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



In previous studies, the authors had shown hyperactivity of the hypothalamo-pituitary-adrenal (HPA) system in multiple sclerosis (MS) patients, which was significantly correlated to the clinical course of MS, with relapsing-remitting MS showing the mildest, and primary-progressive MS the most pronounced, changes compared to healthy controls.

In this study, the same authors wanted to determine the longitudinal evolution of HPA system activity in patients with MS. Patients recruited were untreated or naı̈ve to (immunomodulatory or immunosuppressive) disease modifying therapies (DMT) when undergoing the baseline evaluation. Neuroendocrine testing was performed on an outpatient basis. Patients were examined clinically to rule out acute illness and MS relapse, and neurological impairment was rated using the expanded disability status scale (EDSS). Complete blood count, serum chemistry, CRP, TSH and free thyroid hormones, and a urinalysis were performed.

Patients with normal results underwent the combined dexamethasone/CRH test two days later. Sixty patients who had undergone the combined dexamethasone/CRH test at least 12 months before agreed to retesting. At baseline, 53 patients had RR-MS, five had SP-MS, and two PP-MS. Hormone concentrations were determined using commercial radio-immuno assays. In order to control for potential systematic drifts in test results, archived plasma samples from eight randomly selected patients were re-analysed in parallel to the follow-up samples; these tests yielded the same plasma concentrations for cortisol and ACTH as the original determinations. In untreated patients, most indicators of cortisol release increased from baseline to follow-up; conversely, most ACTH curve indicators were lower at follow-up than at baseline. Patients who received immunomodulating or immunosuppressive DMT showed little change of either cortisol or ACTH indicators. Even though the ACTH/cortisol ratios changed slightly in the same direction as in untreated patients, these changes were small.

Our longitudinal analysis of HPA axis reactivity shows that, in untreated MS patients, stimulated cortisol secretion slightly increases over time; at the same time, this increased cortisol output is mediated by lower (rather than higher) ACTH secretion; consequently, the ACTH/cortisol ratio most prominently changes between baseline and follow-up. In contrast to the spontaneous increase, treated patients tended to have lower cortisol indices, while ACTH remained almost unchanged.

One general conclusion which can be drawn is that HPA dysregulation is a state marker rather than a trait of people suffering from MS. Hypercortisolism could desensitize the immune system for the immunoregulatory effects of endogenous corticosteroids and could thus impair the body’s ability to curtail autoimmunity. Also, elevated concentrations of glucocorticoid may contribute to neurodegeneration. By the way, correlations to future clinical evolution cannot be firmly established from the study sample.

Authors:
Kümpfel T, Schwan M
Source: Psychoneuroendocrinology. 2014 Jul;45:87-95. doi: 10.1016/j.psyneuen.2014.03.012. Epub 2014 Apr 2.
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