ESPE Abstracts

Background: Hyperinsulinemic hypoglycemia is a heterogeneous condition characterized by inappropriate insulin secretion in the presence of low blood glucose levels. It can have various causes, including genetic, metabolic, syndromic, autoimmune, insulinoma, non-insulinoma pancreatogenous hypoglycemia or non-islet cell tumor hypoglycemia. On the other hand, oculofaciocardiodental syndrome is a rare X-linked dominant condition characterized by multiple congenital abnormalities, such as congenital cataracts, multiple minor facial dysmorphic features, congenital heart defects, and dental anomalies. To our knowledge, there is one single case of hyperinsulinemic hypoglycemia due to pancreatic microadenomatosis associated with oculofaciocardiodental syndrome described until present.

Case presentation: We want to report the case of a 17 years old female adolescent, who presented in our service for recurrent hypoglycemic episodes. She was diagnosed at the age of 10 with hyperinsulinemic hypoglycemia, having no visible pancreatic lesion on abdominal ultrasound and CT. At time, she was successfully treated with diazoxide for two years. She is also known with cryptogenic epilepsy, cerebral arachnoid cyst and congenital cataract, and her mother had a history of pancreatic neuroendocrine tumor. At physical examination, she associated nystagmus, dental anomalies and congenital camptodactyly. Laboratory tests in our clinic showed glucose level of 24 mg/dL with inappropriate detectable insulin (6,05 uUI/mL) and C-peptide (0,502 ng/mL). Abdominal gadolinium MRI scan showed no pancreatic lesion. The familial history and clinical presentation raised the suspicion for a genetic syndrome, including MEN 1. Genetic evaluation and whole genomic sequencing emphasized a likely pathogenic mutation in BCOR gene, confirming the diagnosis of oculofaciocardiodental syndrome, but with no characteristic mutation for MEN 1 syndrome. Localizing the secretory lesion requires further investigation. Consequently, endoscopic ultrasound and EUS-guided fine needle aspiration are to be performed, and in the case of negative results, exploratory laparotomy and intraoperative ultrasonography of the pancreas will be envisioned. Other investigations, such as intra-arterial calcium stimulation or 68Ga-DOTATATE PET/CT have a high sensitivity for pancreatic mass detection, but are unavailable for now due to resource limitations.

Conclusion: This case poses multiple challenges for diagnosis and treatment. First, it is the insulin hypersecretion, most probably of pancreatic origin, with negative conventional anatomical imaging (US, CT, MRI), which requires multiple investigations for diagnosis. Second, it is the high clinical suspicion for MEN 1 syndrome, with no genetic mutation confirmation. Third, it is this rare oculofaciocardiodental syndrome, which, up to now, has been associated with hyperinsulinemic hypoglycemia in one single reported case.