Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil
Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences...
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The Japan Endocrine Society
2024-07-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0135/_html/-char/en |
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| author | Jaeduk Yoshimura Noh Kosuke Inoue Nami Suzuki Ai Yoshihara Miho Fukushita Masako Matsumoto Hideyuki Imai Shigenori Hiruma Masahiro Ichikawa Masakazu Koshibu Akiko Sankoda Rei Hirose Natsuko Watanabe Kiminori Sugino Koichi Ito |
| author_facet | Jaeduk Yoshimura Noh Kosuke Inoue Nami Suzuki Ai Yoshihara Miho Fukushita Masako Matsumoto Hideyuki Imai Shigenori Hiruma Masahiro Ichikawa Masakazu Koshibu Akiko Sankoda Rei Hirose Natsuko Watanabe Kiminori Sugino Koichi Ito |
| author_sort | Jaeduk Yoshimura Noh |
| collection | DOAJ |
| description | Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves’ disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does. |
| format | Article |
| id | doaj-art-2c9df66a660949b9b940fac9ff8396e4 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-2c9df66a660949b9b940fac9ff8396e42025-01-22T05:12:18ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-07-0171769570310.1507/endocrj.EJ24-0135endocrjDose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracilJaeduk Yoshimura Noh0Kosuke Inoue1Nami Suzuki2Ai Yoshihara3Miho Fukushita4Masako Matsumoto5Hideyuki Imai6Shigenori Hiruma7Masahiro Ichikawa8Masakazu Koshibu9Akiko Sankoda10Rei Hirose11Natsuko Watanabe12Kiminori Sugino13Koichi Ito14Department of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Social Epidemiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8315, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Internal Medicine, Ito Hospital, Tokyo 150-8308, JapanDepartment of Surgery, Ito Hospital, Tokyo 150-8308, JapanDepartment of Surgery, Ito Hospital, Tokyo 150-8308, JapanAgranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves’ disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0135/_html/-char/enagranulocytosismethimazolepropylthiouracildose dependency |
| spellingShingle | Jaeduk Yoshimura Noh Kosuke Inoue Nami Suzuki Ai Yoshihara Miho Fukushita Masako Matsumoto Hideyuki Imai Shigenori Hiruma Masahiro Ichikawa Masakazu Koshibu Akiko Sankoda Rei Hirose Natsuko Watanabe Kiminori Sugino Koichi Ito Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil Endocrine Journal agranulocytosis methimazole propylthiouracil dose dependency |
| title | Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| title_full | Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| title_fullStr | Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| title_full_unstemmed | Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| title_short | Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| title_sort | dose dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil |
| topic | agranulocytosis methimazole propylthiouracil dose dependency |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0135/_html/-char/en |
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