Bancos, Irina

Abstract Disclosure: R. Gregg Garcia: None. I. Bancos: None. Background: Bilateral adrenalectomy (BLA) is a procedure with limited indications, such as bilateral pheochromocytomas and certain cases of Cushing syndrome. Impaired quality of life (QoL) has been reported in patients with primary adrenal insufficiency (PAI) due to autoimmune adrenalitis (AA). We hypothesized that, when compared to AA, patients post-BLA experience worse QoL due to sequelae of Cushing syndrome or pheochromocytoma. Objective: To compare the QoL and burden of disease in patients with PAI due to BLA versus AA. Methods: A cross-sectional study of adults with PAI due to BLA or AA, August 15 - November 26, 2022. Patients were excluded if PAI was diagnosed within one year from the enrollment date or if active malignancy was present. Participants completed a questionnaire about symptoms, burden of disease, adrenal crisis, and QoL (AddiQoL). Results: Of 120 patients with PAI, 49 (41%) had BLA, and 71 (59%) had AA. Median age was 52 years (range 23-80), without subgroup differences, but a higher proportion of women in the post-BLA vs the AA group (86% vs 69%, p=0.04). Reasons for BLA were Cushing syndrome (44, 90%) and bilateral pheochromocytomas (5, 10%). Duration of PAI was higher in patients with AA (median 12 vs 7 years post-BLA, p=0.02). The majority of patients reported wearing a medical bracelet (82%), having injectable glucocorticoid (90%), and comfort injecting (61%), without subgroup differences. Total daily hydrocortisone dose was higher in patients with AA vs patients post-BLA (mean of 23 mg vs 20 mg, p=0.03). A total of 26 (22%) patients reported at least one adrenal crisis within the last year, with a greater proportion in the post-BLA group (33% vs 14% in AA, p=0.02). No subgroup differences were noted in risk factors for adrenal crisis development, such as hydrocortisone equivalent dose, type of glucocorticoid therapy, duration of PAI, having a medic alert bracelet and injectable glucocorticoids, comfort injecting, or physical activity. Compared to AA, patients post-BLA had a similar QoL (median AddiQoL score 86 vs 84, p-value 0.72). Duration of PAI was not associated with QoL. Physical activity ≥3 times/week was associated with a better QoL (median AddiQoL score 90 vs 80 in those with lower level of physical activity, p=0.001); no subgroup differences in physical activity ≥3 times/week were found (57% in BLA vs 62% in AA, p=0.59). Since the initial diagnosis of PAI, more patients with AA reported that PAI was “harder” to manage (23% vs 6% post-BLA, p-value 0.04), with most patients reporting that management was easier (52% in AA and 63% in BLA) or not different (25% in AA and 31% in BLA). Conclusions: Despite a higher prevalence of adrenal crisis, more patients with BLA vs AA found PAI easier to manage. Moreover, patients with BLA and AA had a similar level of comfort and education managing PAI, similar QoL, and engaged in similar levels of physical activity, despite history of Cushing syndrome. Presentation: Saturday, June 17, 2023

Abstract Disclosure: M. Moazzami: Grant Recipient; Self; Rochester Epidemiology Project. S. Achenbach: None. E. Atkinson: None. I. Bancos: None. Background: Epidemiology of adrenal insufficiency (AI) is incompletely characterized with most data originating from referral centers and registries. We aimed to determine the incidence, morbidity index, risk of hospitalizations, and mortality in patients with AI living in Olmsted County, Minnesota. Methods: We assessed the standardized incidence rate, morbidity index, risk of hospitalizations and mortality of AI in residents (aged 18+) in Olmsted County, MN, USA, from Jan 1, 2005, to December 31, 2021. The data was collected using the Rochester Epidemiology Project (REP), a database of medical records for all Olmsted County residents since 1966. Incidence rates were standardized for age and sex according to the 2020 US white population. Sex- and age- matched referent subjects were selected from the REP. AI was