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/m²), 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.