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Abstract

Background: Heterogeneous hypothalamo-pituitary-adrenal (HPA) system dysregulation has been shown in multiple sclerosis (MS), and cross-sectional studies suggested increasing hyperactivity with longer, progressing disease. Longitudinal studies to confirm this hypothesis and to study the impact of disease modifying treatment (DMT) have not been performed. Objective/method: In order to determine the longitudinal evolution of HPA system activity in patients with MS, we performed an open follow-up evaluation of sixty patients with definite MS. Patients were untreated at baseline; at follow-up, 40 received DMT. From the combined dexamethasone/CRH test, performed at baseline and follow-up, we derived neuroendocrine indicators (maximum, maximum rise, mean location and area under the curve) for cortisol, ACTH and ACTH/cortisol ratio. Results: In 20 patients who remained untreated (test-retest interval 28.8 +/- 5.4 months), ACTH/ cortisol ratios decreased significantly, driven by both mild increase in cortisol and reduction of ACTH secretion. In 40 patients with DMT (test-retest interval 15.5 +/- 2.5 months), secretion of cortisol, ACTH and ACTH/cortisol ratios did not change significantly. There was significant, moderate correlation between baseline and follow-up tests for cortisol, but not for ACTH indicators. In untreated, but not in treated patients, change in ACTH/cortisol ratios showed moderate inverse correlation to the time interval between tests (Pearson: beta -0.52 to -0.56, p < 0.05); the relation to progression of neurological disability was not significant. Conclusions: HPA axis activation in untreated MS drifts from hypothalamo-pituitary to more adrenal activation, consistent with adrenal sensitization or hypertrophy due to chronic 1-IPA axis activation. HPA system regulation remains more stable in MS patients on DMT. (C) 2014 Elsevier Ltd. All rights reserved.