defined based on presence of oral chronic glucocorticoid therapy (hydrocortisone, prednisone, prednisolone, or dexamethasone) defined as (1) any hydrocortisone use or (2) 6 months of consecutive use of prednisone, prednisolone, or dexamethasone or (3) two AI diagnosis codes 6+ months apart plus at least one glucocorticoid prescription within 1 year of the second diagnosis. Elixhauser morbidity index was used. Findings: Between 2005 and 2021, 5419 patients were diagnosed with AI (median age of 62 years, range 18-103), 56% women). Overall standardized incidence rates for AI increased from 206 (95% CI 174-238) in 2005 to 252 (223-280) per 100 000 person-years in 2021. At baseline, patients with AI had a higher morbidity index (median 3 vs median 1, p <0.001) and a higher history of hospitalizations within 5 years prior to baseline (57% vs 30%; p<0.001) when compared to referent subjects. When comparing patients with AI to referent subjects, and after adjusting for age, sex, morbidity index and prior history of hospitalizations, patients with AI were more likely to be hospitalized during follow-up (aHR 1.4, 95% CI 1.3-1.5). When comparing patients with AI to referent subjects, and after adjusting age, sex, and morbidity index, patients with AI had higher mortality (aHR 1.7, 95% CI 1.6-1.9). Patients with AI demonstrated a higher risk of dying from musculoskeletal disorders (aHR 4.9, 95% CI 2.2-10.8), respiratory disorders (aHR 4.7, 95% CI 3.3-6.6), neoplasms (aHR 2.4, 95% CI 2.0-2.9), and infectious disorders (aHR 2.3, 95% CI 1.2-4.3) than referent subjects. Interpretation: We demonstrate an increase in AI incidence between 2005 and 2021. Surprisingly, even after controlling for morbidity and prior hospitalizations, patients with AI were more likely to be hospitalized. In comparison to referent subjects, mortality was higher in patients with AI, even after adjustment for morbidity index. Presentation: Friday, June 16, 2023

Abstract Disclosure: J.P. Frias: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.J. Auchus: Consulting Fee; Self; Corcept Therapeutics. Grant Recipient; Self; Corcept Therapeutics. Speaker; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. I. Bancos: None. L. Blonde: Advisory Board Member; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.S. Busch: Consulting Fee; Self; Corcept Therapeutics. Speaker; Self; Bayer, Inc., Novo Nordisk, Amgen Inc, Eli Lilly & Company, AstraZeneca. J.B. Buse: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Jansen Pharmaceuticals, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, GentiBio, Glycadia, Glyscend, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Stability Health, Valo, Zealand Pharma. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Janssen, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, Dasman Diabetes Center (Kuwait), Fortress Biotech, GentiBio, Glycadia, Glyscend, Mediflix, Medscape, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Valo, Zealand Pharma. Grant Recipient; Self; Novo Nordisk, Sanofi, VTV Therapeutics, Nanotype, NIH, NovaTarg, Tolerion, Dexcom. Stock Owner; Self; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, Stability Health. Other; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Novo Nordisk, Dasman Diabetes Institute, Zealand, Association for Clinical and Translational Science. R.A. DeFronzo: None. J.W. Findling: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. V. Fonseca: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics, Lantheus, Recordati Rare Diseases, Neurocrine Biosciences, Amryt, Novo Nordisk, Strongbridge. Consulting Fee; Self; Corcept Therapeutics. Y. Handelsman: Consulting Fee; Self; Amgen Inc, Applied Therapeutic, AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Corcept Therapeutics, Esperion, Mannkind Corporation, Merck, Pfizer, Inc., Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Vertis. Grant Recipient; Self; Amgen Inc, Applied Therapeutic, Ionis Pharmaceuticals Inc., Regor. Speaker; Self; AstraZeneca, Bayer, Inc., Esperion, Novo