Endocrine Abstracts

Hypercalcaemia is the commonest endocrine complication of malignant disease. In most cases the underlying cause is a combination of excessive bone resorption and increased tubular reabsorption of calcium brought about by the effect of the onco-feto protein parathyroid hormone related protein (PTHrP). Other causes of hypercalcaemia of malignancy include direct interaction of malignant cells with bone; this is most commonly seen with haematological malignancies where there is stimulation of the RANK signalling pathway increasing osteoclastic bone resorption. Rare causes include the activation of vitamin D within malignant tissue and the true production of ectopic PTH.

Clinical manifestations of hypercalcaemia in malignant patients are frequently confused with the underlying malignant disease process and clinicians need to be vigilant for hypercalcaemia in patients with malignant disease in whom there is a deterioration in the clinical circumstances. In patients presenting de novo with hypercalcaemia malignancy must be considered the most likely differential diagnosis if PTH levels are suppressed.

Management of hypercalcaemia associated with malignancy requires proper assessment of the patient and understanding of the prognosis of the underlying disease. If clinical circumstances suggest that treatment of the hypercalcaemia is likely to be beneficial to the patient the initial approach should be to ensure adequate salt and water balance by the administration of intravenous saline. Once the patient is rehydration consideration should be given to administration of an intravenous bisphosphonate. If this fails to control the hypercalcaemia corticosteroid treatment is the next approach. Better understanding of the mechanisms by which hypercalcaemia comes about have allowed development of new agents such as those acting on the RANK signalling pathway which may have a role in the management of hypercalcaemia of malignancy in the future.