Growth Hormone Treatment in Adolescent Males with Idiopathic Short Stature: Changes in Body Composition, Protein, Fat, and Glucose Metabolism

Abstract

Abstract Context: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH. Objective: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion. Participants and Setting: Eight males with ISS (10.8–16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center. Study Design: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg·wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m2·min) euglycemic clamp. Results: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels. Conclusions: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.