Management of the Patient with Suspected Hyperinsulinism
Diagnosis of hyperinsulinism
Clues to diagnosis of hyperinsulinism
- Large for gestational age
- Severe, persistent hypoglycemic requiring high GIR (>8 mg/kg/min)
Laboratory findings at the time of hypoglycemia (BS <50 mg/dL)- provoked or spontaneous
- Inappropriately low beta-hydroxybutyrate (<0.6 mmol/L)
- Inappropriately low free fatty acids (<0.5 mmol/L)
- +/- Inappropriately elevated insulin
Glucagon stimulation test
- When glucose <50 mg/dL , give glucagon 1 mg IV/IM
- Monitor blood sugar every 10 minutes for 40 minutes; if there is no increase in blood sugar by 20 minutes, terminate test and rescue with IV dextrose
- A positive response is a rise of more than 30 mg/dL and indicates that the hypoglycemia is due to increased insulin action
Cautions in diagnosing and managing HI
- Low cortisol and/or growth hormone at time of hypoglycemia not diagnostic of cortisol or GH deficiency ► other stimulation testing needed to prove cortisol or GH deficiency
- Insulin levels are not always elevated at the time of hypoglycemia in children with hyperinsulinism, but suppressed beta-hydroxybutyrate (and free fatty acids) and a positive response to glucagon are sufficient to make the diagnosis
- Children who have undergone a Nissen fundoplication or other gastric surgeries are at risk of postprandial hypoglycemia (“late dumping syndrome”) which is due to excessive insulin response to feeding and therefore could look like hyperinsulinism. Establishing the timing of the hypoglycemia in relationship with feedings is helpful to distinguishing these cases.
- Do not use glucocorticoids to treat hyperinsulinism or unspecified hypoglycemia
- Do not force feed to control blood glucose (can develop feeding aversion)
Medication trial
1st line therapy- 5 day trial of Diazoxide 15 mg/kg/day (dosed 5-15 mg/kg/day)
- Wean GIR as tolerated to maintain BS >70 mg/dL
- After 5 days, attempt 8-18 hour (depending on the age of the child) safety fast off of IV dextrose ► if unable to fast, considered medical failure and should refer to CHOP (suggests KATP-HI)
- Side effects: fluid retention, hypertrichosis, neutropenia and thrombocytopenia. Young infants, especially if receiving fluids, may need diuretics for fluid retention.
If diazoxide failure, stop diazoxide and initiate glucagon infusion 1 mg/day if unable to maintain BS >70 mg/dL with IV dextrose
Genetic testing - should be sent after diagnosis of HI is made
- Send to the Hospital of the University of Pennsylvania or University of Chicago
- For UPenn, please select tier 1 reflex tier 2 option
- For Chicago, please select tier 1 reflex Congenital Hyperinsulinism Panel
- Also should send parental samples (mother and father) at same time- Test 042- Parent testing
- If diazoxide-responsive and high ammonia levels, consider sending only Test 822- GLUD1 (CH) DNA sequencing test
To refer to CHOP
- Call 215-590-7682 and speak with a physician or APN
- Fax face sheet (demographics), clinical summary, pertinent labs to 215-590-3053
- Have your discharge planner contact insurance company to initiate referral AND call our center, 215-590-7682
- Discharge planner to complete pre-admission checklist
Other considerations
- Octreotide, which has been 2nd-line therapy for congenital HI has been associated with NEC; for this reason we do NOT recommend its usage prior to surgery
- Double-lumen PICC would be helpful prior to transfer
- Hypertrophic cardiomyopathy is common in infants with congenital HI- consider ECHO +/- Cardiology consult prior to transfer
References
- Lord K, De León DD. Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. Int J Pediatr Endocrinol. 2013 Feb 6;2013(1):3.
- Palladino, AA., Stanley, CA. A specialized team approach to diagnosis and medical versus surgical treatment of infants with congenital hyperinsulinism. Semin Pediatr Surg. 20(1):32-7, 2011 Feb.
