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

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.

Fig. 1.

Effect of pump compared with twice-daily PTH 1-34 delivery on serum (A) and urine (B) calcium, magnesium, phosphorus and serum and urine markers of bone turnover (C), at the end of each 3-month treatment period.

Fig. 2.

Serum calcium, magnesium, phosphorus, and 1,25-dihydroxyvitamin D values from consecutive 2-h collections for 24 h, during pump and twice-daily delivery, at the end of each 3-month treatment period.

Fig. 3.

TRCa and phosphate reabsorption (TmP/GFR), urine excretion of magnesium, and cAMP from successive 4-h urine collections for 24 h, during pump and twice-daily delivery, at the end of each 3-month treatment period.