Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism

Abstract

Context: Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. Long-term conventional therapy with vitamin D and analogs may lead to nephrocalcinosis and renal insufficiency.

Objective: Our objective was to compare the response of once-daily vs. twice-daily PTH 1-34 treatment in children with hypoparathyroidism.

Setting: The study was conducted at a clinical research center.

Subjects: Fourteen children ages 4-17 yr with chronic hypoparathyroidism were studied.

Study design: This was a randomized cross-over trial, lasting 28 wk, which compared two dose regimens, once-daily vs. twice-daily PTH1-34. Each 14-wk study arm was divided into a 2-wk inpatient dose-adjustment phase and a 12-wk outpatient phase.

Results: Mean predose serum calcium was maintained at levels just below the normal range. Repeated serum measures over a 24-h period showed that twice-daily PTH 1-34 increased serum calcium and magnesium levels more effectively than a once-daily dose. This was especially evident during the second half of the day (12-24 h). PTH 1-34 normalized mean 24-h urine calcium excretion on both treatment schedules. This was achieved with half the PTH 1-34 dose during the twice-daily regimen compared with the once-daily regimen (twice-daily, 25 +/-15 microg/d vs. once-daily, 58 +/- 28 microg/d; P < 0.001).

Conclusions: We conclude that a twice-daily PTH 1-34 regimen provides a more effective treatment of hypoparathyroidism compared with once-daily treatment because it reduces the variation in serum calcium levels and accomplishes this at a lower total daily PTH 1-34 dose. The results showed, as in the previous study of adult patients with hypoparathyroidism, that a twice-daily regimen produced significantly improved metabolic control compared with once-daily PTH 1-34.

Figure 1

Twenty-four hour profile of serum calcium (A), magnesium (B) and phosphorus (C), values (mean ± sd) obtained at 14 wk comparing once vs. twice-daily sc PTH injections given at times zero or 0 and 12 h, respectively.P < 0.05 once vs. twice-daily PTH administration.

Figure 2

Twenty-four hour profile of urine excretion of mean calcium (A), magesium (B) and phosphorus (C), and cAMP (D) values (mean ± sd) obtained at the conclusion of each study arm comparing once-daily and twice-daily PTH sc injections at times zero or 0 and 12 h, respectively.P < 0.05 once vs. twice-daily PTH administration.