The effect of GH replacement therapy on endothelial function and oxidativestress in adult growth hormone deficiency

Objectives: Controversy persists with regard to the atherogenic risk associ ated with adult growth hormone deficiency (GHD). Endothelial dysfunction an d enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied the effect of three months of low dose GH replacement ther apy (0.03 IU/kg/day) on these parameters in GHD adults. Subjects and Methods: Eight hypopituitary GHD adults (4 male, 4 female), wh o were receiving conventional hormone replacement therapy, were studied bef ore and after 3 months of GH replacement (0.03 IU/kg/day). All observations obtained were compared with similar measurements made in 8 matched control subjects. All study subjects were non-smokers, normotensive and gave no pe rsonal or family history of premature vascular disease. Endothelial functio n was assessed using a specialised vessel wall tracking system to measure e ndothelium-dependent, now-mediated, brachial artery dilatation (FMD). Measu rements were repeated following glyceryl-trinitrate (GTN) (endothelium-inde pendent dilatation). Oxidative stress was assessed by directly measuring li pid-derived free radicals in venous blood by electron paramagnetic resonanc e spectroscopy. Fasting lipids, insulin, plasma glucose and IGF-I were also measured at baseline and following GH replacement. Results: FMD, expressed as a percentage change from resting base-line diame ter, was significantly impaired in the pre-treatment GHD patients compared with controls (3.1 +/- 2.1% vs 6.1 +/- 0.9%, P < 0.001; means +/- S.D.) ind icating endothelial dysfunction, Significant increase in FMD was noted foll owing GH therapy (3.1 +/- 2.1% vs 6.5 +/- 1.9%, P < 0.001). Free radicals ( arbitrary units) were elevated in the pre-treatment GHD patients compared w ith controls (0.36 +/- 0.09 vs 0.11 +/- 0.12, P < 0.05) and fell significan tly following GH therapy (0.23 +/- 0.03 vs 0.36 +/- 0.09, P < 0.05), althou gh they remained elevated compared with controls. Fasting insulin was signi ficantly higher (25.9 +/- 18.8 vs 13.9 +/- 6.7 mu/l, P < 0.05) and IGF-I co ncentrations lower (10.8 +/- 4.7 vs 20.2 +/- 6.3 nmol/l, P < 0.05) in the p re-treatment GHD subjects. After treatment there were no changes in insulin concentration, although IGF-I levels were normalised (10.8 +/- 2.3 vs 23.6 +/- 11.4 nmol/l, P < 0.05). Conclusions: Endothelial dysfunction and enhanced oxidative stress are feat ures of adult GHD. This study suggests plausible mechanisms underlying any proatherogenic tendency in adult. GHD and demonstrates improvement of these factors following GH replacement.