Ahmadian, Sarina

Abstract Context Salivary cortisol and cortisone provide non-invasive measures of biologically active cortisol, but their performance during dynamic testing remains incompletely defined. The utility of salivary dexamethasone to confirm exposure during dexamethasone suppression testing (DST) is unknown. Objective To compare salivary cortisol, cortisone, and dexamethasone with serum measurements during dynamic adrenal testing and to derive salivary cortisol and cortisone thresholds corresponding to clinically relevant serum cortisol concentrations. Design and Setting Cross-sectional study at a tertiary referral center. Participants Adults undergoing DST (n = 473), cosyntropin stimulation testing (CST; n = 163), or overnight metyrapone testing (OMT; n = 11). Measurements Serum cortisol was measured by immunoassay. Serum and salivary dexamethasone, salivary cortisol and cortisone were quantified by liquid chromatography–tandem mass spectrometry. Results Among 640 participants, 815 paired serum and salivary samples were analyzed. Salivary cortisol and cortisone correlated well with serum cortisol across dynamic testing, with the greatest difference following 1-mg DST (r = 0.86 vs 0.53 for cortisone and cortisol, respectively; both P < 0.001). During CST, correlations ranged from r = 0.75–0.87 for both analytes (all P < 0.001). Salivary dexamethasone correlated with serum dexamethasone (r = 0.61, P < 0.001). Salivary cortisone thresholds corresponding to prespecified clinically relevant serum cortisol concentrations of 1.8, 5, 10, and 18 µg/dL (50, 138, 276, and 497 nmol/L) were 117, 329, 585, and 1262 ng/dL (3.25, 9.13, 16.23, and 35.01 nmol/L), respectively; corresponding salivary cortisol thresholds were 16.5, 38, 80, and 278 ng/dL (0.46, 1.05, 2.21, and 7.67 nmol/L). Conclusions These findings support saliva-based dynamic adrenal testing and identify clinically relevant salivary thresholds.

Abstract Context Evidence on the evolution of cardiometabolic comorbidities following surgical remission of hypercortisolism is scarce. Objective To determine the impact of surgical remission on cardiometabolic comorbidities in patients with endogenous hypercortisolism and to identify factors associated with cardiometabolic improvement. Methods Prospective single-center cohort study (2019-2025) of adults with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS) with surgical remission of hypercortisolism. Outcomes included (1) changes in severity of hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity between baseline, 3, and 12 months postremission and (2) factors associated with improvement in comorbidities. Results Among 357 patients (49% MACS, 36% pituitary CS, 10% adrenal CS, 5% ectopic CS; median age 53 years [interquartile range 42-62]; 81% women), 336 (94%) had hypertension, 241 (68%) had obesity, and 122 (35%) had DM. At a median of 12 months postsurgery, improvement in hypertension occurred in 70% (90/128) of patients with CS and 51% (60/117) of patients with MACS, DM in 90% (46/51) patients with CS and 37% (13/35) patients with MACS, and obesity in 79% (77/97) patients with CS and 20% (14/71) patients with MACS. In a multivariable analysis, higher baseline biochemical severity scores were associated with improvement in hypertension [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5), DM (OR 2.5, 95% CI 1.7-4.1), and obesity (OR 1.5, 95% CI 1.2-1.8) at a median of 12 months postremission of hypercortisolism. Conclusion Postsurgical improvement of cardiometabolic comorbidities was observed in both patients with CS and MACS. Higher baseline biochemical severity scores were associated with higher postremission improvement in comorbidities.

