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Vol. 8/2009 Nr 2(27)
Endokrynologia Pediatryczna
Pediatric Endocrinology
Beta-endorphin Levels in Children with Endocrine Disturbances
Poziomy beta-endorfin u dzieci z zaburzeniami endokrynnymi
Leszek Szewczyk, 1Anna Bury, 2Helena Jankowska, 1Robert Piekarski
1
Department of Pediatric Endocrinology and Neurology, Medical University in Lublin
Department of Nuclear Medicine, Medical University in Lublin
1
2
Adres do korespondencji:
Leszek Szewczyk, Klinika Endokrynologii i Neurologii Dziecięcej, Uniwersytet Medyczny w Lublinie,
ul. Chodźki 2, 20-093 Lublin, l.szewczyk@wp.pl
Key words: beta-endorphin, GHD, type 1 diabetes mellitus, hyperthyroidism, hypothyroidism
Słowa kluczowe: beta-endorfina, SNP, cukrzyca typu 1 nadczynność tarczycy, niedoczynność tarczycy
ABSTRACT/STRESZCZENIE
Background. A few data of experiments indicate that opioids play an important role in behavior, appetite and
hormonal secretion control. The data suggest neuro-modulatory role of endogenic opioids in GH secretion; the
participation in glucose-homeostasis regulation processes and relation between opioid system and pituitary thyroid
axis function. Materials. 90 children, 10–17 years of age with endocrinal dysfunction: 20 children with GH deficiency;
30 children with type 1 DM; 30 children with hyperthyroidism and 10 children with hypothyroidism before and during
treatment. The control group consisted with 30 healthy peers. Methods. Beta-endorphin (ß-E) levels (RIA Kit Incstar
Corp.) were in those groups investigated. Results. ß-E levels in healthy individuals was M = 8.43±1.41 pmol/l, in
GH deficiency was M = 6.02±2.05 pmol/l, in hyperthyroidism before and during treatment was M= 8.77±2.57 and
M = 5.71±2.29 pmol/l, respectively; in hypothyroidism before and during treatment was M = 5.56±1.20 pmol/l and
M = 10.57±1.92 pmol/l, respectively; in IDDM group with ketoacidosis was M = 5.12±2.02 pmol/l and after achieving
metabolic balance was 8.26±2.37 pmol/l. Conclusions. In GH deficiency there was low levels of ß-E. The lowest
values are determined in children with bigger bone age delay. The changes of TSH and ß-E levels during treatment
of adolescents with hyper- and hypothyroidism suggest the correlation between opioid system and thyroid activity. In
diabetic children with ketoacidosis and increased fructosamine values – ß-E levels were lower than in children with
normal fructosamine level and during balance period. Pediatr. Endocrinol. 8/2009;2(27):9-14.
Wstęp. Dane z literatury wskazują na rolę opioidów w regulacji zachowania, apetytu i kontroli sekrecji hormonalnej.
Badania sugerują neuromodulacyjną rolę endogennych opioidów w sekrecji GH; uczestniczenie w procesach regulacji homeostazy glukozy i zależności pomiędzy układem opioidowym a czynnością osi przysadka–tarczyca. Materiał/
metody. Badania dotyczyły 90 dzieci w wieku 10–17 lat z zaburzeniami endokrynnymi (20 dzieci z SNP, 30 dzieci
z cukrzycą, 30 dzieci z nadczynnością i 10 z niedoczynnością tarczycy). Próbę kontrolną stanowiło 30 zdrowych dzieci.
Wyniki. Poziomy beta-endorfin u zdrowych dzieci wynosiły średnio M = 8,43±1,41 pmol/l, u dzieci z SNP – M =
6,02±2,05 pmol/l, w grupie z nadczynnością przed leczeniem – M = 8,77±2,57 pmol/l i podczas leczenia M = 5,71±2,29
pmol/l, w grupie z niedoczynnością odpowiednio przed leczeniem M = 5,56±1,20 pmol/l i w trakcie leczenia M =
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10,57±1,92 pmol/l, u dzieci z cukrzycą typu 1 w stanie ketoacidozy M = 5,12±2,02 pmol/l, zaś po uzyskaniu wyrównania
metabolicznego M = 8,26±2,37 pmol/l. Wnioski. 1. U dzieci z SNP stwierdzano niskie poziomy beta-endorfiny, najniższe
u dzieci z większym opóźnieniem wieku kostnego. 2. Zmiany poziomu TSH i beta-endorfiny podczas leczenia nadczynności i niedoczynności tarczycy sugerują korelację pomiędzy układem opioidowym i czynnością tarczycy.
3. U dzieci z cukrzycą typu 1 w stanie ketoacidozy i niewyrównania poziomy beta-endorfin były niższe niż w stanie
wyrównania metabolicznego. Endokrynol. Ped. 8/2009;1(26):9-14.
Introduction
A few data of experiments indicate that besides
analgetic action opioids play an important role in
behavior, appetite [1, 2, 3] and hormonal secretion
control [4, 5]. The data suggest neuro-modulatory
role of endogenic opioids in GH secretion [5, 6, 7];
participation in glucose-homeostasis regulation
processes [8, 9, 10], relation between opioid system
and pituitary thyroid axis function [11, 12, 13],
activation of hypothalamic–pituitary–adrenal axis
[14, 15, 16, 17] and regulation od LH secretion [18].
Material and methods
The study compromised 90 children 10–17 years
of age with endocrinal dysfunction: 20 children with
GH deficiency – short stature < 3c., bone age delay
(M = 32% in comparison to chronological age);
30 children with type 1 DM (both in ketoacidosis
state and during balance period); 30 children
with hyperthyroidism (hyper-T); 10 children with
hypothyroidism (hypo-T). The control group
consisted of 30 healthy peers.