Nordisk, Vertis, Amarin. R.E. Pratley: Consulting Fee; Self; Bayer, Inc., Corcept Therapeutics, Gasherbrum Bio, Inc, Hanmi, Hengrui (USA) Ltd, Merck, Novo Nordisk, Pfizer, Inc., Rivus Pharmaceuticals Inc, Sun Pharmaceutical Industries, Sanofi, Scohia Pharma Inc, Dexcom. Grant Recipient; Self; Hanmi, Metavention, Novo Nordisk, Poxel SA. Speaker; Self; Novo Nordisk. J. Rosenstock: Advisory Board Member; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Consulting Fee; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Grant Recipient; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Merck, Oramed, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Inc., Sanofi. I. Tudor: Employee; Self; Corcept Therapeutics. Stock Owner; Self; Corcept Therapeutics. A.G. Moraitis: Employee; Self; Corcept Therapeutics. D. Einhorn: Employee; Self; Corcept Therapeutics. Studies suggest that the prevalence of hypercortisolism in persons with difficult-to-control type 2 diabetes (T2D) is higher than is currently appreciated. A recently published meta-analysis suggests that the prevalence of hypercortisolism is higher in persons with T2D who require a greater number of antihyperglycemic agents and/or who have more comorbidities. To better understand the prevalence and whether treatment of hypercortisolism may result in better control of diabetes and other hypercortisolism-associated comorbidities, we describe a 2-part phase 4 study in adults with difficult-to-control T2D (HbA1c 7.5-11.5%) despite receiving multiple antihyperglycemic agents. The study will be conducted at approximately 30 sites in the United States. In Part 1, approximately 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test. Those responding with serum cortisol >1.8 µg/dL (50 nmol/L) and dexamethasone levels ≥140 ng/dL (3.6 nmol/L) will have adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, and cortisol measured in fasting blood samples obtained between 7-9 AM and a non-contrast adrenal computed tomography scan. Patients who may have ACTH-dependent hypercortisolism will be discontinued from the study and referred for further evaluation. The primary study endpoint is determining the prevalence of ACTH-independent hypercortisolism and will be evaluated in Part 1. Patients identified to have ACTH-independent hypercortisolism will advance to Part 2, a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of treatment with the glucocorticoid receptor antagonist mifepristone. Patients will be randomized 2:1 to mifepristone or placebo, stratified by the presence or absence of adrenal adenomas on CT, and receive treatment for 24 weeks. The mifepristone dose will be 300 mg once daily for 4 weeks, then increased to 600 mg daily for 20 weeks based on clinical assessment of tolerability and degree of improvement. There will be an option to increase to mifepristone 900 mg. Placebo will be titrated accordingly from 1 up to 3 tablets. Part 2 will assess the secondary endpoint of change in HbA1c from baseline to 24 weeks, as well as changes in hypercortisolism-related comorbidities (e.g., blood pressure, weight, waist circumference, quality of life). This will be the first prospective study to assess the prevalence of ACTH-independent hypercortisolism in persons with difficult-to-control T2D and the first prospective, randomized, placebo-controlled trial to assess the potential benefits and safety of treatment with mifepristone in this patient population. Presentation: Friday, June 16, 2023

