Hypercalcemia associated with malignancies is reported in up to 20 to 30% of patients with cancer during the course of the disease, and points to a poor prognosis. Symptoms related to the central nervous system, as progressive mental impairment, stupor and coma, predominate. Alterations in kidney function (water-concentrating defect leading to polyuria) and gastrointestinal tract (anorexia, nausea, vomiting) corroborate to dehydration and a further increase in serum calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space; 2) humoral hypercalcemia of malignancy, caused by the secretion of parathyroid hormone-related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism; 4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary to give the patient time to respond to anti-cancer therapy. Volume expansion with saline will correct dehydration, improve glomerular filtration and increase urinary calcium excretion, which may be further stimulated by loop diuretics. Intravenous bisphosphonates are the most effective agents to control hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral effects, decreasing bone metastases. New approaches to control the skeletal manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies, osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.
Hypercalcemia; Cancer; PTHrP; Metastases; Bisphosphonates
