甲硫咪唑与丙基硫氧嘧啶治疗甲亢的临床疗效与副作用的对比研究

目的 比较甲硫咪唑与丙基硫氧嘧啶治疗甲亢的临床疗效与副作用。方法 选取2016年10月～2018年9月本院收治的甲亢患者80例,随机分为两组,各40例,甲硫咪唑(MMI)组给予MMI药物治疗,丙基硫氧嘧啶(PTU)组给予PTU药物治疗。观察记录两组治疗前及治疗后6个月的临床症状、甲状腺功能指标、血常规、肝功能指标及其他不良反应,比较分析两组药物疗效与副作用的差异。结果 两组患者治疗后6个月,体质量明显高于治疗前(P 0.05),心率、甲亢指数积分均明显低于治疗前(P 0.05);甲状腺功能指标FT3、FT4与治疗前相比明显降低,TSH明显升高,差异均有统计学意义(P 0.05);两组治疗前或治疗后体质量、心率、甲亢指数积分与甲状腺功能指标的差异均无统计学意义(P 0.05);MMI组患者的治疗总有效率为95.0%,PTU组为90.0%,差异无统计学意义(P 0.05);两组血细胞减少和皮疹发生率与PTU组的差异无统计学意义(P 0. 05),PTU组肝功能指标异常发生率明显高于MMI组,差异有统计学意义(P 0.05)。结论 两种药物对甲亢患者甲状腺功能与临床症状的改善效果相当,而MMI肝功能受损的发生率低,相对PTU安全性更高。     

丙基硫氧嘧啶和甲巯咪唑与抗中性粒细胞胞浆抗体相关性血管炎

目的:研究抗甲状腺药物丙基硫氧嘧啶(PTU)、甲巯咪唑(MMI)与抗中性粒细胞胞浆抗体(ANCA)的关系.方法:收集甲状腺功能亢进患者199例,按用药情况分为4组:初发未治组30例、服用PTU组61例、服用MMI组65例、混合用药组43例.应用间接免疫荧光法(IIF)检测所有患者血清中的P-ANCA和C-ANCA.应用酶联免疫吸附法(ELISA)测定抗MPO抗体及抗PR3抗体.ANCA阳性患者行尿常规、肾功能、血沉、胸片、五管科检查.对于检测时正在服用PTU的AN-CA阳性患者,停用PTU,改用MMI治疗.随访每例ANCA阳性患者的临床表现并监测血清中的ANCA.结果:初发未治组30例患者的血清中无一例检测到ANCA阳性,PTU组中有8/61(13.11%)例p-ANCA阳性,其中3例识别MPO.MMI组中仅1/65(1.53%)例P-ANCA阳性,无一例识别MPO.混合组中7/43(16.28%)例P-ANCA阳性,其中4例识别MPO.PTU组和混合组ANCA阳性率高于初发未治组和MMI组(P＜0.05).16例ANCA阳性患者中7例出现血管炎临床表现.共8例ANCA阳性患者换用MMI后随访1年,6例ANCA转阴,2例仍为阳性.结论:PTU与甲亢患者出现ANCA阳性相关,并导致其中的一部分患者出现血管炎临床表现.PTU引起的ANCA阳性患者在密切监测的情况下可试换用MMI进一步治疗甲亢.     

丙硫氧嘧啶与甲巯咪唑对妊娠合并甲状腺功能亢进症患者肝功能、妊娠结局及新生儿甲状腺功能的影响

目的探讨甲巯咪唑与丙硫氧嘧啶对妊娠合并甲状腺功能亢进症(甲亢)患者肝功能、妊娠结局及新生儿甲状腺功能的影响。方法选取2014年1月~2017年1月我院收治的80例妊娠合并甲亢患者作为研究对象,以随机数字表法分为propylthiouracilum组(PTU组)和methimazole组(MMI组),每组40例。PTU组给予丙硫氧嘧啶(PTU)治疗,MMI组给予甲巯咪唑(MMI)治疗。观察两组药物性肝损伤发生情况、妊娠结局、新生儿甲状腺功能异常情况。结果基线期,两组药物性肝损伤发生率基本相同,差异无统计学意义(P0.05);治疗后,PTU组药物性肝损伤发生率显著高于MMI组,差异有统计学意义(P0.05)。两组早产的发生率和阿氏评分基本相同,差异无统计学意义(P0.05);PTU组胎儿丢失的发生率显著低于MMI组,差异有统计学意义(P0.05)。两组新生儿甲状腺功能异常发生率基本相同,差异无统计学意义(P0.05)。结论两种药物均不能兼顾到孕产妇和胎儿的现实情况。妊娠合并甲亢要科学利用抗甲状腺药物,以期改善母婴预后。     

