Hybrid Imaging and Radionuclide Therapy for Thyroid Disorders

  • Federica Guidoccio
  • Gayane Aghakhanyan
  • Mariano GrossoEmail author


The thyroid gland is a butterfly-shaped organ located anteriorly to the trachea at the level of the second and third tracheal rings. It consists of two lobes connected by the isthmus in the midline. Anteriorly, its surface is convex; posteriorly, it is concave. The gland’s upper extremities are known as the upper poles. Similarly, the lower extremities of the lateral lobes are known as the lower poles (or base of the lobe). The weight of the thyroid of the normal non-goitrous adult is 6–20 g depending on the body size and iodine supply. From upper pole to base, the thyroid lobes usually measure 4 cm. Their width is 15–20 mm, and their thickness is 20–39 mm. The isthmus is 12–15 mm high, lies across the trachea anteriorly just below the level of the cricoid cartilage, and connects the two lobes. The shape and attachments of the organ and its relationship to the trachea are important in examination and diagnosis and from the point of view of pressure symptoms.


Anaplastic thyroid cancer, ATC Graves’ disease Differentiated thyroid cancer, DTC Fine needle aspiration biopsy, FNAC Follicular thyroid cancer, FTC Hashimoto’s thyroiditis Medullary thyroid cancer, MTC Multinodular goiter Nontoxic multinodular goiter Papillary thyroid cancer, PTC Poorly differentiated thyroid cancer, PDTC Radioiodine uptake test Thyroid cancer Thyroid gland Thyroid gland scintigraphy Thyroid nodules Thyroid ultrasonography Thyroid-stimulating hormone, TSH Toxic adenoma Multinodular toxic goiter, MTG Thyroglobulin Radioiodine therapy of hyperthyroidism Radioiodine therapy of differentiated thyroid cancer Iodine-refractory thyroid cancer 


  1. 1.
    Maenhaut C, Christophe D, Vassart G, et al. Ontogeny, anatomy, metabolism and physiology of the thyroid. [Updated 2015 Jul 15]. In: De Groot LJ, Chrousos G, Dungan K, et al, eds. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000. Available from:
  2. 2.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1–133.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Popoveniuc G, Jonklaas J. Thyroid nodules. Med Clin North Am. 2012;96:329–49.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Kravets I. Hyperthyroidism: diagnosis and treatment. Am Fam Physician. 2016;93:363–70.PubMedGoogle Scholar
  5. 5.
    Carlè A, Bulow Pedersen I, Knudsen N, et al. Epidemiology of subtypes of hyperthyroidism in Denmark. A population-based study. Eur J Endocrinol. 2011;164:801–9.PubMedGoogle Scholar
  6. 6.
    Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental issues in thyroid diseases. Front Endocrinol. 2017;8:50. eCollection 2017.CrossRefGoogle Scholar
  7. 7.
    Menconi F, Marcocci C, Marinò M. Diagnosis and classification of Graves’ disease. Autoimmun Rev. 2014;13:398–402.PubMedGoogle Scholar
  8. 8.
    Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev. 2015;14:174–80.PubMedGoogle Scholar
  9. 9.
    Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13:391–7.PubMedGoogle Scholar
  10. 10.
    Shrestha RT, Hennessey J. Acute and subacute, and Riedel’s thyroiditis. [Updated 2015 Dec 8]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000. Available from:
  11. 11.
    Dean DS. Thyroiditis. In: Baskin HJ, Duick DS, Levine RA, editors. Thyroid ultrasound and ultrasound-guided FNA. 2nd ed. Boston, MA: Springer US; 2008. p. 63–75.Google Scholar
  12. 12.
    Garberoglio S, Testori O. Role of nuclear medicine in the diagnosis of benign thyroid diseases. Front Horm Res. 2016;45:24–36.PubMedGoogle Scholar
  13. 13.
    Metso S, Jaatinen P, Huhtala H, Luukkaala T, Oksala H, Salmi J. Long-term follow-up study of radioiodine treatment of hyperthyroidism. Clin Endocrinol (Oxf). 2004;61:641–8.Google Scholar
  14. 14.
    Sridama V, Mccormick M, Kaplan EL, Fauchet R, Degroot LJ. Long-term follow-up study of compensated low-dose 131I therapy for Graves’ disease. N Engl J Med. 1984;311:426–32.PubMedGoogle Scholar
  15. 15.
    Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21:593–646.Google Scholar
  16. 16.
    Farrar JJ, Toft AD. Iodine-131 treatment of hyperthyroidism: current issues. Clin Endocrinol (Oxf). 1991;35:207–12.Google Scholar
  17. 17.
