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Hormones

, Volume 9, Issue 2, pp 109–117 | Cite as

Autoimmunity in differentiated thyroid cancer: Significance and related clinical problems

  • Ulla Feldt-Rasmussen
  • Åse Krogh Rasmussen
Review

Abstract

Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto’s disease has been variably reported at between 0.5 and 22.5 % and of DTC with Graves’ disease between 0 and 9.8 %. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated for autoimmune thyroid diseases should have a careful follow-up. Furthermore, the presence of thyroglobulin antibodies (TgAb) in patients with DTC may limit the use of serum thyroglobulin as a tumor marker due to methodological problems in the determination of serum thyroglobulin. However, in such cases serial TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients.

Key words

Autoimmune thyroiditis Graves’ disease Hashimoto’s thyroiditis Thyroglobulin antibodies Thyroid cancer 

References

  1. 1.
    Spencer CA, Takeuchi M, Kazarosyan M, et al, 1998 Serum thyroglobulin autoantibodies: Prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 83: 1121–1127.PubMedGoogle Scholar
  2. 2.
    Pacini F, Schlumberger M, Dralle H, et al, and the European Thyroid Cancer Taskforce 2006 European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154: 787–803CrossRefGoogle Scholar
  3. 3.
    Cooper DS, Doherty GM, Haugen BR, et al, The American Thyroid Association Guidelines Taskforce 2006 Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16: 109–142.CrossRefGoogle Scholar
  4. 4.
    Dailey ME, Lindsay S, Skahen R, 1955 Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg 70: 291–297.CrossRefGoogle Scholar
  5. 5.
    Pollock WF, Sprong DH, 1958 The rationale of thyroidectomy for Hashimoto’s thyroiditis: a premalignant lesion. West J Surg Obstet Gynecol 66: 17–20.PubMedGoogle Scholar
  6. 6.
    Meier DW, Woolner LB, Beahrs OH, McConahey WM, 1959 Parenchymal findings in thyroidal carcinoma: pathologic study of 256 cases. J Clin Endocrinol 19: 162–171.CrossRefGoogle Scholar
  7. 7.
    Woolner LB, McConaley WM, Beahrs OH, 1959 Struma lymphomatosa (Hashimoto’s thyroiditis) and related thyroidal disorders. J Clin Endocrinol Metab 19: 53–58.CrossRefGoogle Scholar
  8. 8.
    Schlicke CP, Hill JE, Schultz GF, 1960 Carcinoma in chronic thyroiditis. Surg Gynecol Obstet 111: 552–556.PubMedGoogle Scholar
  9. 9.
    Shands WC, 1960 Carcinoma of the thyroid in association with struma lymphomatosa. Ann Surg 151: 675–682.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chesky VE, Hellwing CA, Welch JW, 1962 Cancer of the thyroid associated with Hashimoto’s disease: an analysis of forty-eight cases. Am Surg 28: 678–685.PubMedGoogle Scholar
  11. 11.
    Crile G Jr, Hazard JB, 1962 Incidence of cancer in struma lymphomatosa. Surg Gynecol Obstet 115: 101–103.Google Scholar
  12. 12.
    Hirabayashi RN, Lindsay S, 1965 The relation of thyroid carcinoma and chronic thyroiditis. Surg Gynecol Obstet 121: 243–252.PubMedGoogle Scholar
  13. 13.
    Holmes HB, Kreutner A, O’Brien PH, 1977 Hashimoto’s thyroiditis and its relationship to other thyroid diseases. Surg Gynecol Obstet 144: 887–890.PubMedGoogle Scholar
  14. 14.
    Figg DM, Bratt HJ, Vliet PD, Dean RE, 1978 Thyroid cancer: diagnosis and management based on a review of 142 cases. Am J Surg 135: 671–674.CrossRefGoogle Scholar
  15. 15.
    Ott RA, Calandra DB, McCall A, Shah KH, Lawrence AM, Paloyan E, 1985 The incidence of thyroid carcinoma in patients with Hashimoto’s thyroiditis and solitary cold nodules. Surgery 98: 1202–1206.Google Scholar
  16. 16.
    Ott RA, McCall AR, McHenry C, et al, 1987 The incidence of thyroid carcinoma in Hashimoto’s thyroiditis. Am Surg 53: 442–445.Google Scholar
