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

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 HPA axis activation. HPA system regulation remains more stable in MS patients on DMT.

journal_name

Psychoneuroendocrinology

journal_title

Psychoneuroendocrinology

authors

Kümpfel T,Schwan M,Weber F,Holsboer F,Trenkwalder C,Then Bergh F

doi

10.1016/j.psyneuen.2014.03.012

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

87-95

eissn

0306-4530

issn

1873-3360

pii

S0306-4530(14)00108-5

journal_volume

pub_type

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