Paraneoplastic Hypercalcemia as the Initial Presenting Sign of Metastatic Renal Cell Carcinoma

Abstract

Introduction: Malignant hypercalcemia can occur in patients with renal cell carcinoma as part of a paraneoplastic syndrome. The suggested mechanisms of malignant hypercalcemia include overproduction of parathyroid hormone-related peptide (PTHrP), interleukin-6 (IL-6), prostaglandins, and tumor necrosis factor-alpha (TNF-α). This report describes an unusual case of paraneoplastic hypercalcemia as the initial manifestation of metastatic renal cell carcinoma (RCC). Case presentation: A 44-year-old Caucasian male with no past medical history who presented to his PCP complaining of unintentional weight loss of 25 lbs, increasing fatigue, occasional right flank pain, and nausea. His family history is significant for multiple myeloma of his mother. The physical exam was unremarkable. Labs were remarkable for serum calcium of 11.5 mg/dL, Albumin of 4.5 g/dL, intact parathyroid hormone (PTH) of 9 pg/mL, undetectable PTHrP, 25 hydroxy VitD of 26.4 ng/mL, and 1, 25 hydroxy VitD of 18 pg/mL. Serum and urine protein electrophoresis and PSA were unremarkable. CXR revealed the right lower lobe noncalcified nodule of 15×11×7 mm. CT abdomen/Pelvis revealed a right renal mass of 13×14×12 cm without lymphadenopathy or local metastasis. The patient was referred to a medical oncologist and further workup including PET/CT scan that demonstrated increased uptake in right lung nodule of SUV 6, right renal mass uptake of SUV 72, and MRI brain without metastasis. The patient treated with right total nephrectomy that revealed a sarcomatoid renal cell carcinoma. Right lung nodule biopsy revealed a clear cell renal carcinoma. The patient further treated with two cycles of Gemcitabine/oxaliplatin and four cycles of nivolumab/ipilimumab. A repeated PET/CT scan showed a complete resolution of a right lung nodule. Repeated labs were unremarkable, including serum calcium of 8.7 mg/dL. Discussion: Hypercalcemia is a frequent occurrence in patients with RCC, but it is an unusual presenting symptom. The initial evaluation should focus on whether the hypercalcemia is parathyroid-dependent or medication-related. Basic laboratory investigations for hypercalcemia include PTH, PTHrP, and 1, 25(OH)2D. Bone-resorbing cytokines may be present in those patients in which the cause of the hypercalcemia is unclear. In our case, we could not determine the specific cytokine that caused hypercalcemia, as IL-6 and TNF-α were unavailable. If laboratory tests are unavailable, bone scan, CT scan, or PET-CT should be considered to evaluate for lytic bone lesions or underlying malignancy. Evaluation for carcinoma should be persistently pursued in a patient who has symptoms suggestive of paraneoplastic hypercalcemia. Finally, symptomatic malignant hypercalcemia can be treated with IV fluids and bisphosphonates. Approximately 50% of patients who undergo nephrectomy and/or tumor debulking will revert to normocalcemia.