Does a 58-year-old patient with serum calcium 10.6 mg/dL, albumin 5.2 g/dL and total protein 8.2 g/dL have true hypercalcemia, and what is the appropriate management?

Corrected Calcium Assessment and Clinical Significance

This Patient Does NOT Have True Hypercalcemia

The measured calcium of 10.6 mg/dL is falsely elevated due to marked hemoconcentration (albumin 5.2 g/dL, total protein 8.2 g/dL), and when corrected for the elevated albumin, the true calcium status is normal. 1, 2

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Corrected Calcium Calculation

Using the standard correction formula 1:

Corrected Calcium = 10.6 + 0.8 × [4.0 - 5.2] = 9.64 mg/dL

This falls well within the normal range of 8.6-10.3 mg/dL 1. The apparent hypercalcemia is entirely artifactual, caused by the elevated albumin concentration increasing protein-bound calcium without affecting physiologically active ionized calcium 3, 4.

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Why This Matters Clinically

Understanding the Physiology

• Approximately 40% of total serum calcium is bound to albumin, 48% exists as free (ionized) calcium, and 12% is complexed with anions 1
• When albumin rises above normal (as in this case with albumin 5.2 g/dL), more calcium binding sites become available, artificially elevating total calcium measurements without increasing the biologically active ionized fraction 3, 4
• The ionized calcium—which determines clinical symptoms and physiologic effects—remains normal in this scenario 1, 2

Critical Limitation of Correction Formulas

• Albumin correction formulas become increasingly unreliable when albumin exceeds 4.0 g/dL, systematically underestimating true calcium status and potentially masking real hypercalcemia 4
• Studies demonstrate that correction formulas can lead to errors of -0.20 mmol/L when albumin values exceed 44 g/L (4.4 g/dL) 4
• In patients with albumin >4.0 g/dL, correction formulas may fail to detect true hypercalcemia in up to 50% of cases 4

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Recommended Management Approach

Immediate Next Step

Measure ionized calcium directly to definitively establish true calcium status, as this is the gold standard and bypasses all albumin-related artifacts 1, 2, 5. Normal ionized calcium ranges from 4.65-5.28 mg/dL (1.16-1.32 mmol/L) 1.

If Ionized Calcium Cannot Be Measured Immediately

• Recognize that the corrected calcium of 9.64 mg/dL strongly suggests normocalcemia, making urgent intervention unnecessary 1, 2
• Investigate the cause of hemoconcentration (albumin 5.2 g/dL, total protein 8.2 g/dL): assess hydration status, recent fluid losses, or conditions causing relative plasma volume contraction 6
• Repeat total calcium and albumin measurements after addressing any volume depletion to confirm stability 1

Clinical Context Assessment

At age 58 with these laboratory values, consider:

• Dehydration or volume contraction as the most likely cause of elevated albumin and total protein 6
• Rule out spurious elevation from prolonged tourniquet application during phlebotomy (can falsely elevate protein-bound calcium) 1
• If corrected calcium remains >10.2 mg/dL on repeat testing, measure intact PTH to distinguish PTH-dependent (primary hyperparathyroidism) from PTH-independent causes 7, 2

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Common Pitfalls to Avoid

1. Do not treat based on uncorrected total calcium when albumin is abnormal—this leads to unnecessary interventions in 44% of cases with elevated albumin 5, 4

2. Do not assume correction formulas are accurate when albumin exceeds 4.0 g/dL—they systematically underestimate calcium and may miss true hypercalcemia 4

3. Do not order parathyroid imaging or extensive hypercalcemia workup before confirming biochemical abnormality with ionized calcium or properly corrected values 7

4. Do not overlook the total protein value (8.2 g/dL)—this confirms hemoconcentration and supports the interpretation that elevated total calcium is artifactual 6

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When to Pursue Hypercalcemia Workup

Only if any of the following are present:

• Ionized calcium >5.28 mg/dL (>1.32 mmol/L) 1
• Corrected calcium persistently >10.3 mg/dL after rehydration 1, 2
• Clinical symptoms of hypercalcemia: polyuria, polydipsia, nausea, confusion, constipation, or bone pain 7, 2
• Albumin normalizes but total calcium remains elevated 1

If true hypercalcemia is confirmed, measure intact PTH as the single most important initial test to distinguish primary hyperparathyroidism (PTH elevated or inappropriately normal) from malignancy-associated or other causes (PTH <20 pg/mL) 7, 2.