Hormonal changes in girls with precocious adrenarche: a possible role for estradiol or prolactin.

Serum concentrations of dehydroepiandrosterone, DHA sulfate, estradiol, and prolactin in 20 girls with precocious adrenarche were compared with those of healthy girls of varying age and degrees of breast and sex hair development. Production of adrenal androgens, as reflected by serum DHA and DHA-sulfate concentrations, was significantly increased in PA above that in age-matched control subjects. Surprisingly, in spite of their lack of breast growth, the patients with PA also had serum estradiol levels that were higher than in the prepubertal girls and similar to those found in girls with both breast and pubic hair development. Serum prolactin concentrations in the patients with PA were not increased over those of the age-matched (less than 8 years) prepubertal girls. In the older prepubertal ( greater than 8 years) and early pubertal girls serum prolactin levels were lower. The finding of increased estradiol levels suggests that precocious adrenarche is not a distinct endocrine entity, but merely represents a variant of early adolescence in which estrogen secretion is sufficient to influence adrenal 3beta-hydroxysteroid dehydrogenase activity with a resultant rise in DHA production, but not sufficient to produce clinically apparent breast changes. The data do not support a similar role for prolactin.     

The influence of labor and delivery on preterm fetal adrenal function

The influence of labor and route of delivery upon umbilical cord serum levels of cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A, n = 89) presented a higher mean cord cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n = 80). Although there were no differences in cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n = 42) and those without labor (group B-II, n = 38), the mean cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal cortisol and dehydroepiandrosterone sulfate in preterm infants.     

Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome

Prenatal maternal therapy with glucocorticoid reduces the incidence of respiratory distress syndrome (RDS) in premature infants. To investigate the effects of this treatment on the fetal endocrine system, we determined serum concentrations of betamethasone, cortisol, dehydroepiandrosterone sulfate, growth hormone, and prolactin in cord blood of 215 treated infants and 117 untreated infants of 26--36 wk of gestation. Cortisol levels are suppressed within 6 hr of betamethasone treatment, decrease to 45% of the concentration in untreated infants (8.4 micrograms/dl), and return to normal by 7 days. Dehydroepiandrosterone sulfate is reduced maximally by 65% and returns to normal concentrations (123.5 micrograms/dl in 7 1/2 days. The suppression of both steroids was similar after treatment with 12 mg betamethasone (acetate and phosphate) daily 2 times or with 6 mg betamethasone (alcohol) twice daily 4 times. Peak betamethasone levels were higher after the 12 mg dose, but the two-treatment regimens produced a similar total exposure of the fetus to elevated serum glucocorticoid activity for 2 1/2 days and decreased plasma activity for the subsequent 4 1/2 days. Treated infants with low cortisol concentrations at birth increased their cortisol levels severalfold after birth in response to either intrapartum asphyxia or RDS. Betamethasone therapy did not affect cord serum prolactin levels, but the concentration of growth hormone was reduced at all ages. The suppression was greatest (53% decrease) among infants of 28 less than 32 wk, and, among older infants, there was a subsequent increase above control levels between 2 and 4 days after treatment. This study indicates that prenatal betamethasone treatment causes a transient suppression of fetal growth hormone and presumably those pituitary hormones which regulate steroid production by both the definitive and fetal zones of the fetal adrenal. However, the suppression of fetal cortisol does not interfere with the pituitary-adrenocortical response to stress after birth.     

The relation between the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the onset of puberty in patients of small stature

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGF I was slightly but highly significantly correlated to growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

