The combined dexamethasone-suppression/CRH-stimulation test in alcoholics during and after acute withdrawal

Background: Chronic alcoholism is often accompanied by disturbances of the hypothalamic-pituitary-adrenal (PIPA) system. Patients with alcoholism frequently show nonsuppression in the dexamethasone (Dex) suppression test and also a blunted increase of adrenocorticotropin (ACTH) after injection of corticotropin-releasing hormone (hCRH). However, the underlying mechanisms have not been fully elucidated. The combined Dex/CRH test (pretreatment with 1.5 mg dexamethasone at 2300 hr, injection of 100 mug hCRH at 1500 hr the next day) has been established as a more sensitive tool to investigate HPA system regulation in depressed patients. Methods: We studied the effect of the combined Dex/CRH test in 19 alcoholic inpatients (9 male, 10 female) during and after withdrawal along with 19 healthy controls. Results: Compared to normal controls, patients showed a severely dysregulated HPA system during withdrawal, with significantly elevated cortisol and ACTH response to hCRH after pretreatment with dexamethasone. After completed withdrawal, cortisol levels after injection of hCRH were almost normalized while ACTH values were partially lower in patients, compared to controls. Conclusions: We conclude that the HPA system is severely disturbed during alcohol withdrawal, possibly reflecting an exaggerated release of hypothalamic corticotropin and vasopressin.