Hashimoto’s Thyroiditis

  • Wilmar M. WiersingaEmail author
Reference work entry
Part of the Endocrinology book series (ENDOCR)


Hashimoto’s thyroiditis is best defined as an organ-specific autoimmune disease, characterized by autoimmune-mediated destruction of the thyroid gland. Diagnostic criteria have changed dramatically since the first description in 1912; they now include the presence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin, hypoechogenicity on thyroid ultrasound, and often but not always hypothyroidism. Distinct pathologic phenotypes are recognized: goitrous and atrophic variants but also an IgG4-related variant, hashitoxicosis, juvenile thyroiditis, and silent or painless thyroiditis. With a prevalence of 10–12% in the general population, it is the most common autoimmune disease. The prevalence is higher in females than in males, increases with advancing age, and is highest in Whites and lowest in Blacks. The incidence of autoimmune hypothyroidism is about 350 cases/100,000/year for women and 60 cases/100,000/year for men in iodine-sufficient regions and 44 (females) and 12 (males) per 100,000 per year in iodine-deficient areas. Breakdown of self-tolerance against thyroid antigens may lead to thyroid autoimmunity. Loss of Treg inhibitory actions and gain of Th17 proinflammatory actions (reflected by a shift to higher values of Th17/Th10 ratio in peripheral blood) play a crucial role in the loss of tolerance against thyroid antigens. Cytotoxic CD8+ T cells directed against TPO and Tg mediate thyroid gland destruction, either by the granule exocytosis pathway or apoptosis (programmed cell death). TPOAb and TgAb may cause antibody-dependent cell-mediated cytotoxicity (ADCC) via complement-mediated lysis of thyrocytes. Hashimoto’s thyroiditis often runs in families as evident from a high sibling risk ratio of 28. Twin studies suggest genes contribute about 73% of the liability to the development of TPOAb and TgAb; environmental factors would thus contribute about 20–30%. Polymorphisms in TSHR, Tg, HLA, CTLA-4, IL2RA, and FOXP3 have all been associated with Hashimoto’s thyroiditis but account for only a small proportion of the heritability. Genome-wide association studies continue to detect novel genetic loci linked to TPOAb. Smoking and moderate alcohol consumption to a certain extent protect against Hashimoto’s thyroiditis. Low selenium or vitamin D intake are presumably related to a higher prevalence of TPOAb, but presently there is no convincing evidence that selenium or vitamin D supplementation may lower TPOAb concentration. Infections may provoke Hashimoto’s thyroiditis, but available epidemiological studies do not support a causative role.


Hashimoto’s thyroiditis History Diagnosis Epidemiology Immunopathogenesis IgG4 Genetic polymorphisms Environment 


  1. Aijan RA, Weetman AP. The pathogenesis of Hashimoto’s thyroiditis: further developments in our understanding. Horm Metab Res. 2015;47:702–10.CrossRefGoogle Scholar
  2. Andersen SL, Olsen J, Wu CS, Laurberg P. Smoking reduces the risk of hypothyroidism and increases the risk of hyperthyroidism: evidence from 450,842 mothers giving birth in Denmark. Clin Endocrinol. 2014;80:307–14.CrossRefGoogle Scholar
  3. Asvold BO, Bjoro T, Nilsen TIL, Vatten LJ. Tobacco smoking and thyroid function: a population-based study. Arch Intern Med. 2007;167:1428–32.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Azizi F. The occurrence of permanent thyroid failure in patients with subclinical postpartum thyroiditis. Eur J Endocrinol. 2005;153:367–71.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Baker Jr JR. Dying (apoptosing?) for a consensus on the Fas pathway in the thyroid. J Clin Endocrinol Metab. 1999;84:2593–5.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Baker JR, Saunders NB, Wartofsky L, Tseng Y-C, Burman KD. Seronegative Hashimoto thyroiditis with thyroid autoantibody localized to the thyroid. Ann Intern Med. 1988;108:26–30.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Ban Y, Tozaki T, Tobe T, Ban Y, Jacobson EM, Concepcion ES, Tomer Y. The regulatory T cell gene FOXP3 and genetic susceptibility to thyroid autoimmunity: an association analysis in Caucasian and Japanese cohorts. J Autoimmun. 2007;28:201–7.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Ban Y, Tozaki T, Taniyama M, Skrabanek L, Nakano Y, Ban Y, Hirano T. Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune thyroid disease in the Japanese population. PLoS ONE. 2012;7:e37501. Scholar
  9. Belin RM, Astor BC, Powe NR, Ladenson PW. Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2004;89:6077–86.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bell PM, Sinnamon DG, Smyth PPA, Drexhage HA, Haire M, Botazzo GF, Atkinson AB. Hyperthyroidism following primary hypothyroidism in association with polyendocrine autoimmunity. Acta Endocrinol. 1985;108:491–7.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bennedbaek FN, Hegedus L. Imaging of the normal and affected thyroid in childhood. Paediatr Adolesc Med. 2007;11:225–69.Google Scholar
