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

Objective: To evaluate factors influencing the TSH reference range.

Design: Non-pregnant subjects aged 12 yr and older from NHANES III were used to study the relationships between TSH, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) in different ethnic groups.

Results: TPOAb prevalence was lowest (< 3%) when TSH was between 0.1 and 1.5 mIU/L in women and between 0.1 and 2.0 mIU/L in men and progressively increased to above 50% when TSH exceeded 20 mIU/L. TSH reference range parameters (2.5, 50 and 97.5 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 thyroxine (TT4) was within the reference range. For each age group of each ethnicity the inclusion of antibody-positive subjects increased TSH medians and upper limits (97.5 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.