Congenital growth hormone (GH) deficiency and atherosclerosis: Effects of GH replacement in GH-naive adults

Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. Methods: We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 ± 14.5 yr; 122 ± 7.7 cm; 36.7 ± 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout. Results: Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline. Conclusion: In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intimamedia thickness and in the number of atherosclerotic carotid plaques.