ICU · Oncology

Hypercalcaemia of malignancy

Also known as Hypercalcaemic crisis · Humoral hypercalcaemia of malignancy · Local osteolytic hypercalcaemia · Tumour-induced hypercalcaemia · PTHrP-mediated hypercalcaemia · Calcitriol-mediated hypercalcaemia

Hypercalcaemia of malignancy is the most common metabolic complication of malignancy, reported in up to 30% of cancer patients, and is considered an oncologic emergency. Mechanisms: (1) HUMORAL hypercalcaemia of malignancy — PTHrP-mediated, the commonest cause; (2) LOCAL OSTEOLYTIC — osteolytic cytokine production, classically multiple myeloma and breast cancer bone metastases; (3) CALCITRIOL (1,25-dihydroxyvitamin D)-mediated — excess production by lymphoma. Ectopic PTH secretion is rare, and a non-malignancy contributor (primary hyperparathyroidism, granulomatous disease) can coexist. Presentation: stones, bones, abdominal groans and psychic moans, plus polyuria/polydipsia; severe disease causes altered mental status, coma, seizures, AKI and arrhythmias, with short QT the ECG signature. Treatment: aggressive IV saline rehydration WITH an antiresorptive — denosumab or an IV bisphosphonate (strong recommendation); zoledronic acid 4 mg IV is the recommended initial dose (complete response by day 10 in 88.4% versus 69.7% with pamidronate 90 mg); calcitonin is combined with an IV bisphosphonate or denosumab for severe HCM (conditional); denosumab 120 mg SC on days 1, 8, 15 and 29 then every 4 weeks for refractory or recurrent disease (64% respond by day 10) or for renal insufficiency/bisphosphonate non-response, monitoring for and preventing hypocalcaemia; glucocorticoid-context therapy for calcitriol-associated tumours; haemodialysis for refractory severe hypercalcaemia with advanced kidney disease. Diagnosis includes measuring the mediators (PTHrP, 1,25-vitamin D, PTH). Treat the underlying malignancy.

Checked against its sources on 1 Oct 2026