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.

Automated summary

In the investigation of adrenal incidentalomas, ACTH(ONDST) and ACTH ratio were found to be markers of HPA axis suppression. For patients with cortisol(ONDST) >= 50 nmol/L, ACTH(ONDST) >= 0.6 pmol/L and ACTH ratio >= 18% were effective in detecting inadequate suppression of the HPA axis.