Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS

Objective: To investigate whether dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis is related to clinical characteristics in MS. Methods: The authors performed the combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators. Results: The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05) indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing-remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2 +/- 38.9 arbitrary units [AU], mean +/- SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8 +/- 60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 610.6 +/- 148.6 AU). Differences were significant between the three patient groups (p < 0.005); and between control subjects (n = 29; AUC-Cort, 150.8 +/- 34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke's Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied. Conclusion: HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.