Radioiodine Therapy of Benign Thyroid Diseases

  • Alfredo CampennìEmail author
  • Desiree Deandreis
  • Monica Finessi
  • Rosaria Maddalena Ruggeri
  • Sergio Baldari


Thyrotoxicosis represents a clinical condition that results from excess thyroid hormone(s) levels and action in peripheral tissues, either with or without increased synthesis of thyroid hormone(s) by the gland. It has multiple different etiologies and potential therapies; therefore, an accurate diagnosis is mandatory for appropriate treatment.

131-Radioiodine has been used since 1941 to cure hyperthyroidism due to toxic thyroid disease [diffuse or (multi)-nodular].

From its first use, millions of people have been treated worldwide and today it represents the first example of “theranostic” radiotracer [(−ve)-beta electrons to obtain the therapeutic effect, gamma-emission to show its distribution in the gland].

131-Radioiodine therapy has two main aims: the first is to correct hyperthyroidism (by fixed or calculated dose) reaching a euthyroid state [the optimal result for patients affected by (multi)-nodular toxic disease] or a hypothyroid state (the optimal result for patients with diffuse toxic disease); the second is to reduce whole gland or toxic (multi)-nodular volume.

Despite RAI therapy being a safe and generally well-tolerated treatment, either acute or late side effects (e.g., radiation thyroiditis, sialadenitis, worsening or appearance of orbitopathy) may occur, principally related to insufficient clinical control of hyperthyroidism and active thyroid orbitopathy due to Graves’ disease.

The purpose of this chapter is to provide advice to nuclear medicine physicians in evaluating patients with benign thyroid disease for 131-radioiodine therapy.

Diagnosis of hyperthyroidism and clinical management, along with advantages, optimal activities, and possible side effects of 131-radioiodine therapy, are discussed.


Hyperthyroidism 131-Radioiodine therapy Benign thyroid disease Side effects 131-Radioiodine activity 


  1. 1.
    Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–421.PubMedCrossRefGoogle Scholar
  2. 2.
    Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29:76–131.PubMedCrossRefGoogle Scholar
  3. 3.
    Burch HB. Overview of the clinical manifestations of thyrotoxicosis. In: Werner SC, Ingbar SC, editors. The thyroid. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 434–40.Google Scholar
  4. 4.
    Cooper DS. Hyperthyroidism. Lancet. 2003;362(9382):459–68.PubMedCrossRefGoogle Scholar
  5. 5.
    Flynn RW, Macdonald TM, Morris AD, et al. The thyroid epidemiology, audit, and research study: thyroid dysfunction in the general population. J Clin Endocrinol Metab. 2004;8989:3879–84.CrossRefGoogle Scholar
  6. 6.
    Nyström HF, Jansson S, Berg G. Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003–2005. Clin Endocrinol. 2013;78(5):768–76.CrossRefGoogle Scholar
  7. 7.
    Laurberg P, Bulow PI, Knudsen N, et al. Environmental iodine intake affects the type of non-malignant thyroid disease. Thyroid. 2001;11:457–69.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375:1552–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Bartalena L, Masiello E, Magri F, Veronesi G, Bianconi E, Zerbini F, et al. The phenotype of newly diagnosed Graves’ disease in Italy in recent years is milder than in the past: results of a large observational longitudinal study. J Endocrinol Investig. 2016;39:1445–51.CrossRefGoogle Scholar
  10. 10.
    Ruggeri R, Giuffrida G, Campennì A. Autoimmune endocrine disease. Minerva Endocrinol. 2018;43(3):305–22.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Bahn RS. Mechanisms of disease: Graves’ ophthalmopathy. N Engl J Med. 2010;362(2):726–38.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cooper G, Bynum M, Somers E. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun. 2009;33:197–207.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Boelaert K, Newby P, Simmonds M, Holder R, Carr-Smith J, Heward J, et al. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123:183.e1–9.CrossRefGoogle Scholar
  14. 14.
