Citations

Abstract Use of Direct oral anticoagulants (DOAC) has increased exponentially since their introduction in 2010. Over the years they have been used without any systematic oversight, there have been ongoing concerns related to inappropriate or incorrect dosing, incorrect duration, and non-adherence to the drugs leading to adverse patient outcomes. Several factors have been attributed to DOAC non-adherence such as presence or fear of adverse effects, affordability, lack of perceived benefit, or concerns for reversibility. These barriers impact both primary (first time prescription) and secondary adherence (longer term prescription). Poor adherence can lead to adverse outcomes such as stroke, death, and higher medical resource utilization hence increased cost to the patient and payors. This study was conducted as a quality improvement (QI) initiative to improve the adherence to the prescription DOACS. We included patients 18 years old, a diagnosis of Atrial fibrillation and flutter who had a primary care provider writing the prescription for chronic DOAC therapy. Patients with venous thrombosis, pregnancy or who were institutionalized were excluded. The charts were reviewed for primary and secondary adherence using Surescripts functionality which can provide baseline information about prescription fills from the participating pharmacies. In the preimplementation phase we identified 1030 patients meeting inclusion criteria associated with the pilot sites within Mayo Clinic practice in preceding 6 months. For this population, Surescripts data found that the rates of primary and secondary adherence to be 84% and 86% respectively. We then implemented a 6-month pilot where we created workflow for a pharmacy led DOAC management unit. Herein, once a DOAC prescription was made for patients meeting inclusion criteria, they would enter a registry where the pharmacy team would review the charts for primary adherence by utilizing Surescripts data. If adherent these patients would be marked for follow up in the secondary adherence phase. However, if non adherent, the team would initiate intervention including engagement with patient online services which was further escalated to phone calls by the pharmacy team. Once the barriers were identified several remediation approaches were incorporated in the process, these included education about DOACS, medicare education, social work assistance to even switching to warfarin if necessary. The same process was followed for secondary adherence management. In the intervention cohort, we had 411 patients during the pilot, for primary adherence 87.1% of patients were adherent at baseline and an additional 3.4% became adherent with interventions, while 9.5% remain nonadherent. The primary causes of nonadherence, amongst 9.5%, were cost (86%) while 1% were concerned about side effects and 3% were concerned about lack of perceived benefit. The inverntions lead to impoved adherence in most patients and very few patients were transitioned to warfarin. For secondary adherence 92% of the patients were adherent without any intervention, an additional 4% of patients benefited with the interventions of the DOAC management unit with approaches to address cost considerations, while another 4% remained nonadherent where cost remained the primary reason for nonadherence, other reasons being lack of perceived benefit and side effect concerns. In summary, with active intervention, in our patient population we were able to improve the primary adherence from 84% to 91% and secondary adherence from 86% to 96% . Cost remained the biggest barrier for adherence followed by concern for side effects and lack of perceived benefit. Our engaged team of pharmacy staff was able to manage those concerns with the education and cost mitigation strategies leading to improved adherence. Based on previously published literature even a 5% difference in adherence to DOACS can make a huge difference in population-based outcomes. Our work was able to demonstrate a positive impact of the intervention, highlighting the need for a well-managed DOAC unit especially for complex care populations.

Abstract Introduction: T-PLL is a rare, aggressive leukemia with poor prognosis and limited therapies. Previous studies on T-PLL patients receiving an allogeneic stem cell transplant (alloSCT) are limited by small numbers with limited data on disease and transplant characteristics. Further, recent data from our large national cohort of patients demonstrated significant survival difference between TCL1A+ and TCL1A- T-PLL, and CD8+ T-PLL vs CD8- T-PLL. In this large multi-center series, utilizing comprehensive disease subtype and alloSCT clinical data, we evaluated prognostic and survival therapeutic outcomes in T-PLL patients that had an alloSCT with a particular focus on T-PLL disease subtypes. Methods: We retrospectively evaluated 572 diagnosed with T-PLL at 21 academic cancer centers throughout the USA between 2000-2023, of which we performed a further evaluation on the169 that proceeded with alloSCT. