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The effects of growth hormone (GH) replacement therapy on lipid metabolism and carbohydrate tolerance in adults with GH deficiency
Poster abstracts 147
The effect of growth hormone (GH) replacement therapy on endothelial function and oxidative stress in patients with hypopituitarism and GH deficiency L. M. Evans, ~ J. S. Davies, ~ R. A. Anderson$ G. R. Ellis$ M. P. Frennaux$ J. A. E. Rees ~ and M. F. Scanlon ~ Departments of 1Medicine and 2Cardiology, University of Wales College of Medicine, Cardiff, UK
Endothelial dysfunction and the excess generation of oxygen free radicals are key factors in the pathogenesis of atherosclerosis. Growth hormone deficiency (GHD) has been associated with accelerated atherosclerosis. Therefore, the aim of this study was to investigate the effect of growth hormone (GH) replacement therapy on endothelial function and oxygen free radical status in adults with GHD. Eight adults with GHD were studied before and after 3 months of GH therapy (Genotropin®, Pharmacia & Upjohn, Stockholm, Sweden), 0.02 IU/kg/day (0.007 mg/kg/day). ' Results were compared with matched control individuals at baseline. Endothelial function was assessed using an ultrasonic vessel wall tracking system to measure peak flow mediated (endothelium-dependent) brachial artery dilatation, and compared with endothelium-independent responses to glyceryl trinitrate, 400 pg. Oxidative stress was assessed directly by measuring carbon-centred oxygen free radicals in fasting venous blood using electron paramagenetic resonance spectroscopy. Fasting venous blood was collected into a prepared spintrap (aphenyl N-tert butyl nitrone [PBN]) and immediately analysed for oxygen free radicals. The PBN adduct derived from toluene
extraction was then dissolved in chloroform and analysed in a spectrometer. Results are expressed in arbitrary units. At baseline, flow-mediated dilatation (% change in diameter) was significantly impaired in the patients with GHD compared with controls (3.1 -+ 1.9 vs 6.9 ± 2.5, P < 0.001), hut glyceryl trinitrate-mediated dilatation was similar in both groups. Oxygen free radical status was significantly elevated in the patients with GHD compared with controls (0.36 ___0.09 vs 0.11 _+0.12, P< 0.05). Following GH therapy, flow-mediated dilatation improved in the patients with GHD to a level comparable with controls (5.9 _+ 1.2 vs 3.1 _+ 1.9, P < 0.02). Oxygen free radical status also significantly improved in patients with GHD following GH therapy (0.23 _+0.03 vs 0.36 + 0.09, P< 0.05), although this remained elevated compared with controls. In conclusion, the demonstration of endothelial dysfunction and enhanced oxidative stress provides an insight into the pathogenesis of atherosclerosis in adults with GHD. Furthermore, following therapy, endothelial dysfunction returns to normal levels and generation Df oxygen free radicals is significantly reduced, suggesting that GH replacement therapy is anti-atherogenic.
The effects of growth hormone (GH) replacement therapy on lipid metabolism and carbohydrate tolerance in adults with GH deficiency J. Pehafiel, E. Torres, M. Mu6oz-Torres and R Escobar-Jimenez Endocrine Unit, University Hospital, Granada, Spain
The aim of this study was to investigate the effects of growth hormone (GH) replacement therapy on lipid metabolism and carbohydrate tolerance in adults with hypopituitarism and GH deficiency (GHD). A total of 24 patients (ten men, 14 women; mean age, 37.2 years; range, 22-60 years; body mass index, 28.5 _+ 3.2 kg/m 2) with GHD (mean duration, 13.2 years) were included in the study. For the first 6 months, the study was placebo-controlled and double-blind. All patients received GH replacement therapy for the second period (18 months) of the trial. The dose of GH, given as daily subcutaneous injections, was 0.125 1U/kg/week (0.04 mg/kg/week) for the first month, and 0.25 1U/kg/week (0.08 mg/kg/week) thereafter, adjusted according to levels of insulin-like growth factor I). All patients were receiving replacement therapy with thyroid, gonadal and adrenal hormones as appropriate. Levels of fasting plasma glucose, glycosylated haemoglobin (HbAI~), and plasma lipids were measured every 6 months, and an oral glucose tolerance
test was performed at 0 and 12 months. No significant changes in levels of fasting plasma glucose, glucose after an oral glucose tolerance test or HbA~c were detected at any stage of the study. Further, no significant changes in levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol or fasting triglyceride were observed during the 6 months of GH or placebo treatment. However, in the open phase of the trial, a sustained downward trend in LDL-cholesterol levels was observed following GH therapy (158.4 _+ 34.8 mg/dl before treatment vs 122.1 _+ 26.7 mg/dl after 24 months of GH treatment, P < 0.001) and in fasting triglyceride levels (139.5 _+48.1 vs 111.0 _+39.9 mg/dl, P< 0.05). No significant change in levels of HDL-cholesterol was observed. In conclusion, our results confirm that GH replacement therapy in adults with GHD significantly reduces LDL-cholesterol and fasting triglyceride levels. Furthermore, no minor detrimental effects on carbohydrate tolerance were observed.
