Epidemiology

Hypercalcemia occurs in 20% to 30% of patients with cancer.[1][2]​​​ Cancer represents the most common etiology of hypercalcemia in the inpatient setting.[3] Humoral hypercalcemia of malignancy (parathyroid hormone-related peptide [PTHrP]-mediated) is believed to account for 80% of cases (however, retrospective studies report elevated serum PTHrP levels in <40% of patients).[1][14][15][16]​​​​​​​ Tumors associated with humoral hypercalcemia include squamous cell cancer, renal cancer, ovarian cancer, endometrial cancer, breast cancer, and human T-lymphotropic virus-associated lymphoma.[1][2]​​​[10]​​ Local osteolytic hypercalcemia (local production of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and activity) accounts for 20% of cases, with typical tumors including breast cancer, multiple myeloma, and lymphoma.[1][5][10]​​​ Hypercalcemia mediated by increased calcitriol (1,25-dihydroxyvitamin D) synthesis or ectopic parathyroid hormone secretion accounts for <1% of cases.[1][10]

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