Antithyroid autoantibodies in extrathyroid autoimmune diseases

Main Article Content

T.V. Sorokman
M.G. Gingulyak
O.V. Makarova


This review summarizes data on the incidence of autoimmune diseases and examines the prevalence of antithyroid antibodies in extrathyroid autoimmune diseases. In the world, about 5–7 % of the population suffers from one or another type of autoimmune diseases. Among the six most common autoimmune diseases, thyroid and associated diseases predominate. The high prevalence of autoimmune thyroid diseases raises questions about the potential role of antithyroid antibodies in the course of extrathyroid autoimmune diseases. It is believed that autoimmune di­seases are the result of interactions between triggers, autoantigens, genetic predisposition, impaired tolerance of autoantigens and mechanisms of apoptosis. Among the currently known antithyroid autoantibodies, antibodies to thyroglobulin (TgAb), thyroid peroxi­dase (TPO), as well as bispecific autoantibodies to thyroglobulin and thyroid peroxidase are of particular importance. Categories of functionally significant autoantibodies that mimic hormone function and provoke the development of autoimmune pathology as a result of binding to the receptor and subsequent stimulation of thyrocytes include antibodies to thyroid-stimulating hormone receptor (rTSH-Ab). Circulating antibodies against thyroid antigens are not limited to autoimmune diseases of the thyroid gland, but are also found in other autoimmune diseases, most often in rheumatoid arthritis, type 1 diabetes mellitus and celiac disease. The association with other immune pathologies further confirms that TPO antibodies were also detected in 15 % of patients with asthma, in 10–29 % of those with idiopathic purpura and vitiligo. The prevalence of TPO antibodies is slightly higher than TgAb, and rTSH-Ab are rarely registered in non-thyroid immunological diseases.

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How to Cite
Sorokman, T., M. Gingulyak, and O. Makarova. “Antithyroid Autoantibodies in Extrathyroid Autoimmune Diseases”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 17, no. 3, June 2021, pp. 234-40, doi:10.22141/2224-0721.17.3.2021.232653.
Original Researches


Sardu C, Cocco E, Mereu A, et al. Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity. PLoS One. 2012;7(3):e32487. doi:10.1371/journal.pone.0032487.

Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental Issues in Thyroid Diseases. Front Endocrinol (Lausanne). 2017 Mar 20;8:50. doi:10.3389/fendo.2017.00050.

Tolentino Júnior DS, de Oliveira CM, de Assis EM. Population-based Study of 24 Autoimmune Diseases Carried Out in a Brazilian Microregion. J Epidemiol Glob Health. 2019 Dec;9(4):243-251. doi:10.2991/jegh.k.190920.001.

Lerner A, Jeremias P, Matthias T. The World Incidence and Prevalence of Autoimmune Diseases is Increasing. International Journal of Celiac Disease. 2015;3(4):151-155. doi:10.12691/ijcd-3-4-8.

Júnior DST. Environmental and individual factors associated with protection and predisposition to autoimmune diseases. Int J Health Sci (Qassim). 2020 Nov-Dec;14(6):13-23.

Leso V, Vetrani I, De Cicco L, et al. The Impact of Thyroid Diseases on the Working Life of Patients: A Systematic Review. Int J Environ Res Public Health. 2020 Jun 16;17(12):4295. doi:10.3390/ijerph17124295.

Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun. 2009 Nov-Dec;33(3-4):197-207. doi:10.1016/j.jaut.2009.09.008.

Sisó-Almirall A, Kostov B, Martínez-Carbonell E, et al. The prevalence of 78 autoimmune diseases in Catalonia (MASCAT-PADRIS Big Data Project). Autoimmun Rev. 2020 Feb;19(2):102448. doi:10.1016/j.autrev.2019.102448.

Komisarenko YI, Bobryk MI. Vitamin D Deficiency and Immune Disorders in Combined Endocrine Pathology. Front Endocrinol (Lausanne). 2018 Oct 9;9:600. doi:10.3389/fendo.2018.00600.

Tronko MD, Brenner AV, Olijnyk VA, et al. Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000). J Clin Endocrinol Metab. 2006 Nov;91(11):4344-51. doi:10.1210/jc.2006-0498.

Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K. Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. Eur Respir J. 2019 Nov 14;54(5):1900476. doi:10.1183/13993003.00476-2019.

Bartalena L, Masiello E, Magri F, et al. The phenotype of newly diagnosed Graves' disease in Italy in recent years is milder than in the past: results of a large observational longitudinal study. J Endocrinol Invest. 2016 Dec;39(12):1445-1451. doi:10.1007/s40618-016-0516-7.

Seldin MF. The genetics of human autoimmune disease: A perspective on progress in the field and future directions. J Autoimmun. 2015 Nov;64:1-12. doi:10.1016/j.jaut.2015.08.015.

De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019 Jan;195(1):74-85. doi:10.1111/cei.13158.

Fallahi P, Ferrari SM, Ruffilli I, et al. The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients. Autoimmun Rev. 2016 Dec;15(12):1125-1128. doi:10.1016/j.autrev.2016.09.009.

Fröhlich E, Wahl R. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Front Immunol. 2017 May 9;8:521. doi:10.3389/fimmu.2017.00521.

Gleicher N, Barad D, Weghofer A. Functional autoantibodies, a new paradigm in autoimmunity? Autoimmun Rev. 2007 Nov;7(1):42-45. doi:10.1016/j.autrev.2007.06.001.

Cárdenas Roldán J, Amaya-Amaya J, Castellanos-de la Hoz J, et al. Autoimmune thyroid disease in rheumatoid arthritis: a global perspective. Arthritis. 2012;2012:864907. doi:10.1155/2012/864907.

