Hypercalcemia of Malignancy

This chapter discusses hypercalcemia of malignancy, which is the most common biochemical complication of cancer and is recognized as a medical emergency. Hypercalcemia presents with a wide range of clinical symptoms, which in some cases can be severe and life-threatening. Clinicians need to consider hypercalcemia as a differential diagnosis in patients with nonspecific symptoms, as hypercalcemia is potentially reversible. The following sections will review normal calcium homeostasis and discuss the mechanisms of how cancer disrupts this tightly regulated system. It is recognized that hypercalcemia is usually associated with advanced disease and, unless antineoplastic treatments are available, is a poor prognostic sign. It is, therefore, essential to consider the individual clinical situation before deciding on an appropriate management plan. Where active treatment is appropriate, initial management should consist of rehydration as hypercalcemia results in hypovolemia. Following this, specific calcium-lowering treatment should be considered. Following rehydration, intravenous bisphosphonates have been the treatment of choice for the last 20 years and are effective in the initial treatment for most cases. However, denosumab has become one of the preferred treatments. Guidance to manage recurrent and refractory hypercalcemia is also discussed in this chapter.