Citations

Abstract Context Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. Objective To characterize the effect of MACS on bone density, metabolism, and microstructure as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Design Cross-sectional study, 2019-2022 Setting Tertiary referral center Participants Seventy-five patients with MACS and 75 age-, sex-, and gonadal status–matched referent subjects. Measurements Bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan, and HR-pQCT. Outcomes Areal and volumetric bone mineral density (aBMD, vBMD), trabecular bone score (TBS), microstructural parameters including trabecular bone volume to total volume (BV/TV) ratio. Results While no differences in aBMD were observed at any skeletal site, patients with MACS had decreased TBS (1.389 vs 1.475, P < .001) and lower osteocalcin concentration (17.1 vs 19.5 ng/mL, P = .030) than referent subjects. On HR-pQCT at the tibia, patients with MACS had reduced trabecular BV/TV (0.220 vs 0.233, P = .015) compared to referent subjects. On multivariable analysis, MACS was associated with lower TBS (odds ratio [OR] per SD decrease 2.87 [1.65-5.00]), lower trabecular BV/TV at the radius (OR per SD decrease 2.58 [1.33-5.00]), and lower trabecular BV/TV at the tibia (OR per SD decrease 4.06 [2.10-7.86]). Conclusion Patients with MACS have microstructural deterioration that may not be evident on routine DXA aBMD testing.

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 Context Patients with endogenous hypercortisolism experience glucocorticoid withdrawal syndrome (GWS) after surgery. Meditation may be an effective intervention to alleviate the severity of GWS. Objective To determine the acceptability of a portable, wearable electroencephalography device for guided meditation (MUSE headband) and the impact of MUSE use on GWS and quality of life 12 weeks postsurgery. Methods We conducted a single-center prospective cohort study of adults with endogenous hypercortisolism undergoing curative surgery from 2019 to 2024. Patients had baseline and postsurgical assessments over 12 weeks. The study comprised 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 GWS symptoms were assessed with AddiQoL, CushingQoL, and 36-item Short Form Health Survey 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 after surgery. At baseline, compared to 88 matched subjects, 22 MUSE participants demonstrated similar prevalence of comorbidities and clinical and biochemical hypercortisolism severity, but lower AddiQoL (mean 73 vs 66, P = .031) and SF-36 MCS (mean 39 vs 33, P = .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 postsurgery (beta 4.2, 95% CI: 0.5-7.9, P = .026). Conclusion Postsurgical meditation intervention may improve physical symptoms and accelerate recovery.

Abstract Objectives The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition. Methods We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021 to 9/2023) of adults with MACS and referent subjects. Cognition was assessed with National Institute of Health Toolbox Cognition Battery and reported as standardized T scores (adjusted for age, sex, race/ethnicity, and education) for fluid, crystallized, and total composite cognition. Participants were assessed with urine steroid profiling (liquid chromatography-tandem mass spectrometry), frailty index, Beck’s Depression Inventory (BDI), and Short Form-36 (SF-36). Results A total of 84 patients (median age 57 years, 67% women) and 201 referent subjects (median age 63 years, 58% women) were included. Patients with MACS demonstrated lower mean (SD) total composite (50.9 [9.3] vs 55.4 [8.9], P < .001) and fluid composite T score (49.3 [10.6] vs 55.2 [10.2], P < .001), but not crystallized composite T score (52.3 [8.4] vs 54.0 [8.4], P = .130) when compared with referent subjects. Multivariable analysis adjusted for age, sex, BDI, SF-36, frailty index, total glucocorticoids, and androgens demonstrated that MACS status was associated with lower cognition. When cognition was reassessed in 37 patients post-adrenalectomy and 31 referent subjects, adjusted group differences of cognition change were similar except for a higher comparative increase in attention and executive functioning in patients with MACS. Conclusion Patients with MACS demonstrate lower cognition than referent subjects. Adrenalectomy for MACS had a minor positive impact on cognition.

