How to manage a patient with hypercalcemia?

Management of Hypercalcemia

The initial management of hypercalcemia should include aggressive IV normal saline hydration to restore extracellular volume, promote calciuresis, and target urine output of at least 100 mL/hour, followed by bisphosphonate therapy with zoledronic acid 4 mg IV as the first-line pharmacological treatment. 1

Diagnostic Evaluation

1. Initial laboratory assessment:

   • Measure serum intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), vitamin D metabolites, calcium, albumin, magnesium, and phosphorus 1
   • PTH level is crucial for distinguishing between PTH-dependent (elevated/normal PTH) and PTH-independent (suppressed PTH) causes 2

2. Identify underlying cause:

   • Primary hyperparathyroidism and malignancy account for ~90% of hypercalcemia cases 2
   • Other causes include granulomatous diseases, medications (thiazides), vitamin supplements, endocrinopathies 2

Treatment Algorithm

Step 1: Assess Severity and Symptoms

• Mild hypercalcemia (Ca <12 mg/dL): Often asymptomatic, may not require acute intervention 2
• Severe hypercalcemia (Ca ≥14 mg/dL) or symptomatic: Requires immediate treatment 2
• Symptoms to monitor: Fatigue, weakness, GI symptoms, polyuria, polydipsia, renal injury, cardiac arrhythmias, QT interval changes 1

Step 2: Initial Management

1. Hydration:

   • Aggressive IV normal saline to restore volume and promote calciuresis 1
   • Target urine output of at least 100 mL/hour 1

2. For severe or symptomatic hypercalcemia:

   • First-line pharmacological treatment: Zoledronic acid 4 mg IV over 15 minutes 1
   • Alternative: Pamidronate 90 mg IV over 2 hours 1
   • For rapid, short-term effect: Calcitonin 4 International Units/kg body weight every 12 hours by subcutaneous or intramuscular injection 3
     • May increase to 8 International Units/kg every 12 hours if response is inadequate 3
     • Maximum dose: 8 International Units/kg every 6 hours 3

Step 3: Management of Refractory Cases

• For bisphosphonate-refractory hypercalcemia:

  • Consider denosumab (subcutaneous), especially in patients with severe renal impairment 1
  • Lowers serum calcium in 64% of patients within 10 days 1

• For hypercalcemia due to vitamin D intoxication, granulomatous disorders, or lymphomas:

  • Consider glucocorticoids 2, 4

• For patients with kidney failure:

  • Consider denosumab and dialysis 2

Monitoring and Follow-up

1. Regular monitoring:

   • Serum calcium, phosphorus, magnesium, and renal function 1
   • ECG for QT interval changes and arrhythmias 1

2. Calcium and vitamin D supplementation:

   • For patients on long-term treatment, ensure adequate calcium (at least 1000 mg elemental calcium per day) and vitamin D (at least 400 International Units per day) 3

3. Monitor for hypocalcemia:

   • Particularly after denosumab treatment 1

Common Pitfalls to Avoid

1. Inadequate hydration before administering bisphosphonates 1
2. Overlooking renal function when dosing bisphosphonates 1
3. Not monitoring for hypocalcemia after treatment, especially with denosumab 1
4. Delaying treatment of severe hypercalcemia while awaiting complete diagnostic workup 1
5. Treating the laboratory value without addressing the underlying cause 1

Special Considerations

• Cardiac disease: Optimize heart failure management before surgery; continue beta-blockers through perioperative period 1
• Diabetes: Maintain perioperative glycemic control (glucose <180 mg/dL); consider insulin infusion protocol; discontinue SGLT2 inhibitors before surgery 1
• Renal dysfunction: Adjust bisphosphonate dosing based on renal function 1
• Primary hyperparathyroidism: Consider parathyroidectomy based on age, calcium level, and evidence of end-organ damage 2

By following this structured approach to hypercalcemia management, focusing on prompt hydration and appropriate pharmacological intervention, you can effectively reduce serum calcium levels and prevent complications while addressing the underlying cause.