Prolactin response to thyrotropin-releasing hormone in children with Turner's syndrome and hyperthyroidism

Plasma prolactin (PRL) response to synthetic thyrotropin-releasing hormone (TRH) was studied in 26 prepubertal and 19 pubertal children with constitutional short stature, 7 patients with Turner's syndrome and 10 patients with hyperthyroidism. The mean basal concentrations of plasma PRL did not differ among groups. In prepubertal children PRL responses to TRH were comparable in both sexes, while pubertal children plasma PRL levels after TRH in females were significantly higher (P<0.05) than those in age-matched males. Plasma PRL levels after TRH in patients with Turner's syndrome were significantly higher (P<0.05) than those in age-matched males, but were not significantly different from those in age-matched females. Plasma PRL response to TRH was markedly suppressed in patients with hyperthyroidism before treatment, but it returned to normal after treatment when patients became euthyroid. A significant correlation (P<0.05) between peak concentrations of plasma PRL after TRH stimulation and plasma T₃ but not T₄ levels was observed.These data suggest that a sex difference in TRH-stimulated PRL secretion appears around puberty and that plasma PRL response to TRH is suppressed in children with hyperthyroidism. The magnitude of plasma PRL response to TRH is closely correlated with the severity of hyperthyroidism when judged by plasma T₃ but not T₄ concentrations.     

Normoprolactinemia in boys with marked gynecomastia

Pubertal gynecomastia normally occurs as a transient phenomenon of several months duration, whereas marked pubertal gynecomastia (more than 6 cm in diameter) may persist into aduldhood. In the present study the possible involvement of prolactin (PRL) secretion in the development of marked pubertal gynecomastia was investigated. The diurnal variations of PRL, luteinizing hormone (LH), follicle-stimulating hormone (FSH), as well as the basal values of testosterone (T) and estradiol (E₂) were determined in 5 pubertal boys with marked gynecomastia and in 5 age-matched controls. Mean age of all patients was 14.4 years. The pubertal development was classified as P 3–4.In comparison to controls, boys with marked gynecomastia revealed no differences in basal values of PRL, LH and FSH, as well as in peak values of all hormones during sleep. The response of PRL, LH and FSH to LHRH/TRH stimulation was normal for pubertal age in both groups. In comparison to controls, decreased mean plasma T levels (P<0.05) and slightly increased E₂ levels (P<0.05) were found in boys with marked gynecomastia. The E₂/T ratio was also higher in boys with gynecomastia (P<0.005).These data suggest that prolactin, a hormone which may be increased in galactorrhea, is not involved in the development of marked pubertal gynecomastia in boys. The above findings suggest that slightly elevated day-time E₂ levels may be involved in the development of female-appearing breasts in pubertal boys.     

Differences of hexarelin-induced prolactin and cortisol responses between prepubertal and early pubertal short children and lack of correlation with gonadotropin-releasing hormone-induced gonadotropin response

Hexarelin (HEX), a synthetic hexapeptide with strong GH-stimulating activity, is known to induce the release of prolactin (PRL) and cortisol (F). The responses of GH and F vary according to age and pubertal development, correlating with serum levels of sex steroids, while the release of PRL does not. We evaluated GH, PRL and F responses to HEX (2 microg/kg i.v.) in 19 children with short stature, 12 prepubertal (Tanner stage I) and 7 early pubertal (stage II), and their correlation with those of FSH and LH to GnRH and with the serum levels of testosterone (T) or estradiol (E2). At baseline, the GH, PRL, F and sex steroid serum levels did not vary in the two groups of patients. HEX induced a strong GH and a slight PRL increase in prepubertal and early pubertal children, with no differences in the extent of the response, while F secretion was not affected in either group; these responses did not correlate with those of the gonadotropins to GnRH nor with basal T or E2.     

