Thyrotropin-axis adaptation in aging and chronic disease

Existing data suggest that healthy elderly humans experience a decline in thyroid function similar (but smaller in magnitude) to that observed in what may otherwise be termed central hypothyroidism-reduced TSH, reduced TSH response to TRH stimulation, decreased free T3, and decreased T4 secretion by the thyroid, but little or no change in circulating T4 levels. The changes in T3 levels are also mediated by decreased peripheral conversion from T4 because of decreased activity of peripheral 5′DI. This phenomenon also contributes to the preservation of circulating T4 levels (Box 1) [121-123]. The incidence of subclinical and clinical hypothyroidism increases with age. The frequency of hyperthyroidism appears unchanged, although toxic multinodular disease is a more common cause of thyrotoxicosis than in younger individuals and, in regions of iodine, deficiency may represent the most common etiology. Serum TSH is the most important screening test Box 1. Changes in HPT axis with aging TSH No change to slight decrease in basal level (centenarians) [28,32-35,67,121,122] Decreased response to TRH stimulation [33,40-47] Decreased amplitude to absent (centenarians) circadian variation [33,38,41,42] Thyroxine Normal serum level [28,32-35,122] Decreased secretion [2,123] Decreased degradation [2,123] T3 Slight decrease in serum level [28,32-35,122] Decreased production [2,49,73] Decreased (peripheral) and increased (thyroid?) T4/T3 conversion (5′DI activity) [34,35,122] Increased RT3 [4,31,34,35,49] Thyroglobulin Increased (within normal limits) [31] Antithyroid Antibodies Increased chronic disease/number of hospitalized patients [35,82,85] Normal healthy elderly [28,34,35,82] in elderly persons to detect thyroid dysfunction. Because low TSH is much more common in elderly individuals, obtaining a full thyroid panel (ie, free T4 and free or total T3) before diagnosing hyperthyroidism is necessary. Changes in HPT axis function with age were observed in healthy well-functioning elderly persons, so it is difficult to describe them as pathologic. Rather, we believe that they are better regarded as the result of a new balance between the metabolic requirement for thyroid hormone and the mechanisms regulating hormone production [28,84]. Further evaluation of these phenomena is needed to answer this question more carefully.