Citations

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: L.J. Plaza Enriquez: None. R. ibrahim: None. L. Ayari: None. R. Gavrilova: None. Y. Kudva: None. Introduction: Mitochondrial diabetes(mtDB) is a rare disease; hence its prevalence and associated comorbidities are not well defined. The aim of this study is to describe prevalence, glycemic control, treatment used for diabetes and comorbidities associated with this condition using a Mayo Clinic cohort of patients with mitochondrial mutations. Methods: We identified 23 patients with diabetes from an institutional cohort of patients with, mitochondrial mutations. Genetic mutations included the classic MTTL1 m.3243A>G in 22 of the patients and MTND5m.13513G>A in one patient. Statistical analysis was performed using BlueSky Statistics version 10.3.4 software. Categorical variables were compared using Fisher’s exact test and continuous variables were compared using ANOVA. Kaplan Meier survival curves were created. Unless otherwise stated, value of p of <0.05 was considered significant. Results: The cohort consisted of predominantly females (14 vs 9). The mean age at initial diabetes diagnosis was 39.5 years (CI: 30.6–48.4) for females and 32.0 years (CI: 20.9–43.1) for males (p = 0.253). Over 75% of patients were initially diagnosed with type 2 diabetes (T2D). The mean age at mtDB diagnosis was 51.7 years (SD 11.9) for females and 46.0 years (SD 8.5) for males, reflecting a >15-year gap between T2D and mtDB diagnosis. The mean BMI at initial diagnosis was similar between males and females (26.0 (CI: -8.4, 60.4)), though it was higher than the average reported in the literature. Most patients had multiple comorbidities associated with mtDB, including retinopathy, macular defects, cerebrovascular disease, CVD, arrhythmias, nephropathy, and gastrointestinal conditions. Retinopathy and macular defects typically developed within 5-10 years of diabetes diagnosis, while cerebrovascular disease and CVD had a later onset, at a mean of 8.25 years (SD = 6.76) and 5.0 years (SD = 5.75), respectively. However, the difference in onset times between these comorbidities was not statistically significant (p = 0.3228).Regarding glycemic control, there was no significant difference in HbA1c levels at diagnosis or later (HbA1c < 8% in >90% of the cohort). Various treatment modalities (13 on insulin therapy vs 10 on non-insulin treatments) did not show significant differences in glycemic control (p = 0.463), with mean HbA1c of 6.59 (SD 1.36). Mortality rates increased 10-15 years after initial diagnosis of mtDB, with 3 patients dying from complications related to the mitochondrial disorder. Conclusion: mtDB is associated with significant comorbidities/complications that developed earlier compared to T2D or even T1D from the literature. Initial misdiagnosis of this condition as T2D remains high. Different treatment modalities (insulin vs non-insulin) did not differ in glycemic control hence consideration as first options of treatment should be given to oral hypoglycemics. Presentation: Saturday, July 12, 2025

Abstract Disclosure: A. Al Nofal: None. K. Benkhadra: None. M. Nduwimana: None. A. Mohammad: None. A. Abbas: None. Z. Wang: None. M. Murad: None. Background: Hybrid closed-loop (HCL) systems for automated insulin delivery are increasingly used in diabetes management. However, their safety and efficacy in pregnant women with pre-existing type 1 diabetes remain uncertain. Aim: To assess the safety and effectiveness of HCL systems in pregnant women with pre-existing type 1 diabetes compared to current standard of care. Methods: A comprehensive search of several databases was conducted from inception to January 3rd, 2024. Pairs of independent reviewers screened abstracts. Abstracts included by at least one reviewer were reviewed in full text by a pair of independent reviewers. The DerSimonian and Laird random effects model with the Hartung-Knapp-Sidik-Jonkman method was used to pool effect sizes across the included studies. Results: Five randomized controlled trials (RCTs) with 274 pregnant women with type I diabetes met the inclusion criteria. Our meta-analysis showed no