Age-Related Resistance to Thyroid Hormone Action

The age-related resistance to thyroid hormones (THs) explains the paucity of symptoms and signs of hyperthyroidism in older adults and may partly explain the myriad of symptoms and signs of hypothyroidism in biochemically euthyroid older people. This review considers the available data on the mechanisms underlying TH resistance with aging and compares these physiologic changes with the changes observed in congenital TH resistance syndromes. Aging is associated with alterations in TH economy along with a host of changes in the responsiveness of various tissues to THs. The age-related resistance to THs can be attributed to decreased TH transport to tissues, decreased nuclear receptor occupancy, decreased activation of thyroxine to triiodothyronine, and alterations in TH responsive gene expression. Although an increase in serum TH levels is expected in syndromes of TH resistance, unchanged serum TH levels in the euthyroid elderly is the result of increased sensitivity to TH negative feedback with increased suppression of thyroid-stimulating hormone, decreased thyroidal sensitivity to thyroid-stimulating hormone, and decreased TH production and secretion. The current clinical evidence suggests that the age-related TH resistance is mostly an adaptive response of the aging organism. It is tempting to speculate that similar changes can occur prematurely in a group of younger people who present with signs and symptoms of hypothyroidism despite normal serum thyroid function tests.