Hypercalcemia associated with infection by Cryptococcus neoformans and Coccidioides immitis.
Of the 13 reported cases of hypercalcemia associated with fungal infection, 1 was caused by Cryptococcus neoformans and probably mediated by increased levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. Eight others were associated with Coccidioides immitis, of which only 2 had measured 1,25(OH)2D levels; in both, they were diminished. We report a patient with human immunodeficiency virus infection and simultaneous C. immitis and C. neoformans pneumonia and C. immitis fungemia associated with hypercalcemia. Consecutive measurements of serum total and ionized calcium, phosphorous, blood urea nitrogen, creatinine, 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrp) and albumin were performed over a period of 46 months. While the patient was hypercalcemic, intact serum PTH and PTHrp were undetectable, serum 25(OH)D levels were normal, and serum 1,25(OH)2D levels were in the high normal range. Successful treatment of the C. immitis and C. neoformans infections resulted in resolution of the hypercalcemia and increase of PTH and PTHrp to the normal range. In some patients with HIV infection, coincident hypercalcemia, and severe fungal infection, the responsible factor may be 1,25(OH)2D. Although total serum levels of this compound may not be frankly elevated, they are inappropriately high for the circumstances. Free 1,25(OH)2D levels should be determined in this situation.