甲巯咪唑治疗甲亢致严重粒细胞缺乏的临床特征和骨髓形态分析  

Clinical features and bone marrow morphology of methimazole-induced severe agranulocytosis in patients with hyperthyroidism

作　　者：应双伟 郑瑞[1] 胡超 王直滔 邵燕萍[1] Ying Shuangwei;Zheng Rui;Hu Chao;Wang Zhitao;Shao Yanping(Taizhou Hospital of Zhejiang Province,Linhai 317000,China)

机构地区：[1]浙江省台州医院,浙江临海317000

出　　处：《实用药物与临床》2025年第4期283-287,共5页Practical Pharmacy and Clinical Remedies

摘　　要：目的探讨甲巯咪唑(Methimazole,MMI)治疗甲状腺功能亢进导致严重粒细胞缺乏(中性粒细胞<0.1×10^(9)/L)患者的临床特征、治疗和预后。方法回顾2011年8月至2022年8月入住浙江省台州医院血液科病房诊断为MMI致严重粒细胞缺乏的甲亢患者,并对其临床特征和治疗转归进行分析。结果共收集到24例MMI致严重粒细胞缺乏甲亢患者,男女比例为1∶5,中位年龄41.5(34.3,49.0)岁,8例有过敏史。最常见的首发症状为发热(100%)和咽痛(70.8%)。16.7%(4/24)、20.8%(5/24)和58.3%(14/24)的患者在发生严重粒细胞缺乏时的MMI服用剂量分别为10、15、20 mg/d。29.2%(7/24)、37.5%(9/24)和29.2%(7/24)的患者分别于应用MMI治疗第1个月、第2个月和第3个月发生严重粒细胞缺乏。6例在严重粒细胞缺乏前2周内监测过粒细胞水平,其中50%(3/6)的患者存在粒细胞轻微减少,50%(3/6)的患者粒细胞计数正常,33.3%(2/6)的患者在严重粒细胞缺乏发生前1周内的粒细胞计数正常。10例(41.7%)患者在严重粒细胞缺乏期间行骨髓检查,60%(6/10)为Ⅰ型(主要特征是粒细胞前体的缺失或减少),40%(4/10)为Ⅱ型(主要特征是粒细胞增生良好伴成熟障碍)。24例患者脱离粒细胞缺乏(中性粒细胞>0.5×10^(9)/L)中位时间为5.5(4.0,7.0)d,而在10例骨髓检查患者中,6例Ⅰ型和4例Ⅱ型患者脱离粒细胞缺乏中位时间分别为8.5(6.8,10.3)d和5.5(3.5,7.5)d(P=0.056)。91.7%(22/24)的患者体温恢复正常和粒细胞恢复的时间间隔均不超过1 d。结论MMI诱导的严重粒细胞缺乏往往发生在服药后3个月内,既往有过敏史的患者可能存在易感性。1~2周内粒细胞水平并不能准确预测粒细胞缺乏发生风险,其发生存在突发性。不同的骨髓特征对治疗反应存在一定差异。Objective To investigate the clinical characteristics,treatment and prognosis of hyperthyroid patients with severe agranulocytosis(neutrophils<0.1×10^(9)/L)caused by methimazole(MMI).Methods Hyperthyrodism patients with MMI-induced severe agranulocytosis who were admitted to the Hematology Ward of Taizhou Hospital of Zhejiang Province from August 2011 to August 2022 were enrolled,and their clinical characteristics and treatment outcomes were analyzed.Results The male to female ratio of totally 24 hyperthyroidism patients with MMIinduced severe agranulocytosis was 1∶5,the median age was 41.5(34.3,49.0)years old.Eight patients had a history of allergies.Fever(100%)and sore throat(70.8%)were the most common symptoms.About 16.7%(4/24),20.8%(5/24)and 58.3%(14/24)of patients experienced severe agranulocytosis at 10 mg/d,15 mg/d,and 20 mg/d of MMI,respectively.Severe agranulocytosis occurred in 29.2%(7/24),37.5%(9/24),and 29.2%(7/24)patients within the first,second and third month after initiation of MMI therapy,respectively.Six patients had granulocyte measurement within 2 weeks before diagnosis of severe agranulocytosis,of whom 3(50%)developed mild granulocytopenia and 3(50%)had normal granulocyte counts;2(33.3%)had normal granulocyte counts within 1 week.Ten(41.7%)patients received a bone marrow examination during severe agranulocytosis and 6 cases(60%,6/10)were type I(absence or reduction of granulocytic precursors being the main characteristics),whereas 4 cases(40%,4/10)were type Ⅱ(the main features being good granulocytosis with dysmaturity of granulocytic cells).The median time of recovery of agranulocytosis(neutrophils>0.5×10^(9)/L)in 24 patients was 5.5(4.0,7.0)d,while in the 10 patients with bone marrow examination,the median time of recovery of agranulocytosis in 6 cases of typeⅠwas 8.5(6.8,10.3)d and in 4 cases of type Ⅱ was 5.5(3.5,7.5)d(P=0.056).The time interval between the recovery of temperature and recovery of granulocyte counts was no more than one day in 91.7%(22/24)patients.Conclusion Seve

关 键 词：甲巯咪唑 粒细胞缺乏症 甲状腺功能亢进症 骨髓形态 

分 类 号：R581.1[医药卫生—内分泌]