significant difference between HCL and standard of care regarding overall time in range (TIR), time above range (TAR), and time below range (TBR). However, overnight, women using HCL showed significantly higher TIR (mean difference: 10.18%, CI 7.42-12.94%) and lower TBR (mean difference: -0.67%, CI -0.91 to -0.43%) compared to those using standard care. Additionally, there were no significant differences between HCL and standard of care in term of LGA, SGA, neonatal hypoglycemia, and maternal severe hypoglycemia or hyperglycemia. Conclusion: HCL systems for management of pre-existing type I diabetes during pregnancy are associated with similar outcomes without increased risk of complications when compared to standard of care. This is derived from limited number of RCTs with low risk of bias but significant imprecision, which warrant low confidence. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. M. Hussein: None. S. Fatima: None. F. Arshad: None. D. Rizwan: None. A. Qadeer: None. M. Khawar: None. R. Haider: None. S. Batool: None. H. Jawad: None. N.U. saleem: None. H. Ahmad: None. F. Ahmed: None. R. Kirchoff: None. R. Kirchoff: None. Background: With a global prevalence of 586,000 cases of thyroid cancer, thyroid cancer is the 10th most common malignancy. Despite advancements in early detection and treatment, the incidence of thyroid cancer continues to increase in the United States. This study aims to assess disparities in mortality trends stratified by age, sex, race, geography, urbanization status, and location of death, to guide clinical decision making. Methodology: Mortality data on thyroid cancer were extracted from the CDC-WONDER database, from 1999 to 2020. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 were stratified by age, sex, race, geography, urbanization status, and place of death. Joinpoint regression software was used to determine annual percent change (APC) and average APC. Results: From 1999 to 2020, a total of 46,777 deaths attributed to thyroid cancer occurred in the United States, among individuals aged ≥ 25 years. The overall AAMRs showed a positive trend, increasing from 0.6 per 100,000 (95% CI: 0.5-0.6) in 1999, to 0.7 (95% CI: 0.7 - 0.7) in 2020. 56.63% of those deaths, or 26,493 deaths, occurred in women. When stratified by age group, the 85+ age group had the highest CMR of 9 (95% CI: 8.3-9.7). The racial group with the highest AAMRs were Whites, with an AAMR of 0.7 per 100,000. Mortalities in the South region accounted for 33.5% of total deaths. Moreover, metro areas also had higher mortality rates than non-metro areas. Information regarding place of death was only available for 8242 deaths, with 2763 of them occurring in medical settings. Conclusion: Mortality rates in all population groups increased from 1999 to 2020, with variations in mortality rates noted among them. Risk stratification of high-risk groups, such as older people and women, and targeted interventions are key for addressing disparities in mortality rates. Presentation: Saturday, July 12, 2025

Abstract Disclosure: R. Castaneda: None. D. Bechenati: None. R.D. Rivera Gutierrez: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. P. Bennett: None. A. Acosta: Novo Nordisk, Gila Therapeutics, Amgen Inc, Regeneron Pharmaceuticals, Boehringer Ingelheim, Rhythm Pharmaceuticals, General Mills, Currax, Nestle, Phenomix Sciences, Busch Health, RareDiseases, National Institute of Health, Vivus Pharmaceuticals, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical. S. Faubion: Era Women’s Health Platform, PriMed, MedAll, AiCME, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix. Introduction: Tirzepatide, a dual GIP and GLP-1 receptor agonist, is an FDA-approved medication demonstrating the highest efficacy for weight loss among currently available treatments. However, the influence of sex and age on weight loss outcomes with tirzepatide remains unclear. Objective: To investigate the influence of sex and age on weight loss outcomes in patients treated with tirzepatide. Methods: This retrospective study evaluated weight loss outcomes associated with tirzepatide across sex and age groups. Patients with active