ACTH following overnight dexamethasone suppression can be used in the verification of autonomous cortisol secretion in patients with adrenal incidentalomas

During the investigation of adrenal incidentalomas, it is important to accurately diagnose autonomous cortisol secretion (ACS) but the specificity of cortisol ≥50 nmol/L after overnight dexamethasone suppression (cortisolONDST ) is low. Therefore, ACTH following overnight dexamethasone suppression (ACTHONDST ) and cortisol following a 2-day dexamethasone suppression test (cortisol2-DAYDST ) were examined as markers of HPA axis suppression during ONDST.This cross-sectional study examined patients with adrenal incidentalomas and basal ACTH ≥ 2.0 pmol/L who underwent ONDST.ACTHONDST /ACTH ratio (ACTH ratio) was calculated for all patients. To define cut-off levels for ACTHONDST and ACTH ratio as markers of HPA axis suppression, ROC curves were used to separate patients with cortisolONDST <50 and ≥50 nmol/L.CortisolONDST was ≥50 nmol/L in 140 out of 373 patients. In patients with cortisolONDST <50 nmol/L, ACTHONDST was 0.28 pmol/L (<0.23-2.7). DHEAS was positively correlated to ACTHONDST , demonstrating a 9% increase with a doubling in ACTHONDST , p = 0.02. The best cut-off levels for ACTHONDST and ACTH ratio to detect cortisolONDST ≥50 nmol/L were ≥0.6 pmol/L and ≥18% respectively. These cut-off levels were tested on patients with cortisolONDST <50 nmol/L, considered to have adequate suppression (n = 233), and patients with reduction of ≥50 nmol/L from cortisolONDST to cortisol2-DAYDST , who were considered to have inadequate suppression (n = 16). ACTHONDST ≥0.6 pmol/L and ACTH ratio ≥18% had a sensitivity of 75% and 81% respectively, and a specificity of 78% and 85% respectively, for detecting patients with inadequate suppression.ACTHONDST and ACTH ratio can be markers of HPA axis suppression in the investigation of adrenal incidentalomas. CortisolONDST ≥50 nmol/L with ACTHONDST <0.6 pmol/L or ACTH ratio <18% should lead to the suspicion of ACS.