Hypercalcemia and Renal Mass: A Diagnostically Challenging Case

Hypercalcemia of malignancy frequently occurs in patients with solid tumors as a paraneoplastic syndrome known as humoral hypercalcemia of malignancy (HHM), caused by the secretion of parathyroid hormone-related peptide (PTHrP). On the other hand, 1,25-dihydroxyvitamin D [1,25(OH)2D]-mediated hypercalcemia is a less common cause of hypercalcemia of malignancy and is mostly observed in lymphoma patients. Here, we report an interesting case of a 77-year-old male nursing home resident with suspected renal cell carcinoma (RCC) presenting with severe hypercalcemia (18.7 mg/dL), which was initially presumed to be HHM. However, workup revealed nonsuppressed parathyroid hormone, low PTHrP, and elevated 25-hydroxyvitamin D and 1,25(OH)2D levels. Steroids were initiated due to an inadequate response to bisphosphonate therapy and elevated vitamin D metabolites, resulting in further reduction in serum calcium levels. This case highlights the need to consider multiple concurrent etiologies in the differential diagnosis of severe hypercalcemia, including the possible role of calcitriol-mediated hypercalcemia in RCC.