Abstract Context Diagnosing adrenal insufficiency (AI) often requires complex testing, which can be time-consuming and expensive. Dehydroepiandrosterone sulfate (DHEAS) is a promising marker of hypothalamic-pituitary-adrenal axis function; however, its diagnostic performance has not yet been evaluated in a large-scale study. Objective Evaluate the performance of DHEAS and baseline cortisol in assessing AI. Design Single-center retrospective cohort study. Setting Referral center. Patients Adults who underwent cosyntropin stimulation testing (CST) between 2005 and 2023 and had DHEAS measured within 3 months prior to CST. Main Outcome Measures Area under receiver operating characteristic curve (AUROC) for DHEAS and baseline cortisol. Prevalence of AI based on various DHEAS and baseline cortisol concentrations. Results Among 1135 patients, 195 (17.2%) had AI. Both baseline cortisol and DHEAS independently had good diagnostic performance with AUROC 0.81 [95% confidence interval (CI) 0.77-0.84 and 0.81 (95% CI 0.78-0.85)], respectively. Time of CST performance had no significant effect on diagnostic accuracy of baseline cortisol while recent glucocorticoid use decreased diagnostic performance of DHEAS (AUROC 0.72 vs 0.83). Only 1.2% of patients with baseline cortisol ≥10 mcg/dL had AI based on CST. Among patients with baseline cortisol between 5 and 9.9 mcg/dL, only 1.3% had AI if DHEAS was ≥60 mcg/dL. Conversely, the majority (72.2%) of patients with both baseline cortisol <5 mcg/dL and DHEAS <25 mcg/dL were found to have AI. Conclusion DHEAS has good diagnostic performance in assessing AI. Measuring both baseline cortisol and DHEAS concentrations may eliminate the need for further dynamic testing in many patients.

Abstract Disclosure: J. Saini: None. B. Bahrani Fard: None. M. Suresh: None. R. Sandooja: None. Y. Hleibiehova: None. E. Atkinson: None. S. Achenbach: None. I. Bancos: None. Background: Patients with endogenous hypercortisolism experience glucocorticoid withdrawal syndrome (GWS) following curative surgery. The symptoms of GWS include fatigue, weakness, muscle aches, joint pain, mood changes, and sleep disturbance. Limited interventions have been explored to alleviate the symptoms of GWS and improve patients’ quality of life. The use of meditation as an intervention has been reported to enhance postsurgical recovery in patients with other conditions and offers a promising intervention for GWS. Objective: To determine the impact of a portable, wearable, electroencephalographic device (MUSE headband device) used for guided meditation practices on the quality of life of patients in the first 12 weeks post-surgery for endogenous hypercortisolism. Methods: We conducted a single-center prospective longitudinal study of adults with endogenous hypercortisolism undergoing curative surgery between 2018 and 2024. The patients were enrolled before the surgical intervention and were followed for 2 years. Only patients who completed at least 4 weeks of follow-up were included. The study comprised of 2 groups; (1) The interventional group included consecutive patients who were offered a MUSE headband with instructions to meditate for at least 10 minutes per day for 3 months (MUSE cohort) and (2) the comparison group included age-, sex-, clinical score, hypercortisolism type, and BMI-matched 3:1 patients (Referent cohort). Quality of life and symptoms of GWS were assessed with AddiQoL and Short Form-36 (SF-36) surveys. Results: At least 4 weeks post-surgical follow-up was completed by 27 patients in the MUSE cohort and 81 referent subjects. Age (median 51 vs 47 years), women (82% vs 84%), BMI (median 31 vs 32 kg/m2), the subtype of hypercortisolism (pituitary 48% vs 52%), clinical (median 16 vs 15) and biochemical (median 6 vs 7) severity scores were similar between the two groups (P>0.05 for all). At baseline, AddiQoL score was similar in groups (median of 66 vs 70, P=0.083), though symptoms of fatigue (92.6% vs 69.1%, P=0.015) and lightheadedness (37% vs 17.3%, P=0.033) were more frequent in MUSE cohort. After 12 weeks, 20 patients using MUSE demonstrated improvement compared to 67 no muse patients in the SF-36 physical component (mean delta 3.9 (SD 11.77) vs -2.19 (SD 9.67), P=0.010). The physical functioning SF-36 subcomponent (4.94 (8.77) vs 0.92 (9.24), P=0.048) and body pain SF-36 subcomponent (2.69 (11.89) vs -3.69 (8.32), P=0.008) domains improved in the MUSE intervention group, when compared to referent cohort. No significant improvement in SF-36 mental component scores was seen in both groups. Conclusions: The use of wearable electroencephalographic device for meditation was associated with improvement in the quality of life of patients recovering from hypercortisolism, particularly in the domains of body pain and physical functioning. Presentation: 6/3/2024

