Citations

Abstract Context Preclinical studies demonstrate that treatment with calcitriol attenuates skeletal complications in mice with X-linked hypophosphatemia (XLH). Objective This work aimed to assess serum markers of mineral metabolism, nephrocalcinosis, skeletal microarchitecture, growth, and evidence of rickets following calcitriol monotherapy in children and adults with XLH. Methods A 1-year, prospective, single-arm, open-label study was conducted comparing baseline and 12-month outcomes. Participants were recruited from outpatient endocrinology clinics in the United States. Data were collected in a research unit. Eligible participants were aged 4 years or older, not pregnant, with baseline 25-hydroxyvitamin D of 20 ng/mL or greater and normal serum calcium. Participants were treated with calcitriol, with dose based on serum and urinary calcium concentrations, for 1 year. The primary end points were change in serum phosphate and nephrocalcinosis (all participants) and rickets severity score (children). Secondary end points included changes in additional markers of mineral metabolism, skeletal microarchitecture parameters via high-resolution peripheral quantitative computed tomography (all participants), and height z-scores (children). Results Serum phosphate did not change over 12 months of optimized calcitriol treatment. Rickets improved in 2 of 4 children with open epiphyses; height z-scores were unchanged. Nephrocalcinosis scores remained stable. Adults had increased cortical thickness at the radius diaphysis (P = .012). Serum alkaline phosphatase decreased in children (P = .021) and parathyroid hormone trended lower both in children (P = .065) and adults (P = .063). Four participants developed mild hypercalcemia and 2 developed hypercalciuria that resolved with calcitriol titration. Conclusion Calcitriol monotherapy is safe and well-tolerated in XLH, with modest benefits on laboratory indices of mineral metabolism and rickets.

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: M. Kakakhel: None. S. Cheema: None. R. Haider: None. R. Noor: None. S. N.l: None. S.M. Irshad: None. A. Ullah: None. H. Jawad: None. A. Nawaz: None. M. Khawar: None. A. Qadeer: None. H. Ahmad: None. R. Alcaraz: None. F. Ahmed: None. Background: Bone density and structure-related disorders, such as osteoporosis and related fractures, significantly contribute to morbidity and mortality, particularly among aging populations. Monitoring temporal trends and geographic variations in mortality is essential to inform targeted public health interventions. In this study, we aimed to examine temporal and geographic variations in mortality associated with bone density and structure-related disorders in the United States from 1999 to 2022. Methods: Using ICD-10 codes M80-M85, this retrospective ecological study utilized mortality data extracted from the CDC WONDER database for the years 1999-2022. Age-adjusted mortality rates (AAMRs) were calculated and stratified by demographic variables (age, sex, and race/ethnicity) and geographic regions. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs). Geographic variations were visualized using choropleth maps, and subgroup analyses were performed to explore disparities. Statistical significance was set at p < 0.05. Results: Age-adjusted mortality rates (AAMRs) for bone density and structure-related disorders decreased overall from 1999 to 2019, with a subsequent rise observed in 2020 and 2022. Joinpoint regression revealed a significant negative trend from 2007-2016 (APC = -7.46%, p < 0.000001), followed by a positive reversal from 2019-2022 (APC = 3.78%, p = 0.013). Both males and females experienced declines in mortality, but females had a slightly higher APC of -3.10% compared to -2.82% for males. Asian/Pacific Islander groups exhibited the most pronounced decrease in mortality (APC = -11.92%, p < 0.000001) from 2009-2015, with a positive rebound in recent years. Black or African American populations had the smallest decline (APC = -1.35%). The Southern U.S. experienced the steepest decline in mortality from 2010-2016 (APC = -10.92%, p < 0.000001), followed by a strong positive trend from 2019-2022 (APC = 6.61%, p < 0.000001). Conversely, the West and Northeast regions showed milder trends with less pronounced reversals. Older