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Congenital Growth Hormone (GH) Deficiency and Atherosclerosis: Effects of GH Replacement in GH-Naive Adults

Departments of Endocrinology and Cardiology (J.L.M.O., M.H.A.-O., A.D., R.M.C.P., C.R.P.O., C.T.F., J.A.B.-F., F.D.A.-A., C.M.-S., A.C.N.-J., E.O.A., F.T.O. V.C.C., R.X.), Federal University of Sergipe, Aracaju, SE Brazil 49060-100; and The Sidney Kimmel Comprehensive Cancer Center (A.B., G.P.) and the Division of Endocrinology (R.S.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Address all correspondence and requests for reprints to: Roberto Salvatori, M.D., Division of Endocrinology, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: salvator{at}jhmi.edu.

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 intima-media thickness and in the number of atherosclerotic carotid plaques.