抗甲状腺药物与哺乳

长久以来国内外的医生们一直建议在服用抗甲状腺药物(ATDs)治疗甲状腺功能亢进症(甲亢)期间最好不要哺乳，如果一定需要哺乳，应选用丙基硫氧嘧啶(PTU)，而不要选用甲巯咪唑(MMI)。新近的研究结果显示，无论是在服用PTU还是在服用MMI治疗期间哺乳，无论是在服用小剂量ATDs还是服用大剂量ATDs期间哺乳，对喂养婴幼儿的甲状腺功能和智力发育都未产生不良影响。但报道仅局限在几个研究中心，还需要大样本、多中心、跨地域的协作研究，以进一步证实目前的研究结果。     

甲状腺功能亢进症的药物治疗

甲状腺功能亢进症（甲亢）病因较复杂,在临床上以弥漫性毒性甲状腺肿伴甲亢（Graves病）最常见。甲亢的药物治疗包括抗甲状腺药（ATD）、碘剂、B受体阻滞剂、糖皮质激素、碳酸锂等。ATD是治疗甲亢的主要手段,常用药物为丙基硫氧嘧啶（PTU）和甲巯咪唑（MMI）。总的来说,ATD治疗安全且有效,但其临床不良反应亦较常见,一般程度较轻,及时停药能自行恢复,但亦可出现少见、严重的副作用。MMI与PTUI：L较,其不良反应显著低于PTU,且前者大多具有剂量依赖性。因此轻中度甲亢及甲亢维持治疗首选MMI。复方碘溶液用于术前准备及甲亢危象等;糖皮质激素主要用于甲状腺相关性眼病、甲亢危象等;B受体阻滞剂多用于控制甲亢初治期的症状;碳酸锂一般不作为常规使用,仅适合短期治疗。临床医师根据患者的病情及个体差异综合考虑,选用合适的治疗方案,密切监测疗效及不良反应。     

抗甲状腺药物与哺乳

长久以来国内外的医生们一直建议在服用抗甲状腺药物 (ATDs)治疗甲状腺功能亢进症 (甲亢 )期间最好不要哺乳 ,如果一定需要哺乳 ,应选用丙基硫氧嘧啶 (PTU) ,而不要选用甲巯咪唑 (MMI)。新近的研究结果显示 ,无论是在服用PTU还是在服用MMI治疗期间哺乳 ,无论是在服用小剂量ATDs还是服用大剂量ATDs期间哺乳 ,对喂养婴幼儿的甲状腺功能和智力发育都未产生不良影响。但报道仅局限在几个研究中心 ,还需要大样本、多中心、跨地域的协作研究 ,以进一步证实目前的研究结果。     

甲状腺功能亢进症与妊娠

本文研究甲状腺功能亢进症（甲亢）伴妊娠的安全性,无论是妊娠或哺乳,首选丙基硫氧嘧啶,也可用他巴唑;调整抗甲状腺药物（ATD）剂量,以游离T4为指标。甲亢患者应选择妊娠时机。妊娠早期病情会加重,ATD剂量需增加,晚期由于免疫耐受,甲亢可缓解,需减少剂量或停药,产后甲亢易复发。     

甲状腺功能亢进症与妊娠

本文研究甲状腺功能亢进症(甲亢)伴妊娠的安全性,无论是妊娠或哺乳,首选丙基硫氧嘧啶,也可用他巴唑;调整抗甲状腺药物(ATD)剂量,以游离T_4为指标.甲亢患者应选择妊娠时机.妊娠早期病情会加重,ATD剂量需增加,晚期由于免疫耐受,甲亢可缓解,需减少剂量或停药,产后甲亢易复发.     

