Changes in subcutaneous and visceral fat mass during growth hormone replacement therapy in adult men

OBJECTIVES : To assess the degree of subcutaneous and intraabdominal fat accumulation in growth hormone (GH) deficient adult men, and to evaluate the lipolytic effects of GH replacement therapy. DESIGN : Placebo-controlled, double-blind, dose-response study. All patients, including those initially starting on placebo, received GH for a period of one year. SUBJECTS : 46 adult men (mean age 28.0 ± 4.5 y) with childhood-onset GH deficiency (GHD). MEASUREMENTS : Subcutaneous fat mass and fat distribution was assessed by measurement of skinfold thicknesses at seven different sites. Intraabdominal fat mass was assessed by computerized tomography (CT). Reference values were obtained from age- and sex-matched controls with a normal body mass index. RESULTS : The sum of skinfolds (SKFs) was 75% (95% CI : 52-98% higher, and intraabdominal fat area was 84% (95% CI : 45-122%) greater in GHD patients than in age- and sex-matched controls. Patients with multiple pituitary hormone deficiencies (MPHD, n = 30), who were all receiving conventional hormone replacement therapy, were more obese than patients with isolated GHD (IGHD, n = 16). This difference was attributed to a more severe impairment in GH secretion, as well as to the lower androgen levels in patients with MPHD. GH treatment was associated with a gradual decline in subcutaneous fat that continued for approximately six months. Thereafter, a new steady-state was reached. The GH-induced decline in subcutaneous and intraabdominal fat was dose-dependent (r = 0.84, p < 0.001 and r = 0.52, p < 0.001, respectively). The efficacy of GH treatment was similar in IGHD and MPHD patients. Optimal GH replacement, defined as treatment resulting in normalization of serum insulin-like growth factor-I (IGF-I) concentration, was achieved in 25 patients. In this subgroup the sum of SKFs decreased by 27% (95% CI : 22-32%) and intraabdominal fat was reduced by 47% (95% CI : 38-57%). CONCLUSION : We conclude that subcutaneous as well as intraabdominal fat mass are abnormally high in GHD men, and that GH treatment with doses within the physiological range profoundly reduces the sizes of both fat compartments. In addition, GH replacement therapy was found to be equally effective in men with IGHD as in those with MPHD.