Abstract Disclosure: R. Sandooja: None. A. Kittithaworn: None. P. Dogra: None. D. Gruppen: None. E. Atkinson: None. S. Achenbach: None. K. Yu: None. M. Connelly: None. V. Simha: None. R.P. Dullaart: None. I. Bancos: None. INTRODUCTION: Based on the spectrum of cortisol excess, adrenal adenomas are classified as adenomas with Cushing syndrome (CS), adenomas with mild autonomous cortisol secretion (MACS), and non-functioning adenomas (NFA). Patients with adrenal adenomas demonstrate a high prevalence of cardiovascular morbidity and mortality proportional to the degree of hypercortisolism. Evidence on whether dyslipidemia is a contributing cardiovascular risk factor in patients with NFA and MACS is discrepant. We aimed to characterize (apo) lipoprotein abnormalities across the spectrum of cortisol excess in patients with adenomas as compared to referent subjects. METHODS: Study Design: Single center cross sectional study between 01/2015 - 05/2021.Patients: Adults with NFA, MACS, or CS were consecutively enrolled. MACS was diagnosed based on post-dexamethasone cortisol >1.8 mcg/dL. Referent subjects were recruited from local population of patients with available abdominal imaging and no adrenal disorders. All subjects provided fasting ethylenediaminetetraacetic acid (EDTA) venous samples. Measurements: Nuclear magnetic resonance (NMR) spectroscopy measurements included total cholesterol (TC), low-density lipoprotein (LDL) and LDL particle concentrations, high-density lipoprotein (HDL) subclasses, apolipoprotein B (apo B), triglycerides (TG) and TG-rich lipoprotein concentrations. RESULTS: Participants included 101 patients with CS (median age 44 years, IQR 31-58, 85% women), 158 patients with MACS (median age 62 years, IQR 51-70, 62% women), 166 patients with NFA (median age 60 years, IQR 53--66, 63% women) and 136 referent subjects (median age 68 years, IQR 57-77, 52% women). Patients had higher BMI (32 vs 27 kg/m2), higher prevalence of hypertension (72% vs 46%) and diabetes mellitus (27% vs 9%) as compared to reference subjects. Statin therapy was used in 32% of patients and referent subjects. After adjusting for age, sex, BMI, smoking, diabetes, hypertension, and statin therapy, as compared to referent subjects, we found inconsistent increase in TC, LDL cholesterol and TG across CS, MACS and NFA and no consistent differences in LDL size, HDL variables, TG and TG-rich lipoproteins. However, when compared to referent subjects, LDL particle concentrations- CS(OR 1.78, 95% CI 1.33-2.39), MACS (OR 1.31, 95% CI 1.03-1.67), and NFA (OR 1.43, 95% CI 1.12-1.82) and Apo B levels were higher in all patient categories: CS (OR 2.26, 95% CI 1.57-3.24), MACS (OR 1.36 95% CI 1.00-1.85 ), and NFA (OR 1.54 95% CI 1.13-2.09). These differences were particularly evident in patients not on statin therapy. CONCLUSIONS: We found that LDL particle and Apo B concentrations were elevated in all patient groups, including those with MACS and NFA. In comparison to conventional lipid measurements, LDL particle and Apo B may serve as a better biomarker of the future cardiovascular risk in patients with adrenal adenomas. Presentation: Friday, June 16, 2023

Abstract Disclosure: A. Blinder: None. K. Nanba: None. D. Sapiro: None. J. Baker: None. C. Liu: None. I. Bancos: None. M. Lyden: None. W. Young: None. H. Wachtel: None. D. Cohen: None. J. Luther: None. T.A. Williams: None. M. Reincke: None. T. Else: None. T.J. Giordano: None. A. Udager: None. W.E. Rainey: None. Background: There is accumulating evidence that changes in adrenal histology and regulation of renin-angiotensin-aldosterone system occur with age. Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Recent clinical studies suggest unique characteristics of PA in elderly patients, including high prevalence of comorbidities and low clinical cure rate after adrenalectomy. However, histologic and genetic features of PA in late adulthood have not been well elucidated. Objective: To determine histologic and genetic characteristics of PA in late adulthood. Methods: Seventy-six patients who underwent unilateral adrenalectomy at the age of 60 or older were included in this study. Formalin-fixed, paraffin-embedded (FFPE) sections of resected adrenal tissue were used for the analysis. