Pathophysiology: Hypercalcaemia of Malignancy

Cancer is the most common cause of hypercalcaemia in inpatients. Several mechanisms can result in hypercalcaemia in malignancy. Hypercalcaemia is often associated with advanced or disseminated malignancy, and therefore carries a poorer prognosis. [2]

1. In humoral hypercalcaemia of malignancy, which is believed to account for around 80% of cases of hypercalcaemia of malignancy, the secretion of Parathyroid Hormone related Peptide (PTHrP) by tumour cells leads to increased release of calcium from bone and increased reabsorption in the kidney. PTHrP secretion is most commonly seen with breast, renal, ovarian and endometrial cancers, as well as Human T-lymphotrophic virus-associated lymphoma and squamous cell carcinomas.

2. Where there is widespread skeletal involvement, osteolysis may lead directly to excessive serum calcium.

3. In calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcaemia, an overexpression of 1-alpha hydroxylase (the enzyme that converts p25-hydroxyvitamin D to active calcitriol) by malignant or adjacent normal cells may lead to hypercalcium due to an excess of active vitamin D. This is seen most commonly with lymphomas.

4. Rarely, tumours may secrete ectopic PTH.