The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults.

Abstract

GH deficiency is associated with increased cardiovascular morbidity, which may be determined by alterations in vascular risk factors. We report the effect of partially treated hypopituitarism and subsequent GH replacement (mean dose, 0.2 IU/kg.week) on putative cardiovascular risk factors in 22 nondiabetic hypopituitary subjects in a 6-month, double blind, controlled study (active/placebo ratio, 11:11). All patients were subsequently treated with GH for a further 6 months. Total fat, percent body fat, and central fat were measured by dual energy x-ray absorptiometry. The hypopituitary patients had increased percent fat (P = 0.03) and central fat (P < 0.01) compared with body mass index-matched controls. Before GH treatment, fasting (total) and specific insulin positively correlated with body mass index (P = 0.02 and P < 0.001, respectively), 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 (IS), calculated by homeostatic model of assessment, were related to total fat (P < 0.001 and P = 0.02). GH treatment for 6 months led to a reduction 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 from 36.9% (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 = 0.016 and P = 0.002). The degree of correlation among indices of IS, body composition, and fat distribution increased after GH treatment. Fasting plasma glucose rose significantly, but was within the reference range. During 12 months of GH therapy, a significant increase in serum lipoprotein-(a) was observed (P < 0.05). Although GH has beneficial effects on central adiposity and lipid fractions, it is also associated with a decrease in IS; these effects may vary between individuals.

Adult GH deficiency throughout lifetime

“…The deleterious effects of GHD on body composition are evident in both obese and non-obese patients and are reversed with GH replacement (35). Importantly, the inverse relationship between various measures of adiposity and indices of insulin sensitivity remains evident in normal weight hypopituitary patients (35), confirming that the adverse consequences of GHD on insulin action are related to specific changes in fat distribution and not simply to increased BMI.…”

Safety aspects of GH replacement

“…During prolonged GH replacement, some studies report still impaired (13)(14)(15) glucose tolerance, whereas other studies report unchanged (16,17) glucose tolerance as compared with baseline. The results of one study, using the hyperinsulinaemic, euglycaemic clamp technique, suggest that the decreased baseline insulin sensitivity persists for at least up to 2 years of GH treatment (18).…”

The effect of recombinant human GH replacement therapy on lipoprotein(a) and other lipid parameters in adults with acquired GH deficiency: results of a double-blind and placebo-controlled trial

“…In an open 36-month study into the effect of GH replacement in 21 adults (17), Lp(a) was reported to increase only in those patients with pretreatment levels >20 mg/dl. In a double-blind placebo-controlled study on 22 patients with hypopituitarism, Weaver et al (18) found no significant increase in Lp(a) after 6 months of GH treatment, but in a subgroup of eight patients who received GH for a total of 12 months a modest but significant rise in Lp(a) was observed. In a double-blind, cross-over study of GH treatment in GHD adults, Eden et al (19) reported a marked almost twofold increase in Lp(a) after only 6 weeks of treatment, which was sustained after 26 weeks.…”