Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease—Methodology and Clinical Applications

Background: Thyroid stimulating hormone receptor antibodies (TSHR-Ab) cause autoimmune hyperthyroidism and are prevalent in patients with related thyroid eye disease (TED). Purpose: To provide a historical perspective on TSHR-Ab and to present evidence-based recommendations for clinical contemporary use. Methods: The authors review the recent literature pertaining to TSHR-Ab in patients with TED and describe the various immunoassays currently used for detecting TSHR-Ab and their clinical applications. Results: We provide a historical summary and description of the various methods used to detect TSHR-Ab, foremost, the functional TSHR-Ab. Increasing experimental and clinical data demonstrate the clinical usefulness of cell-based bioassays for measurements of functional TSHR-Ab in the diagnosis and management of patients with autoimmune TED and in the characterization of patients with autoimmune-induced hyperthyroidism and hypothyroidism. Thyroid stimulating hormone receptor antibodies, especially the functional stimulating antibodies, are sensitive, specific, and reproducible biomarkers for patients with autoimmune TED and correlate well with clinical disease activity and clinical severity. Unlike competitive-binding assays, bioassays have the advantage of indicating not only the presence of antibodies but also their functional activity and potency. Conclusions: Measurement of TSHR-Ab (especially stimulating antibodies) is a clinically useful tool for the management of patients with TED. Accepted for publication November 18, 2017. Tanja Diana has received speaker fees from Quidel, George J. Kahaly consults for and has received research grants and speaker fees from Quidel, U.S.A. Address correspondence and reprint requests to George J. Kahaly, M.D., Ph.D., Department of Medicine, Molecular Thyroid Research Laboratory, JGU Medical Center, Langenbeckstreet 1, Mainz 55131, Germany. E-mail: Kahaly@ukmainz.de. © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.