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

Objective: To investigate whether dysregulation of the hypothalamo-pituitar y-adrenal (HPA) axis is related to clinical characteristics in MS. Methods: The authors performed the combined dexamethasone-corticotropin-releasing h ormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subject s. In addition, the short adrenocorticotropic hormone (ACTH) test was perfo rmed in 39 consecutive patients. All patients had active disease and none w ere treated with glucocorticoids, immunosuppressants, or immunomodulators. Results: The patients had an exaggerated rise in plasma cortisol concentrat ions in the Dex-CRH test (p < 0.05) indicating hyperactivity of the HPA sys tem. The degree of hyperactivity was moderate in relapsing-remitting MS pat ients (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 i n primary progressive MS patients (n = 6; AUC-Cort, 610.6 +/- 148.6 AU). Di fferences were significant between the three patient groups (p < 0.005); an d between control subjects (n = 29; AUC-Cort, 150.8 +/- 34.1 AU) and each p atient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke's Expanded Disability Status Scale), but not with the d uration of the disease, number of previous relapses, previous corticosteroi d treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied. Conclusion: HPA axis hyperacti vity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.