Background: Septo-optic dysplasia (SOD) is an important cause of hypopituitarism, although less common than multiple pituitary hormone deficiency (MPHD). Children with optic nerve hypoplasia (ONH) are at risk of hormone and neurocognitive disturbances.
Objective and Hypotheses: We describe clinical and neuroradiological findings of these three overlapping conditions, aiming to understand their pathophysiology.
Method: Retrospective analysis of clinical and neuroimaging data in 140 patients with hypopituitarism (MPHD, SOD) and ONH, collected at a tertiary endocrinology centre between 2000 and 2013.
Results: Male/female ratio in SOD (n=102), MPHD (n=28) and ONH (n=10) was 1.37, 1.33 and 0.66, respectively. There was no significant difference between the three groups in terms of birth characteristics. Given the mean age at last appointment in all groups (8.328.42 years), the majority of patients remained prepubertal and pre-adrenarcheal, although spontaneous puberty, in those who were of an appropriate age, had started in 86.6% SOD (26/30), 62.5% MPHD (5/8) and in all ONH (4/4). Abnormal male genitalia at birth was found in 27.5% SOD (16/59), 37.5% MPHD (6/16) and in none ONH (0/4). Obesity at last appointment was present in 25.5% SOD (26/102), 32.1% MPHD (9/28) and 30% ONH (3/10). Oral glucose tolerance tests (OGTT) revealed insulin insensitivity in 5/7 SOD patients with metformin administered to four of them. SOD was associated with hearing abnormalities (12.8%), hyposmia (2.9%), cardiovascular accidents (2%), hip dislocation (7.8%), autistic spectrum disorder (24.5%) and sleep disturbances (35.3%). Neurodevelopmental delay was more prevalent in ONH (90%). MPHD had a higher prevalence of certain pituitary abnormalities; hypoplastic adenohypophysis (89.3%), ectopic neurohypophysis (67.9%) and absent stalk (21.4%). SOD more frequently had abnormalities of the septum pellucidum (36.2%), corpus callosum (44.2%), optic chiasm (48.1%) and cortical dysplasia (9.9%).
Conclusion: SOD, MPHD and ONH patients show highly variable phenotypes, but shared clinical characteristics suggest that these conditions form a spectrum of midline brain abnormalities.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology