European Archives of Oto-Rhino-Laryngology

, Volume 274, Issue 3, pp 1677–1681 | Cite as

Thyroid autoimmunity: is really associated with papillary thyroid carcinoma?

  • Alev Selek
  • Berrin Cetinarslan
  • Ilhan Tarkun
  • Zeynep Canturk
  • Berna Ustuner
  • Zeynep Akyay
Head and Neck


The incidence of thyroid cancer has been greatly increasing. Several studies aimed to investigate biomarkers for prediction of thyroid cancer. Some of these studies have suggested that thyroid autoantibodies (TAb) could be used as predictors of thyroid cancer risk, but the correlation between TAb and PTC is still a matter of debate. The aim of this study is to evaluate thyroid autoimmunity and TAbs in patients with PTC and benign multinodular goiter (MNG) to investigate if TAbs and autoimmune thyroid disease (ATD) could predict thyroid malignancy. A total of 577 patients with thyroid papillary carcinoma (PTC) and 293 patients with benign MNG disease were enrolled postoperatively. Demographic features, thyroglobulin (TgAb) and thyroid peroxidase antibodies (TPOAb) and histologic outcome of the patients were evaluated. The prevalence of ATD and TgAb or TPOAb measurements was not statistically different in PTC and MNG groups. However, tumors were significantly smaller and tumor capsule invasion was seen less frequently in patients with PTC and ATD than without ATD. Patients without ATD had more advanced stage (TNM stage III/IV) tumors than with ATD. Only one of the 11 patients with distant organ metastasis had ATD. The present study demonstrated that the prevalence of ATD diagnosed even with histology or TAb positivity was not different in patients with PTC and MNG. However, having ATD might be associated with a better prognosis in PTC patients.


Papillary thyroid cancer Autoimmune thyroid disease Thyroglobulin antibodies Thyroid peroxidase antibodies 


Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest that could be perceived as prejudicing the impartiality of this research.

Ethical approval

The study protocol was approved by the local ethics committee, and the informed consent was obtained from all individual participants included in the study.


