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Although body composition, insulin sensitivity, and lipids are markedly altered in overweight adolescents, hormonal associations with these parameters have not been well characterized. Growth hormone (GH) deficiency and hypercortisolemia predispose to abdominal adiposity and insulin resistance, and GH secretion is decreased in obese adults. We hypothesized that low-peak GH on the GH-releasing hormone (GHRH)-arginine stimulation test and high cortisol in overweight adolescents would be associated with higher regional fat, insulin resistance, and lipids. We examined the following parameters in 15 overweight and 15 bone age-matched control 12- to 18-yr-old girls: 1) body composition using dual-energy X-ray absorptiometry and MR [visceral and subcutaneous adipose tissue at [L.sub.4]-[L.sub.5] and soleus intramyocellular lipid ([sup.1]H-MR spectroscopy)], 2) peak GH on the GHRH-arginine stimulation test, 3) mean overnight GH and cortisol, 4) 24-h urinary free cortisol (UFC), 5) fasting lipids, and 6) an oral glucose tolerance test. Stepwise regression was the major tool employed to determine relationships between measured parameters. Log peak GH on the GHRH-arginine test was lower (P = 0.03) and log UFC was higher (P = 0.02) in overweight girls. Log mean cortisol (overnight sampling) was associated positively with subcutaneous adipose tissue and, with body mass index standard deviation score, accounted for 92% of its variability, whereas log peak GH and body mass index standard deviation score accounted for 88% of visceral adipose tissue variability and log peak GH for 34% of the intramyocellular lipid variability. Log mean cortisol was independently associated with log homeostasis model assessment of insulin resistance, LDL, and HDL and explained 49-59% of the variability. Our data indicate that lower peak GH and higher UFC in overweight girls are associated with visceral adiposity, insulin resistance, and lipids. obesity; body composition; homeostasis model assessment of insulin resistance; lipids

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.000l) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition. growth hormone; cortisol; insulin resistance; estradiol; ghrelin; thyroid hormones

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency. growth hormone; cortisol; total triiodothyronine; estradiol; luteinizing hormone; insulin resistance

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.