malignancy, prior bariatric surgery, or concurrent anti-obesity medication were excluded. The primary endpoint was total body weight loss percentage (TBWL%) at 15 months by sex and age. The influence of age was analyzed as a categorical (≤45, 46-59, ≥60 years) and continuous variable. Secondary outcomes included TBWL% at 3, 6, 9, and 12 months by sex and age. Data were analyzed using independent t-tests, one-way ANOVA, and multivariate regression; results are reported as mean ± standard deviation. Results: The study included 1033 patients (57.1% female; mean age 56 ± 11 years; mean BMI, 37.7 ± 8 kg/m2). By age category, 18.8% (196) were ≤45 years (35.7% males, 64.3% females), 45.9% (473) were 46-59 years (42.7% males, 57.3% females), and 35.3% (364) were ≥60 years (54.7% males, 45.3% females). At all timepoints, TBWL was significantly greater in females compared to males at all timepoints. At 15 months females had a higher TBWL than males: 15.3% ± 10, n=340, vs. 10.2% ± 8, n=244, (p < 0.001). Among females, premenopausal women achieved a higher TBWL than postmenopausal women: 16.9% ± 10 vs 14.4% ± 9, p = 0.04. Analysis by age groups revealed a trend toward higher TBWL in younger patients that did not reach statistical significance (p = 0.152): ≤45 years (14.7% ± 10%), 46-59 years (12.9% ± 10%), and ≥60 years (12.7% ± 9%). After adjusting for baseline age, BMI, and diabetes status, sex remained a strong predictor for weight loss outcomes (PE= 4.5, 95% CI [2.96, 5.97], p < 0.001), following type 2 diabetes status (PE= 4.8, 95% CI [3.0, 6.7], p < 0.001). Conclusion: Sex but not age was a strong predictor of weight loss with tirzepatide. Female sex was associated with greater weight loss than male sex. These results emphasize the importance of considering sex-specific factors in weight loss strategies and warrant further investigation into the underlying biological mechanisms. Differential weight loss by menopause, underscores the role of sex hormones. Presentation: Monday, July 14, 2025

Abstract Disclosure: S.R. Chacko: None. C.A. Villavicencio Torres: None. K. Yu: None. S.G. Waguespack: None. L. Lu: None. Z. Belaya: None. T. Bandgar: None. A. Sada: None. O. Ragnarsson: None. B. Altieri: None. A. Newman: None. P. Vibhatavata: None. M. Tóth: None. E.V. Varlamov: None. C. Badiu: None. A. Paissan: None. M. St-Jean: None. H. Falhammar: None. N. Imamudeen: None. L. Haberbosch: None. M. Bobrowicz: None. A. Tabarin: None. R. Shah: None. M.R. Gadelha: None. A. Peersen: None. W.F. Young: None. J. Kaplan: None. J. Varghese: None. M.A. Habra: None. O. Golounina: None. G.A. Melnichenko: None. A.R. Lila: None. C. Yamichannaiah: None. I. Bancos: None. Context: Cushing syndrome (CS) due to ectopic ACTH secretion (EAS) is a rare condition, associated with severe hypercortisolism and consequent morbidity and mortality. Its varied and often emergent presentation make diagnosis and treatment challenging. Objectives: 1.Characterize clinical and biochemical presentation of EAS. 2.Describe the scope of hypercortisolism-related complications, overall and CS-specific mortality. 3.Identify factors associated with CS-specific mortality. Methods: We conducted a multicenter retrospective cohort study in patients with EAS at 37 centers. Outcomes were clinical/biochemical severity scores, complications, overall and CS-specific mortality. Results: In 1053 patients [median age at diagnosis 52 years (IQR 37-64), 57% women], metastatic disease was present at diagnosis in 585 (56%). The most common sources of EAS were bronchial neuroendocrine neoplasm (NEN) (304, 29%), pancreatic NEN (114, 11%) and small cell lung carcinoma (114, 11%), with the source of EAS being occult in 192 (18%). Clinical and biochemical severity scores were severe in 475 (45%) and 873 patients (92%) respectively. Hypokalemia was present in 819 patients (78%) in the year prior to diagnosis. Of 342 patients (32%) who had IPSS, 301 (88%) suggested an ectopic source, 7 (2%) a pituitary source, and 23 (7%) were non-diagnostic. Of 595 patients who had both functional and cross-sectional imaging, discordant findings were seen in 122 (21%), concordant lesion was seen on both in 326 (55%), and