Serum leptin concentration, body composition, and gonadal hormones during puberty.

BACKGROUND: Recent evidence has suggested that leptin concentration is associated with gonadal hormone levels, and that changes in leptin concentration may trigger the onset of reproductive function in children. However, the concurrent changes in body composition during puberty make the independent associations between leptin and gonadal hormone concentrations in children difficult to resolve. METHODS: To investigate the nature of associations between leptin levels and pubertal maturation, serum concentrations of leptin, estradiol, and testosterone and body composition measures were examined in a sample of 152 healthy pre-pubertal, pubertal, and post-pubertal children. RESULTS: Leptin concentration was nearly three-fold higher in post-pubertal girls than in pre-pubertal girls, but was relatively similar in pre- and post-pubertal boys. Significant sex differences in leptin concentration existed in prepubertal, pubertal and post-pubertal children, and these remained significant after controlling for adiposity. After adjusting for total body fat, fat-free mass and age, testosterone concentration was negatively associated with leptin levels in pubertal boys, while estradiol concentration was positively associated with leptin level in pubertal girls. CONCLUSIONS: Girls have higher serum leptin concentration before, during, and after puberty than boys, even after accounting for the development of greater female adiposity. Although other factors may be involved, sexual dimorphism in leptin concentrations during puberty appears to be partly due to a stimulatory effect of estradiol on leptin concentration in females and a suppressive effect of testosterone on leptin concentration in males.     

Effect of sex hormone administration on circulating ghrelin levels in peripubertal children

BACKGROUND: Ghrelin levels gradually decrease throughout childhood and with advancing pubertal stage. The change during puberty is more pronounced in boys than girls. OBJECTIVE: The objective of the study was to investigate whether the pubertal drop in ghrelin secretion is modified by the increase in sex hormones. PATIENTS AND METHODS: Ghrelin levels were measured in 34 short peripubertal children (17 boys and 17 girls) aged 8-12.5 yr before and after sex hormone priming for GH stimulation testing. RESULTS: In boys, priming with testosterone increased testosterone to pubertal levels (23.7 +/- 7.1 nmol/liter), which in turn induced a marked decrease in ghrelin (from 1615.8 +/- 418.6 to 1390.0 +/- 352.0 pg/ml) and leptin (from 8.0 +/- 4.5 to 5.8 +/- 3.2 ng/ml) and an increase in IGF-I (from 162.7 +/- 52.8 to 291.1 +/- 101.6 ng/ml) (P < 0.001 for all parameters). In girls, priming with estrogen led to a supraphysiological increase in estradiol levels (1313.8 +/- 438.0 pmol/liter), which had no effect on ghrelin, leptin, or IGF-I. There was no correlation between ghrelin levels and levels of sex hormones, leptin, or body mass index in either boys or girls. CONCLUSIONS: A pharmacological increase in sex hormones is associated with a marked decline in circulating levels of ghrelin in boys but not girls. Additional longitudinal studies through puberty are needed to elucidate the physiological interaction between sex hormones and ghrelin.     

Leptin levels show diurnal variation throughout puberty in healthy children, and follow a gender-specific pattern.

OBJECTIVE: To investigate the levels and diurnal rhythm of serum leptin in healthy children, and to investigate the association between leptin levels and sex steroids. METHODS: Four girls and four boys, all healthy volunteers, were followed longitudinally throughout puberty. Their chronological ages ranged from 8.7 to 19.5 years, and body composition, expressed as weight-for-height standard deviation scores (SDS), ranged between -1.7 and +2.4. Serum leptin, oestradiol and testosterone concentrations were measured by radioimmunoassay at 1000, 1400, 1800, 2200, 0200 and 0600 h. RESULTS: In all girls and boys, both prepubertally and during pubertal development, serum leptin levels increased during the night, with no difference in relative peak amplitude. In boys, the leptin concentrations increased until the initiation of puberty and then declined, whereas in girls, the concentrations increased throughout puberty. The inter-individual variation in mean leptin levels among girls decreased to 11% at the time of menarche. A positive correlation was found for both oestradiol and testosterone versus leptin in girls throughout puberty (r=0.64 and r=0.71 respectively, P<0.001). A negative correlation was found between leptin and testosterone in boys in mid- and late puberty (r=-0.66, P<0.01). No correlation was found between oestradiol and leptin in boys or between testosterone and leptin in pre- and early pubertal boys. CONCLUSION: Serum leptin concentrations show diurnal variation throughout pubertal development in both girls and boys. The changes in leptin levels during puberty follow a gender-specific pattern, probably due to an influence of sex steroids on leptin production.     

Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids

OBJECTIVES: To investigate the circulating levels of adiponectin, resistin, interleukin 6 (IL-6), and leptin/receptor ratio in healthy Spanish children throughout the different stages of pubertal development. To analyze the relationship between adipokines and sex steroid level changes during puberty. STUDY DESIGN: Serum adiponectin, resistin, IL-6 levels, and leptin/receptor ratio were studied in 160 healthy Spanish children grouped according to their pubertal stage (Tanner I, 23 girls and 22 boys; Tanner II, 19 girls and 16 boys; Tanners III and IV, 21 girls and 20 boys; and Tanner V, 20 girls and 19 boys). In addition, circulating levels of sex hormone-binding globulin (SHBG) were determined in every subject, and testosterone and estradiol levels in boys and girls respectively. RESULTS: Adiponectin levels decreased in boys from mid puberty (P < 0.05) to become significantly lower than in girls (P < 0.001), whereas IL-6 decreased in both sexes (P < 0.05). Resistin levels and leptin/receptor ratio showed no differences between sexes or according to pubertal stage, except in adult females, who had the highest levels of both parameters (P < 0.001). Serum IL-6 levels correlated significantly (P < 0.05) with testosterone and estradiol levels (r=-0.37 and -0.42 respectively), whereas estradiol, but not testosterone, correlated with leptin/receptor ratio (r=0.59; P < 0.001). Furthermore, a positive relationship was found between SHBG and adiponectin and IL-6 (P < 0.001 and P < 0.05 respectively). In addition, a direct correlation between leptin/receptor and body mass index was found in both sexes (P < 0.001). CONCLUSION: Variations in adipokine profiles throughout pubertal development appear to be related with progression of gonadal function.     

Serum lipoproteins and endogenous sex hormones in early life: observations in children with different lipoprotein profiles

Relationships of endogenous testosterone, androstenedione, dehydroepiandrosterone, estradiol, and progesterone to lipoprotein cholesterol levels were examined concurrently in four groups of children (N = 375, age range 6 to 18 years) whose earlier VLDL-cholesterol and/or LDL-cholesterol levels were in the extreme quintiles or quartiles. In terms of significant correlations, estradiol related inversely with VLDL-cholesterol in prepubertal boys (-0.28) and pubertal girls (-0.34), while estradiol/testosterone ratios related inversely with LDL-cholesterol in pubertal girls (-0.27). HDL-cholesterol related negatively with testosterone in pubertal boys (-0.24) and positively with estradiol in pubertal girls (0.40). With respect to contrasting lipoprotein profiles, high LDL-cholesterol groups had significantly high progesterone/estradiol ratio (boys: 8.6 v 6.9; girls: 8.3 v 5.1), high progesterone (girls only: 0.40 v 0.29 ng/mL) and low estradiol/testosterone ratio (girls: 0.15 v 0.21; prepubertal boys: 0.09 v 0.21). Pubertal girls from high VLDL-cholesterol groups showed markedly low estradiol (71 v 120 pg/mL) and estradiol/testosterone ratio (0.11 v 0.19). These results emphasize the role of endogenous sex hormones in modulating lipoprotein concentrations as well as in the sexual divergence of lipoprotein profiles between males and females following puberty.     

Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children

OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.     

Growth of asthmatic children before long-term treatment with inhaled corticosteroids.

The aim of this study was to examine the growth of asthmatic children before any long-term inhaled corticosteroid treatment. We studied 436 asthmatic children (254 boys and 182 girls), age range 3.9-15.4 years, that had not been treated with long-term inhaled corticosteroids. In each child height and weight were measured, and the height standard deviation score (HSDS) and the weight for height ratio (%WFH) were calculated. We also estimated asthma severity and tested atopic status by skin testing. Children were grouped into three age groups: prepuberty (3.9-7.9 years), peripuberty (8-11.9 years), and puberty (12-15.5 years). HSDS was correlated to asthma severity and duration, atopic status, and other coexisting allergic diseases. Seven hundred ten healthy children (345 boys, 365 girls) ages 4.1-15.5 years were used as controls for height and weight. There was no statistically significant difference in HSDS and %WFH between patients and controls, except for HSDS of pubertal female patients that was significantly less than that of controls, x: 0.06 (0.80) vs. x: 0.40 (0.90), respectively, p < 0.02. There was also no significant correlation between HSDS or %WFH and severity or duration of the disease, allergy status and other coexisting allergic diseases. However, there was significant difference in menarcheal age between asthmatic girls x: 12.49 (0.12) and controls x: 12.00 (0.10), p < 0.001. In conclusion, our data show that the growth of asthmatic children before any long-term treatment with inhaled corticosteroids is not different from the control population, except for the asthmatic girls of pubertal age who are shorter than control girls probably because of delay in pubertal maturation.     

