• Ninety per cent of hypercalcaemia cases are due to either primary hyperparathyroidism or malignancy.
• Mild elevations (<3.0 mmol/L) are often asymptomatic, whereas more severe elevations may present as an emergency.

2.1 Primary Causes

• Primary hyperparathyroidism
• Malignancy (e.g. bone metastases, myeloma, PTH-related protein production)

2.2 Less Common Causes

• Thiazide diuretics
• Familial hypocalciuric hypercalcaemia
• Non-malignant granulomatous disease (e.g. sarcoidosis)
• Thyrotoxicosis
• Tertiary hyperparathyroidism
• Hypervitaminosis D
• Rhabdomyolysis
• Lithium
• Immobilisation
• Adrenal insufficiency
• Milk-alkali syndrome
• Hypervitaminosis A
• Theophylline toxicity
• Phaeochromocytoma

2.3 Severity Thresholds

Below is a table summarising typical serum calcium thresholds for hypercalcaemia:

• Use of medications that contribute to elevated calcium levels (e.g. thiazide diuretics, lithium, calcium supplements)
• Underlying conditions such as malignancy, primary hyperparathyroidism, or granulomatous diseases
• Renal impairment (affecting fluid balance and drug excretion)

4.1 General Clinical Features

• Polyuria and thirst
• Anorexia, nausea, and constipation
• Cognitive dysfunction, confusion, and potential progression to coma
• Mood disturbances and depression
• Muscle weakness

4.2 Additional Manifestations

• Ectopic calcification
• Abdominal pain, vomiting
• Weight loss and lethargy
• Hypertension; possible cardiomyopathy
• Renal impairment including nephrolithiasis and nephrocalcinosis
• Shortened QT interval and other ECG conduction abnormalities
• Band keratopathy (calcium deposition in the cornea)

5.1 History

• Document symptoms of hypercalcaemia and their duration
• Identify symptoms suggestive of underlying causes (e.g. weight loss, night sweats, cough)
• Review family history and all medications (including over-the-counter supplements)

5.2 Examination

• Assess for cognitive impairment
• Evaluate fluid balance status
• Examine for signs of underlying disease (e.g. neck, respiratory system, abdomen, breasts, lymph nodes)

5.3 Investigations

• Electrocardiogram (ECG): Look for a shortened QT interval or conduction abnormalities
• Blood Tests:
  • Serum calcium (adjusted for albumin)
  • Phosphate
  • Parathyroid hormone (PTH)
  • Urea and electrolytes

PTH Interpretation:

• High calcium with high/inappropriately normal PTH → Suggestive of primary or tertiary hyperparathyroidism
• High calcium with low PTH → Suggestive of malignancy or other less common causes

Further Tests (as indicated):

• 24-hour urinary calcium excretion (to exclude familial hypocalciuric hypercalcaemia)
• Full blood count
• Protein electrophoresis
• Serum ACE
• Vitamin D levels
• Thyroid function tests
• PTH-related peptide (PTHrP)
• Chest X-ray
• Isotope bone scan

6.1 General Principles

• Identify and treat the underlying cause alongside acute management
• Discontinue any medications contributing to hypercalcaemia (e.g. thiazide diuretics, calcium supplements)

6.2 Rehydration

• Intravenous 0.9% Saline: 4–6 L over 24 hours
  • Monitor for fluid overload, especially in elderly or renally impaired patients
  • Loop diuretics only if fluid overload develops (they do not directly reduce calcium)
  • Consider dialysis if severe renal failure is present

6.3 Bisphosphonates

• Inhibit osteoclast activity and reduce bone resorption
• Common Options:
  • Zoledronic acid: 4 mg IV over 15 minutes (preferred in malignancy-related hypercalcaemia)
  • Pamidronate: 30–90 mg at 20 mg/h (dose depends on severity)
  • Ibandronic acid: 2–4 mg IV
• Use slower infusions and/or dose adjustments in renal impairment
• Monitor serum calcium; nadir typically at 2–4 days
• Watch for hypocalcaemia, especially with vitamin D deficiency or suppressed PTH

6.4 Second-Line Treatments

• Dialysis may be indicated in severe hypercalcaemia complicated by oliguric AKI

7.1 Addressing Underlying Causes

• Definitive management of primary hyperparathyroidism may involve parathyroidectomy, especially in severe cases or those resistant to medical therapy
• Malignancy-related hypercalcaemia may require ongoing oncology treatments (e.g. chemotherapy) and additional agents (e.g. calcimimetics)

7.2 Ongoing Monitoring

• Adjust treatments based on ongoing clinical and biochemical assessments
• Regular follow-up to monitor serum calcium levels, renal function, and symptom recurrence