Hypercalcemia of malignancy--new insights into an old syndrome

Hypercalcemia is a common paraneoplastic syndrome. Tumors induce hypercalcemia by a local mechanism associated with the tumor's production of various cytokines increasing bone osteolysis. In addition, many tumors release humoral factors, mainly parathyroid hormone (PTH)-related protein (PTHrP), which stimulates bone resorption and/or tubular calcium reabsorption leading to hypercalcemia. Interaction of PTHrP with other tumor-elaborated cytokines might explain some nonPTH-like features associated with the hypercalcemia of malignancy syndrome. Using assays recognizing various PTHrP epitopes, the majority of hypercalcemic cancer patients have higher immunoreactive PTHrP levels in either plasma or urine than normal subjects. Present data support the concept that PTHrP might also be a factor which promotes tumor growth and also the development of osteolytic metastasis. A variety of therapeutic approaches are available to lower serum calcium in hypercalcemic cancer patients. The pathophysiological mechanisms of hypercalcemia appear to be a determinant of the efficacy of different antihypercalcemic treatments.