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

Pediatric hypoglycemia has heterogeneous, age-dependent causes. Both growth hormone (GH) deficiency and adrenal insufficiency (AI) may be present with hypoglycemia; AI can lead to fatal adrenal crisis. Our objectives were to assess cortisol and GH responses to spontaneous hypoglycemia and determine the prevalence of AI (cortisol <500 nmol/L).

Retrospective cohort was comprised of 133 children (1992-2022) with laboratory glucose ≤50 mg% during hypoglycemia.

In critical samples (CSs), 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).

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 GH responses are also common, and further assessment should be guided by clinical judgment.