Hypergonadotropic hypogonadism,SHBG deficiency and hyperprolactinaemia: A transient phenomenon during induction chemotherapy in leukemic children

Five pubertal boys (puberty stage Iv–V) and four prepubertal girls with acute lymphoblastic leukemia were treated with a combination of prednisone, vincristine, daunorubicin and l-asparaginase for remission induction. The hypothalamopituitary-gonadal axis was investigated by measuring basal plasma levels of LH, FSH, and PRL in both groups as well as the response to LHRH/TRH stimulation in pubertal boys before, on day 10, 21, and 28 during induction therapy and 23 days after the induction phase (day 51). Furthermore, the binding capacity of sex-hormone-binding globulin (SHBG), plasma levels of testosterone (T) and estradiol (E₂) were monitored as well as the testicular volumes of the boys.Within three weeks of induction chemotherapy, plasma T, E₂ and the binding capacity of SHBG decreased in both groups, together with a reduction of testicular volumes in the boys. Concommitantly, basal LH, FSH, and PRL values doubled with a normal gonadotrophin response to LHRH. The PRL response to TRH increased at the end of the induction phase, when chemotherapy with vincristine, daunorubicin and l-asparaginase was terminated, but prednisone treatment was continued for 7 another days.During the subsequent prophylactic irradiation of the central nervous system combined with other antileukemic drugs, all hormonal values including testicular volumes in pubertal boys became normal within a period of 3 weeks. Our data clearly demonstrate that an induction chemotherapy regimen such as that employed by the Berlin protocol leads to a transient castrating effect at the gonadal level and to a transient failure of synthesis of SHBG at the hepatic level. Increased prolactin values as well as an increased response to TRH may be related to a decrease in T indicating the existence of a negative feed-back-loop mechanism between T and PRL.Presented in part at the 20th Meeting of the European Society for Paediatric Endocrinology, September 7–11th, 1981, Genf, Switzerland     

Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study

The objective of the present study was to investigate potential differences at presentation of type I diabetes and during its long-term clinical course in children and adolescents with prepubertal and pubertal manifestation. Clinical, immunological and biochemical characteristics at diabetes onset of 453 patients (320 prepubertal, 133 pubertal; median age at manifestation 7.1 years (0.7–13.9) and 13.1 years (9.2–17.6), respectively) were evaluated. Glycaemic control and exogenous insulin requirements were followed prospectively, with a median follow up of 9.4 years. At the onset of the disease no differences concerning the degree of metabolic decompensation, impairment of somatic health, and islet cell antibody status could be detected between the groups, except for a smaller body weight loss in pubertal patients (P=0.011). The duration of partial remission (insulin requirements <0.5 IU/kg body weight/day) was unrelated to age or pubertal status at onset. It was found to be longer in boys than in girls in the total cohort (median duration: 279 vs 215 days, P=0.0071). Despite an absence of differences during the early course of the disease, glycaemic control was better, and daily insulin doses were significantly lower in patients with pubertal onset, after 6 years of diabetes. Conclusion Adolescents with a pubertal onset of type I diabetes have a more benign long-term course of the disease demonstrating better glycaemic control and lower insulin requirements, although the presentation of the disease at onset and its course during the first 6 years are not different from those of children with a prepubertal manifestation of diabetes. Received: 7 October 1996/Accepted in revised form: 12 August 1997     

Effect of human chorionic gonadotropin on growth velocity and biological growth parameters in adolescents with thalassaemia major

The effect of long-term human chorionic gonadotropin (HCG) therapy on the linear growth and biological growth parameters was studied in six thalassaemic boys aged 14.5–15.5 years old with hypogonadotropic hypogonadism. A significant (P<0.001) increase in growth velocity (from 3.3±0.3 to 7.6±0.6 cm/year) was found after 6–12 months of therapy, without acceleration of bone age. A striking improvement in pubertal development was observed. The treatment significantly increased growth hormone (GH) response to l-dopa administration (P<0.025) as well as sleep GH secretion (P<0.025). Serum growth factors, evaluated as thymidine activity during deep sleep, increased (P<0.001), but somatomedin C (Sm-C) levels did not. Prior to treatment, baseline and peak values of plasma growth hormone releasing hormone (GH-RH) following l-dopa were low. After HCG therapy, GH-RH response to l-dopa increased significantly (from 9.2±5.6 to 20.2±6.2 pg/ml; P<0.05), but remained (P<0.001) lower than in normal prepubertal children. This study suggests that in thalassaemia major an impaired GH-RH release can be observed, in addition to the described alteration in Sm-C generation.Abbreviations LH luteinising hormone - FSH follicle stimulating hormone - HCG human chorionic gonadotropin - GH growth hormone - GH-RH growth hormone releasing hormone - GnRH gonadotropin releasing hormone - TA thymidine activity - Sm-C somatomedin C     

The effects of androstenediol and dehydroepiandrosterone on the immune response to BCG at puberty

