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Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2005 Jan;20(1):9–17. doi: 10.1007/BF02893034

Autoimmune thyroid disorders—An update

Manorama Swain 1,, Truptirekha Swain 2,3, Binoy Kumar Mohanty 4
PMCID: PMC3454167  PMID: 23105486

Abstract

Background: Autoimmune thyroid disease (AITD), a common organ specific autoimmune disorder is seen mostly in women between 30–50 yrs of age. Thyroid autoimmunity can cause several forms of thyroiditis ranging from hypothyroidism (Hashimoto’s thyroiditis) to hyperthyroidism (Graves’Disease). Prevalence rate of autoimmune mediated hypothyroidism is about 0.8 per 100 and 95% among them are women. Graves’ disease is about one tenth as common as hypothyroidism and tends to occur more in younger individuals. Both these disorders share many immunologic features and the disease may progress from one state to other as the autoimmune process changes. Genetic, environmental and endogenous factors are responsible for initiation of thyroid autoimmunity. At present the only confirmed genetic factor lies in HLA complex (HLA DR-3) and the T cell regulatory gene (CTLA 4). A number of environmental factors like viral infection, smoking, stress & iodine intake are associated with the disease progression. The development of antibodies to thyroid peroxidase (TPO) thyroglobulin (TG) and Thyroid stimulating hormone receptor (TSH R) is the main hallmark of AITD. Circulating T Lymphocytes are increased in AITD and thyroid gland is infiltrated with CD4+ and CD8+ T Cells. Wide varieties of cytokines are produced by infiltrated immune cells, which mediate cytotoxicity leading to thyroid cell destruction. Circulating antibodies to TPO and TG are measured by immunofluorescense, hemagglutination, ELISA & RIA. TSHR antibodies of Graves’ disease can be measured in bioassays or indirectly in assays that detect antibody binding to the receptor.

Key Words: Autoimmune thyroid disease, thyroid peroxidase antibodies, Thyroglobulin antibodies, and TSHR antibodies

