ORF25-04 - Diagnostic Accuracy of Overnight Dexamethasone Suppression Test in Defining Non-Functioning Adrenal Masses

Introduction: Non-functioning adrenal incidentalomas (NFAI) are defined by post–1 mg dexamethasone suppression test (F-1mgDST) cortisol levels < 1.8 µg/dL. However, emerging evidence suggests that many individuals classified as having NFAI may exhibit subtle cortisol excess link to increased cardiometabolic and skeletal risk.

Objective: To compare F-1mgDST levels between patients with NFAI and control subjects and to identify the F-1mgDST threshold for NFAI detection.

Materials and

Methods: Pooled individual participant data analysis of 7 retrospective and prospective studies evaluating cortisol secretion in patients with type 2 diabetes, osteoporosis and/or fragility fractures, hypertension, or adrenal incidentalomas. The study included 1681 participants (915 with NFAI and 766 controls), all with F-1mgDST < 1.8 µg/dL. Collected date: age, sex, BMI, F-1mgDST, and ACTH (available for all NFAI patients and for 176 controls).

Main outcomes included between-group differences in F-1mgDST and ACTH levels; diagnostic accuracy of F-1mgDST for identifying NFAI via receiver operating characteristic (ROC) analysis; and sensitivity, specificity, and odds ratios (ORs) for predicting NFAI across various F-1mgDST thresholds.

Results: Compared to controls, NFAI patients were younger and had lower BMI and ACTH levels but significantly higher F-1mgDST values. ROC analysis demonstrated that an F-1mgDST threshold of 1.1 µg/dL provided the best balance of sensitivity (54.8%) and specificity (57.2%), while an F-1mgDST threshold of 0.6 µg/dL and of 1.7 µg/dL the best sensitivity (93%) and specificity (93.5%), respectively, for distinguishing between control subjects and patients with NFAI. An F-1mgDST >1.1 µg/dL was independently associated with NFAI (OR, 1.58; 95% CI, 1.30–1.92) after adjusting for age, BMI, sex and presence of hypertension, type 2 diabetes and osteoporosis. The combination of obesity and male sex amplified the association, with obese men and F-1mgDST >1.1 µg/dL showing a nearly 3-fold higher likelihood of NFAI (OR, 2.87; 95% CI, 2.02–4.09).

Conclusions: Among individuals with cortisol concentrations within the currently accepted normal range after dexamethasone suppression, those with NFAI display significantly higher F-1mgDST levels than control subjects. These findings indicate that the widely used threshold of 1.8 µg/dL may not reliably exclude mild autonomous cortisol secretion. A lower threshold of 1.1 µg/dL may improve identification of individuals with NFAI.