1. Glycogen synthesis Glycogenolysis Insulin Epinephrine Glucagon
receptors
Parasympathetic
nervous system
activation
Glycogen
synthesis
Glycogenolysis
Sympathetic
Epinephrine
Insulin
glycogen
glucose 1- phosphate

2. Etiology: Classification
Inadequate production
Increased utilization

3. Hormonal Response to Hypoglycemia
Suppression of insulin secretion
Glucagon release
Epinephrine and cortisol levels increase
Growth hormone levels increase
Results in suppression of glycogenolysis, activates gluconeogenesis, promotes lipolysis, and stimulates ketogenesis

4. Etiology: inadequate production of glucose
Prematurity, IUGR, Perinatal stress
Glycogen storage disease
GSD type 1: glucose-6-phosphatase deficiency, catalyzes final common step in glycogenolysis and gluconeogenesis
GSD type 3: debrancher deficiency, inability to degrade stored glycogen. Autosomal recessive and manifestations include hepatomegaly, hypoglycemia, skeletal myopathy, cardiomyopathy

5. Congenital Hyperinsulinism
Sporadic and familial, incidence from 1/50,000-1/2500
In the presence of hypoglycemia:
inadequately suppressed insulin level and evidence of excessive insulin action for the degree of hypoglycemia:
inappropriately low plasma ketones and free fatty acids, inappropriately large glycemic response to glucagon.

6. Congenital Hyperinsulinism
To date, mutations in 4 different genes have been identified
Mutations in either of the two subunits of the ß-cell ATP-sensitive potassium channel (KATP)
Mutations in glucokinase (glucose sensor of the ß-cell)
Mutations in glutamate dehydrogenase
At least 50% of cases have no identified genetic cause

7. Congenital Hyperinsulinism

8. Congenital Hyperinsulinism
Recessive hyperinsulinism
Previous referred to as nesidioblastosis
Islet hyperplasia throughout pancreas
Severe hypoglycemia
LGA newborns
Genetic defect: SUR1 or kir6.2 components of the KATP channel. Thus, therapeutic interventions that act via the SUR such as diazoxide are ineffective
Most infants require near-total pancreatectomy

9. Congenital Hyperinsulinism
Focal Hyperinsulinism
Area of islet hyperplasia is localized to a small 3-5 mm diameter region described as focal adenomatous hyperplasia
Clinical presentation similar to diffuse disease (severe early hypoglycemia)
Results as a localized clonal loss of the maternal 11p15 region and expression of a paternally inherited SUR1 or Kir6.2 mutation. The 11p15 region contains several maternally imprinted tumor suppressor genes.
Can respond to partial pancreatectomy

10. Treatment of hyperglycemia
Decrease glucose infusion rate!
Only administer insulin if osmotic diuresis is present or glucose levels remain significantly elevated despite a reduction in glucose infusion rate.