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed to identify the source of inappropriate aldosterone production. Histologic classification was made according to the HISTALDO (histopathology of primary aldosteronism) consensus. CYP11B2 IHC-guided DNA capture followed by sequencing analysis using direct Sanger sequencing or ion torrent based next-generation sequencing (NGS) was performed. Results: Median age of the studied patients was 70 (interquartile range: 64-73). Based on the CYP11B2 IHC, histologic diagnosis was made as follows; aldosterone-producing adenoma (APA, n=23), aldosterone-producing nodule (APN, n=41), and non-functioning adrenocortical adenoma (NFA, n=6). The remaining six cases had multiple CYP11B2-expressing neoplastic lesions, including APA with APN (n=2) and multiple APNs (n=4). Co-existence of NFA with APA or APN(s) was also observed in 13. Sequencing analysis revealed that somatic KCNJ5 mutation was the most frequent genetic alteration in APA (7/23, 30%), whereas somatic CACNA1D mutation was the most common genetic cause of APN (20/39 with successful sequencing, 51%). Of the 18 sequenced NFA DNA samples, two had somatic mutations in CTNNB1 (n=1) and GNAS (n=1). Conclusion: APN is the major histologic feature of PA in late adulthood. Co-existence of NFA also appears to be a frequent observation in this age population. Somatic CACNA1D and KCNJ5 mutations are common in APN and APA, respectively. Presentation: Friday, June 16, 2023

Abstract Disclosure: M. Chinthapalli: None. P. Dogra: None. R. Sandooja: None. L. Rahimi: None. N.M. Iniguez Ariza: None. T. Foster: None. I. Bancos: None. Introduction: Adrenal glands are susceptible to hemorrhage due to their unique vasculature and physiological stress response. Scarce data are available on the presentation, etiology, and outcomes of adrenal hemorrhage (AH). Objective: To describe the presentation, etiological associations, and outcomes of patients with unilateral and bilateral AH. Methods: Single-center retrospective longitudinal study of consecutive patients reported to have AH on imaging performed between January 1st 2017-December 31st 2021. Clinical, baseline and follow up imaging, and laboratory data were reviewed. Subgroup analysis was performed based on the laterality (unilateral vs. bilateral) of AH. Results: Of 454 patients with AH (median age 62 years (IQR 50-70), 160 (35%) women), 383 (85%) had unilateral AH, 60 (13%) presented with synchronous bilateral AH, and 9 (2%) had unilateral AH followed by contralateral AH at a later time (metachronous bilateral AH). Only 93 (20%) patients had an evaluation by an endocrinologist. AH was discovered incidentally in 190 (42%) patients, and during evaluation for abdominal or back pain in 133 (29%), trauma in 104 (23%), sepsis in 19 (4%), and adrenal insufficiency in 8 (2%). Primary etiology of AH was a post-procedural complication in 154 (34%), trauma in 126 (28%), coagulopathy in 54 (12%), anticoagulant or antiplatelet therapy in 52 (12%), adrenal neoplasm in 29 (6%) and sepsis in 20 (4%). Metastasis (15, 50%) represented the most common adrenal neoplasm associated with AH. In 208 (46%) patients, diagnosis of AH occurred in the hospital setting, and in 246 (54%) during an outpatient evaluation. In the 393 patients with available baseline imaging, the median size of AH was 3.1 cm (IQR 2.2-4.0). During a median imaging follow-up of 6 months (IQR 3-12), AH reduced in size with a median decrease of -2.6 cm (IQR -1.8 to -3.7) on the right and -2.0 cm (IQR -1.0 to -4.8) on the left. Compared to patients with unilateral AH, those with bilateral AH were more likely to be diagnosed in the hospital setting (61 vs. 43%, P=0.006), have an underlying coagulopathy (50 vs. 4%, P<0.0001), or sepsis (13 vs. 3%, P<0.0001), be on anticoagulant or antiplatelet therapy (48 vs. 21%, P<0.0001), develop primary adrenal insufficiency (61 vs. 0%, P<0.0001) and have larger baseline AH size (4 cm vs. left 2.7 and right 3.1 cm, P=0.0002), but a similar rate of resolution. Conclusions: AH frequently presents as unilateral hemorrhage and can occur secondary to various etiologies, with trauma and postprocedural complication being the most common. Association with an underlying adrenal mass is uncommon, seen only in 6%. Bilateral AH carries a high risk for primary adrenal insufficiency and is more likely to occur in hospitalized patients, possibly due to an increased prevalence of underlying coagulopathy, sepsis and need for anticoagulation or antiplatelet therapy. Presentation: Friday, June 16, 2023

