The increasing clinical relevance of thyroid-stimulating hormone receptor autoantibodies and the concurrent evolution of assay methods in autoimmune hyperthyroidism

The thyrotropin receptor is a central stage for the thyroid function and growth and activates different signaling pathways for hormones synthesis and release by the thyrocyte. Stimulating, blocking and apoptotic autoantibodies directed against the extracellular domain of thyrotropin receptor (A subunit) are pathogenic for autoimmune hyperthyroidism or Graves’ disease (GD). As outlined in the 2016 American Thyroid Association (ATA) guidelines, the measurement of thyrotropin receptor antibodies is now considered the first test for the management of hyperthyroidism. In the last 50 years different assay methods have been used to detect and measure these autoantibodies [bioassays and immunoassays (IMA)]. In this article a diagnostic model is proposed, taking account of the most recent refinements of laboratory assay methods: the IMA is considered the best solution to diagnose and monitor the overt cases of GD, while the bioassays are reserved for fine and complex diagnoses, in the cases of switch between stimulating and blocking antibodies in the same patients.