How should a primary care physician treat hypercalcemia?

Treatment of Hypercalcemia in Primary Care

Primary care physicians should treat hypercalcemia with intravenous hydration using normal saline followed by bisphosphonates, with zoledronic acid 4mg being the preferred agent for moderate to severe cases. 1

Initial Assessment and Management Algorithm

Step 1: Assess Severity and Symptoms

• Mild hypercalcemia (< 12 mg/dL or < 3 mmol/L): Often asymptomatic, may have fatigue, constipation 2
• Moderate to severe hypercalcemia (≥ 12 mg/dL or ≥ 3 mmol/L): Nausea, vomiting, confusion, polyuria, polydipsia, dehydration 1
• Severe hypercalcemia (≥ 14 mg/dL or ≥ 3.5 mmol/L): Mental status changes, bradycardia, hypotension, requires urgent treatment 1, 2

Step 2: Diagnostic Evaluation

• Measure serum intact parathyroid hormone (iPTH), PTHrP, vitamin D metabolites, calcium, albumin, magnesium, and phosphorus 1
• Determine underlying cause: 90% of cases are due to primary hyperparathyroidism or malignancy 2

Treatment Protocol

For Mild Asymptomatic Hypercalcemia

• Oral hydration
• Address underlying cause
• Avoid medications that can worsen hypercalcemia (thiazide diuretics, calcium supplements)
• Monitor serum calcium levels

For Moderate to Severe Hypercalcemia

1. Hydration:

   • Intravenous normal saline to correct hypovolemia and promote calciuresis 1
   • Initial rate of 200-300 mL/hour, adjusted based on cardiovascular status
   • Continue until patient is euvolemic

2. Bisphosphonates:

   • First-line pharmacologic therapy for moderate to severe hypercalcemia 1
   • Zoledronic acid 4mg IV over 15 minutes is preferred (higher normalization rate of 50% by day 4 vs 33% with pamidronate) 1
   • Alternative: Pamidronate 90mg IV over 2 hours 1
   • Reserve zoledronic acid 8mg dose for refractory cases 1

3. Loop Diuretics:

   • Add furosemide after adequate volume repletion 1
   • Do not use in dehydrated patients

4. Calcitonin:

   • Consider for rapid but short-term reduction in severe symptomatic hypercalcemia 3, 4
   • Monitor for hypersensitivity reactions 3
   • Must correct hypocalcemia before initiating therapy 3

5. Denosumab:

   • Consider for hypercalcemia refractory to bisphosphonate therapy 1
   • Particularly useful in patients with renal impairment 2
   • Monitor for hypocalcemia after treatment 1

Special Considerations

Hypercalcemia of Malignancy

• More aggressive treatment often needed
• Higher normalization rates with zoledronic acid (50%) compared to pamidronate (33%) 1
• Poor prognosis (median survival ~1 month after discovery) 1

Renal Impairment

• Adjust bisphosphonate dosing
• Consider denosumab if severe renal impairment 1, 2
• Monitor renal function during treatment
• Discontinue bisphosphonates if unexplained albuminuria >500 mg/24 hours or serum creatinine increase >0.5 mg/dL 1

Vitamin D-Mediated Hypercalcemia

• Add glucocorticoids to treatment regimen for hypercalcemia due to:
  • Granulomatous disorders
  • Vitamin D intoxication
  • Some lymphomas 2, 5

Monitoring and Follow-up

• Monitor serum calcium, renal function, and electrolytes during treatment
• Check magnesium levels (hypomagnesemia can occur) 1
• Ensure adequate calcium and vitamin D intake after normalization of calcium levels 3
• Address underlying cause to prevent recurrence

Common Pitfalls to Avoid

• Do not use loop diuretics before adequate hydration
• Do not overlook monitoring for renal complications with bisphosphonates
• Do not fail to identify and treat the underlying cause
• Do not forget to discontinue medications that can worsen hypercalcemia
• Do not miss monitoring for hypocalcemia after denosumab treatment 1

Remember that while treating the acute hypercalcemia is important, identifying and addressing the underlying cause is essential for long-term management and preventing recurrence.