Objective: The total cortisol (TC) response may be measured during the glucagon stimulation test (GST) for growth hormone (GH) reserve in order to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements of TC are unreliable in conditions of albumin and cortisol-binding globulin (CBG) alterations (e.g., hypoproteinemia or CBG deficiency). We aimed to measure the serum free cortisol (sFC) response to the GST in children and adolescents and determine whether it could predict the GH response to glucagon stimulation.
Methods: Infants and children with either short stature or growth attenuation who were referred for evaluation of GH reserve underwent the GST.
Results: The study population consisted of 103 subjects (62 females), median age 3.9 years (range, 0.5-14). The mean basal and peak TC levels were 13.3 ± 6.7 μg/dL and 29.6 ± 8.8 μg/dL, respectively. The mean basal and peak sFC levels were 0.7 ± 0.8 μg/dL and 1.7 ± 1.1 μg/dL, respectively. There was a negative correlation between peak TC and age ( r = -0.3, P = .007) but not between peak sFC and age ( r = -0.09, P = .36). Ninety-five percent of the patients had peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL.
Conclusion: Our results on a cohort of healthy short-statured children can serve as reference values for the sFC response during GST. Based on these results, we propose peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL for defining normalcy of the HPA axis during the GST in children and adolescents.
Abbreviations: ACTH = adrenocorticotrophic hormone BMI = body mass index CBG = cortisol-binding globulin GH = growth hormone GST = glucagon stimulation test HPA = hypothalamic-pituitary-adrenal SDS = standard deviation score sFC = serum free cortisol TC = total cortisol.