Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism

J Clin Endocrinol Metab. 2007 Dec;92(12):4575-82. doi: 10.1210/jc.2007-1499. Epub 2007 Oct 2.


Context: Measurements from all age groups defined the upper limit of the TSH reference range in National Health and Nutrition Examination Survey III. The TSH median, 97.5 centile and prevalence of subclinical hypothyroidism (SCH), normal serum T(4) and TSH greater than 4.5 mIU/liter, increased progressively with age. Age-adjusted reference ranges would include many people with TSH greater than 4.5 mIU/liter.

Objective: We determined whether increasing 50 and 97.5 centiles with age resulted from more patients with SCH in populations with normal TSH distribution or whether age-specific population shifts to higher serum TSH might account for these findings.

Design/setting/patients: We analyzed TSH, antithyroid antibodies, and TSH frequency distribution curves for specific age deciles in populations without thyroid disease, with or without antithyroid antibodies.

Results: Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter, increasing to 40% in the 80+ group, 14.5% of whom had TSH greater than 4.5 mIU/liter. When TSH was greater than 4.5 mIU/liter, the percentage with antibodies was 67.4% (age 40-49 yr) and progressively decreased to 40.5% in the 80+ group. TSH frequency distribution curves of the 80+ group with or without antibodies was displaced to higher TSH, including TSH at peak frequency. The 97.5 centiles for the 20-29 and 80+ groups were 3.56 and 7.49 mIU/liter, respectively. Seventy percent of older patients with TSH greater than 4.5 mIU/liter were within their age-specific reference range.

Conclusion: TSH distribution progressively shifts toward higher concentrations with age. The prevalence of SCH may be significantly overestimated unless an age-specific range for TSH is used.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Autoantibodies / blood*
  • Child
  • Data Interpretation, Statistical
  • Female
  • Humans
  • Hypothyroidism / blood*
  • Hypothyroidism / epidemiology*
  • Iodide Peroxidase / blood
  • Iodide Peroxidase / immunology
  • Male
  • Middle Aged
  • Reference Values
  • Thyrotropin / blood*
  • Thyroxine / blood
  • United States / epidemiology


  • Autoantibodies
  • Thyrotropin
  • Iodide Peroxidase
  • Thyroxine