    Ruggeri R, Trimarchi F, Giuffrida G, Certo R, Cama E, Campennì A, et al. Autoimmune comorbidities in Hashimoto’s thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol. 2017;176(2):133–41.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Aghini-Lombardi F, Antonangeli L, Martino E, et al. The spectrum of thyroid disorders in an iodinedeficient community: the Pescopagano survey. J Clin Endocrinol Metab. 1999;84:561–6.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Ruggeri R, Campennì A, Sindoni A, Baldari S, Trimarchi F. Benvenga. Association of autonomously functioning thyroid nodules with Hashimoto’s thyroiditis: study on a large series of patients. Exp Clin Endocrinol Diabetes. 2011;119(10):621–7.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Giovanella L, D’Aurizio F, Campenni A, Ruggeri R, Baldari S, Verburg F, et al. Searching for the most effective thyrotropin (TSH) threshold to rule-out autonomously functioning thyroid nodules in iodine deficient regions. Endocrine. 2016;54:757–61.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Gozu H, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic nonautoimmune hyperthyroidism. Mol Cell Endocrinol. 2010;322:125–34.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Tonacchera M, Chiovato L, Pinchera A, Agretti P, Fiore E, Cetani F, et al. Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab. 1998;83(2):492–8.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Vicchio T, Giovinazzo S, Certo R, Cucinotta M, Micali C, Baldari S, et al. Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and gas genes in a mild to moderate iodine-deficient caucasian population. J Endocrinol Investig. 2017;37:625–30.CrossRefGoogle Scholar
  21. 21.
    Boelaert K, Torlinska B, Holder R, Franklyn J. Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. J Clin Endocrinol Metab. 2010;95(6):2715–26.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004;164(15):1675–8.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Ruggeri R, Trimarchi F, Biondi B. MANAGEMENT OF ENDOCRINE DISEASE: l-Thyroxine replacement therapy in the frail elderly: a challenge in clinical practice. Eur J Endocrinol. 2017;177(4):R199–217.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Jolanta MD, Bogsrud TV. Nuclear medicine in evaluation and therapy of nodular thyroid. In: Thyroid nodules. Switzerland: Springer International; 2018.Google Scholar
  26. 26.
    Silberstein E, Alavi A, Balon H, Clarke S, Divgi C, Gelfand MJ, et al. The SNMMI practice guideline for therapy of thyroid disease with 131I 3.0. J Nucl Med. 2012;53(10):1633–51.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Stokkel MPM, Handkiewicz Junak D, Lassmann M, Dietlein M, Luster M. EANM procedure guidelines for therapy of benign thyroid disease. Eur J Nucl Med Mol Imaging. 2010;37(11):2218–28.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Brzozowska M, Roach P. Timing and potential role of diagnostic I-123 scintigraphy in assessing radioiodine breast uptake before ablation in postpartum women with thyroid cancer: a case series. Clin Nucl Med. 2006;31(11):683–7.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med. 2011;364:543–50.Google Scholar
  30. 30.
    Bartalena L, Chiovato L, Vitti P. Management of hyperthyroidism due to Graves’ disease: frequently asked questions and answers (if any). J Endocrinol Investig. 2016;39(10):1105–14.CrossRefGoogle Scholar
  31. 31.
    Bahn R, Burch H, Cooper D, Garber J, Greenlee M, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American thyroid association and american association of clinical endocrinologists. Thyroid. 2011;21(6):593–646.CrossRefGoogle Scholar
  32. 32.
    Träisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, et al. Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab. 2009;94(10):3700–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006;91(9):3464–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Reiners C. Radioactivity and thyroid cancer. Hormones. 2009;8:185–92.PubMedCrossRefGoogle Scholar
  35. 35.
    Ron E, Doody M, Becker D, Harris B 3rd, Hoffman D, McConahey WM, et al. Cancer mortality following treatment for adult hyperthyroidism. Cooperative thyrotoxicosis therapy follow- up study group. JAMA. 1998;280:347–55.PubMedCrossRefGoogle Scholar
  36. 36.
    Kobe C, Eschner W, Sudbrock F, Weber I, Marx K, Dietlein M, et al. Graves’ disease and radioiodine therapy: is success of ablation dependent on the achieved dose above 200 Gy? Nuklearmedizin. 2008;47:13–7.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Reinhardt MJ, Brink I, Joe A, Von Mallek D, Ezziddin S, Palmedo H, et al. Radioiodine therapy in Graves’ disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome. Eur J Nucl Med. 2002;29:1118–24.CrossRefGoogle Scholar
  38. 38.
    Dunkelmann S, Neumann V, Staub U, Groth P, Kuenstner H, Schuemichen C. Results of a risk adapted and functional radioiodine therapy in Graves’ disease. Nuklearmedizin. 2005;44:238–42.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Rivkees S. Controversies in the management of Graves’ disease in children. J Endocrinol Investig. 2016;39(11):1247–57.CrossRefGoogle Scholar
  40. 40.
