SAT-465 Metabolic and Clinical Characteristics of Patients with Mild Autonomous Cortisol Secretion: A Retrospective Analysis of Adrenal Incidentalomas in a Referral Center

Abstract Disclosure: M. Eldib: None. N. Fretes Oviedo: None. V. Mendpara: None. J. Bena: None. P.P. Rao: None. R. Correa: None. Introduction: Mild Autonomous Cortisol Secretion (MACS) is characterized by abnormal circadian rhythm secretion of cortisol by the adrenal glands occurring independently of ACTH regulation. It is associated with adrenal incidentalomas (AI), which are adrenal gland masses detected incidentally through cross-sectional imaging performed for non-adrenal reason. MACS can be linked to various adverse clinical conditions, including dysmetabolism. Methods: We conducted a single-center, cross sectional observational study. Patients with AI, both with AI and normal response and with AI and MACS criteria, were compared using Fisher's exact test or Pearson's chi-square test. Standard deviations were calculated, and comparisons were made using two-sample t-tests. Results: Out of 8,080 patients with adrenal incidentalomas, 1,342 underwent a post-dexamethasone suppression test (DST). Among them, 101 (7.5%) patients met the criteria for MACS (post-DST cortisol 1.8-5.0 µg/dL with ACTH < 20 ng/dL), while 367 had a normal cortisol suppression response. The remaining patients were excluded from the analysis. The mean age of the cohort was 66 years, with no significant differences in age, race, or ethnicity between the two groups. In the MACS group, 77 (76%) were female, with 81 (80%) identifying as White. There were no significant differences between the MACS and Non secreting adrenal incidentaloma (NSAI) groups in the prevalence of hypertension, type 2 diabetes mellitus, osteoporosis, stroke, or myocardial infarction. Regarding biochemical markers, patients with MACS had significantly higher cortisol levels (median [IQR]: 4.5 [2.9, 13.4] vs. 1.5 [1.0, 8.7] µg/dL, p < 0.001) and HDL cholesterol (58 [44, 69] vs. 50 [42, 62] mg/dL, p = 0.033) compared to those with NSAI. They had lower DHEAS levels (45 [28, 67] vs. 64 [36, 102] µg/dL, p = 0.003). Discussion: This cross-sectional study did not identify clear complications directly linked to MACS. However, long-term issues such as central obesity, hypertension, insulin resistance, T2DM, dyslipidemia, cardiovascular disease, osteoporosis, and early mortality may not have been evident at diagnosis. Since patients were not followed longitudinally, potential metabolic sequelae or their progression over time could not be assessed. Conclusion: Patients with MACS, even without hypertension, T2DM, or dyslipidemia, may face adverse cardiovascular outcomes, likely due to insulin resistance and endothelial dysfunction from subtle cortisol excess. This real-world study highlights the need for long-term follow-up, as complications may be undiagnosed at diagnosis. Prospective studies and longitudinal follow up are crucial to identifying high-risk periods, monitoring disease progression, guiding treatment, and assessing the need for adrenalectomy. Presentation: Saturday, July 12, 2025