Graves' disease.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
accepted:
19
05
2020
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
10
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32616746
doi: 10.1038/s41572-020-0184-y
pii: 10.1038/s41572-020-0184-y
doi:
Substances chimiques
Anti-Retroviral Agents
0
nef Gene Products, Human Immunodeficiency Virus
0
tat Gene Products, Human Immunodeficiency Virus
0
vpr Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : BLRD VA
ID : I01 BX000800
Pays : United States
Références
McLeod, D. S. & Cooper, D. S. The incidence and prevalence of thyroid autoimmunity. Endocrine 42, 252–265 (2012).
pubmed: 22644837
Taylor, P. N. et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat. Rev. Endocrinol. 14, 301–316 (2018).
pubmed: 29569622
Adams, D. D. & Purves, H. D. Abnormal responses in the assay of thyrotropin. Proc. Univ. Otago Med. Sch. 34, 11–12 (1956). This is the first short report describing TSHR antibodies as long-acting thyroid stimulators. The author later injected serum from patients with GD into himself and his colleagues to show the presence of stimulating activity.
Perros, P. et al. Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J. Rare Dis. 12, 72 (2017).
pubmed: 28427469
pmcid: 5397790
Fatourechi, V. Thyroid dermopathy and acropachy. Best Pract. Res. Clin. Endocrinol. Metab. 26, 553–565 (2012).
pubmed: 22863396
Koren, S. et al. A 2017 survey of the clinical practice patterns in the management of relapsing Graves disease. Endocr. Pract. 25, 55–61 (2019).
pubmed: 30383500
Carle, A. et al. High age predicts low referral of hyperthyroid patients to specialized hospital departments: evidence for referral bias. Thyroid 23, 1518–1524 (2013).
pubmed: 23745710
Smith, T. J. & Hegedus, L. Graves’ disease. N. Engl. J. Med. 375, 1552–1565 (2016).
pubmed: 27797318
Laurberg, P. et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract. Res. Clin. Endocrinol. Metab. 24, 13–27 (2010).
pubmed: 20172467
Pedersen, I. B. et al. Surveyance of disease frequency in a population by linkage to diagnostic laboratory databases. A system for monitoring the incidences of hyper- and hypothyroidism as part of the Danish iodine supplementation program. Comput. Methods Prog. Biomed. 67, 209–216 (2002).
Carle, A. et al. Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study. Eur. J. Endocrinol. 164, 801–809 (2011).
pubmed: 21357288
Laurberg, P., Pedersen, K. M., Vestergaard, H. & Sigurdsson, G. High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves’ disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J. Intern. Med. 229, 415–420 (1991).
pubmed: 2040867
Petersen, M. et al. Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification. Clin. Endocrinol. 91, 652–659 (2019).
Cerqueira, C. et al. Association of iodine fortification with incident use of antithyroid medication–a Danish nationwide study. J. Clin. Endocrinol. Metab. 94, 2400–2405 (2009).
pubmed: 19366844
Yang, F. et al. Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China. Eur. J. Endocrinol. 156, 403–408 (2007).
pubmed: 17389453
Yang, F. et al. Epidemiological survey on the relationship between different iodine intakes and the prevalence of hyperthyroidism. Eur. J. Endocrinol. 146, 613–618 (2002).
pubmed: 11980615
Lee, H. J., Li, C. W., Hammerstad, S. S., Stefan, M. & Tomer, Y. Immunogenetics of autoimmune thyroid diseases: a comprehensive review. J. Autoimmun. 64, 82–90 (2015).
pubmed: 26235382
pmcid: 4628844
Brix, T. H., Kyvik, K. O., Christensen, K. & Hegedus, L. Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J. Clin. Endocrinol. Metab. 86, 930–934 (2001). This paper describes the classic use of twins to explore the genetic contribution to GD.
pubmed: 11158069
Vos, X. G., Smit, N., Endert, E., Tijssen, J. G. & Wiersinga, W. M. Variation in phenotypic appearance of Graves’ disease: effect of genetic anticipation and duration of complaints. Eur. J. Endocrinol. 161, 113–118 (2009).
pubmed: 19423562
McLeod, D. S., Caturegli, P., Cooper, D. S., Matos, P. G. & Hutfless, S. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA 311, 1563–1565 (2014).
pubmed: 24737370
McLeod, D. S., Cooper, D. S., Ladenson, P. W., Whiteman, D. C. & Jordan, S. J. Race/ethnicity and the prevalence of thyrotoxicosis in young Americans. Thyroid 25, 621–628 (2015).
pubmed: 25744381
Hiromatsu, Y., Eguchi, H., Tani, J., Kasaoka, M. & Teshima, Y. Graves’ ophthalmopathy: epidemiology and natural history. Intern. Med. 53, 353–360 (2014).
pubmed: 24583420
Wong, Y. et al. A British Ophthalmological Surveillance Unit (BOSU) study into dysthyroid optic neuropathy in the United Kingdom. Eye 32, 1555–1562 (2018).
pubmed: 29915191
pmcid: 6189132
Villanueva, R., Greenberg, D. A., Davies, T. F. & Tomer, Y. Sibling recurrence risk in autoimmune thyroid disease. Thyroid 13, 761–764 (2003).
pubmed: 14558919
Yin, X. et al. mRNA-Seq reveals novel molecular mechanisms and a robust fingerprint in Graves’ disease. J. Clin. Endocrinol. Metab. 99, E2076–E2083 (2014).
pubmed: 24971664
pmcid: 4184074
Brix, T. H., Christensen, K., Holm, N. V., Harvald, B. & Hegedus, L. A population-based study of Graves’ disease in Danish twins. Clin. Endocrinol. 48, 397–400 (1998).
Farid, N. R. & Bear, J. C. The human major histocompatibility complex and endocrine disease. Endocr. Rev. 2, 50–86 (1981). This is the first major review of the association between HLA and autoimmune thyroid disease.
pubmed: 7028471
Roman, S. H., Greenberg, D., Rubinstein, P., Wallenstein, S. & Davies, T. F. Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within families. J. Clin. Endocrinol. Metab. 74, 496–503 (1992).
pubmed: 1740483
Barbesino, G., Tomer, Y., Concepcion, E. S., Davies, T. F. & Greenberg, D. Linkage analysis of candidate genes in autoimmune thyroid disease:1. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease. J. Clin. Endocrinol. Metab. 83, 1580–1584 (1998).
pubmed: 9589659
Ban, Y. et al. Analysis of immune regulatory genes in familial and sporadic Graves’ disease. J. Clin. Endocrinol. Metab. 89, 4562–4568 (2004).
pubmed: 15356063
Hodge, S. E. et al. Possible interaction between HLA-DRβ1 and thyroglobulin variants in Graves’ disease. Thyroid 16, 351–355 (2006).
pubmed: 16646680
Qian, W. et al. Association between TSHR gene polymorphism and the risk of Graves’ disease: a meta-analysis. J. Biomed. Res. 30, 466–475 (2016).
pubmed: 27231040
Marin-Sanchez, A. et al. Regulation of TSHR expression in the thyroid and thymus may contribute to TSHR tolerance failure in Graves’ disease patients via two distinct mechanisms. Front. Immunol. 10, 1695 (2019).
