Management of Hypercalcemia with Hyperalbuminemia
The first step in managing a patient with hypercalcemia and hyperalbuminemia is to calculate the corrected calcium level to determine if true hypercalcemia exists, as elevated albumin can falsely elevate total calcium measurements. 1, 2
Calculating Corrected Calcium
- Calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) - 0.8 × [Albumin (g/dL) - 4] 1
- For this patient with total calcium of 10.9 mg/dL and albumin of 5.0 g/dL, the corrected calcium would be: 10.9 - 0.8 × (5.0 - 4.0) = 10.1 mg/dL 1
- Consider measuring ionized calcium as it is more accurate than calculated values, especially when albumin levels are abnormal 2, 3
Initial Diagnostic Workup
- Obtain fasting serum calcium (total and ionized) to confirm hypercalcemia, as non-fasting samples can lead to falsely elevated levels 3
- Measure intact parathyroid hormone (iPTH) to distinguish between PTH-dependent and PTH-independent causes 2
- Check 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 4
- Assess parathyroid hormone-related protein (PTHrP) if PTH is suppressed 2
- Measure serum phosphorus, magnesium, and renal function tests 4, 2
- Obtain urine calcium/creatinine ratio to evaluate for hypercalciuria 4
Differential Diagnosis Considerations
- Primary hyperparathyroidism (most common cause of hypercalcemia, ~90% of cases) 5
- Malignancy (second most common cause, particularly multiple myeloma, breast cancer, lymphoma) 5, 6
- Medication-induced hypercalcemia (thiazide diuretics, lithium, calcium or vitamin D supplements) 5, 6
- Granulomatous diseases (sarcoidosis, tuberculosis) 5
- Endocrinopathies (thyroid disorders, adrenal insufficiency) 5
- Multiple Endocrine Neoplasia syndromes (MEN1, MEN2) 1
- Hyperparathyroid-jaw tumor syndrome (consider if young patient) 1
Management Algorithm
For Mild Asymptomatic Hypercalcemia (corrected calcium <12 mg/dL):
- Ensure adequate hydration with oral fluids 4
- Discontinue medications that may contribute to hypercalcemia (thiazide diuretics, calcium supplements) 5
- Avoid dehydration and high calcium intake 7
- Monitor calcium levels regularly (every 2-3 months) 1, 7
For Moderate to Severe Symptomatic Hypercalcemia (corrected calcium ≥12 mg/dL):
- Administer IV crystalloid fluids (normal saline) to restore intravascular volume and enhance renal calcium excretion 4
- Consider bisphosphonate therapy (zoledronic acid or pamidronate) if hypercalcemia is severe or symptomatic 4, 5
- For refractory cases, consider denosumab, especially in patients with renal impairment 4
- For PTH-dependent hypercalcemia (primary hyperparathyroidism), consider cinacalcet starting at 30 mg twice daily, titrating every 2-4 weeks as needed to normalize calcium levels 8
For Primary Hyperparathyroidism:
- Refer for parathyroidectomy if patient meets surgical criteria: age <50 years, serum calcium >1 mg/dL above upper limit of normal, evidence of kidney or skeletal disease 5
- For patients not meeting surgical criteria, consider medical management and monitoring 5, 9
Follow-up and Monitoring
- For patients on medical management, monitor serum calcium approximately every 2 months 8
- Evaluate for complications of treatment, including renal toxicity with bisphosphonates and hypocalcemia with denosumab 4
- For patients with primary hyperparathyroidism who are being observed, monitor calcium, renal function, and bone mineral density regularly 9
Important Caveats
- Hyperalbuminemia can mask true calcium status; always calculate corrected calcium or measure ionized calcium 1, 3
- Blood samples for calcium measurement should be collected after fasting to avoid transient elevations from dietary intake 3
- Avoid prolonged venous stasis during blood collection as it can cause hemoconcentration and falsely elevated calcium levels 3
- Consider renal ultrasound if hypercalciuria is present to evaluate for nephrocalcinosis 4
- In CKD patients, interpret PTH levels with caution as secondary hyperparathyroidism can coexist with other causes of hypercalcemia 2