老年人甲状腺功能亢进症的特点

老年人甲状腺功能亢进症 (甲亢 )大多因毒性结节性甲状腺肿引起。国外报道 6 0岁以上老年人患病率约为 0 5 %～ 2 3% ,在所有甲亢患者中 6 0岁以上的老年患者约占10 %～ 37%。老年甲亢患者性别之比与中青年患者相似 ,男、女性之比约为 1∶4～ 5。老年人甲亢与中青年人甲亢比较有其特殊性 ,表现多不典型 ,症状轻微 ,发病较隐匿 ,又称为淡漠型、隐蔽型或无力型甲亢 ,容易被误诊、漏诊。老年人甲亢症状不典型的原因不是十分清楚 ,可能因 :(1)老年人甲亢不易被及时诊断、治疗及身体严重消耗 ;(2 )老年人交感神经对甲状腺激素不敏感 ;(3)儿茶酚…     

抗甲状腺药物不良反应的再认识

抗甲状腺药物(ATD)是治疗甲状腺功能亢进症主要手段,其不良反应备受学者们关注.ATD常用药物为丙基硫氧嘧啶(PTU)和甲巯咪唑(MMI).总的来说,ATD治疗是安全且有效的,但其临床不良反应亦较常见,如对肝脏、血液系统的毒性作用、抗中性粒细胞胞浆抗体相关性肺小血管炎、低血糖、变态反应、肌肉损伤等,一般程度较轻,如能及时停用ATD则能够自行恢复,但亦可出现少见、严重的副作用,可能存在潜在致命的危险,故需引起临床医生的重视.MMI与PTU比较,其不良反应显著低于PTU,且前者大多具有剂量依赖性,后者与药物的剂量无显著相关.此外,PTU的肝毒性强于MMI,甚至可能发生致命性肝损伤和肝衰竭,在儿童甲亢治疗中推荐首选MMI.

Abstract：

Antithyroid drugs(ATD)is the main treatment for hyperthyroidism and its adverse reactions have been much concerned by physicians. Methimazole(MMI)and propylthiouracil(PTU)are the two common antitithyroid drugs used currently. Generally, the ATD are safe and effective, though their clinical adverse reactions are also relatively common. The toxic effects include liver damage and leukocytopenia, antineutrophil cytoplasmic antibody-associated pulmonary small-vessel vasculitis, hypoglycemia, allergic reactions, muscle impairment,and so on. They are usually reversible and disappear spontaneously when the drug is discontinued. However,the serious rare side effects can also occur and there may have potentially deadly threatening effects which need to be cautious for the clinicians. MMI is usually preferred over PTU because it has significantly fewer side effects. And unlike the dose-dependent side effects of MMI, there has no significant correlation between adverse reaction and drug dosage in using PTU. Moreover, PTU has more severe hepatotoxity than MMI, even fatal liver impairment and liver failure. The risk of liver damage from PTU is an important concern, particularly in children. For this reason, MMI is the first choice for treating children with hyperthyroidism.     

抗甲状腺药物对131Ⅰ治疗甲状腺功能亢进症疗效的影响

^131Ⅰ是治疗甲状腺功能亢进症（甲亢）的主要药物之一，治疗前应用硫氧嘧啶类药物如丙硫氧嘧啶可能会降低^131Ⅰ治疗甲亢的治愈率，咪唑类药物如甲巯咪唑则不会影响其疗效。^131Ⅰ治疗甲亢后应用丙硫氧嘧啶或甲巯咪唑对^131Ⅰ疗效的影响尚有争议之处。抗甲状腺药物影响^131Ⅰ疗效的机理可能在于改变了^131Ⅰ的有效半衰期和（或）甲状腺对^131Ⅰ的摄取率。     

甲状腺功能亢进症的治疗

甲状腺毒症(thyrotoxicosis)是指血循环中甲状腺激素过多,引起以神经、循环、消化等系统兴奋性增高和代谢亢进为主要表现的一组临床综合征。其中由于甲状腺腺体本身功能亢进,合成和分泌甲状     

老年甲亢的临床特点及131I与抗甲状腺药物的疗效比较

采用配对设计方法对131I与抗甲状腺药物(ATD)治疗的100例老年甲亢患者进行治疗后2年的疗效综合评价,结果显示131I的疗效优于ATD.     

合并病毒性肝炎的甲状腺功能亢进患者抗甲状腺功能亢进药物治疗的安全性及短期疗效

病毒性肝炎和甲状腺功能亢进(以下简称甲亢)都是临床常见的疾病,二者同时存在的情况并不少见.甲亢时机体呈高代谢状态导致内脏对氧的消耗增多,分解代谢亢进,肝细胞因缺氧及营养障碍而功能受损~([1]).     

