Horm Metab Res 2018; 50(12): 922-931
DOI: 10.1055/a-0648-4593
Review
© Georg Thieme Verlag KG Stuttgart · New York

Thyroid Autoimmunity and Thyroid Cancer – The Pathogenic Connection: A 2018 Update

Yuji Nagayama
1   Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
› Author Affiliations
Further Information

Publication History

received 12 March 2018

accepted 13 June 2018

Publication Date:
06 August 2018 (online)

Abstract

The association between thyroid cancer and thyroid autoimmunity has long been suggested, but remains to be elucidated for several decades. Here the data on this issue are updated by summarizing relevant papers published between 2012 and early 2018. Although numerous papers demonstrated the significant increase in the prevalence of thyroid autoimmunity (positive intrathyroidal lymphocyte infiltration and/or anti-thyroglobulin/thyroid peroxidase antibodies) in patients with thyroid cancers as compared to those with benign nodules, and also the significant increase in the prevalence of papillary thyroid cancer (PTC) in patients with thyroid autoimmunity as compared to those without, there are some crucial biases that should be taken into account for their interpretation. However, a difference in the incidence of thyroid autoimmunity in patients with PTCs and those with other types of thyroid cancers appears to support the significant association of two conditions. Thyroid autoimmunity is, at least partly, likely to be elicited against antigens shared by normal and cancerous thyroid tissues, thereby inducing autoimmunity. At the same time, elevated TSH levels (even within the normal reference ranges), which often accompany Hashimoto’s patients are a risk factor for thyroid cancer. However, it is still unclear whether or not the co-existence of thyroid autoimmunity impacts on cancer characteristics and prognosis. This issue needs to be further investigated with large-scale prospective studies.