no lesion in 147 (25%). Of those with discordant results, cross-sectional imaging was accurate in 66 (54%) and functional imaging in 56 (46%).Management included medical therapy alone in 237 (23%), surgical excision of the source of EAS in 158 (15%), bilateral adrenalectomy in 77 (7%) and multimodal therapies in 498 patients (47%). Complications within 5 years after diagnosis included hospitalization related to CS or its therapy in 351 (33%), infection in 337 (32%), thromboembolic event in 102 (10%), cardiovascular event in 83 (8%) and cerebrovascular event in 27 (3%). During a median follow-up of 35 months (IQR 20-122) from CS diagnosis, death occurred in 462 patients (44%), with the cause of death related to CS in 149 (14%). CS-specific mortality was higher in metastatic compared with non-metastatic disease (19% vs. 7%, P<0.001). On multivariable analysis of age, sex, clinical and biochemical severity, older age (HR 1.03, 95% CI: 1.02-1.04) and lower clinical severity score (HR 0.97, 95% CI: 0.94-0.99), were associated with higher CS-specific mortality. Conclusion: Our interim analysis, the largest worldwide, found that most patients with EAS had severe hypercortisolism and hypokalemia. Metastatic disease was present in 56%, and the source of EAS was occult in 18%. CS-related death occurred in 14%, emphasizing the need for urgent management. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. M.H. Alsaadi: None. M. Ikram: None. W. Ftih: None. H. Jawad: None. M.U. Rehman: None. R. Akhtar: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Introduction: Conditions that disrupt the adrenal glands' typical function are known as adrenal gland ailments or diseases. This study examines the distribution of adrenal disorders across various demographic and geographic groups in the United States, including gender, census region, race, age groups, and urbanization levels. Our objective was to identify disparities and trends to inform targeted interventions and resource allocation. Methods: From 1999 to 2020, mortality statistics for adrenal diseases were extracted from the CDC-WONDER database. Age, sex, race, location, urbanization status, and place of death were used to stratify the age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000. We calculated the average annual percentage change (APC) using Joinpoint regression software. Results: A total of 31,028 fatalities were reported due to adrenal disorders from 1999-2020 (AAPC: 1.277; 95% CI, -0.032 to 2.6032, p=0.055916). An initial rising trend was observed from 1999-2003 (APC: 2.4799), followed by a declining trend from 2003-2013 (APC: -3.0094), then a modest rise from 2013-2018 (APC: -0.9188), and finally a sharp increase from 2018-2020 (APC: 2.9445). Males had a higher AAMR (6.8) than females (6.4). The West census region had the highest AAMR (7.2), followed by the Midwest (7.1), South (6.3), and Northeast (5.6). The highest crude mortality rate was observed in individuals aged 85+ years (52.2). Several disparities were noted when stratified by urbanization and race, including the highest AAMR in Non Core (Nonmetro) regions (7.9) and among American Indian or Alaska Native populations (8.2). The highest percentage of deaths occurred in medical facilities. Conclusions: The findings underscore the need for tailored public health strategies to address disparities in adrenal disorders among vulnerable populations. Specific attention should be directed towards the male gender, West census region, American Indian or Alaska Native populations, and the geriatric population. Future research should explore underlying causes and interventions to mitigate these disparities. Presentation: Monday, July 14, 2025