    Dobyns B, Sheline G, Workman J, Tompkins E, McConahey W, Becker D. Malignant and benign neo- plasms of the thyroid in patients treated for hyperthyroidism: a report of the cooperative thyrotoxicosis therapy follow-up study. J Clin Endocrinol Metab. 1974;38:976–98.PubMedCrossRefGoogle Scholar
  41. 41.
    Sheline GE, McCormack K, Galante M. Thyroid nodules occurring late after treatment of thryotoxicosis with radioiodine. J Clin Endocrinol Metab. 1962;22:8–17.PubMedCrossRefGoogle Scholar
  42. 42.
    Rivkees SA, Dinauer C. An optimal treatment for pediatric Graves’ disease is radioiodine. J Clin Endocrinol Metab. 2007;92(3):797–800.PubMedCrossRefGoogle Scholar
  43. 43.
    Chao M, Jiawei X, Guoming W, Jianbin L, Wanxia L, Driedger A, et al. Radioiodine treatment for pediatric hyperthyroid Graves’ disease. Eur J Pediatr. 2009;168:1165–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Tarantini B, Ciuoli C, Di Cairano G, Guarino E, Mazzucato P, Montanaro A, et al. Effectiveness of radioiodine (131-I) as definitive therapy in patients with autoimmune and non-autoimmune hyperthyroidism. J Endocrinol Investig. 2006;29(7):594–8.CrossRefGoogle Scholar
  45. 45.
    Kung A, Yau C, Cheng A. The action of methimazole and L-thyroxine in radioiodine therapy: a prospective study on the incidence of hypothyroidism. Thyroid. 1995;5:7–12.PubMedCrossRefGoogle Scholar
  46. 46.
    Bonnema SJ, Bennedbæk FN, Veje A, Marving J, Hegedüs L. Propylthiouracil before 131I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial. J Clin Endocrinol Metab. 2004;89(9):4439–44.PubMedCrossRefGoogle Scholar
  47. 47.
    Santos R, Romaldini J, Ward L. A randomized controlled trial to evaluate the effectiveness of 2 regimens of fixed iodine (131I) doses for Graves disease treatment. Clin Nucl Med. 2012;37:241–4.PubMedCrossRefGoogle Scholar
  48. 48.
    Braga M, Walpert N, Burch H, Solomon B, Cooper D. The effect of methimazole on cure rates after radioiodine treatment for Graves’ hyperthyroidism: a randomized clinical trial. Thyroid. 2002;12:135–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Hänscheid H, Canzi C, Eschner W, Flux G, Luster M, Strigari M, et al. 2013 EANM Dosimetry committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases. Eur J Nucl Med Mol Imaging. 2013;40:1126–34.PubMedCrossRefGoogle Scholar
  50. 50.
    Willegaignon J, Sapienza M, Buchpiguel CA. Radioiodine therapy for Graves disease: thyroid absorbed dose of 300 Gy-tuning the target for therapy planning. Clin Nucl Med. 2013;38(4):231–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Krohn T, Hänscheid H, Müller B, Behrendt F, Heinzel A, Mottaghy F, et al. Maximum dose rate is a determinant of hypothyroidism after 131i therapy of Graves’ disease but the total thyroid absorbed dose is not. J Clin Endocrinol Metab. 2014;99(11):4109–15.PubMedCrossRefGoogle Scholar
  52. 52.
    Rivkees SA, Sklar C, Freemark M. Clinical review 99: the management of Graves’ disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab. 1998;83(11):3767–76.PubMedGoogle Scholar
  53. 53.
    Goolden A, Davey J. The ablation of normal thyroid tissue with iodine-131. Br J Radiol. 1963;36:340–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Graham G, Burman K. Radioiodine treatment of Graves’ disease. An assessment of its potential risks. Ann Intern Med. 1986;105:900–5.PubMedCrossRefGoogle Scholar
  55. 55.
    McDermott M, Kidd G, Dodson LJ, Hofeldt F. Radioiodine-induced thyroid storm. Case report and literature review. Am J Med. 1983;75:353–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Akamizu T, Satoh T, Isozaki O, Suzuki A, Wakino S, Iburi T, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012;22(7):661–79.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Shafe R, Nuttall F. Acute changes in thyroid function in patients treated with radioactive iodine. Lancet. 1975;2:635–7.CrossRefGoogle Scholar
  58. 58.