  12. Ben-Skowronek I, Szewczyk L, Ciechanek R, Korobowicz E. Interactions of lymphocytes, thyrocytes and fibroblasts in Hashimoto’s thyroiditis: an immunohistochemical and ultrastructural study. Horm Res Paediatr. 2011;76:335–42.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29:76–131.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Bjergved L, Jorgensen T, Perrild H, Carle A, Cerqueira C, Krejbjerg A, Laurberg P, Ovesen L, Bulow Pedersen I, Banke RL, Knudsen N. Predictors of change in serum TSH after iodine fortification: an 11-year follow-up to the DanThyr study. J Clin Endocrinol Metab. 2012;97:4022–9.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Bogner U, Hegedus L, Hansen JM, Finke R, Schleusener H. Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis. Eur J Endocrinol. 1995;132:69–74.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Bossowski A, Moniuszko M, Dabrowska M, Sawicka B, Rusak M, Jeznach M, et al. Lower proportions of CD4+CD25(high) and CD4+FoxP3, but not CD4+CD25+CD127(low)FoxP3+ T cell levels in children with autoimmune thyroid diseases. Autoimmunity. 2013;46:222–30.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Bossowski A, Moniuszko M, Idzkowska E, Grubczak K, Snight P, Bossoska A, Diana T, Kahaly GJ. Decreased proportions of CD4+ IL17+/CD4+CD25+CD127- and CD4+IL17+/CD4+CD25+CD127-FoxP3+ T cells in children with autoimmune thyroid diseases. Autoimmunity. 2016;49:320–8.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Brand OJ, Lowe CE, Heward JM, Franklyn JA, Cooper JD, Todd JA, Gough SC. Association of the interleukin-2 receptor α (IL2Rα)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs. Clin Endocrinol. 2007;66:508–12.Google Scholar
  19. Brix TH, Hegedus L. The complexity of the etiology of autoimmune thyroid disease is gravely underestimated. Thyroid. 2011;12:1289–92.CrossRefGoogle Scholar
  20. Brix TH, Hegedus L. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease. Clin Endocrinol. 2012;76:457–64.CrossRefGoogle Scholar
  21. Brix TH, Kyvik KO, Hegedus L. What is the evidence of genetic factors in the etiology of Graves’ disease? A brief review. Thyroid. 1998;8:627–34.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. Brix TH, Knudsen GPS, Kristiansen M, Kyvik KO, Orstavik KH, Hegedus L. 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. 2005;90:5949–53.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Brix TH, Hansen PS, Hegedus L, Wenzel BE. Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves’ disease: evidence from a twin case-control study. Clin Endocrinol. 2008;69:491–6.CrossRefGoogle Scholar
  25. Bulow Pedersen I, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab. 2002;87:4462–9.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Bulow Pedersen I, Laurberg P, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Rasmussen LB. A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure. Clin Endocrinol. 2005;62:713–20.CrossRefGoogle Scholar
  27. Bulow Pedersen I, Laurberg P, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Rasmussen LB. Lack of association between thyroid antibodies and parity in a population study argues against microchemerism as a trigger of thyroid autoimmunity. Eur J Endocrinol. 2006;154:39–45.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Campbell P, Brix TH, Wilson SG, Ward LC, Hui J, Beilby JP, Hegedus L, Walsh JP. Common genetic variants associated with thyroid function may be risk alleles for Hashimoto’disease and Graves’ disease. Clin Endocrinol. 2015;84:278–83.CrossRefGoogle Scholar
  29. Carlé A, Laurberg P, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Jorgensen T, Pedersen IB. Thyroid peroxidase and thyroglobulin auto-antibodies in patients with newly diagnosed overt hypothyroidism. Autoimmunity. 2006a;39:497–503.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Carlé A, Laurberg P, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Jorgensen T. Epidemiology of subtypes of hypothyroidism in Denmark. Eur J Endocrinol. 2006b;154:21–8.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Jorgensen T, Laurberg P. Thyroid volume in hypothyroidism due to autoimmune disease follows a unimodal distribution: evidence against primary thyroid atrophy and autoimmune thyroiditis being distinct diseases. J Clin Endocrinol Metab. 2009;94:833–9.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Carle A, Bulow Pedersen I, Knudsen N, Perrild H, Ovesen L, Banke Rasmussen L, et al. Smoking cessation is followed by a sharp but transient rise in the incidence of overt autoimmune hypothyroidism – a population-based, case-control study. Clin Endocrinol. 2012a;77:764–72.CrossRefGoogle Scholar
  33. Carle A, Bulow Pedersen I, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, et al. Moderate alcohol consumption may protect against overt autoimmune hypothyroidism: a population-based case-control study. Eur J Endocrinol. 2012b;167:483–90.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Carle A, Bulow Pedersen I, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, et al. Graves’ hyperthyroidism and moderate alcohol consumption: evidence for disease prevention. Clin Endocrinol. 2013;79:111–9.CrossRefGoogle Scholar
  35. Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Laurberg P. Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women. J Clin Endocrinol Metab. 2014;99:2241–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Caturegli P, De Remigis A, Ferlito M, Landek-Salgado MA, Iwama S, Tzou S-C, Ladenson PW. Anatabine ameliorates experimental autoimmune thyroiditis. Endocrinology. 2012;153:4580–7.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A, Iwama S. Hashimoto thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Thyroid. 2013;23:142–50.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13:391–7.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Cerqueira C, Knudsen N, Ovesen L, Laurberg P, Perrild H, Rasmussen LB, Jorgensen T. Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt? Eur J Epidemiol. 2011;26:629–35.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Chiovato L, Vitti P, Santini F, Lopez G, Mammoli C, Bassi P, et al. Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab. 1990;71:40–5.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Chiovato L, Bassi P, Santini F, et al. Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis. J Clin Endocrinol Metab. 1993;77:1700–5.PubMedPubMedCentralGoogle Scholar