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: C.D. Zhang: None. S. Singh: None. J. Saini: None. M. Suresh: None. K. Thangamuthu: None. R. Nathani: None. A.L. Ebbehøj: None. V. Fell: None. S.J. Achenbach: None. E.J. Atkinson: None. S. Khosla: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have higher rates of fractures compared to patients with non-functioning adrenal nodules, but bone mass is typically only modestly reduced. We hypothesized that chronic exposure to mild levels of cortisol excess may lead to a deterioration in bone quality. Objective: To characterize the effect of MACS on bone metabolism and bone microarchitecture, as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In this cross-sectional single-center study, patients with MACS were matched by age, sex, and gonadal status to referent subjects without adrenal nodules. MACS was defined as serum cortisol concentration >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (1-mg DST), in the absence of a classic Cushingoid phenotype. Those with other known secondary causes of osteoporosis and/or on pharmacologic treatment for low bone mass were excluded. All study participants underwent a bone health interview, blood draw for bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan with trabecular bone score (TBS), and HR-pQCT of the non-dominant radius and tibia. Participants with a recent fracture within 12 months were excluded from the analysis of bone turnover markers. The Kruskal-Wallis test was used to compare measurements between groups. Results: A total of 82 patients with MACS and 82 referent subjects were prospectively enrolled between 1/2019 and 7/2022. The median age of study participants at the time of enrolment was 57 years (interquartile range [IQR], 47-65), and 57 (70%) were women. In the MACS cohort, the median cortisol following 1-mg DST was 3.2 mcg/dL (IQR, 2.3-6.5) with median ACTH of 8.7 pg/mL (IQR, 6.0-14.0) and median DHEA-S of 42.0 mcg/dL (IQR 23.0-68.0). While no differences in bone mineral density (BMD) were observed at any site (lumbar spine, total hip, femoral neck, or distal radius) between the two groups, patients with MACS had decreased TBS (1.374 vs 1.467, P <0.001) and lower osteocalcin concentrations (16.9 vs. 19.7 ng/mL, P = 0.005) than referent subjects without adrenal nodules. On HR-pQCT at the tibia, patients with MACS had significantly reduced trabecular volumetric BMD (151.6 vs 167.4 mg hydroxyapatite/cm3, P = 0.002), trabecular bone volume/tissue volume ratio (0.219 vs 0.237, P = 0.011), and number of trabeculae (1.428 vs 1.506 1/mm, P = 0.045), while trabecular separation (0.707 vs 0.656, P = 0.023) was increased compared to referent subjects. Conclusions: Patients with MACS have altered bone metabolism and microstructural deterioration that is not evident on routine DXA BMD testing. These changes may mediate their increased fracture risk and could serve as biomarkers of cortisol-induced changes in the bone. Presentation: Thursday, June 15, 2023