Abstract Objective Evidence on the duration of post-operative adrenal insufficiency (AI) in patients with endogenous hypercortisolism is scarce. We sought to determine the duration of post-operative AI and to identify factors associated with the duration of AI in patients undergoing surgery for endogenous hypercortisolism. Methods We conducted a single-center prospective cohort study, 2019-2025, of patients with endogenous hypercortisolism [Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)] treated with surgery. Associations of demographics, body mass index (BMI), clinical, and biochemical hypercortisolism severity, subtype of hypercortisolism, pre-surgical hypercortisolism duration, glucocorticoid type, and nadir cortisol in relation to duration of AI were investigated. Results The 242 patients [41% MACS, 46% pituitary CS, 12% adrenal CS, 1% ectopic CS, median age 50 years (IQR: 40-60), 85% women] who developed postsurgical AI were followed for a median duration of 13.7 months (IQR 7.2-26.3). The median time to recovery of AI was shorter in MACS vs. overt CS (3.9 months (95% CI: 3.3-6.2) vs. 13.5 months (95% CI 11.3-18.3), P value < .001). On multivariable analysis adjusting for age, sex, BMI, and glucocorticoid type, moderate to severe biochemical severity score (β = 11, P value < .001) and moderate to severe clinical severity score (β=8.7, P < .001), were associated with a longer duration of AI. Conclusions Baseline clinical and biochemical hypercortisolism severity scores may inform individualized counseling on post-operative AI duration in patients treated for CS and MACS.

Abstract Disclosure: C.A. Villavicencio Torres: None. S. Ahmadian: None. K. Moehnke: None. V.M. Fell: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Evaluation of adrenal disorders relies on total cortisol measurements at baseline or during dynamic testing. Accurate cortisol assessment that avoids phlebotomy may simplify the work up of adrenal disorders, decrease healthcare costs, and improve patient experience. Objectives: We aimed to compare cortisol and dexamethasone concentrations between venipuncture-based (clinical) and capillary blood samples. Methodology: We conducted a cross-sectional study (July 2024-April 2025) of adults undergoing standard-of-care cortisol measurements. Capillary blood samples were collected alongside clinical samples. Capillary measurements included total cortisol and dexamethasone (mass spectrometry). Clinical samples were tested for total cortisol (Roche immunoassay) and dexamethasone (mass spectrometry). Results: Of 318 patients (243, 77% women, median age 53 years, IQR 39-66), 227 (71%) underwent dexamethasone suppression test (DST) and 88 (28%) cosyntropin stimulation test (CST). Capillary blood collection failed in 13 (4%) patients. In patients undergoing DST, median post-dexamethasone serum cortisol was 1.3 mcg/dL (IQR 0.8-2.2), and serum dexamethasone was 0.41 mcg/dL (IQR 0.27-0.59), while median capillary cortisol was 1.5 mcg/dL (IQR 1-2.5), and capillary dexamethasone was 0.33 mcg/dL (IQR 0.21-0.51). Capillary cortisol (r=0.95, 95% CI [0.93, 0.96], p<.0001) and capillary dexamethasone (r=0.93, 95% CI [0.90, 0.95], p<.0001) showed strong correlation with their respective clinical measurements. In patients undergoing CST, median baseline serum cortisol was 7.5 mcg/dL (IQR 5-10), and median baseline capillary cortisol was 8.5 mcg/dL (IQR 6-12). Median post-CST 60-minute serum cortisol was 23 mcg/dL (IQR 20-25), while capillary cortisol was 25 mcg/dL (IQR 21-28). Baseline (r=0.77, 95% CI [0.66, 0.85], p<.0001) and post-CST 60-minute capillary cortisol (r=0.88, 95% CI [0.81-92], p<.0001) strongly correlated with clinical measurements. Post-dexamethasone cortisol in paired DST samples showed that capillary measurements were higher than serum cortisol (median difference 0.20 mcg/dL (95% CI [0.12, 0.42], p<.0001), while paired capillary dexamethasone concentrations were lower than serum dexamethasone concentrations (median difference 0.04 mcg/dL (95% CI [0.03, 0.07], p<.0001). In CST, paired baseline capillary and serum cortisol concentrations were similar (median difference 0.10 mcg/dL, 95% CI [0.3, 0.3], p=.3660), while paired post-CST 60-minute capillary cortisol was higher than serum cortisol by a median of 2.8 mcg/dL (95% CI [2, 3.2], p<.0001). Conclusion: Capillary cortisol and dexamethasone concentrations demonstrate excellent correlation with venipuncture-based measurements. Following validation with at-home collection, capillary blood measurements may serve as an alternative for evaluating adrenal disorders. