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Graves’ disease

Abstract

Graves’ disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves’ hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves’ orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon.

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Fig. 1: Incidence of hyperthyroidism in pregnancy.
Fig. 2: Histopathology of Graves’ disease.
Fig. 3: Pathogenesis of Graves’ hyperthyroidism.
Fig. 4: The structure of TSHR.
Fig. 5: TSHR autoantibodies.
Fig. 6: Signalling cascade by TSHR autoantibodies.
Fig. 7: Pathogenesis of Graves’ orbitopathy.
Fig. 8: Diagnosis of Graves’ disease.
Fig. 9: Ultrasonographic examination of the thyroid.
Fig. 10: Radioiodine uptake and scan.
Fig. 11: Clinical features of Graves’ orbitopathy.
Fig. 12: Graves’ dermopathy.
Fig. 13: Management of GO.
Fig. 14: Emerging therapies for Graves’ Disease.

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Acknowledgements

T.F.D. acknowledges NIH funding for his research (grants DK069713, DK052464), the VA Merit Award program and the Segal Family Fund. A.K.E. acknowledges DFG funding for research (BE 3177/1-7, EC 3179/3, GRK 2098) and EU funding IAPP (GAN 612116) INDIGO.

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Introduction (T.F.D.); Epidemiology (S.A.); Mechanisms/pathophysiology (T.F.D., R.L. and Y.N.); Diagnosis, screening and prevention (G.B.); Management (M.B, A.K.E. and A.S.G.); Quality of life (G.J.K.); Outlook (G.J.K.); Overview of Primer (T.F.D.).

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Correspondence to Terry F. Davies.

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Nature Reviews Disease Primers thanks D. Cooper, J. Orgiazzi, J. Lazarus, M. Salvi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Davies, T.F., Andersen, S., Latif, R. et al. Graves’ disease. Nat Rev Dis Primers 6, 52 (2020). https://doi.org/10.1038/s41572-020-0184-y

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