Abstract

Objective. Antibodies (Abs) to the thyroid stimulating hormone receptor (TSHR) play an important role in the pathogenesis of autoimmune thyroid disease (AITD). We define the complex terminology that has arisen to describe TSHR-Abs, and discuss significant advances that have been made in the development of clinically useful TSHR-Abs assays. Methods. Literature review and discussion. Results. TSHR-Abs may mimic or block the action of TSH or be functionally neutral. Stimulating TSHR-Abs are specific biomarkers for Graves’ disease and responsible for many of its clinical manifestations. TSHR-Abs may also be found in patients with Hashimoto thyroiditis in whom they may contribute to the hypothyroidism. Measurement of TSHR-Abs in general, and functional Abs in particular is recommended for the rapid diagnosis of Graves’ disease, differential diagnosis and management of patients with AITD, especially during pregnancy, and in AITD patients with extrathyroidal manifestations such as orbitopathy. Measurement of TSHR-Abs can be done with either immunoassays that detect specific binding of Abs to the TSHR or cell-based bioassays, which also provide information on their functional activity and potency. Application of molecular cloning techniques has led to significant advances in methodology that have enabled the development of clinically useful bioassays. When ordering TSHR-Abs, clinicians should be aware of the different tests available and how to interpret results based on which assay is performed. The availability of an international standard and continued improvement in bioassays will help promote their routine performance by clinical laboratories and provide the most clinically useful TSHR-Abs results. Conclusion. Measurement of TSHR-Abs in general, and functional (especially stimulating) Abs in particular is recommended for the rapid diagnosis, differential diagnosis, and management of patients with Graves hyperthyroidism, related thyroid eye disease, during pregnancy, as well as in Hashimoto thyroiditis patients with extrathyroidal manifestations and/or thyroid-binding inhibiting immunoglobulin positivity.

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