pubmed: 31379878
pmcid: 6657650
Stefan, M. et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc. Natl Acad. Sci. USA 111, 12562–12567 (2014).
pubmed: 25122677
Villanueva, R. et al. Limited genetic susceptibility to severe Graves’ ophthalmopathy: no role for CTLA-4 but evidence for an environmental etiology. Thyroid 10, 791–798 (2000).
pubmed: 11041456
Yin, X., Latif, R., Bahn, R. & Davies, T. F. Genetic profiling in Graves’ disease: further evidence for lack of a distinct genetic contribution to Graves’ ophthalmopathy. Thyroid 22, 730–736 (2012).
pubmed: 22663548
pmcid: 3387758
Ban, Y. et al. The regulatory T cell gene FOXP3 and genetic susceptibility to thyroid autoimmunity: an association analysis in Caucasian and Japanese cohorts. J. Autoimmun. 28, 201–207 (2007).
pubmed: 17418529
Yuan, F. F. et al. Genetic study of early-onset Graves’ disease in the Chinese Han population. Clin. Genet. 93, 103–110 (2018).
pubmed: 28598035
Heiberg, B. T. et al. High frequency of skewed X chromosome inactivation in females with autoimmune thyroid disease. A possible explanation for the female predisposition to thyroid autoimmunity. J. Clin. Endocrinol. Metab. 90, 5949–5953 (2005).
Brix, T. H. et al. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity. J. Clin. Endocrinol. Metab. 90, 5949–5953 (2005).
pubmed: 16105963
Yin, X., Latif, R., Tomer, Y. & Davies, T. F. Thyroid epigenetics: X chromosome inactivation in patients with autoimmune thyroid disease. Ann. N. Y. Acad. Sci. 1110, 193–200 (2007).
pubmed: 17911434
Santiwatana, S. et al. Skewed X chromosome inactivation in girls and female adolescents with autoimmune thyroid disease. Clin. Endocrinol. 89, 863–869 (2018).
Andersen, S. L., Olsen, J., Carle, A. & Laurberg, P. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J. Clin. Endocrinol. Metab. 100, 1164–1171 (2015).
pubmed: 25485728
Amino, N. et al. Aggravation of thyrotoxicosis in early pregnancy and after delivery in Graves’ disease. J. Clin. Endocrinol. Metab. 55, 108–112 (1982). This study demonstrated that the surge in human chorionic gonadotropin in early pregnancy can worsen GD.
pubmed: 6896207
Benhaim Rochester, D. & Davies, T. F. Increased risk of Graves’ disease after pregnancy. Thyroid 15, 1287–1290 (2005).
pubmed: 16356094
Jansson, R. et al. The postpartum period constitutes an important risk for the development of clinical Graves’ disease in young women. Acta Endocrinol. 116, 321–325 (1987).
pubmed: 3687319
Rotondi, M. et al. The post partum period and the onset of Graves’ disease: an overestimated risk factor. Eur. J. Endocrinol. 159, 161–165 (2008).
pubmed: 18483014
Tada, H. et al. Prevalence of postpartum onset of disease within patients with Graves’ disease of child-bearing age. Endocr. J. 41, 325–327 (1994).
pubmed: 7951587
Mintziori, G., Kita, M., Duntas, L. & Goulis, D. G. Consequences of hyperthyroidism in male and female fertility: pathophysiology and current management. J. Endocrinol. Invest. 39, 849–853 (2016).
pubmed: 26956000
Andersen, S. L., Olsen, J. & Laurberg, P. Maternal thyroid disease in the Danish National Birth Cohort: prevalence and risk factors. Eur. J. Endocrinol. 174, 203–212 (2016).
pubmed: 26582484
Cooper, D. S. & Laurberg, P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 1, 238–249 (2013).
pubmed: 24622372
La Rocca, C., Carbone, F., Longobardi, S. & Matarese, G. The immunology of pregnancy: regulatory T cells control maternal immune tolerance toward the fetus. Immunol. Lett. 162, 41–48 (2014).
pubmed: 24996040
Stagnaro-Green, A. et al. A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction. J. Clin. Endocrinol. Metab. 74, 645–653 (1992).
pubmed: 1740500
Sharif, K. et al. The role of stress in the mosaic of autoimmunity: an overlooked association. Autoimmun. Rev. 17, 967–983 (2018).
pubmed: 30118900
Falgarone, G., Heshmati, H. M., Cohen, R. & Reach, G. Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves’ disease. Eur. J. Endocrinol. 168, R13–R18 (2013).
pubmed: 23027804
Sakkas, E. G. et al. Associations of maternal oestradiol, cortisol, and TGF-beta1 plasma concentrations with thyroid autoantibodies during pregnancy and postpartum. Clin. Endocrinol. 89, 789–797 (2018).
Wickham, S. & Carr, D. J. Molecular mimicry versus bystander activation: herpetic stromal keratitis. Autoimmunity 37, 393–397 (2004).
pubmed: 15621563
Srinivasappa, J. et al. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J. Virol. 57, 397–401 (1986).
pubmed: 3753614
pmcid: 252745
Hargreaves, C. E. et al. Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves’ disease. J. Immunol. 190, 5373–5381 (2013).
pubmed: 23630351
Menconi, F., Hasham, A. & Tomer, Y. Environmental triggers of thyroiditis: hepatitis C and interferon-alpha. J. Endocrinol. Invest. 34, 78–84 (2011).
pubmed: 21297381
Faustino, L. C. et al. Interferon-alpha triggers autoimmune thyroid diseases via lysosomal-dependent degradation of thyroglobulin. J. Clin. Endocrinol. Metab. 103, 3678–3687 (2018).
pubmed: 30113675
pmcid: 6179164
Bartalena, L., Bogazzi, F. & Martino, E. Amiodarone-induced thyrotoxicosis: a difficult diagnostic and therapeutic challenge. Clin. Endocrinol. 56, 23–24 (2002).
Basaria, S. & Cooper, D. S. Amiodarone and the thyroid. Am. J. Med. 118, 706–714 (2005).
pubmed: 15989900
Vitale, M. et al. Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 141, 598–605 (2000).
pubmed: 10650940
DeGroot, L. Effects of irradiation on the thyroid gland. Adolesc. Endocrinol. 22, 607 (1993).