Abstract Disclosure: C.A. Villavicencio Torres: None. S. Ahmadian: None. V.M. Fell: None. K. Moehnke: None. Y. Chai: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Current standard-of-care assessment of adrenal disorders relies on the venipuncture-based total cortisol measurements. Salivary cortisol (SalF) and cortisone (SalE) measurements have advantages such as a more accurate assessment of patients with cortisol-binging globulin abnormalities and the convenience of at-home non-invasive testing. Aims: This study aimed to compare concentrations of cortisol and dexamethasone between clinical (venipuncture-based) and saliva samples. Methodology: We conducted a cross-sectional study (July 2024-January 2025) of adults undergoing overnight dexamethasone suppression test (DST) or cosyntropin stimulation test (CST). Saliva samples were collected alongside clinical samples. Saliva measurements included cortisol, cortisone, and dexamethasone (mass spectrometry), while clinical samples were tested for total cortisol (Roche immunoassay) and, in a subgroup, dexamethasone (mass spectrometry). Results: Of 241 patients (186 (77%) women, median age 53 years (IQR 39-66)), 178 (74%) provided samples as a part of DST and 63 (26%) as a part CST. An inability to provide sufficient saliva for analysis was found in 5 patients (2%). In patients undergoing DST, median post-dexamethasone serum total cortisol was 1.3 mcg/dL (IQR 0.8-2.2), and median serum dexamethasone (SerD) was 0.43 mcg/dL (IQR 0.3-0.6) based on clinical samples, while median SalF was 10.2 ng/dL (IQR 6.6-23.6), SalE was 78.6 ng/dL (IQR 52.8-131.1), and saliva dexamethasone (SalD) was 60 ng/dL (IQR 41-93). SalE (r=0.92, p<.0001) demonstrated a stronger correlation than SalF (r=0.85, p<.0001) when compared with post-dexamethasone serum total cortisol measurements. SalD (r=0.85, p<.0001) correlated with SerD measurements. In patients undergoing CST, median baseline serum total cortisol was 7.2 mcg/dL (IQR 4.6-10) based on clinical samples, while median baseline SalF was 86.6 ng/dL (IQR 38.3-166.3), and median SalE was 707 ng/dL (IQR 347-906). Median peak 60-minute serum total cortisol was 21.5 mcg/dL (IQR 18-24), while SalF was 870.4 ng/dL (IQR 440-2904) and SalE was 2501 ng/dL (IQR 1770-3193). Both baseline (r=0.92, p<.0001) and 60 min peak post-cosyntropin SalE (r=0.84, p<.0001) demonstrated a strong correlation with venipuncture-based measurements. SalF had a weaker than SalE correlation at both baseline (r=0.88, p<.0001) and 60 min peak post-cosyntropin (r=0.79, p<.0001). Conclusion: Our study demonstrates that salivary measurements of cortisone, cortisol and dexamethasone strongly correlate with standard-of-care venipuncture concentrations following DST and CST. SalE showed the stronger than SalF correlation with venipuncture-based serum total cortisol concentrations. Presentation: Sunday, July 13, 2025

Abstract Disclosure: S. Ahmadian: None. S.R. Chacko: None. S. Sharma Sharma: None. V.M. Fell: None. A. Peersen: None. E.J. Atkinson: None. K.L. Moehnke: None. Y. Chai: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Cortisol secretion follows a circadian pattern with highest concentrations in the morning, and lowest at night. Loss of circadian cortisol variation has been reported in patients with Cushing syndrome (CS), however, is scarcely investigated in patients with mild autonomous cortisol secretion (MACS). Outpatient assessment of late night and early morning salivary cortisol and cortisone may serve as a valuable diagnostic tool in patients with hypercortisolism. Methods: We conducted a single-center cross-sectional study of adults evaluated at our center between 04/2024 and 04/2025. The study included patients with Cushing’s syndrome (CS), mild autonomous cortisol secretion (MACS), and referent subjects without known adrenal disorders. Participants were provided with two cotton swabs (Salivettes) and instructed to collect saliva samples at two standardized time points: at bedtime (PM) and on waking (AM). Each swab was kept in the mouth for 2-2.5 minutes. Saliva was analyzed for cortisol and cortisone using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Delta cortisol and delta cortisone were defined as the difference between AM and PM concentrations for each individual and were calculated for all participants. Results: A total of 82 patients (32 with ACTH-dependent CS, 5 with ACTH-independent CS, and 45 with MACS), median age of 55 years [IQR 44-65], 63 (77%) women, and 71 referent subjects, median age of 34 years [IQR 28-42], 54 (76%) women, were included. Delta cortisol was higher in referents (median of 212 