Age and the thyrotropin response to hypothyroxinemia

J Clin Endocrinol Metab. 2010 Aug;95(8):3675-83. doi: 10.1210/jc.2010-0281. Epub 2010 May 19.


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 T4 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-T4 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 T4 (FT4) concentrations (<35 yr, 69 mIU/liter; 35-49 yr, 49 mIU/liter; 50-64 yr, 43 mIU/liter; >64 yr, 29 mIU/liter). With iatrogenic hypothyroidism, the mean TSH concentration decreased significantly in each ascending age group (<35 yr, 156 mIU/liter; 35-49 yr, 115 mIU/liter; 50-64 yr, 74 mIU/liter; >64 yr, 46 mIU/liter; P<0.001) despite similar FT4 concentrations. The relationship between the log-transformed TSH and FT4 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 T4 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging / blood*
  • Analysis of Variance
  • Female
  • Humans
  • Hypothyroidism / blood*
  • Male
  • Middle Aged
  • Thyroid Function Tests
  • Thyroid Neoplasms / blood
  • Thyrotropin / blood*
  • Thyroxine / blood*


  • Thyrotropin
  • Thyroxine