Malignant Hypercalcaemia

Safety

Recognise & Confirm Hypercalcaemia

Done

Symptoms are non-specific and overlap with dying — a low threshold to check calcium in a deteriorating cancer patient is essential.

"Bones, stones, groans, moans" Bone pain, renal stones/polyuria & thirst, abdominal groans (nausea, anorexia, constipation), psychic moans (fatigue, confusion, drowsiness).

Confirm Check corrected calcium with U&E, creatinine and eGFR.

Consider also PTH, magnesium, phosphate and vitamin D.

Commonest cancers Myeloma, breast, lung, renal, squamous tumours.

Beware Hypercalcaemia may present as rapid clinical decline mimicking the dying phase — but it can be reversible.

Because the symptoms (drowsiness, confusion, nausea) mimic many things including dying, hypercalcaemia is easily missed; yet it is one of the few oncological emergencies that is readily reversible if caught.

Diagnose

Confirm & Grade Severity

Done

Always use the albumin-corrected calcium and grade it — the band drives the urgency.

Mild

Corrected Ca <3.0 mmol/L and asymptomatic — often managed with hydration and a recheck.

Moderate

Corrected Ca 3.0–3.5 mmol/L — symptomatic; needs active treatment.

Severe

Corrected Ca >3.5 mmol/L, or any level with reduced consciousness, severe dehydration, AKI or cardiac features — emergency.

ECG / cardiac

Shortened QT, bradyarrhythmias; rare risk of arrest at very high levels.

Rate matters

A rapid rise is tolerated far less well than a chronically elevated calcium — grade on symptoms as well as the number.

Corrected calcium adjusts for albumin, without which a low-albumin cancer patient's true ionised calcium is underestimated; banding then matches treatment intensity to risk, while the rate of rise explains why two patients with the same level can be very differently unwell.

Diagnose

Causes & Mechanism

Done

PTHrP (commonest, ~80%)

Humoral hypercalcaemia — tumour secretes parathyroid-hormone-related peptide (squamous lung, head & neck, renal, breast).

Osteolytic

Direct bone destruction by metastases or marrow infiltration — myeloma, breast.

Calcitriol-mediated

Excess 1,25-vitamin D — lymphoma.

Don't miss

Co-existing primary hyperparathyroidism (raised/unsuppressed PTH), drugs (thiazides, calcium/vitamin D, lithium), dehydration.

Mechanism guides treatment and prognosis: PTHrP and osteolytic disease respond to rehydration plus a bisphosphonate, calcitriol-mediated lymphoma hypercalcaemia responds well to corticosteroids, and an unsuppressed PTH points to coincident primary hyperparathyroidism rather than the malignancy — a different management path.

Diagnose

Investigations

Done

Core bloods

Corrected calcium, U&E, creatinine, eGFR, PTH (suppressed in malignancy), phosphate, magnesium, vitamin D, ALP.

Myeloma screen

FBC, ESR/plasma viscosity; if myeloma suspected (hypercalcaemia, anaemia, renal impairment, bone pain) send 2WW very urgent serum & urine protein electrophoresis + Bence-Jones protein (NICE NG12 — direct access, within 48 hours where the picture fits).

Find the primary

Imaging directed by history (CXR/CT chest, mammography, myeloma skeletal survey) if cancer not yet known.

ECG

For severe hypercalcaemia / cardiac symptoms.

A suppressed PTH confirms the hypercalcaemia is malignancy-driven rather than parathyroid, and because myeloma is a leading cause, NG12 provides fast-track access to protein electrophoresis and Bence-Jones testing — catching a treatable haematological malignancy that frequently presents exactly this way.

Treat

Treatment — Rehydrate, Then Bisphosphonate

Done

In primary care, seek specialist advice. Points to weigh first: first episode / long interval, good prior quality of life, willing & able to have IV treatment and blood tests, and that treatment takes ~a week to work (may be inappropriate if prognosis very poor).

If corrected Ca <3.0 & asymptomatic

Check U&E/creatinine/eGFR; review nephrotoxic/contributory meds (diuretics, calcium/vitamin D supplements, ACE inhibitors); correct dehydration with 0.9% saline 2–3 L/24h or adequate oral intake; recheck in 2–3 days and treat if rising.