两种不同抗甲状腺药物治疗甲亢的疗效分析

目的比较2种不同抗甲状腺药物治疗甲状腺功能亢进症的疗效,为临床用药提供参考。方法 120例初诊的甲亢患者按随机分组的原则随机分成甲巯咪唑(M M I,商品名:赛治)组和丙硫氧嘧啶(PTU)组,每组60例,随诊观察2年后比较各自的临床改善情况。结果与PTU组比较,MMI组临床症状控制时间较短[(6.9±3.7)周vs.(9.8±3.5)周,P<0.05],TSH恢复正常较快[(7.5±4.1)个月vs.(10.3±5.2)个月,P<0.05],且依从性好,治疗2年后的停药人数较多(26 vs.18,P<0.05)。两组白细胞减少、皮疹、甲状腺功能减退、胃肠道反应发生率比较差异无统计学意义(P>0.05);MMI组的ALT、AST分别为(38.2±7.9)、(37.8±6.5)U/L,且均低于PTU组[(73.6±12.5)、(69.6±10.3)U/L],差异有统计学意义(P<0.05)。结论 M M I、PTU对甲亢的治疗均有效,但MMI组临床症状控制快,TSH恢复正常快,依从性好,停药早,肝功能损害小,整体疗效较好。     

甲巯咪唑与丙硫氧嘧啶对Graves病患者细胞因子的影响

目的：探讨甲巯咪唑（ MMI）与丙硫氧嘧啶（ PTU）对Graves病（ GD）患者细胞因子的影响。方法选取2013年6月—2014年6月南京市中西医结合医院收治的GD患者63例,随机分为MMI组（31例）和PTU组（32例）。MMI组患者予以MMI治疗,PTU组患者予以PTU治疗。观察两组患者临床疗效、治疗前后细胞因子〔白介素-2（IL-2）、白介素-6（IL-6）及促甲状腺素受体抗体（TRAb）〕水平及不良反应发生情况。结果两组患者总有效率比较,差异无统计学意义（ P﹥0.05）;治疗前两组患者IL-2、IL-6、TRAb水平比较,差异无统计学意义（ P﹥0.05）,治疗6个月MMI组患者IL-2水平高于PTU组,IL-6、TRAb水平低于PTU组,差异有统计学意义（P﹤0.05）;两组患者不良反应发生率比较,差异无统计学意义（P﹥0.05）。结论 MMI与PTU治疗GD的效果相当,但MMI的免疫抑制作用强于PTU,药物t1/2长于PTU,故临床更倾向于使用MMI。     

甲巯咪唑与丙硫氧嘧啶治疗甲亢的疗效及对肝功能影响

目的 观察甲巯咪唑(MMI)与丙硫氧嘧啶(PTU)在甲状腺功能亢进症(甲亢)治疗中的效果,及其对患者肝功能的影响.方法 选取我院附属医院收治的甲亢患者126例为研究对象,按照1:1比例分为两组,各63例,MMI组患者给甲巯咪唑治疗,PIU组给予丙硫氧嘧啶治疗,疗程结束后,对两组患者的临床疗效及肝功能进行比较.结果 A、B两组患者治疗的总有效率、不良反应的发生率相比差异均不具有显著性(P>0.05).A组患者治疗的总成本为3955.31元,B组患者治疗的总成本为3876.09元,B组患者治疗的总成本低于A组患者,但二者相比差异不具有显著性(P>0.05).结论 甲巯咪唑与丙硫氧嘧啶治疗甲亢均有效,但丙硫氧嘧啶较甲巯咪唑更易发生肝功能损伤,而甲巯咪唑出现ALT升高时间早于丙硫氧嘧啶,但二者均为轻度肝功能损伤.     

