Laboratory Thyroid Tests: A Historical Perspective

This review presents a timeline showing how technical advances made over the last seven decades have impacted the development of laboratory thyroid tests. Thyroid tests have evolved from time-consuming manual procedures using isotopically labeled iodine as signals (¹³¹I and later ¹²⁵I) performed in nuclear medicine laboratories, to automated nonisotopic tests performed on multianalyte instruments in routine clinical chemistry laboratories. The development of isotopic radioimmunoassay techniques around 1960, followed by the advent of monoclonal antibody technology in the mid-1970s, led to the development of a nonisotopic immunometric assay methodology that forms the backbone of present-day thyroid testing. This review discusses the development of methods for measuring total thyroxine and triiodothyronine, direct and indirect free thyroid hormone measurements and estimates (free thyroxine and free triiodothyronine), thyrotropin (TSH), thyroid autoantibodies (thyroperoxidase, thyroglobulin [Tg] and TSH receptor autoantibodies), and Tg protein. Despite progressive improvements made in sensitivity and specificity, current thyroid tests remain limited by between-method differences in the numeric values they report, as well as nonspecific interferences with test reagents and interferences from analyte autoantibodies. Thyroid disease affects ∼10% of the U.S. population and is mostly managed on an outpatient basis, generating 60% of endocrine laboratory tests. In future, it is hoped that interferences will be eliminated, and the standardization/harmonization of tests will facilitate the establishment of universal test reference ranges.