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References

  • 1.Canaris G.J., Manowitz N.R., Mayor G.M., Ridgway E.C. The Colorado thyroid disease prevalence studies. Arch. Int. Med. 2000;160:526–534. doi: 10.1001/archinte.160.4.526. [DOI] [PubMed] [Google Scholar]
  • 2.Larry J. J., Weetman A.P. Disorders of the Thyroid gland. In: Brunwald E., Fauci A., editors. Harrison’s Principles of Internal Medicine. 15th Edn. USA: Mc Graw-Hill Publication; 2001. pp. 2060–2084. [Google Scholar]
  • 3.Marcocci C., Chiovato L. Thyroid-directed antibodies. In: Braverman LE, Utiger RD, editors. The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. pp. 414–31. [Google Scholar]
  • 4.Weetman A.P., McGregor A.M. Autoimmune thyroid disease: Further developments in our understanding. Endocr. Rev. 1994;15:788–830. doi: 10.1210/er.15.6.788. [DOI] [PubMed] [Google Scholar]
  • 5.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. 2001;86:930–934. doi: 10.1210/jc.86.2.930. [DOI] [PubMed] [Google Scholar]
  • 6.Ban Y., Tomer Y. The contribution of immune regulatory and thyroid specific genes to the etiology of Graves’ and Hashimoto’s disease. Autoimmunity. 2003;36(6–7):367–79. doi: 10.1080/08916930310001603037. [DOI] [PubMed] [Google Scholar]
  • 7.Weetman A.P. Endocrinology. In: Lechler RI, Warrens A., editors. Handbook of HLA and Disease. 2nd Edn. London: Academic Press; 2000. [Google Scholar]
  • 8.Onuma H., Ota M., Sugenoya A., Inoko H. Association of HLA-DPB-0501 with early-onset Graves’ disease in Japanese. Hum Immunol. 1994;39:195–201. doi: 10.1016/0198-8859(94)90260-7. [DOI] [PubMed] [Google Scholar]
  • 9.Tandon N., Mehera N.K., Taneja V., Vaidya M.C., Kochupillai N. HLA antigens in Asian Indian Patients with Graves’ disease. Clin Endocrinol (oxf) 1990;33:21–26. doi: 10.1111/j.1365-2265.1990.tb00461.x. [DOI] [PubMed] [Google Scholar]
  • 10.Omar M.A., Hammond M.G., Desai R.K., Motala A.A., Aboo N., Seedat M.A. HLA class I and II antigens in South African blacks with Graves’ disease. Clin Immunopathol. 1990;54:98–102. doi: 10.1016/0090-1229(90)90009-F. [DOI] [PubMed] [Google Scholar]
  • 11.Furugaki K., Shirasawa S, Ishikawa N, Ito K, Kobota S, Kuma K, Tamai H, Akamizu T, Hiratani H, Tanaka M, Sasazuki T. Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese. J. Hum. Genet. 2004;49(3):166–8. doi: 10.1007/s10038-003-0120-5. [DOI] [PubMed] [Google Scholar]
  • 12.Ueda H., Howson J.M., Esposito L. Association of the T-Cell regulatory gene CTLA-4 with susceptibility to autoimmune disease. Nature, May 29. 2003;423(6939):506–11. doi: 10.1038/nature01621. [DOI] [PubMed] [Google Scholar]
  • 13.Wang Pei-Win, Liu Rue-Tsuan, Hank Juo Suh-Hang, et al. Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves’ Hyperthyroidism after Antithyroid withdrawal. The J. Clin. Endocrinol. Metab. 2004;8(No. 1):169–173. doi: 10.1210/jc.2003-030854. [DOI] [PubMed] [Google Scholar]
  • 14.Noel R.R., Raphael B., Burek C.L. Iodine: an environmental trigger of thyroiditis. Autoimmun. Rev. Feb. 2002;1(1–2):97–103. doi: 10.1016/s1568-9972(01)00016-7. [DOI] [PubMed] [Google Scholar]
  • 15.Tomer Y., Davies T.F. Infection, thyroid disease and autoimmunity. Endocr. Rev. 1993;14:107–120. doi: 10.1210/er.14.1.107. [DOI] [PubMed] [Google Scholar]
  • 16.Jaspan J.B., Sullivan K., Garry R.F. The interaction of a type A retroviral particle and class II human leukocyte antigen susceptibility genes in the pathogenesis of Graves’ disease. J. Clin. Endocrinol. Metab. 1996;81:2271–2279. doi: 10.1210/jc.81.6.2271. [DOI] [PubMed] [Google Scholar]
  • 17.Bartalena L., Bogazzi F., Tanda M.L. Cigarete smoking and the thyroid. Eur. J. Immunol. 1995;133:507–512. doi: 10.1530/eje.0.1330507. [DOI] [PubMed] [Google Scholar]
  • 18.Strieder T.G., Prummel M.F. Risk factors for and prevalence of thyroid disorders in a cross sectional study among healthy female relatives of patients with autoimmune thyroid disorder. Clin Endocrinol (OXF) Sep. 2003;59(3):396–401. doi: 10.1046/j.1365-2265.2003.01862.x. [DOI] [PubMed] [Google Scholar]
  • 19.Prasad KV, Prabhakar BS. Apoptosis and autoimmune disorders. Autoimmunity. 2003;36(6–7):323–30. doi: 10.1080/08916930310001604207. [DOI] [PubMed] [Google Scholar]
  • 20.McLachian S.M., Rapport B. The molecular biology of thyroid peroxidase: Cloning, expression and role as autoantigen in autoimmune thyroid disease. Endo. Rev. 1992;13:192–206. doi: 10.1210/er.13.2.192. [DOI] [PubMed] [Google Scholar]
  • 21.McIntosh R., Waston P, Weetman A. Somatic hypermutation in autoimmune thyroid disease. Immunol. Rev. 1998;162:219–231. doi: 10.1111/j.1600-065X.1998.tb01444.x. [DOI] [PubMed] [Google Scholar]
  • 22.Silva L.M., Chavej J., Canalli M.H., Zanetti C.R. Determination of IgG sub classes and avidity of antithyroid peroxidase antibodies in patients with subclinical hypothyroidism—a comparison with patient with overt hypothyroidism. Horm Res. 2003;59(3):118–24. doi: 10.1159/000069069. [DOI] [PubMed] [Google Scholar]
