1,25-dihydroxyvitamin D3-treated hypoparathyroidism: 35 patients years in 10 children

Ten hormone-deficient hypoparathyroid children have been successfully treated with orally administered 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] within a dose range of 0.01--0.10 microgram/kg . day for a total of 35 patient yr. Resistance to 1,25-(OH)2D3 therapy was not observed. By monitoring the blood ionized calcium level (normal range, 4.05--5.14 mg/dl) at monthly intervals, 8 hypercalcemic and 10 hypocalcemic episodes were recognized during the entire treatment experience, though the patients were asymptomatic. In the former cases, cessation of treatment for 3 days resulted in normocalcemia; in the latter, half of the episodes were transient and related to intercurrent febrile illnesses. The remaining hypocalcemic occurrences responded to an increase in the dosage of 1,25-(OH)2D3. During 1,25-(OH)2D3 treatment, the mean ionized calcium level for individual patients ranged from 4.04--4.39 mg/dl. Urinary Ca excretion, expressed as a ratio of calcium to creatinine, ranged from 0.177--0.244. Twenty-four-hour mean levels of serum 1,25-(OH)2D did not correlate with the blood ionized calcium concentration in 4 patients who underwent sequential blood sampling every 1--2 h for a total of 59 time points (r = 0.05; P greater tha 0.10). To elucidate the temporal relationship between hormonal and mineral responses to exogenous PTH, we administered bovine PTH to four untreated hypoparathyroid children. Serum concentrations of PTH increased before the rise in ionized calcium, which in turn preceded the elevation in circulating 1,25-(OH)2D. This order was followed also in the fall in serum concentrations of these blood constituents to pre-PTH infusion values. These results indicate responsiveness of the l alpha-hydroxylase enzyme to exogenous PTH in hormone-deficient hypoparathyroid children.