Twice-Daily Subcutaneous Injections vs. Pump Delivery of PTH 1-34 in the Treatment of Children with Severe Congenital Hypoparathyroidism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-212
Karen K Winer*1, Kara A. Fulton1, Paul S. Albert1, Debra Nixon-Jones1 and Gordon B Cutler Jr.2
1NIH, Bethesda, MD, 2Consultant, Deltaville, VA
Background and Aims: Hypoparathyroidism remains among the few hormonal insufficiency states not treated by the replacement of its missing hormone. Conventional therapy with vitamin D analogs and calcium supplementation may lead to renal insufficiency or failure due to progressive nephrocalcinosis.  This is especially true for congenital hypoparathyroidism due to an activating mutation in the calcium sensing receptor (CaR), in which hypercalciuria may occur even when serum calcium levels are low normal or below the normal range. Furthermore, patients with autoimmune polyglandular syndrome type 1 (APS-1) may not respond to conventional therapy due to chronic malabsorption.                        

Methods: This randomized, controlled crossover study was composed of two 3-month study periods each consisting of a 1-week inpatient and 3-month outpatient phase. 12 children/adolescents with hypoparathyroidism (7-20 yo; 5 males) with APS-1(n=5) or CaR (n=7) were studied.  Each patient was randomly assigned to receive synthetic PTH 1-34 either by pump or twice-daily injection delivery during the initial treatment arm and crossed over to the opposite treatment arm at 3 months. At the end of each 3-month study period, serum and 24-h urine mineral levels and bone turnover markers were measured daily for 3 days during an inpatient evaluation. Serial (every 2 h) blood and urine (every 4 h) were obtained on the 4thday of each admission.                                                                                     

Results: PTH 1-34 delivered by an insulin pump resulted in simultaneous normalization of blood (Ca=2.02 mmol/L [N: 2.05-2.5]) and urine calcium (5.17 mmol/24h/1.73 m2body surface area; [N: 1.25-7.5]) levels and markers of bone turnover. Twice-daily injections produced lower mean serum Ca (1.88 mmol/L ; P<0.02 injections vs. pump) and higher mean urine calcium (6.67 mmol/24h).  The mean daily PTH dose was 0.85 mcg/kg body weight for the injection arm and 0.32 mcg/kg for the pump arm(P<0.01, injections vs. pump).  Markers of bone turnover were within the normal range during pump delivery, but were above the normal range, and significantly higher, during twice-daily injection delivery.  Serial testing during twice-daily injections revealed a biphasic diurnal pattern for serum and urine calcium and magnesium, and for urine cyclic AMP excretion, compared to minimal fluctuation during pump delivery.

Conclusions: PTH replacement therapy is more physiologic when delivered by an insulin pump than by twice-daily injection.  Pump delivery simultaneously normalized bone turnover markers and urine and serum mineral levels, whereas twice-daily injection delivery did not, either in this study or in previous studies of patients with congenital hypoparathyroidism due to CaR and APS-1. The improved metabolic control with pump delivery was achieved at a fraction of the daily PTH dose needed for twice-daily injection delivery.

Disclosure: GBC Jr.: , Eli Lilly & Company, , Eli Lilly & Company. Nothing to Disclose: KKW, KAF, PSA, DN

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