Endocrinol Metab.  2016 Sep;31(3):379-385. 10.3803/EnM.2016.31.3.379.

Recent Advances in Autoimmune Thyroid Diseases

• Yoo WS
• Chung HK

• KMID: 2352975
• DOI: http://doi.org/10.3803/EnM.2016.31.3.379

Abstract

Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs.

Keyword

Autoimmune thyroid disease; Graves disease; Hashimoto disease

MeSH Terms

Causality
Consensus
Drug Therapy
Genes, rel
Graves Disease
Hashimoto Disease
Hyperthyroidism
Hypothyroidism
Risk Assessment
Thyroid Diseases*
Thyroid Gland*
Thyroiditis, Autoimmune
Thyroxine
Thyroxine

Reference

1. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev. 2015; 14:174–180.

2. Brand OJ, Barrett JC, Simmonds MJ, Newby PR, McCabe CJ, Bruce CK, et al. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease. Hum Mol Genet. 2009; 18:1704–1713.

3. Colobran R, Armengol Mdel P, Faner R, Gartner M, Tykocinski LO, Lucas A, et al. Association of an SNP with intrathymic transcription of TSHR and Graves' disease: a role for defective thymic tolerance. Hum Mol Genet. 2011; 20:3415–3423.

4. Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nat Genet. 1997; 17:393–398.

5. Cetani F, Barbesino G, Borsari S, Pardi E, Cianferotti L, Pinchera A, et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab. 2001; 86:4747–4752.

6. Hasham A, Tomer Y. Genetic and epigenetic mechanisms in thyroid autoimmunity. Immunol Res. 2012; 54:204–213.

7. Ji R, Feng Y, Zhan WW. Updated analysis of studies on the cytotoxic T-lymphocyte-associated antigen-4 gene A49G polymorphism and Hashimoto's thyroiditis risk. Genet Mol Res. 2013; 12:1421–1430.

8. Luo L, Cai B, Liu F, Hu X, Wang L. Association of protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis. Endocr J. 2012; 59:439–445.

9. Li M, Sun H, Liu S, Yu J, Li Q, Liu P, et al. CD40 C/T-1 polymorphism plays different roles in Graves' disease and Hashimoto's thyroiditis: a meta-analysis. Endocr J. 2012; 59:1041–1050.

10. Zaaber I, Mestiri S, Marmouch H, Mahjoub S, Abid N, Hassine M, et al. Polymorphisms in TSHR and IL1RN genes and the risk and prognosis of Hashimoto's thyroiditis. Autoimmunity. 2014; 47:113–118.

11. Yan N, Yu YL, Yang J, Qin Q, Zhu YF, Wang X, et al. Association of interleukin-17A and -17F gene single-nucleotide polymorphisms with autoimmune thyroid diseases. Autoimmunity. 2012; 45:533–539.

12. Xiao L, Muhali FS, Cai TT, Song RH, Hu R, Shi XH, et al. Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune thyroid disease in Chinese individuals. Funct Integr Genomics. 2013; 13:455–461.

13. Santos LR, Duraes C, Mendes A, Prazeres H, Alvelos MI, Moreira CS, et al. A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto's thyroiditis susceptibility. J Clin Endocrinol Metab. 2014; 99:E719–E723.

14. Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D. Selenium supplementation in the treatment of Hashimoto's thyroiditis: a systematic review and a meta-analysis. Thyroid. 2010; 20:1163–1173.

15. 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.

16. Xu MY, Cao B, Yin J, Wang DF, Chen KL, Lu QB. Vitamin D and Graves' disease: a meta-analysis update. Nutrients. 2015; 7:3813–3827.

17. D'Aurizio F, Villalta D, Metus P, Doretto P, Tozzoli R. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? Autoimmun Rev. 2015; 14:363–369.

18. Carle A, Pedersen IB, 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. 2012; 167:483–490.

19. Arena S, Latina A, Baratta R, Burgio G, Gullo D, Benvenga S. Chronic lymphocytic thyroiditis: could it be influenced by a petrochemical complex? Data from a cytological study in South-Eastern Sicily. Eur J Endocrinol. 2015; 172:383–389.

20. Cepon TJ, Snodgrass JJ, Leonard WR, Tarskaia LA, Klimova TM, Fedorova VI, et al. Circumpolar adaptation, social change, and the development of autoimmune thyroid disorders among the Yakut (Sakha) of Siberia. Am J Hum Biol. 2011; 23:703–709.

21. Glick AB, Wodzinski A, Fu P, Levine AD, Wald DN. Impairment of regulatory T-cell function in autoimmune thyroid disease. Thyroid. 2013; 23:871–878.

22. Zhu C, Ma J, Liu Y, Tong J, Tian J, Chen J, et al. Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 2012; 7:943–950.

23. 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; 95:953–962.

24. Bai X, Sun J, Wang W, Shan Z, Zheng H, Li Y, et al. Increased differentiation of Th22 cells in Hashimoto's thyroiditis. Endocr J. 2014; 61:1181–1190.

25. Hiromatsu Y, Satoh H, Amino N. Hashimoto's thyroiditis: history and future outlook. Hormones (Athens). 2013; 12:12–18.

26. Takeshima K, Inaba H, Ariyasu H, Furukawa Y, Doi A, Nishi M, et al. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan. Endocr J. 2015; 62:725–731.

27. Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013; 2:215–228.

28. Wiersinga WM. Guidance in subclinical hyperthyroidism and subclinical hypothyroidism: are we making progress? Eur Thyroid J. 2015; 4:143–148.

29. Collet TH, Bauer DC, Cappola AR, Asvold BO, Weiler S, Vittinghoff E, et al. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis. J Clin Endocrinol Metab. 2014; 99:3353–3362.

30. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002; 87:1068–1072.

31. Asvold BO, Vatten LJ, Bjoro T, Bauer DC, Bremner A, Cappola AR, et al. Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts. JAMA Intern Med. 2015; 175:1037–1047.

32. TRUST project. Thyroid hormone replacement for subclinical hypothyroidism trial (TRUST) [Internet]. TRUST project;2012. cited 2016 Jul 24. Available from: http://www.trustthyroidtrial.com.

33. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000; 160:526–534.

34. Wiersinga WM, Duntas L, Fadeyev V, Nygaard B, Vanderpump MP. 2012 ETA guidelines: the use of LT4 + LT3 in the treatment of hypothyroidism. Eur Thyroid J. 2012; 1:55–71.

35. Piehl S, Hoefig CS, Scanlan TS, Kohrle J. Thyronamines: past, present, and future. Endocr Rev. 2011; 32:64–80.

36. Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011; 21:593–646.

37. Moon JH, Yi KH. The diagnosis and management of hyperthyroidism in Korea: consensus report of the korean thyroid association. Endocrinol Metab (Seoul). 2013; 28:275–279.

38. Bartalena L, Burch HB, Burman KD, Kahaly GJ. A 2013 European survey of clinical practice patterns in the management of Graves' disease. Clin Endocrinol (Oxf). 2016; 84:115–120.

39. Yang Y, Hwang S, Kim M, Lim Y, Kim MH, Lee S, et al. Refractory Graves' disease successfully cured by adjunctive cholestyramine and subsequent total thyroidectomy. Endocrinol Metab (Seoul). 2015; 30:620–625.

40. Min SH, Phung A, Oh TJ, Han KS, Kim MJ, Kim JM, et al. Therapeutic plasmapheresis enabling radioactive iodine treatment in a patient with thyrotoxicosis. J Korean Med Sci. 2015; 30:1531–1534.

41. Okamura K, Sato K, Fujikawa M, Bandai S, Ikenoue H, Kitazono T. Remission after potassium iodide therapy in patients with Graves' hyperthyroidism exhibiting thionamide-associated side effects. J Clin Endocrinol Metab. 2014; 99:3995–4002.

42. Zheng R, Liu K, Chen K, Cao W, Cao L, Zhang H, et al. Lithium carbonate in the treatment of Graves' disease with ATD-induced hepatic injury or leukopenia. Int J Endocrinol. 2015; 2015:694023.

43. Biondi B, Bartalena L, Cooper DS, Hegedus L, Laurberg P, Kahaly GJ. The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. Eur Thyroid J. 2015; 4:149–163.

44. Selmer C, Olesen JB, Hansen ML, Lindhardsen J, Olsen AM, Madsen JC, et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012; 345:e7895.

45. Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA. 2015; 313:2055–2065.

46. Konishi T, Okamoto Y, Ueda M, Fukuda Y, Harusato I, Tsukamoto Y, et al. Drug discontinuation after treatment with minimum maintenance dose of an antithyroid drug in Graves' disease: a retrospective study on effects of treatment duration with minimum maintenance dose on lasting remission. Endocr J. 2011; 58:95–100.

47. Laurberg P, Krejbjerg A, Andersen SL. Relapse following antithyroid drug therapy for Graves' hyperthyroidism. Curr Opin Endocrinol Diabetes Obes. 2014; 21:415–421.

48. Liu X, Qiang W, Liu X, Liu L, Liu S, Gao A, et al. A second course of antithyroid drug therapy for recurrent Graves' disease: an experience in endocrine practice. Eur J Endocrinol. 2015; 172:321–326.

49. Liu X, Shi B, Li H. Valuable predictive features of relapse of Graves' disease after antithyroid drug treatment. Ann Endocrinol (Paris). 2015; 76:679–683.

50. Vos XG, Endert E, Zwinderman AH, Tijssen JG, Wiersinga WM. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with Graves' hyperthyroidism. J Clin Endocrinol Metab. 2016; 101:1381–1389.

51. Ladenson PW. Precision medicine comes to thyroidology. J Clin Endocrinol Metab. 2016; 101:799–803.

52. Sanders J, Miguel RN, Furmaniak J, Smith BR. TSH receptor monoclonal antibodies with agonist, antagonist, and inverse agonist activities. Methods Enzymol. 2010; 485:393–420.

53. Gershengorn MC, Neumann S. Update in TSH receptor agonists and antagonists. J Clin Endocrinol Metab. 2012; 97:4287–4292.

54. van Koppen CJ, de Gooyer ME, Karstens WJ, Plate R, Conti PG, van Achterberg TA, et al. Mechanism of action of a nanomolar potent, allosteric antagonist of the thyroid-stimulating hormone receptor. Br J Pharmacol. 2012; 165:2314–2324.

55. Neumann S, Nir EA, Eliseeva E, Huang W, Marugan J, Xiao J, et al. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology. 2014; 155:310–314.