    Howarth D, Epstein M, Lan L, Tan P, Booker J. Determination of the optimal minimum radioiodine dose in patients with Graves’ disease: a clinical outcome study. Eur J Nucl Med. 2001;28:1489–95.PubMedGoogle Scholar
  18. 18.
    Orsini F, et al. Personalization of radioiodine treatment for Graves’ disease: a prospective, randomized study with a novel method for calculating the optimal 131I-iodide activity based on target reduction of thyroid mass. Q J Nucl Med Mol Imaging. 2012;56:496–502.PubMedGoogle Scholar
  19. 19.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Brierley JD, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th ed. Weinheim, Germany: Wiley; 2017. p. 69–71.Google Scholar
  21. 21.
    Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214.PubMedGoogle Scholar
  22. 22.
    Tuttle RM, Tala H, Shah J, et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010;20:1341–9.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Grimm D Current knowledge in thyroid cancer—from bench to bedside. Int J Mol Sci. 2017;18(7). pii: E1529. doi:
  24. 24.
    Neff RL, Farrar WB, Kloos RT, Burman KD. Anaplastic thyroid cancer. Endocrinol Metab Clin N Am. 2008;37:525–38.Google Scholar
  25. 25.
    Samaan NA, Ordonez NG. Uncommon types of thyroid cancer. Endocrinol Metab Clin N Am. 1990;19:637–48.Google Scholar
  26. 26.
    Rusinek D, Chmielik E, Krajewska J, Jarzab M, Oczko-Wojciechowska M, Czarniecka A, Jarzab B. Current advances in thyroid cancer management. Are we ready for the epidemic rise of diagnoses? Int J Mol Sci. 2017;18(8). pii: E1817. doi:
  27. 27.
    Li Q, Lin X, Shao Y, Xiang F, Samir AE. Imaging and screening of thyroid cancer. Radiol Clin North Am. 2017;55:1261–71.PubMedGoogle Scholar
  28. 28.
    Rago T, Vitti P, Chiovato L, et al. Role of conventional ultrasonography and color flow-Doppler sonography in predicting malignancy in “cold” thyroid nodules. Eur J Endocrinol. 1998;138:41–6.PubMedGoogle Scholar
  29. 29.
    Frates MCM, Benson CBC, Charboneau JWJ, et al. Management of thyroid nodules detected at US Society of Radiologists in Ultrasound consensus conference statement. Radiology. 2005;237:794–800.PubMedGoogle Scholar
  30. 30.
    Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2009;132:658–65.PubMedGoogle Scholar
  31. 31.
    Eszlinger M, Lau L, Ghaznavi S, Symonds C, Chandarana SP, Khalil M, Paschke R. Molecular profiling of thyroid nodule fine-needle aspiration cytology. Nat Rev Endocrinol. 2017;13:415–24.PubMedGoogle Scholar
  32. 32.
    Lazar V, Bidart JM, Caillou B, Mahé C, Lacroix L, Filetti S, Schlumberger M. Expression of the Na+/I symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab. 1999;84:3228–34.PubMedGoogle Scholar
  33. 33.
    Giovanella S, Suriano S, Maffioli M, Ceriani M. 18FDG-positron emission tomography/computed tomography (PET/CT) scanning in thyroid nodules with nondiagnostic cytology. Clin Endocrinol. 2011;74:644–8.Google Scholar
  34. 34.
    Piccardo A, Puntoni M, Treglia G, Foppiani L, Bertagna F, Paparo F, et al. Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology. Eur J Endocrinol. 2016;174:693–703.PubMedGoogle Scholar
  35. 35.
    Nayan S, Ramakrishna J, Gupta MK. The proportion of malignancy in incidental thyroid lesions on 18F-FDG PET study: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2014;151:190–200.PubMedGoogle Scholar
  36. 36.
    Agrawal K, Weaver J, Ul-Hassan F, Jeannon JP, Simo R, Carroll P, et al. Incidence and significance of incidental focal thyroid uptake on 18F-FDG PET study in a large patient cohort: retrospective single-centre experience in the United Kingdom. Eur Thyroid J. 2015;4:115–22.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Palaniswamy SS, Subramanyam P. Diagnostic utility of PETCT in thyroid malignancies: an update. Ann Nucl Med. 2013;27:681–93.PubMedGoogle Scholar
  38. 38.
    Chiacchio S, Lorenzoni A, Boni G, Rubello D, Elisei R, Mariani G. Anaplastic thyroid cancer: prevalence, diagnosis and treatment. Minerva Endocrinol. 2008;33:341–57.PubMedGoogle Scholar
  39. 39.