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S.R. Chacko: None. J. Saini: None. S. Sharma Sharma: None. S. Ahmadian: None. S.J. Achenbach: None. E. Atkinson: None. V. Fell: None. J.J. Van Gompel: None. W.F. Young, Jr.: None. I. Bancos: None. Context: Evidence on the duration of postoperative adrenal insufficiency (AI) in patients with endogenous hypercortisolism is scarce. Objective: To determine the duration of postoperative AI and to identify factors associated with the duration of AI in patients undergoing surgery for endogenous hypercortisolism.Methods: We conducted a single center prospective cohort study, 2019-2024, of patients with endogenous hypercortisolism [Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)] treated with surgery. Associations of demographics, BMI, clinical and biochemical hypercortisolism severity, subtype of hypercortisolism, presurgical hypercortisolism duration and glucocorticoid type in relation to duration of AI were investigated. Results: The 110 patients [36% MACS, 46% pituitary CS, 15% adrenal CS, 3% ectopic CS, median age 50 years (IQR: 40-60), 82% women] who developed postsurgical AI were followed for a median duration of 26 months (IQR: 15-38). By the end of follow up, 96 patients (87%) had recovery of AI. The median time to recovery of AI was shorter in MACS vs. Overt Cushing syndrome (3.0 months (95% CI: 2.5-6.2) vs. 12.3 months (95% CI 9.0-17.3), P =0.002). Biochemical severity score (r=0.32, P=0.002) and duration of preoperative hypercortisolism symptoms (r=0.29, P=0.005), but not age, sex, BMI, clinical severity, or glucocorticoid type were associated with the duration of AI. We found no differences in the duration of AI between patients with ACTH-dependent vs ACTH-independent CS (12.3 months (95% CI: 6.0-17.2) vs 13.9 months (95% CI: 9.0-25.5), P =0.7).Conclusion: In this interim analysis, we showed that after surgical remission of endogenous hypercortisolism, duration of postoperative AI was longer in CS compared to MACS. Additionally, higher biochemical hypercortisolism severity score and a longer duration of symptoms suggestive of hypercortisolism were associated with a longer duration of postoperative AI. Presentation: Sunday, July 13, 2025

Abstract Disclosure: C.A. Villavicencio Torres: None. S. Ahmadian: None. V.M. Fell: None. K. Moehnke: None. Y. Chai: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Current standard-of-care assessment of adrenal disorders relies on the venipuncture-based total cortisol measurements. Salivary cortisol (SalF) and cortisone (SalE) measurements have advantages such as a more accurate assessment of patients with cortisol-binging globulin abnormalities and the convenience of at-home non-invasive testing. Aims: This study aimed to compare concentrations of cortisol and dexamethasone between clinical (venipuncture-based) and saliva samples. Methodology: We conducted a cross-sectional study (July 2024-January 2025) of adults undergoing overnight dexamethasone suppression test (DST) or cosyntropin stimulation test (CST). Saliva samples were collected alongside clinical samples. Saliva measurements included cortisol, cortisone, and dexamethasone (mass spectrometry), while clinical samples were tested for total cortisol (Roche immunoassay) and, in a subgroup, dexamethasone (mass spectrometry). Results: Of 241 patients (186 (77%) women, median age 53 years (IQR 39-66)), 178 (74%) provided samples as a part of DST and 63 (26%) as a part CST. An inability to provide sufficient saliva for analysis was found in 5 patients (2%). In patients undergoing DST, median post-dexamethasone serum total cortisol was 1.3 mcg/dL (IQR 0.8-2.2), and median serum dexamethasone (SerD) was 0.43 mcg/dL (IQR 0.3-0.6) based on clinical samples, while median SalF was 10.2 ng/dL (IQR 6.6-23.6), SalE was 78.6 ng/dL (IQR 52.8-131.1), and saliva dexamethasone (SalD) was 60 ng/dL (IQR 41-93). SalE (r=0.92, p<.0001) demonstrated a stronger correlation than SalF (r=0.85, p<.0001) when