HETEROGENEITY OF HYPOTHALAMIC-PITUITARY-ADRENAL SYSTEM RESPONSE TO A COMBINED DEXAMETHASONE-CRH TEST IN MULTIPLE-SCLEROSIS

The endocrine system participates in the regulation of the immune and neural systems and therefore hormonal factors probably play an importa nt role in the development and course of multiple sclerosis (MS). Spec ifically, the hypothalamic-pituitary-adrenal (HPA) system seems crucia l because (a) the inflammatory response is accompanied by HPA activati on; (b) animal models with an inherited HPA defect are prone to develo ping experimental autoimmune encephalitis: and (c) most important, cor ticosteroids are still the most widely used treatment. We administered a recently developed neuroendocrine function test that combines dexam ethasone suppression (1.5 mg orally at 2300 h) and corticotropin-relea sing hormone (CRH) stimulation (100 mu g i.v. at 1500 h the following day) and measured the response of plasma cortisol and corticotrophin ( ACTH) secretion in 19 patients with an acute exacerbation of MS. These patients had a significantly higher mean plasma cortisol response tha n age-matched controls (peak minus baseline; 48.1 +/- 10.5 ng/ml [mean +/- SEM] versus 19.8 +/- 4.2 ng/ml; p < 0.05), but the corresponding ACTH values for the two groups were indistinguishable (13.4 +/- 1.4 pg /ml [mean +/- SEM] versus 11.3 +/- 1.4 pg/ml; n.s.). The response rang e in the patients was broader and we identified six patients with exce ssive cortisol release (peak minus baseline: 100.5 +/- 14.4 ng/ml [mea n +/- SEM]), whereas four patients failed to respond at all. The hormo nal response patterns were not related to previous treatments with cor ticosteroids or other immunosuppressants or to psychopathological feat ures. These results point to a heterogeneity of HPA system function, m ost likely at the corticosteroid receptor level, which has clinical im plications for all those treatments that affect the HPA system and the course of MS.