Overview
Hypercalcaemia
Topic Overview
Summary
Hypercalcaemia is elevated serum calcium (corrected calcium over 2.6 mmol/L). The two most common causes are primary hyperparathyroidism (outpatients) and malignancy (inpatients). Symptoms include "stones, bones, moans, and groans" — renal stones, bone pain, psychiatric symptoms, and abdominal pain. Severe hypercalcaemia (over 3.5 mmol/L) is a medical emergency. Treatment is IV fluids, bisphosphonates, and addressing the underlying cause.
Key Facts
- Normal calcium: 2.2-2.6 mmol/L (corrected for albumin)
- Common causes: Primary hyperparathyroidism (↑PTH), malignancy (↓PTH)
- Symptoms: Stones, bones, moans, groans
- Severe (over 3.5): Medical emergency
- Treatment: IV fluids + bisphosphonates + treat cause
Clinical Pearls
Check PTH first — it tells you which pathway to investigate
Corrected calcium = measured calcium + 0.02 × (40 - albumin)
"Bones, stones, moans, and groans" = bone pain, renal stones, psychiatric symptoms, abdominal pain
Why This Matters Clinically
Severe hypercalcaemia can cause cardiac arrhythmias, renal failure, and death. Prompt recognition and treatment is essential. Finding the underlying cause determines long-term management.
Visual Summary
Visual assets to be added:
- Calcium homeostasis diagram
- Hypercalcaemia causes flowchart (PTH-dependent vs PTH-independent)
- ECG changes in hypercalcaemia
- Treatment algorithm
Epidemiology
Incidence
- 1-3% of hospitalised patients
- Primary hyperparathyroidism: 1-3 per 1,000
Demographics
- Primary hyperparathyroidism: Post-menopausal women
- Malignancy-associated: Elderly, cancer patients
Causes
| Category | Examples |
|---|---|
| PTH-mediated (high PTH) | Primary hyperparathyroidism (adenoma 85%), MEN syndromes, lithium |
| Non-PTH-mediated (low PTH) | Malignancy (most common in hospital), sarcoidosis, vitamin D toxicity, thiazides, milk-alkite syndrome |
Malignancy Mechanisms
| Mechanism | Examples |
|---|---|
| Humoral (PTHrP) | Squamous cell carcinoma, renal cell, breast |
| Bone metastases | Breast, prostate, lung, myeloma |
| Vitamin D production | Lymphoma |
Pathophysiology
Normal Calcium Regulation
- PTH: Raises calcium (bone resorption, renal reabsorption, vitamin D activation)
- Calcitonin: Lowers calcium (minor role)
- Vitamin D: Increases gut absorption
Pathological States
| Cause | Mechanism |
|---|---|
| Primary hyperparathyroidism | Autonomous PTH secretion → increased bone resorption and renal reabsorption |
| Malignancy (PTHrP) | PTH-related peptide mimics PTH |
| Bone metastases | Local bone destruction releases calcium |
| Sarcoidosis/lymphoma | Uncontrolled 1,25(OH)2D production by granulomas |
Effects of Hypercalcaemia
- Nephrogenic diabetes insipidus → polyuria → dehydration
- Shortened QT interval → arrhythmias
- Reduced neuromuscular excitability → weakness, confusion
- Gastric hypomotility → constipation, nausea
Clinical Presentation
Classic Mnemonic — "Stones, Bones, Moans, and Groans"
| Category | Symptoms |
|---|---|
| Stones | Renal stones, nephrocalcinosis |
| Bones | Bone pain, fractures, osteoporosis |
| Moans | Psychiatric: depression, confusion, lethargy |
| Groans | Abdominal: constipation, nausea, pancreatitis |
Other Symptoms
Signs
By Severity
| Severity | Calcium (mmol/L) | Features |
|---|---|---|
| Mild | 2.6-3.0 | Often asymptomatic |
| Moderate | 3.0-3.5 | Symptomatic |
| Severe | Over 3.5 | Emergency; confusion, arrhythmias, coma |
Red Flags
| Finding | Significance |
|---|---|
| Calcium over 3.5 | Medical emergency |
| Reduced consciousness | Severe hypercalcaemia |
| Renal impairment | May be acute or chronic |
| Known malignancy | Likely malignancy-associated |
Polyuria, polydipsia
Common presentation.
Fatigue, weakness
Common presentation.
Anorexia, weight loss
Common presentation.
