What is the initial step in the workup and management of hypercalcemia?

Initial Workup and Management of Hypercalcemia

The initial diagnostic step in hypercalcemia workup is measuring serum intact parathyroid hormone (iPTH) levels, followed by immediate IV fluid rehydration for symptomatic or severe cases. 1, 2

Diagnostic Approach

Step 1: Laboratory Assessment

• Confirm hypercalcemia with serum calcium measurement (corrected for albumin if needed)
• Measure intact parathyroid hormone (iPTH) - most critical initial test 2
  • Elevated/normal iPTH → Primary hyperparathyroidism
  • Suppressed iPTH (<20 pg/mL) → Consider malignancy or other causes

Step 2: Additional Laboratory Tests

• Measure serum concentrations of:
  • PTHrP (parathyroid hormone-related protein)
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • Albumin (for calcium correction)
  • Magnesium and phosphorus
  • Renal function tests (BUN, creatinine) 1

Step 3: Evaluate for Common Etiologies

• Primary hyperparathyroidism and malignancy account for >90% of cases 2, 3
• Check for medications that may cause hypercalcemia:
  • Thiazide diuretics
  • Calcium supplements
  • Vitamin D supplements
  • Vitamin A supplements 2

Management Algorithm

For Severe Hypercalcemia (>14 mg/dL or Symptomatic)

1. Immediate IV fluid rehydration with normal saline (cornerstone of initial treatment) 1

   • Promotes calciuresis and corrects dehydration
   • Use caution in patients with heart failure or renal insufficiency

2. Bisphosphonates after adequate hydration 1

   • Zoledronic acid (4 mg IV) - preferred agent 1
   • Pamidronate (90 mg IV) as alternative
   • Reserve 8 mg zoledronic acid dose for refractory cases 1

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

   • Only after correction of intravascular volume
   • Helps prevent fluid overload in patients with cardiac or renal issues 1, 3

For Mild to Moderate Hypercalcemia (<14 mg/dL, Asymptomatic)

• Oral hydration may be sufficient 1
• Treat underlying cause
• Monitor calcium levels regularly

Special Considerations

Hypercalcemia of Malignancy

• Characterized by rapid onset, higher calcium levels, and more severe symptoms 3
• Often associated with PTHrP production, especially in squamous cell lung cancer 1
• Poor prognosis (median survival ~1 month after discovery in lung cancer) 1
• Denosumab may be considered for cases refractory to bisphosphonates 1

Primary Hyperparathyroidism

• Usually presents with lower calcium levels (<12 mg/dL) and longer duration 3
• May require parathyroidectomy depending on age, calcium level, and end-organ damage

Other Treatments Based on Etiology

• Glucocorticoids: Effective for hypercalcemia due to lymphoma, granulomatous diseases, or vitamin D intoxication 1, 3
• Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia 3
• Dialysis: Reserved for severe hypercalcemia complicated by kidney failure 3

Clinical Pearls

• Hypercalcemia symptoms include polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and myalgia 1
• Severe hypercalcemia can lead to mental status changes, bradycardia, and hypotension 1
• Always treat the underlying cause while managing the hypercalcemia itself
• Avoid medications that can worsen hypercalcemia (thiazides, lithium, excessive vitamin D)
• Monitor for nephrocalcinosis in patients with persistent hypercalcemia 1