Pubertal course of persistently short children born small for gestational age (SGA) compared with idiopathic short children born appropriate for gestational age (AGA)

OBJECTIVE: Few data are available on the pubertal development of children born small for gestational age (SGA) who fail to show catch-up growth. DESIGN: A longitudinal analysis compared the pubertal course of persistently short children born SGA compared to children with idiopathic short stature who were appropriate for gestational age (AGA). One hundred and twenty-eight short children (height SDS<-1.7), including 76 (31 boys) born SGA and 52 (22 boys) born AGA, were regularly followed from early childhood to completion of puberty. RESULTS: Puberty was attained at normal age (10.5-14 Years in boys, 9.5-13 Years in girls) for most children in both the SGA and AGA groups (boys, 80% and 77%; girls, 76% and 78% respectively). The duration of puberty was similar in the SGA and AGA groups. Menarche occurred at normal age range but was significantly earlier in the SGA girls (P<0.01 by ANOVA). Despite the similar total pubertal growth, the patterns of growth differed significantly: SGA group - accelerated growth and bone maturation rates from onset of puberty with peak height velocity at Tanner stages 2-3, followed by a decelerated growth rate and earlier fusion of the epiphyses; AGA group - steady progression of bone elongation and maturation throughout puberty (pubertal growth, P<0.05 in both sexes; bone maturation, P<0.001 in both sexes). Final height in the SGA group was compromised compared with their target height (P<0.001). CONCLUSION: Children born SGA have a normal pubertal course with a distinct pubertal growth pattern. This pattern may represent an altered regulation of their growth modalities.     

Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty

OBJECTIVE: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. DESIGN: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. METHODS: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH > or = 7 IU/l, advanced bone age > 1 year, enlarged uterus (> or = 36 mm) and testosterone level > or = 0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. RESULTS: GnRH-stimulated peak LH < or = 3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. CONCLUSIONS: The triptorelin 3-month depot efficiently suppresses the pituitary-gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.     

Nocturnal melatonin patterns in children

Time patterns in nocturnal concentrations of circulating melatonin of children are quantified in 8 girls and 8 boys, 8.7-16.8 yr of age, classified by Tanner pubertal stage. Between 1900 and 0700 h, each provided blood samples at 30-min intervals for melatonin RIA. Associations with gender, body mass index, and chronological and pubertal age determined by multiple linear regression and ANOVA reveal that the area under the curve of 12-h melatonin concentrations was affected by pubertal rather than chronological age, an effect to which data collected during darkness contributed the most. Each data series was also analyzed by a least squares spectrum at frequencies of 1-20 cycles/day. Ultradian changes with periods of 3.4 and 1.5 h, putatively associated with rapid eye movement sleep cycles, characterize nocturnal melatonin in boys and girls.     

Response of normal children to the treadmill exercise test using the Bruce protocol

Fifty nine boys and 41 girls underwent exercise stress testing (ETT), utilizing the Bruce protocol. Their mean age was 10 years. They were grouped by sex, age and body surface area. Blood pressure (BP), heart rate (HR) at rest, during exercise and after were monitored as well as the duration of the test and the energy cost. The HR and-BP had a similar linear relationship in both groups during the different stages of the test. The duration of the test expressed in minutes was 11.8 +/- 1.2 in boys and 10.7 +/- 1.2 in girls (P = 0.001). The oxygen consumption (ML/kg/min) was 45.2 +/- 4.9 and 41.9 +/- 4.5 that is equivalent to 12.9 +/- 1.4 and 11.9 +/- 1.2 mets for each group respectively. The group of boys of 6 (9.8) and 14 years of age (13.6) (P = 0.002) and in the girls in the 7 (9.5) and 10 years age group (11.8) P = 0.05. We conclude that 1) The ETT can be done in children safely but was have to take in consideration their age, sex, and body surface area in evaluating the results. 2) This study gives a reference to evaluate children with an without heart disease.     

