SAT-474 - Prevalence of Hypercortisolism in Patients with Inadequate Weight Loss Response to Anti-Obesity Medications

Objective
Among adults with obesity treated with FDA-approved incretin-based therapy, a subset fails to achieve expected weight loss despite documented adherence, raising concern for unrecognized hypercortisolism. This study aimed to determine the proportion of patients with an inadequate weight-loss response who underwent screening with a 1-mg overnight dexamethasone suppression test (DST) to screen for endogenous hypercortisolism.

Methods
We conducted a retrospective chart review of adults aged 18–75 years with obesity treated with FDA-approved anti-obesity medications (AOMs) at the Saint Vincent Hospital Endocrine Outpatient Office between June 1, 2024, and May 30, 2025, identified using ICD-10 code E66.9. Inadequate response was defined as < 5% total body weight loss after 12 weeks on the maximum tolerated dose with documented clinician-assessed adherence. Patients with factors affecting cortisol interpretation, including prior Cushing’s syndrome or adrenal disease, systemic glucocorticoid use, or oral contraceptive use, were excluded. Charts were reviewed for completion of a 1-mg overnight DST. When available, cortisol values, ACTH levels, and adrenal imaging findings were abstracted. The primary outcome was the proportion of inadequate responders who underwent DST screening; secondary outcomes included biochemical and imaging findings among those with abnormal DST results.

Results
Eighty-two charts were reviewed. Eighteen patients were excluded, leaving 64 eligible patients. Twenty-three patients failed to achieve ≥5% total body weight loss and met criteria for inadequate response. Of these, 17 patients (73.9%) underwent DST screening. Suppression of cortisol to < 1.8 mcg/dL was considered a normal response. Among screened patients, the mean age was 48.5 ± 12.2 years, mean BMI was 38.7 ± 7.8 kg/m², and 76% were female. Hypertension was present in 82.4%, hyperlipidemia in 41.2%, and type 2 diabetes in 30%. One patient (6%) had abnormal DST results with failure of suppression, low ACTH, and a 3-cm unilateral adrenal nodule on CT imaging, concerning for ACTH-independent hypercortisolism.

Conclusion
Our study demonstrated a low prevalence of endogenous autonomous hypercortisolism, as evidenced by non-suppressive cortisol levels following low-dose dexamethasone testing. Although uncommon, selective evaluation for hypercortisolism may uncover reversible contributors to metabolic treatment resistance in a small subset of patients with poor AOM response and supports the need for further prospective studies.

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