Congenital Hyperinsulinemia
The most likely diagnosis is A) Congenital Hyperinsulinemia, based on the combination of hypoglycemia with inappropriately normal insulin levels (41 μU/mL), suppressed ketones (hydroxybutyrate 0.1 mmol/L), and dramatic response to glucose administration.
Diagnostic Reasoning
Critical Laboratory Pattern
The laboratory findings create a classic hyperinsulinemic profile:
Insulin level of 41 μU/mL during hypoglycemia (glucose 2.2 mmol/L) is inappropriately elevated - any detectable insulin during hypoglycemia indicates failure of normal insulin suppression, which is the hallmark of hyperinsulinism 1, 2, 3
Suppressed beta-hydroxybutyrate at 0.1 mmol/L confirms hyperinsulinemia - insulin blocks ketogenesis, and levels <0.6 mmol/L during hypoglycemia are diagnostic of hyperinsulinemic hypoglycemia 2, 3
Dramatic glucose response (2.2 to 35 mmol/L after glucose administration) demonstrates insulin-mediated glucose consumption - this brisk response is characteristic of hyperinsulinism where excess insulin rapidly drives glucose into cells 3, 4
Why Other Diagnoses Are Excluded
Adrenal insufficiency (Option C) is ruled out because:
- The cortisol level is markedly elevated at 551 nmol/L, not low 5, 6
- While neonates with hyperinsulinemic hypoglycemia paradoxically generate inappropriately low cortisol responses relative to the degree of hypoglycemia (typically 150-250 nmol/L), this patient's cortisol of 551 nmol/L is actually quite high and excludes primary adrenal insufficiency 5, 6
- The elevated cortisol likely represents a stress response, though it remains insufficient as a counterregulatory hormone in the context of severe hyperinsulinism 6
Glycogen storage disease (Option B) is excluded because:
- GSD typically presents with elevated lactate and uric acid, which are not mentioned here 2
- In GSD, insulin would be appropriately suppressed during hypoglycemia, and ketones would be elevated (not suppressed at 0.1) 2
- The dramatic response to glucose alone is less characteristic of GSD, which often requires continuous glucose infusion 2
Growth hormone deficiency would show appropriately suppressed insulin with elevated ketones during hypoglycemia, opposite of this presentation 2
Clinical Context Supporting Hyperinsulinism
Weight of 5 kg in a newborn suggests macrosomia - large birth weight is associated with HNF4A-MODY and certain forms of congenital hyperinsulinism 7, 2, 8
Hypotonia is a recognized feature of severe or prolonged hypoglycemia from hyperinsulinism, indicating potential neurological involvement 3, 9
Neonatal presentation - congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates 1, 3, 4
Immediate Next Steps
Genetic testing should be pursued immediately for:
- KATP channel mutations (KCNJ11, ABCC8) - the most common cause of congenital hyperinsulinism 7, 1, 4
- HNF4A mutations - given the large birth weight (5 kg) and neonatal hypoglycemia pattern 7, 2, 8
Treatment implications are critical:
- Some KATP-related forms respond to high-dose sulfonylureas rather than requiring pancreatectomy 7, 1
- HNF4A-MODY may present with transient neonatal hyperinsulinemic hypoglycemia that resolves, but patients develop diabetes later in adolescence/early adulthood and respond well to low-dose sulfonylureas 7, 2, 8
Maintain plasma glucose >70 mg/dL (3.9 mmol/L) to prevent permanent brain damage - this is the primary treatment goal in hyperinsulinism 3, 9
Common Pitfall
The "normal range" insulin of 41 μU/mL misleads clinicians into excluding hyperinsulinism. Any measurable insulin during documented hypoglycemia is pathological - normal physiology should suppress insulin to undetectable levels (<2 μU/mL) when glucose falls below 3.0 mmol/L 2, 3. The combination of detectable insulin with suppressed ketones (<0.6 mmol/L) during hypoglycemia is diagnostic of hyperinsulinemic hypoglycemia regardless of whether the absolute insulin value falls within a laboratory's "normal range" 2, 3.