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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pisciotta AV. Immune and toxic mechanisms in drug-induced agranulocytosis[J]. Semin Hematol, 1973, 10(4): 279-310. PMID: 4139755.
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.
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.
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.
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.
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.