Huysmans, D. et al. Autoimmune hyperthyroidism occurring late after radioiodine treatment for volume reduction of large multinodular goiters. Thyroid 7, 535–539 (1997).
pubmed: 9292939
McGregor, A. M. et al. A prospective study of the effects of radio-iodine therapy on thyroid-stimulating antibody synthesis in Grave’s disease [proceedings]. J. Endocrinol. 81, 114P–115P (1979).
pubmed: 222864
Laurberg, P. et al. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur. J. Endocrinol. 158, 69–75 (2008). This is an important study showing that TSHR autoantibodies disappear most rapidly after surgery and quite quickly with antithyroid drugs but take a long time to fall after radioiodine therapy.
pubmed: 18166819
Bartalena, L. et al. An update on medical management of Graves’ ophthalmopathy. J. Endocrinol. Invest. 28, 469–478 (2005).
pubmed: 16075933
Weetman, A. P. Graves’ disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently? Clin. Endocrinol. 80, 629–632 (2014).
de Filette, J., Andreescu, C. E., Cools, F., Bravenboer, B. & Velkeniers, B. A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors. Hormone Metab. Res. 51, 145–156 (2019).
de Oliveira, G. L. V., Leite, A. Z., Higuchi, B. S., Gonzaga, M. I. & Mariano, V. S. Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology 152, 1–12 (2017).
pubmed: 28556916
pmcid: 5543467
Ishaq, H. M. et al. Molecular alteration analysis of human gut microbial composition in Graves’ disease patients. Int. J. Biol. Sci. 14, 1558–1570 (2018).
pubmed: 30263008
pmcid: 6158725
Yang, M. et al. Alteration of the intestinal flora may participate in the development of Graves’ disease: a study conducted among the Han population in southwest China. Endocr. Connect. 8, 822–828 (2019).
pubmed: 31137015
pmcid: 6590206
Shi, T. T. et al. Alterations in the intestinal microbiota of patients with severe and active Graves’ orbitopathy: a cross-sectional study. J. Endocrinol. Invest. 42, 967–978 (2019).
pubmed: 30674011
INDIGO Project. http://www.indigo-iapp.eu/publishable-summary/ .
Masetti, G. et al. Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease. Microbiome 6, 97 (2018).
pubmed: 29801507
pmcid: 5970527
Moshkelgosha, S. et al. Gut microbiome in BALB/c and C57BL/6J mice undergoing experimental thyroid autoimmunity associate with differences in immunological responses and thyroid function. Hormone Metab. Res. 50, 932–941 (2018).
Lauritano, E. C. et al. Association between hypothyroidism and small intestinal bacterial overgrowth. J. Clin. Endocrinol. Metab. 92, 4180–4184 (2007).
pubmed: 17698907
Paschke, R. et al. Regional stimulation of thyroid epithelial cells in Graves’ disease by lymphocytic aggregates and plasma cells. Acta Endocrinol. 125, 459–465 (1991).
pubmed: 1759536
Morshed, S. A., Ma, R., Latif, R. & Davies, T. F. Cleavage region thyrotropin receptor antibodies influence thyroid cell survival in vivo. Thyroid 29, 993–1002 (2019).
pubmed: 31025602
Arnold, B., Schonrich, G. & Hammerling, G. J. Multiple levels of peripheral tolerance. Immunol. Today 14, 12–14 (1993).
pubmed: 8442855
Nemazee, D. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol. 17, 281–294 (2017).
pubmed: 28368006
pmcid: 5623591
Arata, N., Ando, T., Unger, P. & Davies, T. F. By-stander activation in autoimmune thyroiditis: studies on experimental autoimmune thyroiditis in the GFP
pubmed: 16916620
Mirakian, R., HAMMOND, L. J. & Bottazzo, G. F. Pathogenesis of thyroid autoimmunity: the Bottazzo-Feldmann hypothesis. Immunol. Today 19, 97–98 (1998).
pubmed: 9509765
Piccinini, L. A., Goldsmith, N. K., Schachter, B. S. & Davies, T. F. Localization of HLA-DR alpha-chain messenger ribonucleic acid in normal and autoimmune human thyroid using in situ hybridization. J. Clin. Endocrinol. Metab. 66, 1307–1315 (1988).
pubmed: 2453529
Pujol-Borrell, R. et al. Inappropriate major histocompatibility complex class II expression by thyroid follicular cells in thyroid autoimmune disease and by pancreatic beta cells in type I diabetes. Mol. Biol. Med. 3, 159–165 (1986). This paper is an early summary by the investigators who first showed HLA class II antigen expression on thyroid cells as an important clue to aetiology.
pubmed: 3090400
Mao, C. et al. Impairment of regulatory capacity of CD4
pubmed: 21398613
Pan, D., Shin, Y. H., Gopalakrishnan, G., Hennessey, J. & De Groot, L. J. Regulatory T cells in Graves’ disease. Clin. Endocrinol. 71, 587–593 (2009).
Schwartz, R. H. T cell anergy. Sci. Am. 269, 62–63 (1993).
pubmed: 8351512
ElTanbouly, M. A. et al. VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance. Science 367, eaay0524 (2020).
pubmed: 31949051
Rapoport, B., Chazenbalk, G. D., Jaume, J. C. & McLachlan, S. M. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr. Rev. 19, 673–716 (1998).
pubmed: 9861544
Sanders, J., Miguel, R. N., Furmaniak, J. & Smith, B. R. TSH receptor monoclonal antibodies with agonist, antagonist, and inverse agonist activities. Methods Enzymol. 485, 393–420 (2010).
pubmed: 21050929
Galofre, J. C. & Davies, T. F. Autoimmune thyroid disease in pregnancy: a review. J. Womens Health 18, 1847–1856 (2009).
Furmaniak, J. et al. Photoaffinity labelling of the TSH receptor on FRTL5 cells. FEBS Lett. 215, 316–322 (1987).
pubmed: 3582657
Couet, J. et al. Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain. Biochemistry 35, 14800–14805 (1996).
pubmed: 8942642
Chen, C. R. et al. The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim. J. Clin. Invest. 111, 1897–1904 (2003).
pubmed: 12813025
pmcid: 161420
Nagayama, Y., Wadsworth, H. L., Russo, D., Chazenbalk, G. D. & Rapoport, B. Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors. J. Clin. Invest. 88, 336–340 (1991).
pubmed: 1711544
pmcid: 296038
Chazenbalk, G. D. et al. Thyroid-stimulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor. J. Clin. Invest. 110, 209–217 (2002). This paper describes the extracellular component of TSHR as the most immunogenic form, stimulating its use as an efficient mouse immunization model of hyperthyroidism from TSHR autoantibodies.
pubmed: 12122113
pmcid: 151066
Latif, R., Morshed, S. A., Zaidi, M. & Davies, T. F. The thyroid-stimulating hormone receptor: impact of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on multimerization, cleavage, and signaling. Endocrinol. Metab. Clin. North. Am. 38, 319–341 (2009).
pubmed: 19328414
Latif, R., Michalek, K. & Davies, T. F. Subunit interactions influence TSHR multimerization. Mol. Endocrinol. 24, 2009–2018 (2010).
pubmed: 20719860
pmcid: 2954635
Latif, R., Michalek, K., Morshed, S. A. & Davies, T. F. A tyrosine residue on the TSH receptor stabilizes multimer formation. PLoS One 5, e9449 (2010).
pubmed: 20195479
pmcid: 2829087
Allen, M. D., Neumann, S. & Gershengorn, M. C. Occupancy of both sites on the thyrotropin (TSH) receptor dimer is necessary for phosphoinositide signaling. FASEB J. 25, 3687–3694 (2011).
pubmed: 21705666
pmcid: 3177577
Ando, T., Latif, R. & Davies, T. F. Antibody-induced modulation of TSH receptor post-translational processing. J. Endocrinol. 195, 179–186 (2007).