    Bodet-Milin C, Faivre-Chauvet A, Carlier T, Rauscher A, Bourgeois M, Cerato E, et al. Immuno-PET using anticarcinoembryonic antigen bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the pretargeting parameters in a first-in-human trial. J Nucl Med. 2016;57:1505–11.PubMedGoogle Scholar
  40. 40.
    Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS, Sturgeon C. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg. 2007;246:375–81.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Leboulleux S, Girard E, Rose M, et al. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab. 2007;92:3590–4.PubMedGoogle Scholar
  43. 43.
    Sywak M, Cornford L, Roach P, Stalberg P, Sidhu S, Delbridge L. Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery. 2006;140:1000–5.PubMedGoogle Scholar
  44. 44.
    Palazzo FF, Gosnell J, Savio R, Reeve TS, Sidhu SB, Sywak MS, et al. Lymphadenectomy for papillary cancer: changes in practice over four decades. Eur J Surg Oncol. 2006;32:340–4.PubMedGoogle Scholar
  45. 45.
    Carty SE, Cooper DS, Doherty GM, Duh QY, Kloos RT, Mandel SJ, et al. on behalf of ATA, AAES, AAOHNS, AHNS. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid 2009;19:1153–1158Google Scholar
  46. 46.
    DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414–24.PubMedGoogle Scholar
  47. 47.
    Maxon HR III, Englaro EE, et al. Radioiodine-131 therapy for well-differentiated thyroid cancer – a quantitative radiation dosimetric approach: outcome and validation in 85 patients. J Nucl Med. 1992;33:1132–6.PubMedGoogle Scholar
  48. 48.
    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.PubMedGoogle Scholar
  49. 49.
    Tubiana M, Schlumberger M, Rougier P, et al. Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer. 1985;55:794–804.PubMedGoogle Scholar
  50. 50.
    Baudin E, Travagli JP, Ropers J, et al. Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer. 1998;83:553–9.PubMedGoogle Scholar
  51. 51.
    Simpson WJ, Panzarella T, Carruthers JS, Gospodarowicz MK, Sutcliffe SB. Papillary and follicular thyroid cancer: impact of treatment in 1578 patients. Int J Radiat Oncol Biol Phys. 1988;14:1063–75.PubMedGoogle Scholar
  52. 52.
    Grebe SK, Hay ID. Follicular cell-derived thyroid carcinomas. Cancer Treat Res. 1997;89:91–140.PubMedGoogle Scholar
  53. 53.
    Ruel E, Thomas S, Dinan M, Perkins JM, Roman SA, Sosa JA. Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer. J Clin Endocrinol Metab. 2015;100:1529–36.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Elisei R, Agate L, Viola D, Matrone A, Biagini A, Molinaro E. How to manage patients with differentiated thyroid cancer and a rising serum thyroglobulin level. Endocrinol Metab Clin North Am. 2014;43:331–44.PubMedGoogle Scholar
  55. 55.
    Wang LY, Roman BR, Palmer FL, et al. Effectiveness of routine ultrasonographic surveillance of patients with low-risk papillary carcinoma of the thyroid. Surgery. 2016;159:1390–5.PubMedGoogle Scholar
  56. 56.
    Remy H, Borget I, Leboulleux S, et al. 131I effective half-life and dosimetry in thyroid cancer patients. J Nucl Med. 2008;49:1445–50.PubMedGoogle Scholar
  57. 57.
    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.PubMedGoogle Scholar
  58. 58.
    Sgouros G, Song H, Ladenson PW, Wahl RL. Lung toxicity in radioiodine therapy of thyroid carcinoma: development of a dose-rate method and dosimetric implications of the 80-mCi rule. J Nucl Med. 2006;47:1977–84.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Bolch WE, Bouchet LG, Robertson JS, et al. MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions—radionuclide S values at the voxel level. J Nucl Med. 1999;40(Suppl):11S–36S.PubMedGoogle Scholar
  60. 60.
    Pacini F, Ladenson PW, Schlumberger M, et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab. 2006;91:926–32.PubMedGoogle Scholar
  61. 61.
    Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012;366:1663–73.PubMedGoogle Scholar
  62. 62.
    Mallick U, Harmer C, Yap B, et al. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012;366:1674–85.PubMedGoogle Scholar
  63. 63.
    Silberstein EB, Alavi A, Balon HR, et al. Procedure guideline for therapy of thyroid disease with iodine-131. J Nucl Med. 2002;43:856–61.PubMedGoogle Scholar
  64. 64.
    Park JT II, Hennessey JV. Two-week low iodine diet is necessary for adequate outpatient preparation for radioiodine rhTSH scanning in patients taking levothyroxine. Thyroid. 2004;14:57–63.PubMedGoogle Scholar
  65. 65.
