Session: MON 199-237-Disorders of Parathyroid Hormone & Calcium Homeostasis
Poster Board MON-200
The majority of cases with hypoparathyroidism are well 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.
Evaluate the efficacy of rPTH1-34 as an alternative to vitamin D analogue therapy for ADHH patients, in particular regarding the prevention of hypercalciuria and nephrocalcinosis.
Four patients, three toddlers (8, 18 and 30 months old; P1,P2,P3) and one young adult (19 years old, P4) with ADHH and documented CaSR heterozygous mutations, received rPTH1-34 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 rPTH1-34 0.54, 0.57 and 0.37 μg/kg/day in the toddlers and 0.20 μg/kg/day in the adult patient. Additional treatments received were adjusted calcium supplements and cholecalciferol vitamin D (none received active 1-alpha hydroxylated vitamin D analogues after switching to rPTH).
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 showed a decrease in mean serum calcium 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 from 1.8±0.9 to 0.5±0.5 mM/mM (ns), 2.4±0.5 to 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 3 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).
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.
Nothing to Disclose: AR, JA, RC, KK, LB, MI, WH, PB, AL
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