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Extreme Longevity Is Associated with Increased Serum Thyrotropin

Division of Endocrinology, Departments of Medicine (G.A., N.B., M.I.S., I.G.), Genetics (G.A., N.B.), and Pathology (M.I.S.), Albert Einstein College of Medicine, Bronx, New York 10461; and Department of Pediatrics (J.G.H.), University of Kansas Medical Center, Kansas City, Kansas 66160

Address all correspondence and requests for reprints to: Ilan Gabriely, 1300 Morris Park Avenue, Belfer Building, Suite 707, Bronx, New York 10461. E-mail: Gabriely{at}aecom.yu.edu.

Context: The distribution of serum TSH shifts progressively to higher concentrations with age.

Objective: The aim of the study was to determine whether the population shift in TSH distribution to higher concentrations with aging extends to people of exceptional longevity, namely centenarians, and to assess the relationship between concentrations of TSH and free T₄ (FT4).

Design/Setting/Patients: We analyzed TSH, FT4, and TSH frequency distribution curves in thyroid disease-free Ashkenazi Jews with exceptional longevity (centenarians; median age, 98 yr), in younger Ashkenazi controls (median age, 72 yr), and in a population of thyroid disease-free individuals (median age, 68 yr) from the U.S. National Health and Nutrition Examination Survey 1998–2002 (NHANES controls).

Results: Serum TSH was significantly higher in centenarians [1.97 (0.42–7.15) mIU/liter] than in Ashkenazi controls [1.55 (0.46–4.55) mIU/liter] and NHANES controls [1.61 (0.39–6.29) mIU/liter] (median, 2.5 and 97.5 centiles) (P < 0.001). The TSH frequency distribution curve of centenarians was relatively similar in shape to controls but shifted significantly to higher TSH, including TSH concentration at peak frequency. The TSH distribution curve of the NHANES control group was superimposable to and not significantly different from the Ashkenazi controls. FT4 was similar in centenarians and Ashkenazi controls, and there was a significant inverse correlation between FT4 and TSH in both groups.

Conclusions: The TSH population shifts to higher concentrations with age appear to be a continuum that extends even to people with exceptional longevity. The inverse correlation between TSH and FT4 in our populations suggests that changes in negative feedback may contribute to exceptional longevity.