  42. Cho BY, Kim WB, Chung JH, Yi KH, Shong YK, Lee HK, Koh CS. High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non-goitrous autoimmune thyroiditis. Clin Endocrinol. 1995;43:465–71.CrossRefGoogle Scholar
  43. Choi YM, Kim WG, Kim TY, Bae SJ, Kim HK, Jang EK, et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in pre-menopausal women. Thyroid. 2014;24:655–61.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res. 2010;62:1312–8.CrossRefGoogle Scholar
  45. Davies TF. Ord-Hashimoto’s disease: renaming a common disorder – again. Thyroid. 2003;13:317.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Davies TF, Amino N. A new classification for human autoimmune thyroid disease. Thyroid. 1993;3:331–3.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Dayan CM, Daniels G. Chronic autoimmune thyroiditis. N Engl J Med. 1996;335:99–107.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13:3–126.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Demirbilek H, Kandemir N, Gonc EN, Ozon A, Alikasifoglu A, Yordam N. Hashimoto’s thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease. J Pediatr Endocrinol Metab. 2007;20:1199–205.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Deshpande V, Huck A, Ooi E, Stone JH, Faquin WC, Nielsen GP. Fibrosing variant of Hashimoto thyroiditis is an IgG4-related disease. J Clin Pathol. 2012a;65:725–8.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012b;25:1181–92.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Diana T, Li Y, Olivo PD, Lackner KJ, Kim H, Kanitz M, Kahaly GJ. Analytical performance and validation of a bioassay for thyroid-blocking antibodies. Thyroid. 2016;26:734–40.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Doniach D. Hashimoto’s thyroiditis and primary myxoedema viewed as separate entities. Eur J Clin Investig. 1981;11:245–7.CrossRefGoogle Scholar
  54. Doniach D, Bottazzo GF, Russell RCG. Goitrous autoimmune thyroiditis (Hashimoto’s disease). Clin Endocrinol Metab. 1979;8:63–80.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Effraimidis G, Wiersinga WM. Autoimmune thyroid disease: old and new players. Eur J Endocrinol. 2014;170:R241–52.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Effraimidis G, Tijssen JGP, Wiersinga WM. Discontinuation of smoking increases the risk for developing thyroid peroxidase antibodies and/or thyroglobulin antibodies: a prospective study. J Clin Endocrinol Metab. 2009;94:1324–8.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Effraimidis G, Strieder TGA, Tijssen JGP, Wiersinga WM. Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study. Eur J Endocrinol. 2011a;164:107–13.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Effraimidis G, Tijssen JGP, Strieder TGA, Wiersinga WM. No causal relationship between Yersinia enterocolitica infection and autoimmune thyroid disease: evidence from a propsective study. Clin Exp Immunol. 2011b;165:38–43.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol. 2012a;167:43–8.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Effraimidis G, Tijssen JG, Brosschot JF, Wiersinga WM. Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study. Psychoneuroendocrinology. 2012b;37:1191–8.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Effraimidis G, Tijssen JG, Wiersinga WM. Alcohol consumption as a risk factor for autoimmune thyroid disease: a prospective study. Eur Thyroid J. 2012c;1:99–104.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Ehlers M, Thiel A, Bernecker C, Porwol D, Papewalis C, Willenberg HS, et al. Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 2012;97:1347–54.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Endo K, Kasagi K, Konishi J, Ikekubo K, Okuno T, Takeda Y, Mori T, Torizuka K. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves’ disease and Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 1978;46:734–9.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Endocrine Society. Endocrine facts and figures: thyroid. 1st ed. 2015. Accessed 2 Aug 2016
  65. Evans M, Sanders J, Tagami T, Sanders P, Young S, Roberts E, et al. Monoclonal antibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol. 2010;73:404–12.CrossRefGoogle Scholar
  66. Fatourechi V, McConahey WM, Woolner LB. Hyperthyroidism associated with histologic Hashimoto’s thyroiditis. Mayo Clin Proc. 1971;46:682–9.PubMedPubMedCentralGoogle Scholar
  67. Feng M, Li H, Chen S-F, Li W-F, Zhang F-B. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 2013;43:318–26.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Figueroa-Vega N, Alfonso-Perez M, Benedicto I, Sanchez-Madrid F, Gonzalez-Amaro R, Marazuela M. Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 2010;95:953–62.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Fiore E, Latrofa F, Vitti P. Iodine, thyroid autoimmunity and cancer. Eur Thyroid J. 2015;4:26–35.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Friedriech N, Schwarz S, Thonack J, John U, Wallaschofski H, Volzke H. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity. 2008;41:174–80.CrossRefGoogle Scholar
  71. Furszyfer J, Kurland LT, Woolner LB, Elveback LR, McConahey WM. Hashimoto’s thyroiditis in Olmsted County, Minnesota, 1935 through 1967. Mayo Clin Proc. 1970;45:586–96.PubMedPubMedCentralGoogle Scholar
  72. Furszyfer J, Kurland LT, McConahey WM, Woolner LB, Elveback LR. Epidemiologic aspects of Hashimoto’s thyroiditis and Graves’ disease in Rochester, Minnesota (1935–1967), with special reference to temporal trends. Metabolism. 1972;21:197–204.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Galofre JC, Garcia-Mayor RV, Fluiters E, Fernandez-Calvet L, Rego A, Paramo C, Andrade MA. Incidence of different forms of thyroid dysfunction and its degree in an iodine sufficient area. Thyroidology. 1994;6:49–54.PubMedPubMedCentralGoogle Scholar
