Background/Aims: Pediatric Graves' disease (GD) accounts for 10-15% of all thyroid disorders in patients ≤18 years and is treated with antithyroid medication or definitive therapy [radioactive iodine (RAI) ablation vs. surgery]. Patients with GD may have concurrent differentiated thyroid cancer (DTC). DTC prevalence in pediatric GD is not well established. We examined the prevalence of DTC in pediatric GD and the role of preoperative thyroid ultrasound (US) in selecting the appropriate definitive therapy. Methods: This is a single-institution, retrospective, cross-sectional study of 32 GD patients with a median age of 11 years (range 3-18) who underwent total thyroidectomy as the definitive treatment between 2005 and 2014. Results: DTC was identified in 22% of the GD patients. A total of 97% completed preoperative thyroid US, and thyroid nodules were identified in 13/32 patients (41%). Preoperative fine needle aspiration (FNA) biopsy was performed in 6/13 patients, accounting for four preoperative diagnoses of concurrent DTC. Extra-thyroidal extension was present in 4/7 (63%), regional lymph node metastasis in 3/7 (43%), and lung metastasis in 2/7 patients (29%). Conclusions: Concurrent DTC occurs in pediatric GD patients. Thyroid US is an efficient tool for selecting patients for thyroidectomy. For patients with a nodule on US before definitive therapy, FNA should be performed to appropriately select thyroidectomy versus RAI ablation.

Keywords:
Gravesߣ disease, Differentiated thyroid cancer, Papillary thyroid carcinoma, Thyroid nodule
1.
Zimmerman D, Lteif AN: Thyrotoxicosis in children. Endocrinol Metab Clin North Am 1998;27:109-126.
2.
Gastaldi R, Poggi E, Mussa A, Weber G, Vigone MC, Salerno M, Delvecchio M, Peroni E, Pistorio A, Corrias A: Graves' disease in children: thyroid-stimulating hormone receptor antibodies as remission markers. J Pediatr 2014;164:1189-1194.
3.
Poyrazoğlu S, Saka N, Bas F, Isguven P, Dogu A, Turan S, Bereket A, Sarikaya S, Adal E, Cizmeciglu F, Saglam H, Ercan O, Memioglu N, Günöz H, Bundkar R, Darendeliler F, Yildiz M, Guran T, Akcay T, Akin L, Hatun S: Evaluation of diagnosis and treatment results in children with Graves' disease with emphasis on the pubertal status of patients. J Pediatr Endocrinol Metab 2008;21:745-751.
4.
Lazar L, Kalter-Leibovici O, Pertzelan A, Weintrob N, Josefsberg Z, Phillip M: Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients. J Clin Endocrinol Metab 2000;85:3678-3682.
5.
Shulman DI, Muhar I, Jorgensen EV, Diamond FB, Bercu BB, Root AW: Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and responses to medical therapy. Thyroid 1997;7:755-760.
6.
Kaguelidou F, Alberti C, Castanet M, Guitteny MA, Czemichow P, Léger J; French Childhood Graves' Disease Study Group: Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 2008;93:3817-3826.
7.
Cappelli C, Braga M, De Martino E, Castellano M, Gandossi E, Agosti B, Cumetti D, Pirola I, Mattanza C, Cherubini L, Rosei EA: Outcome of patients surgically treated for various forms of hyperthyroidism with differentiated thyroid cancer: experience at an endocrine center in Italy. Surg Today 2006;36:125-130.
8.
Pellegriti G, Belfiore A, Guiffrida D, Lupo L, Vigneri R: Outcome of differentiated thyroid cancer in Graves' patients. J Clin Endocrinol Metab 1998;83:2805-2809.
9.
Yano Y, Shibuva H, Kitagawa W, Nagahama M, Sugino K, Ito K, Ito K: Recent outcome of Graves' disease patients with papillary thyroid cancer. Eur J Endocrinol 2007;157:325-329.
10.
Wei S, Baloch ZW, LiVolsi VA: Thyroid carcinoma in patients with Graves' disease: an institutional experience. Endocr Pathol 2015;26:48-53.
11.
Niedziela M, Korman E: Thyroid carcinoma in a fourteen-year-old boy with Graves' disease. Med Pediatr Oncol 2002;38:290-291.
12.
Hogan AR, Zhuge Y, Perez EA, Koniaris LG, Lew JI, Sola JE: Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 2009;156:167-172.
13.
Holmes L Jr, Hossain J, Opara F: Pediatric thyroid carcinoma incidence and temporal trends in the USA (1973-2007): race or shifting diagnostic paradigm? ISRN Oncol 2012;2012:906197.
14.
Wu X, Groves FD, McLaughlin CC, Jemal A, Martin J, Chen VW: Cancer incidence patterns among adolescents and young adults in the United States. Cancer Causes Control 2005;16:309-320.
15.
Mostoufi-Moab S, Barakat LP, Bauer AJ: Quality of life in adolescent patients with differentiated thyroid cancer: moving beyond survival. J Clin Endocrinol Metab 2012;97:3453-3456.
16.
Thyroid, in Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds): AJCC Cancer Staging Manual, ed. 7. New York, Springer, 2010, pp 87-96.
17.
Lee JI, Chung YJ, Cho BY, Chong S, Seok JW, Park SJ: Postoperative-stimulated serum thyroglobulin measured at the time of 131I ablation is useful for the prediction of disease status in patients with differentiated thyroid carcinoma. Surgery 2013;153:828-835.
18.
Bauer AJ: Approach to the pediatric patient with Graves' disease: when is definitive therapy warranted? J Clin Endocrinol Metab 2011;93:580-588.
19.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Lauerberg P, McDougall IR, Montori VM, Rivkees SA: Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011;21:593-646.
20.
Leger J, Gelwane G, Kaquelidou F, Benmerad M, Alberti C; French Childhood Graves' Disease Study Group: 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 2012;97:110-119.
21.
Ohye H, Minagawa A, Noh JY, Mukasa K, Kunii Y, Watanabe N, Matsumoto M, Suzuki M, Yoshihara A, Ito K, Ito K: Antithyroid drug treatment for graves' disease in children: a long-term retrospective study at a single institution. Thyroid 2014;24:200-207.
22.
Stocker DJ, Fister DD, Solomon BL, Shriver CD, Burch HB: Thyroid cancer yield in patients with Graves' disease selected for surgery on the basis of cold scintiscan defects. Thyroid 2002;12:305-311.
23.
Livadas D, Psarras A, Koutras DA: Malignant cold thyroid nodules in hyperthyroidism. Br J Surg 1976;63:726-728.
24.
Breuer CK, Solomon D, Donovan P, Rivkees SA, Udelsman R: 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 2013;2013:1.
25.
Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R, Belifore A: Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease. J Clin Endocrinol Metab 2013;98:1014-1021.
26.
Rossi ED, Straccia P, Martini M, Revelli L, Lombardi CP, Pontecorvi A, Fadda G: The role of thyroid fine-needle aspiration cytology in the pediatric population: an institutional experience. Cancer Cytopathol 2014;122:359-367.
© 2015 S. Karger AG, Basel
2015
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