Age-related thyroid hormone resistance: A friend or foe

Clinical experience shows that older people with hyperthyroidism display fewer signs or symptoms compared to younger people with hyperthyroidism. Moreover, older people with normal thyroid function tests display several clinical features of hypothyroidism. These observations suggest that there may be an age-related resistance to the actions of thyroid hormones (TH). Indeed, laboratory experiments have consistently documented an age –related blunting of response to exogenously administered TH. This resistance to TH action has been attributed to reduced cellular transport of TH, possibly reduced nuclear receptors of TH and reduced cytosolic deiodinase activity. In light of these observations, along with epidemiologic studies, the diagnosis and treatment of thyroid disease in older people differ from the current treatment guidelines of younger people with thyroid disease. It is noteworthy that the age-related resistance to TH is distinct from the congenital TH resistance syndromes where plasma TH levels are increased. This distinction is explained by the age-related changes in pituitary responsiveness to the feedback inhibition by TH and reduced thyroid gland response to thyrotropin. The current evidence suggests that the age-related resistance to TH is an adaptive process to prolong life span. At the present time, it is not known if younger people can also experience premature resistance to TH and may have symptoms of hypothyroidism in the face of normal plasma TH concentrations.