ACTH-independent hypercortisolism is most common in patients with diabetes and obesity, secondary analysis shows
Presenter: Andrew J. Newman, MD, Brigham and Women's Hospital/Mass General Brigham, Harvard Medical School, Boston, MA
ACTH-independent hypercortisolism across the cardiometabolic spectrum. Presented June 13, 2026.
Adrenocorticotropic hormone (ACTH)-independent hypercortisolism was more common among participants with greater cardiometabolic risk burden, with the highest prevalence observed in those with both obesity and type 2 diabetes, according to a secondary analysis presented by Andrew J. Newman, MD at ENDO 2026, June 13, 2026, in Chicago, IL.
ACTH-independent hypercortisolism examined across risk groups
ACTH-independent hypercortisolism occurs when the adrenal glands produce excess cortisol independent of ACTH stimulation. Because cortisol excess can contribute to hypertension, diabetes, obesity, and other cardiometabolic abnormalities, the condition may go unrecognized in patients with these common metabolic disorders. Emerging evidence suggests that ACTH-independent hypercortisolism is more prevalent among patients with cardiometabolic risk factors or diabetes than previously recognized.
Dr. Newman and colleagues performed standardized, protocol-defined assessments throughout the study to determine the prevalence of ACTH-independent hypercortisolism among 201 patients with increasing cardiometabolic risk factors in three cohorts:
- Normotensive participants who were overweight or obese (n = 71, mean body mass index 29.5 kg/m2)
- Participants with obesity and hypertension who did not have diabetes (n = 81, mean body mass index 35.2 kg/m2)
- Participants with type 2 diabetes who were also overweight or obese (n = 49, mean body mass index 31.5 kg/m2).
Participants underwent an overnight 1-mg dexamethasone suppression test, cosyntropin stimulation testing, and 24-hour urinary cortisol assessment. The investigators defined ACTH-independent hypercortisolism as a post-dexamethasone serum cortisol level greater than 1.8 µg/dL, with a concomitant plasma ACTH level below 10 pg/mL.
Hypercortisolism increased with cardiometabolic risk
Among the 201 study participants, 14 (7.0%) had ACTH-independent hypercortisolism, with the highest prevalence (5 of 49; 10.2%) among those with type 2 diabetes and overweight or obesity. Prevalence rates were lower in those with obesity and hypertension without diabetes (5 of 81; 6.2%) and in normotensive participants who were overweight or obese (4 of 71; 5.6%).
The investigators designed the three study cohorts to reflect differences in body mass index across cardiometabolic risk groups. However, among all participants, mean body mass index was similar in those with and without ACTH-independent hypercortisolism (31.3 vs 32.3 kg/m², P = .34). Age, hemoglobin A1c levels, blood pressure, and renal function were similar among both groups.
ACTH-independent hypercortisolism was associated with greater ACTH-stimulated cortisol production but not higher total daily cortisol output. These hormonal findings may reflect both a cause and a consequence of adverse cardiometabolic risk profiles, according to the investigators.
Disclosures
No disclosures.
References
Newman AJ, Mahrokhian J, Hanna I. ACTH-independent hypercortisolism across the cardiometabolic spectrum. Presented at ENDO 2026, June 13, 2026, Chicago, IL.
Endocrine Society. EndoBytes: Patient-centered approach to hypercortisolism screening and care. https://education.endocrine.org/AssetListing/EndoBytes-Patient-Centered-Approach-to-Hypercortisolism-Screening-and-Care-23807/Treatment-and-Long-Term-Care-of-Patients-with-Hypercortisolism-Cushing-Syndrome-and-MACS-43827 Accessed June 13, 2026.