What investigations are needed for a 75-year-old female with severe hypercalcemia?

Management of Severe Hypercalcemia in a 75-Year-Old Female

For a 75-year-old female with severe hypercalcemia (15.8 mg/dL), immediate diagnostic workup must include measurement of intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels to determine the underlying cause, while simultaneously initiating aggressive IV fluid resuscitation with normal saline. 1

Initial Diagnostic Workup

Essential Laboratory Tests

• Intact parathyroid hormone (iPTH) - crucial to distinguish between PTH-dependent and PTH-independent causes 1
• Parathyroid hormone-related protein (PTHrP) - to evaluate for malignancy-associated hypercalcemia 1
• Complete blood count
• Serum electrolytes including:
  • Albumin (for corrected calcium calculation)
  • Magnesium
  • Phosphorus
• Renal function tests (BUN, creatinine)
• Liver function tests
• Thyroid-stimulating hormone (TSH)
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 1
• Urinalysis and urine calcium-to-creatinine ratio

Additional Investigations Based on Clinical Suspicion

• Serum and urine protein electrophoresis (to evaluate for multiple myeloma)
• Chest X-ray (to evaluate for malignancy or granulomatous disease)
• Bone scan or skeletal survey (if metastatic bone disease suspected)
• CT scan of chest/abdomen/pelvis (to evaluate for occult malignancy)
• Sestamibi scan (if primary hyperparathyroidism suspected) 2

Management Approach

Immediate Management

1. Aggressive IV fluid resuscitation with normal saline (typically 200-300 mL/hour initially) to correct hypovolemia and promote calciuresis 1
2. Monitor vital signs, cardiac rhythm, and neurological status due to risk of cardiac arrhythmias and altered mental status
3. Monitor serum calcium, electrolytes, and renal function every 6-12 hours initially 1

Pharmacological Management

1. Bisphosphonates - First-line pharmacological therapy for severe hypercalcemia:

   • Zoledronic acid 4 mg IV over 15 minutes (preferred due to higher efficacy) 1, 3
   • Note: Zoledronic acid normalizes calcium in 50% of patients by day 4 1
   • Caution: Monitor renal function before administration; adjust dosing in renal impairment 3

2. Calcitonin - For immediate short-term management while awaiting bisphosphonate effect:

   • 4-8 IU/kg subcutaneously or intramuscularly every 12 hours 1
   • Note: Tachyphylaxis develops within 48-72 hours

3. Denosumab - For patients with severe renal impairment or refractory hypercalcemia:

   • 120 mg subcutaneously, with additional doses on days 8 and 15 of the first month 1

4. Glucocorticoids - If hypercalcemia is suspected to be due to vitamin D toxicity, granulomatous disorders, or certain lymphomas:

   • Prednisone 40-60 mg/day or equivalent 1

5. Loop diuretics - Only after adequate hydration to enhance calcium excretion:

   • Furosemide 20-40 mg IV every 12 hours 1, 4

Monitoring During Treatment

• Serum calcium, phosphate, magnesium every 6-12 hours initially, then daily
• Renal function and electrolytes daily
• Fluid input/output
• Cardiac monitoring if severe hypercalcemia (>14 mg/dL) 1

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia 1
• Failing to correct calcium for albumin 1
• Inadequate hydration before bisphosphonate administration 1
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia 1
• Administering bisphosphonates too rapidly (increased risk of renal toxicity) 3
• Failing to monitor for hypocalcemia after treatment, especially with denosumab 1

Prognosis

• Prognosis depends on the underlying cause
• Malignancy-associated hypercalcemia has a poor prognosis with median survival of about 1 month in lung cancer patients 1
• Primary hyperparathyroidism has excellent prognosis with either medical or surgical management 2
• Hypercalcemic crisis has a 3-year survival rate of approximately 80% in patients with primary hyperparathyroidism 4

Remember that identifying and treating the underlying cause is essential for long-term management of hypercalcemia, while the immediate focus must be on lowering calcium levels to prevent life-threatening complications.