Research Article
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Published Online: 11 February 2014

Antithyroid Drug Treatment for Graves' Disease in Children: A Long-Term Retrospective Study at a Single Institution

Publication: Thyroid
Volume 24, Issue Number 2

Abstract

Background: The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation.
Objective: The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients.
Methods: We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3–18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period.
Results: Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3–24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil.
Conclusion: Long-term ATD treatment is a useful treatment option for GD in children.

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References

1.
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 85:3678–3682.
2.
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 64:1241–1245.
3.
Rudberg C, Johansson H, Akerstrom G, Tuvemo T, Karlsson FA 1996 Graves' disease in children and adolescents. Late results of surgical treatment. Eur J Endocrinol 134:710–715.
4.
Mussa GC, Corrias A, Silvestro L, Battan E, Mostert M, Mussa F, Pellegrino D 1999 Factors at onset predictive of lasting remission in pediatric patients with Graves' disease followed for at least three years. J Pediatr Endocrinol Metab 12:537–541.
5.
Gruneiro-Papendieck L, Chiesa A, Finkielstain G, Heinrich JJ 2003 Pediatric Graves' disease: outcome and treatment. J Pediatr Endocrinol Metab 16:1249–1255.
6.
Barrio R, Lopez-Capape M, Martinez-Badas I, Carrillo A, Moreno JC, Alonso M 2005 Graves' disease in children and adolescents: response to long-term treatment. Acta Paediatr 94:1583–1589.
7.
Poyrazoglu S, Saka N, Bas F, Isguven P, Dogu A, Turan S, Bereket A, Sarikaya S, Adal E, Cizmecioglu F, Saglam H, Ercan O, Memioglu N, Gunoz H, Bundak R, Darendeliler F, Yildiz M, Guran T, Akcay T, Akin L, Hatun S 2008 Evaluation of diagnosis and treatment results in children with Graves' disease with emphasis on the pubertal status of patients. J Pediatr Endocrinol Metab 21:745–751.
8.
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 7:755–760.
9.
Glaser NS, Styne DM 1997 Predictors of early remission of hyperthyroidism in children. J Clin Endocrinol Metab 82:1719–1726.
10.
Raza J, Hindmarsh PC, Brook CG 1999 Thyrotoxicosis in children: thirty years' experience. Acta Paediatr 88:937–941.
11.
Bergman P, Auldist AW, Cameron F 2001 Review of the outcome of management of Graves' disease in children and adolescents. J Paediatr Child Health 37:176–182.
12.
Bhadada S, Bhansali A, Velayutham P, Masoodi SR 2006 Juvenile hyperthyroidism: an experience. Indian Pediatr 43:301–307.
13.
Somnuke PH, Pusuwan P, Likitmaskul S, Santiprabhob J, Sawathiparnich P 2007 Treatment outcome of Graves' disease in Thai children. J Med Assoc Thai 90:1815–1820.
14.
Brownlie BE, Hunt PJ, Turner JG 2010 Juvenile thyrotoxicosis—a South Island, New Zealand experience with long-term outcome. N Z Med J 123:23–31.
15.
Kaguelidou F, Alberti C, Castanet M, Guitteny M-A, Czernichow P, Leger J, for the French Childhood Graves' Disease Study Group 2008 Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 93:3817–3826.
16.
Glaser NS, Styne DM, for the Organization of Pediatric Endocrinologists of Northern California Collaborative Graves' Disease Study Group 2008 Predicting the likelihood of remission in children with Graves' disease: a prospective, multicenter study. Pediatrics 121:e481–488.
17.
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 97:110–119.
18.
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. Clinical Endocrinology 50:127–132.
19.
Kaguelidou F, Carel JC, Léger J 2009 Graves' disease in childhood: advances in management with antithyroid drug therapy. Hormone Res Paediatr 71:310–317.
20.
Bahn Chair 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 2011 Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 21:593–646.
21.
Rivkees SA, Mattison DR 2009 Propylthiouracil (PTU) hepatoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol 2009:132041.
22.
Sato H, Hattori M, Fujieda M, Sugihara S, Inomata H, Hoshi M, Miyamoto S 2000 High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil. J Clin Endocrinol Metab 85:4270–4273.
23.
Rivkees SA, Szarfman A 2010 Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab 95:3260–3267.
24.