  1. 1.
    Pellegriti G, Frasca F, Regalbuto C et al (2013) Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol 2013:965212 (Epub 7 May 2013) CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Verkooijen HM, Fioretta G, Pache JC et al (2003) Diagnostic changes as a reason for the increase in papillary thyroid cancer incidence in Geneva, Switzerland. Cancer Causes Control 14(1):13–17CrossRefPubMedGoogle Scholar
  3. 3.
    Kim ES, Lim DJ, Baek KH et al (2010) Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 20(8):885–891CrossRefPubMedGoogle Scholar
  4. 4.
    Fiore E, Rago T, Latrofa F et al (2011) Hashimoto’s thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with l-thyroxine. Endocr Relat Cancer 18(4):429–437CrossRefPubMedGoogle Scholar
  5. 5.
    Caturegli P, De Remigis A, Chuang K et al (2013) Hashimoto’s thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Thyroid 23(2):142–150CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Chen YK, Lin CL, Cheng FT et al (2013) Cancer risk in patients with Hashimoto’s thyroiditis: a nationwide cohort study. Br J Cancer 109(9):2496–2501CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cunha LL, Morari EC, Guihen AC et al (2012) Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 77(6):918–925CrossRefGoogle Scholar
  8. 8.
    French JD, Kotnis GR, Said SJ et al (2012) Programmed death-1+ T cells and regulatory T cells are enriched in tumor-involved lymph nodes and associated with aggressive features in papillary thyroid cancer. J Clin Endocrinol Metab 97(6):E934–E943CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Qing W, Fang WY, Ye L et al (2012) Density of tumor associated macrophages correlates with lymph node metastasis in papillary thyroid carcinoma. Thyroid 22(9):905–910CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Xu WC, Li ZB, Chen YR et al (2011) Expression and distribution of S-100, CD83, and costimulatory molecules (CD80 and CD86) in tissues of thyroid papillary carcinoma. Cancer Invest 29(4):286–292CrossRefPubMedGoogle Scholar
  11. 11.
    Yu H, Huang X, Liu X et al (2013) Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter. Endocrine 44(1):172–181CrossRefPubMedGoogle Scholar
  12. 12.
    Wu X, Lun Y, Jiang H et al (2014) Coexistence of thyroglobulin antibodies and thyroid peroxidase antibodies correlates with elevated thyroid-stimulating hormone level and advanced tumor stage of papillary thyroid cancer. Endocrine 46(3):554–560CrossRefPubMedGoogle Scholar
  13. 13.
    Hollowell JG, Staehling NW, Flanders WD et al (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489–499CrossRefPubMedGoogle Scholar
  14. 14.
    Spencer CA (2011) Clinical review: clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 96:3615–3627CrossRefPubMedGoogle Scholar
  15. 15.
    Edge SB, Byrd DR, Compton C et al (2010) AJCC cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
  16. 16.
    Lun Y, Wu X, Xia Q et al (2013) Hashimoto’s thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 148:396–402CrossRefPubMedGoogle Scholar
  17. 17.
    Wartofsky L (2010) Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure. Hormones 9(2):103–108CrossRefPubMedGoogle Scholar
  18. 18.
    Ostroumova E, Brenner A, Oliynyk V et al (2009) Subclinical hypothyroidism after radioiodine exposure: Ukrainian–American cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident (1998–2000). Environ Health Perspect 117(5):745–750CrossRefPubMedGoogle Scholar
  19. 19.
    Gomez Segovia I, Gallowitsch HJ, Kresnik E et al (2004) Descriptive epidemiology of thyroid carcinoma in Carinthia, Austria: 1984–2001. Histopathologic features and tumor classification of 734 cases under elevated general iodination of table salt since 1990: population-based age-stratified analysis on thyroid carcinoma incidence. Thyroid 14(4):277–286CrossRefGoogle Scholar
  20. 20.
    Laurberg P, Cerqueira C, Ovesen L et al (2010) Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res 24(1):13–27CrossRefGoogle Scholar
  21. 21.
    Bloodworth JMB, Lechago J, Gould VE (1996) Bloodworth’s endocrine pathology, 3rd edn. Williams & Wilkins, BaltimoreGoogle Scholar
  22. 22.
    Singh B, Shaha AR, Trivedi H et al (1999) Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 126(6):1070–1077CrossRefPubMedGoogle Scholar
  23. 23.
    Ward LS, Assumpção LV (2007) The impact of gender in differentiated thyroid cancer. Clin Endocrinol 66(5):752–753CrossRefGoogle Scholar
  24. 24.
    Cunha LL, Ferreira RC, Marcello MA et al (2011) Clinical and pathological implications of concurrent autoimmune thyroid disorders and papillary thyroid cancer. J Thyroid Res 17(2011):387062Google Scholar
  25. 25.
    Boi F, Lai ML, Marziani B et al (2005) High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies. Eur J Endocrinol 153(5):637–642CrossRefPubMedGoogle Scholar
  26. 26.
    Fiore E, Rago T, Scutari M et al (2009) Papillary thyroid cancer, although strongly associated with lymphocitic infiltration on histology, is only weakly predicted by serum thyroid autoantibodies in patients with nodular thyroid disease. J Endocrinol Invest 32(4):344–351CrossRefPubMedGoogle Scholar
  27. 27.
    Boelaert K, Horacek J, Holder RL et al (2006) Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 91(11):4295–4301CrossRefPubMedGoogle Scholar
  28. 28.
    Rago T, Di Coscio G, Ugolini C et al (2007) Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy. Clin Endocrinol (Oxf) 67(3):363–369CrossRefGoogle Scholar
  29. 29.
    Fiore E, Rago T, Provenzaleetal MA et al (2009) Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 16(4):1251–1260CrossRefPubMedGoogle Scholar
  30. 30.
    Jankovic B, Le KT, Hershman JM (2013) Clinical review: Hashimoto’s thyroiditis and papillary thyroid carcinoma: is there a correlation? J Clin Endocrinol Metab 98(2):474–482CrossRefPubMedGoogle Scholar
  31. 31.
    Wirtschafter A, Schmidt R, Rosen D et al (1997) Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto’s thyroiditis. Laryngoscope 107(1):95–100CrossRefPubMedGoogle Scholar
  32. 32.
    Sheils OM, O’Leary JJ, Uhlmann V et al (2000) Ret/PTC-1 activation in Hashimoto thyroiditis. Int J Surg Pathol 8(3):185–189CrossRefPubMedGoogle Scholar
  33. 33.
    Elisei R, Romei C, Vorontsova T et al (2001) RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab 86(7):3211–3216PubMedGoogle Scholar
  34. 34.
    Guarino V, Castellone MD, Avilla E et al (2010) Thyroid cancer and inflammation. Mol Cell Endocrinol 32(1):94–102CrossRefGoogle Scholar
  35. 35.
    Muzza M, Degl’Innocenti D, Colombo C et al (2010) The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies. Clin Endocrinol 72(5):702–708CrossRefGoogle Scholar
  36. 36.
    Kashima K, Yokoyama S, Noguchi S et al (1998) Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma. Thyroid 8(3):197–202CrossRefPubMedGoogle Scholar
  37. 37.
    Loh KC, Greenspan FS, Dong F et al (1999) Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 84(2):458–463CrossRefPubMedGoogle Scholar
  38. 38.
    Kim EY, Kim WG, Kim WB et al (2009) Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma. Clin Endocrinol 71(4):581–586CrossRefGoogle Scholar
  39. 39.
    Gupta S, Patel A, Folstad A et al (2001) Infiltration of differentiated thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival for children and young adults. J Clin Endocrinol Metab 86(3):1346–1354PubMedGoogle Scholar
  40. 40.
    Medenica S, Radojevic N, Stojkovic M et al (2015) Autoimmunity and thyrotropin level in developing thyroid malignancy. Eur Rev Med Pharmacol Sci 19(15):2824–2829PubMedGoogle Scholar
  41. 41.
    Yano Y, Shibuya H, Kitagawa W et al (2007) Recent outcome of grave’s disease patients with papillary thyroid cancer. Eur J Endocrinol 157(3):325–329CrossRefPubMedGoogle Scholar
  42. 42.
    Kim HS, Choi YJ, Yun JS (2010) Features of papillary thyroid microcarcinoma in the presence and absence of lymphocytic thyroiditis. Endocr Pathol 21(3):149–153CrossRefPubMedGoogle Scholar
  43. 43.
    Sakorafas GH, Giotakis J, Stafyla V (2005) Papillary thyroid microcarcinoma: a surgical perspective. Cancer Treat Rev 31(6):423–438CrossRefPubMedGoogle Scholar
  44. 44.
    Falvo L, D’Ercole C, Sorrenti S et al (2003) Papillary microcarcinoma of the thyroid gland: analysis of prognostic factors including histological subtype. Eur J Surg Suppl 588:28–32Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism, Faculty of MedicineKocaeli UniversityUmuttepe KocaeliTurkey
  2. 2.Department of Internal Medicine, Faculty of MedicineKocaeli UniversityUmuttepe KocaeliTurkey

Personalised recommendations