Related Subjects:
|Familial hypocalciuric hypercalcaemia (FHH)
|Primary Hyperparathyroidism
|Lung Cancer
|Hypercalcaemia
|Multiple Myeloma
|Oncological emergencies
|Bisphosphonates
Hypercalcaemia of malignancy is a common metabolic complication of cancer, affecting around 10-30% of patients with advanced malignancies. It often indicates poor prognosis, as it usually occurs in advanced stages of cancer.
Pathophysiology: four main mechanisms
- Humoral hypercalcaemia of malignancy (HHM): This is the most common mechanism, accounting for about 80% of cases. It is caused by the secretion of parathyroid hormone-related protein (PTHrP) by cancer cells, which mimics the action of parathyroid hormone (PTH), leading to increased calcium levels in the blood.
- Local osteolytic hypercalcaemia: Occurs due to direct bone invasion by tumour cells (e.g., multiple myeloma, breast cancer) leading to bone destruction and release of calcium.
- Excessive calcitriol production: Some lymphomas (particularly Hodgkin's and non-Hodgkin's) can produce excess calcitriol, increasing calcium absorption from the gut.
- Ectopic PTH secretion: Rarely, tumours may secrete actual parathyroid hormone, leading to hypercalcaemia.
Clinical Features
- Symptoms of hypercalcaemia depend on the severity and rate of onset:
- Mild hypercalcaemia: Often asymptomatic or associated with vague symptoms such as fatigue and lethargy.
- Moderate to severe hypercalcaemia: Nausea, vomiting, constipation, polyuria, polydipsia, dehydration, confusion, and in severe cases, coma or cardiac arrhythmias.
Diagnosis
- Total serum calcium: Above 2.6 mmol/L (normal: 2.1-2.6 mmol/L)
- Ionized calcium: Above 1.32 mmol/L (normal: 1.16-1.32 mmol/L)
- Parathyroid hormone (PTH) levels, PTHrP levels, and vitamin D metabolites.
Management
- Basics: Treat the underlying cancer and correcting the high calcium levels:
- Hydration: Intravenous saline is used to correct dehydration and increase renal calcium excretion.
- Bisphosphonates: Drugs such as pamidronate and zoledronic acid inhibit bone resorption and are the mainstay of treatment.
- Calcitonin: Used for rapid reduction of calcium levels, though its effect is short-lived.
- Denosumab: A monoclonal antibody that inhibits RANKL, used in cases resistant to bisphosphonates.
- Dialysis: May be necessary in cases of severe or refractory hypercalcaemia.