    Regalbuto C, Gullo D, Vigneri R, Pezzino V. Measurement of iodine before 131I in thyroid cancer. Lancet. 1994;344:1501–2.PubMedGoogle Scholar
  66. 66.
    Rawson RW, Rall JE, Peacock W. Limitations in the treatment of cancer of the thyroid with radioactive iodine. Trans Assoc Am Phys. 1951;64:179–98.PubMedGoogle Scholar
  67. 67.
    Bajén MT, Mañé S, Muñoz A, Ramòn GJ. Effect of diagnostic dose of 185 MBq 131I on postsurgical thyroid remnants. J Nucl Med. 2000;41:2038–42.PubMedGoogle Scholar
  68. 68.
    McDougall IR, Iagaru A. Thyroid stunning: fact or fiction? Semin Nucl Med. 2011;41:105–12.PubMedGoogle Scholar
  69. 69.
    Park HM. Stunned thyroid after high dose 131I imaging. Clin Nucl Med. 1992;17:501–2.PubMedGoogle Scholar
  70. 70.
    Sisson JC, Avram AM, Lawson SA, Gauger PG, Doherty GM. The so-called stunning of thyroid tissue. J Nucl Med. 2006;47:1406–12.PubMedGoogle Scholar
  71. 71.
    Park HM, Perkins OW, Edmondson JW, Schnute RB, Manatunga A. Influence of diagnostic radioiodines on the uptake of ablative dose of iodine-131. Thyroid. 1994;4:49–54.PubMedGoogle Scholar
  72. 72.
    Muratet JP, Giraud P, Daver A, Minier JF, Gamelin E, Larra F. Predicting the efficacy of first iodine-131 treatment in differentiated thyroid carcinoma. J Nucl Med. 1997;38:1362–8.PubMedGoogle Scholar
  73. 73.
    Nordén MM, Larsson F, Tedelind S, Carlsson T, Lundh C, Forssell-Aronsson E, Nilsson M. Down-regulation of the sodium/iodide symporter explains131I-induced thyroid stunning. Cancer Res. 2007;6:7512–7.Google Scholar
  74. 74.
    Medvedec M. Thyroid stunning in vivo and in vitro. Nucl Med Commun. 2005;26:731–5.PubMedGoogle Scholar
  75. 75.
    Caudill CM, Zhu Z, Ciampi R, Stringer JR, Nikiforov YE. Dose-dependent generation of RET/PTC in human thyroid cells after in vitro exposure to gamma-radiation: a model of carcinogenic chromosomal rearrangement induced by ionizing radiation. J Clin Endocrinol Metab. 2005;90:2364–9.PubMedGoogle Scholar
  76. 76.
    de Geus-Oei LF, Oei HY, Hennemann G, Krenning EP. Sensitivity of 123I whole-body scan and thyroglobulin in the detection of metastases or recurrent differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2002;29:768–74.PubMedGoogle Scholar
  77. 77.
    Sherman SI, Tielens ET, Sostre S, Wharam MD Jr, Ladenson PW. Clinical utility of posttreatment radioiodine scans in the management of patients with thyroid carcinoma. J Clin Endocrinol Metab. 1994;78:629–34.PubMedGoogle Scholar
  78. 78.
    Fatourechi V, Hay ID, Mullan BP, Wiseman GA, Eghbali-Fatourechi GZ, Thorson LM, Gorman CA. Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer? Thyroid. 2000;10:573–7.PubMedGoogle Scholar
  79. 79.
    Chen L, Luo Q, Shen Y, Yu Y, Yuan Z, Lu H, Zhu R. Incremental value of 131I SPECT/CT in the management of patients with differentiated thyroid carcinoma. J Nucl Med. 2008;49:1952–7.PubMedGoogle Scholar
  80. 80.
    Wong KK, Zarzhevsky N, Cahill JM, Frey KA, Avram AM. Incremental value of diagnostic 131I SPECT/CT fusion imaging in the evaluation of differentiated thyroid carcinoma. AJR Am J Roentgenol. 2008;191:1785–94.PubMedGoogle Scholar
  81. 81.
    Aide N, Heutte N, Rame JP, Rousseau E, Loiseau C, Henry-Amar M, Bardet S. Clinical relevance of single-photon emission computed tomography/computed tomography of the neck and thorax in postablation 131I scintigraphy for thyroid cancer. J Clin Endocrinol Metab. 2009;94:2075–84.PubMedGoogle Scholar
  82. 82.
    Schmidt D, Szikszai A, Linke R, Bautz W, Kuwert T. Impact of 131I SPECT/spiral CT on nodal staging of differentiated thyroid carcinoma at the first radioablation. J Nucl Med. 2009;50:18–23.PubMedGoogle Scholar
  83. 83.
