Hormones of the hypothalamic-pituitary-thyroid axis: a psychoneuroendocrine perspective

Although relationships between hormones of the hypothalamic-pituitary-thyroid (HPT) axis and behavior have been suspected for more than two centuries, there existed no framework within which they could be understood. It now appears that disturbances in the HPT-axis have more to do with affective state than with any other aspect of mentation, save possibly cognition. First, depression is the most frequently observed psychiatric symptom in patients suffering from hypothyroidism. Second, approximately 30% of euthyroid patients with major depression show a blunted, i.e., attenuated TSH response after TRH administration. Third, it is now well established that a small dose of thyroid hormone will accelerate the antidepressant effect of tricyclic antidepressants (TCA) in women, and convert TCA non-responders into responders in both sexes. Fourth, administration of TRH may induce an increased sense of well-being and relaxation in some patients and healthy volunteers. However, little is known about the pathophysiologic mechanism whereby evocative emotional factors express their effect on the HPT axis, or whereby thyroid gland alterations express their behavioral effects. Longitudinal, prospective studies of both patients with thyroid disease and patients with depression (through close collaboration between endocrinology and psychiatry) are most likely to separate cause and effect in most instances.