Gómez José Manuel, Sahún Manel, Vila Ramon, Domènech Pere, Catalina Pablo, Soler Juan, Badimón Lina
Servicio de Endocrinología y Nutricíon, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Curr Neurovasc Res. 2007 Feb;4(1):55-62. doi: 10.2174/156720207779940662.
Increased mortality due to cardiovascular disease has been described in adult patients with untreated growth hormone (GH) deficiency. GH replacement therapy has been demonstrate to improve vascular reactivity and reverses early atherosclerotic changes in GH deficient adults. The objective of this study was the assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GH deficiency and with GH replacement therapy. We studied 20 GH deficient patients, 10 men and 10 women (aged, 43.4 +/- 8.4 years) under GH replacement therapy compared with a control group matched for age and body mass index, 9 men and 16 women. All subjects, patients and controls, were life-long non-smokers, normotensive and non-diabetic. The following variables were recorded: anthropometrical and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin fragments and fibrin degradation product D-dimer that were determined by an enzyme-linked-immunosorbent assay (ELISA); IGF-I by radioimmunoassay; C-reactive protein by highly sensitive immunonephelometry; E-selectine, P-selectine, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6 and monocyte chemoattractant protein-1 by ELISA. The assessment of endothelial function in vivo was measured by Doppler. Patients with GH deficiency had higher hip/waist ratio and C-peptide and triglycerides concentrations than controls. Our results demonstrated no difference in fibrinolytic markers among patients and controls. E-selectin concentrations were higher in patients than in controls, 22.5+/-11.4 vs. 10.7+/-6.2 microg/L, p = 0.0001. P-selectin, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1 and C-reactive protein were similar in the 2 groups. Vascular reactivity and carotid intima-media thickness were also similar in patients and controls. In this study we have demonstrated in adults with GH deficiency under GH substitution elevation of E-selectin concentrations that may correlate with potential endothelial dysfunction suggesting that the protective effect of GH in these patients may be enhancing other mechanisms.
在未经治疗的生长激素（GH）缺乏成年患者中，心血管疾病导致的死亡率有所增加。GH替代疗法已被证明可改善血管反应性，并逆转GH缺乏成年人的早期动脉粥样硬化改变。本研究的目的是评估垂体功能减退的GH缺乏成年患者以及接受GH替代疗法患者的纤溶标志物、可溶性黏附分子、炎性细胞因子和内皮功能。我们研究了20例接受GH替代疗法的GH缺乏患者，其中10名男性和10名女性（年龄43.4±8.4岁），并与年龄和体重指数相匹配的对照组进行比较，对照组有9名男性和16名女性。所有受试者，包括患者和对照组，均为终生不吸烟者，血压正常且无糖尿病。记录了以下变量：人体测量学和身体成分变量、血糖、胰岛素和C肽的血清浓度；通过酶联免疫吸附测定（ELISA）测定的凝血酶抗凝血酶片段和纤维蛋白降解产物D-二聚体；通过放射免疫测定法测定的IGF-I；通过高敏免疫比浊法测定的C反应蛋白；通过ELISA测定的E-选择素、P-选择素、可溶性细胞间黏附分子-1、可溶性血管细胞黏附分子-1、白细胞介素-6和单核细胞趋化蛋白-1。通过多普勒测量体内内皮功能。GH缺乏患者的臀腰比、C肽和甘油三酯浓度高于对照组。我们的结果表明，患者和对照组之间的纤溶标志物没有差异。患者的E-选择素浓度高于对照组，分别为22.5±11.4 vs. 10.7±6.2μg/L，p = 0.0001。两组中P-选择素、可溶性细胞间黏附分子-1、可溶性血管细胞黏附分子-1、白细胞介素-6、单核细胞趋化蛋白-1和C反应蛋白相似。患者和对照组的血管反应性和颈动脉内膜中层厚度也相似。在本研究中，我们证明了接受GH替代治疗的GH缺乏成年人中E-选择素浓度升高，这可能与潜在的内皮功能障碍相关，提示GH对这些患者的保护作用可能是通过增强其他机制实现的。