 
  • References

  • 1 Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg 1955; 70: 291-297
  • 2 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
  • 3 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
  • 4 Keutgen XM, Filicori F, Fahey 3rd TJ. Molecular diagnosis for indeterminate thyroid nodules on fine needle aspiration: Advances and limitations. Exp Rev Mol Diagn 2013; 13: 613-623
  • 5 Karatzas T, Vasileiadis I, Zapanti E, Charitoudis G, Karakostas E, Boutzios G. Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology. Am J Surg 2016; 212: 946-952
  • 6 Boi F, Pani F, Mariotti S. Thyroid autoimmunity and thyroid cancer: Review focused on cytological studies. Eur Thyr J 2017; 6: 178-186
  • 7 Iliadou PK, Effraimidis G, Konstantinos M, Grigorios P, Mitsakis P, Patakiouta F, Pazaitou-Panayiotou K. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents. Eur J Endocrinol 2015; 173: 827-833
  • 8 Ehlers M, Schott M. Hashimoto's thyroiditis and papillary thyroid cancer: Are they immunologically linked?. Trends Endocrinol Metab 2014; 25: 656-664
  • 9 Resende de Paiva C, Gronhoj C, Feldt-Rasmussen U, von Buchwald C. Association between Hashimoto's Thyroiditis and Thyroid Cancer in 64,628 Patients. Front Oncol 2017; 7: 53
  • 10 Ye ZQ, Gu DN, Hu HY, Zhou YL, Hu XQ, Zhang XH. Hashimoto's thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer. World J Surg Oncol 2013; 11: 56
  • 11 Zhang Y, Ma XP, Deng FS, Liu ZR, Wei HQ, Wang XH, Chen H. The effect of chronic lymphocytic thyroiditis on patients with thyroid cancer. World J Surg Oncol 2014; 12: 277
  • 12 Giagourta I, Evangelopoulou C, Papaioannou G, Kassi G, Zapanti E, Prokopiou M, Papapostolou K, Karga H. Autoimmune thyroiditis in benign and malignant thyroid nodules: 16-year results. Head Neck 2014; 36: 531-535
  • 13 Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, Borghero A, Mariotti S. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J Endocrinol Invest 2013; 36: 313-320
  • 14 Lun Y, Wu X, Xia Q, Han Y, Zhang X, Liu Z, Wang F, Duan Z, Xin S, Zhang J. Hashimoto's thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 2013; 148: 396-402
  • 15 Azizi G, Keller JM, Lewis M, Piper K, Puett D, Rivenbark KM, Malchoff CD. Association of Hashimoto's thyroiditis with thyroid cancer. Endocr Relat Cancer 2014; 21: 845-852
  • 16 Wu X, Lun Y, Jiang H, Gang Q, Xin S, Duan Z, Zhang J. Coexistence of thyroglobulin antibodies and thyroid peroxidase antibodies correlates with elevated thyroid-stimulating hormone level and advanced tumor stage of papillary thyroid cancer. Endocrine 2014; 46: 554-560
  • 17 Veit F, Graf D, Momberger S, Helmich-Kapp B, Ruschenburg I, Peters A, Kussmann J, Saeger W, Schmidt KW, Toetsch M, Nestler K, Mann K. Papillary thyroid cancer and coexisting autoimmune thyroiditis. Horm Metab Res 2017; 49: 869-872
  • 18 Vasileiadis I, Boutzios G, Charitoudis G, Koukoulioti E, Karatzas T. Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma. Ann Surg Oncol 2014; 21: 2725-2732
  • 19 Qin J, Yu Z, Guan H, Shi L, Liu Y, Zhao N, Shan Z, Han C, Li Y, Teng W. High thyroglobulin antibody levels increase the risk of differentiated thyroid carcinoma. Disease Mark 2015; 648670
  • 20 Campos LA, Picado SM, Guimaraes AV, Ribeiro DA, Dedivitis RA. Thyroid papillary carcinoma associated to Hashimoto's thyroiditis. Braz J Otorhinolaryngol 2012; 78: 77-80
  • 21 Cho YA, Kong SY, Shin A, Lee J, Lee EK, Lee YJ, Kim J. Biomarkers of thyroid function and autoimmunity for predicting high-risk groups of thyroid cancer: A nested case-control study. BMC Cancer 2014; 14: 873
  • 22 Selek A, Cetinarslan B, Tarkun I, Canturk Z, Ustuner B, Akyay Z. Thyroid autoimmunity: Is really associated with papillary thyroid carcinoma?. Eur Arch Otorhinolaryngol Head Neck Surg 2017; 274: 1677-1681
  • 23 de Alcantara-Jones DM, de Alcantara-Nunes TF, Rocha Bde O, de Oliveira RD, Santana AC, de Alcantara FT, de Faria TM, da Silva IC, Araujo LM. Is there any association between Hashimoto's thyroiditis and thyroid cancer? A retrospective data analysis. Radiol Bras 2015; 48: 148-153
