ESPE Abstracts

Introduction: The calcium-sensing receptor (CaSR) detects calcium levels and regulates parathyroid hormone (PTH) secretion to maintain serum calcium within normal ranges. Inactivating mutations in the CASR gene cause hyperparathyroidism and hypercalcemia. Heterozygous mutations lead to familial hypocalciuric hypercalcemia (FHH), homozygous mutations cause neonatal severe hyperparathyroidism (NSHPT). Cinacalcet is an allosteric modulator of CaSR. This report presents the experience of using cinacalcet in a newborn with NSHPT unresponsive to conventional treatment.

Case Presentation: A 33-week gestation, 1970g female infant was admitted to the neonatal intensive care unit (NICU) due to respiratory distress. On postnatal day (PN) 14, she was referred to our clinic for hypercalcemia. The parents were first-degree cousins, with no known family history of similar conditions, her siblings were healthy. The patient's heigt:43cm (0.21SDS), weight:1990g (0.91SDS), head circumference:30cm (0.13SDS). The anterior fontanel measured 2x2cm, and the posterior fontanel was 0.5x0.5cm. Other examination findings were normal. In laboratory tests serum calcium 13.54 mg/dL, phosphorus 4.39 mg/dL, magnesium 2.72 mg/dL, albumin 3.84g/dL, PTH 152ng/L, alkaline phosphatase (ALP) 295U/L, 25OH-vitaminD 18ng/mL, urine calcium/creatinine ratio 0.18, calcium/creatinine clearance ratio 0.003. Parathyroid ultrasound was normal. Family screening revealed mild hypercalcemia in the mother, father, one sibling. Intravenous hydration, calcium-restricted formula feeding were initiated. Furosemide was started. Despite these measures, hypercalcemia persisted, and intravenous pamidronat was administered at a dose of 0.5 mg/kg on PN day 27. Following pamidronate treatment, calcium levels initially decreased but then rose again despite continued hydration and diuretics. On PN day 40, oral cinacalcet was started at 20 mg/m²/day. Calcium levels normalized, and diuretic treatment and hydration ceased. The patient resumed breastfeeding on the second day of cinacalcet treatment and remained normocalcemic, allowing for discharge (Table1). Genetic analysis revealed a homozygous c.-10C>T variant in the CASR gene, confirming the diagnosis of NSHPT. Heterozygous variant was detected in the patient's mother, father and two brothers. At the last follow-up at 10 months of age, serum calcium was 10.8 mg/dL while on cinacalcet at 90 mg/m²/day.

Conclusion: In cases of NSHPT unresponsive to standard treatments, the use of calcimimetic agents like cinacalcet can be effective to control hypercalcemia and delay or avoid parathyroidectomy. This report discusses the successful management of NSHPT with cinacalcet and the implications for future treatment.

Keywords: CaSR, neonatal severe hyperparathyroidism, cinacalcet