxiproline urinary
18.75; N-telopeptides 47.3.
Table. Laboratory Results
Ca 9.8
(8.4-10.2)
AP 145
(44-153)
CT 230
hidroxiproline
urin. 21.6mg/g
Cr (6-25)
Testo.8.1
(3.7-9.5)
Cortisol 75
P 4.1
(2.2-4.3)
Hb 18.3
(14.5-17.7)
HDL 44
N telopep 66.6
(6-25)
LH 3
( 0.5-7)
IGF-1 105ng/
mL
( 71-290)
Alb 4.1
(3.6-5.0)
Hct 53.5
LDL 141
CaU 96
FSH 1
(1-8)
IGFBP-3
1.07 mg/L
(1.4- 3.22)
Mg 2.29
(1.8-2.5)
Leu 5.3
PTH 29.2
pg/mL
(6-54)
PU 363
TSH 1.9
(0.3-3.5)
Cr 0.8
(0.6-1.2)
plat 210
calcitonin
10 pg/mL
(10-500)
Cr U 783
GH 2.8
(0-7)
ESR 1
TG 226
osteocalcin 25 OH-D3 17
67.1 ng/mL ng/mL ( 10-60)
(16-44)
ACTH 37
Discussion: In the United States, approximately 1.5
million men over the age of 65 years have osteoporosis and
8-13 million have osteopenia. The lifetime risk of fracture
among men 50 years of age is 13.5%, increasing to 25.6%
by the age of 60 years. Fractures are less frequent among
men than among women, though mortality associated with
hip fractures is much higher. The causes of osteoporosis in
men can be identified in 40-60% of those with osteoporotic
fractures. The most common causes are steroid use and
hypogonadism; gastrointestinal diseases, alcohol abuse,
anticonvulsant use, vitamin D deficiency, and transplants
are other significant causes. In this patient, the diagnosis
of idiopathic osteoporosis was one of exclusion, and almost 50% of men with osteoporosis fall into this category.
However, idiopathic osteoporosis has been poorly categorized. Usually these men are symptomatic and report back
pain, and their ages vary widely from 23 to 86 years, with
an average age of 60 years. No lifestyle risk factors (alcohol excess or tobacco use) or secondary causes of osteoporosis are present. However there are often inconsistencies
between cases. Some have the following biochemical
findings; hypercalcuria, low IGF-1, low 1-25 hydroxyvitamin D levels, and high urinary hydroxyproline levels.
Studies suggest that the correlation between serum levels
of free estrogen and bone mineral density in elderly men
is greater than that between levels of free testosterone and
bone mineral density. Bone histology shows a reduction in
osteoblastic activity in some patients and in others a greater
degree of bone resorption. It is thought that there are two
types of idiopathic osteoporosis among young adults, one
of high bone turnover and another related to low bone turnover. There is, however, not much information regarding
optimal treatment of these young men. Use of etidronate,
alendronate, calcitriol, testosterone, fluoride and PTH has
been studied with varying results. This patient appears to
have responded well to the treatment prescribed. This case
illustrates the difficulties in the diagnosis and therapy of
idiopathic osteoporosis in men.
Abstract #146
Unusual Glucose-Insulin Response During the Oral
Glucose Tolerance Test of an Insulinoma in a Case of
Multiple Endocrine Neoplasia Type 1: A Case Report
Rodríguez-Vallejo F. MD, J.A. Rull MD,
F. Gómez-Pérez MD, A. Angeles MD,
A. Reza-Albarrán MD, S. Rodríguez MD, S. Hernández
Objective: To report the unusual response to an oral
glucose load of an insulinoma in a woman with multiple
endocrine neoplasia (MEN) type 1.
Methods: A 33-year-old female presented with
episodes of loss of consciousness associated with headache and sometimes tonic-clonic seizures, since November
2002. Her serum glucose level was 0.94 mmol/L (17 mg/
dL); in one of the episodes an intravenous dextrose was
given, with complete recovery. Further studies demonstrated the presence of MEN-1. The table below shows serum
glucose and insulin values during an oral glucose tolerance
test (OGTT).
Abstract #147
TIME
Objective: To describe a case of extra-renal calcitriol
secretion by granuloma due to injection of oil.
