Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis

Background: Fatigue is a common and disabling symptom in patients with multiple sclerosis (MS). Underlying mechanisms postulated so far have involved localization of brain lesions and abnormalities of the neuroendocrine system and cytokine regulation. Objective: To investigate the relationship between fatigue and the hypothalamo-pituitary-adrenal (HPA) axis in patients with MS. Design: A prospective survey. Setting: Outpatient and inpatient study at the Max Planck Institute of Psychiatry, Munich, Germany. Patients: Thirty-one patients with clinically definite MS, a relapsing-remitting disease course, and without MS-specific treatment. Interventions: Assessment of fatigue with 3 questionnaires: the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), and the Visual Analog Scale. Assessment of HPA axis regulation with the combined dexamethasone-corticotropin releasing hormone (Dex-CRH) test. Results: The FSS score was significantly correlated with the MFIS score. Patients with fatigue had significantly elevated adrenocorticotropin (ACTH) levels in the combined Dex-CRH test. Conclusions: In contrast to results for chronic fatigue syndrome, where a hyporeactivity of the HPA axis has been shown, MS patients with fatigue exhibited a higher activity of the HPA axis than those without fatigue, as evidenced by significantly increased ACTH concentrations. Proinflammatory cytokines, known to be elevated in patients with MS, may cause both HPA axis alterations and fatigue.