Hypothalamo-pituitary-adrenal axis activity evolves differentially in untreated versus treated multiple sclerosis.
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
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.
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany.
Tania
T
Kümpfel
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany.
Michaela
M
Schwan
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany.
Frank
F
Weber
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany.
Florian
F
Holsboer
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany.
Claudia
C
Trenkwalder
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany. Electronic address: ThenBerF@medizin.uni-leipzig.de.
Florian
F
Then Bergh
D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003907:Dexamethasone; D003940:Diagnostic Techniques, Endocrine; D018450:Disease Progression; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D010913:Pituitary-Adrenal System / Q000502:physiology*
D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone
Hypothalamo-pituitary-adrenal axis; Multiple sclerosis; Neuroendocrinology