compared with post-dexamethasone serum total cortisol measurements. SalD (r=0.85, p<.0001) correlated with SerD measurements. In patients undergoing CST, median baseline serum total cortisol was 7.2 mcg/dL (IQR 4.6-10) based on clinical samples, while median baseline SalF was 86.6 ng/dL (IQR 38.3-166.3), and median SalE was 707 ng/dL (IQR 347-906). Median peak 60-minute serum total cortisol was 21.5 mcg/dL (IQR 18-24), while SalF was 870.4 ng/dL (IQR 440-2904) and SalE was 2501 ng/dL (IQR 1770-3193). Both baseline (r=0.92, p<.0001) and 60 min peak post-cosyntropin SalE (r=0.84, p<.0001) demonstrated a strong correlation with venipuncture-based measurements. SalF had a weaker than SalE correlation at both baseline (r=0.88, p<.0001) and 60 min peak post-cosyntropin (r=0.79, p<.0001). Conclusion: Our study demonstrates that salivary measurements of cortisone, cortisol and dexamethasone strongly correlate with standard-of-care venipuncture concentrations following DST and CST. SalE showed the stronger than SalF correlation with venipuncture-based serum total cortisol concentrations. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S. Ahmadian: None. S.R. Chacko: None. S. Sharma Sharma: None. V.M. Fell: None. A. Peersen: None. E.J. Atkinson: None. K.L. Moehnke: None. Y. Chai: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Cortisol secretion follows a circadian pattern with highest concentrations in the morning, and lowest at night. Loss of circadian cortisol variation has been reported in patients with Cushing syndrome (CS), however, is scarcely investigated in patients with mild autonomous cortisol secretion (MACS). Outpatient assessment of late night and early morning salivary cortisol and cortisone may serve as a valuable diagnostic tool in patients with hypercortisolism. Methods: We conducted a single-center cross-sectional study of adults evaluated at our center between 04/2024 and 04/2025. The study included patients with Cushing’s syndrome (CS), mild autonomous cortisol secretion (MACS), and referent subjects without known adrenal disorders. Participants were provided with two cotton swabs (Salivettes) and instructed to collect saliva samples at two standardized time points: at bedtime (PM) and on waking (AM). Each swab was kept in the mouth for 2-2.5 minutes. Saliva was analyzed for cortisol and cortisone using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Delta cortisol and delta cortisone were defined as the difference between AM and PM concentrations for each individual and were calculated for all participants. Results: A total of 82 patients (32 with ACTH-dependent CS, 5 with ACTH-independent CS, and 45 with MACS), median age of 55 years [IQR 44-65], 63 (77%) women, and 71 referent subjects, median age of 34 years [IQR 28-42], 54 (76%) women, were included. Delta cortisol was higher in referents (median of 212 ng/dL, [IQR 157-358]) vs patients with CS (median 95 ng/dL [IQR -21-184]) or MACS (median 131 ng/dL, [IQR 91-229]). Similarly, delta cortisone was also highest in referents with a median of 828 ng/dL [IQR 612-1131] versus median of 211 ng/dL [IQR -58-468] in CS and 484 ng/dL [IQR 189-849] in MACS. When compared to referents in an age- and sex-adjusted linear regression model, delta cortisone was lower in both patients with CS (est -1.3 (95%CI -1.75 to -0.85), P<0.001 and MACS (est -0.66, 95%CI of -1.17 to -0.16, P=0.010). Delta cortisol was lower in patients with CS (est -1.32, 95%CI -2.11 to -0.54, P=0.001), but not MACS (est -0.51, 95%CI -1.39 to 0.36). Conclusion: Patients with both CS and MACS demonstrate a blunted circadian salivary cortisol and cortisone secretion, as reflected by a lower delta cortisol and cortisone when compared to referent subjects. Assessment with delta salivary cortisone in patients with MACS may be more valuable than a standard of care late night salivary cortisol assessment. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S. Ahmadian: None. C.A. Villavicencio Torres: None. V.M. Fell: None. K.L. Moehnke: None. Y. Chai: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Salivary cortisol (SalF), and cortisone (SalE) interpretation can be influenced by intra-individual variability arising from cortisol secretion cyclicity, assay performance, and sampling techniques. No studies to date have examined the impact of sampling on intra-individual variability. Methods: We conducted a single-center cross-sectional study of adults evaluated with total serum cortisol measurements as a part of the overnight dexamethasone suppression test (DST) or cosyntropin stimulation test (CST), November 2024- January 2025. Participants were provided with two cotton swabs (salivettes) and asked to collect two consecutive saliva samples immediately after the venipuncture for total cortisol. Each cotton swab was kept in the mouth for 2-2.5 minutes. Saliva was tested for SalF and SalE by mass spectrometry. Variability was examined based on cortisol tertiles. Results: A total of 78 paired saliva samples were obtained from 60 participants (45 [75%] women; median age 55 years [IQR 39-66]), who were undergoing either DST (42 [70%]) or CST (18 [30%]). A total of 10 (17%) saliva samples did not contain a sufficient sample for analysis during the first or second saliva collection (7 [12%] from DST group, and 3 [5%] from CST group).Among 53 patients undergoing DST, the median serum total cortisol was 1.3 mcg/dL [IQR 0.9-3], the median first SalF was 20 ng/dL [IQR 7-28], the median second SalF was 12 ng/dL [IQR 6-23], and the median variability was 11% [IQR 3-22%]. The median first SalE was 69 ng/dL [IQR 54-185], while the median second SalE was 63 ng/dL [IQR 56-178], with a median variability of 6% [IQR 4-10].In patients undergoing CST, peak median serum total cortisol was 20 mcg/dL [IQR 18-24], median first SalF was 809 ng/dL [IQR 536-1227], and median second SalF was 1063 ng/dL [IQR 667-1503], with the median variability of 14% [IQR 8-22]. The median first SalE was 2507 ng/dL [IQR1697-2966], while the median second SalE was 2485 ng/dL [IQR 1530-2976], with a median variability of 9% [IQR 3-12].When examining intra-individual variability of SalF, the variability was lowest in the middle tertile, corresponding to serum cortisol of 1.8-8.9 mcg/dL, at 9% [IQR 5-16]. Variability was higher in the lowest tertile (14% [IQR 0-52]) and the highest tertile (12% [IQR 6-16]). Overall, the variability of SalE was lower than that of SalF: 7% [IQR 4-13] in the lowest tertile, 5% [IQR 2-9] in the middle tertile, and 10% [IQR 4-12] in the highest tertile. Conclusion: We show that saliva sampling may impact the results, with 17% patients providing insufficient sample for analysis, and variability of 9-14% for SalF and 5-10% for SalE. Same time-point sampling-related variability should be considered in interpretation of SalF and SalE measurements. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S. Sharma Sharma: None. J. Saini: None. S.R. Chacko: None. S. Ahmadian: None. V. Fell: None. S.J. Achenbach: None. E.J. Atkinson: None. W.F. Young: None. I. Bancos: None. Context: The impact of active hypercortisolism on sleep is incompletely characterized. Several studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate an abnormal circadian cortisol secretion with mild nocturnal hypercortisolism that could also impact sleep. Objectives: To characterize sleep abnormalities and to identify factors associated with impaired sleep in patients with CS and MACS. Methods: We conducted a single-center cross-sectional study of prospectively enrolled adults with active CS and MACS evaluated between August 31, 2020, and December 2, 2024. Clinical and biochemical severity scores for hypercortisolism were calculated. Quality of life (QoL) was assessed using 1) Short Form-36 (SF-36), physical (PCS) and mental (MCS) component summaries, and 2) Cushing QOL survey, with psychosocial and physical domains. Sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI), a global score of ≥5 was considered abnormal. Pearson correlations and linear regression models were used to explore associations with PSQI scores. Results: In 285 patients (226 [79%] women, 259 [91%] White, median age of 54 [IQR 44-64] years), MACS was diagnosed in 147 (52%) and CS in 138 (48%). Patients reported abnormal sleep (median PSQI of 12 (IQR 8-16) in CS vs 10 (IQR 7-15) in MACS (P=0.086). Most prevalent sleep abnormalities included report of “fairly bad” or “very bad” overall sleep quality (73% in CS and 54% in MACS) and report of severe day dysfunction due to sleepiness (70% in CS and 56% in MACS). In