Endocrinol Metab.  2016 Dec;31(4):493-499. 10.3803/EnM.2016.31.4.493.

Clinical Update in Aspects of the Management of Autoimmune Thyroid Diseases

• Topliss DJ

• KMID: 2373066
• DOI: http://doi.org/10.3803/EnM.2016.31.4.493

Abstract

Aspects of autoimmune thyroid disease updated in this review include: immunoglobulin G4 (IgG4)-related thyroid disease (Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, IgG4-related Hashimoto's thyroiditis, and Graves' disease with elevated IgG4 levels); recent epidemiological studies from China and Denmark indicating that excess iodine increases the incidence of Hashimoto's thyroiditis and hypothyroidism; immunomodulatory agents (ipilimumab, pembrolizumab, nivolumab) activate immune response by inhibiting T-cell surface receptors which down-regulate immune response, i.e., cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 pathways; alemtuzumab is a humanised monoclonal antibody to CD52 which causes immune depletion and thyroid autoimmune disease especially Graves' hyperthyroidism; small molecule ligand (SML) agonists which activate receptors, SML neutral antagonists, which inhibit receptor activation by agonists, and SML inverse agonists which inhibit receptor activation by agonists and inhibit constitutive agonist independent signaling have been identified. SML antagonism of thyroid-stimulating hormone-receptor stimulatory antibody could treat Graves' hyperthyroidism and Graves' ophthalmopathy; and thyroxine treatment of subclinical hypothyroidism can produce iatrogenic subclinical hyperthyroidism with the risk of atrial fibrillation and osteoporosis. The increased risk of harm from subclinical hyperthyroidism may be stronger than the potential benefit from treatment of subclinical hypothyroidism.

Keyword

Immunoglobulin G; Iodine; Immunomodulation; Hashimoto disease; Thyroxine

MeSH Terms

Atrial Fibrillation
Autoimmune Diseases
Cell Death
China
CTLA-4 Antigen
Denmark
Epidemiologic Studies
Graves Disease
Hashimoto Disease
Hyperthyroidism
Hypothyroidism
Immunoglobulin G
Immunoglobulins
Immunomodulation
Incidence
Iodine
Osteoporosis
T-Lymphocytes
Thyroid Diseases*
Thyroid Gland*
Thyroiditis
Thyroxine
CTLA-4 Antigen
Immunoglobulin G
Immunoglobulins
Iodine
Thyroxine

Reference

1. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012; 64:3061–3067. PMID: 22736240.

2. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001; 344:732–738. PMID: 11236777.

3. 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 (Hoboken). 2010; 62:1312–1318. PMID: 20506114.

4. Tabata T, Kamisawa T, Takuma K, Egawa N, Setoguchi K, Tsuruta K, et al. Serial changes of elevated serum IgG4 levels in IgG4-related systemic disease. Intern Med. 2011; 50:69–75. PMID: 21245628.

5. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002; 122:1264–1269. PMID: 11984513.

6. Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annu Rev Pathol. 2014; 9:315–347. PMID: 24111912.

7. Komatsu K, Hamano H, Ochi Y, Takayama M, Muraki T, Yoshizawa K, et al. High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci. 2005; 50:1052–1057. PMID: 15986853.

8. Kottahachchi D, Topliss DJ. IgG4-related thyroid diseases. Eur Thyroid J. Forthcoming 2016.

9. 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; 95:1309–1317. PMID: 20097712.

10. Graham A, Gilliland IC. Riedel's thyroiditis. Br Med J. 1959; 2:225–226.

11. Fatourechi MM, Hay ID, McIver B, Sebo TJ, Fatourechi V. Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. Thyroid. 2011; 21:765–772. PMID: 21568724.

12. Comings DE, Skubi KB, Van Eyes J, Motulsky AG. Familial multifocal fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis, Riedel's thyroiditis, and pseudotumor of the orbit may be different manifestations of a single disease. Ann Intern Med. 1967; 66:884–892. PMID: 6025229.

13. Katz SM, Vickery AL Jr. The fibrous variant of Hashimoto's thyroiditis. Hum Pathol. 1974; 5:161–170. PMID: 4405879.

14. 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. 2012; 65:725–728. PMID: 22659333.

15. 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; 59:636–641. PMID: 19712131.

