Adverse reactions of methimazole in children with hyperthyroidism

ZHOU Xian, XIN Ying

Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (11) : 1252-1258.

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Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (11) : 1252-1258. DOI: 10.7499/j.issn.1008-8830.2205022
CLINICAL RESEARCH

Adverse reactions of methimazole in children with hyperthyroidism

  • ZHOU Xian, XIN Ying
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Abstract

Objective To investigate the incidence rate of adverse reactions of methimazole in children with hyperthyroidism. Methods A retrospective analysis was performed on the medical data of 304 children with hyperthyroidism who were hospitalized in Shengjing Hospital of China Medical University from January 2015 to May 2021. The incidence rate of methimazole-related adverse reactions was analyzed. The risk factors for common adverse reactions were evaluated. Results Among the 304 children, 87 (28.6%) experienced adverse reactions, among whom there were 20 boys (23%) and 67 girls (77%). Common adverse reactions included neutropenia (12.8%), rash (11.8%), elevated alanine aminotransferase (9.5%), and joint pain (3.0%), and some children experienced multiple adverse reactions simultaneously or intermittently. Neutropenia often occurred within 3 months after administration (25/39, 64%), elevated alanine aminotransferase often occurred within 1 month after administration (17/29, 59%), and rash often occurred within 3 months after administration (30/36, 83%). Most of the above adverse reactions returned to normal after symptomatic treatment. The multivariate logistic regression analysis showed that younger age and lower absolute neutrophil count before treatment were risk factors for neutropenia after methimazole treatment (P<0.05). Conclusions The adverse reactions of methimazole are common in children with hyperthyroidism, and most adverse reactions occur within 3 months after administration and can be relieved after symptomatic treatment. Children with a younger age or a lower baseline absolute neutrophil count may have a higher risk of neutropenia.

Key words

Hyperthyroidism / Methimazole / Adverse reaction / Child

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ZHOU Xian, XIN Ying. Adverse reactions of methimazole in children with hyperthyroidism[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(11): 1252-1258 https://doi.org/10.7499/j.issn.1008-8830.2205022

References

1 Caputo M, Pecere A, Sarro A, et al. Incidence and prevalence of hyperthyroidism: a population-based study in the Piedmont Region, Italy[J]. Endocrine, 2020, 69(1): 107-112. PMID: 32056093. DOI: 10.1007/s12020-020-02222-7.
2 Chiang YT, Ting WH, Huang CY, et al. Long-term outcomes of Graves disease in children treated with anti-thyroid drugs[J]. Pediatr Neonatol, 2020, 61(3): 311-317. PMID: 31980413. DOI: 10.1016/j.pedneo.2019.12.009.
3 王婕, 苏颖, 顾艳红, 等. 儿童Graves病的治疗进展及抗甲状腺药物治疗的停药时机[J]. 中国妇幼保健, 2019, 34(19): 4588-4591. DOI: 10.7620/zgfybj.j.issn.1001-4411.2019.19.75.
4 Lane LC, Wood CL, Cheetham T. Graves' disease: moving forwards[J]. Arch Dis Child, 2022. Epub ahead of print. DOI: 10.1136/archdischild-2022-323905.
5 Chalasani NP, Maddur H, Russo MW, et al. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2021, 116(5): 878-898. PMID: 33929376. DOI: 10.14309/ajg.0000000000001259.
6 Watanabe N, Narimatsu H, Noh JY, et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease[J]. J Clin Endocrinol Metab, 2012, 97(1): E49-E53. PMID: 22049174. DOI: 10.1210/jc.2011-2221.
7 Pecere A, Caputo M, Sarro A, et al. Methimazole treatment and risk of acute pancreatitis: a population-based cohort study[J]. J Clin Endocrinol Metab, 2020, 105(12): dgaa544. PMID: 32813014. DOI: 10.1210/clinem/dgaa544.
8 Beernaert L, Vanderhulst J. Antithyroid drug-induced lupus erythematosus and immunoglobulin a deficiency[J]. Am J Case Rep, 2020, 21: e927929. PMID: 33349625. PMCID: PMC7767573. DOI: 10.12659/AJCR.927929.
9 Sun L, Fang W, Yi D, et al. Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole[J]. J Clin Pharm Ther, 2021, 46(2): 470-475. PMID: 33119911. DOI: 10.1111/jcpt.13307.
10 Lane LC, Cheetham T. Graves' disease: developments in first-line antithyroid drugs in the young[J]. Expert Rev Endocrinol Metab, 2020, 15(2): 59-69. PMID: 32133893. DOI: 10.1080/17446651.2020.1735359.
11 毛晓健, 马晓丹, 刘丽, 等. 甲巯咪唑治疗379例甲状腺功能亢进儿童的单中心临床研究[J]. 中华内分泌代谢杂志, 2016, 32(1): 6-10. DOI: 10.3760/cma.j.issn.1000-6699.2016.01.003.
12 黄占克, 李维丽. 甲巯咪唑联合左甲状腺素治疗小儿甲状腺功能亢进症的效果和安全性[J]. 中国实用医刊, 2021, 48(19): 91-94. DOI: 10.3760/cma.j.cn115689-20210530-01889.
13 Mooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association guideline for the management of pediatric Graves' disease[J]. Eur Thyroid J, 2022, 11(1): e210073. PMID: 34981748. PMCID: PMC9142815. DOI: 10.1530/ETJ-21-0073.
14 戴云鹏. 实用儿童血液病学[M]. 长春: 吉林科学技术出版社, 2019: 133-134.
15 中华医学会消化病学分会肝胆疾病协作组. 急性药物性肝损伤诊治建议(草案)[J]. 中华消化杂志, 2007, 27(11): 765-767. DOI: 10.3760/j.issn:0254-1432.2007.11.016.
16 葛均波, 徐永健, 王辰, 等. 内科学[M]. 9版. 北京: 人民卫生出版社, 2018: 401-404.
17 Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2017, 64(1): 154-168. PMID: 27429428. DOI: 10.1097/MPG.0000000000001334.
18 Kim H, Lee J, Ha J. A case of antithyroid drug-induced agranulocytosis from a second antithyroid drugs (ATD) administration in a relapsed Graves' disease patient who was tolerant to the first ATD treatment[J]. Clin Case Rep, 2018, 6(9): 1701-1703. PMID: 30214745. PMCID: PMC6132132. DOI: 10.1002/ccr3.1644.
19 Nagarajan VD, Morales A, Pleasant L, et al. Sepsis and thyroid storm in a patient with methimazole-induced agranulocytosis[J]. BMJ Case Rep, 2020, 13(7): e235536. PMID: 32636230. PMCID: PMC7342222. DOI: 10.1136/bcr-2020-235536.
20 Scappaticcio L, Bellastella G, Maiorino MI, et al. Graves' hyperthyroidism-related pancytopenia: a case report with literature review[J]. Hormones (Athens), 2021, 20(1): 93-100. PMID: 32638234. DOI: 10.1007/s42000-020-00227-5.
21 Nakamura H, Miyauchi A, Miyawaki N, et al. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan[J]. J Clin Endocrinol Metab, 2013, 98(12): 4776-4783. PMID: 24057289. DOI: 10.1210/jc.2013-2569.
22 Pisciotta AV. Immune and toxic mechanisms in drug-induced agranulocytosis[J]. Semin Hematol, 1973, 10(4): 279-310. PMID: 4139755.
23 ü?ler R, Atmaca M, Candar ?, et al. Development of agranulocytosis after discontinuation of methimazole: an unusual case[J]. Case Rep Endocrinol, 2015, 2015: 974524. PMID: 26339512. PMCID: PMC4538967. DOI: 10.1155/2015/974524.
24 Plantinga TS, Arts P, Knarren GH, et al. Rare NOX3 variants confer susceptibility to agranulocytosis during thyrostatic treatment of Graves' disease[J]. Clin Pharmacol Ther, 2017, 102(6): 1017-1024. PMID: 28486791. DOI: 10.1002/cpt.733.
25 Suzuki N, Noh JY, Hiruma M, et al. Analysis of antithyroid drug-induced severe liver injury in 18,558 newly diagnosed patients with Graves' disease in Japan[J]. Thyroid, 2019, 29(10): 1390-1398. PMID: 31573408. DOI: 10.1089/thy.2019.0045.
26 徐如意, 唐红, 白浪. 新发或未控制甲状腺功能亢进症导致肝损伤的诊断与治疗[J]. 中华肝脏病杂志, 2021, 29(10): 926-931. PMID: 34814386. DOI: 10.3760/cma.j.cn501113-20210830-00439.
27 Li X, Yang J, Jin S, et al. Mechanistic examination of methimazole-induced hepatotoxicity in patients with Grave's disease: a metabolomic approach[J]. Arch Toxicol, 2020, 94(1): 231-244. PMID: 31740989. DOI: 10.1007/s00204-019-02618-z.
28 Li X, Jin S, Fan Y, et al. Association of HLA-C*03:02 with methimazole-induced liver injury in Graves' disease patients[J]. Biomed Pharmacother, 2019, 117: 109095. PMID: 31202168. DOI: 10.1016/j.biopha.2019.109095.
29 Arrigo T, Cutroneo PM, Vaccaro M, et al. Lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy[J]. Int J Immunopathol Pharmacol, 2016, 29(4): 707-711. PMID: 27272160. PMCID: PMC5806824. DOI: 10.1177/0394632016652412.
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