Diminished adrenocorticotropin response to insulin-induced hypoglycemia in nondepressed, actively drinking male alcoholics.

Although changes in hypothalamic-pituitary-adrenal axis function have frequently been reported in alcoholics, the majority of studies have used recently detoxified subjects in whom abstinence phenomena and clinical depression may contribute to observed stress axis alterations. To isolate the primary effects of alcohol dependence on the stress axis, the ACTH and cortisol responses to insulin-induced hypoglycemia were measured in seven actively drinking male alcoholics recruited from the general public through a newspaper advertisement along with eight age-matched male controls. The alcoholic subjects met current American Psychiatric Association diagnostic criteria for alcohol dependence, were stably employed, and had no concurrent psychiatric disorders, cognitive impairment, or psychometric evidence of depression. While relatively young (30.0 yr; range, 22-48 yr), they had lengthy histories of alcohol-related problems (11.9 yr; range, 5-30 yr). Insulin administration resulted in similar nadirs in blood sugar in both alcoholic and control groups. However, the plasma ACTH response was markedly blunted in the alcoholics (P = 0.040, by Mann-Whitney U test). There was a nonsignificant trend toward increased cortisol levels in the alcoholic group. The findings suggest that altered hypothalamic-pituitary-adrenal axis function in alcoholics is a primary results of chronic ethanol exposure rather than a confounding effect of clinical depression or recent detoxification.