Graves’ disease (GD) is a common autoimmune thyroid disorder, affecting 20–30 per 100,000 of the population per year. In keeping with other autoimmune diseases, it exhibits a clear female preponderance (F:M 6–7:1) with approximately 3% of women and 0.5% of men developing GD during their lifetime.
GD is a complex genetic condition, with environmental factors precipitating the disease in genetically predisposed individuals who harbor multiple susceptibility alleles. Thyroid-stimulating hormone receptor (TSHR) antibodies are the immunological hallmark of the disease and the key driver for thyrocyte hyperplasia and the resulting hyperthyroidism. Our understanding of the pathogenesis of the condition has developed significantly in recent years, reflecting advances in human genomics, molecular immunology, and the availability of murine models of disease.
Clinical features in GD are widespread, with a myriad of typical symptoms and physical findings at presentation. Frequently reported symptoms include tremor, palpitations, heat intolerance, weight loss, and anxiety. Physical examination may reveal warm, tremulous extremities, atrial fibrillation, signs of thyroid orbitopathy, and a goiter with a bruit. A series of extrathyroidal manifestations can accompany GD at presentation or appear during the course of the disease; these are associated with elevated titers of circulating autoantibodies. The commonest extrathyroidal manifestation is thyroid orbitopathy, which can be sight-threatening and requires a detailed and careful approach to management. Recent developments in our understanding of the pathogenesis of these conditions may lead to the development of novel therapies in coming years.
- Brand OJ, Lowe CE, Heward JM, Franklyn JA, Cooper JD, Todd JA, et al. Association of the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs. Clin Endocrinol. 2007;66(4):508–12.Google Scholar
- Brix TH, Hansen PS, Hegedüs L, Wenzel BE. Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves’ disease: evidence from a twin case-control study. ClinEndocrinol. 2008;69:491–6.Google Scholar
- Chazenbalk GD, Portolano S, Russo D, Hutchison JS, Rapoport B, McLachlan S. Human organ-specific autoimmune disease Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ. J Clin Investig. 1993;92(1):62–74.CrossRefPubMedGoogle Scholar
- Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M, et al. Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620 W allele associates with multiple autoimmune phenotypes. Am J Hum Genet. 2005;76(4):561–71.CrossRefPubMedPubMedCentralGoogle Scholar
- Heward JM, Allahabadia A, Daykin J, Carr-Smith J, Daly A, Armitage M, et al. Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves’ disease: replication using a population case control and family-based study. J Clin Endocrinol Metab. 1998;83(10):3394–7.PubMedGoogle Scholar
- Hollowell JG, Staehling NW, Dana Flanders W, Harry Hannon W, Gunter EW, Spencer CA, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489–99.CrossRefPubMedGoogle Scholar
- Laurberg P, Pedersen KM, 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. 1991;229(5):415–20.CrossRefPubMedGoogle Scholar
- Mitchell AL, Goss L, Mathiopoulou L, Morris M, Vaidya B, Dickinson AJ, Quinn A, Dayan C, McLaren J, Hickey JL, Lazarus JH, Rose GE, Foley P, MacEwen CJ, Perros P. Diagnosis of Graves’ orbitopathy (DiaGO): results of a pilot study to assess the utility of an office tool for practicing endocrinologists. J Clin Endocrinol Metab. 2015;100(3):E458–62.CrossRefPubMedGoogle Scholar
- Smyth D, Cooper JD, Collins JE, Heward JM, Franklyn JA, Howson JMM, et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53(11):3020–3.CrossRefPubMedGoogle Scholar
- Strieder TGA, Tijssen JGP, Wenzel BE, Endert E, Wiersinga WM. Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the thyroid events Amsterdam (THEA) score. Arch Intern Med. 2008;168(15):1657–63.CrossRefPubMedGoogle Scholar