Aziz N Ahmad, Pijl Hanno, Frölich Marijke, van der Graaf A W Maurits, Roelfsema Ferdinand, Roos Raymund A C
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
J Clin Endocrinol Metab. 2009 Apr;94(4):1223-8. doi: 10.1210/jc.2008-2543. Epub 2009 Jan 27.
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.
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.
Multiparameter autodeconvolution and cosinor regression were applied to quantify basal, pulsatile, and total cortisol secretion rates as well as diurnal variations in cortisol levels.
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.
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.
亨廷顿舞蹈症（HD）是一种致命的遗传性神经退行性疾病，其特征为运动、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多种HD体征和症状；然而，目前尚无关于HD患者皮质醇昼夜变化和分泌动态的数据。
本研究旨在详细分析HD患者的HPA轴功能及其与临床体征和症状的关系。
设计、地点和参与者：在临床研究实验室中，对8名早期、未服用药物的HD患者以及8名年龄、性别和体重指数相匹配的对照者进行了24小时皮质醇分泌研究。每10分钟测量一次皮质醇水平。
应用多参数自去卷积和余弦波回归分析来量化基础、脉冲式和总皮质醇分泌率以及皮质醇水平的昼夜变化。
与对照组相比，HD患者的总皮质醇分泌率和皮质醇昼夜曲线的幅度均显著更高（分别为3490±320 vs. 2500±220 nmol/升/24小时，P = 0.023；以及111±14 vs. 64±8 nmol/升，P = 0.012）。患者的皮质醇浓度在上午和下午早期尤其升高。在HD患者中，平均24小时皮质醇水平与总运动评分、总功能能力以及体重指数显著相关。
HPA轴功能亢进是HD的早期特征，可能是由于下丘脑病变导致中枢糖皮质激素反馈紊乱所致。HPA轴功能障碍可能导致HD患者出现一些体征和症状。
