ESPE Abstracts

Introduction: Neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disease characterized by hypercalcemia and bone demineralization due to homozygous or compound heterozygous loss-of-function mutations in the calcium-sensing receptor (CaSR) gene. Most cases require emergency parathyroidectomy to be life-saving. Alternative treatments, such as pamidronate and cinacalcet, may be used until surgery is feasible. We present a case of severe hypercalcemia in the neonatal period managed initially with medication before surgical intervention at the age of 9 months and 21 days.

Case: A female neonate, born vaginally at 40 weeks gestation and weighing 3550 grams, presented to the pediatric emergency department on the fifth postnatal day with symptoms of restlessness, feeding difficulties, and hypotonia. Laboratory tests indicated severe hypercalcemia with serum calcium at 28 mg/dL, phosphorus at 2.72 mg/dL, parathormone at 897.8 ng/L, alkaline phosphatase at 419 U/L, and a spot urine calcium/creatinine ratio of 17. Despite conventional treatments for hypercalcemia, including intravenous hydration and furosemide, her condition persisted with serum calcium at 26.9 mg/dL and PTH at 1098 ng/L, necessitating multiple doses of pamidronate. On postnatal day 50, with persistent hypercalcemia (serum calcium 15.4 mg/dL), cinacalcet treatment was initiated, eventually increasing to 70 mg/m²/day due to resistant hypercalcemia. A family history revealed a fifth degree relative underwent a parathyroidectomy 9 years ago due to NSHPT. Genetic assessment confirmed a homozygous c.1630C>T (p.Arg544Ter) CASR mutation, the same variant found in the patient’s relative. Radiographic findings included generalized osteopenia, metaphyseal cupping and irregularity, subperiosteal resorption, and medial beaking of long bones. Despite ongoing treatment with up to 100 mg/m²/day of cinacalcet, persistent hypercalcemia (serum calcium 11.5-13.0 mg/dL), elevated parathormone (557-1525 ng/L), and alkaline phosphatase levels (1258-1883 U/L) indicated ongoing osteopenia. Total parathyroidectomy was performed when the patient weighed 6.2 kg at age 9 months and 21 days. Normocalcemia was achieved by the second post-operative day, and the patient was discharged on the 28th post-operative day with ongoing calcium lactate and calcitriol treatments. The patient, now 2 years old, continues her follow-up care at our institution.

Conclusion: Cinacalcet can be used to manage hypercalcemia in patients with NSHPT while preparing for surgery. In this case, although serum calcium levels were controlled, the elevated levels of parathormone and alkaline phosphatase necessitated a parathyroidectomy, guiding the clinical decision-making process.

Keywords: Neonatal severe hyperparathyroidism, CaSR, cinacalcet, parathyroidectomy