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Diagnosis and Endocrine Management of Graves’ Disease

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Thyroid Eye Disease

Abstract

Graves’ disease (GD) is the most common cause of hyperthyroidism in the United States. GD occurs more often in women and has a population prevalence of 1–2 %. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues such as orbit and skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. The hyperthyroidism of GD is treated by reducing thyroid hormone synthesis with the use of antithyroid drugs, or by reducing the amount of thyroid tissue with radioiodine treatment or near-total thyroidectomy.

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References

  1. Brent GA. Clinical practice. Graves’ disease. N Engl J Med. 2008;358(24):2594–605.

    Article  CAS  PubMed  Google Scholar 

  2. Vanderpump MP, Tunbridge WM, French GM. The incidence of thyroid disorders in the community; a twenty year follow-up. Clin Endocrinol. 1995;43:55–68.

    Article  CAS  Google Scholar 

  3. Pearce SHS. Graves’ disease. In: Weetman AP, editor. Autoimmune diseases in endocrinology. Humana: Totowa; 2008. p. 117–35.

    Chapter  Google Scholar 

  4. Dittmar M, Libich C, Brenzel T, Kahaly GJ. Increased familial clustering of autoimmune thyroid diseases. Horm Metab Res. 2011;43:200–4.

    Article  CAS  PubMed  Google Scholar 

  5. Dultz G, Matheis N, Dittmar M, Bender K, Kahaly GJ. CTLA-4 CT60 polymorphism in thyroid and polyglandular autoimmunity. Horm Metab Res. 2009;41(6):426–9.

    Article  CAS  PubMed  Google Scholar 

  6. Teufel A, Weinmann A, Kahaly GJ, Centner C, Piendl A, Wörns M, Lohse AW, Galle PR, Kanzler S. Concurrent autoimmune diseases in patients with autoimmune hepatitis. Clin Gastroenterol. 2010;44(3):208–13.

    Article  CAS  Google Scholar 

  7. Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M, Chatterjee KV, Lazarus JH, Pearce SH, Vaidya B, Gough SC, Franklyn JA. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123(2):183.e1–9.

    Article  Google Scholar 

  8. Vaidya B, Kendall-Taylor P, Pearce SHS. The genetics of autoimmune thyroid disease. J Clin Endocrinol Metab. 2002;87:5385–97.

    Article  CAS  PubMed  Google Scholar 

  9. Brix TH, Kyvik KO, 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. 2001;86:930–4.

    CAS  PubMed  Google Scholar 

  10. Holm IA, Manson JE, Michels KB, Alexander EK, Willet WC, Utiger RD. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch Intern Med. 2005;165:1606–11.

    Article  PubMed  Google Scholar 

  11. Weetman AP. Determinants of autoimmune thyroid disease. Nat Immunol. 2001;2:769–70.

    Article  CAS  PubMed  Google Scholar 

  12. Lazarus J, Marino M. Orbit-thyroid relationship. In: Wiersinga WM, Kahaly GJ, editors. Graves’ orbitopathy—a multidisciplinary approach—questions and answers. 2nd revised ed. Basel: Karger; 2010. p. 26–32.

    Google Scholar 

  13. Kahaly GJ. The thyrocyte-fibrocyte link: closing the loop in the pathogenesis of Graves’ disease? J Clin Endocrinol Metab. 2010;95(1):62–5.

    Article  CAS  PubMed  Google Scholar 

  14. Bahn RS. Graves’ opthalmopathy. N Engl J Med. 2010;362(8):726–38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Orgiazzi J, Ludgate M. Pathogenesis. In: Wiersinga WM, Kahaly GJ, editors. Graves’ orbitopathy—a multidisciplinary approach—questions and answers. 2nd revised ed. Basel: Karger; 2010. p. 40–56.

    Google Scholar 

  16. Kahaly GJ, Shimony O, Gellman YN, Lytton SD, Eshkar-Sebban L, Rosenblum N, Refaeli E, Kassem S, Ilany J, Naor D. Regulatory T-cells in graves’ orbitopathy: baseline findings and immunomodulation by anti-T lymphocyte globulin. J Clin Endocrinol Metab. 2011;96(2):422–9.