In order to assess the effects of age-related changes of serum dehydroepiandrosterone sulphate (DHEAS) and androstenediol (AED) concentrations on BCG vaccination throughout the puberty period, we matched 41 prepubertal (mean age 8.63 +/- 1.36 years, range 8-14 years) and 43 pubertal (mean age 13.8 +/- 1.31 years, range 10-16 years) schoolchildren who were PPD negative and free of disease or medication known to affect immune function. The tuberculin test was performed 8 weeks after vaccination and tuberculin response and hormone levels were compared between prepubertal and pubertal subjects. We found a higher tuberculin response in the pubertal group when compared with the prepubertal ones. The pubertal children had 79.1 per cent tuberculin positivity compared with 46.4 per cent of prepubertal children (p < 0.05). Diameters of induration of the tuberculin test among prepubertal students vs. pubertal students were 9.5 +/- 3.8 mm and 11.9 +/- 3.7 mm, respectively (p < 0.005). Pubertal stage, testis volume, and pubic stage were also found to have significant effects on tuberculin test results. No difference was observed between both sexes with regard to responses of the tuberculin test in either the prepubertal or the pubertal group (p > 0.05). DHEAS and AED levels in the tuberculin-positive subjects were found to be significantly higher than tuberculin-negative ones (p = 0.040 and p = 0.046, respectively). Among both these hormones, only AED levels were correlated with tuberculin test responses. These results suggest that AED may play a role in the immunity to BCG vaccination and further immunological investigations are warranted to provide support for this idea.     

Plasma vasoactive intestinal polypeptide and other regulatory peptides in children with neurogenic tumours

Plasma regulatory peptide levels were studied in a group of 21 children with neurogenic tumours and in 22 control children. Plasma vasoactive intestinal polypeptide (VIP) levels were significantly higher in children with neurogenic tumours than in normal children or those with other tumours (P<0.05). There was no significant difference between the groups in plasma levels of gastrin, pancreatic glucagon or pancreatic polypeptide. The plasma VIP level may thus be a helpful diagnostic marker for neurogenic tumours in children.     

Relationship between plasma leptin, insulin and tumor necrosis factor alpha in obese children

OBJECTIVES: 1. To evaluate the relationship between plasma leptin and TNFalpha concentrations in obese children and to assess the differences between hyperinsulinemic and normoinsulinemic groups. 2. To evaluate the relationship between plasma leptin and insulin levels in obese children. 3. To investigate the TNFalpha G308A mutation in obese children. METHODS: Body mass index (BMI), fasting plasma glucose and insulin levels, oral glucose tolerance test results, homeostasis model assessment of insulin resistance (HOMA-IR) results, and plasma leptin and TNFalpha concentrations were evaluated in obese children (n = 45) and age- and gender-matched, lean healthy controls (n = 40). RESULTS: In obese children the fasting insulin, HOMA-IR results, plasma leptin and TNFalpha concentrations were significantly higher than in controls (p <0.05). Furthermore, obese females showed higher plasma leptin and insulin resistance compared to obese males. While plasma leptin, TNFalpha levels and HOMA-IR results were similar in the prepubertal and pubertal groups, insulin levels were significantly higher in the pubertal group. Plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children. In control children, plasma leptin concentrations showed a positive correlation with BMI, age, fasting insulin and HOMA-IR results. In obese children, plasma leptin levels did not correlate with BMI, fasting insulin or TNFalpha. CONCLUSION: Plasma leptin concentrations did not show any correlation with TNFalpha levels in obese children. Furthermore, plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children.     

Accelerated pubertal development in patients with shunted hydrocephalus

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.     

Beat-to-beat blood pressure and heart rate responses to active standing in Japanese children