  17. 17.
    Eisenberg BL, Hensley SD, 1989 Thyroid cancer with coexistent Hashimoto’s thyroiditis. Arch Surg 124: 1045–1047.CrossRefGoogle Scholar
  18. 18.
    McKee RF, Krukowski ZH, Matheson NA, 1993 Thyroid neoplasia coexistent with chronic lymphocytic thyroiditis. Br J Surg 80: 1303–1304.CrossRefGoogle Scholar
  19. 19.
    Sclafani AP, Valdes M, Cho H, 1993 Hashimoto’s thyroiditis and carcinoma of the thyroid: optimal management. Laryngoscope 103: 845–849.CrossRefGoogle Scholar
  20. 20.
    Okayasu I, Fujiwara M, Hara Y, Tanaka Y, Rose NR, 1995 Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese and white and African Americans. Cancer 76: 2312–2318.CrossRefGoogle Scholar
  21. 21.
    Schäffler A, Palitzsch KD, Seiffarth C, et al, 1998 Coexistent thyroiditis is associated with lower tumours stage in thyroid carcinoma. Eur J Clin Invest 28: 838–844.CrossRefGoogle Scholar
  22. 22.
    Loh KC, Greenspan FS, Dong F, Miller TR, Yeo PP, 1999 Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 84: 458–463.CrossRefGoogle Scholar
  23. 23.
    Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP, 1999 Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 126: 1070–1077.CrossRefGoogle Scholar
  24. 24.
    Kebebew E, Treseler PA, Ituarte PHG, Clark OH, 201 Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg 25: 632-637.Google Scholar
  25. 25.
    Tamimi DM, 2002 The association between chronic lymphocytic thyroiditis and thyroid tumors. Int J Surg Pathol 10: 141–146.CrossRefGoogle Scholar
  26. 26.
    Cipolla C, Sandonato L, Graceffa G, et al, 2005 Hashimoto thyroiditis coexistent with papillary thyroid carcinoma. Am Surg 71: 874–878.Google Scholar
  27. 27.
    Kurukahvecioglu O, Taneri F, Yóksel O, Aydin A, Tezel E, Onuk E, 2007 Total thyroidectomy for the treatment of Hashimoto’s thyroiditis coexisting with papillary thyroid carcinoma. Adv Ther 24: 510–516.CrossRefGoogle Scholar
  28. 28.
    Wirtschafter A, Schmidt R, Rosen D, et al, 1997 Expression of the RET/PTC fusion gene as a marker of papillary carcinoma in Hashimoto’s thyroiditis. Laryngoscope 107: 95–100.CrossRefGoogle Scholar
  29. 29.
    Unger P, Ewart M, Wang BY, Gan L, Kohtz DS, Burstein DE, 2003 Expression of p63 in papillary thyroid carcinoma and in Hashimoto’s thyroiditis: a pathobiologic link? Hum Pathol 34: 764–769.CrossRefGoogle Scholar
  30. 30.
    Larson SD, Jackson LN, Riall TS, et al, 2007 Increased incidence of well-differentiated thyroid cancer associated with Hashimoto’s thyroiditis and the role of the PI3k/Akt pathway. J Am Coll Surg 204: 764–763.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Arif S, Blanes A, Diaz-Cano SJ, 2002 Hashimoto’s thyroiditis share features with early papillary thyroid carcinoma. Histopathology 41: 357–362.CrossRefGoogle Scholar
  32. 32.
    Belfiore A, Russo D, Vigneri R, Filetti R, 2001 Graves’ disease, thyroid nodules and thyroid cancer. Clin Endocrinol 55: 711–718.CrossRefGoogle Scholar
  33. 33.
    Rasmussen AK, Feldt-Rasmussen U, Bendtzen K, 1993 The effect of interleukin-1 on the thyroid gland. Autoimmunity 16: 765–769.CrossRefGoogle Scholar
  34. 34.
    Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA, 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 91: 4295–4301.CrossRefGoogle Scholar
  35. 35.
    Williams ED, 2006 Chernobyl and thyroid cancer. J Surg Oncol 94: 670–677.CrossRefGoogle Scholar
  36. 36.
    Vykhovanets EV, Chernyshov VP, Slukvin II, et al, 1997 131I dose-dependent thyroid autoimmune disorders in children living around Chernobyl. Clin Immunol Immunopathol 84: 251–259.CrossRefGoogle Scholar
  37. 37.
