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Adrenal (Excluding Mineralocorticoids)

SUN-423 - Subclinical Coronary Atherosclerosis and Bone Microarchitecture in ACTH-Independent Hypercortisolism: A Cohort from Two Tertiary Centers.

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Endogenous ACTH-independent hypercortisolism is associated with increased cardiovascular and skeletal morbidity. However, cardiovascular risk evaluation focused on subclinical atherosclerosis is often overlooked by conventional stratification tools, while skeletal fragility may be underestimated when assessed solely by bone mineral density (BMD). Real-world data integrating coronary artery calcium score (CAC) and trabecular bone score (TBS) across the spectrum of mild autonomous cortisol secretion (MACS) and overt Cushing’s syndrome remain limited.

This study evaluated two co-primary outcomes. The cardiovascular outcome was defined as discordance between low or intermediate AHA PREVENT ASCVD risk and subclinical atherosclerosis (CAC>0), with lipoprotein(a) [Lp(a)] as a complementary marker. The skeletal outcome was defined as discordance between degraded TBS (TBS < 1.23) and preserved BMD, without densitometric osteoporosis (T-score > −2.5 at all sites), with CTX as a complementary marker.

We conducted a retrospective cohort study of adults with ACTH-independent adrenal hypercortisolism followed at two tertiary endocrine centers over 10 years. Inclusion criteria were post–1 mg dexamethasone suppression test cortisol ≥1.8 µg/dL on two occasions, adrenal nodules ≥1 cm on CT or MRI, and classification as MACS or overt Cushing’s syndrome. CAC was assessed by non-contrast CT using the Agatston score, and 10-year ASCVD risk was estimated using AHA PREVENT equations. Skeletal evaluation included DXA, TBS, and CTX.

Thirty-one patients were included, 93.5% women, with a median age of 60.5 (95%CI 56.0–65.5) years. Active hypercortisolism was present in 61.3%, while 38.7% were in remission. Data availability was: AHA PREVENT in 27/31, CAC in 28/31, DXA with TBS in 21/31, Lp(a) in 21/31, and CTX in 18/31. Median 10-year PREVENT risk was 5.7% (95%CI 4.1–9.2). PREVENT–CAC discordance was observed in 32.0%. Among patients with CAC data (n=28), CAC>0 was present in 42.9% and CAC≥100 in 28.6%. Median Lp(a) was 44.7 mg/dL (95%CI 25.5–82.5), with 29.0% ≥50 mg/dL; the combined phenotype of Lp(a) ≥50 mg/dL and CAC>0 was identified in 10.5%. Degraded TBS was observed in 46.7%, with skeletal discordance in 28.6%. Median CTX was 0.417 ng/mL (95%CI 0.308–0.638). Among MACS patients (n=21), CAC>0 was present in ~44%, PREVENT–CAC discordance in 25%, and skeletal discordance in 33.3%. In overt Cushing’s syndrome, CAC>0 and PREVENT–CAC discordance were observed in 40%, with skeletal discordance in 16.7%.

ACTH-independent hypercortisolism is characterized by a high prevalence of subclinical atherosclerosis and skeletal microarchitectural abnormalities, often discordant with traditional cardiovascular risk estimation and BMD. These findings support evidence that MACS is associated with worse cardiovascular and osteometabolic outcomes, as observed in overt Cushing’s syndrome.

*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.*