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Severe hypercalcemia as the initial presentation of renal cell carcinoma: a diagnostic case report

Title: Severe hypercalcemia as the initial presentation of renal cell carcinoma: a diagnostic case report
Authors: Subedi, Bal Krishna; Modi, Shivani; Gautam, Naveen; Upadhyay, Anuja; Baek, Paul; Bitetto, Daniel
Source: Annals of Medicine & Surgery ; volume 87, issue 5, page 3016-3022 ; ISSN 2049-0801
Publisher Information: Ovid Technologies (Wolters Kluwer Health)
Publication Year: 2025
Description: Introduction and importance: 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. Case presentation: 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. Clinical discussion: 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. Conclusion: Prompt recognition of paraneoplastic hypercalcemia in RCC facilitates timely intervention. This case demonstrates the value of comprehensive diagnostic evaluation and multidisciplinary management combining supportive ...
Document Type: article in journal/newspaper
Language: English
DOI: 10.1097/ms9.0000000000003252
DOI: 10.1097/MS9.0000000000003252
Availability: https://doi.org/10.1097/ms9.0000000000003252; https://journals.lww.com/10.1097/MS9.0000000000003252
Rights: http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.C77913C4
Database: BASE