ESPE Abstracts

Introduction: Congenital hypopituitarism is a heterogeneous disorder with isolated hormone deficiency(IPHD) or combined(CPHD). Main risk factors for CPHD include H-P abnormalities such agenesis corpus callosum(ACC), anterior pituitary hypoplasia(APH), ectopic posterior pituitary(EPP), pituitary stalk interruption(PSI), septo-optic dysplasia(SOD), and holoprosencephaly(HPE).

Patients and Methods: Prospective and longitudinal review of pediatric patients with GH deficiency and pituitary morphology abnormality in a third level hospital.

Inclusion criteria: patients under 18 years at diagnosis with short stature (<-2SDS), GH deficiency and pituitary morphology alteration on MRI.

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 (previous, at diagnosis of GHD and during follow-up), pituitary imaging, genetic study and treatment.

Results: Thirty-nine patients, 23 IGHD and 16 CPHD. Twenty-eight patients were males.

Median age at diagnosis: 0 years (+/-3DS) at CPHD group. Ten patients were diagnosed during neonatal period, they presented severe hypoglycemia and 5 also microphallus, the rest were diagnosed later because of growth retardation at 3 years (+/-2.65DS). Cerebral MRI: 11 APH, 3 EPP, 8 PSI, 8 APH and EPP, 1 empthy sella turca, 2 small sella turca, 3 SOD, 1 HPE and 2 hipotalamic-pituitary dysgeneses, in addition 3 patients presented ACC.

Hormonal deficiencies CPHD group: TSH deficiency was the second more prevalent (12 patients, 75%) followed by LH/FSH deficiency (10 patients, 62%). ACTH deficiency (6 patients) and ADH deficiency(5 patients).

Genetic study: The NGS-panel was performed in 29 patients. Heterozygous pathogenic variants were found in 4 (14%): 3 at IGHD group (HESX1, LHX4, GLI2 genes) and 1 at CPHD group (GLI2 gene). Clinical exome was performed in 9 patients of the CPHD group: Two patients (22%) presented heterozygous pathogenic variants (KIF7, FGFR1 genes).

Conclusions: Pathogenic variants in genes typically described in congenital hypopituitarism and H-P abnormalities were observed in patients with IGHD. The performance of our genetic panel is 14% in this group. CPHD patients had more severe morphological alterations at the pituitary level and presented clinical manifestations at earlier ages.