Congenital hyperinsulinism
Key points
1:50,000
1:2500 in consanguinous births
Previously called nesidioblastosis
Pathophysiology
High glucose - ADP -> ATP in Beta cell
Closes K+ channels, membrane depolarises - Ca enters cell
Ca dependent insulin exocytosis
In CHI there is a K+ channel mutation - persistent insulin release
45% Diffuse: All beta cells affected
55% Focal: Mutated single beta cell leads to hyperplasia
Genetics
Diffuse: Mostly autosomal recessive
Focal: Paternal allele mutation affecting patient + maternal 11p15 region mutation in single beta cell
History and Examination
Neonate with persistent hypoglycaemia
Macrosomia
Differentiate from Beckwith-Wiedemann syndrome
Investigations
3 criteria - for prolong period of time
Glucose <2.8 fasting or postprandial with insulin concentration >36pmol/L
No ketogenesis or lipolysis
Hyperglycaemic response after glucagon administration
Genetic test for both parents - if mother negative then it is focal form - proceed to imaging
If diffuse - no imaging necessary
18F-DOPA PET/CT scan to confirm and locate focal lesion
Histology
Focal lesions retain lobular architecture of normal pancreas
Insulinomas do not
Enlarged cytoplasm and typically normal nuclei although nucleomegaly is not uncommon
Diffuse disease is characterised by nucleomegaly
Medical management
High glucose IVI
Diazoxide: K+ ATP agonist - not effective in recessive mutations (2/3 patients)
If fails after 5 days - give octreotide and glucagon
Laparotomy
Mobilisation of pancreas, palpation for focal lesion
Send frozen sections
If diffuse - near total pancreatectomy, leaving only small piece containing CBD
If focal - partial pancreatectomy - must confirm clear markings with frozen section - as can have octopus like tendrils
If in pancreatic head (45% are) - Beger-like procedure, or Whipples if duodenum involved
Outcome
95% cure in focal
50% cure in diffuse - but patients can be discharged off IV glucose
25% early diabetes - 90% in 10 years
Exocrine dysfunction in 50%
Neurodevelopmental abnormalities common
References
Laje, Pablo, and N. Scott Adzick. "Congenital Hyperinsulinism." Pediatric Surgery NaT, American Pediatric Surgical Association, 2020. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829506/all/Congenital_Hyperinsulinism.