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Updated: Jan 29, 2026

Cortisol Measurement in Koala Phascolarctos cinereus Fur
Published on: August 23, 2019
ACTH Stimulation Testing Is Often Unnecessary After Appropriate Patient Preparation Prior to Screening Cortisol
Christopher J Symonds1, Alexander A Leung1, Gregory A Kline1
1Cumming School of Medicine, Division of Endocrinology & Metabolism, University of Calgary, Calgary, Canada.
Context:
Screening morning serum cortisol is used to select patients for ACTH stimulation testing to diagnose adrenal insufficiency (AI) but may be affected by pre-analytical factors. Careful consideration to discontinue confounding medications beforehand may preclude the need for subsequent stimulation testing.
Objective:
To determine whether serum cortisol collected after discontinuation of confounding medications is more predictive of AI compared to screening morning cortisol without mandatory medication adjustment.
Methods:
Retrospective chart review of 835 patients with ACTH stimulation testing (Short Synacthen Test [SST]). Linear regression to compare Roche Cortisol II immunoassay screening cortisol versus optimally collected cortisol measurements after removal of confounding medications. Receiver operating characteristic (ROC) curve analyses to identify 100% sensitivity threshold for AI.
Results:
The majority of patients passed the SST (n = 756; 90.5%). There was a poor correlation between screening morning cortisol and optimally collected cortisol measurements, r = 0.34 (95% CI, 0.25-0.42). Real-world screening morning cortisol measurements had moderate discrimination for the diagnosis of AI (AUC 0.80; 95% CI, 0.77-0.82; p < 0.001) with a 100% sensitivity threshold for AI of 262 nmol/L. Applying this threshold would save 112 SSTs (13.4% of all tests). In contrast, an optimally collected serum cortisol had strong discrimination for AI (AUC 0.89; 95% CI, 0.87-0.91; p < 0.0001) and the threshold with 100% sensitivity for the diagnosis was 246 nmol/L which would save another 4.8% of all tests.
Conclusion:
Careful attention to pre-test patient preparation and implementation of a lower cortisol threshold may significantly reduce the number of stimulation tests needed to screen for AI.
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