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: To longitudinally assess 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 y) 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/week). 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-hour 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-1 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.