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Controversies in the management of Graves’ disease in children

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Abstract

Graves’ disease (GD) is the most prevalent cause of thyrotoxicosis in children. Because spontaneous and lasting resolution of this condition occurs in only a minority of patients, most pediatric patients with GD will need radioactive iodine treatment (131I) or thyroidectomy. Whereas the medication propylthiouracil (PTU) had been used in the past, only methimazole (MMI) should be now used in children, as PTU is associated with an unacceptable risk of liver failure. However, MMI may be associated minor and major side effects, which may be minimized using lower doses. An area of controversy involves the optimal duration of antithyroid drug (ATD) therapy. For some children, the prolonged use of antithyroid drugs is a valid approach, but for most, this will not increase the chance of remission. When 131I is administered, dosages should be greater than 150 uCi/gm of thyroid tissue, with higher dosages needed for larger glands. Considering that there will be low-level whole body radiation exposure associated with 131I, this treatment is viewed as controversial by some and should be avoided in young children. When surgery is performed, near-total or total thyroidectomy is the recommended procedure. Complications for thyroidectomy in children are considerably higher than in adults. Thus, an experienced thyroid surgeon is needed when children have surgery. Overall, when different treatment options for GD are considered, the benefits, risks and viewpoints of the family need to be considered and discussed in full.

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References

  1. Conference Proceeding: Hepatic Toxicity Following Treatment for Pediatric Graves’ Disease Meeting: October 28, 2008. Eunice Kennedy Shriver National Institute of Child Health and Human Development. http://bpca.nichd.nih.gov/outreach/index.cfm. Accessed Jan 14 2009

  2. Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P (2015) Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig 38(3):283–294. doi:10.1007/s40618-014-0214-2

    Article  CAS  Google Scholar 

  3. Smith J, Brown RS (2007) Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves’ disease treated using antithyroid medication. Thyroid 17(11):1103–1107

    Article  CAS  PubMed  Google Scholar 

  4. Rivkees SA, Sklar C, Freemark M (1998) Clinical review 99: the management of Graves’ disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab 83(11):3767–3776

    CAS  PubMed  Google Scholar 

  5. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC (2015) Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol 2015:249125. doi:10.1155/2015/249125

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bahn RS (2015) Current insights into the pathogenesis of Graves’ ophthalmopathy. Horm Metab Res 47(10):773–778. doi:10.1055/s-0035-1555762

    Article  CAS  PubMed  Google Scholar 

  7. Bartalena L, Fatourechi V (2014) Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Investig 37(8):691–700. doi:10.1007/s40618-014-0097-2

    Article  CAS  Google Scholar 

  8. Leger J, Gelwane G, Kaguelidou F, Benmerad M, Alberti C (2012) Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves’ disease: national long-term cohort study. J Clin Endocrinol Metab 97(1):110–119. doi:10.1210/jc.2011-1944

    Article  CAS  PubMed  Google Scholar 

  9. Kaguelidou F, Alberti C, Castanet M, Guitteny MA, Czernichow P, Leger J (2008) Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 93(10):3817–3826

    Article  CAS  PubMed  Google Scholar 

  10. Havgaard Kjaer R, Smedegard Andersen M, Hansen D (2015) Increasing incidence of juvenile thyrotoxicosis in denmark: a nationwide study, 1998–2012. Horm Res Paediatr 84(2):102–107. doi:10.1159/000430985

    Article  CAS  PubMed  Google Scholar 

  11. Jevalikar G, Solis J, Zacharin M (2014) Long-term outcomes of pediatric Graves’ disease. J Pediatr Endocrinol Metab 27(11–12):1131–1136. doi:10.1515/jpem-2013-0342

    CAS  PubMed  Google Scholar 

  12. Ohye H, Minagawa A, Noh JY, Mukasa K, Kunii Y, Watanabe N, Matsumoto M, Suzuki M, Yoshihara A, Ito K, Ito K (2014) Antithyroid drug treatment for graves’ disease in children: a long-term retrospective study at a single institution. Thyroid 24(2):200–207. doi:10.1089/thy.2012.0612

    Article  CAS  PubMed  Google Scholar 

  13. Glaser NS, Styne DM (1997) Predictors of early remission of hyperthyroidism in children. J Clin Endocrinol Metab 82(6):1719–1726