    Spanu A, Solinas ME, Chessa F, Sanna D, Nuvoli S, Madeddu G. 131I SPECT/CT in the follow-up of differentiated thyroid carcinoma: incremental value versus planar imaging. J Nucl Med. 2009;50:184–90.PubMedGoogle Scholar
  84. 84.
    Kohlfuerst S, Igerc I, Lobnig M, et al. Posttherapeutic 131ISPECT-CT offers high diagnostic accuracy when the findings on conventional planar imaging are inconclusive and allows a tailored patient treatment regimen. Eur J Nucl Med Mol Imaging. 2009;36:886–93.PubMedGoogle Scholar
  85. 85.
    Akram K, Parker JA, Donohoe K, Kolodny G. Role of single photon emission computed tomography/computed tomography in localization of ectopic parathyroid adenoma: a pictorial case series and review of the current literature. Clin Nucl Med. 2009;34:500–2.PubMedGoogle Scholar
  86. 86.
    Barwick T, Murray I, Megadmi H, et al. Single photon emission computed tomography (SPECT)/computed tomography using Iodine-123 in patients with differentiated thyroid cancer: additional value over whole body planar imaging and SPECT. Eur J Endocrinol. 2010;162:1131–9.PubMedGoogle Scholar
  87. 87.
    Mustafa M, Kuwert T, Weber K, et al. Regional lymph node involvement in T1 papillary thyroid carcinoma: a bicentric prospective SPECT/CT study. Eur J Nucl Med Mol Imaging. 2010;37:1462–6.PubMedGoogle Scholar
  88. 88.
    Grewal RK, Tuttle RM, Fox J, et al. The effect of posttherapy 131I SPECT/CT on risk classification and management of patients with differentiated thyroid cancer. J Nucl Med. 2010;51:1361–7.PubMedGoogle Scholar
  89. 89.
    Wong KK, Sisson JC, Koral KF, Frey KA, Avram AM. Staging of differentiated thyroid carcinoma using diagnostic 131I SPECT/CT. AJR Am J Roentgenol. 2010;195:730–6.PubMedGoogle Scholar
  90. 90.
    Avram AM. Radioiodine scintigraphy with SPECT/CT: an important diagnostic tool for thyroid cancer staging and risk stratification. J Nucl Med Technol. 2014;42:170–80.PubMedGoogle Scholar
  91. 91.
    Al Balooshi B, Vinjamuri S. Should all patients with differentiated thyroid carcinoma undergo 131I SPECT-CT scanning rather than 131I whole-body scanning? Nucl Med Commun. 2015;36:540–52.Google Scholar
  92. 92.
    Allweiss P, Braunstein GD, Katz A, Waxman A. Sialadenitis following I-131 therapy for thyroid carcinoma: concise communication. J Nucl Med. 1984;25:755–8.PubMedGoogle Scholar
  93. 93.
    Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM. Intermediate and long-term side effects of high-dose radioiodinetherapy for thyroid carcinoma. J Nucl Med. 1998;39:1551–4.PubMedGoogle Scholar
  94. 94.
    de Vathaire F, Schlumberger M, Delisle MJ, Francese C, Challeton C, de la Genardière E, et al. Leukaemias and cancers following iodine-131 administration for thyroid cancer. Br J Cancer. 1997;75:734–9.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Verkooijen RB, Smit JW, Romijn JA, Stokkel M. The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer. Eur J Endocrinol. 2006;155:801–6.PubMedGoogle Scholar
  96. 96.
    Subramanian S, Goldstein DP, et al. Second primary malignancy risk in thyroid cancer survivors: a systematic review and metaanalysis. Thyroid. 2007;17:1277–88.PubMedGoogle Scholar
  97. 97.
    Garsi J-P, Schlumberger M, Rubino C, et al. Therapeutic administration of 131I for differentiated thyroid cancer: radiation dose to ovaries and outcome of pregnancies. J Nucl Med. 2008;49:845–52.PubMedGoogle Scholar
  98. 98.
    Wichers M, Benz E, Palmedo H, Biersack HJ, Grünwald F, Klingmüller D. Testicular function after radioiodine therapy for thyroid carcinoma. Eur J Nucl Med. 2000;27:503–7.PubMedGoogle Scholar
  99. 99.
    Rosário PW, Barroso AL, Rezende LL, Padro EL, Borges MA, Guimares VC, Purisch S. Testicular function after radioiodine therapy in patients with thyroid cancer. Thyroid. 2006;16:667–70.PubMedGoogle Scholar
  100. 100.
