Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis

Hypercalcemia may occur during the course of various granuloma-forming diseases. Herein we describe a patient who had symptomatic hypercalcemia as a prominent sign of Wegener's granulomatosis. We observed a direct correlation between the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] and both the serum and the urinary calcium levels. Administration of prednisone and cyclophosphamide led to a substantial decrease in the levels of calcium and serum 1,25(OH)2D, but the serum levels of 25-hydroxyvitamin D remained unchanged. Two months after admission of the patient, the levels of calcium and 1,25(OH)2D increased; after we increased the dose of cyclophosphamide, these levels decreased (the dose of corticosteroids was not changed). We suggest that the excessive synthesis of 1,25(OH)2D was inhibited by a direct or indirect action not only of prednisone but also of cyclophosphamide on the 1 alpha-hydroxylation of 25-hydroxyvitamin D in the activated macrophage of Wegener granulomas. Furthermore, in view of this case and two other recently reported cases, we believe that Wegener's granulomatosis must be definitively added to the list of granulomatous diseases that are responsible for 1,25(OH)2D-mediated hypercalcemia.