Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Environmental factors and autoimmune thyroiditis

Abstract

Autoimmune thyroiditis, of which Hashimoto thyroiditis represents the most frequent form, is an inflammatory state of the thyroid gland that results from the interaction between genetic variants that promote susceptibility and environmental factors. High iodine intake, selenium deficiency, pollutants such as tobacco smoke, infectious diseases such as chronic hepatitis C, and certain drugs are implicated in the development of autoimmune thyroiditis, primarily in genetically predisposed people. Long-term iodine exposure leads to increased iodination of thyroglobulin, which increases its antigenicity and initiates the autoimmune process in genetically susceptible individuals. Selenium deficiency decreases the activity of selenoproteins, including glutathione peroxidases, which can lead to raised concentrations of hydrogen peroxide and thus promote inflammation and disease. Such environmental pollutants as smoke, polychlorinated biphenyls, solvents and metals have been implicated in the autoimmune process and inflammation. Environmental factors have not yet, however, been sufficiently investigated to clarify their roles in pathogenesis, and there is a need to assess their effects on development of the autoimmune process and the mechanisms of their interactions with susceptibility genes.

Key Points

  • Excess iodine intake is associated with a raised annual incidence of autoimmune thyroiditis in various parts of the world, probably owing to increased thyroglobulin antigenicity, although the exact mechanism is not yet fully understood

  • Selenium deficiency is thought to be involved in the pathogenesis of autoimmune thyroiditis and to lengthen its duration and exacerbate its severity; these effects may occur via reduced activity of the selenoprotein glutathione peroxidase, which leads to increased production of hydrogen peroxide

  • Environmental pollutants, such as polychlorinated biphenyls, metals and solvents, probably play a part in the development of autoimmune thyroiditis in genetically susceptible individuals, although research is urgently needed to clarify their precise roles

  • Inflammation induced by viral infections or by pollutants can modify cellular-signaling mediators and influence T-cell activity and cytokine-secretion profiles

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: The evolution of autoimmune thyroiditis.

References

  1. Davies TF and Amino N (1993) A new classification for human autoimmune thyroid disease. Thyroid 3: 331–333

    CAS  Article  Google Scholar 

  2. Pearce E et al. (2003) Thyroiditis. N Engl J Med 348: 2646–2655

    Article  Google Scholar 

  3. Weetman AP and McGregor AM (1994) Autoimmune thyroid disease: further developments in our understanding. Endocr Rev 15: 788–830

    CAS  PubMed  Google Scholar 

  4. Ban Y and Tomer Y (2005) Genetic susceptibility in thyroid autoimmunity. Pediatr Endocrinol Rev 3: 20–32

    PubMed  Google Scholar 

  5. Tomer Y and Davies TF (2003) Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocr Rev 24: 694–717

    CAS  Article  Google Scholar 

  6. Tamai H et al. (1985) Immunogenetics of Hashimoto's and Graves' disease. J Clin Endocrinol Metab 60: 62–66

    CAS  Article  Google Scholar 

  7. Caturegli P et al. (2007) Autoimmune thyroid diseases. Curr Opin Rheumatol 19: 44–48

    Article  Google Scholar 

  8. Jacobson EM and Tomer Y (2007) The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun 28: 85–98

    CAS  Article  Google Scholar 

  9. Mysliewiec J et al. (2007) Serum CD40/CD40L system in Graves' disease and Hashimoto's thyroiditis related to soluble Fas, FasL and humoral markers of autoimmune response. Immunol Invest 36: 247–257

    Article  Google Scholar 

  10. Hollowell JG et al. (2002) 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 87: 489–499

    CAS  Article  Google Scholar 

  11. Tunbridge WM et al. (1997) The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol 7: 481–499

    Article  Google Scholar 

  12. Vanderpump MP et al. (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 43: 55–68

    CAS  Article  Google Scholar 

  13. Vanderpump MP et al. (1996) The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid 6: 155–160

    CAS  PubMed  Google Scholar 

  14. O'Leary PC et al. (2006) Investigations on thyroid hormones and antibodies based on a community health service: the Busselton thyroid study. Clin Endocrinol (Oxf) 64: 97–104

