Red flags
- Confusion, seizures + malignancy -> hypercalcaemia or SIADH-related hyponatraemia until excluded
- Recent chemotherapy initiation for high-grade lymphoma/leukaemia + new AKI/arrhythmia -> tumour lysis syndrome
- Corrected calcium >3.5mmol/L or rapidly rising -> hypercalcaemic crisis, treat urgently
- Severe hyponatraemia (<120mmol/L) or rapid onset -> seizure/cerebral oedema risk
- Oliguria/anuria post-chemotherapy -> AKI from tumour lysis or nephrotoxic agents
Differential by mechanism
Hypercalcaemia of malignancy
- PTHrP-mediated (humoral) - commonest mechanism, especially squamous cell lung/head-neck cancers
- Osteolytic - direct bone metastasis-driven resorption (myeloma, breast cancer)
- Rarely, ectopic PTH or calcitriol production (lymphoma)
SIADH -> hyponatraemia
- Small cell lung cancer classically, also head/neck cancers; chemotherapy agents (cyclophosphamide, vincristine, cisplatin) and opioids can also cause SIADH
Tumour lysis syndrome
- Rapid cell death (chemosensitive high-grade lymphoma/leukaemia, especially post-treatment initiation) -> release of intracellular contents -> hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia (calcium-phosphate precipitation) -> AKI
Other
- Chemotherapy-induced renal electrolyte wasting - cisplatin (hypomagnesaemia, hypokalaemia), amphotericin
- GI losses - vomiting/diarrhoea from chemotherapy or obstruction
- Adrenal insufficiency from checkpoint inhibitor-related endocrinopathy (hyponatraemia, hyperkalaemia)
Focused history
- Cancer type and stage (localises likely mechanism - e.g. squamous lung cancer + confusion suggests hypercalcaemia)
- Symptoms of hypercalcaemia - "bones, stones, groans, psychiatric overtones" (bone pain, renal colic, constipation/abdominal pain, confusion/depression), polyuria/polydipsia
- Symptoms of hyponatraemia - headache, nausea, confusion, seizures if severe/rapid
- Recent chemotherapy timing relative to symptom onset (tumour lysis typically within 12-72h of treatment initiation in high-risk regimens)
- Fluid intake/losses, medication review (diuretics, opioids)
Focused examination
- Volume status assessment - essential for classifying hyponatraemia (hypovolaemic/euvolaemic/hypervolaemic)
- Neurological status - confusion, reduced consciousness, seizure activity
- Signs of dehydration (hypercalcaemia causes nephrogenic diabetes insipidus-like polyuria)
- Cardiac monitoring signs if hyperkalaemia suspected (arrhythmia)
Investigation strategy
- Corrected calcium (albumin-adjusted) or ionised calcium
- UEC, magnesium, phosphate, urate - especially before and during treatment of high tumour-burden haematological malignancy (tumour lysis risk stratification)
- Serum osmolality, urine osmolality and sodium if hyponatraemia - confirms SIADH pattern (low serum osm, inappropriately concentrated urine, urine Na >30, euvolaemic)
- ECG if hyperkalaemia or severe hypercalcaemia (short QT) suspected
- PTH, PTHrP if hypercalcaemia mechanism unclear
Management
A. Hypercalcaemia of malignancy
- IV isotonic saline rehydration first - corrects volume depletion and dilutes calcium
- IV bisphosphonate (zoledronic acid) - mainstay, onset over 2-4 days, re-dose if recurrent
- Denosumab - alternative/second-line, particularly useful in renal impairment (bisphosphonates renally cleared and relatively contraindicated at low eGFR) or bisphosphonate-refractory hypercalcaemia
- Calcitonin - rapid but short-lived onset, useful as a bridge in severe/symptomatic hypercalcaemia while bisphosphonate takes effect
- Treat the underlying malignancy where possible - definitive control of tumour burden is the only durable fix
B. SIADH-related hyponatraemia
- Fluid restriction first-line for mild-moderate, chronic SIADH
- Hypertonic saline for severe/symptomatic (seizures, severe confusion) hyponatraemia - correct cautiously, no more than 8-10mmol/L in 24 hours to avoid osmotic demyelination
- Tolvaptan or demeclocycline for refractory chronic SIADH (specialist-guided)
- Treat the underlying cancer/cause where feasible
C. Tumour lysis syndrome - prevention is the priority
- Risk-stratify before chemotherapy (tumour type, bulk, baseline renal function, baseline urate)
- Prophylaxis: aggressive IV hydration +/- rasburicase (high-risk) or allopurinol (intermediate-risk) started before/with chemotherapy
- Established TLS: continue aggressive hydration, correct electrolytes (treat hyperkalaemia per standard protocol, manage hyperphosphataemia), rasburicase for hyperuricaemia, avoid calcium correction unless symptomatic (risk of calcium-phosphate precipitation), renal replacement therapy if severe AKI/refractory electrolyte derangement
D. General
- Correct magnesium/potassium losses from nephrotoxic chemotherapy (e.g. cisplatin) proactively with each cycle
- Screen for checkpoint inhibitor-related endocrinopathy (cortisol, TFTs) if hyponatraemia/hyperkalaemia occurs on immunotherapy without an obvious alternative cause
Traps
- Correcting severe hyponatraemia too quickly, risking osmotic demyelination
- Giving calcium to correct hypocalcaemia in tumour lysis syndrome without checking phosphate first - risks calcium-phosphate precipitation and worsening AKI
- Missing tumour lysis syndrome risk stratification before starting chemotherapy in high tumour-burden haematological malignancy
- Attributing confusion in a cancer patient to disease progression/delirium without checking calcium and sodium
- Using bisphosphonates in significant renal impairment without considering denosumab as an alternative
Talk track
Cancer type predicts the electrolyte problem - PTHrP-mediated hypercalcaemia in squamous cancers, SIADH in small cell lung cancer, tumour lysis syndrome after treating high-grade, high-bulk haematological malignancy. Treat hypercalcaemia with saline then IV bisphosphonate (denosumab if renal impairment), correct SIADH-hyponatraemia cautiously to avoid overcorrection, and prevent tumour lysis syndrome with risk-stratified hydration and rasburicase/allopurinol before chemotherapy rather than treating it once established.
8 of 8 sections written · drafted 2026-09-13