黄芪平甲方联合他巴唑治疗老年性甲状腺功能亢进症42例

目的：观察黄芪平甲方联合他巴唑治疗老年性甲状腺功能亢进症的疗效。方法：分析72例老年性甲状腺功能亢进症和30例中青年性甲状腺功能亢进症患者各自临床特点;并将72例老年甲亢患者随机分为2组,治疗组42例,在对照组基础上加用黄芪平甲方治疗,对照组30例,单用西药治疗。结果：治疗后两组甲状腺激素水平相比无显著性差异（P〉0.05）,治疗组较对照组可减少药物不良反应,缩短疗程,降低复发率。结论：黄芪平甲方联合他巴唑治疗老年性甲状腺功能亢进症效果满意。     

复方甲巯咪唑软膏中甲巯咪唑及氢化可的松体外透皮释药研究

 目的：测定不同基质、不同主药浓度、不同渗透促进剂的各种软膏中他巴唑及氢化可的松的体外透皮释药率，评价各因素对主药经皮渗透的影响。方法：用改良Franz垂直扩散池，HPLC测定。结果：A型、B型基质软膏中，他巴唑的透皮释药率分别为49.10%，29.83%(P＜0.05);氢化可的松的透皮释药率分别为3.17%,1.59%(P＜0.05)。有或无月桂氮酮的软膏中，他巴唑的透皮释药率分别为49.10%,54.14%(P＞0.05),氢化可的松的透皮释药率分别为3.17%,1.61%(P＜0.05)。结论：o/w型基质较w/o型基质更有利于他巴唑及氢化可的松的经皮渗透。月桂氮酮对他巴唑无明显的促进渗透作用，但可提高氢化可的松的经皮渗透率1.92倍。     

Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole‐induced liver injury

Methimazole (MMI) has been used in the therapy of Grave's disease (GD) since 1954, and drug‐induced liver injury (DILI) is one of the most deleterious side effects. Genetic polymorphisms of drug‐metabolizing enzymes and drug transporters have been associated with drug‐induced hepatotoxicity in many cases. The aim of this study was to investigate genetic susceptibility of the drug‐metabolizing enzymes and drug transporters to the MMI‐DILI. A total of 44 GD patients with MMI‐DILI and 118 GD patients without MMI‐DILI development were included in the study. Thirty‐three single nucleotide polymorphisms (SNPs) in twenty candidate genes were genotyped. We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI‐DILI; however, no significant difference existed after Bonferroni correction. Haplotype analysis showed that the frequency of SLCO1B1*1a (388A521T) was significantly higher in MMI‐DILI cases than that in the control group (OR = 2.21, 95% CI = 1.11‐4.39, P = 0.023), while the frequency of SLCO1B1*1b (388G521T) was significantly higher in the control group (OR = 0.52, 95% CI = 0.29‐0.93, P = 0.028). These results suggested that genetic polymorphisms of SLCO1B1 were associated with susceptibility to MMI‐DILI. The genetic polymorphism of SLCO1B1 may be important predisposing factors for MMI‐induced hepatotoxicity.     

甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的临床对照研究

目的探讨甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的疗效。方法选取80例甲状腺功能亢进患者,随机分为两组,甲组（41例）口服甲巯咪唑,乙组（39例）口服丙硫氧嘧啶片。观察并记录两组患者治疗前后甲状腺功能指标,肝功能指标,肝功能受损情况及治疗期间不良反应情况,评价甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能的影响。结果治疗前,两组患者由于甲状腺功能亢进,三碘甲腺原氨酸（FT₃）、四碘甲腺原氨酸（FT₄）均处于高水平状态,且差异无统计学意义。促甲状腺激素（TSH）分泌受到抑制,处于较低水平。治疗后,患者甲状腺功能亢进症状有所改善,患者FT₃、FT₄较治疗前降低,TSH较治疗前升高（P<0.05）,但组间比较差异无统计学意义。治疗前,两组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）水平相比,差异无统计学意义。治疗后乙组ALT、AST、GGT水平均有所升高,并明显高于甲组（P<0.05）,其中,以ALT变化最为明显;甲组治疗前后无明显变化。治疗期间,甲组患者出血5例肝损伤,乙组14例肝损伤,乙组患者肝损伤比例明显高于甲组（P<0.05）,乙组患者肝脏损伤发生时间明显晚于甲组（P<0.05）。治疗期间,两组不良反应发生率无统计学差异。结论甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进的疗效相当。与丙硫氧嘧啶相比,甲巯咪唑对肝脏损伤程度较小,但服药后较早引起肝脏损伤,建议在甲状腺功能亢进治疗期间,应定期复查患者肝功能。     