    Burch HB, Solomon BL, Cooper DS, Ferguson P, Walpert N, Howard R. The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after 131I ablation for Graves’ disease. J Clin Endocrinol Metab. 2001;86(7):3016–21.PubMedGoogle Scholar
  59. 59.
    Andrade V, Gross J, Maia A. Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84:4012–6.PubMedGoogle Scholar
  60. 60.
    Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–35.PubMedCrossRefGoogle Scholar
  61. 61.
    Klein I. Endocrine disorders and cardiovascular disease. In: Libby P, et al., editors. Braunwald’s heart disease: a textbook of cardiovascular medicine. 8th ed. Philadelphia: Saunders/Elsevier; 2008. p. 2033–47.Google Scholar
  62. 62.
    Nygaard B, Hegedus L, Ulriksen P, Nielsen K, Hansen J. Radioiodine therapy for multinodular toxic goiter. Arch Intern Med. 1999;159:1364–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Bonnema S, Bertelsen H, Mortensen J, Andersen P, Knudsen D, Bastholt L, et al. The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function. J Clin Endocrinol Metab. 1999;84:3636–41.PubMedGoogle Scholar
  64. 64.
    Lee Y, Tam K, Lin Y, Leu W, Chang J, Hsiao C, et al. Recombinant human thyrotropin before (131) I therapy in patients with nodular goitre: a meta-analysis of randomized controlled trials. Clin Endocrinol. 2015;83:702–10.CrossRefGoogle Scholar
  65. 65.
    Nieuwlaat W, Hermus A, Sivro-Prndelj F, Corstens F, Huysmans D. Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters. J Clin Endocrinol Metab. 2001;86:5330–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Silva M, Rubió I, Romão R, Gebrin E, Buchpiguel C, Tomimori E, et al. Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres. Clin Endocrinol. 2004;60:300–8.CrossRefGoogle Scholar
  67. 67.
    Nielsen V, Bonnema S, Hegedus L. Transient goiter enlargement after administration of 0.3 mg of recombinant human thyrotropin in patients with benign non-toxic nodular goiter: a randomized, double- blind, cross-over trial. J Clin Endocrinol Metab. 2006;91:1317–22.PubMedCrossRefGoogle Scholar
  68. 68.
    Nielsen V, Bonnema S, Boel-Jorgensen H, Grupe P, Hegedus L. Stimulation with 0.3 mg recombinant human thyrotropin prior to iodine 131 therapy to improve the size reduction of benign non-toxic nodular goiter: a prospective randomized double-blind trial. Arch Intern Med. 2006;166:1476–82.PubMedCrossRefGoogle Scholar
  69. 69.
    Nieuwlaat W, Huysmans D, Van den Bosch HC, Sweep CG, Ross H, Corstens F, et al. Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter. J Clin Endocrinol Metab. 2003;88:3121–9. J Clin Endocrinol Metab. 2003;88:3121–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Amato E, Campennì A, Leotta S, Ruggeri R, Baldari S. Treatment of hyperthyroidism with radioiodine targeted activity: a comparison between two dosimetric methods. Phys Med. 2016;32(6):847–53.PubMedCrossRefGoogle Scholar
  71. 71.
    Zakavi S, Mousavi Z, Davachi B. Comparison of four different protocols of I-131 therapy for treating single toxic thyroid nodule. Nucl Med Commun. 2009;30:169–75.PubMedCrossRefGoogle Scholar
  72. 72.
    Metso S, Jaatinen P, Huhtala H, Luukkaala T, Oksala H, Salmi J. Long-term follow-up study of radioiodine treatment of hyperthyroidism. Clin Endocrinol. 2004;61:641–8.CrossRefGoogle Scholar
  73. 73.
    Ceccarelli C, Bencivelli W, Vitti P, Grasso L, Pinchera A. Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years’ retrospective study. Clin Endocrinol. 2005;62:331–5.CrossRefGoogle Scholar
  74. 74.
    Holm L, Lundell G, Israelsson A, Dahlqvist I. Incidence of hypothyroidism occurring long after iodine-131 therapy for hyperthyroidism. J Nucl Med. 1982;23:103–7.PubMedGoogle Scholar
  75. 75.
    Yano Y, Sugino K, Akaishi J, Uruno T, Okuwa K, Shibuya H, et al. Treatment of autonomously functioning thyroid nodules at a single institution: radioiodine therapy, surgery, and ethanol injection therapy. Ann Nucl Med. 2011;25:749–54.PubMedCrossRefGoogle Scholar
  76. 76.
