Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-defieient adults

Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid arte ry intima-media thickness (IMT) and reduced distensibility] are more preval ent. As GH replacement can reverse some risk factors of atherosclerosis, th e present study examined the effect of GH treatment on morphological and fu nctional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with reco mbinant human GH (0.018 U/kg BW.day) for 18 months. IMT of the common carot id artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothe lium-dependent dilation (EDD) of the brachial artery were measured by B mod e ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentratio ns of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF -binding protein-3 (IGFBP-3) were also measured. In GHD men before treatmen t the IMTs of the CCA [mean(sD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) an d 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.55; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprote in(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and functional atherosclerotic change s in major arteries and, if maintained, may reduce vascular morbidity and m ortality. GH seems to act via IGF-I, which is known to have important effec ts on endothelial cell function.