Age- and Race-Based Serum Thyrotropin Reference Limits

Context: TSH reference limits, particularly the upper limit, are controversial. The traditional and prevailing method for setting limits uses TSH distribution of thyroid disease-free individuals. The curve is not Gaussian, but skewed to higher concentrations, even after log-transformation; values in the skewed area are assumed to reflect mild hypothyroidism. The underlying assumption for this traditional approach, which has not previously been tested, is that the limits derived from this curve are applicable to all people. However, recent studies suggest that distinct subpopulations have unique TSH distribution and reference limits that are significantly different from limits established by the traditional approach. Evidence Acquisition: A search was focused on articles that provide the basis for current recommendations for setting TSH reference limits as well as articles that suggest that the traditional method does not reflect accurately the TSH distribution and reference limits of distinct subpopulations within the United States. Evidence Synthesis: TSH distribution and reference limits shift to higher concentrations with age, even up to centenarians, and are unique for different racial/ethnic groups, being at higher concentrations in Caucasians than either Blacks or Hispanics originating from Puerto Rico or the Dominican Republic. The distribution curve derived by the traditional approach represents a composite of curves from specific subpopulations that do not provide appropriate reference limits for those unique groups. Conclusions: Age- and race-specific TSH distribution and reference limits, possibly influenced by genetic factors, should be employed to provide clinicians accurate limits for specific populations and guidance for further evaluation of thyroid dysfunction. (J Clin Endocrinol Metab 95: 496-502, 2010)