Two cases of diazoxide-responsive congenital hyperinsulinism with diffuse uptake of pancreas by 18F-DOPA PET-CT

Congenital hyperinsulinism is one of the most common causes of severe hypoglycemia in infancy. Brain can be more damaged in the situation of hyperinsulinemic hypoglycemia because there are no sufficient ketones required for brain metabolism. Some patients develop severe symptoms during the newborn period, others at a later age. Several genes including ABCC8, KCNJ11, GCK, GLUD1, and HNF1A are reported as the candidate genes of hyperinsulinemic hypoglycemia. 18F-DOPA PET-CT can be used to localize the extent of the hyperinsulinism.

Here, we report two cases of diazoxide-responsive diffuse form of congenital hyperinsulinism confirmed by positive PET-CT findings, although no specific genetic mutations were identified.

Case 1. A 9-year-old girl developed her first hypoglycemic seizure at the age of 65 days. Her blood glucose, insulin, C-peptide, cortisol, and ammonia levels were 42 mg/dL, 37.14 µIU/mL, 4.20 ng/mL, 21.85 ug/dL, and 54 µmol/L, respectively. Diazoxide was started and she was referred to our Pediatric Endocrinology Clinic at 9 months of age due to recurrent episodes of hypoglycemia. Genetic investigation, including whole exome sequencing, did not reveal any pathogenic mutation. She grew up well while adjusting the medication and showed normal development. 18F-DOPA PET-CT was performed to find the pathologic range, which revealed diffuse uptake of the pancreas from head to tail.

Case 2. A 25-month-old boy developed seizure at the age of 6 months and was diagnosed with epilepsy. Antiseizure medication started. Seizure-associated hypoglycemia was first identified at 11 months of age and he was admitted to our Pediatric Endocrinology Clinic. Initial levels of blood glucose, insulin, C-peptide, cortisol, and ammonia were 35 mg/dL, 10.5 µIU/mL, 2.9 ng/mL, 18.5 ug/dL, and 40.4 µmol/L, respectively. There was no ketonemia. Diazoxide has been added to antiseizure medication. Although blood sugar was well controlled, he exhibited occasional seizures and global developmental delay. Genetic evaluation did not reveal any specific abnormality. 18F-DOPA PET-CT showed a widespread uptake in the pancreas.

The two cases showed very different clinical courses. Here, we report two cases of diazoxide-responsive diffuse form of congenital hyperinsulinism confirmed by positive PET-CT findings.