Beta-endorphin (ß-E) levels using RIA Kit of
Incstar Corporation were in those groups before and
after over monthly therapy investigated. In group of
short stature children GH deficiency after insulin
and clonidine test was determined. In children with
type 1 DM fructosamine levels were determined at
the same time in ketoacidosis state and balanced
period.
Hyperthyroidism and hypothyroidism were
confirmed by TSH, fT3, fT4 level measurement by
means of IMX method Abbott Corporation.
Results and interpretation
Beta-endorphin levels in investigated clinical
groups were illustrated in table I and figure 1.
Among factors which regulate GH secretion opiates
can play a neuromodulatory role in this regulation.
In children with GHD early morning levels of
beta-endorphin were significantly lower compared
to control healthy group (fig. 2). Our proper
observations [19] have found in children with GHD
increased beta-endorphin secretion in nocturnal
hours in time of maximal GH secretion. Decreased
early morning beta-endorphin levels could be one
of postulated factor influencing poor GH secretion.
The experimental studies reported by Chapman et al.
[20] and Willoughby and Medvedev [21] indicated
Table I. ß-Endorphin levels in investigated groups
Tabela I. Poziomy ß-endorfin w badanych grupach
ß-Endorphin levels in investigated groups:
* Healthy individuals
M = 8.43±1.41 pmol/l
* GH deficiency
M = 6.02±2.05 pmol/l
* Hyperthyroidism
before treatment
M = 8.77±2.57 pmol/l
and during treatment
M = 5.71±2.29 pmol/l
* Hypothyroidism
before treatment
M = 5.56±1.20 pmol/l
and during treatment
M =10.57±1.92 pmol/l
* Type 1 DM
10
with ketoacidosis
M = 5.12±2.02 pmol/l
and after achieving metabolic balance
M = 8.26±2.37 pmol/l
Szewczyk L. i inni: Beta-endorphin levels in children with endocrine disturbances
Fig. 1. Beta-endorphin levels (pmol/ml)in investigated
groups
Ryc. 1. Poziom beta-endorfin w badanych grupach (pmol/ml)
Fig. 2. Beta-endorphin levels (pmol/ml)in growth hormone
deficiency
Ryc. 2. Poziom beta-endorfin SNP (pmol/ml)
that activation of hypothalamic opioid receptors have
influenced pulsatile GH secretion and rhythm of its
secretion. Moreover, the studies of Wimmersma-Greidans and Grossman [22] have found that opioids
influenced GH secretion by means of somatomedin
secretion inhibition. The similar observation have
been reported by Korbonits et al. [23].
Our proper studies [24] have found lower plasma
beta-endorphin levels in children with diabetes
compared to healthy children. Experimental
animals diabetes investigation indicates to decrease
of beta-endorphin values in hypophysis, pancreatic
islets and plasma [25, 26, 27]. This situation and
β-E levels in children in ketoacidosis and in balance
state (tab. I and fig. 3) suggest the role of insulin
deficit in decrease of beta-endorphin synthesis.
Results of Hsu et al. [28] suggest that
hyperglycemia is responsible for increase of β-E
biosynthesis in the adrenal gland in diabetic rats and
decrease in β-E release from the anterior pituitary
[29]. On the other hand, beta-endorphin and other
opioids may also play a positive role in the local
Fig. 3. Beta-endorphin levels (pmol/ml) in relation to metabolic balance in type 1 diabetes mellitus
Ryc. 3. Poziom beta-endorfin (pmol/ml) w relacji do stanu wyrównania cukrzycy
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Endokrynol. Ped., 8/2009;2(27):9-14
stimulation of insulin secretion from islets of
Largenhans [10, 30–33].
The data from literature considering influence
of opioid action to TSH secretion is controversial.
There are either evidences for inhibitory [5,
34–36] and stimulatory its influence [37, 38] by
means of hypothalamus. Opiate peptides in man,
therefore, exert a slight tonic stimulatory effect
on TSH secretion [4]. Opiate peptides act at the
pituitary level or median eminence to modulate
the secretion of TSH [37]. Moreover, there are the
evidence for stimulatory influence of thyroxine for
β-E level increase [39, 40] and for opioid receptors
increase [11]. The observations of Ishac et al. [12]
have found the dependency of beta-endorphin
secretion from thyroid functional state. Taken
together, our results (fig. 4, fig. 5) provide evidence
that treatment of hypothyroidism by means of
L-thyroxine increases opioid activity, however
treatment of hyperthyroidism using thyreostatics
contribute to decrease opioid activity.
1. In GH deficiency there were low levels of ß-E.
The lowest values are determined in children with
bigger bone age delay. It suggest, that there is low
endogeous opioid stimulation of GH secretion (may
be via GHRH).
2. The changes of TSH and ß-E levels
during treatment of adolescents with hyper- and
hypothyroidism suggest the relation between
opioid system and thyroid activity imply inhibitory
influence of thyreostatics and stimulatory effect of
thyroid hormones for opioid activity.
3. In diabetic children with ketoacidosis and
increased fructosamine values ß-E levels were
lower than in children with normal fructosamine
level and during balance period. The probable role
of insulinotherapy and good diabetes control in
opioid system normalization is discussed.
Fig. 4. Beta-endorphin levels (pmol/ml) and TSH levels (mU/L)
in hyperthyroidism
Ryc. 4. Poziom beta-endorfin (pmol/ml) oraz TSH (mU/L)
w nadczynności tarczycy
Fig. 5. Beta-endorphin levels (pmol/ml) and TSH levels (mU/L)
in hypothyroidism
Ryc. 5. Poziom beta-endorfin (pmol/ml) oraz TSH (mU/L)
w niedoczynności tarczycy
Conclusions
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