pubmed: 17911409
Rapoport, B., Aliesky, H. A., Chen, C. R. & McLachlan, S. M. Evidence that TSH receptor A-subunit multimers, not monomers, drive antibody affinity maturation in Graves’ disease. J. Clin. Endocrinol. Metab. 100, E871–E875 (2015).
pubmed: 25856215
pmcid: 4454809
Krieger, C. C. et al. TSH/IGF-1 receptor cross talk in Graves’ ophthalmopathy pathogenesis. J. Clin. Endocrinol. Metab. 101, 2340–2347 (2016).
pubmed: 27043163
pmcid: 4891793
Adams, D. D. & Kennedy, T. H. Evidence to suggest that LATS protector stimulates the human thyroid gland. J. Clin. Endocrinol. Metab. 33, 47–51 (1971).
pubmed: 5558041
Morris, J. C. et al. Identification of epitopes and affinity purification of thyroid stimulating auto-antibodies using synthetic human TSH receptor peptides. Autoimmunity 17, 287–299 (1994).
pubmed: 7524706
Tahara, K. et al. Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor. Thyroid 7, 867–877 (1997).
pubmed: 9459630
Ando, T. et al. A monoclonal thyroid-stimulating antibody. J. Clin. Invest. 110, 1667–1674 (2002). This paper describes the first monoclonal TSHR antibody, raised in a hamster, with stimulating activity.
pubmed: 12464672
pmcid: 151640
Sanders, J. et al. Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody. Thyroid 17, 395–410 (2007). This paper shows the first crystal structure of most of the TSHR extracellular sequence stabilized by a TSHR autoantibody.
pubmed: 17542669
McLachlan, S. M. & Rapoport, B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 23, 14–24 (2013).
pubmed: 23025526
pmcid: 3539254
Sanders, P. et al. Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody. J. Mol. Endocrinol. 46, 81–99 (2011).
pubmed: 21247981
Jiang, X. et al. Evidence for follicle-stimulating hormone receptor as a functional trimer. J. Biol. Chem. 289, 14273–14282 (2014).
pubmed: 24692546
pmcid: 4022893
Kleinau, G. & Krause, G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr. Rev. 30, 133–151 (2009).
pubmed: 19176466
Morshed, S. A., Ando, T., Latif, R. & Davies, T. F. Neutral antibodies to the TSH receptor are present in Graves’ disease and regulate selective signaling cascades. Endocrinology 151, 5537–5549 (2010).
pubmed: 20844004
pmcid: 2954721
Sun, S. et al. Antigenic “Hot-Spots” on the TSH receptor hinge region. Front. Endocrinol. 9, 765 (2018).
Allgeier, A., Laugwitz, K. L., Van Sande, J., Schultz, G. & Dumont, J. E. Multiple G-protein coupling of the dog thyrotropin receptor. Mol. Cell Endocrinol. 127, 81–90 (1997).
pubmed: 9099903
Frenzel, R., Voigt, C. & Paschke, R. The human thyrotropin receptor is predominantly internalized by β-arrestin 2. Endocrinology 147, 3114–3122 (2006).
pubmed: 16513835
Boutin, A., Eliseeva, E., Gershengorn, M. C. & Neumann, S. β-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation. FASEB J. 28, 3446–3455 (2014).
pubmed: 24723693
pmcid: 4101659
Morshed, S. A., Ma, R., Latif, R. & Davies, T. F. Biased signaling by thyroid-stimulating hormone receptor-specific antibodies determines thyrocyte survival in autoimmunity. Sci. Signal. 11, eaah4120 (2018).
pubmed: 29363585
pmcid: 5812361
Bahn, R. S. Current insights into the pathogenesis of Graves’ ophthalmopathy. Horm. Metab. Res. 47, 773–778 (2015).
pubmed: 26361262
Kumar, S., Nadeem, S., Stan, M. N., Coenen, M. & Bahn, R. S. A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves’ ophthalmopathy. J. Mol. Endocrinol. 46, 155–163 (2011).
pubmed: 21321093
pmcid: 3074639
Kahaly, G. J., Wuster, C., Olivo, P. D. & Diana, T. High titers of thyrotropin receptor antibodies are associated with orbitopathy in patients with Graves disease. J. Clin. Endocrinol. Metab. 104, 2561–2568 (2019).
pubmed: 30753531
Weightman, D. R., Perros, P., Sherif, I. H. & Kendall-Taylor, P. Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy. Autoimmunity 16, 251–257 (1993).
pubmed: 7517705
Smith, T. J. et al. Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy. Thyroid 18, 983–988 (2008).
pubmed: 18788919
pmcid: 2574420
Smith, T. J. et al. Teprotumumab for thyroid-associated ophthalmopathy. N. Engl. J. Med. 376, 1748–1761 (2017). This paper is a clinical trial report showing the first highly successful use of an IGF1R-blocking monoclonal antibody in the treatment of moderate to severe GO.
pubmed: 28467880
pmcid: 5718164
Prabhakar, B. S., Bahn, R. S. & Smith, T. J. Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr. Rev. 24, 802–835 (2003).
pubmed: 14671007
Douglas, R. S. et al. Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J. Clin. Endocrinol. Metab. 95, 430–438 (2009).
pubmed: 19897675
pmcid: 2805489
Boelaert, K., Torlinska, B., Holder, R. L. & Franklyn, J. A. Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. J. Clin. Endocrinol. Metab. 95, 2715–2726 (2010).
pubmed: 20392869
Bell, L., Hunter, A. L., Kyriacou, A., Mukherjee, A. & Syed, A. A. Clinical diagnosis of Graves’ or non-Graves’ hyperthyroidism compared to TSH receptor antibody test. Endocr. Connect. 7, 504–510 (2018).
pubmed: 29531156
pmcid: 5881005
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. 12, 107–113 (2012).
pubmed: 22776786
Ross, D. S. et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26, 1343–1421 (2016). This paper describes the current guidelines for the treatment of GD from the American Thyroid Association.
pubmed: 27521067
McKee, A. & Peyerl, F. TSI assay utilization: impact on costs of Graves’ hyperthyroidism diagnosis. Am. J. Manag. Care 18, e1–e14 (2012).
pubmed: 22435785
Struja, T. et al. Comparison of five TSH-receptor antibody assays in Graves’ disease: results from an observational pilot study. BMC Endocr. Disord. 19, 38 (2019).
pubmed: 31023276
pmcid: 6482584
Fujimoto, Y., Oka, A., Omoto, R. & Hirose, M. Ultrasound scanning of the thyroid gland as a new diagnostic approach. Ultrasonics 5, 177–180 (1967).
pubmed: 6053923
Blum, M., Weiss, B. & Hernberg, J. Evaluation of thyroid nodules by A-mode echography. Radiology 101, 651–656 (1971).
pubmed: 5171549
Ahn, H. S., Kim, H. J. & Welch, H. G. Korea’s thyroid-cancer “epidemic” – screening and overdiagnosis. N. Engl. J. Med. 371, 1765–1767 (2014).
pubmed: 25372084
Barbesino, G. & Tomer, Y. Clinical review: clinical utility of TSH receptor antibodies. J. Clin. Endocrinol. Metab. 98, 2247–2255 (2013).
pubmed: 23539719
pmcid: 3667257
Saeed, P., Tavakoli Rad, S. & Bisschop, P. Dysthyroid optic neuropathy. Ophthalmic Plast. Reconstr. Surg. 34 (4S Suppl. 1), 60–67 (2018).
