ESPE Abstracts

Background: Congenital combined pituitary hormone deficiency (CPHD) is a spectrum of disorders characterized by deficiencies in one or more pituitary hormones, ranging from isolated hormone deficiencies to complex hypopituitarism and severe midline developmental disorders. This study investigates the relationships between clinical features, laboratory findings, MRI results, and neurodevelopmental outcomes in patients with CPHD.

Methods: This retrospective, multicenter, cross-sectional study examined medical records from 62 patients diagnosed with CPHD across nine pediatric endocrine centers in Israel between 1987 and 2021. Patients were classified based on MRI results into four groups: normal MRI, isolated finding of pituitary stalk interruption syndrome (PSIS), PSIS with additional brain anomalies, and hypoplastic anterior hypophysis. Neurodevelopmental outcomes were categorized as normal, mild (including speech delay, motor clumsiness, learning difficulties), and severe (mental retardation).

Results: The cohort consisted of 62 patients (36 males), initially referred at a median age of 60 days (range 0-8760 days). Presentation at diagnosis were signs that may suggest hypopituitarism in infancy (43.7%), including hypoglycemia, jaundice and micropenis in males and growth failure (30.6%), neurodevelopmental delay during childhood (8.3%). MRI evaluation was normal in 9.7% of patients, while 61.3% exhibited isolated PSIS, 8.1% had PSIS with additional brain anomalies, and 21% showed hypoplastic anterior hypophysis. All patients demonstrated central hypothyroidism and growth hormone deficiency. ACTH deficiency was most prevalent in the PSIS group and least in the normal MRI group (85% vs 25%, P = 0.001). FT4 levels were notably lower in the normal MRI group compared to others (P <0.05). Developmental delays were observed in 43.5% of the cohort, with 25.8% exhibiting mild delays and 17.7% severe. A trend suggested that MRI abnormalities might correlate with more severe developmental delays, particularly evident in the PSIS group with additional brain anomalies, although this was not statistically significant (P = 0.295).

Conclusion: While MRI abnormalities in CPHD patients significantly correlate with hormonal deficiencies they show only a trend towards correlation with severe developmental delays, suggesting that additional factors influence neurodevelopmental outcomes. These findings underscore the importance of detailed neurodevelopmental assessments to better manage and potentially mitigate developmental challenges in CPHD patients. The results advocate for more extensive, multicentric international studies to further explore the correlations between clinical, hormonal, and imaging data with neurodevelopmental outcomes in rare and complex disorder.