Synthetic Human Parathyroid Hormone 1-34 Replacement Therapy: A Randomized Crossover Trial Comparing Pump Versus Injections in the Treatment of Chronic Hypoparathyroidism

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 D3 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. (J Clin Endocrinol Metab 97:391-399, 2012)