From the Research
To work up a patient with hypercalcemia due to elevated vitamin D levels, essential laboratory tests include serum calcium (total and ionized), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), phosphorus, magnesium, blood urea nitrogen (BUN), creatinine, and urinary calcium excretion. These tests help confirm hypercalcemia, determine vitamin D status, and assess end-organ damage. The 25-hydroxyvitamin D level is particularly important as it reflects overall vitamin D status and helps identify exogenous vitamin D toxicity, while 1,25-dihydroxyvitamin D may be elevated in granulomatous diseases or lymphomas 1. A suppressed PTH level is typically seen with vitamin D-mediated hypercalcemia, distinguishing it from primary hyperparathyroidism. Renal function tests are crucial since hypercalcemia can cause kidney injury, and urinary calcium helps assess calcium excretion.
Some key points to consider in the workup include:
- The mechanism of hypercalcemia, which can involve excessive intake of vitamin D, ectopic production of 1,25-dihydroxyvitamin D, or impaired degradation of 1,25-dihydroxyvitamin D 1
- The clinical features of vitamin D-mediated hypercalcemia, which can include hypercalciuria, nephrocalcinosis, and nephrolithiasis 1
- The importance of monitoring for end-organ damage, such as kidney injury, which can be assessed through renal function tests and urinary calcium excretion 2, 3
- The potential for granulomatous diseases, such as sarcoidosis or tuberculosis, to cause hypercalcemia through ectopic production of 1,25-dihydroxyvitamin D 1
Additional tests may include alkaline phosphatase to evaluate bone turnover, complete blood count, and serum protein electrophoresis if multiple myeloma is suspected. In cases where granulomatous diseases are considered, chest imaging and angiotensin-converting enzyme levels may be appropriate. The most recent and highest quality study, published in 2020, highlights the importance of considering the pathophysiology of hypercalcemia from vitamin D intoxication and the use of glucocorticoids and bisphosphonates in treatment 4.