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Diagnosis and management of Graves disease: a global overview

Key Points

  • Diagnosis of Graves disease is now usually based on anti-TSH-receptor antibody assays and thyroid ultrasonography

  • Options for management of Graves disease include antithyroid drugs, 131I-radiotherapy and thyroidectomy; however, drug-treated patients have a high relapse rate, and ablative therapies induce lifelong hypothyroidism

  • In Europe and Japan, antithyroid drugs remain the preferred first-line therapy for Graves disease, whereas in North America 131I-radiotherapy is the preferred option, despite increasing use of antithyroid drugs

  • Thyroidectomy is rarely used as a first-line treatment for Graves disease in any geographical region

  • Methimazole or carbimazole are the preferred thionamide antithyroid drugs; use of propylthiouracil is restricted to patients who cannot tolerate other thionamides and to women in the first trimester of pregnancy

Abstract

Graves disease is an autoimmune disorder characterized by goitre, hyperthyroidism and, in 25% of patients, Graves ophthalmopathy. The hyperthyroidism is caused by thyroid hypertrophy and stimulation of function, resulting from interaction of anti-TSH-receptor antibodies (TRAb) with the TSH receptor on thyroid follicular cells. Measurements of serum levels of TRAb and thyroid ultrasonography represent the most important diagnostic tests for Graves disease. Management of the condition currently relies on antithyroid drugs, which mainly inhibit thyroid hormone synthesis, or ablative treatments (131I-radiotherapy or thyroidectomy) that remove or decrease thyroid tissue. None of these treatments targets the disease process, and patients with treated Graves disease consequently experience either a high rate of recurrence, if receiving antithyroid drugs, or lifelong hypothyroidism, after ablative therapy. Geographical differences in the use of these therapies exist, partially owing to the availability of skilled thyroid surgeons and suitable nuclear medicine units. Novel agents that might act on the disease process are currently under evaluation in preclinical or clinical studies, but evidence of their efficacy and safety is lacking.

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Figure 1: The use of diagnostic tests for Graves disease in North America, Europe, and Asia and Oceania.
Figure 2: Changes over time in the use of antithyroid drugs and 131I-radiotherapy as first-line treatments for Graves disease in North America, Europe, and Asia and Oceania.

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Acknowledgements

This paper is dedicated to Prof. Aldo Pinchera (1934–2012), the author's mentor and an outstanding scientist in the field of endocrinology. The author also thanks Prof. Stefano Mariotti, University of Cagliari, Italy, for critically reviewing the manuscript. L. Bartalena's research is partly supported by grants from the Ministero della Istruzione, Università e Ricerca (MIUR) Rome, and the University of Insubria at Varese.

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Correspondence to Luigi Bartalena.

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Bartalena, L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol 9, 724–734 (2013). https://doi.org/10.1038/nrendo.2013.193

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