Overview of cancer-related hypercalcemia: epidemiology and etiology

Hypercalcemia is one of the most serious metabolic disorders associated with cancer. The incidence and clinical circumstances associated with hypercalcemia vary in different types of cancer. Hypercalcemia is the most frequent metabolic complication of breast cancer and is usually related to widespread osteolytic metastases; however, local and systemic humoral factors mediating bone resorption have been described. In some patients with breast cancer, hypercalcemia results from treatment with estrogens, antiestrogens, androgens, or progestins. Coexisting primary hyperparathyroidism rarely confounds the diagnosis. In patients with lung cancer, the incidence of hypercalcemia varies with histology and is often unrelated to bone metastases. Hypercalcemia may occur either late or early in the disease but is seldom a presenting symptom. In patients with cancers of the head and neck region, hypercalcemia is most often associated with advanced recurrent and terminal disease, presumably humorally mediated. In renal cell carcinoma, hypercalcemia is also an adverse prognostic indicator, commonly mediated by humoral factors. On the other hand, almost all patients with multiple myeloma have extensive osteolytic bone destruction and hypercalcemia is frequently a presenting symptom. Hypercalcemia is uncommon in most lymphomas; however, it is usually a prominent feature of adult T-cell lymphomas and also occurs in some large cell, diffuse B-cell lymphomas. Awareness of the setting in which hypercalcemia of malignancy occurs will lead to its prompt diagnosis and institution of appropriate therapy.