Radioiodine Therapy of Differentiated Thyroid Cancer

  • Ettore Seregni
  • Andrew Mallia
  • Carlo Chiesa
  • Gabriele Scaramellini
  • Maura Massimino
  • Emilio Bombardieri


The incidence of thyroid carcinomas is steadily increasing. Primary tumors of the thyroid gland include carcinomas that originate from epithelial cells (carcinomas of thyrocytes and C-cells), and from non-epithelial cells (lymphomas and sarcomas). Thyrocytes are the main functional cells that produce thyroid hormones (T3 and T4), which are vital for human metabolism. The epithelial tumors can be divided into the well-differentiated (papillary and follicular carcinomas), poorly-differentiated, undifferentiated (anaplastic carcinomas) carcinomas, and tumor of the parafollicular or C-cells (medullary carcinoma). Three common histopathological diagnosis of papillary thyroid carcinomas (PTC) include classical PTC, follicular variant PTC and mixed PTC, and follicular thyroid carcinomas (FTC). Mixed medullary and follicular carcinomas are rare neoplasms which show morphologic features of both follicular and C-cell differentiation. These neoplasms must be distinguished from the follicular variant of medullary carcinoma and from medullary carcinoma with entrapped normal follicles. Table 8.1 summarizes the WHO classification of thyroid tumors published in 2004 [1]. According to the American Cancer Society there are 37,000 new cases of thyroid cancer annually in the United States, with approximately 75 % occurring in women [2].


Thyroid Cancer Papillary Thyroid Carcinoma Thyroid Stimulation Hormone Differentiate Thyroid Cancer Follicular Thyroid Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    DeLellis R, Lloyd R, Heitz P, Eng C. World Health Organization classification of tumors: pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004.Google Scholar
  2. 2.
    Enewold L, Zhu K, Ron E, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev. 2009;18:784–91.PubMedCrossRefGoogle Scholar
  3. 3.
    IAEA. Nuclear medicine in thyroid cancer management: a practical approach [online]. 2009 [cited 2011 Mar 4]; Available from URL:
  4. 4.
    Sherman SI. Thyroid caricinoma. Lancet. 2003;361: 501–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid cancer. J Clin Endocrinol Metab. 2006;91(1):313–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Tuttle RM, Leboeuf R, Martorella AJ. Papillary thyroid cancer: monitoring and therapy. Endocrinol Metab Clin North Am. 2007;36:753–8; vii.Google Scholar
  7. 7.
    Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998;338:297–306.PubMedCrossRefGoogle Scholar
  8. 8.
    Mazzaferri EL, Kloos RT. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001;86:1447–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Montone KT, Baloch ZW, LiVolsi VA. The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical and pathology and cytopathology review. Arch Pathol Lab Med. 2008;132:1241–50.PubMedGoogle Scholar
  10. 10.
    Marqusee E, Benson CB, Frates MC, et al. Usefulness of ultrasonography in the management of nodular thyroid disease. Ann Intern Med. 2000;1339:696–700.Google Scholar
  11. 11.
    Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351:1764–71.PubMedCrossRefGoogle Scholar
  12. 12.
    Hagag P, Strauss S, Weiss M. Role of ultrasounded-guided fine-needle aspiration biopsy in the evaluation of non-palpable thyroid nodules. Thyroid. 1998;8: 989–95.PubMedCrossRefGoogle Scholar
  13. 13.
    American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11): 1167–214.Google Scholar
  14. 14.
    Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biospy of thyroid masses. Thyroid. 1998;8:283–9.CrossRefGoogle Scholar
  15. 15.
    Are C, Hsu JF, Ghossein RA, Schoder H, Shah JP, Shaha AR. Histological aggressiveness of flurode­oxyglucose positron-emission tomogram (FDG-PET)- detected incidental thyroid carcinomas. Ann Surg Oncol. 2007;14:3210–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Pacini F, Castagna MG, Brilli L, Pentheroudakis G. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:v214–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Carter WB, Tourtelot JB, Savell JG, Lilienfeld H. New treatments and shifting paradigms in differentiated thyroid cancer management. Cancer Control. 2011;18(2):96–103.PubMedGoogle Scholar
  18. 18.
