Misleading results from immunoassays of serum free thyroxine in the presence of rheumatoid factor

Abstract

A novel interference with measurements of serum free thyroxine (FT₄) caused by rheumatoid factor (RhF) is described. We found misleading, sometimes gross, increases of FT₄ results in 5 clinically euthyroid elderly female patients with high RhF concentrations. All 5 patients had high FT₄ on Abbott AxSYM^® or IMx^® analyzers. “NETRIA” immunoassays gave misleading results in 4 of the 5 patients; Amerlex-MAB^® in 2 of 4 patients; AutoDELFIA^®in 2 of the 5; and Corning ACS-180^® and Bayer Diagnostics Immuno 1^® in 1 of the 5. BM-ES700^® system results for FT₄ in these women remained within the reference range. Results for serum T₄, thyroid-stimulating hormone, free triiodothyronine, thyroid-hormone-binding globulin, and FT₄ measured by equilibrium dialysis were normal in all 5 patients. Drugs, albumin-binding variants, and anti-thyroid-hormone antibodies were excluded as interferences. Addition to normal serum of the RhF isolated from each of the 5 patients increased the apparent FT₄ (Abbott AxSYM). Screening of 83 unselected patients demonstrated a highly significant positive correlation between FT₄ (Abbott AxSYM) and RhF concentrations. Discrepant, apparently increased FT₄ with a normal result for thyroid-stimulating hormone should lead to measurement of the patient’s RhF concentration.