Dolman, P. J. & Rootman, J. VISA classification for Graves orbitopathy. Ophthalmic Plast. Reconstr. Surg. 22, 319–324 (2006).
pubmed: 16985411
Bartalena, L. et al. Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur. J. Endocrinol. 158, 273–285 (2008).
pubmed: 18299459
Perini, N., Santos, R. B., Romaldini, J. H. & Villagelin, D. Thyroid acropachy: a rare manifestation of Graves disease in joints. AACE Clin. Case Rep. 5, e369–e371 (2019).
pubmed: 31967073
pmcid: 6873845
Wilson, J. M. & Jungner, Y. G. Principles and practice of mass screening for disease [Spanish]. Bol. Oficina Sanit. Panam. 65, 281–393 (1968).
pubmed: 4234760
Dong, A. C. & Stagnaro-Green, A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and meta-analysis. Thyroid 29, 278–289 (2019).
pubmed: 30444186
Kahaly, G. J. et al. 2018 European Thyroid Association guideline for the management of Graves’ hyperthyroidism. Eur. Thyroid. J. 7, 167–186 (2018).
pubmed: 30283735
pmcid: 6140607
Cooper, D. S. Antithyroid drugs. N. Engl. J. Med. 352, 905–917 (2005).
pubmed: 15745981
Van Dijke, C. P., Heydendael, R. J. & De Kleine, M. J. Methimazole, carbimazole, and congenital skin defects. Ann. Intern. Med. 106, 60–61 (1987).
pubmed: 3789581
Yang, J. et al. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China. Thyroid 25, 278–283 (2015).
pubmed: 25384184
Andersen, S. L., Olsen, J. & Laurberg, P. Antithyroid drug side effects in the population and in pregnancy. J. Clin. Endocrinol. Metab. 101, 1606–1614 (2016).
pubmed: 26815881
Wang, M. T., Lee, W. J., Huang, T. Y., Chu, C. L. & Hsieh, C. H. Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study. Br. J. Clin. Pharmacol. 78, 619–629 (2014).
pubmed: 25279406
pmcid: 4243912
Watanabe, N. et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves’ disease. J. Clin. Endocrinol. Metab. 97, E49–E53 (2012).
pubmed: 22049174
Nakamura, H., Miyauchi, A., Miyawaki, N. & Imagawa, J. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J. Clin. Endocrinol. Metab. 98, 4776–4783 (2013).
pubmed: 24057289
Maugendre, D. et al. Antithyroid drugs and Graves’ disease – prospective randomized assessment of long-term treatment. Clin. Endocrinol. 50, 127–132 (1999).
Konishi, T. et al. Drug discontinuation after treatment with minimum maintenance dose of an antithyroid drug in Graves’ disease: a retrospective study on effects of treatment duration with minimum maintenance dose on lasting remission. Endocr. J. 58, 95–100 (2011).
pubmed: 21206137
Kaplowitz, P. B. & Vaidyanathan, P. Update on pediatric hyperthyroidism. Curr. Opin. Endocrinol. Diabetes Obes. 27, 70–76 (2020).
pubmed: 31789723
Franklyn, J. A. The management of hyperthyroidism. N. Engl. J. Med. 330, 1731–1738 (1994).
pubmed: 7910662
Alexander, E. K. & Larsen, P. R. High dose of
pubmed: 11889166
Franklyn, J. A., Sheppard, M. C. & Maisonneuve, P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA 294, 71–80 (2005).
pubmed: 15998893
Gronich, N., Lavi, I., Rennert, G. & Saliba, W. Cancer risk after radioactive iodine treatment for hyperthyroidism: a cohort study. Thyroid 30, 243–250 (2020).
pubmed: 31880205
Kuy, S., Roman, S. A., Desai, R. & Sosa, J. A. Outcomes following thyroid and parathyroid surgery in pregnant women. Arch. Surg. 144, 399–406 (2009).
pubmed: 19451480
Sosa, J. A. et al. The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann. Surg. 228, 320–330 (1998).
pubmed: 9742915
pmcid: 1191485
Stavrakis, A. I., Ituarte, P. H., Ko, C. Y. & Yeh, M. W. Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine surgery. Surgery 142, 887–899 (2007).
pubmed: 18063073
Adam, M. A. et al. Is there a minimum number of thyroidectomies a surgeon should perform to optimize patient outcomes? Ann. Surg. 265, 402–407 (2017).
pubmed: 28059969
Antakia, R., Edafe, O., Uttley, L. & Balasubramanian, S. P. Effectiveness of preventative and other surgical measures on hypocalcemia following bilateral thyroid surgery: a systematic review and meta-analysis. Thyroid 25, 95–106 (2015).
pubmed: 25203484
Geffner, D. L. & Hershman, J. M. Beta-adrenergic blockade for the treatment of hyperthyroidism. Am. J. Med. 93, 61–68 (1992).
pubmed: 1352658
Wiersinga, W. M. Combined thyroid eye clinic: the importance of a multidisciplinary health care in patients with Graves’ orbitopathy. Pediatr. Endocrinol. Rev. 7, 250–253 (2010).
pubmed: 20467372
Terwee, C. B. et al. Measuring disease activity to predict therapeutic outcome in Graves’ ophthalmopathy. Clin. Endocrinol. 62, 145–155 (2005).
Tooley, A. A., Godfrey, K. J. & Kazim, M. Evolution of thyroid eye disease decompression-dysthyroid optic neuropathy. Eye 33, 206–211 (2019).
pubmed: 30390053
Eckstein, A., Esser, J., Oeverhaus, M., Saeed, P. & Jellema, H. M. Surgical treatment of diplopia in Graves orbitopathy patients. Ophthalmic Plast. Reconstr. Surg. 34 (4S Suppl. 1), 75–84 (2018).
Clarke, L. & Eckstein, A. in Graves’ Orbitopathy: A Multidisciplinary Approach - Questions and Answers (eds Wiersinga W. M. & Kahaly G. J.) 247–259 (Karger, 2017).
