胺碘酮相关性甲亢导致抗甲状腺药物粒细胞缺乏症风险增加：一项基于人群的队列研究。

Increased Risk of Antithyroid Drug Agranulocytosis Associated with Amiodarone-Induced Thyrotoxicosis: A Population-Based Cohort Study.

机构信息

1 Departments of Endocrinology and Diabetes, Lady Davis Carmel Medical Center and Linn Medical Center, Haifa, Israel.

2 Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

出版信息

Thyroid. 2019 Feb;29(2):193-201. doi: 10.1089/thy.2018.0274.

DOI:10.1089/thy.2018.0274

PMID:30648930

Abstract

BACKGROUND

Agranulocytosis occurs in 0.2-0.5% of patients treated with the antithyroid drugs (ATDs) methimazole and propylthiouracil. The objectives of this study were to evaluate the risk of ATD-related agranulocytosis in patients with amiodarone-induced thyrotoxicosis (AIT), and to compare it with the agranulocytosis risk in patients with thyrotoxicosis due to other etiologies treated with ATDs.

METHODS

This was a retrospective cohort study. Participants were 14,781 adult patients with thyrotoxicosis, newly treated with an ATD between January 1, 2002, and December 31, 2015. Among them were 593 patients treated by ATDs due to AIT. The main outcome measures were incidence rates and crude and adjusted hazard ratios using univariate and multivariable Cox regression models for ATD-related agranulocytosis within one year of treatment initiation, in association with AIT.

RESULTS

Agranulocytosis occurred in 28 (0.19%) of patients newly treated with methimazole or propylthiouracil during the first year of follow-up. Of these 28 patients, 8/593 (1.35%) were AIT patients and 20/14,188 (0.14%) were thyrotoxic patients that was not AIT related (p < 0.001). Incidence rates were 22 (9.47-43.36) cases/1000 person-years of follow-up in AIT, and 1.79 (1.09-2.76)/1000 person-years of follow-up in non-AIT thyrotoxicosis (p < 0.0001). In univariate Cox regression analysis, risk for ATD agranulocytosis associated with AIT was 9.71 (4.28-22.05) compared to the risk in non-AIT thyrotoxicosis. In a multivariable model, adjusting for age, sex, body mass index, smoking history, year of cohort entry, diabetes mellitus, hypertension, renal failure, beta blockers, calcium channel blockers, anti-aggregants, and dose of ATDs, the risk associated with AIT was 5.70 (2.14-15.21). In a model adjusted for a propensity score to receive amiodarone, risk for ATD agranulocytosis associated with AIT was 6.32 (1.22-32.70).

CONCLUSIONS

ATD use is associated with a higher risk for agranulocytosis in patients with AIT.

摘要

背景

在接受抗甲状腺药物（ATD）甲巯咪唑和丙基硫氧嘧啶治疗的患者中，约有 0.2-0.5%会发生粒细胞缺乏症。本研究的目的是评估胺碘酮诱导性甲状腺毒症（AIT）患者使用 ATD 相关粒细胞缺乏症的风险，并与其他病因导致的甲状腺毒症患者使用 ATD 治疗的粒细胞缺乏症风险进行比较。

方法

这是一项回顾性队列研究。参与者为 2002 年 1 月 1 日至 2015 年 12 月 31 日期间新接受 ATD 治疗的 14781 例成人甲状腺毒症患者，其中 593 例因 AIT 而接受 ATD 治疗。主要结局指标为在治疗开始后 1 年内与 AIT 相关的 ATD 相关粒细胞缺乏症的发生率，以及使用单变量和多变量 Cox 回归模型计算的发生率、粗风险比和调整风险比。

结果

在随访的第一年中，28 例（0.19%）新接受甲巯咪唑或丙基硫氧嘧啶治疗的患者发生了粒细胞缺乏症。这 28 例患者中，8/593（1.35%）为 AIT 患者，20/14188（0.14%）为非 AIT 甲状腺毒症患者（p<0.001）。AIT 患者的发生率为 22（9.47-43.36）例/1000 人年，而非 AIT 甲状腺毒症患者的发生率为 1.79（1.09-2.76）例/1000 人年（p<0.0001）。在单变量 Cox 回归分析中，与非 AIT 甲状腺毒症相比，AIT 与 ATD 粒细胞缺乏症相关的风险为 9.71（4.28-22.05）。在多变量模型中，调整年龄、性别、体重指数、吸烟史、队列进入年份、糖尿病、高血压、肾衰竭、β受体阻滞剂、钙通道阻滞剂、抗血小板药物和 ATD 剂量后，与 AIT 相关的风险为 5.70（2.14-15.21）。在调整胺碘酮使用倾向评分的模型中，与 AIT 相关的 ATD 粒细胞缺乏症的风险为 6.32（1.22-32.70）。