  74. Garcia-Garcia E, Vazquez-Lopez MA, Garcia-Fuentes E, Rodriquez-Sanchez FI, Munoz FJ, Bonillo-Perales A, Soriquer F. Iodine intake and prevalence of thyroid autoimmunity and autoimmune thyroiditis in children and adolescents aged between 1 and 16 years. Eur J Endocrinol. 2012;167:387–92.PubMedCrossRefPubMedCentralGoogle Scholar
  75. Geenen V, Bodart G, Henry S, Michaux H, Dardenne O, Chatlet-Renard C, Martens H, Hober D. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity. Front Neurosci. 2013;7:187. Scholar
  76. Glick AB, Wodzinski A, Fu P, Levine AD, Wald DN. Impairment of regulatory T-cell function in autoimmune thyroid disease. Thyroid. 2013;23:871–7.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Guo J, Jaume JC, Rapoport B, McLachlan SM. Recombinant thyroid peroxidase-specific Fab converted to immunoglobulin G (IgG) molecules: evidence for thyroid cell damage by IgG1, but not IgG4, autoantibodies. J Clin Endocrinol Metab. 1997;82:925–31.PubMedPubMedCentralGoogle Scholar
  78. Hansen PS, Brix TH, Iachine I, Kyvik KO, Hegedus L. The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins. Eur J Endocrinol. 2006;154:29–38.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Hashimoto H. Zur Kentniss der Lymphomatosen Veranderung der Schilddruse (Struma Lymphomatosa). Arch Klin Chir. 1912;97:219–48.Google Scholar
  80. Hayashi Y, Tamai H, Fukuta S, Hirota Y, Katayama S, Kuma K, et al. A long term clinical, immunological, and histological follow-up study of patients with goitrous lymphocytic thyroiditis. J Clin Endocrinol Metab. 1985;61:1172–8.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Hedley AJ, Young RE, Jones SJ, Alexander WD, Bewsher PD. Antithyroid drugs in the treatment of hyperthyroidism of Graves’ disease: long-term follow-up of 434 patients. Clin Endocrinol. 1989;31:209–18.CrossRefGoogle Scholar
  82. Hegedus L. Decreased thyroid gland volume in alcoholic cirrhosis of the liver. J Clin Endocrinol Metab. 1984;58:930–3.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Hegedus L, Bonnema SJ, Winther KH. Selenium in the treatment of thyroid diseases: an element in search of the relevant indication? Eur Thyroid J. 2016;5:149–51.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Hollowell J, Staehling N, Flanders W, Hannon W, Gunter E, Spencer C, Braverman L. Serum TSH, T4 and thyroid antibodies in the United States population (1988–1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–99.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Huang CY, Chang TY, Chu CC, Lo FS, Ting WH, Lin CH, Wu YL, Chu SY, Chang SC, Chen WF, et al. The HLA-B gene and Hashimoto disease in Han children: a case-control and family-based study. Tissue Antigens. 2012;80:431–6.PubMedCrossRefPubMedCentralGoogle Scholar
  86. Inoue N, Watanabe M, Ishido N, Katsumata Y, Kagawa T, Hidaka Y, Iwatani Y. The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol. 2014;178:262–9.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Irvine WJ, Gray RS, Morris PJ, Ting A. HLA in primary atrophic hypothyroidism and Hashimoto goitre. J Clin Lab Immunol. 1978;1:193–5.PubMedPubMedCentralGoogle Scholar
  88. Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 2007;28:85–98.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Jensen EA, Petersen PH, Blaabjerg O, Hansen PS, Brix TH, Hegedus L. Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb). Clin Chem Lab Med. 2006;44:991–8.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Jokisch F, Kleinlein I, Haller B, Seehaus T, Fuerst H, Kremer M. A small subgroup of Hashimoto’s thyroiditis is associated with IgG4-related disease. Virchows Arch. 2016;468:321–7.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Kaczmarek E, Lacka A, Jarmalowska-Jurczyszyn D, Sidor A, Majewski P. Changes of B and T lymphocytes and selected apoptosis markers in Hashimoto’s thyroiditis. J Clin Pathol. 2011;64:626–30.PubMedCrossRefPubMedCentralGoogle Scholar
  92. Kahaly GJ, Diana T, Glang J, Kanitz M, Pitz S, Konig J. Thyroid stimulating antibodies are highly prevalent in Hashimoto’s thyroiditis and associated orbitopathy. J Clin Endocrinol Metab. 2016;101:1998–2004.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Kaloumenou I, Mastorakos G, Alevizaki M, Duntas LH, Mantzou E, Ladopoulos C, Antoniou A, Chiotis D, Papassotiriou I, Chrousos GP, Dacou-Voutetakis C. Thyroid autoimmunity in schoolchildren in an area with long-standing iodine sufficiency: correlation with gender, pubertal stage, and maternal thyroid autoimmunity. Thyroid. 2008;18:747–54.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Katz SM, Vickery AL. The fibrous variant of Hashimoto’s thyroiditis. Hum Pathol. 1974;5:161–70.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Kohrle J. Selenium and thyroid. Curr Opin Endocrinol Diabetes Obes. 2015;5:392–401.CrossRefGoogle Scholar
  96. Konishi J, Iida Y, Endo K, Misaki T, Nohara Y, Matsuura N, et al. Inhibition of thyrotropin-induced adenosine 3′5′-monophosphate increase by immunoglobulins from patients with primary myxedema. J Clin Endocrinol Metab. 1983;57:544–9.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Konturek A, Barczynski M, Wierzchowski W, Stopa M, Nowak W. Coexistence of papillary thyroid cancer with Hashimoto’s thyroiditis. Langenbeck’s Arch Surg. 2013;398:389–94.CrossRefGoogle Scholar
  98. Kotani T, Aratake Y, Hirai K, Fukazawa Y, Sato H, Ohtaki S. Apoptosis in thyroid tissue from patients with Hashimoto’s thyroiditis. Autoimmunity. 1995;20:231–6.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Kristensen B, Hegedus L, Madsen HO, Smith TJ, Nielsen CH. Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto’s thyroiditis. Clin Exp Immunol. 2014;180:58–69.CrossRefGoogle Scholar