抗甲状腺药物对~(131)I治疗甲状腺功能亢进症疗效的影响

131I是治疗甲状腺功能亢进症(甲亢)的主要药物之一,治疗前应用硫氧嘧啶类药物如丙硫氧嘧啶可能会降低131I治疗甲亢的治愈率,咪唑类药物如甲巯咪唑则不会影响其疗效。131I治疗甲亢后应用丙硫氧嘧啶或甲巯咪唑对131I疗效的影响尚有争议之处。抗甲状腺药物影响131I疗效的机理可能在于改变了131I的有效半衰期和(或)甲状腺对131I的摄取率。     

小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤的临床观察

应用小剂量甲巯咪唑+比索洛尔治疗27例亚临床甲状腺功能亢进症合并阵发性房颤患者,治疗前后均接受多普勒超声心动仪、24 h动态心电图检查,放射免疫法测定血清FT3、FT4及TSH,观察期3个月,结果显示治疗后患者左室舒张功能明显改善(P<0.01),窦性心律维持率高,甲减发生率低,提示小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤安全有效.

Abstract：

Twenty-seven patients with subclinical hyperthyroidism(SH)complicated by paroxysmal atrial fibrillation(PAF)were treated with methimazole plus bisoprolol.All patients were examined by Doppler echocardiogram and 24 h ambulatory electrocardiograms before and 3 months after treatment.Serum FT3,FT4,and TSH levels were measured with RIA.The results showed that low-dose methimazole therapy could improve the left ventricular diastolic function(P < 0.01)and help maintain sinus rhythm.The incidence of subclinical hypothyroidism was low.Low-dose methimazole was effective and safe in patients with SH complicated by PAF.     

丙硫氧嘧啶导致症状性肝损伤的临床特征及相关因素分析

目的　探讨丙硫氧嘧啶 (PTU)治疗甲状腺功能亢进症 (甲亢 )过程中导致症状性肝损伤的临床特点及相关因素。方法　对PTU导致症状性肝损伤的临床及实验室特征、肝损伤恢复特点和相关因素进行回顾性分析。结果　PTU导致症状性肝损伤 12例 ,占同期因甲亢住院患者的 1 3%(12 /914 ) ,男 1例 ,女 11例 ,年龄 (30± 9)岁 ,肝损伤出现在服药后 (36± 18)d ,临床表现为腹胀、乏力、恶心、尿色黄等 ,肝功异常的峰值分别为 :ALT (5 31 7± 35 2 0 ) 11314 2 5U/L、血清碱性磷酸酶 (183±97) 84 35 4U/L、总胆红素 [(中位数 )范围 ]6 7 6 (17 15 6 7 7) μmol/L、直接胆红素 4 7 9(5 6 2 71 0 ) μmol/L ;损伤类型中肝细胞性占 6 6 7%、混合性占 2 5 0 %、胆汁淤积性占 8 3% ,肝损伤时PTU服用剂量为15 0～ 30 0mg/d ;停用PTU及治疗后 ,肝功能恢复正常时间 14～ 14 0d。症状性肝损伤、亚临床性肝损伤和无肝损伤 3组比较 ,既往有抗甲状腺药不良反应史者 ,损伤组显著多于无肝损伤发生组 ,PTU的起始剂量也显著低于无肝损伤组 ,治疗前ALT异常者亚临床性肝损伤组显著高于其他 2组。结论　PTU引起症状性肝损伤多发生于治疗初始阶段 ,以肝细胞性肝损伤多见 ,临床过程相对良性 ,停药、保肝和糖皮质激素治疗后 ,肝功能可恢     

