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  • Review Article
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Techniques to quantify TSH receptor antibodies

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 461–468 (2008)Cite this article

Abstract

The presence of antibodies to TSH receptor (TSHR) is the hallmark of Graves disease (GD). These antibodies mimic the action of TSH, resulting in TSHR stimulation and hyperthyroidism, and have been associated with GD-associated extrathyroidal manifestations. TSH binding inhibition assays and bioassays for measurement of TSHR antibody levels have been used for clinical and research purposes. In the former, inhibition of TSH binding to purified or recombinant TSHR by a patient's immunoglobulins is measured by radioactive or chemiluminescent techniques. In the latter, cyclic AMP production is measured by use of radioimmunoassays or chemiluminescent methods in cells natively or artificially expressing TSHR. In this Review, the different techniques used for the detection of antibodies to TSHR are discussed, together with the clinical applications of antibody measurement, including diagnosis of GD and Graves ophthalmopathy. Prediction of relapse after medical treatment and the clinical course of Graves ophthalmopathy are also addressed.

Key Points

  • Antibodies to TSH receptor (TSHR) have key roles in the pathogenesis of Graves disease and have been associated with its extrathyroidal complications

  • TSHR antibodies might have thyroid-stimulating properties, resulting in hyperthyroidism, or blocking activity, causing hypothyroidism

  • TSH binding inhibiting immunoglobulin assays detect the broad range of TSHR antibodies but cannot differentiate between those with stimulating and blocking activity; bioassays can make this differentiation

  • TSH binding inhibiting immunoglobulin assays are commercially available and, unlike bioassays, are easy to perform; second-generation assays have high sensitivity and specificity for diagnostic purposes

  • The main clinical uses for measurement of antibodies to TSHR is diagnosis of atypical cases of Graves disease, prediction of neonatal thyroid dysfunction in pregnant women with this condition and identification of Graves ophthalmopathy in euthyroid individuals

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Figure 1: The principle behind TBII assays.
Figure 2: The principle behind bioassays for the detection of thyroid-stimulating and thyroid-blocking antibodies.
Figure 3: Clinical applications of the measurement of antibodies to the TSHR.

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Acknowledgements

RA Ajjan is funded by a Department of Health Clinician Scientist Award-UK.

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Authors and Affiliations

  1. Division of Diabetes and Cardiovascular Research, RA Ajjan is a Senior Lecturer/Honorary Consultant in Diabetes and Endocrinology, LIGHT Laboratories, University of Leeds, and AP Weetman is Dean of the School of Medicine and Biomedical Sciences at the University of Sheffield, UK.,

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Correspondence to RA Ajjan.

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Ajjan, R., Weetman, A. Techniques to quantify TSH receptor antibodies. Nat Rev Endocrinol 4, 461–468 (2008). https://doi.org/10.1038/ncpendmet0886

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