Some pubertal children are susceptible to orthostatic stress but little is known about mechanisms of circulatory adjustment to the posture change in children. We investigated beat-to-beat blood pressure (BP) and heart rate (HR) responses to active standing in 173 schoolchildren, 92 boys and 81 girls, aged 6–18 years (mean age: 13.4 years) using a non-invasive continuous monitoring system (Finapres 2300, Ohmeda). The subjects were divided into four age groups: prepubertal 1 (7–9 years), prepubertal II (10–12 years), pubertal (13–15 years) and young adult (16–18 years). Supine BP increased and HR decreased with age. At the onset of active standing two older groups showed a significantly larger initial drop than the prepubertal groups (-36 ± 15 versus -15 ± 16% reduction for systolic BP and -36 ± 14 versus -20 ± 19% for diastolic BP, respectively, p < 0.01). Moreover, the pubertal group had a significantly smaller vasoconstrictor index than prepubertals and two older groups had a significantly more prolonged BP recovery time. In keeping with this the pubertal group most frequently had hypotensive symptoms during active standing. The rise in HR at the peak was higher in two older groups than in prepubertals (34 ± 9 versus 29 ± 8 beats/min^-1, respectively, p < 0.001), whereas the baroreflex index was almost identical for the four groups. The effect of body proportion on BP responses was not found. There was no significant difference in BP and HR changes in the later stage during 7min of standing. These results indicated that pubertal children were more susceptible to orthostatic stress, probably due to abnormal BP responses in the initial phase of active standing, which seemed to reflect enhanced cardiopulmonary reflexes and diminished sympathetic activation associated with the age. Moreover, BP reduction at an initial drop of more than 60% or a recovery time of more than 25 s might be postulated to be an abnormal circulatory response.     

Induction of puberty in boys with delayed adolescence by methandrostenolone

Methandrostenolone administration at a daily dose of 0.03 mg/kg for 3 months was successful in inducing puberty in 9 boys (aged 14 6/12±6/12 years, m±SD) with delayed puberty and studied in the prepubertal stage. One year after initiation of treatment they reached a mid-pubertal stage (testicular volume m±SD 6±2 ml and pubic hair development Tanner stage 3–4). At the same time growth velocity accelerated from 5.3±1.5 to 8.5±3.4 cm/yr and bone age advanced from 10 9/12±9/12 to 13±6/12 years (m±SD).During treatment there was suppression of basal plasma LH and FSH (m±SD) from 1.3±0.3 to 0.5±0.2 mIU/ml (P<0.001) and from 1.4±0.8 to 0.8±0.3 mIU/ml (P<0.05) respectively, and of the LH response to LRH (50 mcg/m², i.v.) from 5.2±1.0 to 1.9±0.6 mIU/ml (P<0.001). After discontinuation of methandrostenolone there was a significant and prolonged elevation of the basal plasma LH (2.0±0.4 mIU/ml) and testosterone levels (from 24±7.7 to 175.6±67.5 ng/dl, P<0.01) and an enhanced LH response to LRH (8.3±2.4 mIU/ml, P<0.05), compared to the pre-treatment levels.Eleven prepubertal boys with constitutional short stature (aged 9 3/12±9/12 years, m±SD) maintained their prepubertal state one year following the same therapeutic regime with methandrostenolone. No significant changes in the basal plasma testosterone and gonadotropin levels, or the responses to LRH, were noted in this group.During treatment a significant increase in growth velocity was noted (from 4.1±1.7 to 9.7±3.0 cm/year, P<0.02), with a subsequent decrease to 5.4±2.9 cm/year (m±SD) which was not significantly different to the pre-treatment value. Bone age advanced from 6 3/12±1 before treatment to 8±1 6/12 years 12 months following methandrostenolone administration.It is concluded that methandrostenolone can induce puberty in boys with delayed puberty if administered in the prepubertal stage, but not in younger prepubertal boys with short stature. The concomitant changes in the basal plasma testosterone and gonadotropin levels, and their response to LRH stimulation, which were found in the boys with delayed puberty indicate that a certain degree of maturation of the hypothalamic pituitary gonadal axis is probably needed to permit induction of puberty by methandrostenolone. The effect of this drug is due in part to its androgenic potency and probably also to its modulation of negative feedback in the hypothalamic-pituitary-gonadal axis, causing a rebound phenomenon following brief suppression.Supported in part by the Harry C. Bernard Fund     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Lipoprotein(a) levels in girls with premature adrenarche

