New cortisol assay-specific thresholds for the biochemical diagnosis of adrenal insufficiency after ACTH stimulation.

PURPOSE: Adrenal insufficiency (AI) is traditionally diagnosed using the corticotropin stimulation test (CST) with a cortisol threshold of 18.0μg/dL. However, newer immunoassays suggest revising this threshold to enhance diagnostic accuracy. This study aimed to evaluate the diagnostic performance of baseline cortisol (CB) and stimulated cortisol levels at 30min (C30min) and 60min (C60min) post-CST, using a revised threshold of 15.6μg/dL.

METHODS

This retrospective study analyzed a total of 140 patients with suspected AI who underwent CST from 2016 to 2022. Demographic, clinical, and biochemical data were collected. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis to compare the performance of the traditional 18.0μg/dL threshold with the proposed 15.6μg/dL cutoff.

RESULTS

The study population had a mean age of 45.6±19.3 years (68.6%, women). Mean cortisol levels were CB 12.3±5.7μg/dL, C30min 20.2±6.7μg/dL, and C60min 22.9±7.8μg/dL. A strong correlation was observed between CB and maximum stimulated cortisol (R=0.610, p=0.0003.) The revised 15.6μg/dL threshold reduced false-positive diagnoses by 17.9% (p=0.029). ROC analysis demonstrated high diagnostic accuracy for CB (AUC, 0.901), with CB>13.1μg/dL predicted a normal response, and CB<1.5μg/dL was always suggestive of pathology.

CONCLUSION

The revised 15.6μg/dL cortisol threshold enhances CST diagnostic accuracy by reducing false positives and avoiding unnecessary glucocorticoid therapy. Additionally, CB alone showed strong predictive value, and a single C30min measurement may be sufficient for diagnosis in most cases. Further validation studies across different immunoassay platforms are necessary.