Is hypercalcemia (elevated calcium levels) a medical emergency?

Hypercalcemia as a Medical Emergency

Severe hypercalcemia (calcium >14 mg/dL or >3.5 mmol/L) is a medical emergency requiring urgent treatment, while mild hypercalcemia is typically not an emergency and can be managed on an outpatient basis. 1, 2

Classification and Clinical Significance

Hypercalcemia can be categorized based on severity:

• Mild hypercalcemia (total calcium <12 mg/dL or <3 mmol/L)

  • Usually asymptomatic
  • May cause fatigue and constipation in about 20% of patients
  • Generally does not require emergency intervention

• Severe hypercalcemia (total calcium ≥14 mg/dL or ≥3.5 mmol/L)

  • Constitutes a true medical emergency
  • Can cause life-threatening complications
  • Requires immediate intervention 1, 2, 3

Clinical Presentation of Severe Hypercalcemia

Severe hypercalcemia presents with:

• Gastrointestinal symptoms: nausea, vomiting, constipation, abdominal pain
• Renal complications: dehydration, polyuria, renal insufficiency
• Neurological symptoms: confusion, lethargy, impaired cognitive function, somnolence, coma
• Cardiovascular manifestations: hypertension, arrhythmias, shortened QT interval
• Musculoskeletal symptoms: muscle cramps, weakness, bone pain 1, 2, 3

Emergency Management of Severe Hypercalcemia

The cornerstone of initial management for severe hypercalcemia includes:

1. Aggressive IV fluid resuscitation with normal saline

   • Corrects hypercalcemia-associated hypovolemia
   • Promotes calciuresis
   • First-line intervention before any other treatments 1

2. Bisphosphonates

   • Zoledronic acid 4 mg IV over 15 minutes is the preferred agent
   • First-line pharmacological intervention for cancer-related hypercalcemia
   • Response rate of 50% by day 4 1, 4

3. Calcitonin

   • For immediate short-term management of severe symptomatic hypercalcemia
   • FDA-approved for early treatment of hypercalcemic emergencies
   • Provides rapid but transient effect 1, 5

4. Loop diuretics (e.g., furosemide)

   • Should be used only after adequate hydration
   • Enhances calcium excretion 1, 3

5. Additional therapies for specific situations

   • Denosumab: For hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment
   • Glucocorticoids: Effective for granulomatous disorders, vitamin D toxicity, or some lymphomas
   • Dialysis: May be necessary in severe cases with renal failure 1, 2, 3

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia
• Failing to correct calcium for albumin
• Inadequate hydration before bisphosphonate administration
• Treating laboratory values without addressing the underlying cause
• Delaying treatment of severe hypercalcemia
• Administering bisphosphonates too rapidly
• Failing to monitor for hypocalcemia after treatment 1

Etiology and Diagnostic Approach

The most common causes of hypercalcemia include:

• Primary hyperparathyroidism (PHPT) - approximately 90% of cases along with malignancy
• Malignancy-associated hypercalcemia - poor prognosis with median survival of about 1 month in lung cancer patients
• Other causes: granulomatous diseases, vitamin D toxicity, medications, endocrinopathies 1, 2

Initial diagnostic workup should include:

• Serum intact parathyroid hormone (iPTH)
• Parathyroid hormone-related protein (PTHrP)
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
• Complete blood count
• Serum concentrations of calcium, albumin, magnesium, and phosphorus
• Thyroid-stimulating hormone (TSH) and liver function tests 1

Prognosis

• Hypercalcemia of malignancy is associated with poor survival outcomes
• Primary hyperparathyroidism has excellent prognosis with proper management
• Overall mortality rate in emergency department patients with hypercalcemia can be as high as 23.1% 2, 6