SERUM DEHYDROEPIANDROSTERONE (DHA) AND SULPHATE (DHAS) AFTER ACUTE GROWTH HORMONE THERAPY

Abstract. Rudd, B. T., Rayner, P. H. W., Bassett, R. M. and Williams, J. W. (Institute of Child Health, University of Birmingham and Department of Clinical Endocrinology, Central Birmingham Health District, England). Serum dehydroepiandrosterone (DHA) and sulphate (DHAS) after acute growth hormone therapy. Acta Paediatr Scand, 69:287, 1980. —To test the hypothesis that growth hormone (hGH) may increase adrenal androgen production dehydroepiandrosterone (DHA) and its sulphate (DHAS) concentrations were measured by radioimmunoassay in the serum from 7 children with growth hormone deficiency, 2 of whom had delayed puberty. Two injections of hGH (10 mg) were given 48h apart and the hormone concentrations measured at 3, 6, 24 and 48h after the first injection, 3, 6 and 24h after the second. Basal DHA levels were positively correlated with age and bone age in 6 of the 7 patients ( p > 0.05). Increments of DHA and DHAS above or below basal at each time interval were calculated. The mean increments were higher ( p > 0.01–0.05) at 3h after the first injection and at 24h ( p > 0.025–0.05) after the second when compared to any other time during the test. Basal DHA concentrations were positively correlated with increments in DHA during the first and second 24 h of the test ( p > 0.05). DHAS concentrations showed little change throughout the test for all children. It is suggested that some children with growth hormone deficiency and receptive adrenals, increase their serum DHA concentrations after acute hGH therapy.     

Serum dehydroepiandrosterone (DHA) and sulphate (DHAS) after acute growth hormone therapy

To test the hypothesis that growth hormone (hGH) may increase adrenal androgen production dehydroepiandrosterone (DHA) and its sulphate (DHAS) concentrations were measured by radioimmunoassay in the serum from 7 children with growth hormone deficiency, 2 of whom had delayed puberty. Two injections of hGH (10 mg) were given 48 h apart and the hormone concentrations measured at 3, 6, 24 and 48h after the first injection, 3, 6, and 24h after the second. Basal DHA levels were positively correlated with age and bone age in 6 of the 7 patients (p less than 0.05). Increment of DHA and DHAS above or below basal at each time interval were calculated. The mean increments were higher (p less than 0.01-0.05) at 3 h after the first injection and at 24h (p lesal DHA concentrations were positively correlated with increments in DHA during the first and second 24h of the test (p less than 0.05). DHAS concentrations showed little change throughout the test for all children. It is suggested that some children with growth hormone deficiency and receptive adrenals, increase their serum DHA concentrations after acute hGH therapy.     

Umbilical cord cortisol and prolactin levels in preterm infants. Relation to labor and delivery

The influence of labor and route of delivery upon the umbilical cord serum levels of cortisol and prolactin in ninety-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A) presented a higher mean cord cortisol concentration than those delivered by cesarean section (group B); mean prolactin values, however, were not different between both groups. Although there was no difference in cortisol and prolactin levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I) and those without labor (group B-II), the mean cortisol concentration was significantly higher in group A than in group B-I. The mean prolactin levels did not differ among all the studied groups. It is concluded that there is no association between presence of labor or route of delivery and cord serum levels of prolactin, there is no association between spontaneous preterm labor and cord cortisol values and there is an association between vaginal delivery and high cord cortisol levels in preterm infants. It is suggested that the increase in serum cortisol levels does not precede the initiation of preterm parturition but it is secondary to the stress caused by vaginal delivery.     

Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities.

Serum concentrations of the adrenal androgen, dehydroepiandrosterone sulfate, were measured by radioimmunoassay in normal infants and children, in sick premature and full-term newborn infants, and in patients undergoing evaluation of the hypothalamic-pituitary-gonadal and -adrenal systems. Premature infants had significantly greater (p less than 0.001) levels of DHAS (263 +/- 40)[SE]migrong/dl) than did full-term infants (58.9 +/- 5.2) during the first ten days of life; further increments occurred in stressed "sick" infants. A gradual age- and maturity-related rise in serum concentrations of DHAS was observed during childhood with the earliest increase occurring prior to the onset of pubertal production of gonadal steroids. Serum levels of DHAS rose following administration of ACTH and were increased in patients with congenital adrenal hyperplasia, in whom rapid decrements followed treatment with dexamethasone. hCG or LH-RH treatment did not alter DHAS concentrations. These data suggest that direct secretion of DHAS by the adrenal gland and/or peripheral sulfation of DHA, rather than gonadal secretion, accounts for the majority of DHAS production. The involvement of adrenal androgens in the pubertal maturation of the reproductive endocrine system thus may be evaluated by quantitation of serum DHAS.     

