甲巯咪唑治疗Graves病早期诱发白细胞计数减少的影响因素研究

背景　甲巯咪唑是临床中最常使用的治疗Graves病（GD）的药物，而白细胞计数减少是用药过程中常出现的不良反应，其发生率可达10%左右，严重者可导致粒细胞缺乏，危及患者生命。而白细胞计数减少通常是粒细胞缺乏发生的前兆，因此及时发现甲巯咪唑诱发白细胞计数减少的影响因素能够提高用药安全性。目的　分析甲巯咪唑治疗GD早期诱发白细胞计数减少的影响因素，预防甲巯咪唑诱发白细胞计数减少的发生。方法　选取2015年12月-2017年12月沧州市人民医院内分泌科门诊或住院初发未经治疗的GD患者580例为研究对象。以口服甲巯咪唑治疗的前3个月作为本研究的观察期。依据白细胞计数减少诊断标准（外周血白细胞计数持续<4.0×109/L），将出现白细胞计数减少的GD患者纳入观察组（n=70），将未出现白细胞计数减少的患者纳入对照组（n=510）。比较两组治疗前一般情况及相关实验室检测数据，甲巯咪唑治疗GD早期诱发白细胞计数减少的影响因素采用多因素Logistic回归分析。结果　观察组与对照组患者性别、年龄分布、Graves眼病（GO）活动度、游离甲状腺素（FT4）升高程度、甲状腺过氧化物酶抗体（TPOAb）升高程度比较，差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，女性〔OR=2.083，95%CI（1.174，3.693）〕、年龄<20岁〔20~40岁：OR=0.057，95%CI（0.028，0.117）；>40岁：OR=0.184，95%CI（0.102，0.334）〕，GD合并非活动性GO〔OR=1.809，95%CI（1.172，2.792）〕、活动性GO〔OR=3.238，95%CI（1.723，6.085）〕，高水平FT4〔OR=3.481，95%CI（1.779，6.809）〕，中度水平TPOAb〔OR=2.620，95%CI（1.717，4.000）〕是甲巯咪唑治疗GD早期诱发白细胞计数减少的危险因素（P<0.05）。结论　女性、年龄<20岁、GD伴有GO和甲状腺内自身免疫失衡所导致的活动性炎性反应是甲巯咪唑诱发白细胞计数减少的危险因素。

Factors Associated with Methimazole-induced Leucopenia in Early-phase Treatment of Graves' Disease

Background　Metimazole is a commonly used drug in the treatment of Graves' disease （GD），and leukopenia is an adverse reaction that often occurs during medication with an incidence of about 10%.In severe cases，it can cause agranulocytosis，endangering the patient's life.Leukopenia is usually a precursor to the occurrence of agranulocytosis，so timely finding the factors associated with methimazole-induced leucopenia may improve the safety of medication.Objective　To identify the influencing factors of leukopenia induced by methimazole in early-phase treatment of GD，to prevent the occurrence of methimazole-induced leukopenia.Methods　580 newly diagnosed，untreated GD outpatients and inpatients were recruited from Endocrinology Department，Cangzhou People's Hospital from December 2015 to December 2017.During the first 3 months of oral methimazole treatment，the observation period of this study，those with and without leukopenia were included in the observation group （n=70），and control group （n=510），respectively，by the diagnostic criteria for leucopenia （peripheral leukocyte counts remained lower than 4.0×109/L）.Pre-treatment general conditions and laboratory test data were compared between the two groups.The statistically significant factors were included in the multivariate Logistic regression analysis to find out the influencing factors of leukopenia induced by methimazole.Results　There were significant differences between two groups in terms of distributions of gender，age ，clinical activity score for Graves' ophthalmopathy （GO），free thyroxine （FT4） elevation，and thyroid peroxidase antibody （TPOAb） elevation （P<0.05）.Multivariate Logistic regression analysis showed that female〔OR=2.083，95%CI（1.174，3.693）〕，age <20 years 〔20-40 years: OR=0.057，95%CI（0.028，0.117）；>40 years: OR=0.184，95%CI（0.102，0.334）〕，inactive GO 〔OR=1.809，95%CI（1.172，2.792）〕，active GO 〔OR=3.238，95%CI（1.723，6.085）〕，high-level FT4 〔OR=3.481，95%CI（1.779，6.809）〕，and moderate-level TPOAb 〔OR=2.620，95%CI（1.717，4.000）〕 were risk factors for methimazole-induced leukocytopenia in early-phase treatment of GD （P<0.05）.Conclusion　Female，age <20 years，GD with GO and active inflammatory response caused by autoimmune thyroid imbalance are risk factors for methimazole-induced leukocytopenia in early-phase treatment of GD.