Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism

J Clin Endocrinol Metab. 2012 Feb;97(2):391-9. doi: 10.1210/jc.2011-1908. Epub 2011 Nov 16.

Abstract

Context: Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation.

Objective: Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery.

Research design and methods: In a 6-month, open-label, randomized, crossover trial, PTH 1-34 was delivered by pump or twice-daily sc injection. After each 3-month study period, serum and 24-h urine mineral levels and bone turnover markers were measured daily for 3 d, and 24-h biochemical profiles were determined for serum minerals and 1,25-dihydroxyvitamin D(3) and for urine minerals and cAMP. STUDY PARTICIPANTS AND SETTING: Eight patients with postsurgical hypoparathyroidism (mean ± sd age 46 ± 5.6 yr) participated at a tertiary care referral center.

Results: Pump vs. twice-daily delivery of PTH 1-34 produced less fluctuation in serum calcium, a more than 50% reduction in urine calcium (P = 0.002), and a 65% reduction in the PTH dose to maintain eucalcemia (P < 0.001). Pump delivery also produced higher serum magnesium level (P = 0.02), normal urine magnesium, and reduced need for magnesium supplements. Finally, pump delivery normalized bone turnover markers and significantly lowered urinary cross-linked N-telopeptide of type 1 collagen and pyridinium crosslinks compared with twice-daily injections (P < 0.05).

Conclusion: Pump delivery of PTH 1-34 provides the closest approach to date to physiological replacement therapy for hypoparathyroidism.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Cross-Over Studies
  • Drug Administration Schedule
  • Female
  • Hormone Replacement Therapy / methods*
  • Humans
  • Hypoparathyroidism / blood
  • Hypoparathyroidism / drug therapy*
  • Hypoparathyroidism / etiology
  • Infusion Pumps
  • Injections, Subcutaneous
  • Insulin Infusion Systems
  • Magnesium / blood
  • Male
  • Middle Aged
  • Parathyroid Hormone / administration & dosage*
  • Parathyroid Hormone / chemical synthesis
  • Phosphorus / blood
  • Postoperative Complications / blood
  • Postoperative Complications / drug therapy
  • Vitamin D / blood

Substances

  • Parathyroid Hormone
  • Vitamin D
  • Phosphorus
  • Magnesium