Summary

Hypercalcaemia is defined as serum calcium greater than 2.6 mmol/L (adjusted for albumin). It is a common metabolic abnormality with potentially life-threatening consequences if severe (greater than 3.5 mmol/L). Primary hyperparathyroidism and malignancy account for over 90% of cases. Symptoms classically remembered as "bones, stones, groans, and moans." Treatment of severe hypercalcaemia is an emergency requiring aggressive IV fluid resuscitation followed by bisphosphonates. [1,2]

Key Facts

• Definition: Adjusted calcium greater than 2.6 mmol/L (check albumin correction).
• Severe: Greater than 3.5 mmol/L (medical emergency).
• Two Main Causes: Primary hyperparathyroidism (90% outpatient), Malignancy (70% inpatient). [3]
• Key Discriminator: PTH level - elevated or inappropriately normal in hyperparathyroidism; suppressed in malignancy.
• Classic Symptoms: "Bones, stones, groans, and moans" + polyuria.
• Acute Treatment: IV saline rehydration → bisphosphonates.

Clinical Pearls

The 90-90 Rule: Primary hyperparathyroidism (PHPT) + malignancy cause 90% of hypercalcaemia. In the community, 90% is PHPT. In hospital, malignancy predominates.

Check the PTH First: PTH is the key discriminating test. High/inappropriate normal = PTH-mediated (PHPT, FHH, lithium). Suppressed = non-PTH mediated (malignancy, granulomatous disease, vitamin D toxicity).

Malignancy-Related Hypercalcaemia is a Poor Prognostic Sign: Median survival is 30 days after diagnosis of hypercalcaemia of malignancy. Consider goals of care discussion.

Short QT on ECG: Hypercalcaemia shortens the QT interval (opposite of hypocalcaemia). May cause arrhythmias.

General Assessment

• Hydration status (dry mucous membranes, reduced skin turgor).
• Conscious level (confusion, drowsiness).
• Vital signs (BP, pulse - bradycardia).

Focused Examination

Head and Neck

• Goitre or thyroid nodule (thyrotoxicosis, parathyroid pathology).
• Cervical lymphadenopathy (malignancy, sarcoidosis).
• Band keratopathy (chronic hypercalcaemia - rare).

Chest

• Lung examination (consolidation, effusion - malignancy).
• Breast examination if appropriate.

Abdomen

• Abdominal masses (renal, hepatic).
• Renal angle tenderness (stones).

Skeletal

• Bone tenderness (metastases, myeloma).
• Kyphosis, height loss (osteoporosis).

Neurological

• Muscle weakness (proximal myopathy).
• Hypo/hyperreflexia (variable).
• Mental state assessment.

Clues to Underlying Cause

Prognosis by Cause

Hypercalcaemia of Malignancy

• Indicates advanced or disseminated disease.
• Median survival approximately 30 days from diagnosis.
• Important to discuss prognosis and goals of care.

Monitoring

• Recheck calcium within 24-48 hours of treatment.
• Long-term monitoring for PHPT if conservative management.
• Follow-up for underlying malignancy.

Key Guidelines

Landmark Studies

1. Bilezikian et al. PHPT Guidelines (2014) [5]

• Question: When to operate on asymptomatic PHPT?
• Criteria: Calcium greater than 0.25 mmol/L above normal; age less than 50; T-score less than -2.5; eGFR less than 60; nephrolithiasis.
• Impact: Standardised surgical indications.
• PMID: 25078146.

2. Major et al. Zoledronate vs Pamidronate (2001) [6]

• Question: Zoledronate vs pamidronate for hypercalcaemia of malignancy?
• N: 287 patients.
• Result: Zoledronate superior response rate and duration.
• Impact: Zoledronate became preferred bisphosphonate.
• PMID: 11304472.

3. Hu et al. Denosumab (2014)

• Question: Denosumab for bisphosphonate-refractory hypercalcaemia?
• Result: Effective in reducing calcium in refractory cases.
• Impact: Alternative for bisphosphonate failure.
• PMID: 24446653.

What is Hypercalcaemia?

Hypercalcaemia means there is too much calcium in your blood. Calcium is important for bones, nerves, and muscles, but too much can cause problems.

What Causes It?

The two most common causes are:

1. Overactive parathyroid glands (small glands in the neck that control calcium).
2. Cancer – some cancers can raise calcium levels.

Other causes include excessive vitamin D, certain medications, and some inflammatory conditions.

What Are the Symptoms?

Mild hypercalcaemia may have no symptoms. Higher levels can cause:

• Tiredness and weakness.
• Excessive thirst and urinating a lot.
• Nausea, loss of appetite, constipation.
• Confusion or difficulty thinking clearly.
• Bone pain.
• Kidney stones.

Doctors remember these as: "Bones, stones, groans, and moans."

How is it Diagnosed?

• Blood tests to check calcium levels and parathyroid hormone (PTH).
• Sometimes further tests including scans if a cause like cancer is suspected.

How is it Treated?

• Fluids: Through a drip (IV) to flush out excess calcium.
• Medications: Bisphosphonates (e.g., zoledronate) to reduce calcium.
• Treating the cause: Surgery for parathyroid adenoma; cancer treatment if that's the cause.

When to Seek Help

• Severe confusion or drowsiness.
• Persistent vomiting or not able to drink.
• Palpitations or chest discomfort.
• Severe bone pain.

What is the Outlook?

• If caused by overactive parathyroid glands, surgery is usually very successful.
• If caused by cancer, treatment focuses on controlling calcium levels and managing the underlying disease.