ng/dL, [IQR 157-358]) vs patients with CS (median 95 ng/dL [IQR -21-184]) or MACS (median 131 ng/dL, [IQR 91-229]). Similarly, delta cortisone was also highest in referents with a median of 828 ng/dL [IQR 612-1131] versus median of 211 ng/dL [IQR -58-468] in CS and 484 ng/dL [IQR 189-849] in MACS. When compared to referents in an age- and sex-adjusted linear regression model, delta cortisone was lower in both patients with CS (est -1.3 (95%CI -1.75 to -0.85), P<0.001 and MACS (est -0.66, 95%CI of -1.17 to -0.16, P=0.010). Delta cortisol was lower in patients with CS (est -1.32, 95%CI -2.11 to -0.54, P=0.001), but not MACS (est -0.51, 95%CI -1.39 to 0.36). Conclusion: Patients with both CS and MACS demonstrate a blunted circadian salivary cortisol and cortisone secretion, as reflected by a lower delta cortisol and cortisone when compared to referent subjects. Assessment with delta salivary cortisone in patients with MACS may be more valuable than a standard of care late night salivary cortisol assessment. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. S. Fatima: None. R. Noor: None. H. Javaid: None. P.K. Singh: None. H. Jawad: None. R. Haider: None. A. Qadeer: None. M. Khawar: None. T. Ashraf: None. F. Naveed: None. H. Ahmad: None. F. Ahmed: None. R. Kirchoff: None. Introduction: The health of a nation is often a reflection of the equity within its systems. Yet, when we examine the United States, one of the most developed nations globally, a concerning picture emerges in the realm of public health significant racial and ethnic disparities in disease outcomes. Among these, endocrine- related mortality, which includes conditions like diabetes, thyroid disorders, and hormonal imbalances, stands as a silent yet significant contributor to health inequities. Using data from the CDC WONDER database, this study seeks to explore these trends in depth, not just to identify the gaps but to shed light on the lived experiences of marginalized communities who bear the brunt of these inequities to pave the way for more equitable healthcare interventions. Methods: This descriptive study analyzes Racial and Ethnic Disparities in Endocrine-Related Mortality in the United States from 1999-2022, utilizing data from CDC Wonder database. We searched the Center for Disease Control database from 1999 to 2022 for mortality statistics with an underlying cause of death. The age-adjusted mortality rate (AAMR) was calculated per 1,000,000 deaths. We evaluated the AAMR using demographic variables such as race/ethnicity, geographic density, gender, age (25 or above), place of death, and the US Census Region. Temporal trends were assessed using Joinpoint regression software. Mortality rates by age, demographics, and place of death were examined. Statistical analysis calculated endocrine-related mortality rates and trends, with findings deemed significant at P < 0. 05. Results: Between the years 1999 to 2022, 837203 deaths were recorded to be caused by endocrine-related disorders. An overall rising mortality trend from 1999-2022 among all races and ethnicities is noted, except in Asian or Pacific Islander, Black or African American, and Hispanic patients, which shows a rise till 2020 followed by fall in age-adjusted mortality rates (AAMR) in 2022. A significant dip in mortality rate was seen in 2017 in all racial and ethnic groups. American Indian or Alaska Natives showed highest AAMR (181.87, 95% CI 178.06-185.69) followed by Black or African Americans (149.78, 95% CI 148.9-150.64), Hispanic or Latinos (112.33, 95% CI 111.59-113.07), Whites (94.31, 95% CI 66.6-68.25), Asian or Pacific Islanders (67.45, 95% CI 66.6-68.25). American Indians or Alaska Natives exhibit the steepest rise over time (APC -0.32 TO 8.85) from 1999-2022. Conclusions: Mortality due to endocrine-related disorders has dramatically increased over time. Significant disparities have been noted among different races and ethnic groups, with the highest rate among Americans and the lowest among Asians. This underscores the need for targeted interventions for specific racial groups to reduce the mortality burden of endocrine-related diseases. Presentation: Sunday, July 13, 2025