Aim: Elevated lipoprotein(a) (Lp(a)) level is a risk factor for cardiovasculary disease (CVD). Women with polycystic ovary syndrome (PCOS) have higher Lp(a) and risk for CVD than controls. The girls with premature adrenarche (PA) were shown to share similar hormonal/metabolic properties with PCOS. We compared Lp(a) levels in PA, with healthy and PCOS girls. Methods: In total, 25 PA, 20 controls and 10 girls with PCOS were evaluated. Lp(a), lipid profiles and insulin, glucose, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and androstenedione levels were measured. A family history about CVD was obtained. Results: The mean age of girls with PA, at time of the study, was 10.04 ± 1.53, control 9.83 ± 1.58 and PCOS was 16.58 ± 1.46 years. The median (range) of Lp(a) levels were 22.5 (3.50–99.90), 9.6 (3.33–32.40) and 21.2 (5.89–85.65) mg/dL in PA, control and PCOS groups, respectively (P > 0.05). The median Lp(a)’s were 14.5 (3.50–87.00) and 24.30 (6.20–99.90) mg/dL, in prepubertal (Tanner 1) and pubertal PA girls (Tanner 2–5), respectively (P > 0.05). The median Lp(a) of prepubertal peers was 8.7 (3.33–21.17), while that of pubertal ones was 15.4 (4.72–32.40) mg/dL (P > 0.05). There was no difference between Lp(a) levels of pre‐pubertal PA girls and their peers; however, significant difference was found in Lp(a) levels in pubertal stages of PA and healthy peers (P < 0.05). The positive family history of CVD was 60% in PA; 55% and 80% in the control and PCOS groups, respectively, with no statistical difference. Lp(a) level was correlated with DHEAS (r = 0.386, P = 0.008) and free testosterone (r = 0.337, P = 0.022) levels positively. There was no significant correlation between Lp(a) and body mass index, fasting insulin and fasting glucose/insulin ratio. Conclusions: Lipoprotein(a) levels in pubertal girls with PA differ significantly from healthy peers. However, to clarify whether the girls with PA have an additional risk for CVD with respect to Lp(a), further follow‐up studies with larger number of patients are necessary.     

Intelligence,motor skills and behaviour at 5 years in early-treated congenital hypothyroidism

The cognitive functioning, motor skills and behaviour of 5-year-old children with early-treated congenital hypothyroidism was assessed. The study group was 57 children with congenital hypothyroidism (CH) diagnosed by neonatal screening in N.E. and N.W. Thames regions between 1978 and 1981 along with 51 non-affected controls matched for age, sex, social class and language background. Small differences in I.Q. and behaviour between the patients and the controls were not statistically significant. However, children with CH showed significant deficits in motor skills (M 79.9 SE 3.7) compared to the controls (M 99.8 SE 4.0) (P=0.0003). Deficits were particularly marked for balance. In addition, children with more severe hypothyroidism at diagnosis (Plasma thyroxine <20 nmol/l) did significantly less well in respect to I.Q. and motor skills than those with less severe hypothyroidism (plasma thyroxine >60 nmol/l). These findings provide further evidence for the importance of the severity of hypothyroidism in determining the outcome for intelligence and motor skills in children with early-treated congenital hypothyroidism. Deficits in motor skills, particularly in relation to balance, suggest that early impairment of the vestibular system may occur despite early treatment.     

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH-RETARDED CHILDREN TREATED WITH GROWTH HORMONE: II. Secretion of LH, FSH, TSH, Prolactin and ACTH

Abstract. P. C. Eskildsen, B. B. Jacobsen, K. W. Kastrup, S. Krabbe, P. E. Lebech and K. E. Petersen (The Children's Hospital Fuglebakken, Herlev Hospital and Frederiksberg Hospital, Copenhagen, Denmark). Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. Acta Paediatr Scand, Suppl. 277: 14, 1979.—A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T₄, T₃, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.     

Comparison of maximal oxygen consumption between black and white prepubertal and pubertal children

The purpose of this investigation was to determine whether maximal oxygen consumption (VO2max) differed between two selected groups of black and white children and whether a difference existed to determine whether it was related to hematologic profiles, body composition, and/or physical activity/inactivity level. Forty-five prepubertal and 42 pubertal, clinically normal black and white children participated. Dual-energy x-ray absorptiometry was used to determine body composition. A computed tomography scan of the abdomen was used to determine visceral adipose tissue and s.c. adipose tissue. Daily physical activity/inactivity was assessed by questionnaire. Black prepubertal and pubertal children had lower VO2max values when compared with white children (28.8 +/- 7.8 versus 35.0 +/- 6.5 mL . kg(-1) . min(-1), p < 0.01; 33.7 +/- 6.4 versus 40.4 +/- 10.2 mL . kg(-1) . min(-1), p < 0.05; respectively). Black prepubertal and pubertal children had lower Hb concentrations ([Hb]) and hematocrits than white children (prepubertal: 12.1 +/- 0.5 versus 12.8 +/- 0.9 g/dL, p < 0.001; 35.6 +/- 1.4 versus 37.4 +/- 2.3%, p < 0.01, respectively; pubertal: 13.0 +/- 0.9 versus 13.6 +/- 0.7 g/dL, p < 0.05; 37.7 +/- 2.5 versus 39.5 +/- 2.1%, p < 0.05, respectively). In conclusion, these findings indicate that black prepubertal and pubertal children had lower VO2max when compared with their white peers matched for age, pubertal stage, and body mass index. This difference in VO2max could be attributed at least in part to comparatively lower [Hb] and more sedentary lifestyle in the black children. Further investigations should study Hb flow rate (a function of [Hb] x maximal cardiac output) in black and white children as it relates to VO2max.     

