Citations

Abstract Disclosure: R.D. Rivera Gutierrez: None. D. Bechenati: None. R. Castaneda: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. T.M. Taaffe: None. P.K. Bennett: None. A.J. Acosta: Novo Nordisk, Gila Therapeutics, Rhythm Pharmaceuticals, Amgen Inc, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, 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, AiCME, MedAll, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix Sciences. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular (CV) benefits. Tirzepatide (TZP), a dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist approved for weight management and glycemic control, currently lacks evidence on CV outcomes. This study evaluates TZP’s impact on cardiometabolic parameters and atherosclerotic cardiovascular disease (ASCVD) risk scores. Methods: We conducted a multicenter retrospective study of adults prescribed TZP from June 1, 2022, to November 1, 2024. Inclusion criteria included 12 months of TZP use and age >18 years. Exclusion criteria were pregnancy, active malignancy, concurrent FDA-approved antiobesity medications, and prior bariatric surgery. Endpoints included changes in blood pressure, lipid profiles, liver enzymes, glucose control parameters, medication use (statins, aspirin, antihypertensives), and ASCVD risk scores from baseline to 12 months, stratified by sex. Data were obtained from electronic medical records. We present data as mean differences [95% CI]. We used T-tests and multivariate regression analyses for analyses. Results: Among 831 participants (59.4% female; 91.2% White; mean age: 58 ± 12 years), 12-month weight loss was -12% [-13, -11], p<0.001. We observed significant improvement in systolic blood pressure (SBP) (-4 [-5, -3] mmHg, p<0.001), triglycerides (TG) (-38 [-52, -23] mg/dL, p<0.001), total cholesterol (TC) (-7 [-10, -4] mg/dL, p<0.001), LDL cholesterol (LDL) (-6 [-9, -4] mg/dL, p<0.001), fasting glucose (FG) (-39 [-48, -29] mg/dL, p<0.001), ALT (-10 [-15, -5] U/L, p<0.001), HbA1c (-1.3% [-1.5, -1.2], p<0.001), and HDL cholesterol (HDL) (+4 [+3, +5] mg/dL, p<0.001). The Lifetime and 10-year ASCVD scores did not significantly change after 12 months (p>0.05), underscoring TZP’s potential in mitigating the aging-associated increase in CV risk. Considering sex, females had greater weight loss (-13% [-14, -12] vs. -10% [-11, -9], p<0.001), and greater improvements in TC (-5% [-8, -2] vs -3% [-6, 0.1], p<0.001) and LDL (-10% [-14, -6] vs -4% [-8, 1], p<0.001). Males had a greater reduction in DBP (-2% [-4, -1] vs (-1% [-6, 3], p=0.006). Both males and females demonstrated similar improvements in FG and HbA1c. Conclusion: TZP significantly improved CV and metabolic parameters after 12 months, with greater benefits observed in females. These improvements effectively mitigated the age-related rise in ASCVD risk scores. Larger, prospective studies are warranted to confirm these findings and further investigate TZP’s long-term CV effects. Presentation: Monday, July 14, 2025