Eckstein, A. et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br. J. Ophthalmol. 87, 773–776 (2003).
pubmed: 12770979
pmcid: 1771717
Rotondo Dottore, G. et al. Antioxidant actions of selenium in orbital fibroblasts: a basis for the effects of selenium in Graves’ orbitopathy. Thyroid 27, 271–278 (2017).
pubmed: 27824294
Kahaly, G. J., Pitz, S., Hommel, G. & Dittmar, M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 90, 5234–5240 (2005).
pubmed: 15998777
Bartalena, L. et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 97, 4454–4463 (2012).
pubmed: 23038682
Zhu, W. et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves’ ophthalmopathy. J. Clin. Endocrinol. Metab. 99, 1999–2007 (2014).
pubmed: 24606088
Hart, R. H., Kendall-Taylor, P., Crombie, A. & Perros, P. Early response to intravenous glucocorticoids for severe thyroid-associated ophthalmopathy predicts treatment outcome. J. Ocul. Pharmacol. Ther. 21, 328–336 (2005).
pubmed: 16117697
Zang, S., Ponto, K. A. & Kahaly, G. J. Clinical review: intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J. Clin. Endocrinol. Metab. 96, 320–332 (2011).
pubmed: 21239515
Bartalena, L. et al. Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves’ orbitopathy? J. Endocrinol. Invest. 40, 547–553 (2017).
pubmed: 28176220
Curro, N. et al. Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy. Thyroid 24, 897–905 (2014).
pubmed: 24417307
Sisti, E. et al. Age and dose are major risk factors for liver damage associated with intravenous glucocorticoid pulse therapy for Graves’ orbitopathy. Thyroid 25, 846–850 (2015).
pubmed: 26090805
Kahaly, G. et al. Ciclosporin and prednisone v. prednisone in treatment of Graves’ ophthalmopathy: a controlled, randomized and prospective study. Eur. J. Clin. Invest. 16, 415–422 (1986).
pubmed: 3100309
Prummel, M. F. et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N. Engl. J. Med. 321, 1353–1359 (1989).
pubmed: 2519530
Kahaly, G. J. et al. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol. 6, 287–298 (2018).
pubmed: 29396246
Rajendram, R. et al. Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2×2 factorial, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 6, 299–309 (2018).
pubmed: 29396245
Salvi, M. et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe graves’ orbitopathy: a randomized controlled study. J. Clin. Endocrinol. Metab. 100, 422–431 (2015).
pubmed: 25494967
Mitchell, A. L. et al. The effect of B cell depletion therapy on anti-TSH receptor antibodies and clinical outcome in glucocorticoid-refractory Graves’ orbitopathy. Clin. Endocrinol. 79, 437–442 (2013).
Stan, M. N. et al. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 100, 432–441 (2015).
pubmed: 25343233
Perez-Moreiras, J. V. et al. Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy: a randomized clinical trial. Am. J. Ophthalmol. 195, 181–190 (2018).
pubmed: 30081019
Mourits, M. P. et al. Radiotherapy for Graves’ orbitopathy: randomised placebo-controlled study. Lancet 355, 1505–1509 (2000).
pubmed: 10801172
Shams, P. N., Ma, R., Pickles, T., Rootman, J. & Dolman, P. J. Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease. Am. J. Ophthalmol. 157, 1299–1305 (2014).
pubmed: 24582992
Marcocci, C. et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves’ ophthalmopathy: results of a prospective, single-blind, randomized study. J. Clin. Endocrinol. Metab. 86, 3562–3567 (2001).
pubmed: 11502779
Oeverhaus, M. et al. Combination therapy of intravenous steroids and orbital irradiation is more effective than intravenous steroids alone in patients with Graves’ orbitopathy. Horm. Metab. Res. 49, 739–747 (2017).
pubmed: 28922676
Fatourechi, V. Pretibial myxedema: pathophysiology and treatment options. Am. J. Clin. Dermatol. 6, 295–309 (2005).
pubmed: 16252929
Alexander, E. K. et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 27, 315–389 (2017). This paper reports the American Thyroid Association consensus guidelines for the management of GD in pregnancy.
pubmed: 28056690
Lazarus, J. H. Pre-conception counselling in Graves’ disease. Eur. Thyroid. J. 1, 24–29 (2012).
pubmed: 24782994
pmcid: 3821453
Rotondi, M. et al. The effect of pregnancy on subsequent relapse from Graves’ disease after a successful course of antithyroid drug therapy. J. Clin. Endocrinol. Metab. 93, 3985–3988 (2008).
pubmed: 18664537
Casey, B. M. et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet. Gynecol. 107, 337–341 (2006).
pubmed: 16449121
Ochoa-Maya, M. R., Frates, M. C., Lee-Parritz, A. & Seely, E. W. Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves’ hyperthyroidism. Thyroid 9, 1111–1114 (1999).
pubmed: 10595460
Stagnaro-Green, A. et al. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. Thyroid 21, 1081–1125 (2011).
pubmed: 21787128
pmcid: 3472679
Samuels, S. L., Namoc, S. M. & Bauer, A. J. Neonatal thyrotoxicosis. Clin. Perinatol. 45, 31–40 (2018).
pubmed: 29406005
Wilson, I. B. & Cleary, P. D. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA 273, 59–65 (1995).
pubmed: 7996652
Gerding, M. N. et al. Quality of life in patients with Graves’ ophthalmopathy is markedly decreased: measurement by the medical outcomes study instrument. Thyroid 7, 885–889 (1997).
pubmed: 9459632
Kahaly, G. J., Hardt, J., Petrak, F. & Egle, U. T. Psychosocial factors in subjects with thyroid-associated ophthalmopathy. Thyroid 12, 237–239 (2002).
pubmed: 11952046
Tehrani, M. et al. Disease-specific assessment of quality of life after decompression surgery for Graves’ ophthalmopathy. Eur. J. Ophthalmol. 14, 193–199 (2004).
pubmed: 15206643
Kahaly, G. J., Petrak, F., Hardt, J., Pitz, S. & Egle, U. T. Psychosocial morbidity of Graves’ orbitopathy. Clin. Endocrinol. 63, 395–402 (2005).
Watt, T. et al. Quality of life in patients with benign thyroid disorders. A review. Eur. J. Endocrinol. 154, 501–510 (2006).
pubmed: 16556711
Watt, T. et al. Which domains of thyroid-related quality of life are most relevant? Patients and clinicians provide complementary perspectives. Thyroid 17, 647–654 (2007).
pubmed: 17696835
Egle, U. T. et al. The relevance of physical and psychosocial factors for the quality of life in patients with thyroid-associated orbitopathy (TAO). Exp. Clin. Endocrinol. Diabetes 107, S168–S171 (1999).
pubmed: 10614914
Tehrani, M. et al. Disease-specific assessment of quality of life after decompression surgery for Graves ophthalmopathy. Eur. J. Ophthalmol. 14, 193–199 (2004).
pubmed: 15206643
Ponto, K. A. et al. Quality of life and occupational disability in endocrine orbitopathy. Dtsch. Arztebl Int. 106, 283–289 (2009).
pubmed: 19547630
pmcid: 2689575
Watt, T. et al. Validity and reliability of the novel thyroid-specific quality of life questionnaire, ThyPRO. Eur. J. Endocrinol. 162, 161–167 (2010).
pubmed: 19797502
Terwee, C. B., Gerding, M. N., Dekker, F. W., Prummel, M. F. & Wiersinga, W. M. Development of a disease specific quality of life questionnaire for patients with Graves’ ophthalmopathy: the GO-QOL. Br. J. Ophthalmol. 82, 773–779 (1998).
pubmed: 9924370
pmcid: 1722683
Wong, C. K., Lang, B. H. & Lam, C. L. A systematic review of quality of thyroid-specific health-related quality-of-life instruments recommends ThyPRO for patients with benign thyroid diseases. J. Clin. Epidemiol. 78, 63–72 (2016).
pubmed: 27020087
Watt, T. et al. The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. J. Clin. Endocrinol. Metab. 99, 3708–3717 (2014).
