This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aziz, N. A. Articles by Roos, R. A. C. Search for Related Content PubMed PubMed Citation Articles by Aziz, N. A. Articles by Roos, R. A. C. Related Collections Neuroendocrinology and Pituitary

Increased Hypothalamic-Pituitary-Adrenal Axis Activity in Huntington’s Disease

Departments of Neurology (N.A.A., A.W.M.v.d.G., R.A.C.R.), Endocrinology and Metabolic Diseases (H.P., F.R.), and Clinical Chemistry (M.F.), Leiden University Medical Center, 2300 RC Leiden, the Netherlands

Address all correspondence and requests for reprints to: N. A. Aziz, M.Sc., Leiden University Medical Center, Department of Neurology, K-05-Q 110, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands. E-mail: N.A.Aziz{at}lumc.nl.

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.