    Hebestreit H, Biko J, Drozd V, Demidchik Y, Burkhardt A, Trusen A, et al. Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl. Eur J Nucl Med Mol Imaging. 2011;38:1683–90.PubMedGoogle Scholar
  101. 101.
    Reiners C, Biko J, Haenscheid H, Hebestreit H, Kirinjuk S, Baranowski O, et al. Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2013;98:3039–48.PubMedGoogle Scholar
  102. 102.
    Pilli T, Brianzoni E, Capoccetti F, et al. A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer. J Clin Endocrinol Metab. 2007;92:3542–6.PubMedGoogle Scholar
  103. 103.
    Santini F, Pinchera A, Marsili A, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab. 2005;90:124–7.PubMedGoogle Scholar
  104. 104.
    Sawin CT, Geller A, Hershman JM, Castelli W, Bacharach P. The aging thyroid. The use of thyroid hormone in older persons. JAMA. 1989;261:2653–5.PubMedGoogle Scholar
  105. 105.
    Bartalena L, Martino E, Pacchiarotti A, et al. Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients. J Clin Endocrinol Metab. 1987;64:849–55.PubMedGoogle Scholar
  106. 106.
    Marcocci C, Golia F, Bruno-Bossio G, Vignali E, Pinchera A. Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women. J Clin Endocrinol Metab. 1994;78:818–23.PubMedGoogle Scholar
  107. 107.
    Cooper DS, Specker B, Ho M, et al. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid. 1998;8:737–44.PubMedGoogle Scholar
  108. 108.
    Mazzaferri EL, Jhiang SM. Differentiated thyroid cancer long-term impact of initial therapy. Trans Am Clin Climatol Assoc. 1995;106:151–68.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Schlumberger M. Can iodine-131 whole-body scan be replaced by thyroglobulin measurement in the post-surgical follow-up of differentiated thyroid carcinoma? J Nucl Med. 1992;33:172–3.PubMedGoogle Scholar
  110. 110.
    Mazzaferri EL. Changing paradigms in the follow-up of patients with differentiated thyroid cancer: an alternative to [18F]fluorodeoxyglucose positron emission tomographic scanning. Endocr Pract. 2003;9:324–6.PubMedGoogle Scholar
  111. 111.
    Van Herle AJ. Serum thyroglobulin levels in patients with differentiated thyroid carcinoma. Ann Radiol (Paris). 1977;20:743–5.Google Scholar
  112. 112.
    Spencer CA, Lopresti JS. Measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer. Nat Clin Pract Endocrinol Metab. 2008;4:223–33.PubMedGoogle Scholar
  113. 113.
    Pacini F, Mariotti S, Formica N, Elisei R, Anelli S, Capotorti E, Pinchera A. Thyroid autoantibodies in thyroid cancer: incidence and relationship with tumour outcome. Acta Endocrinol. 1988;119:373–80.Google Scholar
  114. 114.
    Pacini F, Molinaro E, Lippi F, et al. Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2001;86:5686–90.PubMedGoogle Scholar
  115. 115.
    Mazzaferri EL, Robbins RJ, Spencer CA, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:1433–41.PubMedGoogle Scholar
  116. 116.
    Schlumberger M, Hitzel A, Toubert ME, et al. Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab. 2007;92:2487–95.PubMedGoogle Scholar
  117. 117.
    Chindris AM, Diehl NN, Crook JE, Fatourechi V, Smallridge RC. Undetectable sensitive serum thyroglobulin (<0.1 ng/ml) in 163 patients with follicular cell-derived thyroid cancer: results of rhTSH stimulation and neck ultrasonography and long-term biochemical and clinical follow-up. J Clin Endocrinol Metab. 2012;97:2714–23.PubMedGoogle Scholar
  118. 118.
    Pacini F, Capezzone M, Elisei R, Ceccarelli C, Taddei D, Pinchera A. Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab. 2002;87:1499–501.PubMedGoogle Scholar
  119. 119.
    Gerard SK, Cavalieri RR. I-123 diagnostic thyroid tumor whole-body scanning with imaging at 6, 24, and 48 hours. Clin Nucl Med. 2002;27:1–8.PubMedGoogle Scholar
  120. 120.
    Yan W, Roach PJ, Bautovich GJ, Learoyd DL, Robinson BG. Timing of iodine-123 scintigraphy following use of recombinant human thyrotropin in differentiated thyroid carcinoma. Clin Nucl Med. 2007;32:375–7.PubMedGoogle Scholar
  121. 121.
    Pacini F, Lippi F, Formica N, Elisei R, Anelli S, Ceccarelli C, Pinchera A. Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med. 1987;28:1888–91.PubMedGoogle Scholar
  122. 122.
