THE EFFECT OF GROWTH-HORMONE REPLACEMENT ON SERUM-LIPIDS, LIPOPROTEINS, APOLIPOPROTEINS AND CHOLESTEROL PRECURSORS IN ADULT GROWTH-HORMONE DEFICIENT PATIENTS

OBJECTIVE Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We theref ore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipopr oteins and cholesterol precursors in adult growth hormone deficient pa tients. DESIGN Double-blind placebo controlled trial. Patients were ra ndomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/da y for 1 month followed by 0.036 U/kg/day for 1 month). PATIENTS Eighte en patients with severe growth hormone deficiency. MEASUREMENTS Fastin g lipid, lipoprotein and cholesterol precursors (lathosterol and meval onic acid) were measured at baseline and after 2 months. RESULTS In th e rhGH treated group there was a significant fall in serum cholesterol (P < 0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol ( P < 0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P < 0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolip oprotein B (P < 0.01 (1.30 +/- 0.71 to 1.15 +/- 0.11 g/l and mevalonic acid (P < 0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 mu g/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprote in A1 lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fal l in cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and apolipopro tein B (P < 0.01). There were no significant changes in any of the mea sured variables in the placebo group. CONCLUSION We conclude that GH m ay be involved in the regulation of lipid and lipoprotein metabolism a nd that rhGH replacement therapy of adult GHD patients is associated w ith beneficial changes in lipid and lipoprotein profiles. The reductio n in mevalonic acid is consistent with up-regulation of hepatic LDL re ceptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.