What is the next step in evaluating a patient with hypercalcemia and a calcium level of 10.9?

Evaluation of Calcium Level 10.9 mg/dL

Measure serum intact parathyroid hormone (PTH) immediately—this is the single most important test to determine whether hypercalcemia is PTH-dependent (primary hyperparathyroidism) or PTH-independent (malignancy or other causes). 1

Initial Diagnostic Approach

A calcium level of 10.9 mg/dL represents mild hypercalcemia (defined as total calcium <12 mg/dL), which is typically asymptomatic but requires evaluation to identify the underlying cause. 1 Primary hyperparathyroidism and malignancy account for more than 90% of all hypercalcemia cases. 1, 2

Key Distinguishing Test: PTH Level

• Elevated or normal PTH (typically >20 pg/mL depending on assay): Indicates PTH-dependent hypercalcemia, most consistent with primary hyperparathyroidism 1
• Suppressed PTH (<20 pg/mL): Indicates PTH-independent hypercalcemia, suggesting malignancy, granulomatous disease, medications, or other non-parathyroid causes 1

Additional Laboratory Tests to Order Concurrently

Beyond PTH, obtain the following tests to complete the initial evaluation:

• Serum albumin: To calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4.0 - Serum albumin (g/dL)] 3
• Ionized calcium: Provides the most accurate assessment of true hypercalcemia, as total calcium can be falsely low with hypoalbuminemia 3, 4
• 25-hydroxyvitamin D: To assess for vitamin D intoxication or deficiency 1
• Serum creatinine and BUN: To evaluate renal function, as hypercalcemia can cause renal impairment 3, 2
• Serum phosphorus: Helps differentiate causes (low in hyperparathyroidism, variable in malignancy) 3
• Serum magnesium: Magnesium abnormalities can affect calcium homeostasis 3

Clinical Context Matters

If PTH is Elevated or Normal (Primary Hyperparathyroidism)

Primary hyperparathyroidism typically presents with:

• Calcium levels <12 mg/dL 2
• Duration of hypercalcemia >6 months 2
• Fewer and more subtle symptoms 2
• Possible kidney stones and hyperchloremic metabolic acidosis 2
• No anemia 2

If PTH is Suppressed (Non-Parathyroid Causes)

Consider malignancy-associated hypercalcemia, which typically shows:

• Rapid onset with higher calcium levels 2
• More severe symptoms 2
• Marked anemia 2
• No kidney stones or metabolic acidosis 2

Additional PTH-independent causes include granulomatous diseases (sarcoidosis), endocrinopathies, medications (thiazide diuretics, calcium/vitamin D supplements), and immobilization. 1

Management Considerations at This Calcium Level

At 10.9 mg/dL, this represents mild hypercalcemia that usually does not require acute intervention. 1 However, the K/DOQI guidelines define hypercalcemia as calcium >10.2 mg/dL, so adjustments may be warranted depending on the underlying cause and patient context. 5

If Taking Calcium-Raising Medications

• Discontinue or reduce calcium-based phosphate binders 5
• Reduce or discontinue vitamin D supplementation 5
• Ensure total elemental calcium intake (diet + supplements) does not exceed 2,000 mg/day 5

Common Pitfalls to Avoid

• Do not rely on total calcium alone without checking albumin or ionized calcium, as hypoalbuminemia can falsely lower total calcium values 4
• Do not delay PTH measurement, as it is the critical branch point in the diagnostic algorithm 1
• Do not assume asymptomatic hypercalcemia is benign—approximately 20% of patients with mild hypercalcemia have constitutional symptoms like fatigue and constipation 1
• Do not overlook medication review, particularly thiazide diuretics, calcium supplements, vitamin D, and newer agents like SGLT2 inhibitors or immune checkpoint inhibitors 1