What is the initial workup for a patient presenting with hypercalcemia?

Initial Workup for Hypercalcemia

The initial workup for a patient presenting with hypercalcemia should include serum intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, complete blood count, urinalysis, thyroid-stimulating hormone (TSH), liver function tests, and serum concentrations of calcium, albumin, magnesium, and phosphorus. 1

Confirming Hypercalcemia

1. Calculate albumin-corrected calcium to confirm hypercalcemia using the formula:

   • Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
   • Hypercalcemia is defined as calcium levels exceeding 10.2 mg/dL

2. Assess severity of hypercalcemia:

   • Mild: Total calcium <12 mg/dL (<3 mmol/L)
   • Severe: Total calcium ≥14 mg/dL (≥3.5 mmol/L) 2

Essential Laboratory Tests

First-line Tests

• Serum intact parathyroid hormone (iPTH) - most important initial test 1, 2
• Complete blood count
• Serum calcium and albumin
• Serum phosphorus
• Serum magnesium
• Blood urea nitrogen and creatinine
• Urinalysis
• Liver function tests
• Thyroid-stimulating hormone (TSH) 3, 1

Second-line Tests (Based on Clinical Suspicion)

• Parathyroid hormone-related protein (PTHrP)
• 25-hydroxyvitamin D
• 1,25-dihydroxyvitamin D
• Serum protein electrophoresis (if multiple myeloma suspected)
• Tests for granulomatous diseases (if clinically indicated) 1

Diagnostic Algorithm

1. Determine if PTH-dependent or PTH-independent:

   • Elevated or inappropriately normal PTH → Primary hyperparathyroidism
   • Suppressed PTH (<20 pg/mL) → Consider other causes 2

2. If PTH is suppressed, evaluate for:

   • Malignancy (check PTHrP, consider chest X-ray, mammogram, etc.)
   • Vitamin D toxicity (check 25-hydroxyvitamin D levels)
   • Granulomatous disorders (check 1,25-dihydroxyvitamin D)
   • Medication-induced (review medication list for thiazides, lithium, etc.)
   • Endocrinopathies (check thyroid function) 1, 2

3. If PTH is elevated or inappropriately normal, evaluate for:

   • Primary hyperparathyroidism (most common cause in outpatients)
   • Familial hypocalciuric hypercalcemia (check urine calcium)
   • Tertiary hyperparathyroidism (in patients with chronic kidney disease) 2, 4

Special Considerations

• In patients with malignancy: Evaluate for bone metastases, multiple myeloma, and humoral hypercalcemia of malignancy 2
• In patients with renal impairment: Adjust interpretation of laboratory values and consider tertiary hyperparathyroidism 1
• In patients with recent bariatric surgery: Consider calcium and vitamin D malabsorption 1

Common Pitfalls to Avoid

1. Failing to correct calcium for albumin - This can lead to misdiagnosis of hypercalcemia 1
2. Treating laboratory values without addressing the underlying cause - The primary cause must be identified for proper management 1
3. Initiating diuretics before correcting hypovolemia - This can worsen hypercalcemia 1
4. Overlooking medication-induced causes - Review all medications including supplements 1
5. Relying solely on total calcium without measuring ionized calcium in critically ill patients 5

Treatment Considerations

While not the focus of the initial workup, severe symptomatic hypercalcemia (>14 mg/dL) may require urgent treatment:

1. Aggressive IV fluid resuscitation with normal saline (200-300 mL/hour initially)
2. Bisphosphonates (e.g., zoledronic acid 4 mg IV) after adequate hydration
3. Calcitonin for immediate short-term management of severe symptomatic hypercalcemia 1, 6, 7

Remember that approximately 90% of hypercalcemia cases are due to primary hyperparathyroidism or malignancy, making these the most important conditions to rule out in your initial evaluation 2.