Hypercalcemia due to endogenous overproduction of 1,25-dihydroxyvitamin D in Crohn's disease

Hypercalcemia may occur in various granulomatous diseases. Two patients with Crohn's disease who had hypercalcemia, hypercalciuria, and excessively high serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] are described. Both had numerous noncaseating, epithelioid granulomas in bowel biopsy samples. A direct correlation was observed between serum 1,25(OH)2D levels and both serum and urinary calcium concentrations. Also, calcium and 1,25(OH)2D levels strongly paralleled the clinical activity of disease. Prompt therapy with prednisone in the patient who had symptomatic hypercalcemia and with prednisone and mesalamine in the other patient without hypercalcemic symptoms led to normalization of calcium and serum 1,25(OH)2D levels, but 25-hydroxyvitamin D [25(OH)D] levels remained unchanged. Four months after discharge, recurrence of Crohn's disease symptomatology together with an increase in calcium and serum 1,25(OH)2D levels was observed in 1 patient; after increasing the prednisone dose, levels decreased and rapid clinical resolution was noted. These cases appear to be the first reported instances of hypercalcemia in patients with Crohn's disease. Excessive synthesis of 1,25(OH)2D may have been inhibited by an action of corticosteroids on the 1alpha-hydroxylation of 25(OH)D in the activated macrophage of Crohn's granulomas. Crohn's disease should be added to the list of granulomatous diseases responsible for 1,25(OH)2D-mediated hypercalcemia.