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Thyroid-stimulating hormone receptor antibody assays: recommendation for correct interpretation of results in graves disease.

To the Editor:

In Graves disease, the clinical uses of thyrotropin receptor [thyroid-stimulating hormone receptor (TSH-R)[1]] antibody (TRAb) measurements have been reported in the Thyroid Guidelines of the American Thyroid Association (1). First, TRAb measurements are used to investigate the etiology of hyperthyroidism when the diagnosis is not clinically obvious; second, a declining TRAb concentration during long-term antithyroid drug therapy is suggestive of remission, although TRAb measurements can be misleading in 25% of such patients; third, TRAb is used in the follow-up of pregnant women with a history or recent onset of Graves disease to evaluate the risk of fetal and neonatal thyroid dysfunction (1). In the late 1990s, the second-generation TRAb assays that use recombinant human TSH-R replaced the first-generation methods, which were too insensitive in the diagnosis of Graves disease (1). However, third-generation TRAb assays, which use the monoclonal thyroid-stimulating antibody M22 labeled either with biotin in ELISAs or with ruthenium in the automated Elecsys[R]/Cobas[R], have also been developed. It is now established that these third-generation assays have no clinical advantages over second-generation methods in the diagnosis (2, 3) or in the follow-up of Graves disease patients (4). Recently, it has been reported that the automated third-generation TRAb assays should be performed on clinical chemistry platforms and should prompt appropriate revision of the current thyroid guidelines (2). The scientific community should be aware of the consequences of such a decision. We demonstrated that the second-generation and the third-generation TRAb assays exhibited a high intermethod variability, despite the use of the same reference standard for calibration to National Institute for Biological Standards and Control (NIBSC) 90/672 (3, 4). This variability may lead to misinterpretation of results (5), especially in the follow-up of pregnant women with a history or current onset of Graves disease. A new WHO International Standard has been produced by NIBSC (coded 08/204) and has been evaluated by an international collaborative study. For these reasons, on behalf of the Thyroid Research Group of the French Society of Endocrinology, we recommend the use of the human second-generation TRAb assay in the exploration of Graves disease until the recalibration of all the different TRAb assays against the new WHO International Standard is complete.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

Acknowledgments: The authors thank Chris Burns from the NIBSC for helpful discussions.


(1.) Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003;15:54-5.

(2.) Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. Autoimmun Rev 2012;12:107-13.

(3.) Massart C, Sapin R, Gibassier J, Agin A, d'Herbomez M. Inter-method variability in TSH-receptor antibody measurement: implication for the diagnosis of Graves' disease and for the follow-up of Graves' ophthalmopathy. Clin Chem 2009;55:183-6.

(4.) Massart C, Gibassier J, d'Herbomez. Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. Clin Chim Acta 2009;407:62-6.

(5.) Bulow Pedersen I, Handberg A, Knudsen N, Heickendorff L, Laurberg P. Assays for thyroid-stimulating hormone receptor antibodies employing different ligands and ligand partners may have similar sensitivity and specificity but are not interchangeable. Thyroid 2010;20:127-33.

Catherine Massart [2,3,4] *

Michele d'Herbomez [4,5,6]

[1] Nonstandard abbreviations: TSH-R, thyroid-stimulating hormone receptor; TRAb: thyroid receptor antibody; NIBSC, National Institute for Biological Standards and Control.

[2] Unite Fonctionnelle d'Hormonologie Pole de Biologie CHU de Pontchaillou, Rennes, France

[3] Centre d'Investigation Clinique, Inserm 0203 Universite de Rennes-1 Rennes, France

[4] Groupe de Biologie Specialisee Societe Francaise de Medecine Nucleaire Centre Antoine Beclere Paris, France

[5] Laboratoire de Medecine Nucleaire Centre de Biologie-Pathologie CHRU de Lille, France; 6 Faculte de Medecine Universitee Lille 2 Lille, France

* Address correspondence to this author at

Laboratoire d'Hormonologie

CHU Rennes, France

Fax 2-99-28-41-45


Previously published online at DOI: 10.1373/clinchem.2013.202747
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Title Annotation:Letters to the Editor
Author:Massart, Catherine; d'Herbomez, Michele
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:May 1, 2013
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