    CAS  PubMed  Google Scholar 

  14. Glaser NS, Styne DM (2008) Predicting the likelihood of remission in children with Graves’ disease: a prospective, multicenter study. Pediatrics 121(3):e481–e488

    Article  PubMed  Google Scholar 

  15. Hamburger JI (1985) Management of hyperthyroidism in children and adolescents. J Clin Endocrinol Metab 60(5):1019–1024

    Article  CAS  PubMed  Google Scholar 

  16. Lippe BM, Landaw EM, Kaplan SA (1987) Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years. J Clin Endocrinol Metab 64(6):1241–1245

    Article  CAS  PubMed  Google Scholar 

  17. Shulman DI, Muhar I, Jorgensen EV, Diamond FB, Bercu BB, Root AW (1997) Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and responses to medical therapy. Thyroid 7(5):755–760

    Article  CAS  PubMed  Google Scholar 

  18. Chapman EM (1983) History of the discovery and early use of radioactive iodine. JAMA 250(15):2042–2044

    Article  CAS  PubMed  Google Scholar 

  19. Weetman AP (2003) Grave’s disease 1835-2002. Horm Res 59(Suppl 1):114–118

    CAS  PubMed  Google Scholar 

  20. Cooper DS (2005) Antithyroid drugs. N Engl J Med 352(9):905–917

    Article  CAS  PubMed  Google Scholar 

  21. Merkel PA (1998) Drugs associated with vasculitis. Curr Opin Rheumatol 10(1):45–50

    Article  CAS  PubMed  Google Scholar 

  22. Cooper DS (1998) Antithyroid drugs for the treatment of hyperthyroidism caused by Graves’ disease. Endocrinol Metab Clin North Am 27(1):225–247

    Article  CAS  PubMed  Google Scholar 

  23. Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (2007) Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab 92(6):2157–2162

    Article  CAS  PubMed  Google Scholar 

  24. Rivkees SA (2010) 63 Years and 715 days to the “Boxed Warning”: unmasking of the propylthiouracil problem. Int J Pediatric Endocrinol vol. 2010, Article ID 658267, 3 pages, 2010. doi:10.1155/2010/658267

  25. Rivkees SA, Mattison DR (2009) Ending propylthiouracil-induced liver failure in children. N Engl J Med 360(15):1574–1575. doi:10.1056/NEJMc0809750

    Article  CAS  PubMed  Google Scholar 

  26. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII – Phase 2 (2006). National Academies Press, Washington D.C

  27. Rivkees SA, Mattison DR (2009) Propylthiouracil (PTU) hepatoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol 2009:132041. doi:10.1155/2009/132041

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dotsch J, Siebler T, Hauffa BP, Doeker B, Andler W, Bettendorf M, Heinrich U, Gohlke B, Albers N, Willgerodt H, Kiess W (2000) Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study. J Pediatric Endocrinol 13(7):879–885

    Article  CAS  Google Scholar 

  29. Dotsch J, Rascher W, Dorr HG (2003) Graves disease in childhood: a review of the options for diagnosis and treatment. Paediatr Drugs 5(2):95–102

    Article  PubMed  Google Scholar 

  30. Slyper AH, Wyatt D, Boudreau C (2005) Effective methimazole dose for childhood Grave’s disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery. J Pediatr Endocrinol Metab 18(6):597–602

    Article  CAS  PubMed  Google Scholar 

  31. Cassio A, Corrias A, Gualandi S, Tato L, Cesaretti G, Volta C, Weber G, Bona G, Cappa M, Bal M, Bellone J, Cicognani A (2006) Influence of gender and pubertal stage at diagnosis on growth outcome in childhood thyrotoxicosis: results of a collaborative study. Clin Endocrinol (Oxf) 64(1):53–57

    Article  CAS  Google Scholar 

  32. Sato H, Harada S, Yokoya S, Tanaka T, Asayama K, Mori M, Sasaki N (2007) Treatment for childhood-onset Graves’ disease in Japan: results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists. Thyroid 17(1):67–72

    Article  PubMed  Google Scholar 

  33. Nicholas WC, Fischer RG, Stevenson RA, Bass JD (1995) Single daily dose of methimazole compared to every 8 hours propylthiouracil in the treatment of hyperthyroidism. South Med J 88(9):973–976