Abstract Disclosure: J. Saini: None. R. Nathani: None. C. Zhang: None. M. Suresh: None. K. Thangamuthu: None. S. Singh: None. V. Fell: None. E.J. Atkinson: None. S. Achenbach: None. N.H. Stricker: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have impaired cognition compared to patients with non-functioning adrenal adenomas. However, the impact of adrenalectomy on cognitive function in patients with MACS is unclear. Objective: To determine the impact of adrenalectomy on cognitive function in patients with MACS. Methods: Single-center prospective longitudinal study of adults with MACS. MACS was defined as serum cortisol >1.8 mcg/dL after the 1 mg dexamethasone suppression test (DST) in patients with adrenal adenomas without any overt features of hypercortisolism. Patients underwent cognitive evaluation using the standardized National Institute of Health (NIH) Toolbox Cognition Battery (7 tests of attention, episodic and working memory, language, executive function, cognitive flexibility, and processing speed) prior to adrenalectomy and at follow-up at least 10 months post-surgery. Fully corrected T-scores for age, sex, education, and race were compared using a paired t-test before and after adrenalectomy. A T-score of 50 is average performance (SD of 10). Total cognition is composite of fluid cognition (executive function, episodic memory, cognitive flexibility, working memory and processing speed) and crystallized cognition (language and vocabulary). Results: A total of 27 patients with MACS (median age 59.7 years, IQR 51.4-66.9, 17, 63% women) underwent cognitive evaluation prior to and at a median of 1.5 years (IQR, 1.1- 2.0) after adrenalectomy. Before surgery, median post-DST cortisol was 3.8 mcg/dL (IQR, 2.7-6.4) mcg/dL. Of the 27 patients, 21 (78%) patients developed post-operative adrenal insufficiency with 6 (21%) patients still requiring still requiring glucocorticoid replacement at the time of the last follow-up. At baseline, the mean total composite T-score was 50.7 (9.3), with fluid composite T-score of 49.9 (9.4) and crystallized composite T-score of 51.3 (8.7). Following adrenalectomy, all three composite T-scores improved compared to baseline. The crystallized composite T-score (composed of language and vocabulary) increased by a mean of 3.7 (5.5), P=0.001, the fluid composite T-score (composed of episodic, executive, working memory, cognitive flexibility, and processing speed) increased by a mean of 3.1 (8.3), P=0.068, and the total composite T-score improved by a mean of 3.9 (6.2), P=0.004. Conclusion: We showed that adrenalectomy in patients with MACS is associated with improvement in cognition. However, as test results may improve with practice (i.e., improvement due to taking the test the second time), to determine whether the improvements observed represent a reliable change in cognition, the next step is to evaluate for cognition score changes in referent subjects. Presentation: Friday, June 16, 2023

Abstract Disclosure: A. Kittithaworn: None. P. Dogra: None. L. Rahimi: None. R. Sandooja: None. I. Bancos: None. Background: Adrenal calcification is discovered incidentally on imaging performed for reasons other than adrenal pathology and represents <1% of benign adrenal lesions. Data on the etiology and morphology of adrenal calcifications are scarce. Objective: To determine the etiology and imaging characteristics of adrenal calcification. Methods: We conducted a single-center retrospective study of patients with adrenal calcification on abdominal computed tomography between January 1st,2017 and December 31st, 2021. Medical records were reviewed for demographics, discovery mode, etiology and morphology. Subgroup analysis of patients with calcification/s associated with an adrenal mass was performed. Results: Adrenal calcification was reported in 540 patients (245, 