Assessment of thyroid status by laboratory methods: developments and perspectives

Abstract

Serum protein-bound iodine and in vivo radioiodine tests were employed for over three decades although their usefulness was hampered by interference from iodinated compounds. Tests reflecting thyroid hormone action were therefore used for additional information on thyroid status. Competitive saturation analysis of serum T4 was introduced in the 60s. RIAs for T4 and T3 were not developed until ten years later because of problems in raising polyclonal antibodies to small haptens. Methods for FT4 and FT3 based on equilibrium dialysis of serum labelled with radioiodinated hormone emerged in the 60s, and in the 70s sensitive RIAs enabled direct determination of free hormone concentrations in serum dialysate. Dialysis and ultrafiltration methods are tedious and therefore various free hormone indices, based on total hormone concentrations and tests for unoccupied thyroid hormone-binding sites, have been used right up to our times. In the 80s rapid assays for FT4 and FT3 based on varying principles were developed particularly by commercial companies. Free hormone assays utilizing thyroid hormone analogs as tracers have been criticized because binding of analogs to serum proteins results in spurious values in conditions characterized by thyroid hormone-binding protein abnormalities. Bioassay of TSH was not adopted by the clinical service laboratory because of insufficient analytical sensitivity. The first immunological TSH assay, based on cross-reaction of human and bovine TSH in a hemagglutination inhibition test, was also too insensitive for practical purposes. RIAs for direct determination of normal TSH concentrations were developed in the 60s. The breakthrough in measurement of low TSH concentrations occurred in the 80s with the advent of immunometric assays utilizing monoclonal antibodies. Recently chemiluminescence, fluorescence and enzyme labels have been used for the development of non-isotopic methods for thyroid hormones and TSH. Immunoassay systems for bed-side measurement of analyte concentrations are being developed and immunosensors for continuous monitoring of analyte levels will probably be available in the future.