    Article  CAS  PubMed  Google Scholar 

  34. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN, American Thyroid A, American Association of Clinical E (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17(3):456–520

    Article  PubMed  Google Scholar 

  35. Abraham P, Avenell A, Watson WA, Park CM, Bevan JS (2005) Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev (2):CD003420

  36. Razvi S, Vaidya B, Perros P, Pearce SH (2006) What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves’ disease. Eur J Endocrinol 154(6):783–786

    Article  CAS  PubMed  Google Scholar 

  37. Cooper DS, Goldminz D, Levin AA, Ladenson PW, Daniels GH, Molitch ME, Ridgway EC (1983) Agranulocytosis associated with antithyroid drugs. Effects of patient age and drug dose. Ann Intern Med 98(1):26–29

    Article  CAS  PubMed  Google Scholar 

  38. Woeber KA (2002) Methimazole-induced hepatotoxicity. Endocr Pract 8(3):222–224

    Article  PubMed  Google Scholar 

  39. Rivkees SA, Stephenson K, Dinauer C (2010) Adverse events associated with methimazole therapy of graves’ disease in children. Int J Pediatr Endocrinol 2010:176970. doi:10.1155/2010/176970

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tajiri J, Noguchi S (2005) Antithyroid drug-induced agranulocytosis: how has granulocyte colony-stimulating factor changed therapy? Thyroid 15(3):292–297

    Article  CAS  PubMed  Google Scholar 

  41. Weetman AP (2006) Graves’ hyperthyroidism: how long should antithyroid drug therapy be continued to achieve remission? Nat Clin Pract Endocrinol Metab 2:2–3

    Article  PubMed  Google Scholar 

  42. Allannic H, Fauchet R, Orgiazzi J, Madec AM, Genetet B, Lorcy Y, Le Guerrier AM, Delambre C, Derennes V (1990) Antithyroid drugs and Graves’ disease: a prospective randomized evaluation of the efficacy of treatment duration. J Clin Endocrinol Metab 70(3):675–679

    Article  CAS  PubMed  Google Scholar 

  43. García-Mayor RV, Paramo C, Cano RL, Mendez LP, Galofre JC, Andrade A (1992) Antithyroid drug and Graves’ hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. J Endocrinol Investig 15(11):815–820

    Article  Google Scholar 

  44. Maugendre D, Gatel A, Campion L, Massart C, Guilhem I, Lorcy Y, Lescouarch J, Herry JY, Allannic H (1999) Antithyroid drugs and Graves’ disease—prospective randomized assessment of long-term treatment. Clin Endocrinol (Oxf) 50(1):127–132

    Article  CAS  Google Scholar 

  45. Laurberg P, Nygaard B, Andersen S, Carle A, Karmisholt J, Krejbjerg A, Pedersen IB, Andersen SL (2014) Association between TSH-Receptor autoimmunity, hyperthyroidism, goitre, and orbitopathy in 208 patients included in the remission induction and sustenance in Graves’ disease study. J Thyroid Res 2014:165487. doi:10.1155/2014/165487

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Torring O (2008) TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 158(1):69–75. doi:10.1530/EJE-07-0450

    Article  CAS  PubMed  Google Scholar 

  47. Lazar L, Kalter-Leibovici O, Pertzelan A, Weintrob N, Josefsberg Z, Phillip M (2000) Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients. J Clin Endocrinol Metab 85(10):3678–3682

    Article  CAS  PubMed  Google Scholar 

  48. Gruneiro-Papendieck L, Chiesa A, Finkielstain G, Heinrich JJ (2003) Pediatric Graves’ disease: outcome and treatment. J Pediatr Endocrinol Metab 16(9):1249–1255

    PubMed  Google Scholar 

  49. Chen YK, Lin CL, Chang YJ, Cheng FT, Peng CL, Sung FC, Cheng YH, Kao CH (2013) Cancer risk in patients with Graves’ disease: a nationwide cohort study. Thyroid 23(7):879–884. doi:10.1089/thy.2012.0568

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mazzaferri EL (2000) Thyroid cancer and Graves’ disease: the controversy ten years later. Endocr Pract 6(2):221–225. doi:10.4158/EP.6.2.221

