Medical Oncology, Ohio State University James Cancer Hospital, Suite 1335 Lincoln Tower, 1800 Cannon Drive, Columbus, OH, 43210, USA.
BMC Urol. 2021 Apr 1;21(1):51. doi: 10.1186/s12894-021-00825-4.
Severe hypercalcemia is often associated with uncontrolled malignancy through several mechanisms. However, calcitriol-mediated hypercalcemia is a rare etiology for advanced solid tumors.
We report a case of calcitriol-mediated hypercalcemia secondary to immune checkpoint inhibition in a responder with metastatic clear cell renal cell carcinoma (ccRCC). In this case, a 68 year old male with metastatic ccRCC to the liver within 4 months of right radical nephrectomy went on to develop hypercalcemia (12.8 mg/dL) shortly following 2 cycles of nivolumab and ipilimumab. Additional testing showed an elevated calcitriol level (142 pg/mL), low parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) levels, and a normal 25-hydroxyvitamin D level. FDG-PET imaging showed hypermetabolic mediastinal, hilar, and intra-abdominal lymphadenopathy, however the subsequent lymph node biopsy only showed reactive lymphoid cells without malignancy or granuloma. The hypercalcemia was resistant to initial therapy with calcitonin, hydration, and zoledronic acid but quickly responded to high-dose prednisone (1 mg/kg), followed by normalization of calcitriol levels. The patient was rechallenged with nivolumab and ipilimumab which provided a partial response after 4 cycles. He was maintained on low dose prednisone (10 mg daily) leading to a sustained resolution of his hypercalcemia.
This case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event.
严重高钙血症通常通过多种机制与未控制的恶性肿瘤相关。然而，骨化三醇介导的高钙血症是晚期实体瘤的罕见病因。
我们报告了一例免疫检查点抑制剂抑制后发生的转移性透明细胞肾细胞癌（ccRCC）患者的骨化三醇介导的高钙血症。在本例中，一名 68 岁男性在右肾根治性切除术后 4 个月内发生肝转移的 ccRCC，在接受纳武单抗和伊匹单抗 2 个周期后很快出现高钙血症（12.8mg/dL）。进一步的检查显示骨化三醇水平升高（142pg/mL），甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）水平降低，25-羟维生素 D 水平正常。FDG-PET 成像显示代谢活跃的纵隔、肺门和腹腔内淋巴结肿大，但随后的淋巴结活检仅显示反应性淋巴细胞，无恶性肿瘤或肉芽肿。高钙血症最初对降钙素、水化和唑来膦酸治疗无效，但很快对大剂量泼尼松（1mg/kg）有反应，随后骨化三醇水平恢复正常。该患者再次接受纳武单抗和伊匹单抗治疗，在 4 个周期后获得部分缓解。他接受低剂量泼尼松（10mg/天）维持治疗，导致高钙血症持续缓解。
该病例提示骨化三醇介导的高钙血症是一种新的免疫相关不良事件。