    Siedlin SM, Marinelli LD, Oshry E. Radioactive iodine-therapy: effect on functioning metastases of adenocarcinoma of thyroid. JAMA. 1946;132: 838–47.CrossRefGoogle Scholar
  19. 19.
    Klain M, Ricard M, Leboulleux S, et al. Radioiodine therapy for papillary and follicular thyroid carcinoma. Eur J Nucl Med. 2002;29:S479–85.CrossRefGoogle Scholar
  20. 20.
    Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418–28.PubMedCrossRefGoogle Scholar
  21. 21.
    Lind P, Igerc I, Kohlfürst S. Radioiodine therapy: malignant thyroid disease. In: Biersack HJ, Freeman LM, editors. Clinical nuclear medicine. Berlin: Springer; 2007. p. 418–32.CrossRefGoogle Scholar
  22. 22.
    Reiners C. Radioiodine therapy in patients with pulmonary metastases of thyroid cancer: when to treat, when not to treat? Eur J Nucl Med Mol Imaging. 2003;30(7):939–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Jonklaas J, Sarlis NJ, Litofsky D, et al. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid. 2006;16:1229–42.PubMedCrossRefGoogle Scholar
  24. 24.
    Sawka AM, Brierley JD, Tsang RW, et al. An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinol Metab Clin North Am. 2008;37:457–80.PubMedCrossRefGoogle Scholar
  25. 25.
    Shattuk TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med. 2005;352:2406–12.CrossRefGoogle Scholar
  26. 26.
    Pacini F, Schlumberger M, Dralle H, et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006;154:787–803.PubMedCrossRefGoogle Scholar
  27. 27.
    Society of Nuclear Medicine. Procedure guideline for therapy of thyroid disease with iodine-131 (sodium iodide): version 2.0. 2005.
  28. 28.
    Luster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35(10):1941–59.PubMedCrossRefGoogle Scholar
  29. 29.
    Muresan MM, Olivier P, Leclère J, et al. Bone metastases from differentiated thyroid carcinoma. Endocr Relat Cancer. 2008;15(1):37–49.PubMedCrossRefGoogle Scholar
  30. 30.
    Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma; benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Haugen BR, Kane MA. Approach to the thyroid cancer patient with extracervical metastases. J Clin Endocrinol Metab. 2010;95(3):987–93.PubMedCrossRefGoogle Scholar
  32. 32.
    O’Neill CJ, Oucharek J, Learoyd D, Sidhu SB. Standard and emerging therapies for metastatic differentiated thyroid cancer. Oncologist. 2010;15(2): 146–56.PubMedCrossRefGoogle Scholar
  33. 33.
    Bernier MO, Leehardt L, Hoang C, et al. Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2001;86:1568–73.PubMedCrossRefGoogle Scholar
  34. 34.
    Petrich T, Widjaja A, Musholt TJ, et al. Outcome after radioiodine therapy in 107 patients with differentiated thyroid carcinoma and initial bone metastases: side-effects and influence of age. Eur J Nucl Med. 2001;28: 203–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hindié E, Mellière D, Lange F, et al. Functioning pulmonary metastases of thyroid cancer: does radioiodine influence the prognosis? Eur J Nucl Med. 2003;30(7):974–81.CrossRefGoogle Scholar
  36. 36.
    Hachshaw A, Harmer C, Mallick U, Haq M, Franklyn JA. 131I activity for remnant ablation in patients with differentiated thyroid cancer: a systematic review. J Clin Endocrinol Metab. 2007;92:28–38.CrossRefGoogle Scholar
  37. 37.
    Jarzab B, Handkiewicz-Junak D, Wloch J. Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review. Endocr Relat Cancer. 2005;12:773–803.PubMedCrossRefGoogle Scholar
  38. 38.
    Benua RS, Cicale NR, Sonenberg M, Rawson RW. The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer. Am J Roentgenol Radium Ther Nucl Med. 1962;87:171–82.PubMedGoogle Scholar
  39. 39.
    Lassman M, Hӓnscheid H, Chiesa C, Hindorf C, Flux G, Luster M. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging. 2008;35(7):1405–12.CrossRefGoogle Scholar
  40. 40.
    Maxon 3rd HR, Smith HS. Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin North Am. 1990;19(3):685–718.PubMedGoogle Scholar
  41. 41.