    Pineda JD, Lee T, Ain K, Reynolds JC, Robbins J. Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab. 1995;80:1488–92.PubMedGoogle Scholar
  123. 123.
    Elisei R, Pinchera A, Romei C, et al. Expression of thyrotropin receptor (TSH-R), thyroglobulin, thyroperoxidase, and calcitonin messenger ribonucleic acids in thyroid carcinomas: evidence of TSH-R gene transcript in medullary histotype. J Clin Endocrinol Metab. 1994;78:867–71.PubMedGoogle Scholar
  124. 124.
    Arturi F, Russo D, Schlumberger M, du Villard JA, Caillou B, Vigneri P, Wicker R, et al. Iodide symporter gene expression in human thyroid tumors. J Clin Endocrinol Metab. 1998;83:2493–6.PubMedGoogle Scholar
  125. 125.
    Pacini F. Follow-up of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2002;29(Suppl 2):492–4966.Google Scholar
  126. 126.
    Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med. 2003;139:346–51.PubMedGoogle Scholar
  127. 127.
    Schlumberger M, Challeton C, De Vathaire F, et al. Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J Nucl Med. 1996;37:598–605.PubMedGoogle Scholar
  128. 128.
    Urken ML, Milas M, Randolph GW, et al. Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: a multifactorial decision-making guide for the Thyroid Cancer Care Collaborative. Head Neck. 2015;37:605–14.PubMedGoogle Scholar
  129. 129.
    Ceccarelli C, Pacini F, Lippi F, Elisei R, Arganini M, Miccoli P, Pinchera A. Thyroid cancer in children and adolescents. Surgery. 1988;104:1143–8.PubMedGoogle Scholar
  130. 130.
    Vassilopoulou-Sellin R, Klein MJ, Smith TH, et al. Pulmonary metastases in children and young adults with differentiated thyroid cancer. Cancer. 1993;71:1348–52.PubMedGoogle Scholar
  131. 131.
    Piekarski JD, Schlumberger M, Leclere J, Couanet D, Masselot J, Parmentier C. Chest computed tomography (CT) in patients with micronodular lung metastases of differentiated thyroid carcinoma. Int J Radiat Oncol Biol Phys. 1985;11:1023–7.PubMedGoogle Scholar
  132. 132.
    Schlumberger M, Arcangioli O, Piekarski JD, Tubiana M, Parmentier C. Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays. J Nucl Med. 1988;29:1790–4.PubMedGoogle Scholar
  133. 133.
    Sumimura J, Nakagawa K, Kawamura J, Tayama M, Takahashi E, Moritomo T, Miyata M. Thyroid cancer metastasis to the lumbar spine successfully treated by embolization and radioiodine. A case report. Nippon Geka Gakkai Zasshi. 1990;91:910–3.PubMedGoogle Scholar
  134. 134.
    Court C, Noun Z, Gagey O, Nordin JY. Surgical treatment of metastases from thyroid cancer in the axial skeleton. A retrospective study of 18 cases. Acta Orthop Belg. 2000;66:345–52.PubMedGoogle Scholar
  135. 135.
    Smit JW, Links TP, Hew JM, Goslings BM, Vielvoye GJ, Vermey A. Embolization of skeletal metastases in patients with differentiated thyroid carcinoma. Ned Tijdschr Geneeskd. 2000;144:1406–10.PubMedGoogle Scholar
  136. 136.
    Van Tol KM, Hew JM, Jager PL, Vermey A, Dullaart RP, Links TP. Embolization in combination with radioiodine therapy for bone metastases from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2000;52:653–9.Google Scholar
  137. 137.
    van Tol KM, Hew JM, Links TP. Images in thyroidology. Embolization of a bone metastasis of follicular thyroid carcinoma. Thyroid. 2000;10:621–2.PubMedGoogle Scholar
  138. 138.
    Klain M, Ricard M, Leboulleux S, Baudin E, Schlumberger M. Radioiodine therapy for papillary and follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2002;29:479–85.Google Scholar
  139. 139.
    Franzius C, Dietlein M, Biermann M, et al. Procedure guideline for radioiodine therapy and 131iodine whole-body scintigraphy in paediatric patients with differentiated thyroid cancer. Nuklearmedizin. 2007;46:224–2231.PubMedGoogle Scholar
  140. 140.
    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.PubMedGoogle Scholar
  141. 141.
    Van Nostrand D, Wartofsky L. Radioiodine in the treatment of thyroid cancer. Endocrinol Metab Clin N Am. 2007;36:807–22.Google Scholar
  142. 142.