  • 24 Hacihamdioglu B, Ocal G, Berberoglu M, Savas Erdeve S, Camtosun E, Kocaay P, Fitoz S, Ceyhan K, Dindar H, Yagmurlu A, Kir M, Unal E, Siklar Z. The evaluation of thyroid carcinoma in childhood and concomitance of autoimmune thyroid disorders. J Pediatr Endocrinol Metab 2014; 27: 901-908
  • 25 Zayed AA, Ali MK, Jaber OI, Suleiman MJ, Ashhab AA, Al Shweiat WM, Momani MS, Shomaf M, AbuRuz SM. Is Hashimoto's thyroiditis a risk factor for medullary thyroid carcinoma? Our experience and a literature review. Endocrine 2015; 48: 629-636
  • 26 Castagna MG, Belardini V, Memmo S, Maino F, Di Santo A, Toti P, Carli AF, Caruso G, Pacini F. Nodules in autoimmune thyroiditis are associated with increased risk of thyroid cancer in surgical series but not in cytological series: Evidence for selection bias. J Clin Endocrinol Metab 2014; 99: 3193-3198
  • 27 Hadjisavva IS, Dina R, Talias MA, Economides PA. Prevalence of cancer in patients with thyroid nodules in the Island of Cyprus: Predictive value of ultrasound features and thyroid autoimmune status. Eur Thyr J 2015; 4: 123-128
  • 28 Konturek A, Barczynski M, Wierzchowski W, Stopa M, Nowak W. Coexistence of papillary thyroid cancer with Hashimoto thyroiditis. Langenbeck Arch Surg 2013; 398: 389-394
  • 29 Zhang Y, Dai J, Wu T, Yang N, Yin Z. The study of the coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. J Cancer Res Clin Oncol 2014; 140: 1021-1026
  • 30 Chen YK, Lin CL, Cheng FT, Sung FC, Kao CH. Cancer risk in patients with Hashimoto's thyroiditis: A nationwide cohort study. Br J Cancer 2013; 109: 2496-2501
  • 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
  • 32 Boutzios G, Vasileiadis I, Zapanti E, Charitoudis G, Karakostas E, Ieromonachou P, Karatzas T. Higher incidence of tall cell variant of papillary thyroid carcinoma in Graves' Disease. Thyroid 2014; 24: 347-354
  • 33 Pazaitou-Panayiotou K, Michalakis K, Paschke R. Thyroid cancer in patients with hyperthyroidism. Horm Metab Res 2012; 44: 255-262
  • 34 Medas F, Erdas E, Canu GL, Longheu A, Pisano G, Tuveri M, Calo PG. Does hyperthyroidism worsen prognosis of thyroid carcinoma? A retrospective analysis on 2820 consecutive thyroidectomies. J Otolaryngol Head Neck Surg 2018; 47: 6
  • 35 Yeh NC, Chou CW, Weng SF, Yang CY, Yen FC, Lee SY, Wang JJ, Tien KJ. Hyperthyroidism and thyroid cancer risk: a population-based cohort study. Exp Clin Endocrinol Diabetes 2013; 121: 402-406
  • 36 Dvorkin S, Robenshtok E, Hirsch D, Strenov Y, Shimon I, Benbassat CA. Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimotos thyroiditis. J Clin Endocrinol Metab 2013; 98: 2409-2414
  • 37 Durante C, Tognini S, Montesano T, Orlandi F, Torlontano M, Puxeddu E, Attard M, Costante G, Tumino S, Meringolo D, Bruno R, Trulli F, Toteda M, Redler A, Ronga G, Filetti S, Monzani F. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid 2014; 24: 1139-1145
  • 38 Li TJ, Lin YS, Liang J, Li F. Time to disappearance of thyroglobulin antibodies and influencing factors in patients with papillary thyroid carcinoma. Acta Acad Med Sinicae 2012; 34: 258-261
  • 39 Yoshioka W, Miyauchi A, Ito M, Kudo T, Tamai H, Nishihara E, Kihara M, Miya A, Amino N. Kinetic analyses of changes in serum TSH receptor antibody values after total thyroidectomy in patients with Graves' disease. Endocr J 2016; 63: 179-185
  • 40 Takamura Y, Nakano K, Uruno T, Ito Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma K, Miyauchi A. Changes in serum TSH receptor antibody (TRAb) values in patients with Graves' disease after total or subtotal thyroidectomy. Endocr J 2003; 50: 595-601
  • 41 Spencer C, Fatemi S. Thyroglobulin antibody (TgAb) methods - Strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab 2013; 27: 701-712
  • 42 Fiore E, Latrofa F, Vitti P. Iodine, thyroid autoimmunity and cancer. Eur Thyroid J 2015; 4: 26-35
  • 43 Lupoli GA, Okosieme OE, Evans C, Clark PM, Pickett AJ, Premawardhana LD, Lupoli G, Lazarus JH. Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer. J Clin Endocrinol Metab 2015; 100: 100-108
  • 44 Frohlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol 2017; 8: 521
  • 45 Teixeira Mendes LS, Wotherspoon A. Marginal zone lymphoma: Associated autoimmunity and auto-immune disorders. Best Pract Res Clin Haematol 2017; 30: 65-76