Hirokazu S, Nozomu S, Shohei H, Toshiaki T, Fumito A, Kohtaro A, Naoko A, Hiroaki I, Hidemi O, Kazumichi O, Susumu K, Shigetaka S, Junichi T, Hiroyuki T, Soroku N, Tomonobu H, Yukihiro H, Shuji F, Naoko M, Susumu Y, Hiroshi Y, Masatomo M, Kenji F 2008 Guidelines for the treatment of childhood-onset Graves' disease with antithyroid drug in Japan, 2008. J Japan Pediatr Soc 112:946–952.
25.
Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS 2010 Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev:CD003420.
26.
Bauer AJ 2011 Approach to the pediatric patient with Graves' disease: when is definitive therapy warranted? J Clin Endocrinol Metab 96:580–588.
27.
Okubo T 1959 The determination of thyroid weight in vivo with the scintigram. Nihon Igaku Hosyasen Gakkai Zasshi 19:120–128.
28.
Quadbeck B, Hoermann R, Roggenbuck U, Hahn S, Mann K, Janssen OE 2005 Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease. Thyroid 15:1047–1054.
29.
Takasu N, Yamashiro K, Komiya I, Ochi Y, Sato Y, Nagata A 2000 Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment. Thyroid 10:891–896.
30.
Kashiwai T, Hidaka YOH, Takano T, Tatsumi K-I, Izumi Y, Shimaoka Y, Tada H, Takeoka K, Amino N 2003 Practical treatment with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves' disease. Endocr J 50:45–49.
31.
Okamoto Y, Tanigawa S-i, Ishikawa K, Hamada N 2006 TSH receptor antibody measurements and prediction of remission in Graves' disease patients treated with minimum maintenance doses of antithyroid drugs. Endocr J 53:467–472.
32.
Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore E, Rocchi R, Martino E, Pinchera A 1997 Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment. Thyroid 7:369–375.
33.
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 93:3058–3065.
34.
Brent GA 2010 Environmental exposures and autoimmune thyroid disease. Thyroid 20:755–761.
35.
Davies TF, Latif R, Yin X 2012 New genetic insights from autoimmune thyroid disease. J Thyroid Res 2012:623852.
36.
Brix TH, Kyvik KO, Christensen K, Hegedus L 2001 Evidence for a major role of heredity in Graves' disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab 86:930–934.
37.
Rivkees SA, Stephenson K, Dinauer C 2010 Adverse events associated with methimazole therapy of Graves' disease in children. Int J Pediatr Endocrinol 2010:176970.
38.
Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N, Working Group of the Japan Thyroid Association for the Guideline of the Treatment of Graves' Disease 2007 Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab 92:2157–2162.
39.
Otsuka F, Noh JY, Chino T, Shimizu T, Mukasa K, Ito K, Taniyama M 2012 Hepatotoxicity and cutaneous reactions after antithyroid drug administration. Clin Endocrinol 77:310–315.
40.
Japan Thyroid Association 2011 Guideline for the Drug Treatment of Graves' Disease 201 First edition. Nankodo, Japan.
41.
Rivkees SA, Mattison DR 2009 Ending propylthiouracil-induced liver failure in children. New Engl J Med 360:1574–1575.
42.
Sato H, Minagawa M, Sasaki N, Sugihara S, Kazukawa I, Minamitani K, Wataki K, Konda S, Inomata H, Sanayama K, Kohno Y 2011 Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: efficacy and adverse reactions during initial treatment and long-term outcome. J Pediatr Endocrinol Metab 24:257–263.

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Published In

cover image Thyroid®
Thyroid
Volume 24Issue Number 2February 2014
Pages: 200 - 207
PubMed: 23926918

History

Published online: 11 February 2014
Published in print: February 2014
Published ahead of print: 13 November 2013
Published ahead of production: 8 August 2013

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Hidemi Ohye
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Akinobu Minagawa
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Jaeduk Yoshimura Noh
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Koji Mukasa
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Yo Kunii
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Natsuko Watanabe
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Masako Matsumoto
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Miho Suzuki
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Ai Yoshihara
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Koichi Ito
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.
Kunihiko Ito
Department of Internal Medicine, Ito Hospital, Tokyo, Japan.

Notes

Address correspondence to:Hidemi Ohye, MD, PhD4-3-6 JingumaeShibuya-kuTokyo 150-8308Japan
E-mail: [email protected]

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