Reduced levels of growth hormone,insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

Accepted 25 March 1997
OBJECTIVE—Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern.
STUDY DESIGN—One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured.
RESULTS—The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p< 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p< 0.001). There was a correlation between height SD score and IGF-I levels in the total patientpopulation (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01).
CONCLUSION— Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.

• Prepubertal children with shunted hydrocephalus have reduced circulating IGF-I and IGFBP-3 concentrations • Pubertal children with shunted hydrocephalus have reduced basal serum growth hormone concentrations • Reduced growth hormone secretion may contribute to slow linear growth and reduced final height in hydrocephalic children • Carbamazepine treatment may increase IGF-I and IGFBP-3 concentrations in the peripheral circulation     

Insulin induced hypoglycaemia: comparison of glucose and glycerol concentrations in plasma and microdialysate from subcutaneous adipose tissue

AIMS—To investigate the dynamics between plasma and dialysate glucose during hypoglycaemia in children.
STUDY DESIGN—Six children in prepuberty or early puberty were investigated by multiple blood sampling and microdialysis of subcutaneous adipose tissue during a standard arginine-insulin tolerance test. Glucose and glycerol, as an index of lipolysis, were measured in samples from both compartments. Plasma concentrations of insulin and the main counterregulatory hormones were also measured.
RESULTS—Plasma and dialysate glucose concentrations were very similar at baseline and increased in concert after infusion of arginine, probably in response to glucagon release. After insulin injection, glucose in both plasma and dialysate fell in parallel. The subsequent hypoglycaemic stress response induced a rapid rebound in the plasma concentration with a mean (SD) delay in the dialysate of 16 (3) minutes. Plasma glycerol was approximately fivefold lower than in the dialysate and did not fluctuate significantly. Dialysate glycerol decreased with arginine infusion and reached a nadir immediately following insulin administration. Subsequently, the antilipolytic effect of insulin was overcome by the hypoglycaemic stress response, and lipolysis prevailed in spite of hyperinsulinaemia.
CONCLUSION—After rapidly induced hypoglycaemia, rebound of interstitial glucose concentrations is significantly delayed compared with plasma concentrations, and the antilipolytic effect of hyperinsulinaemia is opposed possibly by the hypoglycaemic stress response.

     

长期延误治疗的甲状腺功能减低症患儿的追赶生长

目的研究长期延误治疗的甲状腺功能减低症(甲减)患儿治疗后身高增长的规律及青春期对其身高的影响,探讨使用促性腺激素释放激素拟似物(GnRHa)和生长激素(GH)治疗辅助生长的可能性。方法分析28例长期被忽视(3a以上)的甲减患儿的追赶生长,其中青春前期13例(A组),青春期诊断并开始治疗15例(B组)。治疗过程中每3个月门诊随访1次,监测患儿身高、体质量、性发育情况、骨龄、血清甲状腺功能等指标。在左旋甲状腺素治疗的基础上,应用GnRHa和GH联合治疗2例长期延误治疗且已进入青春期的患儿。结果2组患儿初诊时均有明显的生长落后、骨龄落后。A组年龄(7.1±2.0)岁,骨龄(3.0±1.5)岁,身高标准差评分(HTSDS)为-3.89±1.29;B组开始治疗的年龄(14.3±1.6)岁,骨龄(5.6±2.3)岁,HTSDS-5.55±1.38。2组靶身高(TH)比较无差异。治疗第3年末,A组HTSDS提高至-1.12±1.14,B组上升至-1.94±1.39;治疗后2组患儿骨龄改变3a依次为A组(2.5±0.5)岁.a-1、(1.6±0.5)岁.a-1、(1.4±0.6)岁.a-1;B组分别为(5.2±1.8)岁.a...