  • 46 Mizokami T, Hamada K, Maruta T, Higashi K, Yamashita H, Noguchi Y, Noguchi H, Tajiri J. Development of primary thyroid lymphoma during an ultrasonographic follow-up of Hashimoto's Thyroiditis: A report of 9 cases. Intern Med (Tokyo, Japan) 2016; 55: 943-948
  • 47 Benvenga S, Antonelli A, Vita R. Thyroid nodules and thyroid autoimmunity in the context of environmental pollution. Rev Endocr Metab Disord 2015; 16: 319-340
  • 48 Yoon YH, Kim HJ, Lee JW, Kim JM, Koo BS. The clinicopathologic differences in papillary thyroid carcinoma with or without co-existing chronic lymphocytic thyroiditis. Eur Arch Otorhinolaryngol Head Neck Surg 2012; 269: 1013-1017
  • 49 Jeong JS, Kim HK, Lee CR, Park S, Park JH, Kang SW, Jeong JJ, Nam KH, Chung WY, Park CS. Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: Clinical manifestation and prognostic outcome. J Korean Med Sci 2012; 27: 883-889
  • 50 Girardi FM, Barra MB, Zettler CG. Papillary thyroid carcinoma: does the association with Hashimoto's thyroiditis affect the clinicopathological characteristics of the disease?. Braz J Otorhinolaryngol 2015; 81: 283-287
  • 51 Zhu F, Shen YB, Li FQ, Fang Y, Hu L, Wu YJ. The effects of Hashimoto Thyroiditis on lymph node metastases in unifocal and multifocal papillary thyroid carcinoma: A retrospective Chinese cohort study. Medicine 2016; 95: e2674
  • 52 Ieni A, Vita R, Magliolo E, Santarpia M, Di Bari F, Benvenga S, Tuccari G. One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007-2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging. Front Endocrinol 2017; 8: 337
  • 53 Shen CT, Zhang XY, Qiu ZL, Sun ZK, Wei WJ, Song HJ, Luo QY. Thyroid autoimmune antibodies in patients with papillary thyroid carcinoma: A double-edged sword?. Endocrine 2017; 58: 176-183
  • 54 Jo K, Kim MH, Ha J, Lim Y, Lee S, Bae JS, Jung CK, Kang MI, Cha BY, Lim DJ. Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer. Clin Endocrinol 2017; 87: 292-299
  • 55 Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R, Belfiore A. Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease. J Clin Endocrinol Metab 2013; 98: 1014-1021
  • 56 Ergin AB, Saralaya S, Olansky L. Incidental papillary thyroid carcinoma: Clinical characteristics and prognostic factors among patients with Graves' disease and euthyroid goiter, Cleveland Clinic experience. Am J Otolaryngol 2014; 35: 784-790
  • 57 Paparodis R, Imam S, Todorova-Koteva K, Staii A, Jaume JC. Hashimoto's thyroiditis pathology and risk for thyroid cancer. Thyroid 2014; 24: 1107-1114
  • 58 Yu H, Huang X, Liu X, Jin H, Zhang G, Zhang Q, Yu J. Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter. Endocrine 2013; 44: 172-181
  • 59 Lewinski A, Sliwka PW, Stasiolek M. Dendritic cells in autoimmune disorders and cancer of the thyroid. Folia Histochem Cytobiol 2014; 52: 18-28
  • 60 Imam S, Paparodis R, Sharma D, Jaume JC. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity. Endocr Relat Cancer 2014; 21: 505-516
  • 61 Fang W, Ye L, Shen L, Cai J, Huang F, Wei Q, Fei X, Chen X, Guan H, Wang W, Li X, Ning G. Tumor-associated macrophages promote the metastatic potential of thyroid papillary cancer by releasing CXCL8. Carcinogenesis 2014; 35: 1780-1787
  • 62 Zeng RC, Jin LP, Chen ED, Dong SY, Cai YF, Huang GL, Li Q, Jin C, Zhang XH, Wang OC. Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer. Head Neck 2016; 38 (Suppl. 01) E1019-E1025
  • 63 Xing M, Clark D, Guan H, Ji M, Dackiw A, Carson KA, Kim M, Tufaro A, Ladenson P, Zeiger M, Tufano R. BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. J Clin Oncol 2009; 27: 2977-2982
  • 64 Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O'Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 2013; 309: 1493-1501
  • 65 Marotta V, Guerra A, Zatelli MC, Uberti ED, Di Stasi V, Faggiano A, Colao A, Vitale M. BRAF mutation positive papillary thyroid carcinoma is less advanced when Hashimoto's thyroiditis lymphocytic infiltration is present. Clin Endocrinol 2013; 79: 733-738
  • 66 Kim SJ, Myong JP, Jee HG, Chai YJ, Choi JY, Min HS, Lee KE, Youn YK. Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer. Head Neck 2016; 38: 95-101
  • 67 Kim SK, Woo JW, Lee JH, Park I, Choe JH, Kim JH, Kim JS. Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma. Endocr Relat Cancer 2016; 23: 27-34