21st June 2023

Aetiology

Malignant hypercalcaemia is a common electrolyte abnormality occurring in up to 30% of patients with cancer. There are several mechanisms which can lead to hypercalcaemia in the context of cancer:

• PTH-related protein (PTHrP) secretion – this is the most common cause. PTHrP is typically secreted by squamous cell carcinomas, breast, ovarian, kidney and bladder cancers. The protein shares homology with PTH and so binds to the PTH-1 receptor, resulting in bone resorption distal tubular calcium reabsorption.
• Osteolytic metastases – caused by the local breakdown of bone due to the presence of bony metastases, promoting osteoclast production. Most commonly associated with breast cancer and multiple myeloma.
• Ectopic PTH secretion – a rarer entity, seen associated with ovarian cancers, small cell and squamous cell cancers of the lung.