  100. Kristensen B, Hegedus L, Lundy SK, Brimnes MK, Smith TJ, Nielsen CH. Characterization of regulatory B cells in Graves’ disease and Hashimoto’s thyroiditis. PLoS ONE. 2015;10:e0127949. Scholar
  101. Kucharska AM, Gorska E, Wasik M, Demkow U. Expression of cytotoxic T lymphocyte antigen-4 in T cells from children with Hashimoto’s thyroiditis. Adv Exp Med Biol. 2013;756:163–8.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Latrofa F, Fiore E, Rago T, Antonangeli L, Montanelli L, Ricci D, et al. Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin. J Clin Endocrinol Metab. 2013;98:E1768–74.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Laurberg P. The Danish investigation of iodine intake and thyroid disease: DanThyr – 20 years of iodine monitoring and research. Thyroid Int. 2015; issue 2, pp. 3–26.Google Scholar
  104. Laurberg P, Bulow Pedersen I, Pedersen KM, Vestergaard H. Low incidence rate of overt hypothyroidism compared with hyperthyroidism in an area with moderately low iodine intake. Thyroid. 1999;9:33–8.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Laurberg P, Andersen S, Bulow Pedersen I, Knudsen N, Carlé A. Prevention of autoimmune hypothyroidism by modifying iodine intake and the use of tobacco and alcohol is manoeuvring between Scylla and Charibdis. Hormones. 2011;12:30–8.CrossRefGoogle Scholar
  106. Lee HJ, Li CW, Hammerstad SS, Stefan M, Tomer Y. Immunogenetics of autoimmune thyroid disease: a comprehensive review. J Autoimmun. 2015;64:82–90.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Leese GP, Flynn RV, Jung RT, Macdonald TM, Murphy MJ, Morris AD. Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: the Thyroid Epidemiology Audit and Research Study (TEARS). Clin Endocrinol. 2008;68:311–6.Google Scholar
  108. Leskela S, Rodriguez-Munoz A, de la Fuente H, Figueroa-Vega N, Bonay P, Martin P, et al. Plasmacytoid dendritic cells in patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 2013;98:2822–33.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Li Y, Bai Y, Liu Z, Ozaki T, Taniguchi E, Mori I, et al. Immunohistochemistry of IgG4 can help subclassify Hashimoto’s autoimmune thyroiditis. Pathol Int. 2009;59:636–41.PubMedCrossRefPubMedCentralGoogle Scholar
  110. Li Y, Nishihara E, Hirokawa M, Taniguchi E, Miyauchi A, Kakudo K. Distinct clinical, serological, and sonographic characteristics of Hashimoto’s thyroiditis based with and without IgG4-positive plasma cells. J Clin Endocrinol Metab. 2010;95:1309–17.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Li M, Sun H, Liu S, Yu J, Li Q, Liu P, Shen H, Sun D. CD40 C/T-1 polymorphism plays different roles in Graves’ disease and Hashimoto’s thyroiditis: a meta-analysis. Endocr J. 2012;59:1041–50.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Li D, Cai W, Gu R, Zhang Y, Zhang H, Tang K, et al. Th17 cells play a role in the pathogenesis of Hashimoto’s thyroiditis in patients. Clin Immunol. 2013a;149:411–20.PubMedCrossRefPubMedCentralGoogle Scholar
  113. Li Y, Kim J, Diana T, Klasen R, Olivo PD, Kahaly GJ. A novel bioassay for anti-thyrotropin receptor antibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol. 2013b;173:390–7.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Liu L, Wu HQ, Wang Q, Zhu YF, Zhang W, Guan LJ, Zhang JA. Association between thyroid stimulating hormone receptor intron polymorphisms and autoimmune thyroid disease in a Chinese Han population. Endocr J. 2012;59:717–23.PubMedCrossRefPubMedCentralGoogle Scholar
  115. Liu Y, Tang X, Tian J, Zhu C, Peng H, Rui K, et al. Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto’s thyroiditis. Int J Mol Sci. 2014;15:21674–86.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Livolsi VA. The pathology of autoimmune thyroid disease: a review. Thyroid. 1994;4:333–9.PubMedCrossRefPubMedCentralGoogle Scholar
  117. Lombardi AF, Fiore E, Tonacchera M, Antonangeli L, Rago T, Frigeri M, et al. The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later. J Clin Endocrinol Metab. 2013;98:1031–9.CrossRefGoogle Scholar
  118. Mao J, Pop VJ, Bath SC, Vader HL, Redman CWG, Rayman MP. Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency. Eur J Nutr. 2016;55:55–61.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Marazuela M, Garcia-Lopez MA, Figueroa-Vega N, et al. Regulatory T cells in human autoimmune thyroid disease. J Clin Endocrinol Metab. 2006;91:3639–46.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A. Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab. 1991;72:209–13.PubMedCrossRefPubMedCentralGoogle Scholar
  121. Mariotti S. Chronic autoimmune thyroiditis. In: Monaco F, editor. Thyroid diseases. Boca Raton: CRC Press; 2012. p. 77–96.CrossRefGoogle Scholar
  122. Marique L, Van RV, Gerard AC, Craps J, Senou M, Marbaix E, et al. The expression of dual oxidase, thyroid peroxidase, and caveolin-1 differs according to the type of immune response (Th1/Th2) involved in thyroid autoimmune disorders. J Clin Endocrinol Metab. 2014;99:1722–32.PubMedCrossRefPubMedCentralGoogle Scholar
  123. Masi AT, Sartwell PE, Hartmann WH, Shulman LE. Hashimoto’s disease. A study of the consistency of its histopathological diagnosis. J Chronic Dis. 1965;18:23–33.PubMedCrossRefPubMedCentralGoogle Scholar
  124. Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J Nucl Med. 2015;18:222–7.PubMedPubMedCentralGoogle Scholar
  125. McGrogan A, Seaman HE, Wright JW, de Vries CS. The incidence of autoimmune thyroid disease: a systematic review. Clin Endocrinol. 2008;69:687–96.CrossRefGoogle Scholar