    Tronko MD, Brenner AV, Olijnyk VA, et al, 2006 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 91: 4344–4351.CrossRefGoogle Scholar
  38. 38.
    Pacini F, Vorontsova T, Molinaro E, et al, 1998 Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chornobyl radioactive fallout. Lancet 352: 763–766.CrossRefGoogle Scholar
  39. 39.
    Vermiglio F, Castagna MG, Volnova E, et al, 1999 Post-Chernobyl increased prevalence of humoral thyroid autoimmunity in children and adolescents from a moderately iodine-deficient area in Russia. Thyroid 9: 781–786.CrossRefGoogle Scholar
  40. 40.
    Shinkarkina AP, Podgorodnichenko VK, Poverennyi AM, 1994 Antibodies to the thyroid microsomal antigen in children and adolescents subjected to radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station. Radiats Biol Radioecol 34: 3–7.PubMedGoogle Scholar
  41. 41.
    Imaizumi M, Usa T, Tominaga T, et al, 2006 Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure. JAMA 295: 1011–1022.CrossRefGoogle Scholar
  42. 42.
    Vanderpump MP, Tunbridge WM, French JM, et al, 1995 The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 43: 55–68.CrossRefGoogle Scholar
  43. 43.
    Volzke H, Werner A, Wallaschofski H, et al, 2005 Occupational exposure to ionising radiation is associated with autoimmune thyroid disease. J Clin Endocrinol Metab 90: 4587–4592.CrossRefGoogle Scholar
  44. 44.
    Davis S, Kopecky KJ, Hamilton TE, Onstad L, 2004 Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the Hanford nuclear site. JAMA 292: 2600–2613.CrossRefGoogle Scholar
  45. 45.
    Boi F, Lai ML, Marziani B, Minerba L, Faa G, Mariotti S, 2005 High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies. Eur J Endocrinol 153: 637–642.CrossRefGoogle Scholar
  46. 46.
    Baker JR Jr, 1995 The immune response to papillary thyroid cancer. J Clin Endocrinol Metab 80: 3419 3420.Google Scholar
  47. 47.
    Kollur SM, El Sayed S, El Hag A, 2003 Follicular thyroid lesions coexisting with Hashimoto’s thyroiditis: Incidence and possible sources of diagnostic errors. Diagn Cytopathol 28: 35–38.CrossRefGoogle Scholar
  48. 48.
    Ohmori N, Miyakawa M, Ohmori K, Takano K, 2007 Ultrasonographic findings of papillary thyroid carcinoma with Hashimoto’s thyroiditis. Intern Med 46: 547–550.CrossRefGoogle Scholar
  49. 49.
    Pacini F, Mariotti S, 1988 Thyroid autoantibodies in thyroid cancer: incidence and relationship with tumour outcome. Acta Endocrinol 119: 373–380.PubMedCrossRefGoogle Scholar
  50. 50.
    Rubello D, Girelli ME, Casaro D, Piccolo M, Perin A, Busnardo B, 1990 Usefulness of the combined antithyroglobulin antibodies and thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer. J Endocrinol Invest 13: 737–742.CrossRefGoogle Scholar
  51. 51.
    Rubello D, Casara D, 1992 Clinical meaning of circulating ATG in differentiated thyroid cancer: a prospective study. J Nucl Med 33: 1478–1480.PubMedGoogle Scholar
  52. 52.
    Kumar A, Shah DH, Shrihari U, Dandekar SR, Viyojan U, Sharma SM, 1994 Significance of anti-Tg autoantibodies in differentiated thyroid carcinoma. Thyroid 4: 199–202.CrossRefGoogle Scholar
  53. 53.
    Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS, 2005 Clinical Impact of Thyroglobulin (Tg) and Tg Autoantibody Method Differences on the Management of Patients with Differentiated Thyroid Carcinomas. J Clin Endocrinol Metab 90: 5566–5575.CrossRefGoogle Scholar
  54. 54.
    Feldt-Rasmussen U, Holten I, Hansen HS, 1983 Influence of thyroid substitution therapy and thyroid autoantibodies on the value of serum thyroglobulin in recurring thyroid cancer. Cancer 51: 2240–2244.CrossRefGoogle Scholar
  55. 55.
    Hjiyiannakis P, Mundy J, Harmer C, 1999 Thyroglobulin antibodies in differentiated thyroid cancer. Clin Oncol 11: 240–244.CrossRefGoogle Scholar