    Article  CAS  PubMed  Google Scholar 

  51. Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, Harris BS 3rd, Hoffman DA, McConahey WM, Maxon HR, Preston-Martin S, Warshauer ME, Wong FL, Boice JD Jr (1998) Cancer mortality following treatment for adult hyperthyroidism. Cooperative thyrotoxicosis therapy follow-up study group. JAMA 280(4):347–355

    Article  CAS  PubMed  Google Scholar 

  52. Dobyns BM, Sheline GE, Workman JB, Tompkins EA, McConahey WM, Becker DV (1974) Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism: a report of the cooperative thyrotoxicosis therapy follow-up study. J Clin Endocrinol Metab 38:976–998

    Article  CAS  PubMed  Google Scholar 

  53. Ron E, Doody Becker DV, Brill Curtis, Goldman Harris B, Hoffman McConahey, Maxon Preston-Martin, Warshauer Wong, Boice JDJ (1998) Cancer mortality following treatment for adult hyperthyroidism. Cooperative thyrotoxicosis therapy follow-up study group. JAMA 280:347–355

    Article  CAS  PubMed  Google Scholar 

  54. Harper L, Chin L, Daykin J, Allahabadia A, Heward J, Gough SC, Savage CO, Franklyn JA (2004) Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves’ disease. Clin Endocrinol (Oxf) 60(6):671–675

    Article  CAS  Google Scholar 

  55. Guma M, Olive A, Juan M, Salinas I (2002) ANCA antibodies in Graves’ disease. Ann Rheum Dis 61(1):90–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Radice A, Sinico RA (2005) Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity 38(1):93–103

    Article  CAS  PubMed  Google Scholar 

  57. Marshall EG (2011) Do young adults have unmet healthcare needs? J Adolesc Health 49(5):490–497. doi:10.1016/j.jadohealth.2011.03.005

    Article  PubMed  Google Scholar 

  58. Society for Adolescent M (2004) Access to health care for adolescents and young adults. J Adolesc Health 35(4):342–344

    Article  Google Scholar 

  59. Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, Laurberg P, McDougall IR, Rivkees SA, Ross D, Sosa JA, Stan MN (2009) The role of propylthiouracil in the management of Graves’ disease in adults: report of a meeting jointly sponsored by the American thyroid association and the food and drug administration. Thyroid 19(7):673–674. doi:10.1089/thy.2009.0169

    Article  CAS  PubMed  Google Scholar 

  60. Hertz BE, Schuller KE (2010) Saul Hertz, Md (1905–1950): a pioneer in the use of radioactive iodine. Endocrine Pract 16(4):713–715. doi:10.4158/Ep10065.Co

    Article  Google Scholar 

  61. Sheline GE, McCormack KR, Galante M (1962) Thyroid nodules occurring late after treatment of thryotoxicosis with radioiodine. J Clin Endocrinol Metab 22:8–17

    Article  CAS  PubMed  Google Scholar 

  62. Goolden AWG, Davey JB (1963) The ablation of normal thyroid tissue with iodine-131. Br J Radiol 36:340–345

    Article  CAS  PubMed  Google Scholar 

  63. Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL (1983) Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med 309:937–941

    Article  CAS  PubMed  Google Scholar 

  64. Levy WM, Schumacher OP, Gupta M (1988) Treatment of childhood Graves’ disease. A review with emphasis on radioiodine treatment. Cleveland Clin J Med 55:373–382

    Article  CAS  Google Scholar 

  65. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H (1997) Treatment of Graves’ hyperthyroidism with radioiodine: results of a prospective randomized study. Thyroid 7(2):247–251

    Article  CAS  PubMed  Google Scholar 

  66. Graham GD, Burman KD (1986) Radioiodine treatment of Graves’ disease. An assessment of its potential risks. Ann Intern Med 105:900–905

    Article  CAS  PubMed  Google Scholar 

  67. Nebesio TD, Siddiqui AR, Pescovitz OH, Eugster EA (2002) Time course to hypothyroidism after fixed-dose radioablation therapy of Graves’ disease in children. J Pediatr 141(1):99–103