  126. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating antibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23:14–24.PubMedPubMedCentralCrossRefGoogle Scholar
  127. McLachlan SM, Rapoport B. Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity. Endocr Rev. 2014;35:59–105.PubMedCrossRefPubMedCentralGoogle Scholar
  128. McLeod DS, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42:252–65.PubMedCrossRefPubMedCentralGoogle Scholar
  129. McLeod DS, Caturegli P, Cooper DS, Matos PG, Hutfless S. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA. 2014;311:1563–5.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Medici M, Porcu E, Pistis G, Teumer A, Brown SJ, Jensen RA, et al. Identification of novel genetic loci associated with thyroid peroxidase antibodies and clinical thyroid disease. PLoS Genet. 2014;10:e1004123. Scholar
  131. Meng S, He ST, Jiang WJ, Xiao L, Li DF, Xu J, et al. Genetic susceptibility to autoimmune thyroid diseases in a Chinese Han population: role of vitamin D receptor gene polymorphisms. Ann Endocrinol (Paris). 2015;76:684–9.CrossRefGoogle Scholar
  132. Meyer G, Donner H, Herwig J, Bohles H, Usadel KH, Badenhoop K. Screening for an AIRE-1 mutation in patients with Addison’s disease, type 1 diabetes, Graves’ disease and Hashimoto’s thyroiditis as well as APECED syndrome. Clin Endocrinol. 2001;54:335–8.CrossRefGoogle Scholar
  133. Minamino H, Inaba H, Ariyasu H, Furuta H, Nishi M, Yoshimasu T, et al. A novel immunopathological association of IgG4-RD and vasculitis with Hashimoto’s thyroiditis. Endocrinol Diabetes Metab Case Rep. 2016. Scholar
  134. Mizukami Y, Michigishi T, Hashimoto T, et al. Silent thyroiditis: a histological and immunohistochemical study. Hum Pathol. 1988;19:423–31.PubMedCrossRefPubMedCentralGoogle Scholar
  135. Mizukami Y, Michigishi T, Kawato M, Sato T, Nonomura A, Hashimoto T, Matsubara F. Thyroid function and histologic correlations in 601 cases. Hum Pathol. 1992;23:980–8.PubMedCrossRefPubMedCentralGoogle Scholar
  136. Mizukami Y, Michigishi T, Nonomura A, et al. Postpartum thyroiditis: a clinical, histological and immunopathological study of 15 cases. Am J Clin Pathol. 1993;100:200–5.PubMedCrossRefPubMedCentralGoogle Scholar
  137. Muixi L, Carrascal M, Alvarez I, Daura X, Marti M, Armengol MP, et al. Thyroglobulin peptides associate in vivo to HLA-DR in autoimmune thyroid glands. J Immunol. 2008;181:795–807.PubMedCrossRefGoogle Scholar
  138. Nabhan ZM, Kreher NC, Eugster EA. Hashitoxicosis in children: clinical features and natural history. J Pediatr. 2005;146:533–6.PubMedCrossRefPubMedCentralGoogle Scholar
  139. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92:1263–8.PubMedCrossRefPubMedCentralGoogle Scholar
  140. Nithiyananthan R, Howard JM, Allahabadia A, Barnett AH, Franklyn JA, Cough SCL. A heterozygous deletion of the autoimmune regulator (AIRE1) gen, autoimmune thyroid disease, and type 1 diabetes: no evidence for association. J Clin Endocrinol Metab. 2000;85:1320–2.PubMedPubMedCentralGoogle Scholar
  141. Nystrom E, Bengtsson C, Lindquist O, Noppa H, Lindstedt G, Lundberg PA. Thyroid disease and high concentration of serum thyrotrophin in a population sample of women. A 4-year follow-up. Acta Med Scand. 1981;210:39–46.PubMedCrossRefPubMedCentralGoogle Scholar
  142. Oryoji D, Ueda S, Yamamoto K, Yoshimura Noh J, Okamura K, Noda M, et al. Identification of a Hashimoto thyroiditis susceptibility locus via a genome wide comparison with Graves’ disease. J Clin Endocrinol Metab. 2015;100:E319–24.PubMedCrossRefPubMedCentralGoogle Scholar
  143. Owen CJ, Eden JA, Jennings CE, Wilson V, Cheetham TD, Pearce SH. Genetic association studies of the FOXP3 gene in Graves’ disease and autoimmune Addison’s disease in the United Kingdom population. J Mol Endocrinol. 2006;37:97–104.PubMedCrossRefPubMedCentralGoogle Scholar
  144. Patel H, Mansuri MS, Singh M, Begum R, Shastri M, Misra A. Association of cytotoxic T-lymphocyte antigen 4 (CTLA4) and thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS ONE. 2016;11:e0149441. Scholar
  145. Pellegrini FP, Marinoni M, Frangione V, Tedeschi A, Gandini V, Ciglia F, et al. Down syndrome, autoimmunity and T regulatory cells. Clin Exp Immunol. 2012;169:238–43.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Popko K, Osinska I, Kucharska A, Demkow U. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study. J Pediatr Endocrinol Metab. 2015;28:789–92.PubMedCrossRefPubMedCentralGoogle Scholar
  147. Prummel MF, Laurberg P. Interferon-alpha and autoimmune thyroid disease. Thyroid. 2003;13:547–51.PubMedCrossRefPubMedCentralGoogle Scholar
  148. Prummel MF, Wiersinga WM. Autoimmune thyroid diseases. In: Gill RG, Harmon JT, Maclaren NK, editors. Immunologically mediated endocrine diseases. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 373–96.Google Scholar
  149. Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Rolinski J. Immune disorders in Hashimoto’s thyroiditis: what do we know so far? J Immunol Res. 2015. Scholar
  150. Radetti G. Clinical aspects of Hashimoto’s thyroiditis. Endocr Dev. 2014;26:158–70.PubMedCrossRefPubMedCentralGoogle Scholar
  151. Radetti G, Gottardi E, Bona G, Corrias A, Salardi S, Loche S, et al. The natural history of euthyroid Hashimoto’s thyroiditis in children. J Pediatr. 2006;149:827–32.PubMedCrossRefPubMedCentralGoogle Scholar
  152. Rasmussen LB, Ovesen L, Bulow I, Jorgensen A, Knudsen N, Laurberg P, Perrild H. Dietary iodine intake and urinary iodine excretion in a Danish population: effect of geography, supplements and food choice. Br J Nutr. 2002;87:61–9.PubMedCrossRefPubMedCentralGoogle Scholar