    Article  CAS  PubMed  Google Scholar 

  17. Bartalena L, Tanda ML. Clinical practice. Graves’ ophthalmopathy. N Engl J Med. 2009;360(10):994–1001.

    Article  CAS  PubMed  Google Scholar 

  18. Boelaert K, Torlinska B, Holder RL, Franklyn JA. Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. J Clin Endocrinol Metab. 2010;95(6):2715–26.

    Article  CAS  PubMed  Google Scholar 

  19. Biondi B, Kahaly GJ. Cardiovascular involvement in patients with different causes of hyperthyroidism. Nat Rev Endocrinol. 2010;6(8):431–43.

    Article  PubMed  Google Scholar 

  20. Kahaly GJ. Imaging in thyroid-associated orbitopathy. Eur J Endocrinol. 2001;145(2):107–18.

    Article  CAS  PubMed  Google Scholar 

  21. Hales IB, Rundle FF. Ocular changes in Graves’ disease. A long-term follow-up study. Q J Med. 1960;29:113–26.

    CAS  PubMed  Google Scholar 

  22. Ponto KA, Kahaly GJ. Quality of life in patients suffering from thyroid orbitopathy. Pediatr Endocrinol Rev. 2010;7 Suppl 2:245–9.

    PubMed  Google Scholar 

  23. Werner SC. Modification of the classification of the eye changes in Graves’ disease. Am J Ophthalmol. 1977;83(5):725–7.

    Article  CAS  PubMed  Google Scholar 

  24. Dickinson AJ. Clinical manifestation. In: Wiersinga WM, Kahaly GJ, editors. Graves’ orbitopathy—a multidisciplinary approach—questions and answers. 2nd revised ed. Basel: Karger; 2010. p. 1–25.

    Google Scholar 

  25. Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid. 2008;18(3):333–46.

    Article  PubMed  Google Scholar 

  26. Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol. 1989;73(8):639–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J Clin Endocrinol Metab. 2010;95(5):2123–31.

    Article  CAS  PubMed  Google Scholar 

  28. Bartalena L, Martino E, Marcocci C, Bogazzi F, Panicucci M, Velluzzi F, Loviselli A, Pinchera A. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest. 1989;12(10):733–7.

    Article  CAS  PubMed  Google Scholar 

  29. Bartalena L, Marcocci C, Tanda ML, Manetti L, Dell’Unto E, Bartolomei MP, Nardi M, Martino E, Pinchera A. Cigarette smoking and treatment outcomes in Graves’ ophthalmopathy. Ann Intern Med. 1998;129(8):632–5.

    Article  CAS  PubMed  Google Scholar 

  30. Winsa B, Adami HO, Bergström R, Gamstedt A, Dahlberg PA, Adamson U, Jansson R, Karlsson A. Stressful life events and Graves’ disease. Lancet. 1991;338(8781):1475–9.

    Article  CAS  PubMed  Google Scholar 

  31. Yoshiuchi K, Kumano H, Nomura S, Yoshimura H, Ito K, Kanaji Y, Kuboki T, Suematsu H. Psychosocial factors influencing the short-term outcome of antithyroid drug therapy in Graves’ disease. Psychosom Med. 1998;60(5):592–6.

    Article  CAS  PubMed  Google Scholar 

  32. Fatourechi V, Bartley GB, Eghbali-Fatourechi GZ, Powell CC, Ahmed DD, Garrity JA. Graves’ dermopathy and acropachy are markers of severe Graves’ ophthalmopathy. Thyroid. 2003;13(12):1141–4.

    Article  PubMed  Google Scholar 

  33. Gerding MN, van der Meer JW, Broenink M, Bakker O, Wiersinga WM, Prummel MF. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 2000;52(3):267–71.

    Article  CAS  Google Scholar 

  34. Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves’ disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002;87(2):438–46.