16. Takeshima K, Inaba H, Furukawa Y, Nishi M, Yamaoka H, Miyamoto W, et al. Elevated serum immunoglobulin G4 levels in patients with Graves' disease and their clinical implications. Thyroid. 2014; 24:736–743. PMID: 24256421.

17. Takeshima K, Inaba H, Furukawa Y, Nishi M, Yamaoka H, Miyamoto W, et al. Elevated serum immunoglobulin G4 levels in patients with Graves' disease and their clinical implications. Thyroid. 2014; 24:736–743. PMID: 24256421.

18. 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; 354:2783–2793. PMID: 16807415.

19. Bjergved L, Jorgensen T, Perrild H, Carle A, Cerqueira C, Krejbjerg A, et al. Predictors of change in serum TSH after iodine fortification: an 11-year follow-up to the DanThyr study. J Clin Endocrinol Metab. 2012; 97:4022–4029. PMID: 22962423.

20. Rose NR, Rasooly L, Saboori AM, Burek CL. Linking iodine with autoimmune thyroiditis. Environ Health Perspect. 1999; 107(Suppl 5):749–752. PMID: 10502541.

21. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid. 2001; 11:501–510. PMID: 11396709.

22. Tomer Y, Menconi F. Interferon induced thyroiditis. Best Pract Res Clin Endocrinol Metab. 2009; 23:703–712. PMID: 19942147.

23. Rapoport B, McLachlan SM. Graves' hyperthyroidism is antibody-mediated but is predominantly a Th1-type cytokine disease. J Clin Endocrinol Metab. 2014; 99:4060–4061. PMID: 25210884.

24. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012; 366:2517–2519. PMID: 22658126.

25. Ryder M, Callahan M, Postow MA, Wolchok J, Fagin JA. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer. 2014; 21:371–381. PMID: 24610577.

26. Minagar A, Alexander JS, Sahraian MA, Zivadinov R. Alemtuzumab and multiple sclerosis: therapeutic application. Expert Opin Biol Ther. 2010; 10:421–429. PMID: 20095876.

27. Daniels GH, Vladic A, Brinar V, Zavalishin I, Valente W, Oyuela P, et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab. 2014; 99:80–89. PMID: 24170099.

28. Hartung HP, Aktas O, Boyko AN. Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis. Mult Scler. 2015; 21:22–34. PMID: 25344374.

29. Lee JH, Kim Y, Choi JW, Kim YS. The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis. Eur J Endocrinol. 2013; 168:343–349. PMID: 23211578.

30. Jankovic B, Le KT, Hershman JM. Clinical review: Hashimoto's thyroiditis and papillary thyroid carcinoma: is there a correlation? J Clin Endocrinol Metab. 2013; 98:474–482. PMID: 23293329.

31. Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A, Iwama S. Hashimoto's thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Thyroid. 2013; 23:142–150. PMID: 23151083.

32. Fiore E, Latrofa F, Vitti P. Iodine, thyroid autoimmunity and cancer. Eur Thyroid J. 2015; 4:26–35. PMID: 25960959.

33. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med. 2011; 364:1920–1931. PMID: 21591944.

34. Watt T, Cramon P, Bjorner JB, Bonnema SJ, Feldt-Rasmussen U, Gluud C, et al. Selenium supplementation for patients with Graves' hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial. Trials. 2013; 14:119. PMID: 23782950.

35. 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. PMID: 24716668.

36. Gershengorn MC, Neumann S. Update in TSH receptor agonists and antagonists. J Clin Endocrinol Metab. 2012; 97:4287–4292. PMID: 23019348.

37. Turcu AF, Kumar S, Neumann S, Coenen M, Iyer S, Chiriboga P, et al. A small molecule antagonist inhibits thyrotropin receptor antibody-induced orbital fibroblast functions involved in the pathogenesis of Graves ophthalmopathy. J Clin Endocrinol Metab. 2013; 98:2153–2159. PMID: 23482611.

38. Watanabe T, Maruyama M, Ito T, Fujinaga Y, Ozaki Y, Maruyama M, et al. Clinical features of a new disease concept, IgG4-related thyroiditis. Scand J Rheumatol. 2013; 42:325–330. PMID: 23496326.

39. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004; 292:2591–2599. PMID: 15572717.

40. Taylor PN, Iqbal A, Minassian C, Sayers A, Draman MS, Greenwood R, et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern Med. 2014; 174:32–39. PMID: 24100714.

41. 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. PMID: 24783053.