Increased Hypothalamic-Pituitary-Adrenal Axis Activity in Huntington's Disease
Increased Hypothalamic-Pituitary-Adrenal Axis Activity in Huntington's Disease
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DOI：
10.1210/jc.2008-2543
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发表时间：
2009-04-01
影响因子：
5.8
通讯作者：
Roos, Raymund A. C.
中科院分区：
文献类型：
--
作者：
Aziz, N. Ahmad;Pijl, Hanno;Roos, Raymund A. C.
背景：亨廷顿病（HD）是一种致命的遗传性神经退行性疾病，其特征是运动、认知和行为障碍。下丘脑-垂体-肾上腺（HPA）轴功能障碍可能导致许多HD体征和症状;然而，没有关于HD患者皮质醇昼夜变化和分泌动力学的数据。目的：本研究的目的是详细分析HD患者HPA轴功能与临床体征和症状的关系。设计、设置和参与者：在一个临床研究实验室中，对8名早期、无药物治疗的HD患者和8名年龄、性别和体重指数匹配的对照组进行了24小时皮质醇分泌研究。每10分钟测量一次皮质醇水平。主要结果测量：应用多参数自动去卷积和余弦回归来量化基础、脉动和总皮质醇分泌率以及皮质醇水平的昼夜变化。HD患者的皮质醇总分泌率和昼夜皮质醇曲线的振幅均显著高于对照组（分别为3490 +/- 320 vs. 2500 +/- 220 nmol/L/24 h，P = 0.023; 111 +/- 14 vs. 64 +/- 8 nmol/L，P = 0.012）。患者的皮质醇浓度在上午和下午早些时候特别增加。在HD患者中，平均24小时皮质醇水平显着相关的总运动评分，总功能能力，以及身体质量index.Conclusions：HPA轴活动过度是HD的早期特征，很可能是由于下丘脑病理的中枢糖皮质激素反馈紊乱。HPA轴功能障碍可能导致HD患者的某些体征和症状。（临床内分泌代谢杂志94：1223-1228，2009）
Context: Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction could contribute to a number of HD signs and symptoms; however, no data are available on cortisol diurnal variations and secretory dynamics in HD patients.Objective: The aim of the study was to perform a detailed analysis of HPA axis function in HD patients in relation to clinical signs and symptoms.Design, Setting, and Participants: Twenty-four-hour cortisol secretion was studied in eight early-stage, medication-free HD patients and eight age-, sex-, and body mass index-matched controls in a clinical research laboratory. Cortisol levels were measured every 10 min.Main Outcome Measures: Multiparameter autodeconvolution and cosinor regression were applied to quantify basal, pulsatile, and total cortisol secretion rates as well as diurnal variations in cortisol levels.Results: Total cortisol secretion rate and the amplitude of the diurnal cortisol profile were both significantly higher in HD patients compared with controls (3490 +/- 320 vs. 2500 +/- 220 nmol/liter/24 h, P = 0.023; and 111 +/- 14 vs. 64 +/- 8 nmol/liter, P = 0.012, respectively). Cortisol concentrations in patients were particularly increased in the morning and early afternoon period. In HD patients, mean 24-h cortisol levels significantly correlated with total motor score, total functional capacity, as well as body mass index.Conclusions: HPA axis hyperactivity is an early feature of HD and is likely to result from a disturbed central glucocorticoid feedback due to hypothalamic pathology. HPA axis dysfunction may contribute to some signs and symptoms in HD patients. (J Clin Endocrinol Metab 94: 1223-1228, 2009)