45% women, median age 65 years (IQR 54-74). Only a minority of patients with adrenal calcifications were evaluated by an endocrinologist (167, 31%). Adrenal calcifications were discovered incidentally in 472 (87%) patients, during cancer staging imaging in 66 (12%), and evaluation of other symptoms in 2 (<1%). The etiology of adrenal calcification was most commonly idiopathic (390, 72%), followed by adrenal mass (112, 21%), hemorrhage (20, 6%), and granulomatous disease (8, 1.5%). Adrenal calcifications were bilateral in 34 (6%) patients and unilateral in 506 (94%), with a similar left and right distribution. Unilateral calcifications were more frequently single (399, 79%) with punctate (60%), coarse (28%), linear/curvilinear (9%), or eggshell (3%) morphology. Bilateral adrenal calcifications presented more frequently with multiple lesions (53% vs 21% in unilateral calcifications, p <0.0001), and were coarse (59%), punctate (29%), or linear (9%). When associated with either unilateral or bilateral adrenal mass, calcifications were either central (50, 45%), peripheral (44, 39%), septal (10, 9%), or both central and peripheral (7, 7%) in relation to the adrenal mass. Adrenal masses associated with adrenal calcifications were: adrenal adenomas in 63 (56%), myelolipomas or cysts in 28 (23%), metastases in 12 (11%), adrenal carcinomas in 4 (4%), pheochromocytomas in 2 (2%), and other rare masses in 3 (3%) patients. Patients with adrenal calcifications associated with an adrenal mass were younger at the time of diagnosis (median of 63 vs 66 years, p=0.014), and had a higher proportion of women (61% vs. 41%, p=0.0002), and were more likely to be discovered during cancer staging imaging (21% vs. 10%, p=0.003). Adrenal mass-associated calcifications were more frequently multiple rather than single lesions (46% vs. 17%, p<0.0001). Conclusion: Adrenal calcifications are usually unilateral single punctate or coarse lesions of unclear etiology. The majority of the adrenal masses that demonstrated calcifications were benign, however adrenal malignancy or pheochromocytomas were diagnosed in 17% of cases. Presentation: Friday, June 16, 2023

Abstract Disclosure: C.S. Pan: None. E. Melson: None. T. Ogiliev: None. D. Zhou: None. S.Y. Ng: None. F. Rezai: None. Z. Olateju: None. E. Radcliffe: None. P. Balendran: None. A. Radcliffe: None. G.M. Lau: None. J. Sheikh: None. H. Kaur: None. C. Cooper: None. F. Abdelhameed: None. F. Pang: None. S. Bhatt: None. D. Shabbir: None. M. Davitadze: None. A. Prete: None. C.L. Ronchi: None. I. Bancos: None. V. Chortis: None. J.D. Newell-Price: None. H.L. Simpson: None. H. Gleeson: None. K. Manolopoulos: None. J. Chu: None. M.W. O'Reilly: None. W. Arlt: None. C. Gillett: None. P. Kempegowda: None. O. SIMBA team: None. Introduction: Simulation via Instant Messaging - Birmingham Advance (SIMBA) is an effective educational platform in increasing clinicians’ confidence in managing various endocrine conditions (Melson, 2020). However, it has lacked input from the patients living with these conditions. We hypothesize that engaging patients and members of the public can inform clinicians to better tailor management to suit the concerns and expectations of patients. Methods: Two virtual simulation sessions covering topics related to Polycystic Ovary Syndrome (PPI-PCOS) and Adrenal conditions (PPI-Adrenal) were organized for clinicians. Nine cases were simulated using anonymized real-life patient data. Members of the general public living with PCOS or Adrenal conditions were recruited from several support groups to undergo a workshop-style discussion to provide their opinions on how representative the cases were and how the management of the condition could be improved. At the end of the simulations, all clinicians and patients were invited to a panel discussion led by expert consultants over Zoom incorporating the summaries from the workshops. Pre- and post-simulation surveys were distributed to measure the change in clinicians’ confidence using Wilcoxon signed-rank test. Thematic analysis was used to identify gaps in knowledge and expectations between clinicians and patients with PCOS or Adrenal conditions. Results: Self-reported confidence by clinicians in the management of PCOS (n=25) and Adrenal conditions (n=23) increased post-simulation (PPI-PCOS simulated:+41.0%, p<0.001; non-simulated:+40.0%, p<0.001. PPI-Adrenal simulated:+22.5% (p=0.0001); non-simulated:+24.0% (p=0.0005)). 