pubmed: 25004246
Terwee, C. B. et al. Test-retest reliability of the GO-QOL: a disease-specific quality of life questionnaire for patients with Graves’ ophthalmopathy. J. Clin. Epidemiol. 52, 875–884 (1999).
pubmed: 10529028
McMillan, C., Bradley, C., Razvi, S. & Weaver, J. Psychometric evaluation of a new questionnaire measuring treatment satisfaction in hypothyroidism: the ThyTSQ. Value Health 9, 132–139 (2006).
pubmed: 16626417
Watt, T. et al. Improving a newly developed patient-reported outcome for thyroid patients, using cognitive interviewing. Qual. Life Res. 17, 1009–1017 (2008).
pubmed: 18584308
Watt, T. et al. Establishing construct validity for the thyroid-specific patient reported outcome measure (ThyPRO): an initial examination. Qual. Life Res. 18, 483–496 (2009).
pubmed: 19288224
Aad, G. et al. Combined measurement of the Higgs Boson Mass in pp collisions at sqrt[s]=7 and 8 TeV with the ATLAS and CMS experiments. Phys. Rev. Lett. 114, 191803 (2015).
pubmed: 26024162
Terwee, C. B. et al. Interpretation and validity of changes in scores on the Graves’ ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments. Clin. Endocrinol. 54, 391–398 (2001).
Ponto, K. A. et al. Quality of life in a German Graves orbitopathy population. Am. J. Ophthalmol. 152, 483–490.e1 (2011).
pubmed: 21676374
Marcocci, C. et al. Selenium and the course of mild Graves’ orbitopathy. N. Engl. J. Med. 364, 1920–1931 (2011).
pubmed: 21591944
Bartalena, L. et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy guidelines for the management of Graves’ orbitopathy. Eur. Thyroid. J. 5, 9–26 (2016).
pubmed: 27099835
pmcid: 4836120
Wiersinga, W. & Kahaly, G. Graves’ Orbitopathy a Multidisciplinary Approach 3rd edn (Karger, 2017).
Terwee, C. et al. Long-term effects of Graves’ ophthalmopathy on health-related quality of life. Eur. J. Endocrinol. 146, 751–757 (2002).
pubmed: 12039694
Terwee, C. B. & Wiersinga, W. M. Graves’ quality of life. Ophthalmology 114, 1416–1417 (2007).
pubmed: 17613337
Rapoport, B., Aliesky, H. A., Banuelos, B., Chen, C. R. & McLachlan, S. M. A unique mouse strain that develops spontaneous, iodine-accelerated, pathogenic antibodies to the human thyrotrophin receptor. J. Immunol. 194, 4154–4161 (2015). This paper reports the first mouse model to develop spontaneous autoimmune hyperthyroidism.
pubmed: 25825442
pmcid: 4402262
Furmaniak, J., Sanders, J. & Rees Smith, B. Blocking type TSH receptor antibodies. Autoimmun. Highlights 4, 11–26 (2013).
Marcinkowski, P. et al. A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of Graves’ orbitopathy. Thyroid 29, 111–123 (2019).
pubmed: 30351237
Fassbender, J., Holthoff, H. P., Li, Z. & Ungerer, M. Therapeutic effects of short cyclic and combined epitope peptides in a long-term model of Graves’ disease and orbitopathy. Thyroid 29, 258–267 (2019).
pubmed: 30618332
Jansson, L., Vrolix, K., Jahraus, A., Martin, K. F. & Wraith, D. C. Immunotherapy with apitopes blocks the immune response to TSH receptor in HLA-DR transgenic mice. Endocrinology 159, 3446–3457 (2018).
pubmed: 30099489
Pearce, S. H. S. et al. Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves’ hyperthyroidism: a phase I study. Thyroid 29, 1003–1011 (2019).
pubmed: 31194638
pmcid: 6648194
Paridaens, D., van den Bosch, W. A., van der Loos, T. L., Krenning, E. P. & van Hagen, P. M. The effect of etanercept on Graves’ ophthalmopathy: a pilot study. Eye 19, 1286–1289 (2005).
pubmed: 15550932
Ayabe, R., Rootman, D. B., Hwang, C. J., Ben-Artzi, A. & Goldberg, R. Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease. Ophthalmic Plast. Reconstr. Surg. 30, 415–419 (2014).
pubmed: 24978425
Allison, A. C. Mechanisms of action of mycophenolate mofetil in preventing chronic rejection. Transpl. Proc. 34, 2863–2866 (2002).
Ye, X. et al. Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves’ orbitopathy. Clin. Endocrinol. 86, 247–255 (2017).
Perez-Moreiras, J. V., Alvarez-Lopez, A. & Gomez, E. C. Treatment of active corticosteroid-resistant Graves’ orbitopathy. Ophthalmic Plast. Reconstr. Surg. 30, 162–167 (2014).
pubmed: 24503568
Stan, M. N. & Salvi, M. Management of endocrine disease: rituximab therapy for Graves’ orbitopathy - lessons from randomized control trials. Eur. J. Endocrinol. 176, R101–R109 (2017).
pubmed: 27760790
Cordoba, F. et al. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. Am. J. Transpl. 15, 2825–2836 (2015).
Ristov, J. et al. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and non-depleting anti-CD40 monoclonal antibody. Am. J. Transpl. 18, 2895–2904 (2018).
Kahaly, G. J. et al. A novel anti-Cd40 monoclonal antibody, iscalimab, for control of Graves’ hyperthyroidism - a proof-of-concept trial. J. Clin. Endocrinol. Metab. 105, dgz013 (2020).
pubmed: 31512728
Davies, T. F. & Latif, R. Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies. Expert. Opin. Ther. Targets 19, 835–847 (2015).
pubmed: 25768836
pmcid: 4484771
Gershengorn, M. C. & Neumann, S. Update in TSH receptor agonists and antagonists. J. Clin. Endocrinol. Metab. 97, 4287–4292 (2012).
pubmed: 23019348
pmcid: 3513532
Furszyfer, J., Kurland, L. T., McConahey, W. M. & Elveback, L. R. Graves’ disease in Olmsted county, Minnesota, 1935 through 1967. Mayo Clin. Proc. 45, 636–644 (1970).
pubmed: 5469087
Holm, I. A. et al. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch. Intern. Med. 165, 1606–1611 (2005).
pubmed: 16043678
Phillips, D. I., Barker, D. J., Rees Smith, B., Didcote, S. & Morgan, D. The geographical distribution of thyrotoxicosis in England according to the presence or absence of TSH-receptor antibodies. Clin. Endocrinol. 23, 283–287 (1985).
Cox, S. P., Phillips, D. I. & Osmond, C. Does infection initiate Graves disease? A population based 10 year study. Autoimmunity 4, 43–49 (1989).
pubmed: 2491641
Vanderpump, M. P. et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin. Endocrinol. 43, 55–68 (1995). This paper is the follow-up to the classic epidemiological study of autoimmune thyroid disease in a defined community.
