血清学阴性的丙硫氧嘧啶诱导的可逆性双侧感音神经性听力损失且无系统性血管炎：一例病例报告及文献复习

文献信息

中文摘要

丙硫氧嘧啶（PTU）是一种硫代酰胺类药物，用于特定临床情况下甲状腺功能亢进症的治疗。虽然PTU与肝毒性、粒细胞缺乏症和抗中性粒细胞胞质抗体（ANCA）相关性血管炎等众所周知的不良反应相关，但耳毒性是极为罕见的并发症。我们报告一例PTU治疗后出现可逆性双侧感音神经性听力损失且无系统性血管炎的病例。一名新诊断Graves病的42岁埃塞俄比亚女性开始接受PTU 100 mg口服每日三次及普萘洛尔40 mg每日一次治疗。PTU治疗约两个月后，患者出现逐渐起病的双侧听力损失，并在就诊评估前2周内加重，伴有耳鸣，无眩晕，也无既往耳部疾病史、噪声暴露史或其他耳毒性药物使用史。体格检查显示弥漫性、无压痛性甲状腺肿及双侧第八脑神经麻痹，耳镜检查正常。听力学评估显示双侧对称性、下斜型高频感音神经性听力损失，低中频听力阈值正常，4-8 kHz为中度至重度听力损失。实验室检查排除了感染性、自身免疫性和代谢性病因，包括ANCA和抗核抗体血清学阴性。停用PTU并开始短期口服泼尼松龙（40 mg每日一次，共五天）。听力在数日内开始改善，并在第10天完全恢复正常，经随访听力学检查证实。本病例强调PTU诱导的耳毒性是一种罕见但可逆的不良事件，即使在没有系统性血管炎或ANCA阳性的情况下也可发生。临床医生应对接受PTU治疗患者的听觉症状保持高度警惕。早期识别和及时停药对于预防永久性听力损害至关重要。根据WHO-UMC因果关系评估标准，该不良反应被归类为很可能/可能。

英文摘要

Propylthiouracil (PTU) is a thioamide drug used in the management of hyperthyroidism in selected clinical settings. While PTU is associated with well-known adverse effects such as hepatotoxicity, agranulocytosis, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, ototoxicity is an exceptionally rare complication. We present a case of reversible bilateral sensorineural hearing loss following PTU therapy in the absence of systemic vasculitis. A 42-year-old Ethiopian woman with newly diagnosed Graves' disease was commenced on PTU 100 mg orally three times daily and propranolol 40 mg daily. After approximately two months of PTU therapy, the patient developed gradual onset bilateral hearing loss which worsened within 2 weeks before she presented for evaluation accompanied by tinnitus, without vertigo or prior history of ear disease, noise exposure, or use of other ototoxic medications. Physical examination revealed diffuse, nontender goiter and bilateral eighth cranial nerve palsy, with normal otoscopic findings. Audiometric evaluation demonstrated bilateral, symmetric, down-sloping high-frequency sensorineural hearing loss, with normal hearing thresholds at low and mid frequencies and moderate-to-severe hearing loss at 4-8 kHz. Laboratory work-up excluded infectious, autoimmune, and metabolic causes, including negative ANCA and antinuclear antibody serologies. PTU was discontinued and a short course of oral prednisolone (40 mg daily for five days) was initiated. Hearing began to improve within days and normalized completely by day ten, confirmed by follow-up audiometry. This case highlights PTU-induced ototoxicity as a rare but reversible adverse event, even in the absence of systemic vasculitis or ANCA positivity. Clinicians should maintain a high index of suspicion for auditory symptoms in patients on PTU therapy. Early recognition and prompt drug withdrawal are essential to prevent permanent hearing impairment. Based on the WHO-UMC causality assessment criteria, this adverse reaction was classified as probable/likely.