THYROID AND ADRENAL DYSFUNCTION IN ABSTINENT ALCOHOLIC MEN - LOCUS OFDISTURBANCE

Certain neuroendocrine abnormalities (e.g., blunted plasma adrenocorti cotropic hormone [ACTH] response to corticotropin-releasing hormone [C RH] administration and blunted serum TSH response to thyrotropin-relea sing hormone [TRH] administration) are common in alcoholic patients. I t was the objective of this study to evaluate whether they are central ly mediated: that is, whether they are secondary to increased activity of CRH and/or TRH neurons. We evaluated the nocturnal secretion (2200 hours to 1000 hours, q 15 min) of plasma ACTH, serum cortisol, and se rum TSH, and their responses to the combined administration of CRH and TRH, in 28 acutely abstinent alcoholic (age range: 32 to 57 years; me an: 42.4 years) and 19 normal men (age range: 21 to 52 years; mean: 32 .1 years). To assess the validity of administering CRH and TRH simulta neously, we gave 10 additional abstinent alcoholic men (age range: 36 to 53 years; mean: 45.8 years), in random order and at least 4 days ap art, either CRH, TRH, placebo, or CRH plus TRH. Nocturnal ACTH, cortis ol, and TSH secretion, as well as cortisol and TSH responses after CRH plus TRH administration, were similar in alcoholic and normal men. Ho wever, ACTH peak responses to CRH plus TRH were reduced in the alcohol ic men (p < 0.05). The ACTH, but not cortisol, response was greater af ter combined CRH plus TRH administration than after CRH alone (p < .00 2). The blunted ACTH response does not appear to be the result of incr eased endogenous CRH activity, because all parameters of nocturnal ACT H pulsatility were normal in the alcoholics. It rather appears to be s econdary to an intrinsic defect in the CRH responsiveness of the pitui tary corticotroph, possibly due to genetic vulnerability or to the tox ic effects of prolonged alcohol abuse.