Management of hypercalcaemia

Causes and risk

The most common cause of hypercalcemia is hyperparathyroidism, which is seldom symptomatic and is often discovered through routine blood testing. Hypercalcemia due to cancer can be caused by secretion of the parathyroid hormone-related protein and by osteoclastic bone resorption. Other causes include thiazide diuretics, lithium, vitamin D intoxication, hyperthyroidism, milk alkali syndrome from excessive calcium antacid ingestion, adrenal insufficiency, and lymphoma.

In multiple myeloma the mechanism is a different one. Myeloma cells in bone marrow secrete cytokines like IL-1, IL-6, TNF and RANKL; these stimulate osteoclasts, bone resorption is increased, calcium is released, and hypercalcemia is the outcome. Bone lesions on skull X-ray and a spinal mass compressing the cord support bone involvement rather than humoral hypercalcemia. Set against that, PTHrP is usually a matter of solid tumors with no lytic lesions, the vitamin D mechanism is typically lymphoma, HCTZ gives mild hypercalcemia only, and CKD usually gives low calcium and not high.

Hypercalcemia also turns up inside other diagnoses. It is one of the laboratory features of primary adrenal insufficiency, alongside hyponatremia, hyperkalemia and eosinophilia. It is the laboratory finding in Williams syndrome, which is autosomal dominant with a microdeletion 7q. And refractory peptic ulcer disease with hypercalcemia and low serum phosphorus points to MEN1, the hypercalcemia and low phosphorus being due to hyperparathyroidism.