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Review
. 2020 Dec 1;41(6):873-884.
doi: 10.1210/endrev/bnaa022.

New Therapeutic Horizons for Graves' Hyperthyroidism

Laura C Lane  1   2   3 , Tim D Cheetham  1   3 , Petros Perros  2 , Simon H S Pearce  1   2
Affiliations
Review

New Therapeutic Horizons for Graves' Hyperthyroidism

Laura C Lane et al. Endocr Rev. .

Abstract

Graves' hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves' hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves' patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves' hyperthyroidism.

Keywords: Graves’ disease; hyperthyroidism; immunomodulation; immunotherapy; thyroid hormone; thyroid-stimulating hormone receptor.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Illustration of novel therapeutic approaches in the treatment of Graves’ hyperthyroidism. The therapeutics in red indicate those that are monoclonal antibodies. Abbreviations: BAFF, B-cell activating factor; BAFF-R, B cell activating factor receptor; FcRn, neonatal immunoglobulin Fc receptor; IgGs, immunoglobulins; K1-70, TSHR-blocking antibody; MHC II, major histocompatibility complex class II; RVT-1401, FcRn blocker; TCR, T cell receptor; TSHR, thyroid-stimulating hormone receptor. TSH receptor image reprinted by permission from Springer Nature: Immunologic Research. Morshed SA, Latif R, Davies TF. Delineating the autoimmune mechanisms in Graves’ disease. 2012.
See this image and copyright information in PMC

References

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    1. Morshed SA, Latif R, Davies TF. Delineating the autoimmune mechanisms in Graves’ disease. Immunol Res. 2012;54(1-3):191-203. - PMC - PubMed

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