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TSH receptor autoantibody immunoassay in patients with Graves' disease: Improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis
Abstract
Background TSH receptor antibodies (TRAb) are the diagnostic hallmark of Graves' disease (GD) and immunoassays for their detection have been available for more than 30 years over three generations of laboratory methods. Despite a growing body of data produced by clinical and laboratory research which demonstrates its elevated sensitivity and specificity, TRAb testing is poorly used for diagnosing GD. The aim of our systematic review and meta-analysis is to verify the diagnostic performance of TRAb detected with 2nd and 3rd generation immunoassay methods.Methods We searched for English articles using MEDLINE with the search terms "TSH receptor antibody assay", "TSH Receptor antibody tests" and "Graves' disease". We analyzed studies reporting on TSH receptor antibody tests performed by quantitative immunoassays, on untreated patients with GD as the index disease (sensitivity) and on a control group of either healthy subjects or patients affected by other thyroid diseases (specificity). A total of 681 titles were initially identified with the search strategy described. 560 publications were excluded based on abstract and title. Full-text review was undertaken as the next step on 111 publications providing data on TRAb testing; 58 articles were subsequently excluded because they did not include untreated GD patients, or used either bioassays or 1st generation immunoassays. 32 were also excluded because they included data only on sensitivity or only on specificity of the assay, or were duplicates. Finally, 21 articles were selected for meta-analysis. Extraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with GD and the number of healthy or diseased controls; specification of the analytical method used to detect TRAb; sensitivity and specificity of the assay.Results The meta-analysis showed that the overall pooled sensitivity and specificity of the 2nd and 3rd generation TRAb assays are 97.1% and 97.4%, and 98.3% and 99.2%, respectively, with little difference between the types of immunoassay methods employed (human or porcine receptor, manual or automated procedure). The likelihood of a TRAb-positive individual to have GD is 1367- to 3420-fold greater (depending upon the type of assay) compared to a TRAb-negative person.Conclusions Data from the meta-analysis showed that TRAb measured with 2nd and 3rd generation immunoassay methods have very high sensitivity and specificity in the diagnosis of GD. The difference between 2nd and 3rd generation methods is small and is equally useful. In contrast with recommendations made by clinical endocrinologists who are not familiar with the state of the art in diagnostic technologies of autoimmunology laboratories, we propose a wide application of these tests in clinical practice to screen all hyperthyroid patients.
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“In the setting of overt thyrotoxicosis, newer TRAb binding and bioassays have a sensitivity of 96-97% and a specificity of 99% for GD (56,57).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [57]
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“In the setting of overt thyrotoxicosis, newer TRAb binding and bioassays have a sensitivity of 96–97% and a specificity of 99% for GD (56,57).”
BackgroundSmith, T. J., & Hegedűs, L. D. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1510030 · Cited by 1,338
2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism
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Metadata
- Authors
- Tozzoli, R., Bagnasco, M., Giavarina, D., & Bizzaro, N.
- Affiliations
- Azienda Ospedaliera Santa Maria Degli Angeli (IT)
- University of Genoa (IT)
- Ospedale San Bortolo (IT)
- Venue
- Autoimmunity Reviews
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 12
- Issue
- 2
- Pages
- 107-113
- ISSN
- 1568-9972 (ISSN-L)
- OpenAlex
- W1967526742
- Cited by
- 195
- References
- 56
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 12 · 2022: 22 · 2021: 27 · 2020: 20 · 2019: 11 · 2018: 19 · 2017: 7 · 2016: 19 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 1
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autoimmunity Reviews (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Clinical Neurology › Myasthenia Gravis and Thymoma
- Keywords
- TSH receptor antibodies, Graves' disease, diagnostic accuracy, sensitivity and specificity, automated immunoassay, diagnostic performance, thyroid autoimmunity
- MeSH terms
- Autoantibodies, Graves Disease, Humans, Immunologic Tests, Receptors, Thyrotropin, Sensitivity and Specificity, Reproducibility of Results, Odds Ratio
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