Achenbach, Sara

Abstract Disclosure: A. Bancos: None. Y. Hleibiehova: None. R. Gregg garcia: None. N. Genere: None. S. Achenbach: None. E. Atkinson: None. S. Mahrokhian: None. A. Vaidya: None. I. Bancos: None. Background: Bilateral adrenalectomy (BLA) is a seldomly performed treatment for hypercortisolism, pheochromocytoma, or metastatic adrenal disease that leads to permanent primary adrenal insufficiency (PAI). PAI due to BLA is seldomly studied independently of PAI due to autoimmune adrenalitis (AA), despite differences in onset of disease, and neither group has large-scale data focusing on factors that impact quality of life (QOL) post-PAI. Furthermore, no study to date has compared patients’ burden of disease or number of adrenal crises in patients with PAI due to BLA versus patients with PAI due to AA. Methods: We conducted a dual-center, cross-sectional study of adults with PAI due to AA or BLA, 2022-2025. All participants completed a questionnaire on symptoms, management, adrenal crises, and an adrenal insufficiency-specific QoL survey (AddiQoL). Outcomes included AddiQoL scores and self-reported adrenal crises. Pearson correlations were used to explore relationships with AddiQoL scores. Logistic regression models were used to examine associations with having an adrenal crisis in the past year. Results: Of the 343 participants, 203 had AA (median age of 54 years, IQR 42-67, 72% women) and 140 had BLA (median age of 57 years, IQR 44-67, 76% women). Median duration of PAI was similar for AA and BLA cohorts (13 vs 10 years, P=0.205). Patients with AA and BLA were treated with hydrocortisone (84% vs 78%), prednisone (19% vs 21%), or dexamethasone (1% vs 1%), with a similar median daily hydrocortisone equivalent dose (21 mg vs. 20 mg, P=0.259). No group differences in availability of glucocorticoid injections (85% vs 83%) and medical alert bracelet (81 vs 83%) were reported. AddiQoL scores were similar between patients with AA and BLA (median 84 vs 83, P=0.984). AddiQoL score was better in older patients (R=0.16, P=0.003), men (R=0.17, P=0.002), daily hydrocortisone ≤ 20 mg/day (R=0.11, P=0.04), and those with supportive health insurance (R=0.20, P<0.001). Patients with AA reported a higher number of adrenal crises since diagnosis (median of 0.1/person-years, IQR 0-0.4 vs 0/person-years, IQR 0-0.3, P=0.046), as well as in the last year (25% vs 13%, P=0.022), compared to patients with BLA. In a multivariable model of age, sex, glucocorticoid dose, availability of glucocorticoid injection/medical bracelet, type of PAI, and number of symptoms, patients with AA (OR 2.1, 95%CI 1.0-4.4) and those with more symptoms (OR 1.2, 95% CI 1.1-1.3) were more likely to have an adrenal crisis within the last year. Conclusion: We found no differences in the QoL scores, burden of disease, symptoms, or management of patients with AA and BLA. However, patients with AA reported more adrenal crises both overall and within the last year of assessment. Presentation: Sunday, July 13, 2025

Abstract Context Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol >1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. Objective To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects. Methods Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index–, and menopausal status–matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects was admitted for serum measurements of free and total cortisol every 2 hours. Outcomes were steroids, steroid sums, and ratios. Results Patients with MACS (n = 72) had lower µg/24 hour median androgens (2084 vs 3283, P < .001), higher glucocorticoids (15 754 vs 12936, P < .001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P < .001) than referent subjects. Patients also had lower steroid day/night ratios than referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour areas under the curve for total and free serum cortisol were similar. However, evening mean total (5.3 vs 4.0 µg/dL, P = .056) and free (0.2 vs 0.1 µg/dL, P = .035) cortisol was higher in patients vs referent subjects. Conclusion Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.

Abstract Context Patients with adrenal hormone excess demonstrate increased cardiovascular (CV) risk and mortality. Objective We aimed to determine the effect of adrenal disorders on the inflammation marker glycoprotein acetylation (GlycA), total branched-chain amino acids (BCAAs), ketone bodies, and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. Methods We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFAs), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGLs), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n = 802). Referent individuals included participants in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study (n = 5241). GlycA, BCAAs, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, and statin therapy. Results In age- and sex-adjusted comparison to referent individuals, increased GlycA was noted in all patient categories, increased BCAAs in NFA, MACS, CS, PA, and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS, and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of participants with diabetes and CV disease. Conclusion Patients with functioning and nonfunctioning adrenal masses demonstrated increased GlycA and BCAAs, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

AbstractThe prevalence of liver dysfunction and its association with outcomes in patients with previously untreated chronic lymphocytic leukemia (CLL) is unknown. Newly diagnosed (<12 months) previously untreated CLL patients seen at Mayo Clinic, Rochester, MN between 9/1993 and 4/2016 who had baseline assessment of at least one liver function test (LFT) were included in this analysis. The prevalence of liver dysfunction at baseline, proportion of patients who acquired LFT abnormalities, time to first therapy (TTFT) and overall survival (OS) were assessed. An abnormal LFT was present in 82/2336 (3.5%) patients at diagnosis and was associated with advanced Rai stage (Rai III–IV) (21% vs. 6%; P < .001), lower hemoglobin (13.1 g/dL vs. 13.9 g/dL; P < .001), and lower platelet count (187 × 109/L vs. 200 × 109/L; P = .03). Additionally, 236 patients with normal LFTs at diagnosis developed acquired liver dysfunction during follow‐up. Patients with abnormal LFTs at diagnosis had a shorter OS compared to those with normal LFTs (HR 1.80 95% CI 1.13‐2.87; P = .014, adjusted for age, sex, Rai stage, and treatment), although TTFT was not different. Of 52 patients who underwent a liver biopsy, CLL was present in liver tissue in 39/52 (73%) patients, with the portal tracts the most common region involved. Histopathology findings of liver involvement by CLL had limited correlation with choice of CLL therapy. In conclusion, approximately 1 of 25 newly diagnosed CLL patients has abnormal LFTs at diagnosis. Although the TTFT was not different among patients with abnormal LFTs, these patients have a shorter OS compared to those with normal LFTs.