Memi Eleni, Karras Spiros, Tzotzas Themistoklis, Krassas Gerasimos E
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece.
J Pediatr Endocrinol Metab. 2012;25(3-4):331-43. doi: 10.1515/jpem-2011-0442.
Antithyroid drugs (ATDs) have been widely and effectively used for the treatment of pediatric and adult thyrotoxicosis for more than a half century. Since the very beginning of ATD use, reports of hepatic dysfunction related to propylthiouracil (PTU) therapy have been published. We describe a case of a 12-year-old girl, who, after 4 weeks of therapy for Graves disease (GD) with PTU (300 mg/day at 100 mg given three times a day), developed fatigue, fever, diarrhea, nausea, and vomiting. The initial diagnosis was "viral gastrointestinal infection". Few days after the initiation of her symptoms, the patient developed jaundice, hepatic tenderness, and dark urine. She was admitted to the hospital where, after an extensive investigation, it was found that serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were elevated (2312 and 1435 IU/L, respectively), alkaline phosphatase (ALP) was 171 IU/L and total bilirubin was 12.7 mg/dL, whereas direct bilirubin was 7.6 mg/dL and prothrombin time was 23.2 s (normal ratio, < 14.5 s). Serology for hepatitis A and B was negative. The diagnosis of PTU-induced hepatitis was established. PTU was discontinued, and a treatment with prednisone (50 mg/day) and vitamin K was initiated. Four weeks after admission, her hepatic tests returned to normal. We searched the English literature and we present details of all cases with PTU-related hepatic toxicity in children and adolescents published so far. Also, we provide information regarding the mechanisms and treatment of this appalling clinical entity. Finally, after recent recommendations from American Thyroid Association (ATA) and European Thyroid Association (ETA), PTU should be administered only in the first trimester of pregnancy and in cases of drug allergy to methimazole.
半个多世纪以来，抗甲状腺药物（ATD）一直被广泛且有效地用于治疗儿童和成人甲状腺毒症。自开始使用ATD以来，就有关于丙硫氧嘧啶（PTU）治疗相关肝功能障碍的报道。我们描述了一名12岁女孩的病例，她在使用PTU（每日300mg，每次100mg，每日三次）治疗格雷夫斯病（GD）4周后，出现疲劳、发热、腹泻、恶心和呕吐。最初诊断为“病毒性胃肠道感染”。症状出现几天后，患者出现黄疸、肝区压痛和深色尿。她被收治入院，经过全面检查，发现血清谷草转氨酶（SGOT）和血清谷丙转氨酶（SGPT）升高（分别为2312和1435IU/L），碱性磷酸酶（ALP）为171IU/L，总胆红素为12.7mg/dL，而直接胆红素为7.6mg/dL，凝血酶原时间为23.2s（正常比值，<14.5s）。甲型和乙型肝炎血清学检查均为阴性。确诊为PTU诱导的肝炎。停用PTU，并开始使用泼尼松（每日50mg）和维生素K治疗。入院四周后，她的肝脏检查恢复正常。我们检索了英文文献，并呈现了迄今为止发表的所有儿童和青少年PTU相关肝毒性病例的详细信息。此外，我们提供了有关这一可怕临床病症的机制和治疗的信息。最后，根据美国甲状腺协会（ATA）和欧洲甲状腺协会（ETA）最近的建议，PTU仅应在妊娠的头三个月以及对甲巯咪唑药物过敏的情况下使用。
