ESPE Abstracts

Background: Hypoglycemia etiology in children is heterogeneous and varies by age. Both growth hormone (GH) and cortisol deficiencies may present with hypoglycemia; the latter may result in an adrenal crisis that may be fatal.

Objectives: To evaluate responses of cortisol and GH to spontaneous hypoglycemia in infants and children, and to assess the rate of true cortisol deficiency in children, defined as cortisol<500 nmol/l.

Study design: This retrospective study included 127 children (0-18 years old) who presented with hypoglycemia during 1992-2022, and who had a serum laboratory glucose level ≤50 mg%.

Results: Cortisol <500 nmol/l was detected in critical samples of 50% (n=64) of the patients, and cortisol <270 nmol/L in 12.2% (n=29). A normal cortisol response to Synacthen stimulation was observed in 93.7% (n=119). Compared to the rest of the cohort, among children with cortisol levels <500 nmol/L, the median GH level in the critical samples was higher (6.0 vs. 3.4 ng/ml, P<0.037), and insulin was detected more frequently (59.6% vs. 35.6%, P<0.011). No other biochemical or clinical differences were observed between these groups. A critical sample cortisol level was associated with fast test nadir cortisol (r= 0.574; P<0.001) and Synacthen stimulated cortisol (r= 0.448; P=0.004), but not with age (r= -0.009; P=0.922) or with glucose (r= 0.025; P=0.802), insulin (r= -0.122; P=0.206) or GH (r= -0.163; P=0.088) levels measured in critical samples. Critical sample GH levels were inversely related to age (r= -0.322; P<0.001) and measured glucose (r= -0.431; P<0.001), but not to critical sample cortisol or height-SDS (r= 0.021; P=0.836). True cortisol deficiency was diagnosed in 4.3% (n= 8). Four had multiple pituitary deficiency. The other diagnoses were: primary adrenal insufficiency (n=1), IGF1 receptor mutation (n=1), fructose 1,6 diphosphatase deficiency (n=1) and transient hyperinsulinism (n=1).

Conclusions: While an insufficient cortisol response to hypoglycemia is common among children, true cortisol deficiency is uncommon. As no one clinical parameter can diagnose cortisol deficiency, a Synacthen stimulation test should be performed to rule out adrenal insufficiency.