Background: Hypoparathyroidism is characterized by absence or inadequately low circulating concentrations of parathyroid hormone, resulting in hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. The use of activated vitamin D analogues and calcium supplements are recommended as the primary therapy. To avoid vitamin D and calcium side effects, subcutaneous recombinant human parathormone [rhPTH (1-34)] has been proposed for hypoparathyroidism treatment.
Objective: Our objective was to evaluate rhPTH (1-34) long term safety and efficacy in pediatric patients with genetically proven syndromic hypoparathyroidism.
Methods: The study was a 9.2-year self-controlled trial on six pediatric patients (four males, two females, age 9.4±5.2 years) with syndromic hypoparathyroidism: three subjects with autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED) syndrome (one of those with intestinal malabsorbtion), two with DiGeorge syndrome and one with hypoparathyroidism-deafness-renal dysplasia syndrome. Hypocalcemic clinical signs and biochemical parameters (blood calcium, phosphorus, alkaline phosphatase and urinary calcium-to-creatinine ratio) were compared during conventional treatment and on rhPTH (1-34) (teriparatide, 12.5 µg twice a day).
Results: rhPTH treatment allowed a marked reduction, even not always complete withdraw, of calcium and cacitriol therapy. During rhPTH (1-34), mean blood calcium and alkaline phosphatase were not significantly modified, whereas significant reduction of the urine calcium-to-creatinine ratio (0.55±0.32 vs. 0.16±0.09, P=0.02) and blood phosphorus (2.01 ± 0.23 vs. 1.69 ± 0.21, P=0.03) was obtained. The number of tetanic episodes was reduced in four patients during teriparatide treatment. Renal ultrasound findings worsened in 3 patients (with nefrocalcinosis in 2 patients) and was unmodified in the other 3.
Conclusion: In the presented children with syndromic hypoparathyroidism, substitutive treatment with rhPTH (1-34) allowed to maintain adequate blood calcium and phoshorus levels, to normalize urinary calcium excretion, to reduce the tetanic episodes. In patients with low compliance or with intestinal malabsorbition, its utilization should be considered, even to reduce vitamin D and calcium treatment side effects.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology