Long-Term Results of Continuous Subcutaneous Recombinant PTH (1-34) Infusion in Children with Refractory Hypoparathyroidism

Abstract

Hypoparathyroidism in children is most often due to mutations in genes involved in parathyroid development and calcium homeostasis signaling. Some rare cases result from autoimmune attack on the parathyroid glands as a part of the type 1 polyglandular failure syndrome (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). The majority of cases of pediatric hypoparathyroidism are well controlled under conventional treatment with calcium and vitamin D analogs. However, this treatment may be difficult to manage, especially in two situations: 1) in the context of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and 2) activating mutations in the calcium-sensing receptor. We successfully treated three patients with hypoparathyroidism with continuous subcutaneous administration of rhPTH(1-34) (recombinant human PTH(1-34)), two of which were refractory to conventional therapy.

Continuous Subcutaneous Recombinant Parathyroid Hormone (1–34) Infusion in the Management of Childhood Hypoparathyroidism Associated with Malabsorption

“…Both siblings required intermittent intramuscular vitamin D injections, when adequate serum 25OHD level was not achieved on monthly oral vitamin D supplements (100,000 IU) alone. To our knowledge, P3 and P4 were the first reported children to be commenced on CSPI and P3 has remained on it for the longest duration of 8 years [10]. Here we focus on the initiation of their PTH therapy and highlight the challenges in managing resistant hypocalcemia in the context of malabsorption.…”

“…P2 was on an initial dose of 1 µg/kg/day, which was gradually weaned down to 0.35 µg/kg/day. P3 and P4, the very first patients to have commenced on CSPI were started on a higher initial dose of 2.6 µg/kg/day and weaned down to a maintenance dose of 0.5 µg/kg/day in P3 (Table 2) [10]. …”

“…The role of synthetic subcutaneous PTH injections in the treatment of hypoparathyroidism was first reported in adults in 1996 [6, 7] followed by reports in children in 2008 [8]. Since then, short- [9] and long-term studies [10] have demonstrated the efficacy and safety of continuous subcutaneous recombinant PTH 1–34 infusion (CSPI) in the management of hypocalcaemia in children with activating mutations in CaSR and with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).…”

Drugs Used in Paediatric Bone and Calcium Disorders

“…The use of PTH has traditionally been avoided in children because of reports that high doses of PTH cause sarcomas in growing rats [23] . However, the use of physiological doses of synthetic PTH has been reported in these groups of patients via both subcutaneous and, more recently, continuous subcutaneous infusion [24] .…”

Managing pediatric osteoporosis

“…In fact, several concerns exist regarding its safety, especially in younger patients, because of the development of bone tumors, particularly osteogenic sarcoma in young rats [1,2,16]. However, recombinant human parathyroid hormone is given to hypoparathyroid children [16], although long-term followup studies have not been carried out to assess the risk of osteogenic sarcoma in this population.…”