IMPE Abstracts

Introduction: FHH is an autosomal dominant disorder caused by an inactivating mutation of the CaSR gene in two-thirds of cases. It is considered a "benign"and generally asymptomatic condition. On the other hand, GH and IGF1 stimulate renal synthesis of 1,25-hydroxyvitamin D and increase bone turnover.

Case Report: We present a 9.8-year-old (y) male, referred for growth assessment. He was born at 36 weeks with normal birth weight: 2.130 kg (-1.4 SDS). He had been diagnosed with autism and developmental delay. MRI showed hypoplastic corpus callosum. On physical examination: he was prepuberal and his weight was 29,7 kg (-0.39 SDS) and height was 127 cm (-1.34 SDS). Bone age was delayed: 6.5 y. Laboratory assays showed: normal male karyotype, normal calcemia 10 mg/dl, phosphatemia 3.8 mg/dl, magnesemia 2.1 mg/dl and PTH 70 pg/ml. Serum thyroid hormones, prolactin and cortisol were normal. GH tests showed insufficient response, peak 5.35 ng/ml (normal >6). At 10.8 y of age, he started rGH therapy. At 11.6 y, he presented asymptomatic hypercalcemia (14 mg/dl), ionic calcium 6.65 mg/dl, P 3.6 mg/dl, Mg 1.56 mg/dl, PTH 19 pg/ml, 25-hydroxyvitamin D 22.4 g/ml, non-doseable calciuria. ECG and echocardiogram were normal. Bone X-rays, parathyroid and abdominal-renal ultrasound were normal. Total-body CT scanning and PET/CT were without pathological findings. The rGH treatment was discontinued. Due to the lack of response to hyperhydration and furosemide, intravenous pamidronate was indicated. His father's calcemia was elevated (12.5mg/dl). FHH was suspected. CaSR gene automated sequencing revealed a heterozygous pathogenic variant previously described, c.554G>A (p.Arg185Gln) in the patient, his father and his sister. Fifteen days later he had symptomatic hypercalcemia (13.7mg/dl) with hypertension and shortened QTc interval. Cinacalcet was initiated with increasing doses to maintain calcemia in the upper normal range. After 3 years, he continues with cinacalcet with good response and tolerance.

Discussion: Patient mutation is associated with FHH and neonatal hyperparathyroidism. Treatment with rGH could have contributed to clinical manifestation of FHH. Cinacalcet therapy proved to be effective and safe in this patient.