Increased hypothalamic-pituitary-adrenal axis activity in Huntington's disease

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 diur...

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Published in:The journal of clinical endocrinology and metabolism Vol. 94; no. 4; p. 1223
Main Authors: Aziz, N Ahmad, Pijl, Hanno, Frölich, Marijke, van der Graaf, A W Maurits, Roelfsema, Ferdinand, Roos, Raymund A C
Format: Journal Article
Language:English
Published: United States 01.04.2009
Subjects:
Adult
Behavior
Body Size
Circadian Rhythm
Creatinine - urine
Female
Humans
Huntington Disease - blood
Huntington Disease - genetics
Huntington Disease - physiopathology
Huntington Disease - psychology
Hydrocortisone - blood
Hypothalamo-Hypophyseal System - physiology
Male
Middle Aged
Motor Activity
Pituitary-Adrenal System - physiology
Trinucleotide Repeats
ISSN:1945-7197, 1945-7197
Online Access:Get more information
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Summary: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. 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.
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ISSN:1945-7197
1945-7197
DOI:10.1210/jc.2008-2543