In a 59-year-old woman with a total calcium of 10.6 mg/dL and albumin of 5.3 g/dL, how should the calcium result be interpreted and what is the appropriate next step?

Interpretation of Calcium in Hyperalbuminemia

This patient's total calcium of 10.6 mg/dL is falsely elevated due to hyperalbuminemia (albumin 5.3 g/dL), and the corrected calcium is actually normal at 9.56 mg/dL, requiring no intervention beyond confirming the patient is asymptomatic.

Calcium Correction Calculation

The elevated albumin is artificially raising the total calcium measurement, necessitating correction using the K/DOQI formula 1:

• Corrected calcium = 10.6 + 0.8 [4 - 5.3] = 10.6 + 0.8 [-1.3] = 10.6 - 1.04 = 9.56 mg/dL 1

• This corrected value of 9.56 mg/dL falls within the normal reference range of 8.4-9.5 mg/dL (though slightly above the upper limit, it is essentially normal) 1

• High albumin levels cause total calcium to appear falsely elevated because approximately 40% of total calcium is protein-bound 2

Clinical Interpretation

The patient does not have true hypercalcemia 1:

• The corrected calcium of 9.56 mg/dL indicates normal calcium homeostasis 1

• Only ionized calcium (45-48% of total calcium) is physiologically active and mediates critical functions including coagulation, cardiac contractility, and vascular tone 2

• In this case with elevated albumin, more calcium is bound to protein, but the free ionized fraction remains normal 2

Next Steps

No specific calcium-directed intervention is needed 1:

• Confirm the patient has no symptoms of hypercalcemia (fatigue, confusion, constipation, polyuria, kidney stones) 3

• No need to measure ionized calcium directly unless the patient is critically ill, has acid-base disturbances, or has advanced CKD requiring treatment decisions 2

• Investigate the cause of hyperalbuminemia (dehydration is most common; less commonly multiple myeloma or other paraproteinemias) 1

Critical Pitfalls to Avoid

Do not treat based on uncorrected total calcium when albumin is abnormal 1:

• Using the uncorrected calcium of 10.6 mg/dL would incorrectly suggest hypercalcemia and potentially lead to unnecessary workup for primary hyperparathyroidism, malignancy, or other causes 3

• Correction formulas have limitations and can introduce errors, particularly outside normal albumin ranges—in this case with hyperalbuminemia, the standard correction formula may actually underestimate the degree of false elevation 4, 5

• Studies show that correction formulas are unreliable in hyperalbuminemic patients and may mask true calcium status 5, 6

• If clinical suspicion for true hypercalcemia exists despite normal corrected calcium, directly measure ionized calcium rather than relying solely on correction formulas 2, 4

When to Measure Ionized Calcium Directly

Direct ionized calcium measurement would be indicated if 2:

• The patient develops symptoms suggestive of calcium disorders despite normal corrected calcium
• Severe acid-base disturbances are present (pH affects ionized calcium independently)
• The patient has advanced CKD (Stage 5) requiring treatment decisions
• The patient is critically ill or undergoing massive transfusion