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Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults
M Pfeifer1, R Verhovec, B Zizek
1Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center, Ljubljana, Slovenia.
Insights
Growth hormone (GH) treatment in adults with GH deficiency (GHD) reverses early atherosclerosis markers in arteries. This intervention may reduce vascular disease risk and mortality in hypopituitary patients.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Vascular Biology
Background:
- Hypopituitary patients with GH deficiency (GHD) exhibit increased vascular disease mortality.
- Early atherosclerosis markers, such as increased carotid artery intima-media thickness (IMT) and reduced arterial distensibility, are more prevalent in GHD individuals.
- GH replacement therapy is known to improve some cardiovascular risk factors.
Purpose of the Study:
- To investigate the effects of recombinant human GH treatment on arterial morphology and function in GHD adults.
- To assess changes in carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (EDD) following GH therapy.
Main Methods:
- Eleven GHD hypopituitary men received recombinant human GH for 18 months.
- Carotid artery IMT (CCA and CB) and brachial artery EDD were measured using B-mode ultrasound at baseline and various time points.
- Serum lipid profiles, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were analyzed.
Main Results:
- GH treatment significantly reduced carotid artery IMT, normalizing CCA and CB measurements within 3-6 months.
- Flow-mediated EDD of the brachial artery showed significant improvement, sustained throughout the 18-month treatment period.
- GH therapy increased HDL cholesterol but did not affect LDL cholesterol or lipoprotein(a); IMT and EDD changes correlated negatively with serum IGF-I levels.
Conclusions:
- GH treatment effectively reverses early atherosclerotic changes in the carotid and brachial arteries of GHD adults.
- Sustained GH therapy may potentially decrease vascular morbidity and mortality in this patient population.
- GH's beneficial vascular effects are likely mediated, at least in part, by IGF-I, impacting endothelial function.
Abstract:
Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode 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 concentrations 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 treatment 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) and 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 = -0.53; 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 lipoprotein(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 changes in major arteries and, if maintained, may reduce vascular morbidity and mortality. GH seems to act via IGF-I, which is known to have important effects on endothelial cell function.