    Article  PubMed  Google Scholar 

  68. Kalinyak JE, McDougall IR (2003) How should the dose of iodine-131 be determined in the treatment of Graves’ hyperthyroidism? J Clin Endocrinol Metab 88(3):975–977

    Article  CAS  PubMed  Google Scholar 

  69. Leslie WD, Ward L, Salamon EA, Ludwig S, Rowe RC, Cowden EA (2003) A randomized comparison of radioiodine doses in Graves’ hyperthyroidism. J Clin Endocrinol Metab 88(3):978–983

    Article  CAS  PubMed  Google Scholar 

  70. Rivkees SA, Cornelius EA (2003) Influence of iodine-131 dose on the outcome of hyperthyroidism in children. Pediatrics 111(4 Pt 1):745–749

    Article  PubMed  Google Scholar 

  71. Levy WJ, Schumacher OP, Gupta M (1988) Treatment of childhood Graves’ disease. A review with emphasis on radioiodine treatment. Cleveland Clin J Med 55(4):373–382

    Article  CAS  Google Scholar 

  72. Kadmon PM, Noto RB, Boney CM, Goodwin G, Gruppuso PA (2001) Thyroid storm in a child following radioactive iodine (RAI) therapy: a consequence of RAI versus withdrawal of antithyroid medication. J Clin Endocrinol Metab 86(5):1865–1867

    Article  CAS  PubMed  Google Scholar 

  73. Rohrs HJ 3rd, Silverstein JH, Weinstein DA, Amdur RJ, Haller MJ (2014) Thyroid storm following radioactive iodine (RAI) therapy for pediatric graves disease. Am J Case Rep 15:212–215. doi:10.12659/AJCR.890366

    Article  PubMed  PubMed Central  Google Scholar 

  74. Becker DV, Hurly (1971) Complications of radioiodine treatment of hyperthyroidism. Semin Nucl Med 1:442–460

    Article  CAS  PubMed  Google Scholar 

  75. Refetoff S, Demeester-Mirkine N, Ermans AM, De Groot LJ (1977) Rapid control of thyrotoxicosis with combined 131I, anthithyroid drugs and KI therapy. J Nucl Med Allied Sci 21:23–29

    CAS  PubMed  Google Scholar 

  76. Ross DS, Daniels GH, De Stefano P, Maloof F, Ridgway EC (1983) Use of adjunctive potassium iodide after radioactive iodine (131I) treatment of Graves’ hyperthyroidism. J Clin Endocrinol Metab 57:250–253

    Article  CAS  PubMed  Google Scholar 

  77. Starr P, Jaffe HL, Oettinger L (1964) Late results of 131I treatment of hyperthyroidism in 73 children and adoloscents. J Nucl Med 5:81–89

    CAS  PubMed  Google Scholar 

  78. Kogut MD, Kaplan SA, Collipp PJ, Tiamsic T, Boyle D (1965) Treatment of hyperthyroidism in children: analysis of fourty-five patients. N Engl J Med 272:217–222

    Article  CAS  PubMed  Google Scholar 

  79. Crile G, Schumacher OP (1965) Radioactive iodine treatment of Graves’ disease. Results in 32 children under 16 years of age. Am J Dis Child 110:501–504

    Article  PubMed  Google Scholar 

  80. Starr HJ, Oettinger L (1969) Later results of 131-I treatment of hyperthyroidism in 73 children and adolescence: 1967 follow-up. J Nucl Med 10:586–590

    CAS  PubMed  Google Scholar 

  81. Hayek A, Chapman EM, Crawford JD (1970) Long term results of treatment of thyrotoxicosis in children and adolescents with radioactive iodine (131I) for hyperthyroidism. N Engl J Med 283:949–953

    Article  CAS  PubMed  Google Scholar 

  82. Freitas JE, Swanson DP, Gross MD, Sisson JC (1979) Iodine131-I: optimal therapy for thyroidism in children and adolescents? J Nucl Med 20:847–850

    CAS  PubMed  Google Scholar 

  83. Moll BRP (1997) Pediatric Graves’ disease: therapeutic options and experinence with radioiodine at the University of Mississippi Medical center. South Med J 90:1017–1022

    Article  PubMed  Google Scholar 

  84. Safa AM, Schumacher OP, Rodriguez-Antunez A (1975) Long-term follow-up results in children and adolescents treated with radioactive iodine (131I) for hyperthyroidism. N Engl J Med 292:167–171

