Suppressed ACTH Is Frequently Unrelated to Autonomous Cortisol Secretion in Patients With Adrenal Incidentalomas

Objective: ACTH is considered a weak marker for autonomous cortisol secretion (ACS) in patients with adrenal incidentalomas (AIs). Our aim was to investigate suppressed basal ACTH as a marker of ACS and to elucidate why this criterion is of limited value. Methods: Basal ACTH and cortisol after overnight dexamethasone suppression test (cortisolONDST) were measured in 198 patients with unilateral AI and at 2-year follow-up. Basal ACTH was measured in 100 control subjects. Results: In patients with cortisolONDST <50 nmol/L (n = 145), ACTH was <2 pmol/L in 19%, compared with 4% in control subjects (P < 0.001). ACTH and size of AI correlated negatively (P = 0.002). Among patients with cortisolONDST ≥50 nmol/L, ACTH was <2 pmol/L in 53%. The patients were grouped according to whether cortisolONDST was <50 or ≥50 nmol/L and whether ACTH was <2.0 or ≥2.0 or pmol/L. At follow-up, these four groups were still separated with statistically significant differences in ACTH and cortisolONDST. Conclusions: This study identifies a previously unrecognized group of patients defined by suppressed ACTH despite normal cortisolONDST. This suppression of ACTH by a factor other than ACS may explain the limitation of suppressed ACTH as a marker for ACS. We suggest increased cortisol secretion in response to ACTH by the AI to be an additional factor.