BASAL MORNING CORTISOL IN PATIENTS REFERRED FOR ACTH STIMULATION TESTING: DIAGNOSTIC PERFORMANCE IN A RETROSPECTIVE COHORT.

Context: Accurate diagnosis of adrenal insufficiency (AI) is crucial to prevent potentially life-threatening complications. Early-morning basal serum cortisol is widely used to guide further testing, its diagnostic performance varies across clinical settings. Objective: To evaluate the diagnostic performance of early-morning basal cortisol in patients referred for ACTH stimulation testing and to determine whether basal cortisol alone can reliably exclude AI. Design and Methods: This retrospective cohort study included 404 adult outpatients (mean age 45.3 years; 18.8% male) who underwent standard-dose ACTH (250 µg) stimulation testing between 2018 and 2022. All consecutive patients with available early-morning basal cortisol measurements were included. AI was defined as a peak cortisol response <18 µg/dL (≈497 nmol/L). Diagnostic performance was assessed using logistic regression and receiver operating characteristic (ROC) analyses. Results: AI was diagnosed in 27 patients (6.7%). Basal cortisol levels were inversely associated with ACTH test failure and demonstrated moderate discriminatory ability (AUC = 0.85). Despite higher basal cortisol being associated with lower AI probability, a small proportion of patients within clinically relevant cortisol ranges still failed stimulation testing. Conclusion: Early-morning basal cortisol provides valuable diagnostic information but cannot reliably exclude adrenal insufficiency when used alone. Confirmatory dynamic testing remains necessary to ensure diagnostic safety.