抗甲状腺药物治疗甲状腺功能亢进合并病毒性肝炎患者的安全性评价

目的 研究抗甲状腺功能亢进药物对甲状腺功能亢进症(甲亢)合并病毒性肝炎患者肝脏功能的影响,以评价其安全性.方法 回顾性分析35例甲亢合并病毒性肝炎患者的临床资料.比较采用丙基硫氧嘧啶(PTU)治疗,采用甲巯咪唑(MM)治疗,未进行抗甲亢治疗三组患者的疗效.结果 加用PTU或MM治疗组疗效明显好于未治疗组(x2=10.262,P＜0.05),PTU或MM治疗对患者短期疗效差异无统计学意义(x2 =0.28,P＞0.05).结论 甲亢会加重病毒性肝炎肝功能的损害,而抗甲亢治疗对甲亢合并病毒性肝炎患者是安全的.     

长疗程使用甲巯咪唑治疗Graves病临床研究

目的了解长疗程甲巯咪唑片(MMI)治疗Graves病的疗效及不良反应.方法 选择155例Graves病甲亢患者为研究对象,全部病例均完成18个月MMI治疗后根据患者意愿分为2组,愿意接受长疗程MMI治疗者为长疗程治疗组,以维持量MMI长疗程治疗,维持甲状腺功能正常;不愿意接受MMI长疗程治疗者,完成18个月疗程后停用MMI,若甲亢复发重新治疗者为常规治疗组.所有患者均使用MMI治疗,最初剂量均为10mg,3次/d,依病情逐渐减量达维持量后,每3～6个月复诊一次,复查甲状腺功能,记录临床表现.结果 长疗程治疗组患者的甲状腺肿、突眼、甲状腺过氧化物酶抗体(TPOAb)、三酰甘油(TG)及总胆固醇(TC)、E/A及LVEF均优于常规治疗组;而且心房纤颤、永久性甲减及甲亢复发的发生率均较低,治疗中未见明显不良反应.结论 Graves病甲亢患者接受MMI长疗程治疗有利于维持甲状腺功能正常、甲状腺肿大及突眼的好转,而且其心功能异常、心房纤颤等心血管事件的发生率较低,无明显不良反应.     

益肝愈瘿汤联合丙基硫氧嘧啶治疗甲亢性肝损害的疗效分析

目的分析对甲亢性肝损害(HLD)患者采用丙基硫氧嘧啶(PTU)、益肝愈瘿汤联合治疗的临床治疗效果。方法对我院2015年4月至2016年4月收治的100例甲亢性肝损害患者进行观察,采用随机分组法分为观察组和参照组,参照组单纯采用PTU治疗,观察组采用PTU、益肝愈瘿汤联合治疗。治疗8周,观察治疗效果。结果观察组患者总有效率、肝功能和甲状腺功能改善情况明显优于参照组,差异有统计学意义(P<0.05)。结论对HLD患者采用PTU、益肝愈瘿汤联合治疗可以明显改善患者的甲状腺和肝功能,提高治疗效果,值得推广。     

硫脲类抗甲亢药物不良反应对比及与HLA-B* 38∶02∶01基因多态性相关性研究

目的 探讨HLA-B* 38∶02∶01基因多态性与硫脲类抗甲亢药物不良反应的相关性.方法 将52例甲状腺功能亢进并行HLA-B* 38∶02∶01(rs185386680)基因位点检测的患者作为研究对象,分析比较服用抗甲亢药物(Antithyroid drugs,ATD)丙硫氧嘧啶(PTU)和甲巯咪唑(MMI)后出现...     