Mostbeck, A. et al. The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990. Eur. J. Nucl. Med. 25, 367–374 (1998).
pubmed: 9553166
Thjodleifsson, B. A study of Graves’ disease in Iceland. Acta Med. Scand. 198, 309–314 (1975).
pubmed: 1242615
Haraldsson, A., Gudmundsson, S. T., Larusson, G. & Sigurdsson, G. Thyrotoxicosis in Iceland 1980–1982. An epidemiological survey. Acta Med. Scand. 217, 253–258 (1985).
pubmed: 3993439
Berglund, J., Christensen, S. B. & Hallengren, B. Total and age-specific incidence of Graves’ thyrotoxicosis, toxic nodular goitre and solitary toxic adenoma in Malmo 1970–1974. J. Intern. Med. 227, 137–141 (1990).
pubmed: 2299305
Lundgren, E. & Borup Christensen, S. Decreasing incidence of thyrotoxicosis in an endemic goitre inland area of Sweden. Clin. Endocrinol. 33, 133–138 (1990).
Winsa, B. et al. Stressful life events and Graves’ disease. Lancet 338, 1475–1479 (1991).
pubmed: 1683917
Berglund, J., Ericsson, U. B. & Hallengren, B. Increased incidence of thyrotoxicosis in Malmo during the years 1988–1990 as compared to the years 1970–1974. J. Intern. Med. 239, 57–62 (1996).
pubmed: 8551201
Abraham-Nordling, M. et al. Incidence of hyperthyroidism in Sweden. Eur. J. Endocrinol. 165, 899–905 (2011).
pubmed: 21908653
Baltisberger, B. L., Minder, C. E. & Burgi, H. Decrease of incidence of toxic nodular goitre in a region of Switzerland after full correction of mild iodine deficiency. Eur. J. Endocrinol. 132, 546–549 (1995).
pubmed: 7749493
Galofre, J. C., Fernandez-Calvet, L., Rios, M. & Garcia-Mayor, R. V. Increased incidence of thyrotoxicosis after iodine supplementation in an iodine sufficient area. J. Endocrinol. Invest. 17, 23–27 (1994).
pubmed: 8006325
Galofre, J. C. et al. Incidence of different forms of thyroid dysfunction and its degrees in an iodine sufficient area. Thyroidology 6, 49–54 (1994).
pubmed: 7536450
Paunkovic, N., Paunkovic, J., Pavlovic, O. & Paunovic, Z. The significant increase in incidence of Graves’ disease in eastern Serbia during the civil war in the former Yugoslavia (1992 to 1995). Thyroid 8, 37–41 (1998).
pubmed: 9492151
Brownlie, B. E. & Wells, J. E. The epidemiology of thyrotoxicosis in New Zealand: incidence and geographical distribution in north Canterbury, 1983–1985. Clin. Endocrinol. 33, 249–259 (1990).
Barbesino, G. Misdiagnosis of Graves’ disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 26, 860–863 (2016).
pubmed: 27043844
Roos, J. C. P., Paulpandian, V. & Murthy, R. Serial TSH-receptor antibody levels to guide the management of thyroid eye disease: the impact of smoking, immunosuppression, radio-iodine, and thyroidectomy. Eye 33, 212–217 (2019).
pubmed: 30401900
Shine, B., Fells, P., Edwards, O. M. & Weetman, A. P. Association between Graves’ ophthalmopathy and smoking. Lancet 335, 1261–1263 (1990).
pubmed: 1971331
Bertelsen, J. B. & Hegedus, L. Cigarette smoking and the thyroid. Thyroid 4, 327–331 (1994).
pubmed: 7833671
Wiersinga, W. M. Smoking and thyroid. Clin. Endocrinol. 79, 145–151 (2013).
Rapoport, B., Alsabeh, R., Aftergood, D. & McLachlan, S. Elephantiasic pretibial myxedema: insight into (and a hypothesis regarding) the pathogenesis of the extrathyroidal manifestations of Graves’ disease. Thyroid 10, 685–692 (2000).
pubmed: 11014313
Sabini, E. et al. Occurrence of Graves’ orbitopathy and Graves’ hyperthyroidism after a trauma to the eye. Eur. Thyroid. J. 7, 51–54 (2018).
pubmed: 29594055
Dutton, J. J. Anatomic considerations in thyroid eye disease. Ophthalmic Plast. Reconstr. Surg. 34 (4S Suppl. 1), 7–12 (2018).
McLachlan, S. M., Nagayama, Y. & Rapoport, B. Insight into Graves’ hyperthyroidism from animal models. Endocr. Rev. 26, 800–832 (2005).
pubmed: 15827111
Nagayama, Y. et al. A novel murine model of Graves’ hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor. J. Immunol. 168, 2789–2794 (2002). This study describes the current classic approach to murine hyperthyroidism, that is, immunization with most of the TSHR ectodomain.
pubmed: 11884447
Kaneda, T. et al. An improved Graves’ disease model established by using in vivo electroporation exhibited long-term immunity to hyperthyroidism in BALB/c mice. Endocrinology 148, 2335–2344 (2007).
pubmed: 17255207
Holthoff, H. P. et al. Prolonged TSH receptor A subunit immunization of female mice leads to a long-term model of Graves’ disease, tachycardia, and cardiac hypertrophy. Endocrinology 156, 1577–1589 (2015).
pubmed: 25562617
Horie, I. et al. Distinct role of T helper type 17 immune response for Graves’ hyperthyroidism in mice with different genetic backgrounds. Autoimmunity 44, 159–165 (2011).
pubmed: 20670120
Nakahara, M. et al. Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice. Endocrinology 153, 2034–2042 (2012).
pubmed: 22334716
Zhao, S. X. et al. Orbital fibrosis in a mouse model of Graves’ disease induced by genetic immunization of thyrotropin receptor cDNA. J. Endocrinol. 210, 369–377 (2011).
pubmed: 21715431
pmcid: 3152291
Schluter, A. et al. Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self-tolerance for a murine model of autoimmune thyroid disease and Graves’ orbitopathy. Clin. Exp. Immunol. 191, 255–267 (2018).
pubmed: 29058307
Milham, S. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy. Teratology 32, 321 (1985). This paper describes methimazole embryopathy, a rare but unpleasant complication of the drug.
pubmed: 4049289
Clementi, M. et al. Methimazole embryopathy: delineation of the phenotype. Am. J. Med. Genet. 83, 43–46 (1999).
pubmed: 10076883
Bahn, R. S. et al. The role of propylthiouracil in the management of Graves’ disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 19, 673–674 (2009).
pubmed: 19583480
Cooper, D. S. & Rivkees, S. A. Putting propylthiouracil in perspective. J. Clin. Endocrinol. Metab. 94, 1881–1882 (2009).
pubmed: 19401361
Andersen, S. L., Olsen, J., Wu, C. S. & Laurberg, P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J. Clin. Endocrinol. Metab. 98, 4373–4381 (2013).
pubmed: 24151287
Seo, G. H., Kim, T. H. & Chung, J. H. Antithyroid drugs and congenital malformations: a nationwide Korean cohort study. Ann. Intern. Med. 168, 405–413 (2018). This paper describes the potential for both propylthiouracil and methimazole to cause congenital defects.
pubmed: 29357398