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National Health and Nutrition Examination Survey III Thyroid-Stimulating Hormone (TSH)-Thyroperoxidase Antibody Relationships Demonstrate That TSH Upper Reference Limits May Be Skewed by Occult Thyroid Dysfunction

Department of Medicine (C.A.S., M.K.), Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California 90032; Department of Pediatrics (J.G.H.), University of Kansas Medical Center, Kansas City, Kansas 66160; and Section of Endocrinology, Diabetes, and Nutrition (L.E.B.), Department of Medicine, Boston University, Boston, Massachusetts 02118

Address all correspondence and requests for reprints to: Carole A. Spencer, University of Southern California, Edmondson Building, Room 111, 1840 North Soto Street, Los Angeles, California 90032. E-mail: cspencer{at}usc.edu.

Context: The setting of the TSH upper reference limit impacts the diagnosis of mild hypothyroidism and is currently controversial.

Objective: Our objective was to evaluate factors influencing the TSH reference range.

Design: Nonpregnant subjects aged 12 yr and older from National Health and Nutrition Examination Survey III were used to study the relationships between TSH, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies in different ethnic groups.

Results: TPOAb prevalence was lowest (<3%) when TSH was between 0.1 and 1.5 mIU/liter in women and between 0.1 and 2.0 mIU/liter in men and progressively increased to above 50% when TSH exceeded 20 mIU/liter. TSH reference range parameters (2.5th, 50th, and 97.5th percentiles) were analyzed according to thyroid antibody status, race/ethnicity, and age for the 14,202 subjects made up of non-Hispanic Blacks (B), non-Hispanic whites (W), and Mexican-Americans (M) who did not report thyroid disease or taking thyroid-altering medications and whose total T₄ was within the reference range. For each age group of each ethnicity, the inclusion of antibody-positive subjects increased TSH medians and upper limits (97.5th percentiles). The TSH upper limit was lower for the entire B cohort vs. W or M. However, this difference was lost when age cohorts with a similar prevalence of TPOAb (B age 40–49 yr vs. W and M age 20–29 yr) were compared.

Conclusions: Ethnic differences in TSH were not present when populations with the same relative frequency of thyroid antibodies were compared. TSH upper reference limits may be skewed by TPOAb-negative individuals with occult autoimmune thyroid dysfunction.

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