Methods: A 42-year-old male received oil implants
in the buttocks several years previously. In 2002, he complained of malaise, fever, weight loss (20 kg in six months),
constipation, pruritus, arthralgias, and myalgias. Physical
examination revealed an indurated mass in the lumbar area.
Initial laboratory evaluation revealed calcium 19.9 mg/dL
(normal value 8.5-10.5 mg/dL), phosphorus 2.93 mg/dL
(normal 2.3-4.3 mg/dL; he have been on hemodyalisis during the last months), and hypercalciuria with a serum creatinine of 3.86 mg/dL (0.6-1.3 mg/dL) and alkaline phosphatase levels in the high normal range. Viral serology for
hepatitis B and C viruses and HIV were negative, as were
PPD results. Serum protein electrophoresis and an radiographic skeletal survey revealed normal findings. A PTH
intact molecule was 1.02 pmol/mL (6 to 54 pmol/mL), a
PTH-rp 0.6 pmol/L (<1.4 pmol/L), 25(OH)-vitamin D 15.2
ng/mL (10-60 ng/mL), angiotensin converting enzyme 89
U (14-70 U) and serum 1,25 (OH) 2-vitamin D 37.2 pg/mL
(25.1-66.1 pg/mL). Ultrasound of the buttocks revealed the
presence of foreign material with extension to the lumbar
area and a renal biopsy showed chronic granulomatous nephropathy. Surgical ressection of the foreign material was
done and the pathology study revealed a granulomatous
reaction to foreign material.
Discussion: It is probable that the severe hypercalcemia noted in this case was due to calcitriol production by
the foreign material granulomas (oil injection). The normal
value of serum cacitriol is inappropiate since 1-alpha-hydroxilase should be inhibited by hypercalcemia; furthermore the loss of functional renal mass caused decreased
renal calcitriol production (this patient had chronic renal
failure). Finally, the very low PTH value should decrease
renal cacitriol production. It is possible that the slightly
decreased 25-(OH) vitamin D value is due to increased
conversion to calcitriol by the granulomatosous tissue (and
had it been corrected, serum 1,25-(OH) 2-vitamin D value
would have increased even more). Some cases of hypercalcemia due to calcitriol production by granulomatous reaction induced by silicone have been reported associated with
renal failure, however, similar cases have been reported
associated with the use of “oils”.
GLUCOSE (MMOL/L)
Basal
30 minutes
60 minutes
90 minutes
2 hours
3 hours
2.2
4.9
2.8
2.1
4.9
4.3
INSULIN (μU/L)
27.8
1322
659
48.5
128
55
A CT scan and MRI of the pancreas revealed enlargement of the tail and part of the body of the pancreas.
In October 2003, a subtotal pancreatectomy (tail and
body) was performed, with resection of multiple tumors.
Pathology findings revealed seven neuroendocrine tumors
(the largest of 3.1 cm x 2.9 cm) that stained positive for
the presence of insulin and glucagon and negative for VIP
and somatostatin. Hyperparathyroidism was diagnosed
and treated by resection of three and a half hyperplastic
glands.
Discussion. In most patients with insulinoma, insulin values follow an autonomous pattern, independent of
glucose values. In this case, however, there was a close
correlation between glucose and insulin changes, although
all insulin concentrations, including the fasting one, were
inappropiately high. This may be explained by overstimulation of normal islets beta cells by the long period of concentrated glucose infusions to avoid hypoglycemia.
Hypercalcemia Associated With Extra-Renal
Calcitriol Secreted by Granuloma due to Oil as
Injection: A Case Report
F. Rodríguez-Vallejo, MD, F. Gómez-Pérez, MD,
Reza-Albarrán, MD, A. Niño, MD, S. Hernández, MD,
A. Uribe, MD, J.A. Rull, MD

2004 Abstracts - American Association of Clinical Endocrinologists

Transcription

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