丙硫氧嘧啶治疗妊娠伴甲状腺功能亢进症对甲状腺功能及新生儿的影响

目的分析甲状腺功能亢进症孕妇采用丙硫氧嘧啶治疗的效果。方法选择在本院进行孕期保健的88例孕妇为研究样本,其均患有甲状腺功能亢进症,同时研究时间均在2018年6月～2019年6月之间。采取随机数字排列表法将其分成为常规组与实验组,各44例,常规组孕妇给予基础保健措施,实验组孕妇给予基础保健措施及丙硫氧嘧啶口服治疗。对比两组孕妇干预前后血清TT3、TT4、FT3、FT4及TSH水平;对比每组新生儿结局。结果干预后,实验组孕妇血清TT3、TT4、FT3及FT4水平均低于常规组,TSH水平高于常规组(P0.05)。实验组与常规组新生儿Apgar评分分别为(9.43±0.37)分、(7.51±0.39)分(P0.05);实验组与常规组新生儿体重分别是(3035.76±203.18)g、(2189.62±187.03)g(P0.05);实验组胎儿窘迫、早产以及甲状腺功能亢进症发生率均低于常规组(P0.05)。结论甲状腺功能亢进症孕妇采用丙硫氧嘧啶治疗可显著改善其甲状腺功能以及新生儿预后,发挥一定作用。     

妊娠合并甲状腺功能亢进症患者抗甲状腺药物治疗后对其新生儿先天畸形的影响

目的探讨妊娠合并甲状腺功能亢进症（甲亢）患者抗甲状腺药物（ATDs）治疗对其新生儿先天畸形的影响。方法采用回顾性分析方法对1983年1月1日-2003年12月31日在北京协和医院分娩的100例妊娠合并甲亢患者及其101例新生儿的临床资料进行研究。根据妊娠合并甲亢患者的甲状腺功能（甲功）状态及服用ATDs的情况对其新生儿先天畸形发生率、影响因素进行分析。结果（1）妊娠合并甲亢患者分娩的101例新生儿中,合并先天畸形7例,新生儿先天畸形发生率为6．9％,显著高于同期出生的新生儿先天畸形发生率的0．9％（212／22765）。其相对危险性为同期出生新生儿的7．9倍（P〈0．01）。（2）101例新生儿中,其母孕早期合并甲功亢进52例,新生儿先天畸形5例,先天畸形发生率为9．6％（5／52）;其母孕早期甲功正常49例,新生儿先天畸形2例,先天畸形发生率为4．1％（2／49）,两者新生儿先天畸形发生率比较,差异无统计学意义（P〉0．05）。（3）其母孕早期服用甲巯咪唑的12例新生儿中,合并新生儿先天畸形5例,先天畸形发生率为41．7％;其母孕早期服用丙基硫氧嘧啶的28例新生儿中,合并新生儿先天畸形1例,先天畸形发生率为3．6％;其母孕早期未服用ATDs的61例新生儿中,合并新生儿先天畸形1例,先天畸形发生率为1．6％。3者之间新生儿先天畸形发生率比较,差异有统计学意义（P〈0．01）。其中服用甲巯咪唑患者的新生儿先天畸形发生率显著高于服用丙基硫氧嘧啶者（P〈0．01）和未用药者（P〈0．01）。妊娠合并甲亢孕早期服用甲巯咪唑患者新生儿发生先天畸形的危险性,为服用丙基硫氧嘧啶患者的19．3倍;为未服用ATDs患者的42．9倍。对数线性模型分析显示,妊娠合并甲亢患者孕早期服用不同种类的ATDs,对新生儿先天畸形的形成存在显著的差异（P=0．0003）。结论妊娠合并甲亢患者其新生儿发生先天畸形的危险性增加。妊娠合并甲亢患者孕早期服用甲巯咪唑可能是导致新生儿先天畸形的主要因素之一。因此,妊娠合并甲亢患者应避免选用甲巯咪唑,以减少发生新生儿先天畸形的危险性。     

Propylthiouracil-induced antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis in a patient with a predisposition to autoimmune abnormalities

 A 65-year-old woman with a history of primary biliary cirrhosis was diagnosed as having myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated crescentic glomerulonephritis (GN) during propylthiouracil (PTU) therapy for Graves' disease. Antinuclear antibodies, as well as various thyroid-associated autoantibodies, had been detected since the diagnosis of Graves' disease was made. The patient carried human leukocyte antigens (HLAs) DR4 and DR9, the two HLA haplotypes that have been reported to be related to ANCA-associated vasculitis. Withdrawal of PTU and the administration of prednisolone resulted in a decrease in the titer of MPO-ANCA, together with an improvement in renal function. It is suggested that in addition to the PTU therapy, her genetic predisposition to autoimmunity had played a role in the production of MPO-ANCA and the development of crescentic GN. Received: January 29, 2002 / Accepted: August 28, 2002     

