Hypercalcemia hyperparathyroidism/cancer causing

Hypercalcemia (total serum calcium >10.5 mg/dL) may be induced by a multitude of causes (Table 49-5). The most common causes of hypercalcemia are cancer and primary hyperparathyroidism. The incidence of primary hyperparathyroidism is approximately 270 new cases per million persons per year. Hypercalcemia of cancer occurs in approximately 20% to 40% of cancer patients at some time during the course of their disease. Cancer-associated hypercalcemia is predominantly encountered in hospitalized patients, while primary hyperparathyroidism accounts for the vast majority of cases in the outpatient setting. ... 

Cancer and hyperparathyroidism are the most common causes of hypercalcemia. The primary mechanisms are increased bone resorption, increased GI absorption, and decreased renal elimination. 

Hypercalcemia causes central nervous system depression, including coma, and is potentially lethal. Its major causes (other than thiazide therapy) are hyperparathyroidism and cancer with or without bone metastases. Less common causes are hypervitaminosis D, sarcoidosis, thyrotoxicosis, milk-alkali syndrome, adrenal insufficiency, and immobilization. With the possible exception of hypervitaminosis D, these latter disorders seldom require emergency lowering of serum calcium. A number of approaches are used to manage the hypercalcemic crisis. 

Hypercalcemia occurs in 10% to 20% of individuals with cancer. Tumors most commonly cause hypercalcemia by producing PTHrP, which is secreted into the circulation and stimulates bone resorptions and/or by invasion of the bone by metastatic tumor, which produces local factors that stimulate bone resorption. PTHrP binds to the PTH receptor and is the principal mediator of humoral hypercalcemia of malignancy (HHM). Cytokines such as lymphotoxin, interleukin-1, tumor necrosis factor, and PTHrP appear to be important mediators of hypercalcemia in multiple myeloma and other hematological malignancies. Some lymphomas associated with acquired immunodeficiency syndrome or HTLV [ infections cause hypercalcemia by producing 1,25(0H)2D. It is estimated that 5% of patients with hypercalcemic cancer have coexisting primary hyperparathyroidism. 

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