    Erickson D, Gharib H, Li H, Van Heerden J. Treatment of patients with toxic multinodular goiter. Thyroid. 1998;8:277–82.PubMedCrossRefGoogle Scholar
  77. 77.
    Kang A, Grant C, Thompson G, Van Heerden J. Current treatment of nodular goiter with hyperthyroidism (Plummer’s disease): surgery versus radioiodine. Surgery. 2002;132:916–23.PubMedCrossRefGoogle Scholar
  78. 78.
    Reinhardt M, Joe A, Von Mallek D, Zimmerlin M, Manka-Waluch A, Palmedo H, et al. Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake. Eur J Nucl Med Mol Imaging. 2002;29:480–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Dunkelmann S, Endlicher D, Prillwitz A, Rudolph F, Groth P, Schuemichen C. Results of a TcTUs-optimized radioiodine therapy of multifocal and disseminated functional thyroid autonomy. Nuklearmedizin. 1999;38:131–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Reiners C, Schneider P. Radioiodine therapy of thyroid autonomy. Eur J Nucl Med. 2002;29(Suppl 2):S471–8.CrossRefGoogle Scholar
  81. 81.
    Reinhardt M, Kim B, Wissmeyer M, Juengling F, Brockmann H, Von Mallek D, et al. Dose selection for radioiodine therapy of borderline hyperthyroid patients according to thyroid uptake of 99mTc-pertechnetate: applicability to unifocal thyroid autonomy? Eur J Nucl Med Mol Imaging. 2006;33:608–12.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Allahabadia A, Daykin J, Sheppard M, Gouch S, Franklyn J. Radioiodine treatment of hyperthyroidism—prognostic factors for outcome. J Clin Endocrinol Metab. 2001;86(8):3611–7.PubMedPubMedCentralGoogle Scholar
  83. 83.
    ICRP (1987). Protection of the patient in nuclear medicine (and statement from the 1987 Como Meeting of ICRP). ICRP Publication 52. Ann. ICRP 17 (4). ICRP Publ 52 Ann ICRP 17 (4). 1987;Google Scholar
  84. 84.
    Sisson J, Anca M, Avram A, Rubello D, Milton D, Gross M. Radioiodine treatment of hyperthyroidism: fixed or calculated doses; intelligent design or science? Eur J Nucl Med Mol Imaging. 2007;34:1129–30.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    European Union Council Directive 97/43/EURATOM on health protection of individuals against the dangers of ionising radiation in relation to medical exposure. Luxembourg: Council of the European Union. 1997.
  86. 86.
    Szumowski P, Mojsak M, Abdelrazek S, Sykala M, Filonowicz A, Dorota Jurgilewicz D, et al. Calculation of therapeutic activity of radioiodine in Graves’ disease by means of Marinelli’s formula, using technetium (99mTc) scintigraphy. Endocrine. 2016;54:751–6.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Giovanella L, Verburg F, Ceriani L. One-stop-shop radioiodine dosimetry in patients with Graves’ disease. Endocrine. 2017;56(1):220–1.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    De Rooij A, Vandenbroucke J, Smit J, Stokkel M, Dekkers O. Clinical outcomes after estimated versus calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-analysis. Eur J Endocrinol. 2009;161(5):771–7.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Leslie W, Ward L, Salamon E, Ludwig S, Rowe R, Cowden E. A randomized comparison of radioiodine doses in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 2003;88:978–83.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Peters H, Fischer C, Bogner U, Reiners C, Schleusener H. Treatment of Graves’ hyperthyroidism with radioioidine; results of a prospective study. Thyroid. 1997;2:247–51.CrossRefGoogle Scholar
  91. 91.
    Alexander EK, Larsen PR. High dose 131I therapy for the treatment of hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab [Internet]. 2002;87(3):1073–7. Scholar
  92. 92.
    Kendall-Taylor P, Keir M, Ross W. Ablative radioiodine therapy for hyperthyroidism: long term follow up study. Br Med J. 1984;289:361–3.CrossRefGoogle Scholar
  93. 93.
