Sakai Haruna, Tsuchiya Kyoichiro, Nakayama Chisato, Iwashima Fumiko, Izumiyama Hajime, Doi Masaru, Yoshimoto Takanobu, Tsujino Motohiro, Yamada Shozo, Hirata Yukio
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Japan.
Endocr J. 2008 Oct;55(5):853-9. doi: 10.1507/endocrj.k07e-125. Epub 2008 May 28.
Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age- and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, low-density lipoprotein cholesterol (LDL-C), hemoglobin HA(1C), fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.
血流介导的血管舒张功能(FMD)是一种用于检测心血管疾病早期内皮功能障碍的血管功能测试。活动性肢端肥大症患者因心血管事件导致的发病率和死亡率较高。为了确定活动性肢端肥大症是否与内皮功能障碍有关,我们研究了17例活动性肢端肥大症患者,在经蝶窦手术(TSS)前后测量了FMD、颈动脉内膜中层厚度(IMT)和臂踝脉搏波速度(baPWV)以及其他生化参数。活动性肢端肥大症患者的基线FMD百分比显著低于年龄和性别匹配的对照受试者。TSS后,肢端肥大症患者的平均FMD百分比从5.3%显著增加到7.4%;12例患者的FMD百分比增加(反应者),而5例患者的FMD百分比降低或未改变(无反应者)。然而,TSS后颈动脉IMT和baPWV均未改变。血清生长激素(GH)、胰岛素样生长因子(IGF)-1、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、血红蛋白HA(1C)、空腹血糖和胰岛素水平以及稳态模型评估(HOMA)-R显著降低,而高密度脂蛋白胆固醇显著增加。反应者的基线FMD百分比显著低于无反应者,并且TSS后反应者的胰岛素水平和HOMA-R均显著降低,而无反应者则未降低。简单回归分析显示,在反应者中,FMD百分比的变化与LDL-C的变化呈显著负相关,而与IGF-1或GH的变化无关。总之,提示与活动性肢端肥大症相关的内皮功能障碍在TSS后很快改善,这与LDL-C和/或胰岛素抵抗有关,而与过量的GH和/或IGF-1本身无关。