Precocious Puberty and Normal Variant Puberty: Definition, etiology, diagnosis and current management

This review describes several aspects of the management of precocious puberty (PP) and variants in girls and boys. PP is characterized by early pubertal changes, acceleration of growth velocity and rapid bone maturation that often result in reduced adult height. Onset of pubertal signs before the age of 8 years in girls and 9 years in boys should always be evaluated carefully. The main principles of therapy are to stop the progression of secondary sex characteristics and menses (in girls), to increase final adult height, to promote psychosocial well-being, and to treat the underlying cause if known.     

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

AIMS/HYPOTHESIS: We determined the longitudinal relationship between adiponectin levels and the development of microalbuminuria in an inception cohort of children with type 1 diabetes. METHODS: Blood samples collected annually over a median of 9.0 (range 1.3-14.9) years were assayed for adiponectin and HbA(1c) in 55 children (36 girls) with type 1 diabetes and microalbuminuria whose age of onset of diabetes was 9.4 years (range 2.2-15.4). Samples were also assayed from normoalbuminuric children (controls) matched for age, sex and duration of diabetes. RESULTS: Overall, adiponectin levels were higher in girls than in boys, but only after 11 years of age (median [range]: 15.3 [5.8-124.4] vs 11.6 [4.1-26.5] mg/l, p < 0.001). Furthermore, adiponectin levels were higher in girls with microalbuminuria than in control girls, but this was only apparent after the onset of microalbuminuria (p = 0.001, adjusted for BMI, daily insulin dose, HbA(1c) and age). In boys, adiponectin levels did not differ between those with microalbuminuria and controls. Further sex-related discordant associations with adiponectin levels were observed; in girls, adiponectin levels were positively related to HbA(1c) levels (r = 0.2, p = 0.05) and urine albumin excretion (r = 0.3, p < 0.05) and inversely related to BMI (r = -0.2, p < 0.05). These associations were absent in boys. CONCLUSIONS/INTERPRETATION: In adolescent girls with type 1 diabetes but not in boys, adiponectin levels increase with increasing urine albumin excretion and onset of microalbuminuria. Although causal links cannot be inferred, this sexual dimorphism may reflect interactive effects of hyperglycaemia and sex steroids on risk of complications and adiponectin production.     

Constant Pineal Output and Increasing Body Mass Account for Declining Melatonin Levels During Human Growth and Sexual Maturation

Twenty-four-h urine samples, divided into two fractions representing night- and daytime melatonin production, were collected from 115 healthy individuals between the ages of 3 and 80, of known height and weight, and assayed for 6-hydroxy melatonin sulphate (SaMT), a major urinary metabolite of melatonin, by gas chromatography mass spectrometry. The population was divided for analytical purposes into children (boys aged 3-10.99, girls aged 3-9.59), adolescents (males aged 11-17.99, females aged 9.60-17.99), and adults (men and women over 18). The results showed approximately the same excretion over 24 h in all 3 groups but that the night/day ratio was considerably greater in children and adolescents compared to adults (P less than 0.001). However, when the results were expressed as a function of body weight (BW), body surface area (BSA), or creatinine excretion (CE), nocturnal SaMT was higher in children than in adults (P less than 0.001 for all 3 parameters) or adolescents (BW, P less than 0.001; BSA, P less than 0.002; CE, P less than 0.001) and was higher in adolescents than in adults (BW and BSA, P less than 0.001). Children also excreted more during the day than adults (BW, P less than 0.01; CE, P less than 0.001) or adolescents (BW alpha CE, P less than 0.02). Our results show that pineal output barely changes during childhood and adolescence. However, there is an age related decrease in SaMT excretion/unit body mass which correlates with an age-related increase in body mass. We therefore conclude that the decrease in circulating levels of melatonin during growth and sexual maturation is brought about by an increase in body mass.     

Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls

The aim of the current study is to analyze the interaction of the muscle and bone system (muscle-bone unit) during puberty in males and females by computed tomography of the nondominant forearm. The data presented here are the first results from 318 healthy children (159 boys and 159 girls), aged 6-22 yr, and 336 adults (parents) participating in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). Cortical area (CA) of the radius representing bone strength and muscle area (MA) representing muscle strength were measured with peripheral quantitative computed tomography (XCT 2000; Stratec, Pforzheim, Germany). A single slice measurement at a site corresponding to 65% of the ulnar length proximal to the radial endplate was used. MA and CA of the radius have been determined by a built-in software algorithm using density differences. There was a strong correlation between MA (x) and CA (y) in all children, adolescents, and adults (y = 0.019x + 10.93; r2 = 0.77). Before puberty, boys and girls displayed a similar relation between MA and CA. CA in relation to MA was greater in girls than in boys during puberty. Analysis of covariance was performed investigating the dependency of CA on MA, five pubertal stages, sex, and interaction of sex and pubertal stages. MA representing muscle strength was the strongest predictor of CA (P < 0.001) representing bone mass. Pubertal stage (P < 0.001) and interaction of pubertal stage*sex (P = 0.002) also had a significant influence on CA. r2 of the model was 0.85. These data suggest that in pubertal girls and women rather than in pubertal boys and men an additional factor shifts the relationship between MA and CA to higher values of cortical area. The present data confirm previous studies of the influence of puberty and estrogens or related factors on the muscle-bone interaction.     

