SUN-480 GLP-1 Agonist Therapy Managing the Effects of Excess Glucocorticoid Production

Abstract Disclosure: B.R. Bedell: None. S. Chandran: None. S. Gandhi: None. Background: Adrenal incidentalomas can be associated with mild autonomous cortisol secretion (MACS) . Patients with MACS have a high likelihood of developing signs/symptoms associated with cortisol excess, such as diabetes, hypertension, and hyperlipidemia (1). Adrenalectomy can improve metabolic parameters in many cases. We present a case of MACS where GLP-1 agonist administration reversed the metabolic impact of excess cortisol despite ongoing autonomous secretion. Clinical Case: The patient is a 59-year-old male with history of obesity, HTN, and HLD who initially presented for weight gain refractory to aggressive lifestyle change. His exam was notable only for central adiposity. Imaging prior to the visit showed three incidental bilateral adrenal nodules, with imaging features consistent with adenomas. Biochemical testing revealed an AM cortisol of 20.57 ug/dL (5.30 – 22.50), with an ACTH of 8 pg/mL (0 – 47). 1mg dexamethasone suppression testing was positive three times. 8mg dexamethasone suppression showed cortisol level of 4.8 ug/dL (< 1.8 mg/dL). DHEA-S was low at 29.61 ug/dL (34.50 -568.90), consistent with ACTH-independent MACS. These values were suggestive of mild autonomous cortisol secretion. Other tests were within normal limits or negative, including midnight salivary cortisol testing, 24-hour urine cortisol, fractionated metanephrines, aldosterone/plasma renin activity ratio, and 17-hydroxyprogrestone. His A1C was 5.1%. He was found to have mild osteopenia on DEXA with lowest T score -1.4 in femoral neck, possibly due to both MACS and recently diagnosed hypogonadism, for which he was started on testosterone. Given that he had bilateral nodules making lateralization via adrenal vein sampling difficult, immediate adrenalectomy was deferred. He was started on semaglutide for weight management. Over the course of 18 months, he achieved significant resultant weight loss (25% of body weight, 245 lbs to 180 lbs) along with control of his HTN and HLD despite ongoing autonomous cortisol production. Conclusion: Although adrenalectomy is generally considered the preferred definitive treatment, GLP-1 receptor agonist administration improved metabolic parameters and resulted in significant weight loss in this patient with MACS.. This suggests a possible role for GLP-1 RAs in managing the effects of excess glucocorticoid production in patients with MACS as an adjunct or bridge to definitive therapy. References: 1.Pelsma ICM, Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis. Eur J Endocrinol. 2023 Oct 17;189(4):S88-S101. doi: 10.1093/ejendo/lvad134. PMID: 37801655. Presentation: Sunday, July 13, 2025