1,25-Dihydroxycholecalciferol: Its Use in the Long-Term Management of Idiopathic Hypoparathyroidism in Children*

Abstract

The production of 1,25-dihydroxycholecalciferol, 1,25(OH)₂D₃, is reduced in the absence of parathyroid hormone (PTH), because conversion of 25-hydroxycholecalciferol (25-OHD₃) to 1,25(OH)₂D₃ is primarily under PTH control. By managing idiopathic hypoparathyroidism (IHP) in children with very small doses of 1,25(OH)₂D₃, 0.40-0.50 µg/day, given orally, the intestinal absorption of calcium (Ca) can be increased to normal and thereby restore and maintain normal serum levels of Ca. Three children with previously untreated, undiagnosed and isolated IHP have been managed in this manner for 2650 treatment days. Two 4-year-old children achieved and maintained normal serum levels of Ca after 1-4 days on 0.03 µg/kg/day of 1,25(OH)₂D₃. While the hormone was continued, each child was placed on a low Ca diet: the total serum Ca fell by 0.80 to 1.0 mg/dl within 2 days. During 2300 treatment days, both children have remained normocalcemic on a regular diet. The third child, who required phenobarbital throughout treatment, also responded rapidly, but required 0.16 µg/kg/day of 1,25(OH)₂D₃. During 350 days of therapy, 4 brief episodes of hypercalcemia (total serum Ca: 10.5-11.7 mg/dl) occurred. On each occasion, 1,25(OH)₂D₃ was discontinued for 2 days, with prompt return to normocalcemia, and the dose was decreased each time by 0.03 µg/kg/day of the hormone. Prior to therapy, serum concentrations of 1,25- (OH)₂D₃, in pg/ml, were 51, 19, and 24 in each child, respectively. After hormonal treatment for several months, all 3 children exhibited similar rises in serum levels 4-6 h after oral dosing and rapid decreases by 16 h, far below normal values. This new physiologic approach avoids the treatment with large doses of long-acting vitamin D₃, and its analogues, and provides ease in dose adjustment. Minute doses of the potent hormone, 1,25- (OH)₂D₃, given orally, present considerable advantages in the long-term management of IHP in children.