SUN-012 - Post Dexamethasone Measurement of ACTH Helps Distinguish between ACTH-Independent and ACTH-Dependent Cushing Syndrome

Introduction
Basal ACTH levels historically have distinguished between ACTH-independent (adrenal) Cushing syndrome (aCS) and ACTH-dependent Cushing syndrome (Cushing disease [CD]). However, approximately 30% of patients have levels that fall into an indeterminate range of 5-20 pg/ml and some patients with CD have adrenal nodules. The overnight dexamethasone suppression test (DST) is a sensitive screening test routinely used for the diagnosis of endogenous hypercortisolism. This study evaluated whether post-DST ACTH levels in patients with hypercortisolism can distinguish between aCS and CD.

Methods
Retrospective analysis of 196 patients with Cushing syndrome from 2017 to 2024 (95 with aCS and 101 with CD) was performed. Correct diagnoses were confirmed using surgical confirmation (163 patients), post-operative adrenal insufficiency, and long-term follow-up. The full data set was used to find the post-DST ACTH cutoff with highest accuracy to distinguish between aCS and CD. A p-value of < 0.05 was considered significant.

Results
Median age was 57 for aCS patients and 42 for CD patients (p < 0.001). aCS patients were 83% female with median BMI of 34.2 kg/m2. CD patients were 77% female with median BMI of 34.7 kg/m2. Median post-DST cortisol was 3.6 µg/dl for aCS and 11.3 µg/dl for CD (p < 0.001). Median basal morning ACTH was 7.0 pg/ml (range 1.0-33.1) for aCS and 57.6 pg/ml (9.5-295.9) for CD (p < 0.001). Median post-DST ACTH was 3.1 pg/ml (1.0-26.5) for aCS and 35.8 pg/ml (5.0-166) for CD (p < 0.001). Odds ratios (95% CI) to diagnose CD for post-DST ACTH (1.37 [1.24-1.57]) and basal ACTH (1.31[1.15-1.29]) were both significant (p < 0.001). Basal ACTH was 5-20 pg/ml in 30.1% of patients (55 patients with aCS and 4 with CD). Using basal ACTH cutoffs of < 5 pg/ml or < 10 pg/ml, aCS was correctly diagnosed in only 37.2% and 61.7% of patients, respectively. A post-DST ACTH cutoff of 8 pg/ml had an accuracy of 92.4% in the diagnosis of aCS and CD with sensitivity 93.1% (CD) and specificity 91.6% (aCS). In a subgroup analysis of patients with basal ACTH 5-20 pg/ml, post-DST ACTH cutoff of 6 pg/ml had a 93.2% accuracy for the correct diagnosis of aCS and CD. The cutoff of 6 pg/ml correctly diagnosed 46 of 49 aCS patients with basal ACTH ≥5 pg/ml and 3 of 3 CD patients with basal ACTH ≤20 pg/ml.

Conclusions
ACTH values after DST are significantly lower in patients with aCS compared to CD. Measurement of post-DST ACTH helps reduce diagnostic uncertainty when differentiating between aCS and CD.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*