age groups (65-74, 75-84) showed significant decreases in mortality, particularly the 65-74 group, which reversed to a positive trend (APC = 6.97%) from 2019-2022. The highest number of deaths occurred at the decedent’s home (3,330 in 2022). Subgroup analyses indicated significant temporal shifts in the mortality patterns across different racial/ethnic groups and geographic regions. Hispanic/Latino and Asian/Pacific Islander populations exhibited an increase in mortality rates post-2019, particularly in 2020. Conclusion: From 1999 to 2022, mortality from bone density and structure-related disorders in the U.S. exhibited significant temporal and geographic variations. These findings highlight the need for targeted public health strategies. 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: 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 Disclosure: A.J. Han: None. S.J. Achenbach: None. B.J. Atkinson: None. I. Bancos: None. Background: The prevalence of adrenal adenomas continues to rise with increased utilization of imaging. However, much remains unknown about what risk factors may predispose individuals to develop adrenal adenomas. In this study, we aimed to identify modifiable and non-modifiable risk factors associated with development of adrenal adenomas. Methods: Historical case-control population study was performed. Patients diagnosed with adrenal adenoma between 2005-2017 with no evidence of overt hormone excess were paired with age- and sex-matched individuals without a diagnosis of adrenal adenoma who had a CT/MRI scan performed within 5 years prior to index date. The prevalence of various social and metabolic risk factors present within 10 years prior to index date (date of adrenal adenoma diagnosis) was compared. Results: Total of 670 patients (median age 63, IQR 53-74 years, 56% women) with adrenal adenomas were identified. At 10 years prior to index date, patients with adrenal adenomas had a higher body mass index (BMI) (median 30.1 vs 28.2 kg/m2, p<0.001), lower socioeconomic status (SES) based on Area Deprivation Index (36.2% with national percentile score >50 vs 30.9%, p=0.037), and more tobacco use (70.2% vs 61.4%, p=0.001), compared to referent subjects. Patients also had a higher prevalence of diabetes (17.5% vs 11.7%, p=0.003) 5-10 years prior to index date, but no difference in prevalence of hypertension, myocardial infarction, chronic kidney disease, atrial fibrillation, stroke, or heart failure was observed between groups. Based on multivariable analysis, increased BMI and tobacco use 10 years prior to index date was associated with increased odds of adrenal adenoma diagnosis with odds ratio (OR) of 1.18 (95% Confidence Interval 1.06-1.32) and 1.41 (1.06-1.87), respectively. Conclusions: Compared to controls, patients with adrenal adenoma were more likely to be obese, have lower SES, endorse tobacco use, and demonstrate evidence of impaired glucose metabolism at least 5-10 years prior to diagnosis. In particular, increased BMI and prior tobacco use was associated with increased odds of adrenal adenoma diagnosis. Further exploration of these intricate relationships may help identify modifiable risk factors for development of adrenal adenomas. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. R. Haider: None. S. Cheema: None. S.M. Irshad: None. M.U. Hussain: None. A. Ullah: None. A.Z. Khan: None. F. Naveed: None. H. Jawad: None. F. Naveed: None. M.F. Hemida: None. A. Qadeer: None. M. Khawar: None. H. Ahmad: None. F. Ahmed: None. R.W. Kirchoff: None. R. Alcaraz: None. Background: Hypertension has been a significant cause of morbidity and mortality for ages. Coupled with endocrine disorders, it poses a greater risk of indisposition to the U.S population. This CDC wonder analysis explores the trends and patterns of these disorders, stratified by states and rural/urban. Methods: To attain this objective, this retrospective study has utilized data from the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to assess endocrine disorder-related mortality rates in the pediatric population from 1999 to 2011. Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were used to evaluate trends and produce age-adjusted mortality rates (AAMRs) per 100,000 people. Data was stratified by year, sex, race/ethnicity, state-wise and geographical regions. Statistical significance and confidence intervals were used to assess the reliability of the observed trends. Results: Between 1999 and 2020, 2383332 deaths in the United States were attributed to endocrine-related mortality with underlying hypertension. The Overall AAMR initially rose steeply from 10.7 in 1999 to 24.9 in 2001 (APC: 34.3; 95% CI: 9.5 to 56.7), followed by a period of further steady increase in AAMR till 36.5 in 2018 (APC: 1.6; 95% CI: 0.6 to 2.1). This progressive increase in AAMR then sharply spiked from 2018 onwards, reaching 51.7 in 2020 (APC: 18.1*; 95% CI: 9.3 to 23.5). Notable discrepancies were observed in urbanization. Non-metropolitan areas showed a higher AAMR (35.5) than metropolitan (31.5). State-level analysis revealed substantial heterogeneity, including Mississippi as the state of the highest AAMR (58.6). Conclusion: The concerning rise of AAMR in non-metropolitan areas and Mississippi calls for more targeted health-care policies. These findings underscore the need for geographically tailored public health interventions to address disparities in endocrine disorder-related mortality in these groups. Presentation: Monday, July 14, 2025

Abstract Disclosure: J. Herndon: None. Y. Hleibiehova: None. A. Bancos: None. S. Achenbach: None. E. Atkinson: None. D. Donegan: Camarus, Recordati. I. Bancos: None. Introduction: Studies show that quality of life (QOL) among patients with adrenal insufficiency (AI) (primary (PAI) or secondary (SAI)) improves following adequate glucocorticoid replacement, however decreased QOL persists. SAI due to hypophysitis or infrequently PAI due to adrenalitis are recognized complications of immune-checkpoint-inhibitors (ICI). It is unknown if patients with ICI induced AI (ICI-AI) would report similar findings in QOL. Aim: To assess the impact of ICI-AI on specific determinants of health-related QOL (HRQOL) and compare management and outcomes to SAI due to other etiologies (oSAI). Methods: A cross-sectional survey study of adult patients who completed at least 1 AddiQOL survey with a diagnosis of ICI- AI or oSAI evaluated between 2015 and 2024 were included. Patients with opioid- or glucocorticoid-induced-AI were excluded. A study survey obtained information regarding diagnosis and treatment. Results: 112 patients with ICI-AI were included (SAI n=109, PAI n=3). Among those with ICI-AI, 59% were female, median age at diagnosis was 59.7 ±12.8 years and melanoma was the most common indication for ICI use (51%). The median time to ICI-AI diagnosis was 5.5 (range 0.3-80.8) months and 46% used combination ICI therapy. When compared to those with oSAI (n=139), patients with central ICI-AI were older at diagnosis (59 ±12.7 vs 46 ±18.1 years, p <0.01), more were female (59 vs 43%, p=0.015) and most were diagnosed in the last year (88% vs 42%, p<0.01). Those with ICI-AI received higher hydrocortisone (HC) equivalent daily doses than those with oSAI (25.1± 18.3 vs 22.1 ±16.9 mg/day, p<0.01), however there was no difference in the number of adrenal crises (AC) reported within the last year (14 vs 16, p=0.78). Patients with ICI-AI felt that emergency personnel understood their diagnosis and treated them promptly (75% vs 0% p=0.012). Logistic regression analysis of the entire group (ICI-AI + oSAI) did not identify an association between the occurrence of AC in the last year and HC dose >20 mg/day or type of glucocorticoid. Furthermore, there was no difference in number of AC per person year assessed between the ICI-AI and oSAI (0.23 ±0.5 vs 0.21 ±0.5, p= 0.4). The mean total AddiQOL score was higher in those with ICI-AI (87.2 ±13.9 vs 81.8 ±15.8, p=0.02). When adjusted for age and sex, total AddiQOL score was inversely related to number of symptoms present (r: -0.49, p<0.01; r: -0.58, p<0.01), occurrence of AC in the last year (r: -0.27, p=0.01; r: -0.33, p<0.01) and positively related to current employment (r:0.33 p<0.01 0.2,p=0.02) in ICI-AI and oSAI respectively. Conclusion: This is the first study to compare management and HRQOL in patients with ICI-AI compared to oSAI and although there were no significant differences in total number of AC events between the 2 groups, differences exist in terms of AI presentation, management and reported QOL. 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