24例甲巯咪唑致胆汁淤积性肝损伤文献分析

目的 分析甲巯咪唑致胆汁淤积性肝损伤发生特点与规律,为防治及临床安全用药提供参考。方法 检索国内外文献数据库中有关甲巯咪唑致胆汁淤积性肝损伤（黄疸）的个案报道,并进行计量学分析。结果 获8篇个案报道,共计24例患者,其中男性1例,女性23例;年龄48~58岁共8例,均为女性,占33.33%;其次为37~47岁共7例,均为女性,占29.17%。合并用药与甲巯咪唑单次给药相比,致胆汁淤积性肝损伤发生率未见差异（25.00% vs 25.00%,P>0.05）;诱导期以21~35 d为主,占比58.33%,其次为7~21 d,占比37.50%。药物与不良事件因果关系诺氏（Naranjo''s）评分肯定4例（16.67%）,很可能20例（83.33%）。结论 中年女性甲亢患者为甲巯咪唑致胆汁淤积性肝损伤的高危人群,宜对其进行中短期用药监护,权衡利弊,尽量避免和减少药源性胆汁淤积性肝损伤发生。     

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol ®) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypo-thyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF. © 1992 Wiley-Liss, Inc.     

甲巯咪唑在酞菁钴修饰碳糊电极上的示差脉冲伏安法测定

目的:研究甲巯咪唑在酞菁钴(CoPc)修饰碳糊电极上的电化学行为并测定其含量。方法:循环伏安(CV)法和示差脉冲伏安(DPV)法。结果:在 pH=7.0、修饰电极中 CoPc 含量为6.25%(w/w)、富集电位-0.3 V(vs SCE)、富集时间40 s 的条件下,甲巯咪唑的氧化峰电流(i_p)与其浓度在2.0×10~(-6)～7.0×10~(-4)mol·L~(-1)范围内呈良好的线性关系,检出限为0.3 μmol·L~(-1)。结论:该方法应用到实际样品含量测定,其结果令人满意。     

Massive plasmocytosis due to methimazole-induced bone marrow toxicity.

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.     

他巴唑体外抑制酪氨酸碘化的机制

目的　探讨抗甲状腺药物的作用机制。方法　①在甲状腺过氧化物酶（ＴＰＯ）中加入他巴唑、碘化钾、过氧化氢,然后进行透析,用３,３,５,５, 四甲基联苯胺（ＴＭＢ）测ＴＰＯ的活性;②在ＴＰＯ催化酪氨酸碘化的反应体系中,加入他巴唑,并逐渐增加过氧化脲的浓度,观察过氧化脲浓度对他巴唑干扰酪氨酸碘化的影响。结果　ＴＰＯ中加入他巴唑,与加入磷酸盐缓冲液（ＰＢ）对照,经透析后,两者酶活性没有明显的区别。在ＴＰＯ催化的酪氨酸碘化的反应体系中,提高过氧化脲的浓度,能抵消他巴唑对酪氨酸碘化的抑制作用。结论　他巴唑对ＴＰＯ无直接抑制作用,其作用机制是夺去酪氨酸碘化所必需的活性氧（他巴唑本身被氧化）从而抑制甲状腺素的合成。     

131I治疗甲状腺功能亢进症合并2型糖尿病101例

目的评估甲状腺功能亢进症(甲亢)合并2型糖尿病(T2DM)患者131I治疗的临床疗效。方法 197例甲亢合并T2DM患者随机分为131I治疗组(101例)和甲巯咪唑对照组(96例),治疗1年后比较两组的临床疗效。结果治疗组的甲亢缓解总有效率88.12%(89/101),明显高于对照组的75.00%(72/96)(P<0.01)。结论 131I治疗甲亢合并T2DM患者疗效优于甲巯咪唑。