    Benua RS, Leeper RD. A method and rationale for treating metastatic thyroid carcinoma with the largest safe dose of I-131. In: Medeiros-Neto G, Gaitan G, editors. Frontiers in thyroidology. New York: Plenum; 1986. p. 1317–21.Google Scholar
  143. 143.
    Traino AC, Ferrari M, Cremonesi M, Stabin MG. Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry. Phys Med Biol. 2007;52:5231–48.PubMedGoogle Scholar
  144. 144.
    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.PubMedGoogle Scholar
  145. 145.
    Lippi F, Capezzone M, Angelini F, Taddei D, Molinaro E, Pinchera A, Pacini F. Radioiodine treatment of metastatic differentiated thyroid cancer in patients on l-thyroxine, using recombinant human TSH. Eur J Endocrinol. 2001;144:5–11.PubMedGoogle Scholar
  146. 146.
    Jarzab B, Handkiewicz-Junak D, Roskosz J, et al. Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single-centre study of 54 patients. Eur J Nucl Med Mol Imaging. 2003;30:1077–86.PubMedGoogle Scholar
  147. 147.
    Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review. Endocr Relat Cancer. 2005;12:49–64.PubMedGoogle Scholar
  148. 148.
    Eschmann SM, Reischl G, Bilger K, et al. Evaluation of dosimetry of radioiodine therapy in benign and malignant thyroid disorders by means of iodine-124 and PET. Eur J Nucl Med. 2002;29:760–7.Google Scholar
  149. 149.
    Freudenberg LS, Jentzen W, Görges R, Petrich T, Marlowe RJ, Knust J, Bockisch A. 124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact. Nuklearmedizin. 2007;46:121–8.PubMedGoogle Scholar
  150. 150.
    Erdi YE, Macapinlac H, Larson SM, Erdi AK, Yeung H, Furhang EE, Humm JL. Radiation dose assessment for I-131 therapy of thyroid cancer using I-124 PET imaging. Clin Positron Imaging. 1999;2:41–6.PubMedGoogle Scholar
  151. 151.
    Jentzen W, Weise R, Kupferschläger J, et al. Iodine-124 PET dosimetry in differentiated thyroid cancer: recovery coefficient in 2D and 3D modes for PET/CT systems. Eur J Nucl Med Mol Imaging. 2008;35:611–23.PubMedGoogle Scholar
  152. 152.
    Jentzen W, Freudenberg L, Eising EG, Sonnenschein W, Knust J, Bockisch A. Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer. J Nucl Med. 2008;49:1017–723.PubMedGoogle Scholar
  153. 153.
    Kolbert KS, Pentlow KS, Pearson JR, Sheikh A, Finn RD, Humm JL, Larson SM. Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124IPET and 3-dimensional internal dosimetry software. J Nucl Med. 2007;48:143–9.PubMedGoogle Scholar
  154. 154.
    Lassmann M, Hänscheid H, Verburg FA, Luster M. The use of dosimetry in the treatment of differentiated thyroid cancer. Q J Nucl Med Mol Imaging. 2011;55:107–15.PubMedGoogle Scholar
  155. 155.
    Jentzen W, Verschure F, van Zon A, van de Kolk R, Wierts R, Schmitz J, et al. Response assessment of bone metastases from differentiated thyroid cancer patients in the initial radioiodine treatment using iodine-124 PET imaging. J Nucl Med. 2016;57:1499–504.PubMedGoogle Scholar
  156. 156.
    Schlumberger M, Brose M, Elisei R, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2014;2:356–8.PubMedGoogle Scholar
  157. 157.
    Samaan NA, Schultz PN, Hickey RC, Goepfert H, Haynie TP, Johnston DA, Ordonez NG. The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. J Clin Endocrinol Metab. 1992;75:714–20.PubMedGoogle Scholar
  158. 158.
    Matuszczyk A, Petersenn S, Bockisch A, Gorges R, Sheu SY, Veit P, Mann K. Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium. Horm Metab Res. 2008;40:210–3.PubMedGoogle Scholar
  159. 159.
    Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol (R Coll Radiol). 2010;22:464–8.Google Scholar
  160. 160.
    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;56:2155–60.PubMedGoogle Scholar
  161. 161.
    Williams SD, Birch R, Einhorn LH. Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial. Cancer Treat Rep. 1986;70:405–7.PubMedGoogle Scholar
  162. 162.
    Santini F, Bottici V, Elisei R, et al. Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab. 2002;87:4160.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Federica Guidoccio
    • 1
  • Gayane Aghakhanyan
    • 1
  • Mariano Grosso
    • 2
    Email author
  1. 1.Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
  2. 2.Regional Center of Nuclear MedicineUniversity Hospital of PisaPisaItaly

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