Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism

Thyroid dysfunction is a prominent finding in alcoholism. Subclinical and clinical hypothyroidism have been associated with clinical depression and cognitive impairment and may increase the relapse risk among alcoholics. In spite of these important clinical associations, there is no consensus on thyroid dysfunction in alcoholism in the literature. In this paper, we present a review of the literature and develop a hypothesis that may explain dysfunction of the hypothalamic-pituitary-thyroid axis in alcoholism. Based on a Medline research of the years 1980-2001 we found 33 empirical studies that assessed thyroid function in alcoholism. The most consistent findings were a reduction in total thyroxine and total and free triiodothyronine concentrations during early abstinence. About one-third of all alcoholics also displayed a blunted thyroid stimulation hormone (TSH) response in the thyrotrophin-releasing hormone test (TRH-test). Blunting was observed frequently during detoxification, but was also present in some alcoholics after several weeks of abstinence. We suggest that a reduction in peripheral thyroid hormones may be caused by a direct toxic effect of alcohol on the thyroid gland, which induces a central compensatory activation of the hypothalamic-pituitary axis with an increased TRH release. The TRH release induces a downregulation of pituitary TRH receptors, which manifest as a blunted TSH response to the TRH test. We discuss further additional effects of alcohol on thyroid-hormone metabolizing deiodinases and on monoaminergic systems, which may interact directly with mood states among abstinent alcoholics.