The effect of growth hormone (GH) replacement therapy on endothelial function and oxidative stress in patients with hypopituitarism and GH deficiency L. M. Evans, ~ J. S. Davies, ~ R. A. Anderson$ G. R. Ellis$ M. P. Frennaux$ J. A. E. Rees ~ and M. F. Scanlon ~ Departments of 1Medicine and 2Cardiology, University of Wales College of Medicine, Cardiff, UK
Endothelial dysfunction and the excess generation of oxygen free radicals are key factors in the pathogenesis of atherosclerosis. Growth hormone deficiency (GHD) has been associated with accelerated atherosclerosis. Therefore, the aim of this study was to investigate the effect of growth hormone (GH) replacement therapy on endothelial function and oxygen free radical status in adults with GHD. Eight adults with GHD were studied before and after 3 months of GH therapy (Genotropin®, Pharmacia & Upjohn, Stockholm, Sweden), 0.02 IU/kg/day (0.007 mg/kg/day). ' Results were compared with matched control individuals at baseline. Endothelial function was assessed using an ultrasonic vessel wall tracking system to measure peak flow mediated (endothelium-dependent) brachial artery dilatation, and compared with endothelium-independent responses to glyceryl trinitrate, 400 pg. Oxidative stress was assessed directly by measuring carbon-centred oxygen free radicals in fasting venous blood using electron paramagenetic resonance spectroscopy. Fasting venous blood was collected into a prepared spintrap (aphenyl N-tert butyl nitrone [PBN]) and immediately analysed for oxygen free radicals. The PBN adduct derived from toluene
extraction was then dissolved in chloroform and analysed in a spectrometer. Results are expressed in arbitrary units. At baseline, flow-mediated dilatation (% change in diameter) was significantly impaired in the patients with GHD compared with controls (3.1 -+ 1.9 vs 6.9 ± 2.5, P < 0.001), hut glyceryl trinitrate-mediated dilatation was similar in both groups. Oxygen free radical status was significantly elevated in the patients with GHD compared with controls (0.36 ___0.09 vs 0.11 _+0.12, P< 0.05). Following GH therapy, flow-mediated dilatation improved in the patients with GHD to a level comparable with controls (5.9 _+ 1.2 vs 3.1 _+ 1.9, P < 0.02). Oxygen free radical status also significantly improved in patients with GHD following GH therapy (0.23 _+0.03 vs 0.36 + 0.09, P< 0.05), although this remained elevated compared with controls. In conclusion, the demonstration of endothelial dysfunction and enhanced oxidative stress provides an insight into the pathogenesis of atherosclerosis in adults with GHD. Furthermore, following therapy, endothelial dysfunction returns to normal levels and generation Df oxygen free radicals is significantly reduced, suggesting that GH replacement therapy is anti-atherogenic.
The effects of growth hormone (GH) replacement therapy on lipid metabolism and carbohydrate tolerance in adults with GH deficiency J. Pehafiel, E. Torres, M. Mu6oz-Torres and R Escobar-Jimenez Endocrine Unit, University Hospital, Granada, Spain
The aim of this study was to investigate the effects of growth hormone (GH) replacement therapy on lipid metabolism and carbohydrate tolerance in adults with hypopituitarism and GH deficiency (GHD). A total of 24 patients (ten men, 14 women; mean age, 37.2 years; range, 22-60 years; body mass index, 28.5 _+ 3.2 kg/m 2) with GHD (mean duration, 13.2 years) were included in the study. For the first 6 months, the study was placebo-controlled and double-blind. All patients received GH replacement therapy for the second period (18 months) of the trial. The dose of GH, given as daily subcutaneous injections, was 0.125 1U/kg/week (0.04 mg/kg/week) for the first month, and 0.25 1U/kg/week (0.08 mg/kg/week) thereafter, adjusted according to levels of insulin-like growth factor I). All patients were receiving replacement therapy with thyroid, gonadal and adrenal hormones as appropriate. Levels of fasting plasma glucose, glycosylated haemoglobin (HbAI~), and plasma lipids were measured every 6 months, and an oral glucose tolerance
test was performed at 0 and 12 months. No significant changes in levels of fasting plasma glucose, glucose after an oral glucose tolerance test or HbA~c were detected at any stage of the study. Further, no significant changes in levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol or fasting triglyceride were observed during the 6 months of GH or placebo treatment. However, in the open phase of the trial, a sustained downward trend in LDL-cholesterol levels was observed following GH therapy (158.4 _+ 34.8 mg/dl before treatment vs 122.1 _+ 26.7 mg/dl after 24 months of GH treatment, P < 0.001) and in fasting triglyceride levels (139.5 _+48.1 vs 111.0 _+39.9 mg/dl, P< 0.05). No significant change in levels of HDL-cholesterol was observed. In conclusion, our results confirm that GH replacement therapy in adults with GHD significantly reduces LDL-cholesterol and fasting triglyceride levels. Furthermore, no minor detrimental effects on carbohydrate tolerance were observed.