Endocrine Abstracts

Introduction: To date, few cases with both congenital hypopituitarism (CH) and hyperinsulinaemic hypoglycemia (HH) have been reported in the literature. We now report a cohort of 12 cases with CHI associated with HH.

Clinical Phenotype: An association between congenital hypopituitarism (CH) and hyperinsulinaemic hypoglycemia (HH) was present in 12 patients (M:F 9:3). Mean age at diagnosis of HH was 0.9 months, whereas mean age at diagnosis of CH was 2.0 years (data based on n=10). Seven out of 12 patients have developmental delay, one has epilepsy, and four children have normal development. Nine patients had a small anterior pituitary identified on MRI, two had a normal pituitary gland, and no comment was made on the pituitary gland in one patient. Three patients with a small anterior pituitary also had an ectopic posterior pituitary gland. Ten out of 12 patients were diazoxide-responsive, although 50% of patients came off treatment in the first year of life. Molecular analysis led to the identification of genetic changes in a number of patients (dominant maternal ABCC8 mutation (n=1), denovo ABCC8 mutation (n=1), paternal intronic change in ABCC8 (n=1), KvDMR1 hypomethylation (n=1), EIF2S3 (n=3, three males from a single pedigree). Although EIF2S3 mutations have been previously associated with microcephaly and intellectual disability, this is the first description of disordered pancreatic function and hypopituitarism associated with EIF2S3 mutations.

Conclusion: This study reports a significant cohort of children in whom HH is associated with CH. A transient form of HH was identified in the majority of cases, and this was diazoxide-responsive in majority of cases too. Molecular analysis identified mutations in 7 of 12 children; although apart from the pedigree with the EIF2S3 mutation, the cause of hypopituitarism remains yet to be elucidated.