丙基硫氧嘧啶治疗甲状腺功能亢进症引起显著性肝损伤

Propylthiouracil-induced Overt Hepatic Injury in Patients with Hyperthyroidism

目的 探讨丙基硫氧嘧啶 (propylthiouracil PTU )治疗甲状腺功能亢进症过程中引起肝损伤的发生率、特点及相关因素。方法 采用前瞻性研究方法,对 2001年 2月至 2002年 1月间,在北京协和医院确诊为甲状腺功能 亢 进症 并 开 始 使 用 PTU 治 疗的 70例 患 者的 肝 损 伤 发 生情 况 , 进 行 为 期 6个 月 的 临 床 研 究 , 初 始 给 予 PTU 300m g/d,甲状腺功能恢复正常后减量并维持治疗 6个月,治疗前和治疗后每个月查肝功、甲状腺功能。结果 70例患者中有 64例完成 治 疗 观察 。PTU 导 致 肝 损 伤的 发 生 率 为 51.6% (33例 ), 其 中 亚临 床 性 肝 损伤 的 发 生 率 为 34.4%(22例),轻度症状性肝损伤的发生率为 9.4% (6例),显著性肝损伤的发生率为 7.8% (5例)。肝损伤最多出现在服药后 2个月内 (84.8%)。不同程度肝损伤者 PTU 的使用剂量差异无显著性 (P >0.05)。亚临床性肝损伤不需停用PTU ,肝损伤可自行恢复;轻度症状性肝损伤者应减少 PTU 剂量,加用一般的保肝治疗,肝损伤可完全恢复;显著性肝损伤者需停用 PTU ,停药 4周后肝功能检查恢复正常。结论 PTU 可引起肝损伤,且多发生在治疗的初始阶段,绝大多数为亚临床性肝损伤和轻度症状性肝损伤,不需停用 PTU ,但少数患者可发生显著性肝损伤,必须及时?

Objective To study the incidence, clinical features and related factors of propylthiouracil(PTU)-induced hepatic injury in patients with hyperthyroidism. Methods A prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT),alkaline phosphatase(ALP),aspartate aminotransferase(AST),total bilirubin(TBIL)and direct bilirubin(DBIL),thyroid function(serum thyroxine,triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin)and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun. Results Sixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients(51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients(34.4%). Slight symptomatic hepatic injury occured in 6 cases(9.4%)and overt hepatic injury in 5 patients(7.8%)after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury. Conclusions PTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.