Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism

Abstract

Objective: To compare the response with synthetic human parathyroid hormone (PTH) 1-34 delivered by twice-daily injection vs insulin pump in children with severe congenital hypoparathyroidism due to calcium receptor mutation or autoimmune polyglandular syndrome type 1.

Study design: Children and young adults aged 7-20 years with congenital hypoparathyroidism (N = 12) were randomized to receive PTH 1-34, delivered either by twice-daily subcutaneous injection or insulin pump for 13 weeks, followed by crossover to the opposite delivery method. The principal outcome measures were serum and urine calcium levels. Secondary outcomes included serum and urine magnesium and phosphate levels and bone turnover markers.

Results: PTH 1-34 delivered via pump produced near normalization of mean serum calcium (2.02 ± 0.05 [pump] vs 1.88 ± 0.03 [injection] mmol/L, P < .05, normal 2.05-2.5 mmol/L), normalized mean urine calcium excretion (5.17 ± 1.10 [pump] vs 6.67 ± 0.76 mmol/24 h/1.73 m(2), P = .3), and significantly reduced markers of bone turnover (P < .02). Serum and urine calcium and magnesium showed a biphasic pattern during twice-daily injection vs minimal fluctuation during pump delivery. The PTH 1-34 dosage was markedly reduced during pump delivery (0.32 ± 0.04 vs 0.85 ± 0.11 μg/kg/d, P < .001), and magnesium supplements were also reduced (P < .001).

Conclusion: Compared with twice-daily delivery, pump delivery of PTH 1-34 provides more physiologic calcium homeostasis and bone turnover in children with severe congenital hypoparathyroidism.

Trial registration: ClinicalTrials.gov NCT00743782.

Figure 1

Serum levels of calcium, magnesium, phosphorus, and 1,25-dihydroxyvitamin D measured every 2 hours for 24 hours starting at 8:00 a.m. at the conclusion of each 3-month treatment arm comparing pump with twice-daily injection delivery of PTH 1-34 in children with hypoparathyroidism. The circadian patterns for serum calcium and magnesium differed significantly between delivery methods (P < .001).

Figure 2

Urine calcium, magnesium, phosphate, and cAMP excretion per unit of glomerular filtrate, measured every 4 hours for 28 hours starting at 4:00 a.m. at the conclusion of each 3-month treatment arm comparing pump with twice-daily injection delivery of PTH 1-34 in children with hypoparathyroidism. The circadian patterns for urine calcium, magnesium, and cAMP excretion differed significantly between delivery methods (P < .01).

Figure 3

Circadian patterns of serum and urine calcium for patients with hypoparathyroid with APS-1 vs those with CaR during pump vs injection delivery of PTH 1-34.

Figure 4

A, Mean serum, B, 24-hour urine, and C, calcium, magnesium, and phosphorus levels and bone turnover markers obtained daily for 4 days at the end of each 3-month treatment arm comparing pump with twice-daily injection delivery of PTH 1-34 in children with hypoparathyroidism. *P < .05, **P < .01, ***P < .001. Urine measures were corrected to a body surface area of 1.73 m².