丙基硫氧嘧啶治疗妊娠合并甲状腺功能亢进54例临床疗效观察

目的探讨丙基硫氧嘧啶治疗妊娠合并甲状腺功能亢进的疗效。方法将108例妊娠合并甲状腺功能亢进的患者平均分为丙基硫氧嘧啶（PTU）组和甲巯咪唑（MMI）组。前者采用PTU,后者采用MMI进行诊治。定期检查两组患者甲状腺功能,测定血清中促甲状腺激素（TSH）、血清游离甲状腺激素（FT4）和血清游离三碘甲腺原氨酸（FT3）的含量,根据监测结果调整药物剂量。结果治疗后,丙基硫氧嘧啶组孕妇的血清FT4和FT3含量比甲巯咪唑组低,且并发症发生率低于甲巯咪唑组,差异具有统计学意义沪〈0．05）。结论门u是目前临床上治疗妊娠期甲状腺功能亢进的首选药物,能够有效缓解甲状腺功能亢进症状,控制病情的发展,不会对孕妇和胎儿造成不良影响,值得在临床上推广应用。     

Toxicological considerations for antithyroid drugs in children

INTRODUCTION: Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA. AREAS COVERED: Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU). EXPERT OPINION: The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.     

甲巯咪唑致粒细胞缺乏合并ANCA阳性1例并文献复习

抗甲状腺药物是Graves’病的一线治疗药物,粒细胞缺乏是其少见但严重的副作用,发生机制仍不十分清楚,目前认为主要和免疫反应有关。PTU能诱导ANCA的产生及ANCA相关性血管炎的发生,部分患者合并出现粒细胞减少。虽然粒细胞减少症并未列入ANCA相关的疾病谱,近年越来越多文献报道支持ANCA参与粒细胞减少的发生。这里报道一个MMI治疗后出现ANCA阳性合并严重粒细胞减少不伴血管炎的病例,并对相关的文献进行复习。     

Effect of anti-thyroid agents, methimazole and propylthiouracil, on brain noradrenaline content.

1 Methimazole (1-methyl-2-mercaptoimidazole, MMI) and propylthiouracil (6-propyl-2-thiouracil, PTU) which are used in the therapy of hyperthyroidism were found to reduce brain noradrenaline (NA) content. Endogenous NA levels in rat brain were reduced from 1 to 6 h after intraperitoneal injection of MMI by doses in excess of 25 mg/kg and by PTU at a dose of 50 mg/kg. However, endogenous NA in the rat heart was only slightly reduced after 50 mg/kg of MMI, and was not affected by PTU (50 mg/kg). 2 Both MMI and PTU effectively inhibited the in vivo conversion of [3H]-dopamine into [3H]-noradrenaline ([3H]-NA) in the brain of rats after a single intraperitoneal injection of doses above 10 mg/kg (MMI) and 25 mg/kg (PTU). This inhibition by MMI and PTU was dose-dependent over the range of 10 mg/kg to 50 mg/kg, was highest after 2-3 h and continued for at least 6 h after their injection; The conversion rates returned to normal after 24 hours. 3 The results suggest that the reduction of brain NA by these drugs is, at least in part, due to the inhibition of brain dopamine beta-hydroxylase.     

29例丙硫氧嘧啶引起抗中性粒细胞胞浆抗体阳性患者的临床特征及治疗分析

目的:分析我院29例由丙硫氧嘧啶(PTU)引起的抗中性粒细胞胞浆抗体(ANCA)阳性患者的临床特点,观察甲巯咪唑(MMI)替代治疗出现ANCA相关性小血管炎(AASV)患者的改善情况。方法:29例的临床资料,采用一般临床检查和实验室检查,对其临床表现、治疗和预后进行回顾性分析。结果:ANCA阳性而无临床症状16例(55.2%),出现AASV的患者13例(44.8%),其中环核型ANCA(pANCA)阳性患者肾受累的发生率(50.0%)高于胞浆型ANCA(cANCA)阳性患者(40.0%);采用MMI替代治疗1年后ANCA转阴率66.7%。结论:由PTU引起的AASV,采用MMI替代治疗后,病情得到改善。     

A comparison of potency differences among thyroid peroxidase (TPO) inhibitors to induce developmental toxicity and other thyroid gland-linked toxicities in humans and rats

The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol’s potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity.     

