Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency

OBJECTIVE The ob gene product, leptin, is considered to be a marker of adipose tissue mass and a possible homeostatic regulator of body mass. Our objective was to examine the effect of GH replacement on adipose tissue stores and leptin in adult hypopituitarism. SUBJECTS Twenty adults, mean age 47 years (range 20-69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment. MEASUREMENTS Body composition was measured by dual-energy X-ray absorptiometry (DEXA) in the whole body, trunk and limbs. Plasma leptin was measured by radioimmunoassay at baseline and +2, +4, +8 and +12 weeks in each treatment arm. RESULTS Total body tissue fat (mean +/- SE) was 30.1 +/- 2.2% after GH compared with 31.9 +/- 2.2% after placebo, P < 0.001 (ANOVA). There were no significant changes in BMI (kg/m(2)), 29.1 +/- 1.3 after placebo vs 28.8 +/- 1.2 after GH; or waist to hip ratio (WHR), 0.91 +/- 0.01 after both placebo and GH. Baseline plasma leptin showed a significant correlation with baseline BMI, r = 0.67, P < 0.005 and baseline percentage total body fat, R = 0.89, P < 0.001. Plasma leptin (adjusted by using baseline percentage total body fat as a covariate) showed a significant linear decrease with time on GH compared with placebo (P = 0.03, ANOVA). CONCLUSIONS Plasma leptin and total body fat fall promptly in response to low-dose replacement of GH in GH-deficient subjects, Hormone-induced changes in leptin can occur in humans in the absence of change in body mass index.