Background: Most patients with hypoparathyroidism are controlled under conventional treatment with calcium and vitamin D analogues. However, this treatment may be difficult to manage, especially in patients with ADHH who have an increased risk of nephrocalcinosis and chronic renal insufficiency. ADHH is caused by activating mutations in the calcium-sensing receptor (CaSR) resulting in suppressed PTH secretion and decreased calcium reabsorption within the thick ascending limb of loop of Henle. The CaSR modulates urinary calcium reabsorption through a PTH-independent mechanism.
Aim: Evaluate the efficacy of rPTH134 as an alternative to vitamin D analogue therapy for ADHH patients, in particular regarding the prevention of hypercalciuria and nephrocalcinosis.
Patients: Four patients, three toddlers (8, 18, and 30 months old; P1, P2, and P3) and one young adult (19 years old, P4) with ADHH and CaSR mutations, received rPTH134 by continuous subcutaneous infusion via an insulin pump. The observed duration of therapy was 2 to 8 months (ongoing in all patients), with a mean daily dose of rPTH134 0.54, 0.57 and 0.37 μg/kg per day in the toddlers and 0.20 μg/kg per day in the adult patient. Three additional patients received rPTH134 (n=1, 48 months 0.75 μg/kg per day, twice daily injections) of rPTH184 for 6 and 19 months, and (n=2, 100 μg/day). Additional treatments received were adjusted calcium supplements and cholecalciferol (none received vitamin D analogues after switching to rPTH).
Results: On rPTH therapy mean serum calcium levels increased in P1, P3 and P4 respectively from 1.4±0.15 to 2.1±0.25 mmol/l (P<0.05), 1.5±0.3 to 1.8±0.5 mmol/l (NS) and from 2.2±0.3 to 2.38±0.3 mmol/l (NS). P2 decreased her calcemia from 2.13±1.8 to 1.95±0.1 mmol/l (P<0.05). All four patients showed a decrease in mean urinary calcium excretion respectively from1.8±0.9 to 0.5±0.5 mM/mM (NS), 2.4±0.5to 1.1±0.4 mM/mM (P<0.05), 1.3 to 0.6±0.26 mM/mM (NS) and from 4.8±3.4 to 3±0.9 mmol/l (NS) in P1, P2, P3 and P4. When the three toddlers are analyzed as one group, the mean calcium level increased from 1.8±0.4 to 1.95±0.2 mmol/l (NS) and the mean urinary calcium excretion decreased from 2.1±1 to 1±0.5 mM/mM (P<0.05).
Conclusion: Our data show that rPTH allows the maintenance of serum calcium at near-normal levels in ADHH and correction of the clinically severe manifestations of hypocalcaemia. More importantly, even with near-normal blood calcium, rPTH had a significant anticalciuric effect, i.e. decreased significantly the urinary calcium excretion in ADHH patients, likely preventing or delaying renal damage. Treatment was safe and well tolerated.
22 - 25 Jun 2013