UMBILICAL CORD CORTISOL AND PROLACTIN LEVELS IN PRETERM INFANTS

ABSTRACT. The influence of labor and route of delivery upon the umbilical cord serum levels of cortisol and prolactin in ninety-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A) presented a higher mean cord cortisol concentration than those delivered by cesarean section (group B); mean prolactin values, however, were not different between both groups. Although there was no difference in cortisol and prolactin levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I) and those without labor (group B-II), the mean cortisol concentration was significantly higher in group A than in group B-I. The mean prolactin levels did not differ among all the studied groups. It is concluded that there is no association between presence of labor or route of delivery and cord seum levels of prolactin, there is no association between spontaneous preterm labor and cord cortisol values and there is an association between vaginal delivery and high cord cortisol levels in preterm infants. It is suggested that the increase in serum cortisol levels does not precede the initiation of preterm parturition but it is secondary to the stress caused by vaginal delivery.     

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.     

Growth and somatomedin responses to growth hormone in Down's syndrome.

Five growth retarded children with Down''s syndrome, three girls and two boys aged between 3 1/2 and 6 1/2 years with trisomy 21, were treated with human growth hormone for six months. Before treatment the growth hormone response to sleep and insulin-arginine load, as well as serum concentrations of insulin, thyroid hormones, and cortisol was found to be in the normal range. During the treatment with human growth hormone the growth velocity increased in all the children with Down''s syndrome from 2.3-2.8 cm to 3.3-5.8 cm per six months. The serum concentrations of immunoreactive insulin like growth factor 1 (IGF-1) were low before treatment and increased during the treatment with human growth hormone. The serum concentrations of immunoreactive insulin like growth factor 2 (IGF-2), which were within the normal range, however, increased during treatment with human growth hormone. Children with Down''s syndrome respond to treatment with human growth hormone, with an increase in both growth velocity and serum somatomedin concentrations.     

SLEEP RELATED GROWTH HORMONE AND PROLACTIN SECRETION'IN CHILDREN DURING CONSTANT RATE ENTERAL NUTRITION

ABSTRACT. The aim of this study was to investigate the nocturnal secretion of growth hormone and prolactin in a particular model where nutrients are delivered continuously. Six children with severe intestinal diseases undergoing total constant rate enteral nutrition for 1.5 to 8 months have been studied; all children had a normal nutritional status at the time of the recording. Sleep patterns were studied by the usual polygraphic methods from 10 p. m. to 8 a. m. Blood samples were taken every 20 min through an indwelling catheter for growth hormone and prolactin plasma level determination. Several growth hormone peaks were observed with a peak always secreted in connection with stage III-IV of the first cycle. This early peak was significantly higher than the following ones. Nocturnal patterns of prolactin secretion showed individual differences characterized by a series of episodic releases which consisted of a few long rises (4 patients) and several small fluctuations; no correlation was found with the sleep patterns; no increase in the level throughout the night was observed. Loss of the rhythmicity of alimentation does not alter the secretion of growth hormone during sleep.     

1-deamino-8-D-arginine vasopressin in the treatment of central diabetes insipidus in childhood

The effectiveness of therapy with carbamazepine and clofibrate (oral therapy), intramuscular pitressin-in-oil, and intranasal 1-deamino-8-D-arginine vasopressin has been compared in 15 children with partial or complete central diabetes insipidus. Mean daily urine volume without therapy was 5.4 l and dropped to 1.1 and 1.6 l/day while receiving pitressin and DDAVP, respectively. Oral agents decreased the daily urine volume to 2.2 l in patients with partial DI, with good symptomatic control except for some nocturia. These agents had no effect in patients with complete DI and did not alter pitressin requirements. Duration of pitressin action was 24 to 36 hours with a significant incidence of hyponatremia. The duration of DDAVP effect was 8 to 20 hours, varying in individual patients. Children with partial DI required smaller doses of DDAVP and the duration of action was longer than in those with complete DI. Control of serum electrolytes was excellent using two doses per day and nocturia was eliminated. All patients who had received pitressin had growth hormone antibodies, but continued to grow normally unless there was pre-existing growth hormone deficiency. These antibodies gradually disappeared after approximately one year of therapy with oral agents or DDAVP. DDAVP did not alter growth hormone, cortisol, or prolactin levels during sleep. DDAVP is the antidiuretic therapy of choice in children with either complete or partial DI; to date, no side effects have been demonstrated.     

