Hypercalcaemia

Hypercalcaemia: adjusted calcium >2.6 mmol/L. Mild <3.0 (often asymptomatic), moderate 3.0–3.5, severe >3.5 (medical emergency). Causes: 90% either primary hyperparathyroidism (outpatient, usually mild) or malignancy (bone mets, PTHrP secretion…

NICE / BES Hypercalcaemia Management

The pathway

1 · Symptoms & severity

Bones (bone pain, pathological fractures)
Stones (renal calculi, nephrocalcinosis)
Groans (nausea, vomiting, constipation, pancreatitis)
Moans (depression, cognitive slowing)
Psychic Tones (confusion, psychosis, coma)
ECG: short QTc, long PR, broad QRS
Severe >3.5: confusion, cardiac arrhythmias

2 · Confirm and investigate cause

Adjusted Ca2+ (if albumin low, use formula: Ca2+ + [0.02 × (40 - albumin)])
PTH level: high PTH = primary hyperparathyroidism, low PTH = malignancy-related
PTHrP: malignancy
Vitamin D (25-OH): granulomatous disease (sarcoidosis, TB)
Myeloma screen: protein electrophoresis, Bence-Jones protein, serum free light chains

3 · IV fluid rehydration

0.9% NaCl 200–300ml/hr — this is the most important initial step. Hypercalcaemia causes nephrogenic diabetes insipidus — patients are always dehydrated. Aim for UO 100–150ml/hr
Avoid diuretics initially (exacerbate volume depletion)
Reassess fluid status frequently

4 · Bisphosphonate therapy

Zoledronic acid 4mg IV over 15 min (or pamidronate 60–90mg over 4h) — inhibits osteoclast-mediated bone resorption
Takes 24–48h to have effect
Most effective for malignancy-related hypercalcaemia
Check creatinine before (nephrotoxic if eGFR <35)
Effect lasts 2–4 weeks

5 · Other agents

Calcitonin 4 IU/kg IM/SC: rapid onset (hours), short-lived (tachyphylaxis), useful as bridge while waiting for bisphosphonate effect.
Denosumab: for bisphosphonate-refractory cases.
Corticosteroids: for sarcoidosis, lymphoma, vitamin D toxicity.
Dialysis: for renal failure + severe hypercalcaemia.

6 · Treat the underlying cause

Primary hyperparathyroidism: parathyroidectomy (if symptomatic, Ca >2.65, age <50, osteoporosis).
Malignancy: treat cancer, bisphosphonates for bone mets.
Sarcoidosis: steroids.
Review and stop calcium/vitamin D supplements, thiazide diuretics (reduce renal Ca²⁺ excretion).

Drugs

Drug	Dose	Route	Notes
0.9% NaCl	200–300ml/hr	IV	Most important step. Rehydrate vigorously. Target UO 100–150ml/hr.
Zoledronic acid	4mg over 15 min	IV	Check creatinine first. Onset 24–48h. In tumour-induced hypercalcaemia the SmPC needs no dose adjustment below creatinine 400 µmol/L; severe renal impairment is a risk–benefit decision, not a bar. The eGFR <35 rule belongs to the bone-metastasis prevention indication.
Pamidronate	60–90mg over 4h	IV	Alternative bisphosphonate. Slower to give but equally effective.
Calcitonin	4 IU/kg 12-hourly	IM/SC	Rapid onset (4–6h), short-lived. Use as bridge while awaiting bisphosphonate.

When to escalate

Ca2+ >3.5 + confusion/arrhythmia → emergency treatment, ITU if compromised,Malignancy-related hypercalcaemia → oncology input urgently,AKI with severe hypercalcaemia → nephrology, consider dialysis,Ca2+ not falling with bisphosphonate → denosumab, haematology/oncology,Primary hyperparathyroidism confirmed → endocrine surgery referral

Reference: NICE CKS Hypercalcaemia / British Endocrine Society Guidelines 2020

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