Variations in Morning Serum Cortisol Levels Based on Sex and Pubertal Status

Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency.

A retrospective chart review was conducted using electronic medical records of patients seen at Children's Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males - both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation.

Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2-5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2-5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001).

These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the -pediatric population.