Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with Graves’ disease
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment.Methods: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4–0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28).Results: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively).Conclusion: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.
Abstract
Purpose: The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment.Methods: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4–0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28).Results: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively).Conclusion: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.
참고문헌 (29)
- Metso S, "Graves’ disease", N Engl J Med, 359, pp.1408~1409 (2008)
- Weetman AP, "Graves’ disease", N Engl J Med, 343, pp.1236~1248 (2000)
- Rivkees SA, "The treatment of Graves’ disease in children", J Pediatr Endocrinol Metab, 19, pp.1095~1112 (2006)
- Cooper DS, "Antithyroid drugs", N Engl J Med, 352, pp.905~917 (2005)
- Rivkees SA, "Propylthiouracil hepatoxicity in children and recommendations for discontinuation of use", Int J Pediatr Endocrinol, 2009, pp.132041~ (2009)
- Rivkees SA, "Ending propylthiouracil-induced liver failure in children", N Engl J Med, 360, pp.1574~1575 (2009)
- Karras S, "Pathogenesis of propylthiouracil-related hepatotoxicity in children : present concepts", J Pediatr Endocrinol Metab, 25, pp.623~630 (2012)
- Bahn RS, "Hyperthyroidism and other causes of thyrotoxicosis : management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists", Thyroid, 21, pp.593~646 (2011)
- He CT, "Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves’ hyperthyroidism", Clin Endocrinol(Oxf), 60, pp.676~681 (2004)
- Corvilain B, "Treatment of adult Graves’disease", Ann Endocrinol, 79, pp.618~635 (2018)
- Nakamura H, "Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease", J Clin Endocrinol Metab, 92, pp.2157~2162 (2007)
- 이해상, "The treatment of Graves’ disease in children and adolescents", Annals of Pediatric Endocrinology & Metabolism, 19(3), pp.122~126 (2014), 대한소아내분비학회
- Dötsch J, "Graves' disease in childhood : a review of the options for diagnosis and treatment", Paediatr Drugs, 5, pp.95~102 (2003)
- Minamitani K, "Guidelines for the treatment of childhood-onset Graves’disease in Japan, 2016", Clin Pediatr Endocrinol, 26, pp.29~62 (2017)
- Yu W, "Side effects of propylthiouracil and methimazole in the treatment of hyperthyroidism : a systematic review and meta-analysis", Endocr Pract, 26, pp.207~217 (2020)
- 김희경, "Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea", Endocrinology and Metabolism, 30(4), pp.475~480 (2015), 대한내분비학회
- Sato H, "Higher dose of methimazole causes frequent adverse effects in the management of Graves’disease in children and adolescents", J Pediatr Endocrinol Metab, 25, pp.863~867 (2012)
- Kaguelidou F, "Graves' disease in childhood : advances in management with antithyroid drug therapy", Horm Res Paediatr, 71, pp.310~317 (2009)
- Ruiz JK, "Fulminant hepatic failure associated with propylthiouracil", Ann Pharmacother, 37, pp.224~228 (2003)
- Woeber KA, "Methimazole-induced hepatotoxicity", Endocr Pract, 8, pp.222~224 (2002)
- Muldoon BT, "Management of Graves’disease : an overview and comparison of clinical practice guidelines with actual practice trends", Endocrinol Metab Clin North Am, 43, pp.495~516 (2014)
- Abraham P, "Antithyroid drug regimen for treating Graves'hyper thyroidism", Cochrane Database Syst Rev, 2010, pp.CD003420~ (2010)
- Matsushita R, "Initial treatment of pediatric Graves’disease with methimazole : a retrospective follow-up study", Clin Pediatr Endocrinol, 19, pp.101~108 (2010)
- Cooper DS, "Hyperthyroidism", Lancet, 362, pp.459~468 (2003)
- Shiroozu A, "Treatment of hyperthyroidism with a small single daily dose of methimazole", J Clin Endocrinol Metab, 63, pp.125~128 (1986)
- Slyper AH, "Effective methimazole dose for childhood Graves’ disease and use of free triiodothyronine combined with concurrent thyroidstimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery", J Pediatr Endocrinol Metab, 18, pp.597~602 (2005)
- Takata K, "Methimazole-induced agranulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30mg daily than with 15 mg daily", Thyroid, 19, pp.559~563 (2009)
- Ohye H, "Antithyroid drug treatment for Graves’disease in children : a long-term retrospective study at a single institution", Thyroid, 24, pp.200~207 (2014)
- Yasuda K, "Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves’disease", Clin Pediatr Endocrinol, 26, pp.1~7 (2017)
