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

Abstract

Context: In healthy subjects and in patients with primary hyperparathyroidism (PH), the administration of a low dose of 25(OH)D (25 mg/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 1a-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 1a-hydroxylase of hypercalcemia per se, increased metabolic clearance of 1,25(OH) 2 D, or a decreased stimulus of 1a-hydroxylase related to persistently low levels of hCT.

Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism

“…30,90 In parallel with elevated calcitriol levels in PHPT is enhanced intestinal calcium absorption, whereas calcium absorption is normal in FHH. 31 Serum calcitriol levels in FHH, both under baseline conditions 89 and after 2 weeks of supplementation with vitamin D, 91 are intermediate between those of normal subjects and patients with PHPT, presumably because two major regulators of the 25(OH)D 1α-hydroxylase, namely, serum PTH and phosphate, likewise fall between those of normals and patients with PHPT.…”