What is the treatment for hypercalcemia and elevated albumin levels?

Treatment of Hypercalcemia with Elevated Albumin

When both calcium and albumin are elevated, you must first calculate the corrected calcium to determine if true hypercalcemia exists, then treat based on severity using IV hydration and bisphosphonates as first-line therapy.

Critical First Step: Correct for Albumin

• Always calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × (4.0 - albumin [g/dL]) 1, 2, 3
• For a patient with elevated albumin (e.g., 5.0 g/dL) and total calcium of 10.9 mg/dL, the corrected calcium would be: 10.9 + 0.8 × (4.0 - 5.0) = 10.1 mg/dL, which is actually normal 2
• Hyperalbuminemia can mask true calcium status—the corrected value may reveal normocalcemia despite elevated total calcium 2, 4
• If corrected calcium is normal, no treatment for hypercalcemia is needed; investigate the cause of hyperalbuminemia instead 2
• Alternatively, measure ionized calcium directly for the most accurate assessment 1, 5

If True Hypercalcemia Exists After Correction

Severity Classification and Initial Workup

• Classify severity: mild (10-11 mg/dL), moderate (11-12 mg/dL), or severe (>14 mg/dL) 1, 2
• Obtain comprehensive labs: serum calcium, albumin, intact PTH, PTHrP, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, phosphorus, magnesium, creatinine, and BUN 6, 1
• Assess for symptoms: polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain in moderate cases; mental status changes, bradycardia, hypotension in severe cases 6, 1, 2

Immediate Treatment Algorithm

For moderate to severe hypercalcemia (corrected calcium ≥11 mg/dL):

• Start IV normal saline hydration immediately to correct hypovolemia and promote calciuresis, targeting urine output ≥100 mL/hour 1, 3
• Vigorous saline hydration is an integral part of therapy; restore urine output to approximately 2 L/day 3
• Administer IV bisphosphonates after starting hydration—zoledronic acid 4 mg is preferred over pamidronate, given as a single infusion over at least 15 minutes 1, 3
• Add calcitonin for immediate short-term management of severe symptomatic hypercalcemia while waiting for bisphosphonates to take effect (onset 2-4 hours vs. 2-4 days for bisphosphonates) 1
• Use loop diuretics (furosemide) only after volume repletion in patients with renal or cardiac insufficiency to prevent fluid overload 6, 1, 3

For mild hypercalcemia (corrected calcium 10-11 mg/dL):

• Oral hydration may be sufficient for asymptomatic cases 6, 2
• Monitor calcium levels every 2-3 months 2

Cause-Specific Management

Determine the etiology to guide definitive treatment:

• Malignancy-associated hypercalcemia (PTHrP elevated, PTH suppressed): Bisphosphonates are first-line; treat underlying malignancy when possible 6, 1, 7, 3
• For refractory cases or renal impairment: Denosumab 120 mg subcutaneously 1, 7, 8
• Primary hyperparathyroidism (PTH elevated or inappropriately normal): Parathyroidectomy is definitive treatment for symptomatic disease, osteoporosis, impaired kidney function, kidney stones, age <50 years, or calcium >0.25 mmol/L above upper normal 1, 7
• Vitamin D-mediated hypercalcemia (elevated 1,25-dihydroxyvitamin D in granulomatous diseases/lymphomas, or elevated 25-hydroxyvitamin D in intoxication): Glucocorticoids are the primary treatment 6, 1, 7

Critical Monitoring and Pitfalls

• Monitor serum creatinine before each bisphosphonate dose—dose adjustments not needed for mild-moderate renal impairment (creatinine <4.5 mg/dL), but careful monitoring essential 3
• Watch for bisphosphonate complications: renal toxicity and osteonecrosis of the jaw with chronic use 1, 2
• Avoid overhydration in patients with cardiac failure 3
• Do not use diuretics before correcting hypovolemia 3
• If retreatment needed, allow minimum 7 days between doses 3
• Avoid vitamin D supplements in patients with hypercalcemia 1, 7

Special Consideration for Hyperalbuminemia

• The standard correction formula may be unreliable in some cases—recent evidence suggests locally derived formulas may improve accuracy 5
• When albumin is significantly elevated (>5.0 g/dL), consider measuring ionized calcium to avoid treatment errors 5, 9
• Three patients in one study had significant hypercalcemia masked by hypoalbuminemia, but the reverse (pseudohypercalcemia from hyperalbuminemia) is equally important to recognize 9