Evidence for abnormal regulation of circulating 1α,25-dihydroxyvitamin D in patients with sarcoidosis and normal calcium metabolism

The effects of vitamin D, 2.5 mg (100,000 U)/d for 4 d, on serum calcium, serum 25-hydroxyvitamin D (25-OHD), and serum 1α,25-dihydroxyvitamin D [1α,25(OH)₂D] were compared in 17 normal subjects and 6 patients with sarcoidosis who had normocalcemia and no history of hypercalcemia. The diagnosis was confirmed histologically in each of them. Vitamin D increased mean serum 25-OHD from 30±4 to 99±15 ng/ml (P < 0.001) and did not change mean serum 1α,25(OH)₂D (32±3 vs. 29±3 pg/ml) or mean serum calcium (9.5±0.1 vs. 9.6±0.1 mg/dl) in the normal subjects. In contrast, vitamin D increased mean serum 25-OHD from 19±3 to 65±19 ng/ml (p < 0.05), increased mean serum 1α,25(OH)₂D threefold from 40±7 to 120±24 pg/ml, and increased mean serum calcium from 9.4±0.2 to 9.8±0.2 mg/dl (P < 0.01). There was a significant positive correlation between the serum 1α,25(OH)₂D and serum calcium in these individuals (r = 0.663, P < 0.01) but not in the normal subjects. The results (a) provide further evidence for abnormal regulation of circulating 1α,25(OH)₂D in sarcoidosis and (b) indicate that the abnormality may exist in patients with normal calcium metabolism. Thus, the defect in vitamin D metabolism in sarcoid apparently is more common than was previousl recognized.