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

Objective: 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 (cortisol_ONDST) is low. Therefore, ACTH following overnight dexamethasone suppression (ACTH_ONDST) and cortisol following a 2-day dexamethasone suppression test (cortisol_2-DAYDST) were examined as markers of HPA axis suppression during ONDST. Design: This cross-sectional study examined patients with adrenal incidentalomas and basal ACTH ≥ 2.0 pmol/L who underwent ONDST. Measurements: ACTH_ONDST/ACTH ratio (ACTH ratio) was calculated for all patients. To define cut-off levels for ACTH_ONDST and ACTH ratio as markers of HPA axis suppression, ROC curves were used to separate patients with cortisol_ONDST <50 and ≥50 nmol/L. Results: Cortisol_ONDST was ≥50 nmol/L in 140 out of 373 patients. In patients with cortisol_ONDST <50 nmol/L, ACTH_ONDST was 0.28 pmol/L (<0.23–2.7). DHEAS was positively correlated to ACTH_ONDST, demonstrating a 9% increase with a doubling in ACTH_ONDST, p = 0.02. The best cut-off levels for ACTH_ONDST and ACTH ratio to detect cortisol_ONDST ≥50 nmol/L were ≥0.6 pmol/L and ≥18% respectively. These cut-off levels were tested on patients with cortisol_ONDST <50 nmol/L, considered to have adequate suppression (n = 233), and patients with reduction of ≥50 nmol/L from cortisol_ONDST to cortisol_2-DAYDST, who were considered to have inadequate suppression (n = 16). ACTH_ONDST ≥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. Conclusions: ACTH_ONDST and ACTH ratio can be markers of HPA axis suppression in the investigation of adrenal incidentalomas. Cortisol_ONDST ≥50 nmol/L with ACTH_ONDST <0.6 pmol/L or ACTH ratio <18% should lead to the suspicion of ACS.