Hypothalamo-pituitary-adrenal axis activity evolves differentially in untreated versus treated multiple sclerosis

SummaryBackgroundHeterogeneous 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/methodIn 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.ResultsIn 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.ConclusionsHPA axis activation in untreated MS drifts from hypothalamo-pituitary to more adrenal activation, consistent with adrenal sensitization or hypertrophy due to chronic HPA axis activation. HPA system regulation remains more stable in MS patients on DMT.