ACTH Stimulation Testing Is Often Unnecessary After Appropriate Patient Preparation Prior to Screening Cortisol Measurement

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.