Abstract Disclosure: J. Saini: None. R. Nathani: None. S. Singh: None. K. Thangamuthu: None. M. Suresh: None. C. Zhang: None. A.L. Ebbehøj: None. M. Thomas: None. V. Fell: None. E. Atkinson: None. S. Achenbach: None. N. Stricker: None. I. Bancos: None. Introduction: While patients with overt Cushing syndrome are reported to have impaired cognition, the impact of milder, long-standing hypercortisolism on cognition is incompletely characterized. Objective: To determine the impact of MACS on cognition as compared to age, sex, and education-matched referent subjects. Methods: We conducted a single-center cross-sectional study of adults with MACS and referent subjects. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test (DST) in patients with adrenal incidentalomas. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Exclusion criteria were malignancy and exogenous glucocorticoid use within 1 year. All participants underwent a cognitive evaluation using the NIH Toolbox Cognition Battery between 1/2019 to 7/2022. NIH Toolbox assesses 8 cognitive domains using 7 tests and yields 3 composite scores: fluid cognition (executive function, episodic memory, cognitive flexibility, working memory, and processing speed), crystallized cognition (language and vocabulary), and total composite cognition (composite of all). Results are given in fully corrected T scores (adjusted for age, sex, race, and education) with an average of 50 and a standard deviation (SD) of 10. A subgroup analysis was performed based on DST cortisol. The Kruskal-Wallis test was used to compare scores between groups. Results: A total of 94 patients with MACS (median age 57.2 years, IQR 47.8-66.5, 70% women) and 94 referent subjects (median age 58 years, IQR 49.1-66.4, 70% women) were included. The median post-DST cortisol in patients with MACS was 3.3 mcg/dL (IQR, 2.4-6.2). The mean (SD) total composite T-score was lower in patients with MACS vs referent subjects (51 (9.1) vs 56.3 (9.3), P<0.001). Patients with MACS demonstrated lower mean fluid composite T-score when compared to referent subjects (49.5 (10.4) vs 56.9 (9.7), P<0.001). However, mean crystallized composite T-scores were similar in patients with MACS and referent subjects (52.3 (8.1) vs 53.9 (9.6), P=0.342). A subgroup analysis of patients with post-DST cortisol <3 mcg/dL (n=40) vs patients with post-DST cortisol >3 mcg/dL (n=54) did not show any differences in the total, fluid, or crystalized composite scores. Conclusion: Patients with MACS demonstrate lower cognitive performances than a referent group suggesting MACS has a subtle impact on cognitive functioning. The pattern of cognitive impairment in patients with MACS is similar to that seen with normal cognitive aging: impaired fluid cognitions and unaffected crystallized cognition). Cognitive performance did not differ based on the degree of MACS suggesting that in the absence of overt features of hypercortisolism, the degree of MACS is less important than the presence of MACS. Presentation: Thursday, June 15, 2023

Abstract Objective Glucocorticoid withdrawal syndrome (GWS) is a scarcely studied phenomenon that complicates the recovery following surgical remission of hypercortisolism. We aimed to characterize the presence and trajectory of glucocorticoid withdrawal symptoms in the postoperative period and to determine presurgical predictors of GWS severity. Design Longitudinal observational study. Methods Glucocorticoid withdrawal symptoms were prospectively evaluated weekly for the first 12 weeks following surgical remission of hypercortisolism. Quality of life (CushingQoL and Short-Form-36) and muscle function (hand grip strength and sit-to-stand test) were assessed at the baseline and at 12 weeks after surgery. Results Prevalent symptoms were myalgias and arthralgias (50%), fatigue (45%), weakness (34%), sleep disturbance (29%), and mood changes (19%). Most symptoms persisted, while myalgias, arthralgias, and weakness worsened during weeks 5-12 postoperatively. At 12 weeks after surgery, normative hand grip strength was weaker than at baseline (mean Z-score delta −0.37, P = .009), while normative sit-to-stand test performance improved (mean Z-score delta 0.50, P = .013). Short-Form-36 Physical Component Summary score worsened (mean delta −2.6, P = .015), but CushingQoL score improved (mean delta 7.8, P < .001) at 12 weeks compared to baseline. Cushing syndrome (CS) clinical severity was predictive of postoperative GWS symptomology. Conclusion Glucocorticoid withdrawal symptoms are prevalent and persistent following surgical remission of hypercortisolism with baseline CS clinical severity predictive of postoperative GWS symptom burden. Differential changes observed in muscle function and quality of life in the early postoperative period may reflect the competing influences of GWS and recovery from hypercortisolism.