The Influence of Labor and Delivery on Preterm Fetal Adrenal Function

ABSTRACT. The influence of labor and route of delivery upon umbilical cord serum levels of Cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prena-tally to corticosteroids was studied. Vaginally born infants (group A, n=89) presented a higher mean cord Cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n=80). Although there were no differences in Cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n=42) and those without labor (group B-II, n=38), the mean Cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord Cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of Cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord Cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal Cortisol and dehydroepiandrosterone sulfate in preterm infants.     

Changes of serum allopregnanolone levels in the first 2 years of life and during pubertal development.

Allopregnanolone is the best characterized among neurosteroids, and its role in the control of neuroendocrine axes has attracted increasing interest recently. However, there is no available information about circulating levels of allopregnanolone during infancy, childhood and puberty. We studied two groups of children: 1) those aged between 0 and 2 y (n = 72), and 2) those aged between 6 and 18 y, at different Tanner's stages (n = 82). In each of these patients, serum allopregnanolone, progesterone, cortisol, and dehydroepiandrosterone levels were evaluated after informed consent; allopregnanolone was measured by RIA after acid extraction on cartridge. There was no significant variation of serum allopregnanolone levels either in male and female children during the first 2 y of life. Furthermore, although serum dehydroepiandrosterone levels showed a significant decrease, inversely correlated with age of the children (p < 0.01), serum cortisol and progesterone levels showed a significant age-related increase during the first 2 y of life. Cortisol and allopregnanolone levels were positively correlated (p < 0.01). During puberty, we observed a progressive increase in serum allopregnanolone levels in both boys and in girls, which were higher at Tanner' s stage IV-V (0.7+/-0.01 nM; mean +/- SEM) than at stages I-II (0.32+/-0.02 nM; p < 0.01); mean levels were significantly higher at puberty than in the first 2 y of life (p < 0.01). Furthermore, during puberty, serum progesterone and dehydroepiandrosterone levels also increased progressively with age in both boys and girls. Allopregnanolone and dehydroepiandrosterone levels were positively correlated throughout puberty. The present results indicate that serum allopregnanolone levels do not change during the first 2 y of life but increase during pubertal development, suggesting that this steroid may be involved in the adaptive neuroendocrine mechanisms related to puberty.     

Prolactin levels in umbilical cord serum and its relation to fetal adrenal activity in newborns of women with pregnancy-induced hypertension

The effect of hypertension in pregnant women on fetal maturation is an issue of considerable importance. Because of a possible role of prolactin in fetal adrenal steroidogenesis and in fetal lung maturation, we have investigated the relationship between hypertension in pregnant women and levels of prolactin and dehydroepiandrosterone sulfate in serum of newborn infants. It was found that with the mild-to-moderate form of pregnancy-induced hypertension (PIH), there was little effect on prolactin levels in newborn serum. In newborns of women with severe PIH, however, serum prolactin levels were significantly greater (p less than 0.01) than those in newborns of women with uncomplicated pregnancies. Conversely, umbilical serum concentrations of dehydroepiandrosterone sulfate in newborns of women with severe PIH were significantly less (p less than 0.05) than those in newborns of women with uncomplicated pregnancies. These findings are supportive of the view that pituitary function and adrenocortical function of fetuses of women with PIH are different from those of fetuses of normotensive women. These findings are suggestive that PIH alters the function of the fetal pituitary and adrenal cortex.     

