Successful Early Treatment of Severe Neonatal Hyperparathyroidism With Cinacalcet

Abstract

Introduction: Neonatal severe hyperaparathyroidism (NSHPT) can cause significant bone disease early in life and prompt treatment is therefore necessary. Cinacalcet is a calcimimetic primarily used in adult patients with hypercalcemia to treat secondary hyperparathyroidism, but has only been trialed in neonates with NSHPT. Successful treatment appears to be dependent on the mutation leading to hypercalcemia. We describe a neonate born with severe hypercalcemia and a suspected mutation of the calcium sensing receptor (CaSR) who received successful early treatment with cinacalcet and decrease in calcium levels.Case Report: A full-term baby girl was found to have rapid breathing at 2.5 hours of life requiring CPAP. A chest x-ray demonstrated bone demineralization with rib fractures. Lab evaluation demonstrated hypercalcemia (total calcium = 12 mg/dl) with an inappropriately elevated PTH level of 386 pg/mL, hypophosphatemia (3.3 mg/dL), normal magnesium (2.0 mg/dL), a normal urine calcium to creatinine ratio of 0.26 and calcium to creatinine clearance ratio of 0.05 and a slightly low vitamin D-25 of 28.8 ng/mL.The father had a history of asymptomatic hypercalcemia without a diagnosis. Paternal genetic testing identified a heterozygous pathogenic CASR defect: c. 554G>A (p.Arg185Gln). This has been described in patients with NSHPT.The patient was initially treated with IV fluids and Lasix, but calcium levels did not decrease. Cinacalcet therapy was given on day of life 10. Patient had a decreased PTH to 231 pg/ mL after one day. After 26 days of treatment, patient’s PTH level decreased to 63 pg/mL. Patient was weaned off of CPAP and was discharged home.Discussion: Cinacalcet, a calcimimetic that works at the level of the CASR, was able to successfully and significantly decrease PTH levels in a neonate patient with NSHPT. Treatment options are limited in patients with this condition and we believe prompt treatment with this therapy facilitated patient’s discharge. The patient’s osteopenia secondary to the NSHPT and subsequent rib fractures resulted in a prolonged requirement of CPAP. Early recognition and treatment, even prior to results of genetic testing, prevented further fractures. We demonstrate the potential benefit of calcimimetics in a case of NSHPT where conventional treatment was ineffective. More importantly, we anticipate improvement in osteopenia and any future comorbidities secondary to this condition. Continued success with this treatment is yet to be evaluated.