    Freudenberg LS, Jentzen W, Stahl A, Bockisch A, Rosenbaum-Krumme SJ. Clinical applications of 124I-PET/CT in patients with differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2011;38 Suppl 1:S48–56.PubMedCrossRefGoogle Scholar
  42. 42.
    Society of Nuclear Medicine: Procedure Guideline For Scintigraphy For Differentiated Papillary and Follicular Thyroid Cancer. 2006.
  43. 43.
    Rawson RW, Rall JE, Peacock W. Limitations and indications in the treatment of cancer of the thyroid with radioactive iodine. J Clin Endocrinol Metab. 1951;11:1128–31.PubMedCrossRefGoogle Scholar
  44. 44.
    Dam HQ, Kim SM, Lin HC, Intenzo CM. 131 I therapeutic efficacy is not influenced by stunning after diagnostic whole-body scanning. Radiology. 2004;232:527–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109–42.PubMedCrossRefGoogle Scholar
  46. 46.
    Pluijmen MJ, Eustatia-Rutten C, Goslings BM, et al. Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2003;58(4): 428–35.CrossRefGoogle Scholar
  47. 47.
    Jentzen W, Balschuweit D, Schmitz J, et al. The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging. Eur J Nucl Med Mol Imaging. 2010;37(12): 2298–306.PubMedCrossRefGoogle Scholar
  48. 48.
    Abrosetti MC, Colato C, Dardano A, Monzani F, Ferdeghini M. Radioiodine ablation: when and how. Q J Nucl Med Mol Imaging. 2009;53:473–81.Google Scholar
  49. 49.
    Panzegrau B, Gordon L, Goudy GH. Outpatient therapeutic 131I for thyroid cancer. J Nucl Med Technol. 2005;33:28–30.PubMedGoogle Scholar
  50. 50.
    Parthasarathy KL, Crawford ES. Treatment of thyroid carcinoma: emphasis on high-dose 131I outpatient therapy. J Nucl Med Technol. 2002;30:165–71.PubMedGoogle Scholar
  51. 51.
    Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thryoid cancer patients. Br J Cancer. 2003;89(9):1638–44.PubMedCrossRefGoogle Scholar
  52. 52.
    Iyer NG, Morris LG, Tuttle RM, Shaha AR, Ganly I. Rising incidence of second cancers in patients with low-risk (T1N0) thyroid cancer who receive radioactive iodine therapy. Cancer. 2011;117(19):4439–46.PubMedCrossRefGoogle Scholar
  53. 53.
    McLeod DS. Current concepts and future directions in differentiated thyroid cancer. Clin Biochem Rev. 2010;31(1):9–19.PubMedGoogle Scholar
  54. 54.
    Pacini F, Molinaro E, Castagna MG, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2003;88(8): 3668–773.PubMedCrossRefGoogle Scholar
  55. 55.
    Wong KT, Choi FP, Lee YY, Ahuja AT. Current role of radionuclide imaging in differentiated thyroid cancer. Cancer Imaging. 2008;8:159–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Robbins RJ, Wan Q, Grewal RK, et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab. 2006;91:498–505.PubMedCrossRefGoogle Scholar
  57. 57.
    Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985;56(9): 2155–60.PubMedCrossRefGoogle Scholar
  58. 58.
    Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol. 2007;8:148–56.PubMedCrossRefGoogle Scholar
  59. 59.
    Klagge A, Krause K, Schierle K, Steinert F, Dralle H, Fuhrer D. Somatostatin receptor subtype expression in human thyroid tumours. Horm Metab Res. 2010;42(4):237–40. Epub 2010 Jan 21.Google Scholar
  60. 60.
    Carlisle MR, McDougall IR. Familial differentiated carcinoma of the thryoid. In: Biersack HJ, Grünwald F, editors. Thyroid cancer. Berlin: Springer; 2005. p. 57–70.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ettore Seregni
    • 1
  • Andrew Mallia
    • 2
  • Carlo Chiesa
    • 1
  • Gabriele Scaramellini
    • 3
  • Maura Massimino
    • 4
  • Emilio Bombardieri
    • 1
  1. 1.Department of Nuclear MedicineFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  2. 2.School of Specialization in Nuclear MedicineUniversity of MilanoMilanItaly
  3. 3.Division of ORL SurgeryFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  4. 4.Division of Pediatric OncologyFondazione IRCCS Istituto Nazionale TumoriMilanItaly

Personalised recommendations