The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population

Our aims were: 1) to analyze the effect of the methodology used to derive clinically feasible cut-off values for thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), which exhibit highly skewed distributions; and 2) to describe the influence of thyroid antibodies on thyroid stimulating hormone (TSH) and free thyroxine (FT 4 ) reference intervals among thyroid disease-free aged subjects. The reference population consisted of 1086 individuals with a mean age of 73 years. The impacts of TPOAb and/or TgAb positivity on the reference intervals of TSH and FT 4 were evaluated by both including and excluding subjects with elevated thyroid antibodies. The exclusion of subjects with elevated thyroid antibodies had no effect on the FT 4 reference interval in either gender or on the TSH reference interval in men. Among women, the exclusion of 196 (34%) thyroid antibody-positive subjects resulted in lowering of the upper reference limit of TSH from 7.2 to 5.8 mlU/L. When the more stringent mode-method by summing mode+(mode-2.5th percentile) was used, 334 women (58%) were excluded and the upper reference limit of TSH remained essentially identical. Regardless of the statistical methodology used to derive cut-off values, the effect of antibody positivity was found to be less than expected.