    CAS  PubMed  Google Scholar 

  35. Grebe SK, Kahaly GJ. Laboratory testing in hyperthyroidism. Am J Med. 2012;125(9):S2.

    Article  PubMed  Google Scholar 

  36. Sipos JA, Kahaly GJ. Imaging of thyrotoxicosis. Am J Med. 2012;125(9):S1–2.

    Article  PubMed  Google Scholar 

  37. Lytton SD, Li Y, Olivo PD, Kohn LD, Kahaly GJ. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins. Clin Exp Immunol. 2010;162(3):438–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Kamijo K, Murayama H, Uzu T, Togashi K, Kahaly GJ. A novel bioreporter assay for thyrotropin receptor antibodies using a chimeric thyrotropin receptor (mc4) is more useful in differentiation of Graves’ disease from painless thyroiditis than conventional thyrotropin-stimulating antibody assay using porcine thyroid cells. Thyroid. 2010;20(8):851–6.

    Article  CAS  PubMed  Google Scholar 

  39. Lytton SD, Kahaly GJ. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun Rev. 2010;10(2):116–22.

    Article  CAS  PubMed  Google Scholar 

  40. Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, Heckmann C, Esser J, Morgenthaler NG. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006;91(9):3464–70.

    Article  CAS  PubMed  Google Scholar 

  41. Mourits MP. Diagnosis and differential diagnosis of graves’ orbitopathy. In: Wiersinga WM, Kahaly GJ, editors. Graves’ orbitopathy—a multidisciplinary approach—questions and answers. 2nd revised ed. Basel: Karger; 2010. p. 66–76.

    Google Scholar 

  42. Ponto KA, Zang S, Kahaly GJ. The tale of radioiodine and Graves’ orbitopathy. Thyroid. 2010;20(7):785–93.

    Article  CAS  PubMed  Google Scholar 

  43. Marcocci C, Pinchera A. Thyroid treatment. In: Wiersinga WM, Kahaly GJ, editors. Graves’ orbitopathy—a multidisciplinary approach—questions and answers. 2nd revised edition. Basel: Karger; 2010. p. 100–110.

    Google Scholar 

  44. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21(6):593–646.

    Article  Google Scholar 

  45. Kahaly GJ, Bartalena L, Hegedus L. The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective. Thyroid. 2011;21(6):585–91.

    Article  PubMed  Google Scholar 

  46. Pearce EN, Hennessey JV, McDermott MT. New American Thyroid Association and American Association of Clinical Endocrinologists guidelines for thyrotoxicosis and other forms of hyperthyroidism: significant progress for the clinician and a guide to future research. Thyroid. 2011;21(6):573–6.

    Article  PubMed  Google Scholar 

  47. Bartalena L. Diagnosis and management of Graves’ disease: a global overview. Nat Rev Endocrinol. 2013. doi:10.1038/nrendo.2013.193.

    PubMed  Google Scholar 

  48. Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905–17.

    Article  CAS  PubMed  Google Scholar 

  49. Cooper DS. Antithyroid drugs in the management of patients with Graves’ disease: an evidence-based approach to therapeutic controversies. J Clin Endocrinol Metab. 2003;88(8):3474–81.

    Article  CAS  PubMed  Google Scholar 

  50. Emiliano AB, Governale L, Parks M, Cooper DS. Shifts in propylthiouracil and methimazole prescribing practices: antithyroid drug use in the United States from 1991 to 2008. J Clin Endocrinol Metab. 2010;95(5):2227–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W, American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081–125.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Rivkees SA, Szarfman A. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab. 2010;95(7):3260–7.

    Article  CAS  PubMed  Google Scholar 

  53. Rivkees SA. Pediatric Graves’ disease: controversies in management. Horm Res Paediatr. 2010;74(5):305–11.

    Article  CAS  PubMed  Google Scholar 

  54. Rivkees SA, Mattison DR. Ending propylthiouracil-induced liver failure in children. N Engl J Med. 2009;360(15):1574–5.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to George J. Kahaly M.D., Ph.D. .

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Kahaly, G.J. (2015). Diagnosis and Endocrine Management of Graves’ Disease. In: Douglas, R., McCoy, A., Gupta, S. (eds) Thyroid Eye Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1746-4_1

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  • DOI: https://doi.org/10.1007/978-1-4939-1746-4_1

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