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Abstract Disclosure: B. Salama: None. O. Hamidi: None. T.S. Wang: None. A. Sada: None. M.A. Habra: None. P. Dogra: None. A.P. Dackiw: None. S.C. Oltmann: None. S. Mirfakhraee: None. I. Lingvay: None. T. Mckenzie: None. T. Foster: None. M. Lyden: None. B. Dy: None. V. Balderrama Brondani: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. Guidelines recommend initiating glucocorticoid replacement post-adrenalectomy. However, identifying patients at risk and accurately diagnosing AI can enable individualized management. Objectives: Determine the prevalence, duration and predictors of postoperative AI after unilateral adrenalectomy for MACS and compare baseline and peak cortisol post cosyntropin stimulation test (CST) In diagnosing AI. Methods: We conducted a multicenter retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and post-operative CST evaluation between January 1, 2013, and August 31, 2024. MACS was defined as cortisol >1.8 mcg/dL following overnight administration of 1 mg dexamethasone (DST-cortisol). AI was diagnosed when post-operative day 1 early morning baseline cortisol was <10 μg/dL and/or CST peak cortisol was <18 μg/dL. Baseline and peak cortisol levels were considered concordant when both met cut-offs. Biochemical (BSS) and clinical (CSS) severity scores were calculated. Results: Among 281 adults with MACS (80% women, median age 57 years, interquartile range [IQR] (47-64), the median adenoma size was 3.0 cm (IQR, 2.3-3.9), and 62 (22%) had bilateral disease. The median BSS was 4 (IQR, 3-5), and the median CSS was 6 (IQR, 2-11). Postoperative AI was diagnosed in 153 (54.5%) patients. A multivariable analysis showed that a higher BSS (OR = 1.17, 95% CI 1.01-1.36) and younger age at diagnosis (OR = 0.64, 95% CI 0.50-0.81), but not sex, BMI, or laterality, were associated with AI. Diagnosis of AI was concordant based on the baseline and peak CST cortisol cutoffs in 78% of patients. Diagnosis of AI was discordant in 22%: in 35 patients (12%), baseline cortisol was <10 μg/dL, but CST peak cortisol was ≥18 μg/dL, and in 28 cases (10%), baseline cortisol was ≥10 μg/dL, but CST peak cortisol was <18 μg/dL. Patients with bilateral MACS were more likely to have discordant results (32% vs. 19%, P < 0.001). During a median postoperative follow-up period of 15.4 months, 108 patients (70.6%) recovered from AI. The median time to recovery was 3.9 months (IQR, 3-5.9), with 41% recovering by 3 months, 60% by 6 months, and 73% by 12 months. The median time to recovery was associated with baseline BSS: mild: 3 months, moderate: 4.7 months, and severe: 14.5 months. Conclusion: We found that more than half of patients with MACS develop postoperative AI, with 50% recovering by 4 months post-surgery. BSS was associated with both the development and duration of AI. Baseline and CST peak cortisol results were concordant only in 78% of patients, thus performing both should be considered for an accurate diagnosis of AI. Presentation: Sunday, July 13, 2025

Abstract Context Patients with mild autonomous cortisol secretion (MACS) can develop adrenal insufficiency after unilateral adrenalectomy. Objective This work aimed to determine the prevalence, duration, and predictors of adrenal insufficiency, and compare postoperative basal cortisol and cosyntropin stimulation test (CST). Methods In this multicenter retrospective study of patients with MACS, adrenal insufficiency was diagnosed when postoperative basal cortisol was less than 10 µg/dL and/or CST < 18 µg/dL. The results were concordant when both tests met cutoffs. Biochemical (BSS) and clinical severity scores (CSS) were calculated. Results Among 281 patients with MACS (80% women), postoperative adrenal insufficiency was diagnosed in 153 (54.5%) patients. Adrenal insufficiency inversely correlated with age (odds ratio [OR] 0.67 per 10 years; 95% CI, 0.53-0.84). Low basal cortisol and CST were associated with younger age (OR 0.64 per 10 years for both) and higher BSS (OR 1.17 and 1.22, respectively). Basal cortisol and CST were discordant in 22% of patients, and the discordance rate was more common in patients with bilateral nodules (32% vs 19%; P < .001). The median time to adrenal insufficiency recovery was 3.9 months (IQR, 3-5.9 months), with longer duration associated with higher BSS and CSS: 3 months for mild, 4 to 5 months for moderate, and 12 to 14 months for severe BSS and CSS. Conclusion Approximately half of patients with MACS developed postoperative adrenal insufficiency, with 50% recovering by 3.9 months after surgery. BSS correlated with basal cortisol, CST, and duration of adrenal insufficiency. As discordant results were noted in 22%, performing both basal cortisol and CST postoperatively should be considered.

Abstract Disclosure: O. Hamidi: Advisory Board Member; Self; Corcept, Neurocrine Biosciences, Amryt Pharma, Recordati Rare Diseases, Lantheus, Xeris. B.H. Salama: None. P. Dogra: None. A.P. Dackiw: None. F. Nwariaku: None. A. Islam: None. A. Mehta: None. S.C. Oltmann: None. S. Mirfakhraee: None. T. McKenzie: None. T.R. Foster: None. M. Lyden: None. B.M. Dy: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. We aimed to determine the prevalence, predictors, and duration of AI after unilateral adrenalectomy for MACS, and to compare baseline and peak cortisol post cosyntropin stimulation test (CST) in diagnosing AI. Methods: We conducted a dual-center retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and were evaluated with postoperative cosyntropin stimulation test (CST). AI was diagnosed when postoperative morning cortisol was <10μg/dL and/or CST peak cortisol was <18μg/dL. Baseline and CST peak cortisol levels were considered concordant when both met corresponding cut-offs. Biochemical (BSS) and clinical (CSS) severity scores for hypercortisolism were calculated. Results: In 100 adults with MACS (77% women, median age 56 years, interquartile range [IQR] 48-63), median adenoma size was 2.8 cm (IQR, 2.2-3.7), and 25 (25%) had bilateral nodules. Median BSS was 3 (IQR, 2-5) and median CSS was 4 (IQR, 2-8). After adrenalectomy, AI was diagnosed in 56 (56%) patients. AI was associated with higher BSS, larger tumor size, but not age, sex, BMI, tumor laterality. Baseline and CST peak cortisol levels were concordant in 76% of cases. In 14% of cases morning cortisol was <10μg/dL but CST peak cortisol was ≥18μg/dL, and in 10% of cases morning cortisol was ≥10μg/dL, but CST peak cortisol was <18μg/dL. On a multivariable analysis that included age, sex, BMI, BSS, laterality, and tumor size, only higher BSS (odd ratio [OR] = 1.6 per 1 point) was associated with postoperative baseline cortisol <10μg/dL (P<0.05 for all). Independent predictors of CST peak cortisol <18μg/dL were BSS (OR 1.5 per 1 point) and unilateral adenoma (OR 3.7). During a median postoperative follow up of 13 months, 33 (59%) patients recovered from AI. Median time to recovery was 6.0 months, with AI recovery in 28% of patients by 2 months, 42% by 3 months, 53% by 6 months, and 64% by 12 months. Conclusions: Prevalence of postoperative AI in MACS was 56%. Only 76% of patients had concordant baseline and CST peak cortisol, with peak CST cortisol being more commonly abnormal in patients treated for unilateral MACS. Patients with larger adenomas and higher BSS were at higher risk for AI. Patients with MACS should be counseled about the risk and duration of AI after adrenalectomy. Presentation: 6/3/2024