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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Commonest causes: primary hyperparathyroidism (outpatient/chronic) and malignancy (inpatient/acute)
- Measure PTH to differentiate: HIGH PTH = hyperparathyroidism. LOW PTH = malignancy, sarcoidosis, vitamin D excess, thyrotoxicosis
- Symptoms: "bones, stones, moans, groans" — thirst, polyuria, constipation, confusion, fatigue, nausea
- Severe (>3.0 mmol/L) or symptomatic: emergency treatment with aggressive IV 0.9% saline (3–4 L/day)
- IV zoledronic acid 4 mg (or pamidronate 60–90 mg) for malignancy-associated hypercalcaemia — onset 2–4 days
- Treat underlying cause: parathyroidectomy (PHPT), treat malignancy, stop offending drugs (thiazides, lithium, vitamin D)
Overview
Hypercalcaemia is defined as an albumin-adjusted serum calcium above the upper limit of normal (>2.6 mmol/L). The two most common causes account for >90% of cases: primary hyperparathyroidism (the most common cause in the outpatient setting) and malignancy (the most common cause in hospitalised patients). Malignancy-associated hypercalcaemia occurs via several mechanisms: PTHrP secretion (squamous cell cancers of lung, head and neck, renal), osteolytic bone metastases (breast, myeloma), and excess 1,25-dihydroxyvitamin D production (lymphoma). Other causes include sarcoidosis and other granulomatous diseases (macrophage-driven 1-alpha hydroxylation), vitamin D intoxication, thyrotoxicosis, thiazide diuretics, lithium, and immobilisation.
Epidemiology
Hypercalcaemia is found in approximately 1–3% of hospitalised patients. Primary hyperparathyroidism has a prevalence of approximately 1–3 per 1,000 in the community. Malignancy-associated hypercalcaemia occurs in up to 30% of cancer patients at some point during their disease — it is a poor prognostic marker with median survival of approximately 3 months. Sarcoidosis is the third most common cause. Drug-induced hypercalcaemia (thiazides, lithium, excessive vitamin D) should always be considered.
Clinical Features
Symptoms
Polyuria and polydipsia (nephrogenic DI — calcium interferes with ADH action)
Constipation, nausea, vomiting, anorexia
Fatigue, lethargy, muscle weakness
Confusion, drowsiness, depression (severe: coma)
Bone pain (if metastases or PHPT with bone disease)
Abdominal pain (pancreatitis, peptic ulcer, constipation)
Renal colic (from calcium-containing renal stones)
Signs
Dehydration (from polyuria and vomiting)
Reduced consciousness (severe hypercalcaemia >3.5 mmol/L)
Short QT interval and broad T waves on ECG
Hypertension
Band keratopathy on slit-lamp examination (rare)
Investigations
First-line
Albumin-adjusted calciumMild: 2.6–3.0 mmol/L. Moderate: 3.0–3.5 mmol/L. Severe: >3.5 mmol/L. Severity guides urgency of treatment
PTHTHE key discriminating test. Elevated/inappropriately normal = hyperparathyroidism. Suppressed = non-PTH mediated (malignancy, sarcoid, vitamin D, thyrotoxicosis)
Second-line
PhosphateLow in PHPT (PTH promotes phosphate excretion). Normal/high in malignancy, renal failure
Vitamin D (25-OH and 1,25-diOH)25-OH elevated in vitamin D intoxication. 1,25-diOH elevated in sarcoidosis and lymphoma (macrophage-driven)
U&Es, eGFRAssess renal function — AKI common in severe hypercalcaemia from dehydration
Myeloma screenSerum protein electrophoresis, urine Bence-Jones, serum free light chains. Myeloma is a common cause in older patients
ECGShort QT, broad T waves. Severe: bradycardia, heart block, cardiac arrest
Specialist
PTHrPParathyroid hormone-related peptide — elevated in humoral hypercalcaemia of malignancy (squamous cell lung cancer, RCC)
CT chest/abdomen/pelvisIf malignancy suspected — look for primary tumour and metastases
Serum ACE level + chest X-rayIf sarcoidosis suspected (bilateral hilar lymphadenopathy, raised ACE)
1
Emergency management (severe or symptomatic)
- IV 0.9% saline: aggressive rehydration — 3–4 L in first 24 h (adjust for cardiac function and frailty)
- Monitor fluid balance, U&Es (risk of hypokalaemia, hypomagnesaemia during rehydration)
- IV bisphosphonate: zoledronic acid 4 mg over 15 min (preferred) or pamidronate 60–90 mg over 2–4 h
- Bisphosphonates take 2–4 days for full effect — use saline for immediate correction
- Avoid thiazide diuretics (worsen hypercalcaemia). Loop diuretics (furosemide) only if fluid overloaded
- Calcitonin 4 IU/kg SC/IM 12-hourly: rapid onset (4–6 h) but tachyphylaxis within 48 h — bridge until bisphosphonate works
2
Definitive treatment — address underlying cause
- PHPT: parathyroidectomy (see NICE NG132)
- Malignancy: treat underlying cancer (chemotherapy, radiotherapy, surgery)
- Sarcoidosis: corticosteroids (prednisolone 20–40 mg/day) — suppress macrophage vitamin D conversion
- Drug-induced: stop offending agent (thiazide, lithium, vitamin D supplements, calcium supplements)
3
Refractory malignant hypercalcaemia
- Denosumab 120 mg SC: if bisphosphonate-refractory or in renal impairment (not renally cleared)
- Corticosteroids: if lymphoma, myeloma, sarcoidosis (reduce 1,25-diOH vitamin D production)
- Dialysis: in severe refractory cases or renal failure
- Prognosis: malignant hypercalcaemia is a poor prognostic indicator — consider goals of care
Complications
- Cardiac arrhythmias: Short QT, bradycardia, heart block. Severe hypercalcaemia potentiates digoxin toxicity
- Acute kidney injury: Dehydration + direct tubular toxicity. May progress to chronic renal damage (nephrocalcinosis)
- Pancreatitis: Hypercalcaemia can precipitate acute pancreatitis
- Coma and death: Calcium >4.0 mmol/L is immediately life-threatening — "hypercalcaemic crisis"
- Nephrolithiasis: Calcium-containing stones from hypercalciuria
UKMLA Exam Tips
- 1Two commonest causes: hyperparathyroidism (outpatient/chronic) and malignancy (inpatient/acute). PTH discriminates
- 2First step in severe hypercalcaemia: IV 0.9% SALINE. Not bisphosphonate first (takes days to work)
- 3NEVER give thiazides in hypercalcaemia — they worsen it by increasing renal calcium reabsorption
- 4Myeloma: hypercalcaemia + renal failure + anaemia + bone pain in an older patient → serum/urine protein electrophoresis
- 5Sarcoidosis: bilateral hilar lymphadenopathy + hypercalcaemia + raised ACE + raised 1,25-diOH vitamin D. Treat with steroids
- 6ECG: short QT in hypercalcaemia, long QT in hypocalcaemia. Know both
- 7Bisphosphonates: renal-dose adjusted. In severe renal impairment, consider denosumab instead (not renally cleared)
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