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

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.

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.

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.

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.