Antineutrophil cytoplasmic antibodies in patients with Graves’ disease: association of antimyeloperoxidase autoantibodies with propylthiouracil therapy

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic disorders have been reported in patients with Graves disease during propylthiouracil (PTU) therapy. To investigate whether ANCA are found in serum samples from patients with Graves disease, and whether PTU therapy is associated with ANCA positivity, levels of serum ANCA were examined in Graves-disease patients receiving either PTU (n = 49) or 1-methyl-2-mercaptoimidazole (methimazole, MMI) (n = 50), and in untreated Graves-disease patients (n = 32) by enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with Hashimotos thyroiditis (n = 46) were also analyzed. Antimyeloperoxidase (MPO) autoantibodies (MPO-ANCA) were present in 10 (20.4%) of 49 Graves-disease patients receiving PTU therapy, whereas MPO-ANCA were not detected in Graves-disease patients receiving MMI, in untreated Graves-disease patients, or in Hashimotos thyroiditis patients. The MPO-ANCA-positive sera showed a perinuclear staining pattern which was detected by indirect immunofluorescence microscopy using a human polymorphonuclear leukocyte–cytospin preparation. Furthermore, Western blot analysis revealed that MPO-ANCA in the Graves-disease patients, as well as MPO-ANCA in patients with idiopathic pauci-immune necrotizing and crescentic glomerulonephritis, recognize the 105-kD protein of native MPO. These results indicate that MPO-ANCA in Graves-disease patients are strongly associated with PTU therapy, and not simply related to the autoimmune thyroid disease. This study also suggests that the presence of MPO-ANCA alone may not be sufficient for the development of vasculitic disorders.     

Development of Cholinergic Neurons in Rat Brain Regions: Dose-Dependent Effects of Propylthiouracil-Induced Hypothyroidism

The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by measuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter. Various degrees of thyroid deficiency were produced by perinatal exposure to propylthiouracil (PTU) in drinking water ranging from 5 ppm (mg/l) to 25 ppm beginning at gestational day 18 until postnatal day 21. ChAT, a marker for cholinergic nerve terminals, was reduced by PTU in a dose-dependent manner. Concomitant with the enzyme deficits, hemicholinium-3 binding was elevated, suggesting an increase in neuronal impulse activity. Although similar changes were seen in both brain regions examined, the magnitude and duration of these changes were more definitive in the prefrontal cortex. Nonetheless, these neurochemical alterations appeared to be recoverable when the rats returned to a euthyroid state, and no further changes were observed as the animals reached adulthood. In comparison, data reported in a succeeding article indicate that deficits in cognitive function were first seen in weanling hypothyroid rats, but that the behavioral impairments lasted well into adulthood when thyroid status and cholinergic parameters in the brain appeared to have recovered to normal. These results suggest that alterations of cholinergic system caused by perinatal hypothyroidism are associated with neurobehavioral deficits at weaning, and these developmental deviations may cause permanent impairment of cognitive function despite recovery from the hormonal imbalance at adult ages. Published by Elsevier Science Inc.     

抗甲状腺药物治疗Graves甲亢对患者骨密度及血清骨生化影响的探讨

目的探讨抗甲状腺药物丙硫氧嘧啶(PTU)与甲巯咪唑(MMI)对Graves甲亢患者骨密度及骨生化的影响,分析药物治疗Graves甲亢的临床意义。方法收集2015年3月至2017年5月于核医学科就诊的192例Graves甲亢患者,采用随机数字表法将患者分为PTU组与MMI组各96例,分别采用PTU、MMI治疗,观察患者治疗前后促甲状腺激素(TSH)、四碘甲状腺原氨酸(T4)、三碘甲状腺原氨酸(T3)、游离三碘甲状腺原氨酸(FT_3)、游离四碘甲状腺原氨酸(FT4)水平及血清骨钙素(BGP)、降钙素(CT)、碱性磷酸酶(ALP)、β胶原蛋白(β-CTX)的变化,测定患者骨密度(BMD)的变化。结果治疗前,两组甲状腺激素水平及骨生化指标比较差异无统计学意义(P>0.05),MMI组治疗6个月TSH高于PTU组,T_3、T_4、FT_3、FT_4、BGP、CT、ALP、β-CTX水平均低于PTU组(P <0.05);治疗前,两组BMD无显著差异(P> 0.05), MMI组治疗6个月L_1-L_4腰椎、髋部、桡骨、全身BMD水平均高于PTU组(P<0.05)。结论 MMI治疗Craves甲亢可改善患者骨代谢及骨密度,对提高患者生活质量,预防骨质疏松具有较好的临床价值。     

