What is the management of congenital hyperinsulinism according to Endocrine Society guidelines?

Management of Congenital Hyperinsulinism

Diazoxide is the first-line medication for the management of congenital hyperinsulinism (CHI), and should be initiated promptly after diagnosis to prevent neurological damage from hypoglycemia. 1, 2

Diagnostic Approach

• CHI is the most common cause of persistent hypoglycemia in neonates and children, characterized by inappropriate insulin secretion leading to recurrent hypoglycemia 2
• Initial evaluation should include:
  • Blood glucose monitoring to document hypoglycemia (typically <50 mg/dL)
  • Critical sample collection during hypoglycemic episode (insulin, cortisol, growth hormone)
  • Genetic testing for mutations in KATP channel genes (ABCC8, KCNJ11) and other associated genes 3

Medical Management

First-line Treatment

• Diazoxide: FDA-approved for management of hypoglycemia due to hyperinsulinism 1
  • Starting dose: 5-15 mg/kg/day divided into 2-3 doses
  • Maximum dose: up to 15-20 mg/kg/day if needed
  • Monitor for side effects: fluid retention, hypertrichosis, neutropenia 2, 3
  • Add hydrochlorothiazide if fluid retention occurs 3

For Diazoxide-Unresponsive CHI

• Octreotide (off-label): 5-40 μg/kg/day divided into 4-6 subcutaneous injections or continuous infusion 2, 3

  • Monitor for side effects: gastrointestinal symptoms, gallstones, growth suppression
  • May be administered via insulin pump for continuous delivery 4

• Long-acting somatostatin analogs (off-label) for older children with stable disease:

  • Lanreotide acetate: 30 mg deep subcutaneous injection once monthly 4
  • Consider in children >2 years old with stable disease who respond to octreotide 4

• Glucagon (off-label): 1-20 μg/kg/hour as continuous IV infusion for acute management of hypoglycemia 2, 5

Nutritional Management

• Frequent feeding schedule with complex carbohydrates 5
• Continuous enteral feeding may be required for severe cases 2, 5
• Maintain blood glucose levels >70 mg/dL (3.9 mmol/L) 5, 6

Surgical Management

• Indicated for focal CHI or diffuse CHI unresponsive to medical therapy 3, 6
• Preoperative imaging with 18F-DOPA PET scan to differentiate focal from diffuse disease 2, 6
• Surgical options:
  • Focal CHI: Selective lesionectomy (curative) 3
  • Diffuse CHI: Near-total pancreatectomy (95-98%) if medical management fails 2, 3
  • Post-surgical complications include persistent hypoglycemia, diabetes mellitus, and exocrine insufficiency 3

Monitoring and Follow-up

• Regular blood glucose monitoring (consider continuous glucose monitoring for unstable cases) 5, 6
• Monitor for medication side effects and adjust dosages as needed 3
• Neurodevelopmental assessment due to high risk of brain damage from hypoglycemia 3, 6
• Long-term follow-up for development of diabetes, especially after pancreatectomy 3

Special Considerations

• Transient forms of CHI may resolve over time; regular reassessment of medication requirements is necessary 3
• Approximately 50% of children with CHI experience negative cognitive impacts from early-life hypoglycemia 3
• Treatment should be coordinated through specialized centers with expertise in CHI management when possible 5, 6
• Genetic counseling should be offered to families as CHI has significant genetic components 6

Emerging Therapies

• Novel treatments are in development but none have yet been approved for clinical use 2, 6
• Clinical trials are ongoing for GLP-1 receptor antagonists, KATP channel activators, and other agents 2