    Vija Racaru L, Fontan C, Bauriaud-Mallet M, Brillouet S, Caselles O, Zerdoud S, et al. Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response. Nucl Med Commun. 2017;38(9):756–63.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Liu B, Tian R, Peng W, He Y, Huang R, Kuang A. Radiation safety precautions in 131I therapy of Graves’ disease based on actual biokinetic measurements. J Clin Endocrinol Metab. 2015;100(8):2934–41.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Rokni H, Sadeghi R, Moossavi Z, Treglia G, Zakavi S. Efficacy of different protocols of radioiodine therapy for treatment of toxic nodular goiter: systematic review and meta-analysis of the literature. Int J Endocrinol Metab. 2014;12(2):e14424.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Willegaignon J, Sapienza M, Coura-Filho G, Watanabe T, Traino A, Buchpiguel C. Graves’ disease radioiodine-therapy: choosing target absorbed doses for therapy planning. Med Phys. 2014;41(1):12503.CrossRefGoogle Scholar
  97. 97.
    Cooper J. International commission on radiological protection. 2012 radiation protection principles. J Radiol Prot. 2012;32(1):N81–7.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Bonnema SJ, Hegedüs L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr Rev. 2012;33(6):920–80.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;388(10047):906–18.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Bonnema SJ, Nielsen VE, Boel-Jørgensen H, Grupe P, Andersen PB, Bastholt L, et al. Improvement of goiter volume reduction after 0.3 mg recombinant human thyrotropin-stimulated radioiodine therapy in patients with a very large goiter: a double-blinded, randomized trial. J Clin Endocrinol Metab. 2007;92(9):3424–8.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Satoh T, Isozaki O, Suzuki A, Wakino S, Iburi T, Tsuboi K, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J. 2016;63(12):1025–64.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Walter MA, Christ-Crain M, Schindler C, Müller-Brand J, Müller B. Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison. Eur J Nucl Med Mol Imaging. 2006;33(6):730–7.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Hancock LD, Tuttle RM, LeMar H, Bauman J, Patience T. The effect of propylthiouracil on subsequent radioactive iodine therapy in Graves’ disease. Clin Endocrinol. 1997;47(4):425–30.CrossRefGoogle Scholar
  104. 104.
    Santos RB, Romaldini JH, Ward LS. Propylthiouracil reduces the effectiveness of radioiodine treatment in hyperthyroid patients with Graves’ disease. Thyroid. 2004;14(7):525–30.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Bogazzi F, Bartalena L, Brogioni S, Scarcello G, Burelli A, Campomori A, Manetti L, Rossi G, Pinchera AME. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84:499–503.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Robbins J. Perturbations of iodine metabolism by lithium. Math Biosci. 1984;72:337–47.CrossRefGoogle Scholar
  107. 107.
    Temple R, Berman M, Robbins JWJ. The use of lithium in the treatment of thyrotoxicosis. J Clin Invest. 1972;51:2746–56.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Bogazzi F, Bartalena L, Campomori A, Brogioni S, Traino C, De Martino F, et al. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with graves’ disease. J Clin Endocrinol Metab. 2002;87(10):4490–5.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Gayed I, Wendt J, Haynie T, Dhekne R, Moore W. Timing for repeated treatment of hyperthyroid disease with radioactive iodine after initial treatment failure. Clin Nucl Med. 2001;26(1):1–5.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Mandel SJ, Mandel L. Radioactive iodine and the salivary glands. Thyroid. 2003;13(3):265–71.PubMedCrossRefGoogle Scholar
  111. 111.
    Grewal RK, Larson SM, Pentlow CE, Pentlow KS, Gonen M, Qualey R, et al. Salivary gland side effects commonly develop several weeks after initial radioactive iodine ablation. J Nucl Med. 2009;50(10):1605–10.PubMedCrossRefGoogle Scholar
  112. 112.
    Van Nostrand D, Bandaru V, Chennupati S, Wexler J, Kulkarni K, Atkins F, et al. Radiopharmacokinetics of radioiodine in the parotid glands after the administration of lemon juice. Thyroid. 2010;20(10):1113–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Nakada K, Ishibashi T, Takei T, Hirata K, Shinohara K, Katoh S, et al. Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer? J Nucl Med. 2005;46(2):261–6.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Jentzen W, Balschuweit D, Schmitz J, Freudenberg L, Eising E, Hilbel T, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Törring O. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol. 2008;158(1):69–75.PubMedCrossRefGoogle Scholar
  116. 116.
    Chiappori A, Villalta D, Bossert I, Ceresola EM, Lanaro D, Schiavo M, et al. Thyrotropin receptor autoantibody measurement following radiometabolic treatment of hyperthyroidism: comparison between different methods. J Endocrinol Investig. 2010;33(3):197–201.CrossRefGoogle Scholar
  117. 117.