Effect of different photoperiods on concentrations of 5-methoxytryptophol and melatonin in the pineal gland of the Syrian hamster

Specific, sensitive and direct radioimmunoassays have been used to determine the daily patterns of 5-methoxytryptophol (ML) and melatonin in the pineal glands of Syrian hamsters kept in different photoperiods: 8 h light: 16 h darkness (8L:16D), 14L:10D and 16L:8D. A rhythm in pineal ML was evident in animals in all the photoperiods, with high daytime levels (641 +/- 35 (S.E.M.) fmol/gland; n = 162) which dropped to 119 +/- 16 fmol/gland (n = 44) 7.1-7.5 h after lights out. The duration of low night-time ML levels was proportional to the length of the dark phase (1.2 h in 16L:8D, 5.4 h in 14L:10D and 8.4 h in 8L:16D). A marked daily rhythm in melatonin was also present in hamsters in the different photoperiods, with daytime levels of 323 +/- 34 fmol/gland (n = 129) and night-time peak concentrations of 3676 +/- 336 fmol/gland (n = 22). The duration of high nocturnal melatonin levels was dependent upon the length of the dark phase (4.1 h in 16L:8D, 4.5 h in 14L:10D and 12.5 h in 8L:16D). Linear regression analysis revealed a statistically significant inverse relationship between pineal ML and melatonin levels in 8L:16D (P less than 0.001), 14L:10D normal (P less than 0.05) and 14L:10D shifted (P less than 0.001) photoperiods. After advancing the lighting schedule by 10 h (14L:10D, lights off at 04.00 h), pineal ML and melatonin rhythms became entrained to the new lighting regimen. The daily rhythms in pineal ML and melatonin in the Syrian hamster thus depend on the prevailing photoperiod, a reciprocal relationship existing between pineal ML and melatonin concentrations.     

The growth hormone response to pyridostigmine plus growth hormone releasing hormone is not influenced by pubertal maturation

We have evaluated the effect of pubertal maturation on the GH response to growth hormone releasing hormone (GHRH), pyridostigmine (PD) and the combined administration of PD + GHRH in a group of short normal children. Fifteen were prepubertal (13 boys and 2 girls, age 5.0 - 12.5 yr), 10 were early pubertal (8 boys and 2 girls, age 11.5 - 16.9 yr in Tanner stage 2-3 of pubertal maturation), and 6 were late pubertal (6 boys and 2 girls, age 13.6 - 17.1 yr in Tanner stage 4-5 of pubertal maturation). All subjects were tested on three occasions with GHRH 1-29 (1 microgram/Kg iv), PD (60 mg po) and PD + GHRH (60 mg PD administered orally 60 min before GHRH). Peak GH levels after GHRH, PD, and PD + GHRH in the prepubertal children (16.0 +/- 2.8, 8.1 +/- 1.3 and 51.1 +/- 5.5 ng/ml, mean +/- SE, respectively) were not different from those observed in the early pubertal (18.4 +/- 2.1, 9.1 +/- 1.9 and 41.2 +/- 5.6 ng/ml, respectively) and in the late pubertal group (14.9 +/- 2.3, 13.1 +/- 2.4 and 42.6 +/- 2.9 ng/ml, respectively). Evaluation of the area under the curve (AUC) also showed no difference in the GH response to GHRH, PD and PD + GHRH between the three groups studied. These results confirm that the combination PD + GHRH is a powerful test to study the GH secretory capacity of the pituitary, and show that pubertal maturation has no effect on the GH response to this test.     

