A. Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 295: E385-E392, 2008. First published June 10, 2008 doi:10.1152/ajpendo.00052.2008.-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 L4-L5 and soleus intramyocellular lipid ( 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 ϭ 0.03) and log UFC was higher (P ϭ 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 OBESITY IS A GLOBAL PROBLEM, and, according to recent estimates, 17% of US children and adolescents are overweight [body mass index (BMI) Ͼ95th percentile] and 16.5% are at risk for overweight (BMI between 85th and 95th percentiles) (11,19). Commensurate with the rising prevalence of overweight, the prevalence of type 2 diabetes is increasing, such that up to 30 -50% of all newly diagnosed children with diabetes are classified as having type 2 diabetes, in contrast to Ͻ5% before 1994 (13, 23). Although body composition and lipid profiles are markedly altered in overweight compared with normal-weight adolescents, associations of hormonal alterations with body composition and insulin sensitivity changes in overweight teenagers have not been well characterized.Disorders r...