1,25-dihydroxyvitamin D3 is converted to calcitroic acid before being excreted in the bile. Biosynthesis of calcitroic acid has been demonstrated in two target cells of vitamin D, in the kidney and the osteoblastic cell line UMR-106. Calcitroic acid was identified by combinations of h.p.l.c., u.v. spectroscopy and mass spectrometry. Evidence is presented that calcitroate is derived from the 24-oxidation pathway, possibly through the intermediate 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3. The 24-oxidation pathway to calcitroic acid in bone cells is stimulated by 1,25-dihydroxyvitamin D3. The pathway in both bone cells and perfused kidney operates at physiological concentrations of substrate and appears to be capable of rapid clearance of the hormone.

Although corticosteroids are effective in the treatment of hypercalciuria and hypercalcemia in chronic sarcoidosis, complications of their long-term use frequently limit therapy. We studied the efficacy of chloroquine in two patients with sarcoidosis who were unable to tolerate the dosage of corticosteroids required to control hypercalciuria and prevent the formation of renal stones. Over a three-year period, each patient received a 6-month and a 10-month course of oral chloroquine phosphate (500 mg per day) while continuing to receive corticosteroids at a fixed dose. Chloroquine therapy was associated with a significant reduction in levels of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and urinary calcium. We observed a direct correlation between serum 1,25-(OH)2D levels and 24-hour urinary calcium excretion, supporting the hypothesis that excessive serum 1,25-(OH)2D is responsible for the hypercalciuria in sarcoidosis. Serum levels of 25-hydroxyvitamin D (25-(OH)D) did not change with therapy, suggesting that chloroquine may act by inhibiting the conversion of 25-(OH)D to 1,25-(OH)2D. Current dosage guidelines and ophthalmologic-surveillance techniques, which allow chloroquine to be administered with little risk of retinopathy, should permit an expanded role for this agent in the treatment of the calcium abnormalities of sarcoidosis.

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