Hypercalcemia of malignancy

Abstract

A number of malignant tumors affect various aspects of the mineral metabolism and cause laboratory abnormalities and clinical signs and symptoms. Though the bone metastases of breast, prostate, lung or thyroid cancer are the first to come in mind, the calcium homeostasis is more often disturbed by other mechanisms. The review addresses the specific mechanisms in the pathogenesis of these disturbances. The most prevalent cause for hypercalcemia of malignancy is the humoral hypercalcemia - a process of activation of the bone resorption by tumor-secreted humoral factors. Osteolytic metastases might also underlie hypercalcemia - typically from breast or prostate cancer. The multiple myeloma is a disorder that induces very typical and complex changes in the bone microenvironment and in the kidneys that lead to elevation of serum calcium levels. Some lymphomas induce the expression of 1-alfa hydroxylase and the increased formation of the active vitamin D metabolite calcitriol. The condition in essence is equivalent to endogenous vitamin D "intoxication". Despite the immense accumulation of knowledge, the complexity of the mechanisms triggering hypercalcemia of malignancy still poses a serious therapeutic challenge. The current therapeutic approach to hypercalcemia of malignancy includes hydration, aggressive diuresis and inhibition of osteoclastic bone resorption. If no definitive cure for the cancer can be achieved however, the prognosis of the hypercalcemic patient is grave.