含丙硫异烟胺和对氨基水杨酸方案治疗耐多药结核病患者致甲状腺功能减退症的临床分析  

Clinical analysis of hypothyroidism after anti-tuberculosis treatment in patients with multidrug-resistant tuberculosis

作　　者：赵本南 刘大凤 刘亚玲 杨铭 兰丽娟 杜清 ZHAO Ben-nan;LIU Da-feng;LIU Ya-ling;YANG Ming;LAN Li-juan;DU Qing(Department of General Internal Medicine,the Public and Health Clinic Centre of Chengdu,Chengdu 610061,China)

机构地区：[1]成都市公共卫生临床医疗中心综合内科,610061 [2]成都市公共卫生临床医疗中心结核科,610061 [3]成都市公共卫生临床医疗中心重症医学科,610061

出　　处：《中国防痨杂志》2020年第5期465-471,共7页Chinese Journal of Antituberculosis

基　　金：四川省卫生和计划生育委员会科研课题普及应用项目(17P J070);成都市卫生健康委员会医学科研课题项目(2019079);成都市卫生局科研课题项目(2014043);成都市卫生健康委员会重点学科建设项目(2019-2)。

摘　　要：目的分析含丙硫异烟胺(protionamide,Pto)和(或)对氨基水杨酸(para-aminosalicylic acid,PAS)方案治疗耐多药结核病(multidrug resistant tuberculosis,MDR-TB)致甲状腺功能减退症(简称"甲减症")的发生情况及治疗效果。方法收集2017年10月1日至2019年6月30日成都市公共卫生临床医疗中心结核科入院及门诊就诊的MDR-TB患者,符合纳入排除标准且使用含Pto和(或)PAS抗结核方案治疗者336例。依据抗结核药物使用情况分为两组,其中仅含Pto治疗方案的患者91例(简称"Pto组"),含Pto和PAS治疗方案的患者245例(简称"Pto+PAS组")。所有患者均在抗结核药物治疗前及第1、3、6、9、12、18、24个月分别进行甲状腺功能检查,分析甲状腺功能减退症的发生率、出现时机,以及采用优甲乐治疗的时机、治疗率及治疗剂量、疗效情况。结果 336例MDR-TB患者中,药物性甲减症的发生率为28.87%(97/336),其中4例出现黏液性水肿、2例出现乏力伴脱发经检查甲状腺功能后确诊,其余91例患者均无明显自觉症状,均在复诊检测甲状腺功能时发现。Pto+PAS组甲减症的发生率[32.24%(79/245)]明显高于Pto组[19.78%(18/91)](χ^2=5.020,P=0.025),男性甲减症的发生率[24.07%(52/216)]明显低于女性[37.50%(45/120)](χ^2=6.772,P=0.009)。发生药物性甲减症的比率随治疗时间的延长而下降,用药后1.5个月内、3个月内、3~6个月内、6个月后的占比分别为40.20%(39/97)、24.74%(24/97)、17.53%(17/97)、17.53%(17/97);Pto+PAS组在1.5个月内甲减症的发生率[46.83%(37/79)]明显高于Pto组[11.11%(2/18)](Fisher确切概率法,P=0.018)。78例甲减症患者需要采用优甲乐治疗,Pto+PAS组需要采用优甲乐治疗的比率[84.81%(67./79)]明显高于Pto组[61.11%(11/18)](χ^2=5.227,P=0.022)。优甲乐最终使用剂量分别为49例(62.82%)≤50μg/d、20例(25.64%)51~75μg/d、9例(11.54%)>75μg/d;其中4例Pto+PAS组患者使用优甲乐剂量超过125μg/d后甲减症仍控制不佳�Objective To analyze the occurrence and characteristics of hypothyroidism in patients with multidrug-resistant tuberculosis(MDR-TB) after anti-tuberculosis treatment with prothionamide(Pto) and/or paraaminosalicylic acid(PAS).Methods According to the selection criteria,336 MDR-TB patients both from outpatient and hospitalized in Department of Tuberculosis,the Public and Health Clinic Centre of Chengdu between October 1,2017 and June 30,2019 were selected.They were divided into Pto group(n=91,treated only with Pto)and Pto+PAS group(n=245,treated with Pto and PAS).Their thyroid function were tested before antituberculosis treatment and 1,3, 6, 9,12,18,24 months after anti-tuberculosis treatment.The occurrence rate and time of hypothyroidism,and when treat with Levothyroxine Sodium Tablets, the rate of treantment,treatment effect and the dosage were compared.Results Of the 336 MDR-TB patients, incidence of drug-induced hypothyroidism was 28.87%(97/336);among the 97 patients,myxedema was found in 4,fatigue with hair loss was found in 2,and the other 91 were without any obvious symptoms.The occurrence rate of hypothyroidism was19.78%(18/91) in Pto group,which was statistically different from that in Pto+PAS group(32.24%(79/245),χ^2=5.020,P=0.025).Hypothyroidism incidence in male group was significantly lower than that in female group(24.07%(52/216) vs.37.50%(45/120),χ^2=6.772,P=0.009).Occurrence rate of drug-induced hypothyroidism decreased with the treatment duration,rates were 40.20%(39/97),24.74%(24/97),17.53%(17/97) and 17.53%(17/97),respectively,1.5 months,3 months,3-6 months,and 6 months after treatment.Occurrence rate of drug-induced hypothyroidism in Pto+PAS group within 1.5 months after treatment was significantly higher than that in Pto group(46.83%(37/79) vs.11.11%(2/18),Fisher,P=0.018).A total of78 drug-induced hypothyroidism patients needed to be treat with Levothyroxine Sodium Tablets,and the number of cases from Pto+PAS group was significantly more than that from Pto group(84.81%(67/79) vs.61.11%(11/1

关 键 词：结核 抗多种药物性 药物疗法 联合 丙硫异烟胺 对氨水杨酸 甲状腺功能减退症 临床方案 对比研究 

分 类 号：R52[医药卫生—内科学]