  153. Rasmussen LB, Carlé A, Jorgensen T, Knudsen N, Laurberg P, Pedersen IB, Perrild H, Vejbjerg P, Ovesen L. Iodine intake before and after mandatory iodization in Denmark: results from the Danish investigation of iodine intake and thyroid diseases (DanThyr) study. Br J Nutr. 2008;100:166–73.PubMedCrossRefPubMedCentralGoogle Scholar
  154. Rebuffat SA, Kammoun-Krichen M, Charfeddine I, Ayadi H, Bougacha-Elleuch N, Peraldi-Roux S. Il-1β and TSH disturb thyroid epithelium integrity in autoimmune thyroid disease. Immunobiology. 2013;218:285–91.PubMedCrossRefPubMedCentralGoogle Scholar
  155. Rodriguez-Munoz A, Martinez-Hernandez R, Ramos-Levi AM, Serrano-Somavilla A, Gonzalez-Amaro R, Sanchez-Madrid F, de la Fuente H, Marazuela M. Circulating microvesicles regulate Treg and Th17 differentiation in human autoimmune thyroid disorders. J Clin Endocrinol Metab. 2015;100:E1531–9.PubMedCrossRefPubMedCentralGoogle Scholar
  156. Roitt IM, Doniach D, Campbell PN, Hudson RV. Autoantibodies in Hashimoto’s diseases (lymphadenoid goiter). Lancet. 1956;ii:820–2.CrossRefGoogle Scholar
  157. Santos LR, Duraes C, Mendes A, Prazeres H, Alvelos MI, Moreira CS, et al. A polymorphism in the promotor region of the selenoprotein S gene (SEPS1) contributes to Hashimoto’s thyroiditis susceptibility. J Clin Endocrinol Metab. 2014;99:E719–23.PubMedCrossRefPubMedCentralGoogle Scholar
  158. Shan Z, Chen L, Lian X, Liu C, Shi B, Shi L, et al. Iodine status and prevalence of thyroid disorders after introduction of mandatory universal salt iodization for 16 years in China: a cross-sectional study in 10 cities. Thyroid. 2016;26:1125–30.PubMedCrossRefPubMedCentralGoogle Scholar
  159. Shmuely H, Shimon I, Gitter LA. Helicobacter pylori infection in women with Hashimoto thyroiditis: a case-control study. Medicine. 2016;95:e4074. Scholar
  160. Simmonds MJ. GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis. Nat Rev Endocrinol. 2013;9:277–87.PubMedCrossRefPubMedCentralGoogle Scholar
  161. Simmonds MJ, Kavvoura FK, Brand OJ, Newby PR, Jackson LE, Hargreaves CE, Franklyn JA, Gough SC. Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: an association study and meta-analysis. J Clin Endocrinol Metab. 2014;99:E127–31.PubMedCrossRefPubMedCentralGoogle Scholar
  162. Smith TJ, Hegedus L. Graves’ disease. N Engl J Med. 2016;375:1552–65.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Stagnaro-Green A, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Negro R. High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy. J Clin Endocrinol Metab. 2011;96:652–7.PubMedCrossRefPubMedCentralGoogle Scholar
  164. Stefan M, Wei C, Lombardi A, Li CW, Concepcion ES. Inabnet 3rd WB et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc Natl Acad Sci U S A. 2014;111:12562–7.PubMedPubMedCentralCrossRefGoogle Scholar
  165. Strieder TGA, Prummel MF, JGP T, Endert E, Wiersinga WM. Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patient with autoimmune thyroid disease. Clin Endocrinol. 2003a;59:396–401.CrossRefGoogle Scholar
  166. Strieder TGA, Wenzel BE, Prummel MF, Tijssen JGP, Wiersinga WM. Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease. Clin Exp Immunol. 2003b;132:278–82.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 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;168:1657–63.CrossRefPubMedGoogle Scholar
  168. Sundbeck G, Lundberg PA, Lindstedt G, Ingenburg R, Eden S. Incidence and prevalence of thyroid disease in elderly women: results from the longitudinal population study of elderly people in Gothenburg, Sweden. Age Ageing. 1991;20:291–8.PubMedCrossRefPubMedCentralGoogle Scholar
  169. Takasu N, Yamada T, Katakura M, Yamauchi K, Shimizu Y, Ishizuki Y. Evidence for thyrotropin (TSH)-blocking activity in goitrous Hashimoto’s thyroiditis with assays measuring inhibition of TSH receptor binding and TSH-stimulated thyroid adenosine 3′,5′-monophosphate responses/cell growth by immunoglobulins. J Clin Endocrinol Metab. 1987;64:239–45.PubMedCrossRefPubMedCentralGoogle Scholar
  170. Tamai H, Kasagi K, Takaichi Y, Takamatsu J, Komaki G, Matsubayashi S, et al. Development of spontaneous hypothyroidism in patients with Graves’ disease treated with antithyroid drugs: clinical, immunological, and histological findings in 26 patients. J Clin Endocrinol Metab. 1989;69:49–53.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Tasli F, Ozkok G, Argon A, Ersoz D, Yagci A, Uslu A, et al. The role of IgG4(+) plasma cells in the association of Hashimoto’s thyroiditis with papillary carcinoma. APMIS. 2014;122:1259–65.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006;354:2783–93.PubMedCrossRefPubMedCentralGoogle Scholar
  173. Teng X, Shan Z, Chen Y, Lai Y, Yu J, Shan L, et al. More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels. Eur J Endocrinol. 2011;164:943–50.PubMedCrossRefGoogle Scholar
  174. Ting WH, Chien MN, Lo FS, Wang CH, Huang CY, Lin CL, et al. Association of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene polymorphisms with autoimmune thyroid disease in children and adults: case-control study. PLoS ONE. 2016;11:e0154394. Scholar
  175. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol. 1977;7:481–93.CrossRefGoogle Scholar
  176. Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, et al. Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis. J Clin Endocrinol Metab. 2014;99:E379–83.PubMedCrossRefPubMedCentralGoogle Scholar
  177. van Belle TL, Gysemans C, Mathieu C. Vitamin D in autoimmune, infectious and allergic diseases: a vital player? Best Pract Res Clin Endocrinol Metab. 2011;25:617–32.PubMedCrossRefPubMedCentralGoogle Scholar
  178. Vanderpump MPJ. The epidemiology of thyroid disease. Br Med Bull. 2011;99:39–51.PubMedCrossRefPubMedCentralGoogle Scholar
  179. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol. 1995;43:55–68.CrossRefGoogle Scholar
