The mood spectrum and hypothalamic-pituitary-thyroid axis

Of the endocrine axes linked to the pathophysiology of bipolar disorder, the hypothalamic-pituitary-thyroid (HPT) axis has been extensively studied. Hyperthyroidism and hypothyroidism are associated with changes in mood and cognitive function. Abnormal thyroid indices, for example, are more prevalent in patients with mood disorders than in the general population. Most depressed patients are euthyroid, though subclinical hypothyroidism can be seen in approximately 15% of depressed patients. Furthermore, serum triiodothyronine (T ₃) levels are inversely correlated with time to recurrence of depressive episodes. Although most manic patients are euthyroid, thyroid measures in the low-normal range or below-normal range appear to be relevant in the pathophysiology of bipolar disorders and may result in suboptimal mood stabilization. Low thyroid function or frank clinical hypothyroidism has been associated with rapid-cycling bipolar disorder. In contrast to the T ₃/unipolar relapse, illness morbidity in bipolar disorder has more often been correlated with thyroxine (T ₄) indices. These observations have contributed to the clinical use of thyroid hormones both in acceleration and augmentation strategies. T ₃ has been mainly utilized in acute depression, while T ₄ has been used in lithium-maintained bipolar patients or in supraphysiological dosages in acute and maintenance treatment of bipolar depression, rapid cycling, and refractory depressive disorder.