THE EFFECT OF LOW-DOSE RECOMBINANT HUMAN GROWTH-HORMONE REPLACEMENT ON REGIONAL FAT DISTRIBUTION, INSULIN SENSITIVITY, AND CARDIOVASCULAR RISK-FACTORS IN HYPOPITUITARY ADULTS

GH deficiency is associated with increased cardiovascular morbidity, w hich may be determined by alterations in vascular risk factors. We rep ort the effect of partially treated hypopituitarism and subsequent GH replacement (mean dose, 0.2 IU/kg.week) on putative cardiovascular ris k factors in 22 nondiabetic hypopituitary subjects in a 6-month, doubl e blind, controlled study (active/placebo ratio, 11:11). All patients were subsequently treated with GH for a further 6 months. Total fat, p ercent body fat, and central fat were measured by dual energy x-ray ab sorptiometry. The hypopituitary patients had increased percent fat (P = 0.03) and central fat (P < 0.01) compared with body mass index-match ed controls. Before GH treatment, fasting (total) and specific insulin positively correlated with body mass index (P = 0.02 and P < 0.001, r espectively), waist/hip ratio (P = 0.05 and P = 0.01), and central fat (P = 0.03 and P = 0.003). Specific insulin and insulin sensitivity (I S), calculated by homeostatic model of assessment, were related to tot al fat (P < 0.001 and P = 0.02). GH treatment for 6 months led to a re duction in total fat (P < 0.02), percent fat (P = 0.002), central fat (P = 0.012), waist/hip ratio (P < 0.05), total cholesterol (P = 0.03), and apolipoprotein-B (P = 00001), as well as a decrease in the IS fro m 36.98 (range, 12-100%) to 25% (range, 2.5-55%; P = 0.0002). This was paralleled by a rise in fasting (total) and specific insulin (P = 0.0 16 and P = 0.002). The degree of correlation among indices of IS, body composition, and fat distribution increased after GH treatment. Fasti ng plasma glucose rose significantly, but was within the reference ran ge. During 12 months of GH therapy, a significant increase in serum li poprotein-(a) was observed (P < 0.05). Although GH has beneficial effe cts on central adiposity and lipid fractions, it is also associated wi th a decrease in IS; these effects may vary between individuals.