ESPE Abstracts

Introduction: Congenital hypopituitarism is a heterogeneous disorder that involve combined pituitary hormone deficiencies.

Patients and Methods: Longitudinal review of pediatric cases with congenital hypopituitarism follow up in a third level hospital.

Inclusion criteria: patients under 18 years at diagnosis with combined pituitary hormone deficiencies.

Genetic studies include: NGS-panel (HESX1, IGSF1, LHX3, LHX4, OTX2, PAX6, POU1F1, PROK2, PROKR2, PROP1, ROBO1, FGF8, FGFR1, GLI2, GLI3, SOX3), array-CGH or clinical exome. Follow-up data was collected annually by reviewing the medical records including hormonal status, pituitary imaging, genetic study and treatment.

Results: Twenty-two patients, sixteen were males.

Mean age at diagnosis: 1.5 years (±2.6DS). Thirteen patients were diagnosed during neonatal period: eight patients presented microphallus and cryptorchidism, three presented severe hypoglycemia, one patient presented hypernatremia and dehydration and another one septic shock. Five patients were diagnosed during childhood for short stature and another four patients were followed since neonatal period for phenotypic abnormalities and visual impairment and hormonal deficiencies were diagnosed during follow-up.

Cerebral MRI: 7 septo-optic dysplasia (SOD), 6 pituitary stalk interruption (PSIS), 2 holoprosencephaly (HPE), 2 anterior pituitary hypoplasia (APH), 2 APH and ectopic posterior pituitary (EPP). In three patients MRI was normal.

Hormonal deficiencies: GH deficiency was the most prevalent (18 patients) followed by TSH deficiency (15 patients), LH/FSH deficiency (14 patients), ACTH deficiency (8 patients) and ADH deficiency (5 patients). Seven patients presented multiple deficiencies at diagnose in the neonatal period.

Genetic study: The NGS-panel was performed in 11 patients. Heterozygous pathogenic variants in GLI2 and FGFR1 genes were found in 2. Clinical exome was performed in 12 patients: one patient presented homozygous variant in KIF7 gene. Direct Sanger sequencing method was positive in three patients with heterozygous patogentic variants: two in CHD7 and one in SOX2 genes. Array-CGH was performed in 13 patients with one deletion in chromosome 18.

Conclusions: In our serie, CH is more frequent among males patients and the most frequent deficiency is GH followed by TSH.