Background: Growth hormone (GH) deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP).

Methods: We have studied the effects of 6-months GHRT in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD (IGHD) due to a homozygous mutation in GH-Releasing Hormone (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 months of bi-monthly depot GH injections, (Nutropin Depot®, Genentech) (pGH), and after 6 (6 mo) and 12 months (12 mo) of washout.

Results: Despite modest trough serum insulin like growth factor 1 (IGF-1) increase, GHRT caused a decrease in skinfolds and in waist/hip ratio, with a rebound increase at 12 mo. Total and LDL cholesterol were reduced pGH and returned to baseline at 6 mo. High density lipoprotein (HDL) cholesterol increased pGH, but at 12 mo was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 mo, and of carotid intima media thickness (IMT) from 6 mo to 12 mo. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 mo and 12 mo, respectively, when compared to baseline.

Conclusion: In patients with lifetime IGHD, 6 months treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in IMT and in the number of atherosclerotic carotid plaques.