    Article  CAS  PubMed  Google Scholar 

  85. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H (1995) Radioiodine therapy of Graves’ hyperthyroidism: standard vs. calculated 131 iodine activity. Results from a prospective, randomized, multicentre study. Eur J Clin Investig 25(3):186–193

    Article  CAS  Google Scholar 

  86. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H (1996) Reduction in thyroid volume after radioiodine therapy of Graves’ hyperthyroidism: results of a prospective, randomized, multicentre study. Eur J Clin Investig 26(1):59–63

    Article  CAS  Google Scholar 

  87. Safa AM (1975) Treatment of hyperthyroidism with a large initial dose of sodium iodine I 131. Arch Intern Med 135:673–675

    Article  CAS  PubMed  Google Scholar 

  88. Barnes HV, Blizzard RM (1977) Antithyroid drug therapy for toxic diffuse goiter (Graves disease): thirty years experience in children and adolscence. J Pediatr 91:313–320

    Article  CAS  PubMed  Google Scholar 

  89. Miccoli P, Vitti P, Rago T, Iacconi P, Bartalena L, Bogazzi F, Fiore E, Valeriano R, Chiovato L, Rocchi R, Pinchera A (1996) Surgical treatment of Graves’ disease: subtotal or total thyroidectomy? Surgery 120(6):1020–1024 discussion 1024–1025

    Article  CAS  PubMed  Google Scholar 

  90. Sarkar SD, Beierwaltes WH, Gill SP, Cowley BJ (1976) Subsequent fertility and birth histories of children and adolescents treated with 131I for thyroid cancer. J Nucl Med 17:460–464

    CAS  PubMed  Google Scholar 

  91. Boice JD Jr (2005) Radiation-induced thyroid cancer–what’s new? J Natl Cancer Instig 97(10):703–705

    Article  Google Scholar 

  92. Boice JD Jr (2006) Thyroid disease 60 years after Hiroshima and 20 years after Chernobyl. JAMA 295(9):1060–1062

    Article  CAS  PubMed  Google Scholar 

  93. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, Schneider AB, Tucker MA, Boice JD Jr (1995) Thyroid Cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 141:259–277

    Article  CAS  PubMed  Google Scholar 

  94. Dolphin GW (1968) The risk of thyroid cancers following irradiation. Health Phys 15:219–228

    Article  CAS  PubMed  Google Scholar 

  95. Sigurdson AJ, Ronckers CM, Mertens AC, Stovall M, Smith SA, Liu Y, Berkow RL, Hammond S, Neglia JP, Meadows AT, Sklar CA, Robison LL, Inskip PD (2005) Primary thyroid cancer after a first tumour in childhood (the childhood cancer survivor study): a nested case-control study. Lancet 365(9476):2014–2023

    Article  PubMed  Google Scholar 

  96. Goldman RRM, Maloof F (1990) Cancer mortality in women with thyroid disease. Cancer Res 50:2283–2289

    CAS  PubMed  Google Scholar 

  97. Holm LE, Hall P, Wiklund K, Lundell G, Berg G, Bjelkengren G, Cederquist E, Ericsson UB, Hallquist A, Larsson LG (1991) Cancer risk after iodine-131 therapy for hyperthyroidism. J Natl Cancer Inst 83:1072–1077

    Article  CAS  PubMed  Google Scholar 

  98. Franklyn JA, Maisonneuve P, Sheppard MC, Betteridge J, Boyle P (1998) Mortality after the treatment of hyperthyroidism with radioactive iodine. N Engl J Med 338(11):712–718

    Article  CAS  PubMed  Google Scholar 

  99. Franklyn JA, Sheppard MC, Maisonneuve P (2005) Thyroid function and mortality in patients treated for hyperthyroidism. JAMA 294(1):71–80

    Article  CAS  PubMed  Google Scholar 

  100. Flynn RW, Macdonald TM, Jung RT, Morris AD, Leese GP (2006) Mortality and vascular outcomes in patients treated for thyroid dysfunction. J Clin Endocrinol Metab 91(6):2159–2164

