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Review of Neuroendocrine Correlates of Chronic Opiate Misuse: Dysfunctions and Pathophysiological Mechanisms

Although endocrine abnormalities are recognized in opiate users, very little is known about the range of hormones affected, their pathophysiology, and their clinical relevance. The primary aim of this study was to explore the effects of heroin misuse and methadone maintenance treatment on the human endocrine system. A literature search for relevant articles (in English) and appropriate cross-referencing of the following databases-Medline (1952-2002), Embase (1974-2002), and Psychlit (1980-2002)-was done. Two authors independently reviewed over 100 articles and summarized the key findings. Various endocrine abnormalities have been reported in these patients, which include abnormal adrenal metabolism and adrenal insufficiency; abnormalities in circadian rhythm of corticosteroid secretion; increased levels of Thyroxine (T4), Tri-iodothyronine (T3), and Thyroxine Binding Globulin (TBG), and reduced T3 uptake values; increased prolactin levels; insulin and glucose metabolism abnormalities similar to those seen in type 2 diabetes; reductions in testosterone levels; and abnormalities in Follicular Stimulating Hormone/Luteinising Hormone (FSH/LH) levels. Pathophysiological mechanisms postulated to explain these findings include: a direct action of heroin or methadone at the hypothalamic or pituitary level, a more peripheral action at the end organ level, or indirect action via hepatic and/or renal dysfunction. We conclude that many of the hypothalamic and anterior pituitary hormones are adversely affected in heroin misusers and methadone maintained patients. Clinicians need to be aware of these hormonal dysfunctions, their clinical presentations (or as side effects leading to treatment non-compliance), and management. Further research is needed to explore the prevalence, pathophysiology. and clinical implications of these neuroendocrine dysfunctions.