Related Experiment Video
Updated: Apr 7, 2026

A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Post-ACTH peak cortisol response is associated with genotype in children with nonclassic congenital adrenal
Allie N Dayno1, Marissa J Kilberg1, Erin Gonter1
1Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Introduction:
Suboptimal cortisol levels after ACTH stimulation have been recently reported in approximately 30% of patients with nonclassic congenital adrenal hyperplasia (NCCAH). There is little information on the role of genotype on cortisol secretion in NCCAH. The aim of this study is to investigate the association between genotype (i.e compound heterozygote for one mild and one severe CYP21A2 variant vs. homozygous for two mild variants) and peak cortisol response after ACTH stimulation in a pediatric population with NCCAH.
Methods:
Retrospective chart review to identify children with NCCAH who had 1) CYP21A2 genetic information 2) high dose ACTH stimulation test and 3) serum cortisol measurements by LC-MS/MS. The cohort was divided into 2 groups mild/mild (M/M) genotype (mild variants associated with NCCAH include V281L, P30L, P453S) and mild/severe (M/S) genotype (severe variants associated with classic CAH include gene deletion, Q318X, R356W, In2G, I172N) and peak cortisol concentrations were compared. IRB approved.
Results:
The cohort included 23 children - 12 M/M and 11 M/S diagnosed at 6.6 years old (SD 3.6, range 0.25-15). Peak cortisol levels were lower in the M/S group compared to M/M (mean +/- SD, 13.2 +/- 3.3 vs. 19 +/- 3.6 mcg/dL, p=0.001). The overall prevalence of adrenal insufficiency (AI) using cortisol cutoff of <15 mcg/dL (based on recent literature) was 9/23 (39%) and was higher in M/S vs. M/M (8/11, 73% vs. 1/12, 8%, p=0.003).
Conclusion:
The data suggest higher rates of suboptimal cortisol response in children with NCCAH who have mild/severe genotype compared to mild/mild.
Related Concept Videos
Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Hypothalamic-Pituitary Axis
Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Anatomy of the Adrenal Glands
These glands possess a distinctive yellow tinge due to the stored cholesterol and fatty acids required for hormone synthesis. They are encased in a fibrous capsule and cushioned by fat.
The adrenal gland comprises two distinct...
Nature and Nurture

