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丙硫氧嘧啶所致无症状性肝炎

[Asymptomatic hepatitis induced by propylthiouracil].

作者信息

De Castro J J, Nobre E L, Garcia e Costa J, Galvão-Teles A

机构信息

Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa Maria, Lisboa.

出版信息

Acta Med Port. 2001 Sep-Dec;14(5-6):523-7.

Abstract

Propylthiouracil (PTU) is widely used to treat patients with hyperthyroidism. In rare cases this drug has been found to have toxic effects on the liver. We describe the second assymptomatic case, reported in the literature, of PTU induced hepatotoxicity. Sixteen cases have been published so far, all with clinical manifestations. A 20-year-old female patient developed an elevation of AST, ALT and GGT levels after 5 months of PTU (50 mg tid) therapy for Graves disease with hyperthyroidism. The patient showed normal levels of liver aminotransferases before starting PTU. She had no risk factors for or clinical evidence of pre-existing liver disease. She didn't take any regular medication. After stopping PTU, the plasma levels of hepatic enzymes normalised within 6 weeks. Thirteen days after the reinstitution of PTU (150 mg tid), because of the recurrence of hyperthyroidism, another episode of assymptomatic hepatotoxicity was documented. AST, ALT, GGT and AP levels rose again, but bilirrubin levels remained normal, which represents a very unusual laboratory constellation in this kind of patient. The serology for hepatitis A, B, C and for EBV and CMV was negative. After stopping PTU, methimazole (MMI) was started and the liver enzymes normalised within two weeks. After 12 months of MMI therapy, the patient is assymptomatic, with normal liver enzyme levels and normal thyroid function tests. This case is the second to be described where the diagnosis was confirmed by the rechallenge of PTU, being this a major diagnostic criteria. Despite its rarity the disease should be suspected in any patient receiving PTU in whom clinical or laboratorial evidence of hepatocellular injury develops. The drug should be discontinued immediately when the hepatic injury is detected. Recovery is usually complete after the withdrawal of the drug, but there were al least, three fatalities among the 17 cases described.

摘要

丙硫氧嘧啶(PTU)被广泛用于治疗甲状腺功能亢进症患者。在罕见情况下,已发现该药物对肝脏有毒性作用。我们描述了文献中报道的第二例PTU诱发肝毒性的无症状病例。迄今为止已发表了16例病例,均有临床表现。一名20岁女性患者在接受PTU(50毫克,每日三次)治疗5个月以治疗伴有甲状腺功能亢进症的格雷夫斯病后,AST、ALT和GGT水平升高。该患者在开始服用PTU之前肝转氨酶水平正常。她没有既往肝病的危险因素或临床证据。她未服用任何常规药物。停用PTU后,肝酶血浆水平在6周内恢复正常。由于甲状腺功能亢进症复发,在重新开始服用PTU(150毫克,每日三次)13天后,记录到另一例无症状肝毒性发作。AST、ALT、GGT和AP水平再次升高,但胆红素水平仍正常,这在这类患者中是非常不寻常的实验室表现。甲型、乙型、丙型肝炎以及EBV和CMV的血清学检查均为阴性。停用PTU后,开始使用甲巯咪唑(MMI),肝酶在两周内恢复正常。经过12个月的MMI治疗,患者无症状,肝酶水平正常,甲状腺功能检查正常。该病例是第二例通过再次使用PTU确诊的病例,这是一项主要的诊断标准。尽管这种疾病罕见,但在任何接受PTU治疗且出现肝细胞损伤临床或实验室证据的患者中都应怀疑。一旦检测到肝损伤,应立即停用该药物。停药后通常可完全恢复,但在描述的17例病例中至少有3例死亡。

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