  180. Vejbjerg P, Knudsen N, Perrild H, Laurberg P, Carlé A, Pedersen IB, Rasmussen LB, Ovesen L, Jorgensen T. Lower prevalence of mild hypothyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme. Clin Endocrinol. 2009;71:440–5.CrossRefGoogle Scholar
  181. Vickery AL, Hamblin Jr E. Struma lymphomatosa (Hashimoto’s thyroiditis): observations on repeated biopsies in sixteen patients. N Engl J Med. 1961;264:226–9.PubMedCrossRefPubMedCentralGoogle Scholar
  182. Villanueva R, Greenberg DA, Davies TF, Tomer Y. Sibling recurrence risk in autoimmune thyroid disease. Thyroid. 2003;13:761–4.PubMedCrossRefPubMedCentralGoogle Scholar
  183. Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V. Parity and the risk of autoimmune thyroid disease: a community-based study. J Clin Endocrinol Metab. 2005;90:5309–12.PubMedCrossRefPubMedCentralGoogle Scholar
  184. Walsh JP, Bremmer AP, Feddema P, Leedman PJ, Brown SJ, O’Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010;85:1095–104.CrossRefGoogle Scholar
  185. Walsh JP, Berry J, Liu S, Panicker V, Dayan CM, Brix TH, Hegedus L, Hou P, Shi B, Morahan G. The clinical presentation of autoimmune thyroid disease in men is associated with IL12B genotype. Clin Endocrinol. 2011;74:508–12.CrossRefGoogle Scholar
  186. Wang J, Lv S, Chen G, Gao C, He J, Zhong H, et al. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrition. 2015;7:2485–98.Google Scholar
  187. Wasniewska M, Corrias A, Salerno M, Lombardo F, Aversa T, Mussa A, et al. Outcomes of children with Hashitoxicosis. Horm Res Paediatr. 2012a;77:36–40.PubMedCrossRefPubMedCentralGoogle Scholar
  188. Wasniewska M, Corrias A, Salerno M, Mussa A, Capalbo D, Messina MF, Aversa T, Bombaci S, De Luca F, Valenzise M. Thyroid function patterns at Hashimoto’s thyroiditis presentation in childhood and adolescence are mainly conditioned by patient’s age. Horm Res Paediatr. 2012b;78:232–6.PubMedCrossRefPubMedCentralGoogle Scholar
  189. Weetman AP. Autoimmune thyroid disease: propagation and progression. Eur J Endocrinol. 2003;148:1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  190. Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol. 2010;6:311–8.PubMedCrossRefPubMedCentralGoogle Scholar
  191. Weetman AP. Autoimmune thyroid disease. Chapter 18. In: Jameson LJ, et al., editors. Endocrinology: adult and pediatric. 7th ed. Philadelphia: Elsevier/Saunders; 2016. p. 1423–36.CrossRefGoogle Scholar
  192. Wichman J, Winther KH, Bonnema SJ, Hegedus L. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid. 2016. [Epub ahead of print].
  193. Wiersinga WM. Smoking and thyroid. Clin Endocrinol. 2013;79:145–51.CrossRefGoogle Scholar
  194. Wiersinga WM. Thyroid autoimmunity. Endocr Dev. 2014;26:139–57.PubMedCrossRefPubMedCentralGoogle Scholar
  195. Wiersinga WM. Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab. 2016;31:213–22.CrossRefGoogle Scholar
  196. Williams ED, Doniach I. The post-mortem incidence of focal thyroiditis. J Pathol Bacteriol. 1962;83:255–64.PubMedCrossRefPubMedCentralGoogle Scholar
  197. Winther KH, Watt T, Bjorner JB, Cramon P, Feldt-Rasmussen U, Gluud C, et al. The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial. Trials. 2014;15:115.PubMedPubMedCentralCrossRefGoogle Scholar
  198. Winther KH, Wichman JE, Bonnema SJ, Hegedus L, Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis. Endocrine. 2016. [Epub ahead of print].
  199. Wood LC, Ingbar SH. Hypothyroidism as a late sequela in patients with Graves’ disease treated with antithyroid agents. J Clin Invest. 1979;64:1429–36.PubMedPubMedCentralCrossRefGoogle Scholar
  200. Wu Q, Rayman MP, Lv H, Schomburg L, Cui B, Gao C, et al. Low population selenium status is associated with increased prevalence of thyroid disease. J Clin Endocrinol Metab. 2015;100:4037–47.PubMedCrossRefPubMedCentralGoogle Scholar
  201. Xu C, Wu F, Mao C, Wang X, Zheng T, Bu L et al. Excess iodine promotes apoptosis of thyroid follicular epithelial cells by inducing autophagy suppression and is associated with Hashimoto thyroiditis disease. J Autoimmun 2016; [E-pub ahead of print].
  202. Xue H, Yang Y, Zhang Y, Song S, Zhang L, Ma L, et al. Macrophage migration inhibitory factor interacting with Th17 cells may be involved in the pathogenesis of autoimmune damage in Hashimoto’s thyroiditis. Mediat Inflamm. 2015a. Scholar
  203. Xue H, Yu X, Ma L, Song S, Li Y, Zhang L, et al. The possible role of CD4+CD25highFoxp3+/CD4+IL-17A+ cell imbalance in the autoimmunity of patients with Hashimoto thyroiditis. Endocrine. 2015b;50:665–73.PubMedCrossRefPubMedCentralGoogle Scholar
  204. Yasmeh J, Farpour F, Rizzo V, Kheradnam S, Sachmechi I. Hashimoto’s thyroiditis not associated with vitamin D deficiency. Endocr Pract. 2016. [E-pub ahead of print].
  205. Zaletel K, Gaberscek S, Pirnat E, Krhin B, Hojker S. Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization. Croat Med J. 2011;52:615–21.PubMedPubMedCentralCrossRefGoogle Scholar
  206. Zha B, Huang X, Lin J, Liu J, Hou Y, Wu G. Distribution of lymphocyte subpopulations in thyroid glands of human autoimmune thyroid disease. J Clin Lab Anal. 2014;28:249–54.PubMedCrossRefPubMedCentralGoogle Scholar
  207. Zhang J, Zhao L, Gao Y, Liu M, Li T, Huang Y, et al. A classification of Hashimoto’s thyroiditis based on immunohistochemistry for IgG4 and IgG. Thyroid. 2014;24:364–70.PubMedCrossRefPubMedCentralGoogle Scholar
  208. Zophel K, Saller B, Wunderlich G, Gruning T, Koch R, Wilde J, et al. Autoantibodies to thyroperoxidase (TPOAb) in a large population of euthyroid subjects: implications for the definition of TPOAb reference intervals. Clin Lab. 2003;49:591–600.PubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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