Limited Diagnostic Utility of Cortisol and Growth Hormone Levels Obtained During Hypoglycemia in Children.

BACKGROUND: Pediatric hypoglycemia has heterogeneous, age-dependent causes. Both growth hormone (GH) deficiency and adrenal insufficiency (AI) may present with hypoglycemia; AI can lead to fatal adrenal crisis. OBJECTIVES: To assess cortisol and GH responses to spontaneous hypoglycemia and determine the prevalence of AI (cortisol <500 nmol/L). METHODS: Retrospective cohort of 133 children (1992-2022) with laboratory glucose ≤50 mg% during hypoglycemia. RESULTS: In critical samples (CS), cortisol <500 nmol/L was observed in 51.1% (n=68) and <276 nmol/L in 23.3% (n=31). AI was ultimately diagnosed in 5 patients (3.7%): four with multiple pituitary hormone deficiency and one with primary AI. Children with CS cortisol <500 nmol/L had higher median CS GH than the rest of the cohort (7.6 vs. 3.7 ng/mL, p<0.001) and more frequent detectable insulin (53.3% vs. 35.6%, p=0.052), with no other clinical or biochemical differences. CS cortisol correlated with fasting-test nadir cortisol (r=0.574, p<0.001) and Synacthen-stimulated cortisol (r=0.448, p=0.004), but not with age (r=0.026, p=0.765) or CS glucose (r=0.025, p=0.802). CS cortisol was inversely associated with CS insulin (r=-0.242, p=0.009). A CS GH <7.5 ng/mL was present in 56.9% of patients. CS GH showed inverse associations with age (r=-0.489, p<0.001) and glucose (r=-0.332, p<0.001), but not with height-SDS or weight-SDS (r=-0.046, p=0.694; r=-0.021, p=0.819). CONCLUSIONS: Blunted cortisol responses to spontaneous hypoglycemia in children are frequent, whereas AI is rare. In the absence of a reliable clinical discriminator, Synacthen testing is indicated. Suboptimal growth hormone responses are also common, and further assessment should be guided by clinical judgment.