Effects of developmental hypothyroidism induced by maternal administration of methimazole or propylthiouracil on the immune system of rats

Methimazole (MMI) and propylthiouracil (PTU) are popularly used antithyroid drugs (ATDs) for the treatment of Graves' hyperthyroidism. The aim of the present study was to determine the effects of ATDs on the developing immune system of the rats. Maternal Sprague-Dawley rats were given drinking water containing 200 ppm of MMI, 12 ppm of PTU (high-dose PTU), or 3 ppm of PTU (low-dose PTU) between gestational day (GD) 10 and postnatal week (PNW) 3. Exposure to the ATDs was ceased upon weaning at PNW3, and the male offspring were sampled at PNWs 3 or 11. The serum thyroid-related hormone levels and the hematological components in the offspring were then determined. The expressions of surface markers in the spleen, thymus and peripheral blood were determined using flowcytometry. The weights of the body, spleen and thymus and the splenic and thymic cell numbers were decreased in the MMI-treated and the high-dose PTU-treated animals at PNWs 3 and 11. The serum levels of thyroid-related hormones were depressed in the MMI and high-dose PTU groups. FACS analysis revealed that the ATDs caused proportional changes in the lymphoid cell subpopulations. The proportion of B cells among the total lymphocytes was significantly decreased at PNW3, whereas that of T cells, especially of inactive T cells, was dramatically increased. Moreover, the proportion of CD4(+)CD25(+) regulatory T cells was significantly increased in the spleen and peripheral blood at PNW3. Most of the above-described changes had recovered to normal levels at PNW11. These results suggest that ATDs might have temporal immunomodulatory effects on the developing immune system.     

妊娠期和哺乳期妇女抗甲状腺药物的安全性评价

目的 考察抗甲状腺药物甲巯咪唑（methimazole,MMI）和丙硫氧嘧啶（propylthiouracil,PTU）在妊娠期、哺乳期使用的安全性。方法 查阅文献,以近几年国内外代表性的大型研究、指南为依据,进行分析、整理和归纳。结果 早孕期暴露于抗甲状腺药物出生缺陷发生率增高,随访到2岁的大型研究显示,PTU暴露的儿童缺陷发生率8.0%,主要在面部和颈部有畸形。MMI/卡比马唑（carbimazole,CMZ）暴露的儿童缺陷发生率9.1%,常见鼻后孔闭锁、食管闭锁、脐疝、脐肠系膜管异常和发育不全。母亲孕早期MMI/CMZ向PTU转换的儿童缺陷发生率10.1%,主要与泌尿系统畸形相关。未暴露儿童缺陷发生率5.7%。致畸的高风险阶段在妊娠6~10周。哺乳期妇女服用中等剂量的PTU（<300 mg·d^-1）或MMI（20~30 mg·d^-1）都是安全的。结论 MMI和PTU与出生缺陷相关,但畸形谱不同。为减少婴儿的药物暴露量,抗甲状腺药物应分次在母乳喂养后服用。     

Propylthiouracil,and methimazole,and carbimazole-related hepatotoxicity

Introduction: Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.

Areas covered: This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.

Expert opinion: PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.     

甲巯咪唑治疗妊娠合并甲状腺功能亢进孕妇时对新生儿甲状腺功能影响

目的探讨甲巯咪唑（MMI）治疗妊娠合并甲状腺功能亢进患者时,药物剂量对新生儿甲状腺功能的影响。方法对30例妊娠合并甲状腺功能亢进接受不同剂量MMI治疗的孕妇（治疗组）,分娩时测定新生儿脐血的TT3、TT4、FT3,FT4及TSH值,并以同期30例正常孕妇的新生儿脐带血作为对照组,进行比较分析。结果治疗组的新生儿TT3、TT、FT3、FT4及TSH与正常对照组相比,差异均无统计学意义（P〉0．05）。MMI剂量在每天5～15mg内与脐血TT3、TT、FT3,FT4水平无关,与TSH水平呈正相关。结论适量的MMI治疗妊娠合并甲状腺功能亢进是相对安全的,可改善母婴的妊娠结局,预防新生儿甲状腺功能亢进而不会造成新生儿甲状腺功能减退。