  56. 56.
    Chung J-K, Park Y J, Kim T Y, et al, 2002 Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation. Clin Endocrinol 57: 215–221.CrossRefGoogle Scholar
  57. 57.
    Larbre H, Schvartz C, Schneider N, et al, 2000 Positive antithyroglobulin antibodies in patients with differentiated thyroid carcinoma. What significance? Ann Endocrinol (Paris) 61: 422–427.Google Scholar
  58. 58.
    Kücük ÖN, Aras G, Kulak HA, Ibis E, 2006 Clinical importance of anti-thyroglobulin auto-antibodies in patients with differentiated thyroid carcinoma: Comparison with 99mTc-MIBI scans. Nucl Med Commun 27: 873–876.CrossRefGoogle Scholar
  59. 59.
    Whitley RJ, Ain KB, 2004 Thyroglobulin: a specific serum marker for the management of thyroid carcinoma. Clin Lab Med 24: 29–47.CrossRefGoogle Scholar
  60. 60.
    Baker JR, Fosso CK, 1993 Immunological aspects of cancers arising from thyroid follicular cells. Endocr Rev 14: 729–746.PubMedGoogle Scholar
  61. 61.
    Souza SL, Montalli da Assumpção LV, Ward LS, 2003 Impact of Previous Thyroid Autoimmune Diseases on Prognosis of Patients with Well-Differentiated Thyroid Cancer. Thyroid 13: 491–495.CrossRefGoogle Scholar
  62. 62.
    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: 1346–1354.PubMedGoogle Scholar
  63. 63.
    Chiovato L, Latrofa F, Braverman LE, et al, 2003 Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens Ann Intern Med 139: 346–351.CrossRefGoogle Scholar
  64. 64.
    Feldt-Rasmussen U, 1983 Serum thyroglobulin and thyroglobulin autoantibodies in thyroid diseases. Pathogenic and diagnostic aspects. Allergy 38: 369–387.CrossRefGoogle Scholar
  65. 65.
    Mariotti S, Barbesino G, Caturegli P, 1995 Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal? J Clin Endocrinol Metab 80: 468–472.CrossRefGoogle Scholar
  66. 66.
    Feldt-Rasmussen U, Schlumberger M, 1988 European interlaboratory comparison of serum thyroglobulin measurement. J Endocrinol Invest 11: 175–181.CrossRefGoogle Scholar
  67. 67.
    Feldt-Rasmussen U, Rasmussen AK, 1985 Serum thyroglobulin (Tg) in presence of thyroglobulin autoantibodies (TgAb). Clinical and methodological relevance of the interaction between Tg and TgAb in vitro and in vivo. J Endocrinol Invest 8: 571–576.CrossRefGoogle Scholar
  68. 68.
    Schaadt B, Feldt-Rasmussen U, Rasmusson B, 1995 Assessment of the influence of thyroglobulin (Tg) autoantibodies and other interfering factors on the use of serum Tg as tumor marker in differentiated thyroid carcinoma. Thyroid 5: 165–170.PubMedCrossRefGoogle Scholar
  69. 69.
    Persoon ACM, Link TPs, Wilde J, Sluite W Jr, Wolffenbuttel BHR, JMW van den Ouweland, 2006 Thyroglobulin (Tg) Recovery Testing with Quantitative Tg Antibody Measurement for Determining Interference in Serum Tg Assays in Differentiated Thyroid Carcinoma. Clin Chem 52: 1196–1199.CrossRefGoogle Scholar
  70. 70.
    Laboratory support for the diagnosis and monitoring of thyroid disease. National Academy of Clinical Biochemistry — Professional Association 2002. http://www. nacb.orgGoogle Scholar
  71. 71.
    Massart C, Maugendre D, 2002 Importance of the Detection Method for Thyroglobulin Antibodies for the Validity of Thyroglobulin Measurements in Sera from Patients with Graves’ Disease. Clin Chem 48: 102–107.PubMedGoogle Scholar
  72. 72.
    Spencer CA, 1996 Recoveries cannot be used to authenticate thyroglobulin (Tg) measurements when sera contain Tg autoantibodies. Clin Chem 42: 661–663.PubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2010

Authors and Affiliations

  1. 1.Department of Medical Endocrinology PE 2132, RigshospitaletNational University HospitalCopenhagenDenmark

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