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


METHODS
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.


METHODS
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.
Aziz
N Ahmad
NA
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. N.A.Aziz@lumc.nl
Pijl
Hanno
H
Frölich
Marijke
M
van der Graaf
A W Maurits
AW
Roelfsema
Ferdinand
F
Roos
Raymund A C
RA
D000328:Adult; D001519:Behavior; D049628:Body Size; D002940:Circadian Rhythm; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D010913:Pituitary-Adrenal System / Q000502:physiology*; D018911:Trinucleotide Repeats
D003404:Creatinine; D006854:Hydrocortisone