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纤维肌痛综合征患者的生长激素(GH)释放激素-GH-胰岛素样生长因子-1轴

The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome.

作者信息

Leal-Cerro A, Povedano J, Astorga R, Gonzalez M, Silva H, Garcia-Pesquera F, Casanueva F F, Dieguez C

机构信息

Department of Endocrinology, Hospital Universitario Virgen del Rocio, Sevilla, Spain.

出版信息

J Clin Endocrinol Metab. 1999 Sep;84(9):3378-81. doi: 10.1210/jcem.84.9.5982.

Abstract

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. To gain further insight into the mechanisms leading to dysregulation of the GH-IGF-1 axis in these patients, we assessed 24-h spontaneous GH secretion, GH responses to GHRH, and IGF-1 and IGF binding protein (BP)-3 levels before and after 4 days treatment with human (h)GH. We found that, in comparison with controls, patients with FM exhibited a marked decrease in spontaneous GH secretion as assessed by mean GH secretion (2.5 +/- 0.4 microg/L in controls vs. 1.2 +/- 0.1 microg/L in FM, P < 0.05), pulse height (4.7 +/- 0.8 microg/L in controls vs. 2.5 +/- 0.3 microg/L in FM, P < 0.05), and pulse area (4.7 +/- 1 min/mg x L in controls vs. 2.3 +/- 0.3 min/mg x L in FM, P < 0.05). In contrast, GH responses to GHRH (100 microg, i.v.) were similar in controls (mean peak, 13.5 +/- 2.5 microg/L) and in patients with FM (12.2 +/- 3 microg/L). Finally, treatment with hGH (2 IU, s.c. daily), over 4 days, led to a clear-cut increase in plasma IGF-1 and IGFBP-3 levels in patients with FM. In conclusion, our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM.

摘要

纤维肌痛(FM)是一种非关节源性疼痛综合征,其特征为疲劳、广泛的肌肉骨骼疼痛、疲倦和睡眠障碍,检查时无任何其他客观发现。有趣的是,FM的一些临床特征与成人生长激素缺乏综合征中描述的特征相似。此外,FM患者的胰岛素样生长因子(IGF)-1水平经常降低。为了进一步深入了解导致这些患者生长激素-IGF-1轴失调的机制,我们评估了24小时自发性生长激素分泌、生长激素对生长激素释放激素(GHRH)的反应以及人(h)GH治疗4天前后的IGF-1和IGF结合蛋白(BP)-3水平。我们发现,与对照组相比,FM患者的自发性生长激素分泌显著降低,通过平均生长激素分泌评估(对照组为2.5±0.4μg/L,FM患者为1.2±0.1μg/L,P<0.05)、脉冲高度(对照组为4.7±0.8μg/L,FM患者为2.5±0.3μg/L,P<0.05)和脉冲面积(对照组为4.7±1分钟/毫克×升,FM患者为2.3±0.3分钟/毫克×升,P<0.05)。相反,生长激素对GHRH(100μg,静脉注射)的反应在对照组(平均峰值为13.5±2.5μg/L)和FM患者(12.2±3μg/L)中相似。最后,hGH(2 IU,皮下注射,每日一次)治疗4天导致FM患者血浆IGF-1和IGFBP-3水平明显升高。总之,我们的数据表明,FM患者的自发性生长激素分泌显著降低,但垂体对外源性给予的GHRH反应正常,因此提示这些患者在生长激素神经内分泌控制的下丘脑水平存在改变。此外,我们发现GH治疗4天后IGF-1和IGFBP-3水平升高,这为测试hGH对FM患者的治疗潜力开辟了可能性。

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