Diagnosis: Hyperinsulinemia (Congenital Hyperinsulinism)
This newborn has congenital hyperinsulinism, as evidenced by the combination of severe hypoglycemia (glucose 2.2 mmol/L), inappropriately normal fasting insulin level (41 mIU/L), suppressed ketone production (hydroxybutyrate 0.1 mmol/L), and dramatic response to glucose administration.
Critical Diagnostic Features
The laboratory findings definitively point to hyperinsulinism through the following pattern:
Inappropriately detectable insulin during hypoglycemia: A fasting insulin of 41 mIU/L (20-100 range) is pathologically elevated when glucose is 2.2 mmol/L. In normal physiology, insulin should be undetectable (<5 mIU/L) at this glucose level 1, 2.
Suppressed ketone bodies: Hydroxybutyrate of 0.1 mmol/L is markedly low, indicating that insulin is blocking lipolysis and ketogenesis despite severe hypoglycemia. This is the hallmark of hyperinsulinemic hypoglycemia 2, 3.
Elevated cortisol: The cortisol level of 551 nmol/L (high) represents an appropriate counter-regulatory response to hypoglycemia, effectively ruling out adrenal insufficiency 2.
Dramatic glucose response: The glucose rising to 35 mmol/L after glucose administration suggests excessive insulin-mediated glucose uptake once substrate becomes available, consistent with dysregulated insulin secretion 1.
Why Other Diagnoses Are Excluded
Adrenal insufficiency (Option C) is ruled out by the elevated cortisol level. In adrenal insufficiency, cortisol would be inappropriately low during hypoglycemic stress 2.
Growth hormone deficiency (Option D) does not present with this laboratory pattern. GH deficiency causes hypoglycemia through different mechanisms and would not suppress ketone production to this degree 2.
Glycogen storage disease (Option B) is excluded because these disorders typically present with hepatomegaly, lactic acidosis, and elevated ketones during fasting (not suppressed ketones). The insulin level would be appropriately low, not normal-to-elevated 2, 3.
Understanding Congenital Hyperinsulinism
Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates and represents dysregulated insulin secretion that fails to suppress appropriately during hypoglycemia 4, 1.
The condition can result from:
- Mutations in KATP channel genes (KCNJ11, ABCC8) - most common 4
- Glucokinase mutations 3
- Glutamate dehydrogenase mutations (associated with hyperammonemia) 3
- Other genetic causes in approximately 50% of cases 3
Clinical Implications and Management Priorities
Immediate management priorities include:
- Maintaining glucose >3.3-3.9 mmol/L (60-70 mg/dL) to prevent permanent brain injury from recurrent hypoglycemia 1, 2
- High glucose infusion rates (often 10-20 mg/kg/min or higher) may be required 2
- Trial of diazoxide as first-line medical therapy 2, 5
- Consider octreotide if diazoxide-unresponsive 2
Genetic testing should be pursued immediately, as this is a permanent form of neonatal diabetes requiring specific genetic diagnosis 4. Some forms (KATP-related) may respond to sulfonylureas, while others require different management strategies 4.
Surgical evaluation may be necessary if medical management fails, particularly for focal forms of hyperinsulinism that can be cured with partial pancreatectomy 2, 5, 3.
Critical Pitfall to Avoid
The most dangerous error is dismissing a "normal range" insulin level during hypoglycemia. Any detectable insulin when glucose is <3.0 mmol/L is pathological and indicates hyperinsulinism 1, 2. The combination of detectable insulin with suppressed ketones during hypoglycemia is diagnostic, regardless of whether the absolute insulin value appears "normal" 2, 3.