甲状腺功能亢进性肝损害与甲巯咪唑继发性肝损害的临床比较研究

目的分析甲状腺功能亢进症(简称甲亢)性肝损害患者的肝功能与甲状腺功能的相关性,探讨抗甲亢药物甲巯咪唑所致肝损害患者的临床特征及其引起肝损害的相关因素。方法纳入甲亢性肝病患者54例(甲亢性肝损害组)和初诊未治的无肝损害甲亢患者33例(甲亢无肝损害组),收集两组患者用药前的一般资料和临床资料(甲状腺功能和肝功能),分析甲亢性肝损害的相关因素;将同期抗甲亢药物甲巯咪唑致肝损害患者(27例)根据肝功能指标分为肝细胞型组(7例)、胆汁淤积型组(12例)和混合型组(8例),收集其一般资料和临床资料(甲状腺功能和肝功能)并比较。结果甲亢性肝损害组患者治疗前的ALT、AST、碱性磷酸酶(ALP)、谷氨酰转肽酶(γ-GT)、总胆红素(TBIL)、游离三碘甲腺原氨酸(FT 3)、游离甲状腺激素(FT 4)和促甲状腺激素受体抗体(TRAb)水平明显高于甲亢无肝损害组(P<0.05),两组患者ALT、ALP、γ-GT水平均与FT 3、FT 4、TRAb水平呈明显正相关(P<0.05)。肝细胞型组、胆汁淤积型组和混合型组患者的年龄、用药时间、ALT、ALP比较差异均有统计学意义(P<0.05)。结论甲亢患者甲状腺功能异常的严重程度可能与其肝损害相关;抗甲亢药物甲巯咪唑引起的肝损害类型可能与患者年龄、病程及用药时间有关。     

Purpura chez une jeune femme hyperthyroïdienne

IntroductionPropylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis.ObservationA 27-year-old woman diagnosed with Graves’ disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover.ConclusionAll synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.     

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

Objective

To test whether antineutrophil cytoplasmic antibodies (ANCA) and ANCA‐associated vasculitis (AAV) are not only induced during treatment with antithyroid drugs, but can also become evident when medication has been ceased, possibly after years.

Methods

Patients who visited our hospital for the treatment of hyperthyroidism were included (n = 207). Treatment consisted of antithyroid medications, radioactive iodide, thyroidectomy, or a combination of these treatment options. Patients were retested 3–6 years later to evaluate long‐term effects of antithyroid drugs. Patients were tested for the presence of ANCA and, if positive, evaluated for the presence of AAV.

Results

Of 209 patients with hyperthyroidism, 12 patients (6%) were positive for myeloperoxidase‐ (MPO‐), proteinase 3‐, or human leukocyte elastase‐ANCA. Seventy‐seven of 209 patients were retested; 1 patient who had not been treated with antithyroid drugs had developed MPO‐ANCA. In 3 of 6 patients previously positive, ANCA could still be detected. The presence of ANCA was highly associated with treatment with antithyroid drugs (odds ratio 11.8 [95% confidence interval 1.5–93.3]). Of 13 patients with a positive ANCA result on enzyme‐linked immunosorbent assay, AAV with glomerulonephritis was diagnosed in 4 (31%).

Conclusion

The presence of ANCA with or without vasculitis is associated with previous treatment with antithyroid drugs, possibly after years.

     

丙基硫氧嘧啶与甲巯咪唑对Graves病患者细胞因子的影响

将64例Graves病(GD)患者分为甲巯咪唑组(MMI,n=30)和丙基硫氧嘧啶组(PTU,n=34),20名健康志愿者作为对照组.采集各组患者治疗前、治疗后3、6个月血清,分别用酶标记免疫吸附法检测血浆白细胞介素(IL)-2、IL-6及促甲状腺素受体抗体(TRAb)的水平.结果显示,2组治疗前一般情况比较差异无统计学意义.2组用药后6个月IL-2、IL-6水平较治疗前差异均有明显统计学意义(P＜0.05),随时间延长IL-2逐渐升高,IL-6逐渐降低;用药6个月后MMI组IL-6水平较PTU组明显降低(P＜0.05).2组治疗前TRAb水平无显著差异,2组治疗后3和6个月TRAb差异均有统计学意义(均P＜0.01),随时问增加逐渐下降.IL-2/IL-6比值在同一组治疗3、6个月后均较治疗前明显升高(P＜0.05).治疗6个月后MMI组较PTU组更高(P＜0.05).GD治疗前血清中IL-6水平与FT3、FT4呈正相关,IL-2水平与FT3、FT4和TRAb呈负相关;治疗3、6个月后,IL-2、IL-6与FT3、FT4无明显相关性;MMI组治疗前后IL-2、IL-6水平均与TRAb相关.这些结果提示,MMI较PTU更具有改善GD患者自身免疫的作用.     

Intermittent polyarthritis due to propylthiouracil

Summary A case of intermittent polyarthritis developing as a result of long term propylthiouracil (PTU) uptake is described together with successful treatment based on drug replacement.