Subedi Bal Krishna, Modi Shivani, Gautam Naveen, Upadhyay Anuja, Baek Paul, Bitetto Daniel
Department of Internal Medicine, Jefferson Einstein Montgomery Hospital (Einstein Medical Center Montgomery), East Norriton, Pennsylvania, USA.
Medical Officer, Gulmi Durbar Basic Hospital, Gulmi, Nepal.
Ann Med Surg (Lond). 2025 Apr 4;87(5):3016-3022. doi: 10.1097/MS9.0000000000003252. eCollection 2025 May.
Renal cell carcinoma (RCC) represents 90% of renal malignancies with rising global incidence. While the classic triad includes hematuria, flank pain, and palpable masses, paraneoplastic hypercalcemia occurs in 17% of cases and indicates aggressive disease behavior. This case documents severe hypercalcemia as the initial manifestation of metastatic RCC.
A 64-year-old male presented with malaise, bloating, and weight loss. Laboratory evaluation revealed severe hypercalcemia (15.1 mg/dL), suppressed parathyroid hormone (4.2 pg/mL), and elevated parathyroid hormone-related peptide (83 pg/mL). Imaging identified a 5.5 × 5.0 × 5.3 cm left renal mass with metastases to lungs, brain, and possibly bone. Biopsy confirmed metastatic clear-cell RCC. Management comprised aggressive hydration, zoledronic acid, combined immunotherapy (pembrolizumab/lenvatinib), and palliative radiation for cerebral lesions.
This case illustrates PTHrP-mediated humoral hypercalcemia of malignancy in metastatic RCC. The pathophysiology differs from alternative mechanisms such as calcitriol-mediated hypercalcemia or cytokine-driven osteoclast activation. Diagnostic markers demonstrated a classic humoral pattern with PTHrP elevation (83 pg/mL) and PTH suppression (4.2 pg/mL). The multimodal imaging protocol effectively delineated primary tumor dimensions, vascular invasion, and metastatic burden. Treatment efficacy was objectively measured through serial calcium levels and documented radiographic regression of primary and metastatic lesions. This aligns with recent data on combination immunotherapy (anti-PD-1) with tyrosine kinase inhibition in advanced RCC, supporting current therapeutic paradigms for PTHrP-mediated hypercalcemia in metastatic disease.
Prompt recognition of paraneoplastic hypercalcemia in RCC facilitates timely intervention. This case demonstrates the value of comprehensive diagnostic evaluation and multidisciplinary management combining supportive care with targeted immunotherapy. Further prospective studies are needed to optimize therapeutic strategies for patients presenting with metabolic derangements suggestive of underlying malignancy.
肾细胞癌（RCC）占肾脏恶性肿瘤的90%，全球发病率呈上升趋势。虽然经典三联征包括血尿、胁腹痛和可触及肿块，但17%的病例会出现副肿瘤性高钙血症，提示疾病行为侵袭性强。本病例记录了严重高钙血症作为转移性RCC的初始表现。
一名64岁男性出现全身不适、腹胀和体重减轻。实验室检查显示严重高钙血症（15.1mg/dL）、甲状旁腺激素抑制（4.2pg/mL）和甲状旁腺激素相关肽升高（83pg/mL）。影像学检查发现左肾有一个5.5×5.0×5.3cm的肿块，伴有肺、脑及可能的骨转移。活检证实为转移性透明细胞RCC。治疗包括积极补液、唑来膦酸、联合免疫治疗（帕博利珠单抗/乐伐替尼）以及对脑部病变进行姑息性放疗。
本病例说明了转移性RCC中PTHrP介导的恶性肿瘤体液性高钙血症。其病理生理学不同于其他机制，如骨化三醇介导的高钙血症或细胞因子驱动的破骨细胞激活。诊断标志物显示出典型的体液模式，PTHrP升高（83pg/mL）和PTH抑制（4.2pg/mL）。多模态成像方案有效地描绘了原发肿瘤大小、血管侵犯和转移负担。通过连续的钙水平客观测量治疗效果，并记录原发和转移病灶的影像学退缩情况。这与晚期RCC中联合免疫治疗（抗PD-1）与酪氨酸激酶抑制的最新数据一致，支持目前针对转移性疾病中PTHrP介导的高钙血症的治疗模式。
及时识别RCC中的副肿瘤性高钙血症有助于及时干预。本病例展示了综合诊断评估以及将支持性护理与靶向免疫治疗相结合的多学科管理的价值。需要进一步的前瞻性研究来优化针对出现提示潜在恶性肿瘤的代谢紊乱患者的治疗策略。