    CAS  Article  Google Scholar 

  15. Huber G et al. (2002) Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve and thyroid antibodies. J Clin Endocrinol Metab 87: 3221–3226

    CAS  Article  Google Scholar 

  16. Canaris GJ et al. (2000) The Colorado thyroid disease prevalence study. Arch Intern Med 160: 526–534

    CAS  Article  Google Scholar 

  17. Hansen PS et al. (2006) The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins. Eur J Endocrinol 154: 29–38

    CAS  Article  Google Scholar 

  18. Takasu N et al. (1990) Test for recovery from hypothyroidism during thyroxine therapy in Hashimoto's thyroiditis. Lancet 336: 1084–1086

    CAS  Article  Google Scholar 

  19. Friedrich N et al. (2008) Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity 41: 174–180

    Article  Google Scholar 

  20. Weetman AP (2000) Chronic autoimmune thyroiditis. In Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text, edn 8, 721–732 (Eds Braverman LE and Utiger RD) Philadelphia: Lippincott, Williams & Wilkins

    Google Scholar 

  21. Obermayer-Straub P and Manns MP (1998) Autoimmune polyglandular syndromes. Baillieres Clin Gastroenterol 12: 293–315

    CAS  Article  Google Scholar 

  22. Fattori B et al. (2008) Possible association between thyroid autoimmunity and Meniere's disease. Clin Exp Immunnol 152: 28–32

    CAS  Article  Google Scholar 

  23. Prummel MF et al. (2004) The environment and autoimmune thyroid diseases. Eur J Endocrinol 150: 605–618

    CAS  Article  Google Scholar 

  24. Davies TF (2007) Really significant genes for autoimmune thyroid disease do not exist—so how can we predict disease? Thyroid 17: 1027–1029

    CAS  Article  Google Scholar 

  25. Laurberg P et al. (2006) The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur J Endocrinol 155: 219–228

    CAS  Article  Google Scholar 

  26. Carayanniotis G (2007) Recognition of thyroglobulin by T cells: the role of iodine. Thyroid 17: 963–973

    CAS  Article  Google Scholar 

  27. Pedersen IB et al. (2007) An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: a prospective population study. J Clin Endocrinol Metab 92: 3122–3127

    CAS  Article  Google Scholar 

  28. Tsatsoulis A et al. (1999) Thyroid autoimmunity is associated with higher urinary iodine concentrations in an iodine-deficient area of Northwestern Greece. Thyroid 9: 279–283

    CAS  Article  Google Scholar 

  29. Teng W et al. (2006) Effect of iodine intake on thyroid diseases in China. N Engl J Med 354: 2783–2793

    CAS  Article  Google Scholar 

  30. Camargo RY et al. (2006) Prevalence of chronic autoimmune thyroiditis in the urban area neighboring a petrochemical complex and a control area in Sao Paulo, Brazil. Clinics 61: 307–312

    Article  Google Scholar 

  31. Köhrle J et al. (2005) Selenium, the thyroid and the endocrine system. Endocr Rev 26: 944–984

    Article  Google Scholar 

  32. Duntas LH (2006) The role of selenium in thyroid autoimmunity and cancer. Thyroid 16: 455–460

    CAS  Article  Google Scholar 

  33. Contempre B et al. (2004) Thiocyanate induces cell necrosis and fibrosis in selenium- and iodine-deficient rat thyroids: a potential experimental model for myxedematous endemic cretinism in central Africa. Endocrinology 145: 994–1002

    CAS  Article  Google Scholar 

  34. Sato A et al. (2008) Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice. J Pharmacol Exp Ther 352: 380–388

    Article  Google Scholar 

  35. Schmutzler C et al. (2007) Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3. Biol Chem 388: 1053–1059

    CAS  Article  Google Scholar 

  36. Kondrashova A et al. (2008) Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments. J Clin Endocrinol Metab 93: 729–734

    CAS  Article  Google Scholar 

  37. Davies TF (2008) Infection and autoimmune thyroid disease. J Clin Endocrinol Metab 93: 674–676

    CAS  Article  Google Scholar 

  38. Tronko MD et al. (2006) Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: results from the first screening cycle (1998–2000). J Clin Endocrinol Metab 91: 4344–4351

