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Adrenal (Excluding Mineralocorticoids)

SAT-413 - Cortisol Related Morbidities in ACTH-Independent Hypercortisolism: Are There Differences between MACS and Overt Cushing Syndrome?

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Ali Osman Balkan, MD: No financial relationships to disclose


Background:
Hypercortisolism is associated with metabolic, psychiatric, and bone-related comorbidities. Whether the burden of these conditions differs between mild autonomous cortisol secretion (MACS) and overt Cushing syndrome (CS) remains uncertain. We compared comorbidities among adults with MACS and CS undergoing adrenalectomy.

Methods:
A retrospective review of adults undergoing adrenalectomy (2002-2025) for ACTH-independent hypercortisolism was conducted. MACS and CS were defined per societal guidelines: MACS is defined by serum cortisol >1.8 mcg/dL following a 1 mg dexamethasone suppression test while CS was defined by clinical manifestations of CS along with biochemical evidence of hypercortisolemia. Hypertension (HTN), type 2 diabetes mellitus (DM2), hyperlipidemia (HLD), and mood disorders were defined by medical treatment requirements. Body mass index (BMI) and bone disease on DXA were assessed. Analyses used Kruskal-Wallis and Fisher’s exact tests.

Results:
A total of 225 patients were included: 193 (85.7%) had MACS and 32 (14.3%) had CS. Final pathology showed hyperplasia in 29 (13%) and adenoma in 196 (87%) with median (IQR) neoplasm size of 3.7 (2.7, 4.7) cm. BMI, sex distribution, and pathology did not differ between MACS and CS. Patients with CS were younger than those with MACS; median (IQR) age was 46 (36, 56) vs 60 (50, 67), p< 0.01. Overall, 77.6% had HTN, 37.5% DM2, 60% HLD, 53% depression, and 59% anxiety. Rates of HTN, DM2, HLD, and mood disorders were similar across groups. DXA scans were available in 131 patients; 60% had osteoporosis or osteopenia. Rates were higher in MACS (62.5%) than CS (47.4%), though not statistically significant (p=0.31).

Conclusions:
Despite differences in biochemical severity and cortisol autonomy, there were no significant differences in the prevalence of HTN, HLD, DM2, bone disease, or mood disorders among patients with ACTH-independent CS and MACS. The higher bone disease rate in MACS versus CS (62.5% vs 47.4%) likely reflects age differences, as general population prevalence is approximately 30% at ages 45–50 and 50-60% at ages 60–65; notably, both groups exceeded their age‑matched norms. These findings suggest that cortisol-related morbidities are not solely determined by biochemical severity, and that additional factors, such as duration of disease and cumulative cortisol exposure, may play an important role.

*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.*