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier methods and Cox proportional hazard models. Results: Among n=169 alloSCT recipients with T-PLL, the median follow-up time was 20.9 months post-alloSCT (range: 0.2-182.9), the median age at transplant was 59 years (range: 35-77) and 52% were male. In evaluated patients (n=109), TCL1A was positive by cytogenetics or FISH in 69%. As our recent analysis demonstrated significant differences in survival among specific subtypes of T-PLL, we evaluated outcomes in patients with CD4+CD8- T-PLL (n=90, 53%), CD4-CD8+ (n=17, 10%) T-PLL, and CD4+CD8+ T-PLL (n=52, 31%). 53% (87/164) had known nodal involvement at diagnosis identified by PET or CT scan and 45% (43/96) of known patients had minimal residual disease (MRD) at the time of transplant [defined as <5% T-PLL in marrow by flow, or +cytogenetics (e.g. TCL1A)] prior to alloSCT. At the time of alloSCT, 136 (80%) patients were in CR and 23 (14%) patients were in PR. Forty-nine (30%) had a myeloablative (MAC)conditioning regimen and 114 (70%) had a reduced intensity chemotherapy (RIC) conditioning regimen. Eighty (49%) patients had TBI as part of their regimen. The most common regimens were fludarabine (flu)/melphalan based regimens (n=44; 26.0%), flu/cyclophosphamide (cy) based regimens (n=33; 19.5%), flu/busulfan based regimens (n=22; 13.0%), flu/total body irradiation (TBI) (n=8; 4.7%), and cy/TBI (n=4; 2.4%). Across the whole cohort, the median OS and PFS post-alloSCT was 32.6 months (95% CI: 21.0-41.9) and 20.8 months (95% CI: 14.4-30.5) months while the 1-year cumulative incidences (CI) of NRM and relapse were 17% and 20%, respectively. The incidences of grade II-IV acute GVHD and cGVHD were 19% and 23%. There was no difference between patients with myeloablative conditioning (MAC) (n=49, 29%) when compared to patients that received reduced intensity conditioning (RIC) (n=114, 67%) in OS (33.1 vs 29.2; p=0.68) and PFS (20.2 vs 20.8; p=0.97). Patients that were MRD+ (n=31) had worse OS (22.2 vs 48.6; p=0.1) and PFS (14.1 vs 32.5; p=0.04) and higher rates of relapse (1-year relapse 20% vs 8%; p=0.08) than patients that were MRD- (n=50). PFS was improved in those who received alloSCT though only trended towards significance due to low numbers (HR 0.76, p=0.09). In subtype analysis, TCL1A+ T-PLL had significantly worse outcomes compared to TCL1A negative T-PLL. TCL1A+ disease had significantly worse OS (21.6 vs 63.1; p=0.01) and PFS (12.4 vs 50.7; p=0.01) compared to TCL1A-. Additionally, in TCL1A+ disease CI of NRM (24% vs 3%; p=0.02) and relapse (25% vs 12%; p=0.86) was higher vs TCL1A- PLL. CD4+CD8-, CD4-CD8+, and CD4+CD8+ disease had no difference in survival via either OS (28.0 vs 34.4 vs 21.0; p=0.17) or PFS (29.4 vs 23.5 vs 13.6; p=0.09) as well as no difference 1-year CI of NRM ( 11.6 vs 23.5 vs 26.2; p=0.35) and relapse (18.5 vs 23.5 vs 20.0; p=0.67).Conclusions: AlloSCT significantly improved outcomes for patients with T-PLL compared to those who did not proceed to alloSCT and remains he only curative therapy for those with T-PLL. OS, PFS, and CI relapse were significantly worse for patients with TCL1A+ subtype of T-PLL, or those with MRD positivity or PR prior to alloSCT. Novel strategies to decrease relapse such as post-alloSCT maintenance therapy to improve outcomes are urgently needed in these patients.

Abstract The current European Leukemia Net guidelines (ELN22) classify AML patients with intermediate-risk cytogenetics and MDS-associated mutations (MDSm, mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) as adverse-risk but do not use MDSm+ to alter the risk stratification of patients who otherwise classify as favorable-risk. NPM1 mutations (NPM1+) are one of the most common alterations in AML and remain a favorable-risk biomarker for patients without co-occurring FLT3-ITD mutations or adverse-risk cytogenetics (NPM1+/ITD-/ARcyto-). However, prior studies have shown that older patients (≥65 years) with favorable-risk AML, including NPM1+/ITD-/ARcyto- genotype, have significantly higher relapse rates and decreased survival despite receiving comparable intensive chemotherapy regimens to their younger counterparts. Given that MDSm frequency increases with age in patients with NPM1+ AML, it raises the question as to whether MDSm contribute to poorer outcomes in older patients. To date, there have been differing results in retrospective studies examining the effect of MDSm on NPM1+ AML. Some cohorts demonstrate worse outcomes in those that have NPM1+/MDSm+ AML (Chan et al., Blood Adv. 2024), whereas others do not show a significant difference in NPM1+ AML with or without MDSm (Eckardt et al., Leukemia 2023; Othman et al., Blood 2024; Ruhnke et