90% and 100% of patients agreed PPI-PCOS benefits patients to understand their condition better, and helps clinicians and patients understand each other’s perspectives respectively, whereas this is true for 80% of patients from PPI-Adrenal regarding both aspects. Recurring themes identified through thematic analysis included approach to handling complexities resulting in delayed diagnosis or management, the need for personalized care, lack of information provided to patients with regards to the progression of symptoms, complications or treatment received. Conclusion: PPI-PCOS and PPI-Adrenal were effective in increasing the knowledge and understanding of PCOS and Adrenal conditions for both members of the general public and healthcare professionals. They also helped narrow the gap in knowledge and expectations by exchanging perspectives through a common dialogue. Presentation: Thursday, June 15, 2023

Abstract Disclosure: J. Saini: None. R. Gregg Garcia: None. J. Herndon: None. D.Z. Erickson: None. L. Gruber: None. I. Bancos: None. Context: Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). However, it is uncommonly used and the data on the OMT indications and performance are scarce. We aimed to characterize the indications, performance, and safety of outpatient OMT. Methods: Single center retrospective study in adults with OMT between April 1st, 2018 -July 31st, 2022. We evaluated three post-OMT cutoffs diagnostic of SAI: 1) 11-deoxycortisol ≤7 mcg/dL (11D≤7); 2) 11-deoxycortisol ≤10 mcg/dL (11D≤10), or 3) sum of cortisol and 11-deoxycortisol ≤15 mcg/dL (sum≤15), in comparison to pre-test probability and reference standard, defined as clinician-made diagnosis of SAI. When available, OMT-based SAI diagnosis was compared to results from the cosyntropin stimulation test (CST). Results: OMT was performed in 109 patients (76, 70% women) at a median age of 48 (IQR, 37-59) years. Pre-test probability for SAI was high in 13 (12%), moderate in 46 (43%), and low in 49 (45%) patients. Indications for OMT included evaluation of symptoms without clear SAI risk factors (38, 35%), suspected SAI due to chronic opioid use (25, 23%), pituitary pathology/therapies (25, 23%), exogenous glucocorticoid use (8, 7%), other (13, 12%). Overnight metyrapone was administered at a median dose of 2500 (IQR, 2125-3000). Adverse events were reported by 9 (8%) patients and were mild (nausea, fatigue) except for 1 patient who had to be hospitalized. The final diagnosis of SAI was made in 25 (48%) patients: 92%, 52%, and 12% of patients with high, moderate, and low pre-test probability. When compared to the clinician-made SAI diagnosis, OMT-based diagnosis of SAI was made in 60% of patients using the 11D≤7 cutoff, and in 81% of patients using the other cutoffs (11D≤10 or sum≤15). In 50 patients with concomitant CST, the final diagnosis of SAI was made in 23 (46%) patients, despite the normal CST results (post-cosyntropin peak cortisol ≥18 mcg/dL) in 12/23 patients. In patients with post-cosyntropin peak cortisol ≥18 mcg/dL, OMT was abnormal in 14% of patients (using post-OMT cutoff 11D≤7), 29% of patients (based on cutoff 11D≤10), and in 30% of patients (based on sum≤15). Conclusions: Outpatient OMT is well tolerated and was mostly used in patients with low/moderate pre-test probability for SAI. In patients with normal CST, OMT may diagnose SAI in additional 30% of patients, especially if the pre-test probability is high. Post-OMT sum of 11-deoxycortisol and cortisol <15 mcg/dL performs well in diagnosing SAI while allowing confirmation of adequate cortisol suppression. Presentation: Saturday, June 17, 2023