Endocrine Abstracts

Background: Intra-uterine growth restriction (IUGR) is a known risk factor for the development of hyperinsulinaemic hypoglycaemia (HH). The phenotype of a large cohort of neonates who develop HH following IUGR has not been studied previously.

Aim: To characterise the clinical aspects of a cohort of neonates with IUGR who developed HH.

Methodology: Thirty-nine patients with IUGR (defined as birth weight <10th centile) who presented in the neonatal period with biochemically confirmed HH and referred to a tertiary endocrine hospital were recruited. Detailed clinical information was collected, followed by sequencing of KCNJ11 and ABCC8 genes.

Results: All except one patient required initiation of diazoxide therapy. 37/38 responded to treatment with diazoxide (5–10 mg/kg per day) and chlorothiazide (7–10 mg/kg per day) to correct their hypoglycaemia. Each of these patients was followed up at 1–3 monthly intervals and diazoxide withdrawal was undertaken when clinically indicated. In 6 patients, diazoxide and chlorothiazide therapy was stopped within 3 months of age, in 16 further patients within 6 months and in 6 further patients within a year of birth. Five patients had HH requiring diazoxide support for >1 year of age (oldest continuing diazoxide support at 23 years of age). The outcome is not known in four patients.

In 35/37 patients tested, mutations in ABCC8/KCNJ11 were not identified. Two patients were identified to have a paternally inherited ABCC8 mutation, with one confirmed to have a focal lesion requiring pancreatectomy.

Conclusion: Infants with IUGR may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients is important and may have important implications for neurodevelopmental outcome of these patients. The genetic aetiology of HH in the vast majority of infants with IUGR is not understood. Further studies are needed to understand the underlying mechanism of these observations.