Chronic alcoholism is sometimes associated with pseudo-Cushing's syndrome and euthyroid sick syndrome. There are specific abnormalities in HPA and HPT axis function that characterize these syndromes. It is as yet unclear, however, whether these functional abnormalities (1) are caused by or associated with the actual abuse of alcohol or (2) are present in the alcoholic individual even during abstinence from alcohol and may, therefore, represent manifestations of some underlying dysfunction of the hypothalamus or of hypothalamic inputs in alcoholic individuals. (3) tend to coexist in the same individuals, and (4) tend to be associated with specific cognitive behavioral manifestations. We hypothesize that a significant percentage of abstinent alcoholics, like patients with primary depression, will have blunted responses to CRH and TRH, as has been indicated by the results of preliminary studies by us and by other investigators. We further postulate that the blunting is due to a chronic increase in the tonic and/or pulsatile release of CRH and TRH secondary to an alteration in the activity of the pulse generator(s) for these releasing hormones, as has been suggested for the HPA axis in primary depression. We propose to study both the basal, unstimulated diurnal pattern of release of ACTH and TSH -- and the hormonal products of their target glands - - and their responses to i.v. administration of synthetic CRH and TRH in chronic alcoholic men who have been abstinent for six weeks. We will use a computer-assisted pulse analysis program to examine the diurnal rhythm study data. This program has an enhanced ability to exclude false-positive pulses, resulting in more accurate definition of a smaller number of daily pulsatile events than had previously been assumed to exist. The responses to CRH and TRH will be analyzed on the basis of the amplitude and timing of the peak hormone concentrations and the total integrated quantities of hormones released. Because of the lack of suitable control data, we will examine both the diurnal rhythm and responses to CRH and TRH in age-, race-, and socioeconomic-matched nonalcoholic volunteer men. Finally, the alcoholic patients' cognitive behavioral profiles will be studied to determine if there are clinical psychiatric correlates of the neuroendocrinologic dysfunction.
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