Gender-related differences in urinary 6-sulfatoxymelatonin levels in obese pubertal individuals

The objective of this study was to measure the urinary excretion of the main melatonin metabolite 6-sulfatoxymelatonin in obese and normal weight (wt) boys and girls. The study included 94 subjects, aged 4-15.7 yr (50 obese and 44 normal wt; 48 boys) classified as: mid-childhood (4-7.99 yr), late-childhood (8-12 yr) and pubertal (10.1-15.7 yr, Tanner II-IV). Normal wt subjects were children with a body mass index (BMI) between the 25th and 75th percentiles, and the group of obese subjects included children whose BMI was above the 97th percentile. A 24-hr urine sample was collected during two intervals: (i) 18:00-08:00 hr, and (ii) 08:00-18:00 hr. Analysis of urinary 6-sulfatoxymelatonin levels was performed by radioimmunoassay. Excretion of 6-sulfatoxymelatonin was expressed as: (i) total amount excreted (microg); (ii) mug excreted per time interval, nocturnal or diurnal; and (iii) the difference between nocturnal and diurnal samples (microg, estimated amplitude). A factorial analysis of variance indicated that nocturnal 6-sulfatoxymelatonin excretion and amplitude were significantly higher in the obese individuals. A significant interaction 'BMI x age' was detected, i.e. the effect of BMI was significant in the pubertal group only. Total, nocturnal and diurnal 6-sulfatoxymelatonin excretion was significantly higher in girls. The increase in 6-sulfatoxymelatonin excretion found in obesity occurred only in boys and at the pubertal age. To what extent this increase in melatonin production contributes to a delayed puberty in some pubertal obese males remains to be established.     

Effect of clonidine on plasma ACTH, cortisol and melatonin in children

An interaction between melatonin and adrenocorticotropin (ACTH) seems to occur in humans and both hormones respond to beta-adrenergic stimulation. As in lower animal species, human pineal gland also contains alpha2-adrenergic receptors as does the hypothalamus-pituitary axis. In this study the response of the pineal gland and of the hypothalamus-pituitary-adrenal axis to alpha2-adrenergic stimulation was assessed. Twenty-nine children (21 males, mean age 11.2 +/- 0.6 yr and eight females, mean age 9.1 +/- 1.1 yr) from the University of Granada Hospital were studied. The children were diagnosed as having growth problems but with a normal response of growth hormone (GH) to clonidine test. Changes in plasma levels of ACTH, cortisol and melatonin were evaluated in these children after oral administration of the alpha2-adrenoceptor agonist clonidine (100 microg/m2) or a placebo. Plasma ACTH, cortisol and melatonin were measured before (basal) and at 30, 60 and 90 min after oral clonidine or placebo administration. Hormonal determinations were carried out by commercial radioimmunoassay kits, previously standardised in our laboratory. The results show a significant decrease in plasma ACTH, cortisol and melatonin 30 min after clonidine administration (P < 0.001), reaching lowest values at 90 min after the drug was administered. The reduction in the levels of these hormones is independent of their normal circadian decay since the control group showed a significantly different pattern of behaviour. These data support the existence of an inhibitory alpha2-adrenergic influence on both the pineal gland and the hypothalamus-pituitary-adrenal in children and further support the presence of alpha2-adrenoceptors in the human pineal gland.     

Influence of gender and pubertal stage at diagnosis on growth outcome in childhood thyrotoxicosis: results of a collaborative study

OBJECTIVE: To evaluate the influence of sex as well as pubertal stage at diagnosis on the growth outcome of childhood thyrotoxicosis. DESIGN: Retrospective, collaborative study. PATIENTS AND METHODS: Longitudinal auxological evaluation in 101 patients (M/F 23/78) for 4.7 +/- 3.1 years subdivided according to pubertal stage at diagnosis into prepubertal (group I) and pubertal (group II). RESULTS: At diagnosis height and bone age (BA) standard deviation score (SDS) were positive both in girls and boys of groups I and II. In boys of group II, height SDS was significantly higher than in girls of the same group (P = 0.007) and in boys of group I (P = 0.026). During the follow-up, in group I, height SDS remained positive without significant differences between boys and girls, and in group II, height SDS remained significantly lower in girls than in boys. The age at onset of puberty and the age at menarche were within the normal range. Final height (FH) was within target height (TH) range in all groups The FH SDS and the height gain (FH-TH) were similar in girls and in boys in group I and significantly higher in boys than in girls (P < 0.05) in group II. The boys of group II showed a mean height gain significantly greater than that found in all the other groups. CONCLUSIONS: Despite the advancement of BA at presentation, there were no adverse effects on subsequent growth and FH; the growth outcome seems to be better in boys than in girls in group II.