If symptomatic, or corrected Ca >3.0

Potentially life-threatening. Review meds as above; give IV 0.9% saline 2–4 L/24h (amount/rate per renal function, calcium level, cardiovascular status); then a single IV bisphosphonate.

Bisphosphonate

EITHER zoledronic acid OR pamidronate disodium (per local guideline/BNF/SPC) — do not give both.

Renal caution

If eGFR <30 ml/min do NOT give a bisphosphonate — seek specialist advice.

Onset

Zoledronic acid: effect <4 days, max 4–7 days, lasts ~4 weeks. Pamidronate: effect <3 days, max 5–7 days, lasts ~2.5 weeks.

Volume depletion from calcium-driven polyuria worsens hypercalcaemia, so saline rehydration is the essential first step; bisphosphonates then inhibit osteoclastic bone resorption but act too slowly to be used alone in a crisis.

Treat

Second-Line & Refractory Options

Done

Denosumab

For hypercalcaemia refractory to bisphosphonates or where bisphosphonates are contraindicated (e.g. eGFR <30) — specialist-initiated; watch for later hypocalcaemia.

Calcitonin

Rapid but short-lived adjunct for severe symptomatic hypercalcaemia while bisphosphonate takes effect (acts within hours).

Corticosteroids

Effective in calcitriol-mediated hypercalcaemia (lymphoma, myeloma, sarcoid).

Severe / AKI

Consider renal/critical-care input; dialysis is reserved for life-threatening levels with renal failure.

When a bisphosphonate cannot be used (poor renal function) or fails, denosumab provides an alternative anti-resorptive that is not renally cleared; calcitonin buys time by acting within hours, and corticosteroids specifically target the vitamin-D-driven mechanism seen in lymphoma — matching the agent to the cause and the renal function.

Refer

Specialist Advice & Admission

Done

Admit

Severe (Ca >3.5), reduced consciousness, AKI, severe dehydration or unable to take oral fluids — needs IV rehydration and IV bisphosphonate in hospital.

Seek specialist advice

From acute oncology / palliative care for any treatment decision in primary care, refractory calcium, or eGFR <30.

New presentation

If the underlying cancer is unknown, admission/oncology referral allows simultaneous diagnosis and treatment.

Balance of treatment

Weigh first episode vs recurrent, prior quality of life, willingness/ability to have IV treatment, and that bisphosphonates take ~a week — may be inappropriate if prognosis is very short.

The decision to treat is as much a goals-of-care decision as a biochemical one: in a patient with a reasonable prognosis and good prior function, correcting hypercalcaemia restores days to weeks of lucidity, whereas in someone in the last days of life, IV treatment that takes a week to work may simply prolong dying — which is why specialist advice is advised.

Support

Medication Review & Supportive Care

Done

Stop contributors Review/withhold thiazide diuretics, calcium & vitamin D supplements, lithium and other contributory drugs.

Maintain hydration Encourage oral fluids; mobilise where possible (immobility worsens hypercalcaemia).

Dental care Dental review/hygiene before and during repeated bisphosphonates to reduce osteonecrosis of the jaw.

Symptom control Treat nausea, constipation and delirium; clear, honest communication with patient and family.

Several everyday factors — thiazides, calcium/vitamin D supplements, dehydration and immobility — stack on top of the malignant drive and are reversible in primary care, so addressing them both helps control calcium and reduces recurrence between infusions; dental care specifically mitigates the main long-term hazard of repeated bisphosphonates.

Follow-up

Monitor, Re-treat & Safety-net

Done

Recheck

If symptoms persist, repeat calcium & renal function after 7 days; re-treat with bisphosphonate if indicated.

Recurrence

Repeat infusion every 3–4 weeks if symptoms recur; check calcium & renal function before each dose.

Refractory

Calcium not responding → seek specialist advice (consider denosumab).

Prognosis & ACP

Hypercalcaemia of malignancy carries a poor prognosis — begin advance care planning.

Return urgently

Recurring drowsiness, confusion, vomiting, severe thirst/polyuria or reduced urine output → recheck calcium & renal function.

Recurrence is the rule because the underlying malignancy keeps driving calcium release, so a single infusion is rarely the end of the story — scheduled monitoring, pre-dose renal checks and a clear symptom safety-net catch the next episode early, while the poor prognosis makes parallel advance care planning appropriate.