Fetal Goiter Mimicking Anomalous Pulmonary Venous Connection

Fetal thyroid dysfunction is a well-recognized cause of secondary cardiac disease, including arrhythmias and hydrops fetalis, but has not previously been reported to mimic structural heart disease. We describe a case of fetal goiter presenting as suspected anomalous pulmonary venous connection and highlight lessons for the obstetrician and pediatric cardiologist with regard to imaging as well as communication.     

丙硫氧嘧啶联合曲安西龙治疗AITD伴甲状腺功能亢进症的疗效分析

[目的]探讨丙硫氧嘧啶联合曲安西龙治疗AITD伴甲状腺功能亢进症患者的临床疗效。[方法]运用随机数字表法将2006年9月～2011年9月在某院内分泌科住院治疗的86例AITD伴甲状腺功能亢进症患者分为丙硫氧嘧啶组和丙硫氧嘧啶联合曲安西龙组,每组各43例,4月后再次检测AITD伴甲状腺功能亢进症患者的血清游离甲状腺素(FT4)、血清游离三碘甲状腺原氨酸(FT3)、血清促甲状腺激素(TSH)、血清甲状腺过氧化酶抗体(TPOAb)和甲状腺球蛋白抗体(TGAb)的含量评价其临床治疗效果。[结果]治疗前,丙硫氧嘧啶组和丙硫氧嘧啶联合曲安西龙组AITD伴甲状腺功能亢进症患者的血清学指标FT3、FT4、TSH、TPOAb和TGAb差异无统计学意义(P﹥0.05),治疗后,丙硫氧嘧啶联合曲安西龙组AITD伴甲状腺功能亢进症患者的TSH较丙硫氧嘧啶组AITD伴甲状腺功能亢进症患者上升明显,而丙硫氧嘧啶联合曲安西龙组AITD伴甲状腺功能亢进症患者的FT3、FT4、TPOAb和TGAb较丙硫氧嘧啶组AITD伴甲状腺功能亢进症患者下降明显(P﹤0.05)。[结论]丙硫氧嘧啶联合曲安西龙用于治疗AITD伴甲状腺功能亢进症患者,能有效降低AITD伴甲状腺功能亢进症患者的血清FT3、FT4、TPOAb和TGAb的水平,抑制AITD伴甲状腺功能亢进症患者甲状腺的免疫反应,阻止AITD病情的进一步发展,在临床治疗AITD伴甲状腺功能亢进症患者过程中可推广应用该治疗方案。     

妊娠期及哺乳期抗甲状腺药物的使用研究进展

正常的甲状腺功能是保证胎儿生长发育的重要前提,但妊娠期甲状腺功能亢进是极为常见的内分泌系统疾病,甲状腺功能亢进的母亲在哺乳期的治疗也关系到母亲及胎儿甲状腺功能的恢复。本文介绍了抗甲状腺药物包括甲巯咪唑（MMI）、丙硫氧嘧啶（PTU）的作用机制以及不良反应,简述了妊娠期和哺乳期甲状腺功能亢进母亲在不同时间服用不同剂量抗甲状腺药物对于母儿甲状腺功能的影响,最终推荐孕早期首选PTU,孕中/晚期首选MMI,并且鼓励甲状腺功能亢进母亲哺乳期服用抗甲状腺药物,推荐服用低到中度剂量的MMI作为一线治疗方案,PTU作为二线用药。此外,指出妊娠期和哺乳期合理服用抗甲状腺药物不会严重影响婴儿的甲状腺功能、身体以及智力的发育。 甲状腺功能亢进症;抗甲状腺药;甲巯咪唑;丙硫氧嘧啶;妊娠;哺乳期     

19例丙基硫氧嘧啶引起抗中性粒细胞胞浆抗体相关小血管炎的临床分析

分析19例丙基硫氧嘧啶（PTU）引起抗中性粒细胞胞浆抗体相关小血管炎患者的临床资料，其中17例患Graves病，18例服用PTU超过2年。多表现为多系统受累，78．9％肾受累，42．1％肺受累，关节痛、皮疹及发热也很常见。所有患者均停用了PTU，内脏受累较重的患者应用了免疫抑制治疗。