al., Blood Adv. 2025). We examined the mutational landscape in a large group of pre-treatment, diagnostic specimens from 271 patients, which included 119 patients enrolled in SWOG clinical trials (SWOG-9031, SWOG-9333, S0106, and S0112), 96 patients from the UW/FHCC Hematopoietic Repository, and 56 patients from the BeatAML cohort. All patients were treated with curative intent as per standard practice or on clinical trials and had adequate cytogenetic information and long-term follow-up data. Event-free and overall survival (EFS, OS) were estimated using the Kaplan-Meier method and compared using Cox regression models stratified by cohort. MDSm+ occurred in 17% of patients, with the most common mutations being in SRSF2 (7%) and SF3B1 (3%). To assess the impact of MDSm on outcomes of favorable-risk NPM1+ AML, we performed univariate analyses comparing OS and EFS for NPM1+ AML grouped by ELN22 favorable risk/MDSm-, ELN22 favorable/MDSm+, and ELN22 intermediate/adverse risk. Compared to NPM1+/MDSm- (n=116), favorable-risk NPM1+/MDSm+ (n=33) had worse OS with HR 2.0 [95% CI (1.1, 3.3), p=0.008] and had similar OS to those that are classified as ELN22 intermediate/adverse risk (n=122). There was no significant difference in EFS or complete remission rates between NPM1+ favorable risk with and without MDSm (p=0.36 and p=0.6, respectively). When we grouped the ELN22 favorable risk patients by age (<65 years vs. 65+ years), MDSm+ in younger patients did not show a difference for OS (HR 0.99, p=0.98). Older ELN22 favorable-risk patients (≥65) had poor OS regardless of presence of MDSm compared to younger MDSm- patients: older MDSm- (n=91) with HR 2.4, 95% CI (1.3, 4.6), p=0.005 and older MDSm+ (n=25) with HR 3.5, 95% CI (1.9, 6.3), p<0.0001. There was a trend toward worse OS in MDSm+ compared to MDSm- older patients, but this was not statistically significant (HR 1.42, p=0.33). Since most MDSm are in splicing factor genes (SF3B1, SRSF2, U2AF1, ZRSR2), we examined the effect of splicing factor mutations vs. other MDSm+ in ELN22 favorable risk and did not find a significant difference in OS (HR=1.01, p=0.97). Those with non-splicing MDSm+ had worse EFS compared to MDSm- and splicing MDSm+ (HR 4.12, p=0.0037), although no difference in OS. In this study, MDSm+ in the context of favorable-risk NPM1+ AML are associated with worse OS in a univariate analysis. However, this difference is likely due to the increased prevalence of MDSm with increasing age and overall worse outcomes of NPM1+ AML in older patients. When stratified by age, older NPM1+ AML patients had worse OS than younger NPM1+ patients overall, although presence of MDSm trended toward even worse OS in older patients. In younger patients, MDSm+ are not associated with a significant difference in OS, which is a similar finding compared to prior studies. Our findings suggest that NPM1+ AML is not necessarily “favorable-risk” in older patients, particularly with concurrent MDSm. Therefore, further understanding of the underlying biology of age in the context of NPM1+ AML is needed to improve outcomes for older patients.

Abstract Disclosure: K. Yu: None. J. Saini: None. E.J. Atkinson: None. S.J. Achenbach: None. V. Fell: None. I. Bancos: None. Background: Data on cognition in patients with primary aldosteronism (PA) are scarce. Mild autonomous cortisol secretion (MACS), defined based on post-dexamethasone cortisol >1.8 mcg/dL, is diagnosed in 20-30% of patients with PA. The impact of MACS on the cognition of patients with PA is unclear. Objectives: 1) to assess cognition in patients with PA versus sex-matched referent subjects with hypertension, 2) determine the differences in cognition of patients with PA (with and without MACS) and patients with MACS. Methods: A cross-sectional study, 2019-2023. Cognition was assessed by National Institute of Health Toolbox Cognition Battery and reported as T-score corrected for age, sex, race, and education. Only subjects with hypertension were included. Results: Cognitive assessment was performed in 52 patients with PA (including 11 patients with both PA and MACS, median age of 51 yrs, 30, 58% women), 47 patients with MACS (median age of 57 yrs, 31, 66% women), and 52 referent subjects (median age of 66 yrs, 30, 58% women). When compared to referents, and after age adjustment, patients with PA had lower cognition: fluid composite cognition β of -6.3 (P=0.014) and total composite of -5.6 (P=0.016). When compared to patients with MACS, and after age and sex adjustment, patients with PA had a similar total composite cognition score (β=3.6, P=0.108) but a higher fluid composite score (β=4.7, P=0.044). No differences in cognition were found between patients with PA with and without MACS, possibly due to low sample size. Conclusion: Patients with PA demonstrate lower cognition when compared to referents with hypertension. Patients with PA had a higher