Anupam Kotwal1, Marius Stan. 1. Department of Medicine and Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, U.S.A.
Abstract
PURPOSE: Thyroid autoimmunity affects approximately 5% of the population, and its investigation relies heavily on the use of autoantibodies. Thyroid stimulating hormone receptor (TSHR) autoantibodies (TRAb) play a central role in the evaluation of Graves disease (GD), Graves ophthalmopathy (GO) and pretibial myxedema (PTM). However, there is still controversy regarding overall TRAb assay diagnostic accuracy and their prognostic utility. METHODS: We reviewed and analyzed the literature reporting TRAb assays and their clinical utility. RESULTS: Current assays measure the overall TRAb titer in a competitive manner (TSH binding inhibiting immunoglobulin assay) or biologic activity of the stimulating TSHR autoantibodies (thyroid stimulating immunoglobulin assay). Both types of assays have improved over time with advances in sensitivity and specificity. TRAb are particularly relevant in hyperthyroidism cases where use of iodinated contrast is not an option (e.g., pregnancy or recent use of iodinated contrast) or in cases of euthyroid eye disease, suspicious for GO. Third generation TRAb assays are useful for therapy selection in GD, prognostic predictions in GO and risk prediction for fetal and neonatal thyrotoxicosis. DISCUSSION: Given the pathogenic role of TRAb, we expect that the future will bring useful evidence regarding their predictive role with respect to efficacy of therapeutic modalities for GO and PTM. We also hope to better understand the role of blocking and neutral antibodies against TSHR, and harness that ability for modulation of thyroid function or therapy of differentiated thyroid carcinoma managed with TSH suppression. CONCLUSIONS: Thyroid autoimmune diseases have seen tremendous gains in understanding their pathophysiology, largely antibody mediated. Better TRAb testing is becoming a springboard for providing individualized patient care.
PURPOSE: Thyroid autoimmunity affects approximately 5% of the population, and its investigation relies heavily on the use of autoantibodies. Thyroid stimulating hormone receptor (TSHR) autoantibodies (TRAb) play a central role in the evaluation of Graves disease (GD), Graves ophthalmopathy (GO) and pretibial myxedema (PTM). However, there is still controversy regarding overall TRAb assay diagnostic accuracy and their prognostic utility. METHODS: We reviewed and analyzed the literature reporting TRAb assays and their clinical utility. RESULTS: Current assays measure the overall TRAb titer in a competitive manner (TSH binding inhibiting immunoglobulin assay) or biologic activity of the stimulating TSHR autoantibodies (thyroid stimulating immunoglobulin assay). Both types of assays have improved over time with advances in sensitivity and specificity. TRAb are particularly relevant in hyperthyroidism cases where use of iodinated contrast is not an option (e.g., pregnancy or recent use of iodinated contrast) or in cases of euthyroid eye disease, suspicious for GO. Third generation TRAb assays are useful for therapy selection in GD, prognostic predictions in GO and risk prediction for fetal and neonatal thyrotoxicosis. DISCUSSION: Given the pathogenic role of TRAb, we expect that the future will bring useful evidence regarding their predictive role with respect to efficacy of therapeutic modalities for GO and PTM. We also hope to better understand the role of blocking and neutral antibodies against TSHR, and harness that ability for modulation of thyroid function or therapy of differentiated thyroid carcinoma managed with TSH suppression. CONCLUSIONS: Thyroid autoimmune diseases have seen tremendous gains in understanding their pathophysiology, largely antibody mediated. Better TRAb testing is becoming a springboard for providing individualized patient care.
Authors: Jelte van der Vaart; Lynn Bosmans; Stijn F Sijbesma; Kèvin Knoops; Willine J van de Wetering; Henny G Otten; Harry Begthel; Inne H M Borel Rinkes; Jeroen Korving; Eef G W M Lentjes; Carmen Lopez-Iglesias; Peter J Peters; Hanneke M van Santen; Menno R Vriens; Hans Clevers Journal: Proc Natl Acad Sci U S A Date: 2021-12-21 Impact factor: 11.205