Decreased prolactin secretion in childhood obesity

Twelve obese patients and 7 control subjects, age and sex matched, whose weights were greater than 200% of ideal weight and 100% of ideal body weight, respectively, underwent intravenous insulin and thyroid releasing hormone (TRH) tests. Serial prolactin growth hormone, insulin, blood sugar, cortisol, glucagon, thyrotropin stimulating hormone, thyroxine, and triiodothyronine were obtained by RIA. Obese patients showed no significant differences from controls in basal and nadir glucose, basal and peak glucagon, cortisol, and thyroid responses to both tests. Basal insulin levels were higher (36 +/- 9.4 vs 10 +/- 2.3 microU/ml, P less than 0.05) and peak growth hormone responses after insulin were lower in the obese group (6.1 +/- 1.1 vs 12.7 +/- 3.7 ng/ml, P less than 0.05) than in controls. Whereas all control subjects had prolactin responses to both tests, five of 12 obese patients had no responses to insulin. Obese patients had lower prolactin responses at 30 minutes after insulin (5.4 +/- 0.7 vs 12.9 +/- 3.7 ng/ml, P less than 0.05) and lower prolactin responses at 60 minutes after TRH (9.9 +/- 1.7 vs 20.4 +/- 5.9 ng/ml, P less than 0.05). Maximum prolactin responses after TRH were lower in obese patients (9.9 +/- 2.0 vs 28.8 +/- 10.9 ng/ml, P less than 0.05). Maximum prolactin responses after insulin were lower in obese patients (6.2 +/- 4.1 vs 28.9 +/- 18.3 ng/ml). Thus prolactin secretion in childhood obesity is decreased after both stimuli, but more so after IV insulin that TRH, and suggests that, as in adult hypothalamic obesity, neuroendocrine regulation of prolactin release in obese children is impaired.     

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, and cortisol in very-low-birth-weight infants receiving total parenteral nutrition

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, cortisol, and glucose were measured during four time periods (0 to 4, 5 to 11, 12 to 18, and greater than or equal to 19 days of life) in 16 mechanically ventilated very-low-birth-weight infants (mean [+/- SD] birth weight, 1017 +/- 196 g) receiving total parenteral nutrition and in 21 very-low-birth-weight infants not requiring mechanical ventilator support (mean [+/- SD] gestational age, 30 +/- 1.7 weeks; mean [+/- SD] birth weight, 1149 +/- 210 g) fed enterally. There were no significant differences in the serum concentrations of the hormones or in the glucose levels between the two groups at any time interval. Present data demonstrate no significant difference in the serum concentration of glucose, insulin, growth hormone, cortisol, free thyroxine, and thyrotropin between very-low-birth-weight infants fed enterally and those maintained on a regimen of total parenteral nutrition.     

Endocrinological study on growth retardation in Rett syndrome

Aim: To determine whether primary or secondary growth hormone (GH) deficiency has a causative role in linear growth retardation, a key feature in Rett syndrome (RTT). Methods: In 38 patients with Rett syndrome a variable set of investigations was performed including assays of growth and thyroid hormones, gonadotropins, gonadal and adrenal steroids and determination of bone age. Not all measurements were attainable from all patients. In three patients the 24-h growth hormone secretion profile was evaluated using the pulsar method. Results: The bone age determined in 24 patients was found to be normal in 8, retarded in 9 and accelerated in 7 patients. Insulin-like growth factor (IGF)-1 was low in 8 out of 23 patients. IGF-binding protein (IGFBP)-3 and insulin and arginine-stimulated growth hormone secretion were both normal, indicating normal GH secretion in the majority of patients. The 24-h GH secretion profile in the first patient showed a normal day/night rhythm and a normal increase in nocturnal GH secretion. The second patient's overall GH secretion was normal but there was no day/night rhythm. The third patient showed borderline low GH secretion. Normal age-appropriate plasma values were found for the thyroid hormones (T4, TSH), TSH-night rhythm, oestradiol, prolactin and cortisol (08.00, 18.00).

Conclusion: Our study provides no evidence that growth retardation in RTT is caused by growth hormone deficiency. A disturbed hypothalamic control cannot be excluded but it is unlikely that this is the major cause of growth retardation in RTT.     

Growth hormone secretory dynamics in subjects with normal stature

To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.