Different vitamin D substrate-product relationship after oral vitamin D supplementation in familial benign hypercalcemia, primary hyperparathyroidism, and healthy controls.

CONTEXT: In healthy subjects and in patients with primary hyperparathyroidism (PH), the administration of a low dose of 25(OH)D (25 μg/day) increases the serum levels of both 25(OH)D and 1,25(OH)(2)D. It is unknown whether this relationship is present in patients affected by familial benign hypocalciuric hypercalcemia (FBH).

OBJECTIVE

To evaluate the different vitamin D substrate-product relationship after oral vitamin D supplementation in familial benign hypercalcemia, PH, and healthy controls.

DESIGN

We evaluated the main physiological regulators of 1α-hydroxylase and the substrate-product relationship of 25(OH)D and 1,25(OH)(2)D in 20 patients with PH, 25 with FBH, and 122 healthy sex- and age-matched controls before and after administration of 25(OH)D for 2 weeks.

RESULTS

25(OH)D increased significantly in all subjects, whereas 1,25(OH)(2)D serum levels increased significantly in PH patients and healthy controls but not in patients with FBH. Therefore, a significant positive substrate-product relationship of 25(OH)D-1,25(OH)(2)D was found in PH and healthy controls, but not in FBH. Monomeric calcitonin (hCT-M) was significantly lower at baseline and after 25(OH)D supplementation in the FBH group compared with the other two groups.

CONCLUSIONS

The lack of 1,25(OH)(2)D increase in FBH may be due to a direct inhibitory effect on 1α-hydroxylase of hypercalcemia per se, increased metabolic clearance of 1,25(OH)(2)D, or a decreased stimulus of 1α-hydroxylase related to persistently low levels of hCT.