    Article  CAS  PubMed  Google Scholar 

  101. Metso S, Auvinen A, Huhtala H, Salmi J, Oksala H, Jaatinen P (2007) Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer 109(10):1972–1979

    Article  CAS  PubMed  Google Scholar 

  102. Read CH Jr, Tansey MJ, Menda Y (2004) A thirty-six year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' pateints. J Clin Endocrinol Metab 89(9):4229–4233

    Article  CAS  PubMed  Google Scholar 

  103. Toohey RE, Stabin MG, Watson EE (2000) The AAPM/RSNA physics tutorial for residents: internal radiation dosimetry: principles and applications. Radiographics 20(2):533–546

    Article  CAS  PubMed  Google Scholar 

  104. Toohey RE, Stabin MG (1996) Comparative analysis of dosimetry parameters for nuclear medicine. ORISE Report 99-1064, 1999. In: Proceedings of the sixth international radiopharmaceutical dosimetry symposium, Gatlinburg, TN, 1996. pp 532–551

  105. Ching T, Warden MJ, Fefferman RA (1977) Thyroid surgery in children and teenagers. Arch Otolaryngol 103:544–546

    Article  CAS  PubMed  Google Scholar 

  106. Buckingham BA, Costin G, Roe TF, Weitzman JJ, Kogut MD (1981) Hyperthyroidism in children. A reevaluation of treatment. Am J Dis Child 135(2):112–117

    Article  CAS  PubMed  Google Scholar 

  107. Rudberg Johansson H, Akerstrom G, Tuvemo Karlsson FA (1996) Graves’ disease in children and adolescents. Late results of surgical treatment. Eur J Endocrinol 134:710–715

    Article  CAS  PubMed  Google Scholar 

  108. Sosa JA, Tuggle CT, Wang TS, Thomas DC, Boudourakis L, Rivkees S, Roman SA (2008) Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab 93(8):3058–3065

    Article  CAS  PubMed  Google Scholar 

  109. Breuer CK, Solomon D, Donovan P, Rivkees SA (2013) Udelsman R (2013) Effect of patient Age on surgical outcomes for Graves’ disease: a case-control study of 100 consecutive patients at a high volume thyroid surgical center. Int J Pediatr Endocrinol 1:1. doi:10.1186/1687-9856-2013-1

    Article  Google Scholar 

  110. Lal G, Ituarte P, Kebebew E, Siperstein A, Duh QY, Clark OH (2005) Should total thyroidectomy become the preferred procedure for surgical management of Graves’ disease? Thyroid 15(6):569–574

    Article  PubMed  Google Scholar 

  111. Boger MS, Perrier ND (2004) Advantages and disadvantages of surgical therapy and optimal extent of thyroidectomy for the treatment of hyperthyroidism. Surg Clin North Am 84(3):849–874

    Article  PubMed  Google Scholar 

  112. Witte J, Goretzki PE, Dotzenrath C, Simon D, Felis P, Neubauer M, Roher HD (2000) Surgery for Graves’ disease: total versus subtotal thyroidectomy-results of a prospective randomized trial. World J Surg 24(11):1303–1311

    Article  CAS  PubMed  Google Scholar 

  113. Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R (1998) The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann Surg 228(3):320–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Breuer C, Tuggle C, Solomon D, Sosa JA (2013) Pediatric thyroid disease: when is surgery necessary, and who should be operating on our children? J Clin Res Pediatric Endocrinol 5(Suppl 1):79–85. doi:10.4274/jcrpe.817

    Google Scholar 

  115. Peroni E, Angiolini MR, Vigone MC, Mari G, Chiumello G, Beretta E, Weber G (2012) Surgical management of pediatric Graves’ disease: an effective definitive treatment. Pediatr Surg Int 28(6):609–614. doi:10.1007/s00383-012-3095-5

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by NIH grant 7R01FD003707.

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  1. Department of Pediatrics, University of Florida College of Medicine, Pediatrics – Chairman’s Office, 1600 SW Archer Road – Room R1-118, Gainesville, FL, 32610-0296, USA

    S. A. Rivkees

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Correspondence to S. A. Rivkees.

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Rivkees, S.A. Controversies in the management of Graves’ disease in children. J Endocrinol Invest 39, 1247–1257 (2016). https://doi.org/10.1007/s40618-016-0477-x

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