Clinical Examination
General
- Dehydration
- Confusion
- Lethargy
Specific
- Bone tenderness
- Abdominal tenderness
- Signs of underlying cause (neck mass, lymphadenopathy)
Investigations
Blood Tests
| Test | Purpose |
|---|---|
| Corrected calcium | Confirm hypercalcaemia |
| PTH | Key discriminator |
| U&E | Renal function |
| Phosphate | Low in hyperparathyroidism |
| ALP | Elevated in bone disease |
| Vitamin D (25-OH and 1,25-OH) | If sarcoidosis/toxicity suspected |
| Myeloma screen | Serum protein electrophoresis, Bence Jones protein |
| TFTs | Hyperthyroidism can cause mild hypercalcaemia |
Interpretation of PTH
| PTH | Likely Diagnosis |
|---|---|
| High or inappropriately normal | Primary hyperparathyroidism |
| Low (suppressed) | Malignancy, vitamin D toxicity, sarcoidosis |
Urine
- 24-hour urinary calcium (familial hypocalciuric hypercalcaemia)
Imaging
| Modality | Indication |
|---|---|
| Neck USS/sestamibi | Localise parathyroid adenoma |
| CT CAP | If malignancy suspected |
| Skeletal survey | Myeloma |
ECG
- Shortened QT interval
- Bradycardia
- Heart block (severe)
Classification & Staging
By Severity
| Severity | Corrected Calcium |
|---|---|
| Mild | 2.6-3.0 mmol/L |
| Moderate | 3.0-3.5 mmol/L |
| Severe | Over 3.5 mmol/L |
By Cause
- PTH-dependent (primary hyperparathyroidism)
- PTH-independent (malignancy, sarcoidosis, vitamin D)
Management
Severe Hypercalcaemia (Over 3.5) — Emergency
| Step | Action |
|---|---|
| 1. IV fluids | 0.9% saline 3-4L in first 24h (fluid resuscitation) |
| 2. Bisphosphonate | Zoledronic acid 4mg IV OR pamidronate 60-90mg IV |
| 3. Monitor | Calcium, renal function, fluid balance |
| 4. Cardiac monitoring | If severe |
| 5. Treat underlying cause | Urgent |
Moderate Hypercalcaemia (3.0-3.5)
| Action | Details |
|---|---|
| IV fluids | Rehydrate |
| Consider bisphosphonate | If symptomatic or not improving |
| Investigate cause |
Mild Hypercalcaemia (2.6-3.0)
| Action | Details |
|---|---|
| Oral hydration | Encourage fluids |
| Investigate cause | Check PTH |
| Outpatient follow-up | If asymptomatic |
Specific Treatments
| Cause | Treatment |
|---|---|
| Primary hyperparathyroidism | Parathyroidectomy (definitive) |
| Malignancy | Treat underlying cancer; bisphosphonates; denosumab |
| Sarcoidosis | Corticosteroids |
| Vitamin D toxicity | Stop vitamin D; steroids |
Drugs to Avoid
- Thiazide diuretics (increase calcium)
- Lithium (increases calcium)
Other Agents (Specialist Use)
- Calcitonin: Rapid but transient effect
- Denosumab: RANK-L inhibitor; useful in malignancy
- Dialysis: Refractory cases with renal failure
Complications
Renal
- Nephrolithiasis
- Nephrocalcinosis
- Acute kidney injury
- Chronic kidney disease
Cardiac
- Arrhythmias
- Hypertension
Skeletal
- Osteoporosis
- Fractures
Neurological
- Confusion
- Coma
Prognosis & Outcomes
Prognosis
- Primary hyperparathyroidism: Excellent with surgery
- Malignancy-associated: Poor prognosis (reflects underlying cancer)
Mortality
- Severe hypercalcaemia can be fatal if untreated
Evidence & Guidelines
Key Guidelines
- NICE Guidelines on Primary Hyperparathyroidism
- Endocrine Society Guidelines
Key Evidence
- IV fluids are first-line for acute hypercalcaemia
- Bisphosphonates are effective but take 2-4 days to work
Patient & Family Information
What is Hypercalcaemia?
Hypercalcaemia means the calcium level in your blood is too high. This can affect your bones, kidneys, and brain.
Symptoms
- Feeling very thirsty and passing a lot of urine
- Tiredness and weakness
- Confusion
- Tummy pain and constipation
Causes
- Overactive parathyroid gland
- Some cancers
- Taking too much vitamin D
Treatment
- Fluids through a drip
- Medication to lower calcium
- Treating the underlying cause
Resources
References
Key Reviews
- Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003;67(9):1959-1966. PMID: 12751658
- Minisola S, et al. The diagnosis and management of hypercalcaemia. BMJ. 2015;350:h2723. PMID: 26037642
Guidelines
- Bilezikian JP, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-3569. PMID: 25162665