fluid cognition compared to patients with MACS. Future studies should delineate the impact of hyperaldosteronism vs MACS on cognition of patients with PA. Presentation: Monday, July 14, 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: J. Saini: None. E. Ferreira Taveras: None. Y. Hleibiehova: None. B. Bahrani Fard: None. M. Suresh: None. R. Sandooja: None. B. Salama: None. V. Fell: None. S. Achenbach: None. E.J. Atkinson: None. I. Bancos: None. Context: Patients with endogenous hypercortisolism experience glucocorticoid withdrawal syndrome (GWS) post-surgery. Meditation may be an effective intervention to alleviate the severity of GWS. Objective: To determine the acceptability of portable, wearable EEG device for guided meditation (MUSE headband) and the impact of MUSE use on GWS and quality of life 12 weeks post-surgery. Methods: We conducted a single-center prospective cohort study of adults with endogenous hypercortisolism undergoing curative surgery, 2019-2024. Patients had baseline and post-surgical assessments over 12 weeks. The study comprised of patients using MUSE for ≥ 6 weeks (MUSE cohort) and patients matched by age, sex, BMI, hypercortisolism type, and glucocorticoid type at 1:4 ratio. Quality of life and symptoms of GWS were assessed with AddiQoL, Cushing Quality of Life, and Short Form-36 mental and physical component (SF-36 MCS and PCS) questionnaires. Results: MUSE was offered to 52 patients, and 22 (42%) used MUSE for ≥ 6 weeks within 12 weeks post-surgery. At baseline, when compared to 88 matched subjects, 22 MUSE participants demonstrated a similar prevalence of comorbidities, clinical and biochemical hypercortisolism severity, but lower AddiQoL (mean 73 vs 66, P=0.031) and SF-36 MCS (mean 39 vs 33, P=0.022). At 12 weeks, these differences in quality of life were no longer present. After adjusting for age, sex, BMI, clinical severity score, and baseline quality of life, MUSE use was an independent predictor of improved SF- 36 PCS at 12 weeks post-surgery (beta 4.2, 95% CI: 0.5-7.9, P=0.026). Conclusions: Meditation intervention post-surgery may improve symptoms of GWS and accelerate recovery. 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

Abstract Disclosure: B. Salama: None. M. Bassiony: None. J. Saini: None. P. Dogra: None. E. Atkinson: None. J. Larson: None. I. Vodanovic: None. D. Kastelan: None. D.A. Delivanis: None. J. Hubska: None. U. Ambroziak: None. I. Bancos: None. Background: Frailty is a clinical syndrome characterized by diminished physiological reserve and increased vulnerability to stressors. Patients with Mild Autonomous Cortisol Secretion (MACS) demonstrate a high prevalence of frailty, however, no data are available on the impact of management on frailty progression. Objectives: To determine the impact of conservative vs surgical management on and the progression of frailty in patients with MACS. Methods: We conducted a multicenter prospective cohort study of patients with (MACS), primary aldosteronism (PA), or non-functioning adrenal adenomas (NFA) between June 2020 and April 2025. Participants completed standardized frailty assessment (frailty index) at baseline and annually. Results: A total of 691 patients were included: 253 with MACS (median age 62 years, 73% women, 230 with NFA (median age 62 years, 67% women), and 208 with PA (median age 54 years, 50% women). At baseline, prevalence of frailty was highest patients with MACS (39%), followed by patients with PA (31%) and NFA (24%). Frailty was reassessed at 1 year post baseline in 189 patients with NFA (22% frail, median frailty index of 0.17) and 116 patients with MACS (27% frail, median frailty index of 0.16) managed conservatively, as well as in 108 patients with MACS treated with adrenalectomy (49% frail, median frailty score of 0.24). Conservatively treated patients with MACS and those treated with adrenalectomy had similar post-dexamethasone cortisol (median 2.9 mcg/dL vs 3.1 mcg/dL, p=0.396), but were older (median age 65 years vs 58 years, p=0.001) At one year follow up, patients with MACS treated with adrenalectomy demonstrated an improvement in frailty when compared to conservative management (delta frailty index: Est of −0.044, p = 0.004), after adjusting for age and sex. In contrast, when compared to conservatively managed patients with NFA, conservatively managed patients with MACS demonstrated worse frailty at 1 year follow up (delta frailty index: Est of 0.028, p = 0.013). Conclusion: In comparison to patients with NFA, conservatively managed patients with MACS demonstrated worse frailty at 1 year follow up. In contrast, adrenalectomy in patients with MACS led to improvement of frailty. Frailty index could be valuable to identify patients most likely to benefit from adrenalectomy. Patients with higher baseline frailty scores were more likely to undergo adrenalectomy, Presentation: Sunday, July 13, 2025