  • 23.malthiery Y., Lissitzky S. Primary structure of human Thyroglobulin deduced from the sequence of its 8848-base complementary DNA. Eur. J. Biochem. 1987;105:491–498. doi: 10.1111/j.1432-1033.1987.tb11466.x. [DOI] [PubMed] [Google Scholar]
  • 24.Canayanniotis G., Rao V.P. Searching for pathogenic epitopes in Thyroglobulin: Parameters and caveats. Immunol. Today. 1997;18:83–88. doi: 10.1016/S0167-5699(96)10073-6. [DOI] [PubMed] [Google Scholar]
  • 25.Brown T.R., Zhao G., Palmer K.C. Thyroid injury, autoantigen availability and the initiation of autoimmune thyroiditis. Autoimmunity. 1997;27:1–12. [PubMed] [Google Scholar]
  • 26.Collison K.S., Banga J.P., Barnett P.S. Autoantibody stimulation of the human thyrotropin receptor: Regulation of adenlyate cyclase activity, Thyroglobulin and thyroid peroxidase mRNA levels in primary cultures of Graves’ thyroid tissue. Clin. Exp. Immunol. 1991;86:61–5. doi: 10.1111/j.1365-2249.1991.tb05774.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Prabhakar B.S., Fan J.L., Seetharamaiah G.S. Thyrotropin-receptor-mediated diseases: A paradigm for receptor autoimmunity. Immunol. Today. 1997;18:437–442. doi: 10.1016/S0167-5699(97)01089-X. [DOI] [PubMed] [Google Scholar]
  • 28.Ajjan R.A., Findlay C., Metcalfe R.A. The modulation of the human sodium iodine symporter activity by Graves’ disease sera. J. Clin. Endocrinol. Metab. 1998;83:1217–1221. doi: 10.1210/jc.83.4.1217. [DOI] [PubMed] [Google Scholar]
  • 29.Stassi G, Maria R. Autoimmune thyroid disease: new models of cell death in autoimmunity. Nat. Rev. Immunol. 2002;2(3):195–204. doi: 10.1038/nri750. [DOI] [PubMed] [Google Scholar]
  • 30.Smallridge R.C. Postpartum thyroid dysunction: A frequently undiagnosed endocrine disorder. Endocrinologist. 1996;6:44–50. [Google Scholar]
  • 31.Nilsson M., Husmark J., Bjokman U., Ericson L.E. Cytokines and thyroid epithelial integrity: Interleukin-1 a induces dissociation of the junctional complex and paracellular leakage in filter-cultured human hydrolytes. J. Clin. Endocrinol. Metab. 1998;83:945–952. doi: 10.1210/jc.83.3.945. [DOI] [PubMed] [Google Scholar]
  • 32.Weetman A.P., Ajjan R.A., Watson P.F. Cytokines and Graves’ disease. Baillieres Clin Endocrinol Metab. 1997;11:481–497. doi: 10.1016/S0950-351X(97)80708-2. [DOI] [PubMed] [Google Scholar]
  • 33.Weetman A.P., Freeman M.A., Borysiewicz L.K. Functional analysis of intercellular adhesion molecule-1 expressing human thyroid cells. Eur. J. Immunol. 1990;20:271–275. doi: 10.1002/eji.1830200207. [DOI] [PubMed] [Google Scholar]
  • 34.Wu Z., Podack E.R., McKenzie J.M. Perforin expression by thyroid infiltrating T cells in autoimmune thyroid disease. Clin. Exp. Immunol. 1994;98:470–477. doi: 10.1111/j.1365-2249.1994.tb05515.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Giordano C., Stassi G., Maria R. Potential involvement of Fas and its Ligand on the pathogenesis of Hashimoto’s thyroiditis. Science. 1997;275:960–963. doi: 10.1126/science.275.5302.960. [DOI] [PubMed] [Google Scholar]
  • 36.Chiovato L., Bassi P., Santini F. Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis. J. Clin. Endocrinol. Metab. 1993;77:1700–1705. doi: 10.1210/jc.77.6.1700. [DOI] [PubMed] [Google Scholar]
  • 37.Simons P.J., Delemarre F.G.A., Drexhage H.A. Antignen-presenting dendritic cells as regulators of the growth of hydrolytes: A role of interleukin-1b and interleukin-6. Endocrinology. 1998;139:148–3156. doi: 10.1210/en.139.7.3148. [DOI] [PubMed] [Google Scholar]
  • 38.Hegedus L., Hansen J.M., Feldt-Rasmussen U., Hansen B.M., Moier-Madsen M. Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto’s thyroiditis. Clin. Endocrinol. 1991;35:235–238. doi: 10.1111/j.1365-2265.1991.tb03528.x. [DOI] [PubMed] [Google Scholar]
  • 39.Volpe R. Evidence that the immunosuppressive effects of antithyroid drugs are mediated through actions on the thyroid cell, modulating thyrocyte-immunocyte signaling. Thyroid. 1994;4:217–221. doi: 10.1089/thy.1994.4.217. [DOI] [PubMed] [Google Scholar]
  • 40.Lee S, Scherberg N, DeGroot LJ, et al. Induction of oral tolerance in human autoimmune thyroid disease. Thyroid. 1998;8:229–234. doi: 10.1089/thy.1998.8.229. [DOI] [PubMed] [Google Scholar]
  • 41.Baker J.R., Fosso C.K. Immunological aspects of cancers arising from thyroid follicular cells. Endocr. Rev. 1993;13:729–746. doi: 10.1210/er.14.6.729. [DOI] [PubMed] [Google Scholar]
  • 42.Matsuzuka F.M., Miyauchi A., Katyama S. Clinical aspects of primary thyroid lymphoma: Diagnosis and treatment based on our experience of 119 cases. Thyroid. 1993;3:93–99. doi: 10.1089/thy.1993.3.93. [DOI] [PubMed] [Google Scholar]
  • 43.Giani C., Fierabracci P., Bonacci R. Relationship between breast cancer and thyroid disease: Relevance of autoimmune thyroid disorders in breast malignancy. J. Clin. Endocrinol. Metab. 1996;81:990–994. doi: 10.1210/jc.81.3.990. [DOI] [PubMed] [Google Scholar]

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