Initial Workup for Hypercalcemia

First-line Laboratory Tests

The initial workup for a patient presenting with hypercalcemia should include measurement of intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, albumin, magnesium, and phosphorus levels to determine the underlying cause 1, 2, 3
Serum calcium (total and ionized) should be measured to confirm and quantify the severity of hypercalcemia 1, 3
Albumin level should be measured to correct for calcium binding 3
Intact parathyroid hormone (iPTH) is the most important initial test to differentiate PTH-dependent from PTH-independent causes 2
Serum phosphorus level should be measured, as it is typically low in primary hyperparathyroidism and high in vitamin D toxicity 1, 3
Serum creatinine and blood urea nitrogen should be measured to assess renal function 1, 4
25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels should be measured 1, 3
Parathyroid hormone-related protein (PTHrP) should be measured if malignancy is suspected 1, 3
Magnesium level should be measured 3

Patients with hypercalcemia should be evaluated for symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia, dehydration, and mental status changes 1, 3

Elevated or normal PTH with hypercalcemia suggests primary hyperparathyroidism 2
Suppressed PTH (<20 pg/mL) suggests non-PTH mediated causes (malignancy, vitamin D toxicity, granulomatous disease) 2

If PTH is suppressed, PTHrP measurement should be performed to evaluate for humoral hypercalcemia of malignancy 1, 3
If PTH is suppressed, chest X-ray and age-appropriate cancer screening should be performed 1, 3
If PTH is suppressed, 1,25-dihydroxyvitamin D level should be measured if granulomatous disease is suspected 1, 3
If PTH is elevated or normal, renal ultrasound should be performed to assess for nephrocalcinosis or nephrolithiasis 4, 5
If PTH is elevated or normal, bone mineral density testing should be performed 4, 5

For patients with malignancy, the diagnostic evaluation should be expedited as hypercalcemia may indicate advanced disease with poor prognosis (median survival approximately 1 month after discovery of hypercalcemia in lung cancer) 1, 3
Urine calcium/creatinine ratio should be obtained if hypercalciuria is suspected 4, 5
Rare causes such as granulomatous diseases, thyroid disorders, or adrenal insufficiency should be considered 1, 3