Pathogenesis and management of cancer associated hypercalcaemia.

Hypercalcaemia is the most common metabolic complication of malignant disease. It is an important cause of morbidity in cancer patients and is potentially amendable to treatment. Bone metastases are rarely the cause of hypercalcaemia in malignancy, the elevation in calcium concentrations usually resulting from the effects of humoral mediators released by the tumour. Many factors isolated from tumours have the potential to cause hypercalcaemia, but the most important is parathyroid hormone related protein (PTHrP), a peptide which mimics the effect of PTH. Treatment of cancer associated hypercalcaemia is based on an initial phase of volume repletion with isotonic saline, followed by drug treatment to inhibit bone resorption. Bisphosphonates are the most widely used agents in the treatment of such bone resorption, are very effective and have minimal toxicity. Gallium nitrate is also effective but less widely used. The combination of bisphosphonates and calcitonin has been found to be particularly useful in patients with severe hypercalcaemia, since this gives a more rapid reduction in serum calcium values than can be achieved with bisphosphonate alone. In the longer term, effective control of hypercalcaemia depends on treating the primary tumour. In the majority of cases this is not possible, however, because of the state of disease progression or the nature of the tumour. Anti-hypercalcaemic therapy is an important palliative measure in cancer patients who have symptoms of hypercalcaemia. Treatment does little to alter the long term prognosis but often results in an improvement in symptoms such that the majority may be made well enough to be discharged from hospital care.