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Teriparatide (rhPTH 1–34) treatment in the pediatric age: long-term efficacy and safety data in a cohort with genetic hypoparathyroidism

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Abstract

Background

Hypoparathyroidism is characterized by the absence or inadequately low circulating concentrations of the parathyroid hormone, resulting in hypocalcemia, hyperphosphatemia, and elevated fractional excretion of calcium in the urine. The use of activated vitamin D analogs and calcium supplements represent conventional therapy. Subcutaneous recombinant human parathormone [rhPTH(1–34)] has been proposed as a substitutive treatment, even to avoid side effects of vitamin D and calcium.

Objective

To assess the long-term safety and efficacy of rhPTH(1–34) in a pediatric cohort of patients with genetic hypoparathyroidism.

Methods

The study is a 9.2-year self-controlled study of six pediatric patients (four males and two females, aged 9.4 ± 5.2) with DiGeorge, hypoparathyroidism-deafness-renal dysplasia (HDR) or autoimmune-candidiasis-polyendocrinopathy-ectodermal-dysplasia (APECED) syndrome, associated with autoimmune intestinal malabsorption in a patient. The presence of clinical signs of hypocalcemia and biochemical parameters, such as calcium, phosphate, alkaline phosphatase in the blood and calcium–creatinine ratio in urine, were compared during conventional treatment and rhPTH(1–34) (teriparatide, 12.5 μg twice daily).

Results

The rhPTH(1–34) treatment allowed a reduction, although not always a complete suspension, of calcium supplementation and a slight reduction of calcitriol therapy. The number of tetanic episodes was reduced in four patients during the rhPTH(1–34) treatment. Mean blood calcium, alkaline phosphatase, and phosphate did not significantly change, while a significant reduction of the urinary calcium-to-creatinine ratio (0.55 ± 0.32 vs 0.16 ± 0.09, p = 0.03) was obtained. Renal ultrasound examination showed a worsening in three patients, while it did not change in the remaining three subjects during the follow-up.

Conclusions

In children with syndromic hypoparathyroidism presented here, replacement therapy with rhPTH(1–34) allowed to maintain adequate levels of the calcium and phosphate in the blood, normalize urinary calcium excretion, and reduce tetanic episodes. In patients with low compliance to conventional therapy or intestinal malabsorption, the use of rhPTH(1–34) could be considered, also to reduce the side effects of treatment with vitamin D and calcium.

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Author contributions

All authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results (G.T., R.B. and L.D.S. contributed to the study design, the manuscript writing and final revisions; D.T., S.E., P.M. contributed to the study design and the conceptual part of this manuscript)

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Authors and Affiliations

  1. Department of Pediatric Endocrinology, Regina Margherita Children’s Hospital, City of Health and Science University Hospital of Turin, Turin, Italy

    Gerdi Tuli, Raffaele Buganza, Daniele Tessaris, Silvia Einaudi, Patrizia Matarazzo & Luisa de Sanctis

  2. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy

    Gerdi Tuli, Raffaele Buganza, Daniele Tessaris, Silvia Einaudi, Patrizia Matarazzo & Luisa de Sanctis

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  1. Gerdi Tuli
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Tuli, G., Buganza, R., Tessaris, D. et al. Teriparatide (rhPTH 1–34) treatment in the pediatric age: long-term efficacy and safety data in a cohort with genetic hypoparathyroidism. Endocrine 67, 457–465 (2020). https://doi.org/10.1007/s12020-019-02128-z

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