Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma
Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma
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DOI：
10.21873/invivo.11244
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发表时间：
2018-03-01
期刊：
影响因子：
2.3
通讯作者：
Akamizu, Takashi
中科院分区：
文献类型：
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作者：
Ariyasu, Hiroyuki;Inaba, Hidefumi;Akamizu, Takashi
背景：免疫检查点抑制剂（ICI）是治疗恶性肿瘤的新型药物。然而，经常发生ICI的关键内分泌免疫相关不良事件（irAE）。病例报告：一名患有晚期恶性黑色素瘤的63岁女性接受了8个周期（从第0天到第147天）的抗PD- 1抗体（nivolumab，2 mg/kg，每3周一次）。在第168天，将纳武单抗转换为抗CTLA-4抗体（伊匹单抗，每3周3 mg/kg）。28天后，她被诊断为无痛性甲状腺炎引起的甲状腺毒症（第196天）。35天后（第231天），甲状腺毒症转为甲状腺功能减退症。此外，25天后（第256天），她被诊断为肾上腺皮质激素（ACTH）缺乏导致的肾上腺皮质功能不全。给予左旋甲状腺素和氢化可的松替代激素。在诊断为ACTH不足之前，她表现出嗜酸性粒细胞增多、ESR/CRP/LDH升高、肝功能障碍和低钠血症。嗜酸性粒细胞增多、血小板减少、ESR/CRP/LDH升高和肝功能异常可能是早期发现甲状腺毒症的重要因素。结论：本报告提供了第一个详细介绍合并甲状腺毒症和单独的ACTH缺乏症引起的ICI。由于ICI治疗期间可能引起快速进行性致命内分泌系统衰竭，因此准确诊断和及时治疗以及密切随访至关重要。我们建议在ICI治疗期间常规监测内分泌功能和相关症状（疲劳加重、低血糖、低血压或低钠血症）以及其他实验室检查。
Background: Immune-checkpoint inhibitors (ICIs) are novel promising agents for the treatment of malignant tumors. However, critical endocrine immune-related adverse events (irAEs) by ICIs often occur. Case report: A 63-year-old woman with advanced malignant melanoma had received antiPD- 1 antibody (nivolumab, 2 mg/kg every 3 weeks) for 8 cycles (from day 0 to day 147). On day 168, nivolumab was switched to anti-CTLA-4 antibody (ipilimumab, 3mg/kg every 3 weeks). Twenty-eight days later, she was diagnosed with thyrotoxicosis due to painless thyroiditis (day 196). Thirty-five days later (day 231), thyrotoxicosis turned to hypothyroidism. In addition, twenty-five days later (day 256), she was diagnosed with adrenocortical insufficiency due to adrenocortical hormone (ACTH) deficiency. Hormone replacements with levothyroxine and hydrocortisone were administered. She showed eosinophilia, ESR/CRP/LDH elevation, liver dysfunction and hyponatremia before diagnosis of ACTH insufficiency. Eosinophilia, thrombocytopenia, ESR/CRP/LDH elevation, and liver dysfunction might be important for early detection of thyrotoxicosis in our case. Conclusion: The present report provides the first detailed presentation of combined thyrotoxicosis and isolated ACTH deficiency induced by ICIs. Since rapidly progressive fatal endocrine system failure may be provoked during ICI therapy, precise diagnosis and prompt treatment as well as close follow-up is critical. We propose routine monitoring of endocrine functions and related symptoms (worsened fatigue, hypoglycemia, hypotension or hyponatremia), as well as other laboratory tests during ICI therapy.