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而停用Pto及PAS,其余74例患者均达到治疗效果。结论MDR-TB患者采用含Pto联合PAS方案较单含Pto方案治疗更易出现甲减症,抗结核药物治疗前3个月甲减症发生率高,需密切监测甲状腺功能。采用优甲乐治疗的药物性甲减症患者,如果在不同剂量治疗后效果较好而不必停用Pto及PAS。
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%(11/18),χ^2=5.227,P=0.022).The dosage of Levothyroxine Sodium Tablets were≤50 μg/d for 49 patients(62.82%),51-75 μg/d for 20 patients(25.64%),>75 μg/d for 9 patients(11.54%).Four patients in Pto+PAS group were treated with the dosage of over 125 μg/d,but the effect was little, therefore, the Pto and PAS were discontinued;however,the other 74 patients had better prognosis.Conclusion Hypothyroidism are more likely to occur in MDR-TB patients treated with Pto+PAS than those treated with Pto alone.The incidence of hypothyroidism is high within 3 months after anti-tuberculosis treatment,and thyroid function needs to be closely monitored.If patients with drug-induced hypothyroidism have better prognosis when treated with Levothyroxine Sodium at different dosages,the Pto and PAS could be continued.
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)
出处
《中国防痨杂志》
CAS
CSCD
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)。
