Age and the Thyrotropin Response to Hypothyroxinemia

摘要

Context: Some studies suggest altered pituitary functioning and TSH production with aging.Objective: Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age.Design: We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T_(4) concentrations.Participants: Two populations of 112 patients were subdivided into four age groups: 1) patients newly diagnosed with primary hypothyroidism and 2) thyroid cancer patients undergoing l-T_(4) withdrawal in preparation for diagnostic or therapeutic radioiodine.Main Outcome Measure: The relationship between paired free T_(4) and TSH concentrations and patient age was studied.Results: With spontaneous hypothyroidism, the mean TSH concentration decreased nonsignificantly in each ascending age group with comparable free T_(4) (FT_(4)) concentrations ( 64 yr, 29 mIU/liter). With iatrogenic hypothyroidism, the mean TSH concentration decreased significantly in each ascending age group ( 64 yr, 46 mIU/liter; P < 0.001) despite similar FT_(4) concentrations. The relationship between the log-transformed TSH and FT_(4) was significantly and inversely affected by age in multivariate analyses in both spontaneous hypothyroidism ( P = 0.0005) and in iatrogenic hypothyroidism ( P < 0.0001).Conclusions: Age modifies the pituitary set point or response to comparably reduced free T_(4) concentrations, resulting in lesser serum TSH elevation in older individuals. This phenomenon occurs with both spontaneous and iatrogenic hypothyroidism. This may be an adaptive response in normal aging or a pathological alteration of pituitary function with age.