    Schmidt M, Gorbauch E, Dietlein M, Faust M, Stützer H, Eschner W, et al. Incidence of postradioiodine immunogenic hyperthyroidism/Graves’ disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease. Thyroid. 2006;16(3):281–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Nygaard B, Knudsen JH, Hegedüs L, Veje AH. Thyrotropin receptor antibodies and Graves’ disease, a side effect of 131I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab. 1997;82:2926–30.PubMedGoogle Scholar
  119. 119.
    Gamstedt A, Wadman B, Karisson A. Methimazole, but not betamethasone, prevents 131 I treatment-induced rises in thyrotropin receptor autoantibodies in hyperthyroid Graves’ disease. J Clin Endocrinol Metab. 1986;62:773–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Andrade VA, Gross JL, Maia AL. Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves’ patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study. Eur J Endocrinol. 2004;151:467–74.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Aizawa Y, Yoshida K, Kaise N, Fukazawa H, Kiso Y, Sayama N, et al. The development of transient hypothyroidism after iodine-131 treatment in hyperthyroid patients with Graves’ disease: prevalence, mechanism and prognosis. Clin Endocrinol. 1997;46(1):1–5.CrossRefGoogle Scholar
  122. 122.
    Sawers JSA, Toft AD, Irvine WJ, Brown NS, Seth J. Transient hypothyroidism after iodine-131 treatment of thyrotoxicosis. J Clin Endocrinol Metab. 1980;50:226–9.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Connell JM, Hilditch TE, McCruden DCAW. Transient hypothyroidism following radioiodine therapy for thyrotoxicosis. Br J Radiol. 1983;56(665):309–13.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Uy HL, Reasner CA, Samuels MH. Pattern of recovery of the hypothalamic-pituitary-thyroid axis following radioactive iodine therapy in patients with Graves’ disease. Am J Med. 1995;99(2):173–9.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Gómez N, Gómez JM, Orti A, Gavaldà L, Villabona C, Leyes P, Soler J. Transient hypothyroidism after iodine-131 therapy for Grave’s disease. J Nucl Med. 1995;36(9):1539–42.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Investig. 2014;37(8):691–700.CrossRefGoogle Scholar
  127. 127.
    Smith T. Pathogenesis of Graves’ orbitopathy: a 2010 update. J Endocrinol Investig. 2010;33:414–21.CrossRefGoogle Scholar
  128. 128.
    Iyer S, Bahn R. Immunopathogenesis of Graves’ ophthalmopathy: the role of the TSH receptor. Best Pract Res Clin Endocrinol Metab. 2012;26(3):281–9.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Bahn RS, Dutton CM, Joba W, Heufelder AE. Thyrotropin receptor expression in cultured Graves’ orbital preadipocyte fibroblasts is stimulated by thyrotropin. Thyroid. 1998;8:193–6.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J Clin Endocrinol Metab. 2010;95:2123–31.PubMedCrossRefGoogle Scholar
  131. 131.
    Gerding MN, van der Meer JW, Broenink M, Bakker O, Wiersinga WM, Prummel MF. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol. 2000;52:267–71.CrossRefGoogle Scholar
  132. 132.
    Li HX, Xiang N, Hu WK, Jiao XL. Relation between therapy options for Graves’ disease and the course of Graves’ ophthalmopathy: a systematic review and meta-analysis. J Endocrinol Investig. 2016;39(11):1225–33.CrossRefGoogle Scholar
  133. 133.
    Bartalena L, Marcocci C, Tanda ML, Manetti L, Dell’Unto E, Bartolomei MP, et al. Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med. 1998;129(8):632–5.PubMedCrossRefGoogle Scholar
  134. 134.
    Stan MN, Bahn RS. Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid. 2010;20(7):777–83.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Thornton J, Kelly SP, Harrison RA, Edwards R. Cigarette smoking and thyroid eye disease: a systematic review. Eye. 2007;21(9):1135–45.PubMedCrossRefGoogle Scholar
  136. 136.
    Tallstedt L, Lundell G, Tørring O, Wallin G, Ljunggren JG, Blomgren H, Taube A. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. N Engl J Med. 1992;326:1733–8.PubMedCrossRefGoogle Scholar
  137. 137.
    Mourits M, Prummel M, Wiersinga W, Koornneef L. Clinical activity score as a guide in the management of patients with Graves´ ophthalmopathy. Clin Endocrinol. 1997;47(1):9–14.CrossRefGoogle Scholar
  138. 138.
    Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid. 2008;18(3):333–46.PubMedCrossRefGoogle Scholar
  139. 139.
    Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ orbitopathy guidelines for the management of graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9–26.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda M, Dell’Unto E, et al. Relation between therapy for hyperthyroidism and the course. N Engl J Med. 1998;338:73–8.PubMedCrossRefGoogle Scholar
  141. 141.
    Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, Altea MA, Nardi M, Pitz S, Boboridis K, Sivelli P, von Arx G, Mou-rits MP, Baldeschi L, Bencivelli W, Wiersinga W, European Group on Graves’ Orbitopathy. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364:1920–31.PubMedCrossRefGoogle Scholar
  142. 142.
    Metso S, Auvinen A, Huhtala H, Salmi J, Oksala H, Jaatinen P. Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer. 2007;109(10):1972–9.PubMedCrossRefGoogle Scholar
  143. 143.
    Vanderpump M. Cardiovascular and cancer mortality after radioiodine treatment of hyperthyroidism. J Clin Endocrinol Metab. 2007;92(6):2033–5.PubMedCrossRefGoogle Scholar
  144. 144.
    Boice JD. Radiation-induced thyroid cancer - What’s new? J Natl Cancer Inst. 2005;97(10):703–5.PubMedCrossRefGoogle Scholar
  145. 145.
    Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y, Khrouch V, et al. Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst. 2005;97(10):724–32.PubMedCrossRefGoogle Scholar
  146. 146.
    Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves’ patients. J Clin Endocrinol Metab. 2004;89:4229–33.PubMedCrossRefGoogle Scholar
  147. 147.
    Lee JA, Grumbach MM, Clark OH. The optimal treatment for pediatric Graves’ disease is surgery. J Clin Endocrinol Metab. 2007;92(3):801–3.PubMedCrossRefGoogle Scholar
  148. 148.
    Lucignani G. Long-term risks in hyperthyroid patients treated with radioiodine: is there anything new? Eur J Nucl Med Mol Imaging. 2007;34(9):1504–9.PubMedCrossRefGoogle Scholar
  149. 149.
    Berg G, Jacobsson L, Nyström E, Gleisner KS, Tennvall J. Consequences of inadvertent radioiodine treatment of Graves’ disease and thyroid cancer in undiagnosed pregnancy. Can we rely on routine pregnancy testing? Acta Oncol. 2008;47(1):145–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Garsi J-P, Schlumberger M, Rubino C, Ricard M, Labbe M, Ceccarelli C, et al. Therapeutic administration of 131I for differentiated thyroid cancer: radiation dose to ovaries and outcome of pregnancies. J Nucl Med. 2008;49(5):845–52.PubMedCrossRefGoogle Scholar
  151. 151.
    Sawka AM, Lakra DC, Lea J, Alshehri B, Tsang RW, Brierley JD, et al. A systematic review examining the effects of therapeutic radioactive iodine on ovarian function and future pregnancy in female thyroid cancer survivors. Clin Endocrinol. 2008;69(3):479–90.CrossRefGoogle Scholar
  152. 152.
    Hyer S, Vini L, O’Connell M, Pratt B, Harmer C. Testicular dose and fertility in men following L131 therapy for thyroid cancer. Clin Endocrinol. 2002;56(6):755–8.CrossRefGoogle Scholar
  153. 153.
    Ceccarelli C, Canale D, Battisti P, Caglieresi C, Moschini C, Fiore E, et al. Testicular function after 131I therapy for hyperthyroidism. Clin Endocrinol. 2006;65(4):446–52.CrossRefGoogle Scholar
  154. 154.
    Krassas GE, Pontikides N. Male reproductive function in relation with thyroid alterations. Best Pract Res Clin Endocrinol Metab. 2004;18(2):183–95.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Alfredo Campennì
    • 1
    Email author
  • Desiree Deandreis
    • 2
  • Monica Finessi
    • 2
  • Rosaria Maddalena Ruggeri
    • 3
  • Sergio Baldari
    • 1
  1. 1.Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Nuclear Medicine UnitUniversity of MessinaMessinaItaly
  2. 2.Department of Medical Sciences, Nuclear Medicine UnitUniversity of TurinTurinItaly
  3. 3.Department of Clinical and Experimental Medicine, Unit of EndocrinologyUniversity of MessinaMessinaItaly

Personalised recommendations