The effect of 24 months recombinant human growth hormone (rh-GH) on LDL cholesterol, triglyceride-rich lipoproteins and apo [a] in hypopituitary adults previously treated with conventional replacement therapy

Hypopituitary adults receiving conventional hormone replacement therapy are reported to have increased cardiovascular mortality. Previous studies indi cate that these patients have several abnormalities in lipoprotein metaboli sm, including reduced low density lipoprotein (LDL) uptake and impaired met abolism of triglyceride-rich lipoproteins. The effects of 24 months of 0.21 IU/kg per week recombinant growth hormone (rh-GH) on the lipoprotein profi les of 22 GH-deficient adults were studied. Samples were collected after a 12-h fast at baseline and 24 months. Total cholesterol, triglyceride, high- density lipoprotein (HDL) cholesterol, LDL cholesterol, apolipoprotein (apo ) A, apo B and apo [a] were determined by routine laboratory methods. LDL p article size was determined by non-denaturing gradient gel electrophoresis. Visceral adiposity was determined by dual energy X-ray absorptiometry (DEX A). Insulin sensitivity was measured in a subset of 17 subjects using a two -stage hyperinsulinaemic-euglycaemic clamp. Significant reductions were observed in total cholesterol (5.3 +/- 0.17 vs 4.9 +/- 0.23 mmol/l; P<0.05) and LDL cholesterol (3.4 +/- 0.17 vs 2.9 +/- 0 .17 mmol/l; P<0.001) at 24 months when compared to baseline. No significant changes were observed in triglyceride level, HDL cholesterol level, apo B, apo A and LDL size. A significant increase in apo [a] [160 (96-416) vs 204 (127-534) U/l; P<0.05] was observed which appeared to be dose-dependent. V isceral adiposity was reduced significantly, insulin sensitivity did not al ter significantly. Replacement for 24 months with rh-GH has a differential effect on the lipid profile with a decrease in LDL, but little effect upon the metabolism of t riglyceride-rich lipoproteins, manifested by unchanged triglyceride, HDL ch olesterol levels and LDL size, despite the reduction in visceral adiposity. Conversely, apo [a], an independent risk factor for cardiovascular disease was increased. The ultimate effect of GH therapy upon cardiovascular morta lity remains to be determined and may be dose-related. (C) 1999 Harcourt Pu blishers Ltd.