Karen K Winer1, Kara A Fulton2, Paul S Albert2, Gordon B Cutler2. 1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Electronic address: karenwiner@gmail.com. 2. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
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. Published by Mosby, Inc.
RCT Entities:
OBJECTIVE: To compare the response with synthetic humanparathyroid 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. Published by Mosby, Inc.
Authors: Karen K Winer; Ninet Sinaii; James Reynolds; Donna Peterson; Karen Dowdy; Gordon B Cutler Journal: J Clin Endocrinol Metab Date: 2010-04-14 Impact factor: 5.958
Authors: Karen K Winer; Bo Zhang; Joseph A Shrader; Donna Peterson; Michaele Smith; Paul S Albert; Gordon B Cutler Journal: J Clin Endocrinol Metab Date: 2011-11-16 Impact factor: 5.958
Authors: Karen K Winer; Andrea Kelly; Alicia Johns; Bo Zhang; Karen Dowdy; Lauren Kim; James C Reynolds; Paul S Albert; Gordon B Cutler Journal: J Pediatr Date: 2018-12 Impact factor: 4.406
Authors: John P Bilezikian; Maria Luisa Brandi; Natalie E Cusano; Michael Mannstadt; Lars Rejnmark; René Rizzoli; Mishaela R Rubin; Karen K Winer; Uri A Liberman; John T Potts Journal: J Clin Endocrinol Metab Date: 2016-03-03 Impact factor: 5.958
Authors: Venkatesh Krishnan; Yanfei L Ma; Catherine Z Chen; Natasha Thorne; Heather Bullock; Gregory Tawa; Christy Javella-Cauley; Shaoyou Chu; Weiming Li; Wayne Kohn; Mary D Adrian; Charles Benson; Lifei Liu; Masahiko Sato; Wei Zheng; Andre M Pilon; N Nora Yang; Henry U Bryant Journal: Br J Pharmacol Date: 2017-11-28 Impact factor: 8.739