an age-, sex- and BMI- adjusted univariable analysis of patients with hypercortisolism, higher clinical hypercortisolism severity score (r=0.13, P=0.024) and worse QoL, as measured by SF-36 and Cushing QoL (P=<0.001 for all), were associated with higher PSQI scores, a reflection of poor sleep. In a multivariable analysis of patients with hypercortisolism, we found that younger age (est -0.08, P=<0.001), female sex (est 1.95, P=0.004), lower BMI (est -0.07, P=0.041), and higher clinical severity score (est 0.12, P=0.024) were associated with higher PSQI scores, indicating impaired sleep. In a multivariable analysis of only patients with MACS, female sex (est 2.17, P=0.012), lower BMI (est -0.12, P=0.017), and higher clinical severity score (est 0.24, P=0.003), but not age were associated with higher PSQI scores, indicating impaired sleep. In patients with CS, only younger age (est -0.12, P=<0.001), but not other variables were associated with higher PSQI scores. Conclusion: We found that patients with MACS have impaired sleep, possibly due to nocturnal hypercortisolism. In patients with MACS, but not CS, clinical hypercortisolism severity score was associated with more impaired sleep. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S. Sharma Sharma: None. J. Saini: None. S.R. Chacko: None. S. Ahmadian: None. V. Fell: None. S. Achenbach: None. A. Peersen: None. E. Atkinson: None. W.F. Young: None. I. Bancos: None. Context: Patients with MACS demonstrate an abnormal circadian cortisol secretion with mild nocturnal hypercortisolism that could impact sleep. Objectives: 1) To characterize sleep abnormalities and to identify factors associated with impaired sleep in patients with MACS. 2) To compare sleep abnormalities between patients with MACS and referent subjects. Methods: We conducted a single-center cross-sectional study of prospectively enrolled adults with MACS evaluated between August 31, 2020, and April 03, 2025. In parallel, we conducted a referent subject study between May 15, 2019, and May 02, 2023. Referent subjects were eligible if they had abdominal cross-sectional imaging without evidence of an adrenal mass. For patients with MACS, clinical and biochemical severity scores for hypercortisolism were calculated. In both groups, quality of life was assessed using Short Form-36 (SF-36), physical (PCS) and mental (MCS) component summaries. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), a global score of ≥5 was considered abnormal. Pearson correlations and linear regression models were used to explore associations with PSQI scores. Results: The total cohort included 167 patients with MACS and 89 referent subjects. No differences in age (median 60 vs 56 years, P= 0.122) and sex (71% vs 67% females, P= 0.523) were observed between patients with MACS and referents. However, median BMI was higher in patients with MACS (32 28 kg/m2 [IQR 28-38] vs 28 kg/m2 [IQR 24-32], P= < 0.001). Patients with MACS had more impaired sleep than referent subjects (median PSQI 11 [IQR 7-15] vs 5 [IQR 3-7], P= <0.001). In an age-, sex- and BMI- adjusted univariable analysis, lower PCS and MCS scores were associated with poor sleep in both referents (r= -0.45, P= <0.001 and r= -0.29, P= 0.008) and patients with MACS (r= -0.36 and -0.38, P= <0.001), however, the presence of obstructive sleep apnea (OSA) was not. In patients with MACS, both higher clinical and biochemical severity scores were associated with poor sleep (r=0.20, P=0.012) and (r= 0.15, P= 0.050). Multivariable analysis of age, sex, BMI, clinical severity and OSA demonstrated that women (est 2.35, P= 0.004), lower BMI (est -0.13, P= 0.014) and higher clinical severity score (est 0.17, P=0.026), but not OSA were associated with impaired sleep in patients with MACS. All PSQI subcomponents were higher in patients with MACS vs referents, indicating poor sleep-most significantly, sleep quality score (OR 3.93, 95% CI: 2.58-6.29), sleep disturbance score (OR 3.73, 95% CI: 2.28-6.37) and daytime dysfunction score (OR 4.74, 95% CI: 2.29-10.75). Conclusion: Patients with MACS report impaired sleep, and women with lower BMI and higher clinical hypercortisolism severity scores are more affected. Reversing abnormal nocturnal hypercortisolism may improve sleep. Presentation: Saturday, July 12, 2025