What is the initial step in managing a patient with hypercalcemia?

Hypercalcemia Work-Up

Initial Diagnostic Step

The initial step in managing hypercalcemia is to obtain serum calcium, albumin, and intact parathyroid hormone (iPTH) levels, followed by immediate IV normal saline hydration if the patient is symptomatic or severely hypercalcemic. 1, 2

Comprehensive Laboratory Evaluation

The diagnostic workup should include the following laboratory tests to determine the underlying etiology:

• Serum calcium and albumin to calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) - 0.8 × [Albumin (g/dL) - 4] 1, 2
• Intact parathyroid hormone (iPTH) - this is the single most important test to differentiate PTH-dependent from PTH-independent causes 2, 3
• Parathyroid hormone-related protein (PTHrP) if PTH is suppressed, to evaluate for malignancy-associated hypercalcemia 1, 2
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to assess for vitamin D-mediated hypercalcemia 1, 2
• Serum phosphorus, magnesium, blood urea nitrogen, and creatinine to evaluate renal function and electrolyte status 1, 2

Severity Classification

Classify the severity to guide urgency of intervention:

• Mild hypercalcemia: 10-11 mg/dL (>5.0 to <5.5 mEq/L) - typically asymptomatic but may have fatigue and constipation 1, 2, 3
• Moderate hypercalcemia: 11-12 mg/dL (5.5 to 6.0 mEq/L) - presents with polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain 1, 2
• Severe hypercalcemia: >14 mg/dL (>6.0 mEq/L) - associated with mental status changes, bradycardia, hypotension, dehydration, acute renal failure 1, 2, 3

Interpretation of PTH Results

The iPTH level is the critical branch point in the diagnostic algorithm:

• Elevated or inappropriately normal iPTH indicates primary hyperparathyroidism, characterized by hypophosphatemia and hyperchloremic metabolic acidosis 2, 4, 5
• Suppressed iPTH (<20 pg/mL) indicates PTH-independent causes and requires further workup with PTHrP, vitamin D metabolites, and evaluation for malignancy 2, 3, 5

Etiology-Specific Patterns

Primary hyperparathyroidism:

• Elevated or inappropriately normal PTH with hypercalcemia 2, 4
• Hypophosphatemia and hyperchloremic metabolic acidosis 2
• Typically mild hypercalcemia (<12 mg/dL) with duration >6 months 5
• May present with kidney stones but no anemia 5

Malignancy-associated hypercalcemia:

• Suppressed PTH with elevated PTHrP (humoral hypercalcemia of malignancy) 2, 4
• Rapid onset with higher calcium levels (often >12 mg/dL) 2, 5
• Marked anemia present, but no kidney calculi or metabolic acidosis 5
• Low or normal 1,25-dihydroxyvitamin D 2

Vitamin D-mediated hypercalcemia:

• Suppressed PTH with elevated 1,25-dihydroxyvitamin D in granulomatous diseases (sarcoidosis) or lymphomas 2, 4
• Elevated 25-hydroxyvitamin D in vitamin D intoxication 2, 4

Common Pitfalls to Avoid

• Do not rely on total calcium alone - hyperalbuminemia can mask true calcium status; always calculate corrected calcium or measure ionized calcium directly 1, 2
• Do not restrict calcium intake without medical supervision in patients with normocalcemia 1
• Avoid NSAIDs and intravenous contrast media in patients with renal impairment to prevent worsening renal function 1
• Do not delay bisphosphonate administration in moderate to severe hypercalcemia while waiting for complete workup - initiate hydration and bisphosphonates after starting IV fluids 1, 2