Walsh SJ, Rau LM. Autoimmune diseases: a leading cause of death among young and middle-aged women in the United States. Am J Public Health. 2000 Sep;90(9):1463-6. doi:10.2105/ajph.90.9.1463.

Latrofa F, Ricci D, Grasso L, et al. Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies. J Clin Endocrinol Metab. 2008 Feb;93(2):591-6. doi:10.1210/jc.2007-1199.

Kahaly GJ, Diana T, Olivo PD. TSH RECEPTOR ANTIBODIES: RELEVANCE & UTILITY. Endocr Pract. 2020 Jan;26(1):97-106. doi:10.4158/EP-2019-0363.

Subekti I, Boedisantoso A, Moeloek ND, Waspadji S, Mansyur M. Association of TSH receptor antibody, thyroid stimulating antibody, and thyroid blocking antibody with clinical activity score and degree of severity of Graves ophthalmopathy. Acta Med Indones. 2012 Apr;44(2):114-21.

Diana T, Kahaly GJ. Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease-Methodology and Clinical Applications. Ophthalmic Plast Reconstr Surg. 2018 Jul/Aug;34(4S Suppl 1):S13-S19. doi:10.1097/IOP.0000000000001053.

Xie LD, Gao Y, Li MR, Lu GZ, Guo XH. Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto's thyroiditis with different thyroid functional status. Clin Exp Immunol. 2008 Nov;154(2):172-6. doi:10.1111/j.1365-2249.2008.03756.x.

Liu C, Hermsen D, Domberg J, et al. Comparison of M22-based ELISA and human-TSH-receptor-based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases. Horm Metab Res. 2008 Jul;40(7):479-83. doi:10.1055/s-2008-1077051.

Li Y, Teng D, Guan H, et al. Dynamic Changes in Antithyroperoxidase and Antithyroglobulin Antibodies Suggest an Increased Risk for Abnormal Thyrotropin Levels. Front Endocrinol (Lausanne). 2020 Aug 4;11:521. doi:10.3389/fendo.2020.00521.

Hutfless S, Matos P, Talor MV, Caturegli P, Rose NR. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab. 2011 Sep;96(9):E1466-71. doi:10.1210/jc.2011-0228.

Li L, Liu S, Yu J. Autoimmune thyroid disease and type 1 diabetes mellitus: same pathogenesis; new perspective? Ther Adv Endocrinol Metab. 2020 Sep 14;11:2042018820958329. doi:10.1177/2042018820958329.

Kyritsi EM, Kanaka-Gantenbein C. Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence. Front Endocrinol (Lausanne). 2020 Aug 19;11:543. doi:10.3389/fendo.2020.00543.

Hatzioannou A, Kanistras I, Mantzou E, et al. Effect of Advanced Glycation End Products on Human Thyroglobulin's Antigenicity as Identified by the Use of Sera from Patients with Hashimoto's Thyroiditis and Gestational Diabetes Mellitus. Int J Endocrinol. 2015;2015:849615. doi:10.1155/2015/849615.

Kalyoncu D, Urganci N. Antithyroid antibodies and thyroid function in pediatric patients with celiac disease. Int J Endocrinol. 2015;2015:276575. doi:10.1155/2015/276575.

Mihailova S, Ivanova M, Mihaylova A, Quin L, Mikova O, Naumova E. Pro- and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients. J Neuroimmunol. 2005 Nov;168(1-2):138-43. doi:10.1016/j.jneuroim.2005.06.020.

Harel L, Prais D, Uziel Y, et al. Increased prevalence of antithyroid antibodies and subclinical hypothyroidism in children with juvenile idiopathic arthritis. J Rheumatol. 2006 Jan;33(1):164-6.

Samareh Fekri M, Shokoohi M, Gozashti MH, et al. Association between anti-thyroid peroxidase antibody and asthma in women. Iran J Allergy Asthma Immunol. 2012 Sep;11(3):241-5. doi:10.1016/j.ejcdt.2015.08.018.

Ruggeri RM, Imbesi S, Saitta S, et al. Chronic idiopathic urticaria and Graves' disease. J Endocrinol Invest. 2013 Jul-Aug;36(7):531-6. doi:10.3275/8940.

Biondi B, Kahaly GJ, Robertson RP. Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders. Endocr Rev. 2019 Jun 1;40(3):789-824. doi:10.1210/er.2018-00163.

Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves' disease: a 2014 update. J Endocrinol Invest. 2014 Aug;37(8):691-700. doi:10.1007/s40618-014-0097-2.

Pankiv I. The Impact of Vitamin D Status and Supplementation on Thyroid Autoimmunity. Mìžnarodnij endokrinologìčnij žurnal. 2020;16(8):681-685, doi:10.22141/2224-0721.16.8.2020.222889.

Woo YJ, Jang SY, Lim TH, Yoon JS. Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy. Korean J Ophthalmol. 2015 Aug;29(4):213-9. doi:10.3341/kjo.2015.29.4.213.

Chiarella G, Tognini S, Nacci A, et al. Vestibular disorders in euthyroid patients with Hashimoto's thyroiditis: role of thyroid autoimmunity. Clin Endocrinol (Oxf). 2014 Oct;81(4):600-5. doi:10.1111/cen.12471.

Plowden TC, Schisterman EF, Sjaarda LA, et al. Subclinical Hypothyroidism and Thyroid Autoimmunity Are Not Associated With Fecundity, Pregnancy Loss, or Live Birth. J Clin Endocrinol Metab. 2016 Jun;101(6):2358-65. doi:10.1210/jc.2016-1049.

Busnelli A, Paffoni A, Fedele L, Somigliana E. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. Hum Reprod Update. 2016 Nov;22(6):775-790. doi:10.1093/humupd/dmw019.

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