Abstract Disclosure: A. Shah: None. A. Barnett: None. G. Elshimy: None. Introduction: Hypercalcemia has a broad differential of causes, while hypercalcemia of malignancy is critical to identify as it affects up to one in five cancer patients. Hypercalcemia of malignancy can be caused by the elevation of PTHrP, 1,25-dihydroxy vitamin D, or osteolytic lesions. Few cases reported in the literature combined local osteolytic hypercalcemia and humoral hypercalcemia of malignancy mechanisms in patients with multiple myeloma. We present a case of hypercalcemia due to two simultaneous malignancies: squamous cell carcinoma and multiple myeloma. Case: A 54-year-old African American female presented with altered mentation. She had a known diagnosis of oropharyngeal squamous cell cancer with lung metastasis since June 2022. At the time of evaluation in September 2022, she was actively on cetuximab chemotherapy and completed her initial radiation. Her labs showed a white blood cell count of 10,200 (4000-11000 cells/μL), hemoglobin 9 (12-14 gm/dL), creatinine 0.85 (0.7-1.4 mg/dL), calcium 14.7 (8.8-10.4 mg/dL), phosphorus 3.6 (2.9-5 mg/dL), albumin 2.5 (3.4-5.4 g/dL), total protein 11 (6-8.3 g/dL). She was treated with IV fluids, calcitonin, and IV bisphosphonates. A review of prior labs was significant for persistent mild hypercalcemia since August 2022 as well as serum protein 10 and albumin 3. Further evaluation was pursued which showed PTH 14.2 (11.1-79.5pg/ml), PTHrP 37 (less than 4.2 pmmol/L), 1,25-Vitamin D 24 (19.9-79.30 pg/ml), 25-Vitamin D 7.86 (25-80 ng/ml). Elevated protein-albumin gradient caused concern for multiple myeloma, so further investigation was performed. Serum protein electrophoresis had a monoclonal spike of 3.94 gm/dL, Kappa: Lambda light chain ratio of 18.94 (0.96-1.65), and a 24-hour urine protein of 172 mg. Bone marrow biopsy showed 80% plasma cells consistent with multiple myeloma. Skeletal survey did not show any lytic lesions. Her hypercalcemia was attributed to two simultaneously occurring malignancies given the elevated PTHrP and newly diagnosed multiple myeloma. The patient improved with medical management for the hypercalcemia and was started on dexamethasone for the multiple myeloma. Discussion: Hypercalcemia of malignancy is commonly associated with both liquid malignancies like multiple myeloma, leukemia, and lymphoma as well as solid malignancies of squamous cell origins. PTHrP is elevated in squamous cell and renal cell carcinomas while high 1,25-dihydroxy vitamin D is seen in lymphomas. Multiple myeloma causes hypercalcemia through cytokine secretion resulting in the activation of osteoclasts causing osteolytic lesions. Our patient had hypercalcemia due to high PTHrP from squamous cell carcinoma as well as newly diagnosed multiple myeloma. This case highlights the importance of recognizing that hypercalcemia may be multifactorial and a complete evaluation is needed to treat all causes appropriately. Presentation: Saturday, June 17, 2023
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