    CAS  Article  Google Scholar 

  39. Belin RM et al. (2004) 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 89: 6077–6086

    CAS  Article  Google Scholar 

  40. Vestergaard P (2002) Smoking and thyroid disorders—a meta-analysis. Eur J Endocrinol 146: 153–161

    CAS  Article  Google Scholar 

  41. Erdogan MF (2003) Thiocyanate overload and thyroid disease. Biofactors 19: 107–111

    CAS  Article  Google Scholar 

  42. Ellingsen DG et al. (1997) Cadmium and selenium in blood and urine related to smoking habits and previous exposure to mercury vapour. J Appl Toxicol 17: 337–343

    CAS  Article  Google Scholar 

  43. Baccarelli A (1999) Occupational agents and endocrine function: an update of the experimental and human evidence [Italian]. Med Lav 90: 650–670

    CAS  PubMed  Google Scholar 

  44. Langer P et al. (1998) Increased thyroid volume and prevalence of thyroid disorders in an area heavily polluted by polychlorinated biphenyls. Eur J Endocrinol 139: 402–409

    CAS  Article  Google Scholar 

  45. Langer P et al. (2007) Thyroid ultrasound volume, structure and function after long-term high exposure of large population to polychlorinated biphenyls, pesticides and dioxin. Chemosphere 69: 118–127

    CAS  Article  Google Scholar 

  46. Schmutzler C et al. (2007) Endocrine disruptors and the thyroid gland—a combined in vitro and in vivo analysis of potential new biomakers. Environ Health Perspect 115: 77–83

    Article  Google Scholar 

  47. Boas M et al. (2006) Environmental chemicals and thyroid function. Eur J Endocrinol 154: 599–611

    CAS  Article  Google Scholar 

  48. Rueda FL et al. (1999) Atypical thyroiditis in Huelva, Spain. Endocr Pract 5: 109–113

    CAS  Article  Google Scholar 

  49. Mizokami T et al. (2004) Stress and thyroid autoimmunity. Thyroid 14: 1047–1055

    CAS  Article  Google Scholar 

  50. Tsatsoulis A (2006) The role of stress in the clinical expression of thyroid autoimmunity. Ann NY Acad Sci 1088: 382–395

    CAS  Article  Google Scholar 

  51. Schuppert F et al. (1997) Patients treated with interferon-alpha, interferon-beta, and interleukin-2 have a different thyroid autoantibody pattern from patients than patients suffering from endogenous autoimmune thyroid disease. Thyroid 7: 837–842

    CAS  Article  Google Scholar 

  52. Rotondi M et al. (2007) Role of chemokines in endocrine autoimmune diseases. Endocr Rev 28: 492–520

    CAS  Article  Google Scholar 

  53. Strieder TG et al. (2003) Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease. Clin Exp Immunol 132: 278–282

    CAS  Article  Google Scholar 

  54. Testa A et al. (2006) Prevalence of HCV antibodies in autoimmune thyroid disease. Eur Rev Med Pharmacol Sci 10: 183–186

    CAS  PubMed  Google Scholar 

  55. Frossi B et al. (2008) Oxidative microenvironment exerts an opposite regulatory effect on cytokine production by TH1 and TH2 cells. Mol Immunol 45: 58–64

    CAS  Article  Google Scholar 

  56. Gärtner R et al. (2002) Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab 87: 1687–1691

    Article  Google Scholar 

  57. Duntas LH et al. (2003) Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur J Endocrinol 148: 389–393

    CAS  Article  Google Scholar 

  58. Turker O et al. (2006) Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol 190: 151–156

    CAS  Article  Google Scholar 

  59. Mazokopakis E et al. (2007) Effects of 12 month treatment with l-selenomethionine on serum anti-TPO levels in patients with Hashimoto's thyroiditis. Thyroid 17: 609–612

    CAS  Article  Google Scholar 

  60. Negro R et al. (2007) The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantobodies. J Clin Endocrinol Metab 92: 1263–1268

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Duntas, L. Environmental factors and autoimmune thyroiditis. Nat Rev Endocrinol 4, 454–460 (2008). https://doi.org/10.1038/ncpendmet0896

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0896

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing