Tobimatsu Aoki, Mukai Kosuke, Obata Yoshinari, Isohashi Kayako, Miyashita Kazuyuki, Fukuhara Atsunori, Kato Hiroki, Shimomura Iichiro
Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan.
Department of Radiology, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan.
Endocr J. 2025 Jul 8. doi: 10.1507/endocrj.EJ24-0713.
Pheochromocytoma/paraganglioma (PPGL) is a rare neuroendocrine tumor with metastatic potential. Peptide receptor radionuclide therapy with Lu-DOTATATE, a radiolabeled somatostatin analog, has been used for the treatment of somatostatin receptor-positive PPGLs and has shown promising efficacy and generally mild toxicity. However, rare instances of fatal crises following treatment have been reported. A 50-year-old man with pheochromocytoma was admitted for Lu-DOTATATE therapy. At the age of 49, he received I-MIBG therapy for the recurrence of pheochromocytoma with bone metastasis. He rejected additional radionuclide treatment because of work commitments. However, the patient's plasma normetanephrine levels increased to >7,200 pg/mL, which worsened his pain from bone metastasis. Therefore, the patient resumed radionuclide treatment. Because his markedly elevated catecholamine levels might have induced a hypertensive crisis, Lu-DOTATATE therapy was applied to reduce staff radiation exposure in an emergency. He developed a fever and tachycardia approximately 30 hours after Lu-DOTATATE administration followed by cardiopulmonary arrest with hemoptysis approximately 35 hours after the administration. He was not revived. Postmortem imaging suggested alveolar hemorrhage. Lu-DOTATATE administration might induce a fatal crisis, alveolar hemorrhage, and subsequent death. This is the first detailed report of a patient with PPGL who died shortly after Lu-DOTATATE therapy. A review of five reported cases of fatal crises after Lu-DOTATATE treatment suggests that high catecholamine levels are associated with a risk of crisis. In conclusion, while Lu-DOTATATE therapy is generally considered safe, our findings underscore the potential risks of fatal crisis after therapy. Careful monitoring of patients with PPGL should be performed after treatment.
嗜铬细胞瘤/副神经节瘤（PPGL）是一种具有转移潜能的罕见神经内分泌肿瘤。使用放射性标记的生长抑素类似物镥-奥曲肽进行肽受体放射性核素治疗已用于治疗生长抑素受体阳性的PPGL，并显示出有前景的疗效且毒性一般较轻。然而，已有治疗后发生致命危象的罕见病例报道。一名患有嗜铬细胞瘤的50岁男性因镥-奥曲肽治疗入院。49岁时，他因嗜铬细胞瘤骨转移复发接受了碘-间碘苄胍（I-MIBG）治疗。由于工作原因，他拒绝了额外的放射性核素治疗。然而，患者的血浆去甲肾上腺素水平升至>7200 pg/mL，这使他骨转移引起的疼痛加重。因此，患者恢复了放射性核素治疗。由于其显著升高的儿茶酚胺水平可能诱发高血压危象，在紧急情况下应用镥-奥曲肽治疗以减少工作人员的辐射暴露。在给予镥-奥曲肽后约30小时，他出现发热和心动过速，随后在给药后约35小时出现咯血伴心肺骤停。他未能复苏。尸检影像提示肺泡出血。给予镥-奥曲肽可能诱发致命危象、肺泡出血及随后的死亡。这是首例关于PPGL患者在镥-奥曲肽治疗后不久死亡的详细报告。对五例镥-奥曲肽治疗后致命危象的报道病例回顾表明，高儿茶酚胺水平与危象风险相关。总之，虽然镥-奥曲肽治疗一般被认为是安全的，但我们的研究结果强调了治疗后发生致命危象的潜在风险。治疗后应对PPGL患者进行仔细监测。
