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Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients, occurring in 10-30% of cancer patients during their disease course. It represents a serious oncologic emergency that can lead to altered mental status, cardiac arrhythmias, and death if left untreated.
The condition primarily results from two mechanisms: paraneoplastic PTH-related protein (PTHrP) secretion by tumors (80-90% of cases) causing increased bone resorption and renal calcium retention, or osteolytic bone metastases (10-20% of cases) directly destroying bone tissue. Common malignancies include squamous cell carcinomas, renal cell carcinoma, breast cancer, and hematologic malignancies like multiple myeloma.
Patients typically present with symptoms of hypercalcemia including confusion, fatigue, polyuria, constipation, and the classic mnemonic 'stones, bones, groans, and psychiatric moans.' Laboratory findings show elevated serum calcium with suppressed or inappropriately normal PTH levels, while PTHrP levels are elevated in paraneoplastic cases. Treatment involves aggressive IV hydration, bisphosphonates, and addressing the underlying malignancy.