ESPE Abstracts

Background: Congenital combined pituitary hormone deficiency (CPHD) has various clinical presentations and can be caused by genetic defects related to pituitary development. We investigated the clinical features and genetic analysis in Korean patients with congenital CPHD.

Method: Among 444 patients diagnosed with CPHD between 1994 and 2021 from Seoul National University Children’s Hospital, 43 patients with congenital CPHD were included, after excluding 401 with acquired causes. Data on birth history, anthropometrics, hormonal evaluation, brain magnetic resonance imaging(MRI) findings, extra-pituitary phenotypes, and adulthood outcomes were collected. Next generation sequencing(NGS) analysis was performed in 24 patients using targeted exome (n= 18) or whole exome sequencing (n= 6).

Result: Median age of diagnosis was 2.0 (range, 0-14) years, and 18 (41.9%) were diagnosed 1 year of age. Mean height z-score at diagnosis was -2.4±3.8. Initial presentation at diagnosis were neonatal features suggesting hypopituitarism such as jaundice, hypoglycemia, and micropenis/cryptorchidism in 18 (41.9%), and short stature in 16 (37.2%). Despite suspicious presentation in neonatal period, 8 were diagnosed at later age (range, 1-13 years). Extra-pituitary phenotypes were shown in 31 (72.1%); developmental delay in 15 (34.9%), visual disorder in 9 (20.9%), or others. Growth hormone deficiency was most common (42, 97.7%), followed by thyroid stimulating hormone, adrenocorticotropic hormone, gonadotropin, and anti-diuretic hormone deficit in order. Brain MRI was done in 41 patients, and 33 (80.5%) had abnormalities including pituitary gland ectopia/hypoplasia/aplasia and thin pituitary stalk/aplasia. Those with MRI abnormalities had higher number of hormone deficiencies (P for trend 0.049) than those without. Height and metabolic outcomes were evaluated in 17 adult patients, final height z-scores was -0.8±1.9, and 8 (47.1%) had dyslipidemia without other metabolic disturbances. Pathogenic or likely pathogenic variants were detected in 6 (25%) patients; 1 POU1F1, 1 GLI2, 1 HESX1, 1 TBC1D32 and 2 ROBO1.

Conclusion: Considering high proportion of neonatal presentation, it is important to early identify suspicious symptoms related to hypopituitarism to early manage pituitary and extra-pituitary phenotypes. Detection rate of genetic variant using NGS was 25%, and genetic causes in congenital hypopituitarism remain to be further determined.