Abstract Disclosure: N. Lanka: None. S. Palakodeti: None. O. Oluwasolabomi: None. R. Nalam: None. G. Rangari: None. Introduction: PCOS is a complex condition with multifactorial etiology. GLP-1 RAs are used in insulin-resistant disorders like PCOS for their effects on weight and glycemic control. Recent studies suggest they may also improve follicular growth, endometrial health, ovulation, and fertility, independent of weight loss. This study evaluates the effects of GLP-1 RAs on anthropometric, metabolic, and reproductive parameters in PCOS. Methods: We followed PRISMA 2020 guidelines. We searched PubMed and Cochrane Library (2015-Feb 2025) using relevant keywords. We included RCTs and cohort studies with PCOS patients (per Rotterdam criteria) receiving GLP-1 RA monotherapy compared to placebo, metformin, or other interventions, reporting anthropometric, metabolic, or reproductive outcomes. Statistical analysis was performed using RevMan 5.4 with random-effects models, and heterogeneity was assessed using the I2 coefficient (p<0.05 considered significant). Results: We identified 73 studies, with 10 RCTs included (730 participants). Of these, 50.13% received GLP-1 RAs (49.5% liraglutide, 41% exenatide, 9.56% dulaglutide, 2.73% semaglutide), and 45.9% were controls (42.2% metformin, 20.3% placebo, others combination therapy). The meta-analysis findings are as follows: Anthropometric Outcomes: GLP-1 RAs caused significant reductions in BMI (9 studies, MD = -1.41, 95% CI: -1.73 to -1.10, p<0.00001, I2=100%) and waist circumference (8 studies, MD = -2.69, 95% CI: -4.06 to -1.32, p=0.0001, I2=100%). 1 study showed liraglutide reduced VAT (p=0.006). Metabolic Outcomes: GLP-1 RAs had a non-significant effect on HOMA-IR (7 studies, MD = -0.03, 95% CI: -0.82 to 0.76, p=0.94, I2=100%) and LDL (7 studies, MD = -0.45, 95% CI: -1.31 to 0.40, p=0.30, I2=100%). 3 studies showed improvement in OGTT, and 1 showed a significant reduction in HbA1C (p=0.015). Reproductive Health Outcomes: GLP-1 RAs caused a significant decrease in total testosterone (10 studies, MD = -0.78, 95% CI: -1.02 to -0.55, p<0.00001, I2=99%). LH decreased non-significantly (4 studies, MD = -1.96, 95% CI: -4.18 to 0.26, p=0.08, I2=99%), while FSH increased non-significantly (4 studies, MD = 0.29, 95% CI: -0.69 to 1.27, p=0.56, I2=99%). Two studies showed significant improvements in menstrual regularity with liraglutide and exenatide (p=0.0001 and <0.001, respectively). Conclusion: Our findings suggest GLP-1 RAs could become key therapies for managing this condition. However, heterogeneity among studies—due to differences in design, drug used, control, and dosing—requires further studies to explore optimal dosages, durations, combination therapies, and their impact on ovulation and fertility. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. F. Saleem: None. A. Ullah: None. K. Abdul Rehman: None. M.H. Alsaadi: None. H. Ahmad: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. H. Jawad: None. J. Ikram: None. M. Filal: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Thyroid disorders are common endocrine disorders including thyrotoxicosis, thyroiditis, hypothyroidism, and autoimmune thyroid diseases. Although it affects an estimated 200 million people globally, the epidemiology of this condition remains underexplored. Here we aimed to investigate mortality trends attributable to thyroid disorders in the US stratified by year, sex, race, and region. Methods: Using data from the CDC WONDER database, we calculated the crude and age-adjusted mortality rates (AAMRs) per 1,000,000 individuals (≥25 years) and used Joinpoint regression to determine annual and average annual percent change (AAPC) in the mortality trends. Results: Between 1999 and 2020, 561,089 deaths were recorded among patients with thyroid disorders in the United States, with an overall increasing trend in mortality (AAPC = 0.78). The age-adjusted mortality rate (AAMR) declined gradually from 1999 to 2018 (APC = -0.43, 95% CI: -0.65 to -0.22) before rising sharply from 2018 to 2020 (APC = 13.05, 95% CI: 6.39 to 20.12). Females had a higher AAMR (139.75) than males (81.99). Among racial and ethnic groups, Whites exhibited the highest AAMR (124.09), followed by American Indian or Alaskan Natives (121.36), Hispanics (89.13), Black or African Americans (88.44), and Asian or Pacific Islanders (59.36). Regional disparities showed the highest AAMR in the Midwest (130.45) and the lowest in the South (109.40). West Virginia (199.93) and North Dakota (198.82) reported the highest state-level AAMRs, while Nevada (60.18) and Florida (65.49) had the lowest. Non-metropolitan areas experienced higher mortality rates (141.04) than metropolitan areas (112.21), underscoring significant geographical and demographic variations in thyroid disorder-related mortality. Conclusion: Adults in the US have shown a rising trend in Thyroid-related deaths, with the highest mortality rates seen in females, Whites, and people living in the Midwest and Non-metropolitan areas. Our study also highlights the disparities across different demographics. Policy makers should focus on equitable access to healthcare to control this increasing mortality. Presentation: Monday, July 14, 2025

Background Data on national trends in mortality due to infective endocarditis (IE) in the United States are limited. Methods and Results Utilizing the multiple causes of death data from the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database from 1999 to 2020, IE and substance use were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Between 1999 and 2020, the IE‐related age‐adjusted mortality rates declined. IE‐related crude mortality accelerated significantly in the age groups 25–34 years (average annual percentage change, 5.4 [95% CI, 3.1–7.7]; P <0.001) and 35–44 years (average annual percentage change, 2.3 [95% CI, 1.3–3.3]; P <0.001), but remained stagnant in those aged 45–54 years (average annual percentage change, 0.5 [95% CI, −1.9 to 3]; P =0.684), and showed a significant decline in those aged ≥55 years. A concomitant substance use disorder as multiple causes of death in those with IE increased drastically in the 25–44 years age group ( P <0.001). The states of Kentucky, Tennessee, and West Virginia showed an acceleration in age‐adjusted mortality rates in contrast to other states, where there was predominantly a decline or static trend for IE. Conclusions Age‐adjusted mortality rates due to IE in the overall population have declined. The marked acceleration in mortality in the 25‐ to 44‐year age group is a cause for alarm. Regional differences with acceleration in IE mortality rates were noted in Kentucky, Tennessee, and West Virginia. We speculate that this acceleration was likely due mainly to the opioid crisis that has engulfed several states and involved principally younger adults.

AbstractFirst‐degree relatives of patients diagnosed with schizophrenia (SZ‐FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First‐degree relatives of patients diagnosed with bipolar disorder (BD‐FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD‐FDRs are inconsistent. Here, we performed a meta‐analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ‐FDRs, 867 BD‐FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ‐FDRs showed a pattern of widespread thinner cortex, while BD‐FDRs had widespread larger cortical surface area. IQ was lower in SZ‐FDRs (d = −0.42,p = 3 × 10−5), with weak evidence of IQ reductions among BD‐FDRs (d = −0.23,p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group‐effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ‐FDRs and more pronounced effects in BD‐FDRs. To conclude, SZ‐FDRs and BD‐FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ‐FDRs and BD‐FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Abstract Introduction: Brain tumors, including benign pituitary adenomas (PA), cause high levels of anxiety and distress. Patients with PA also report high unmet needs for information, a factor correlated with anxiety. Although many factors can contribute to anxiety, condition-specific education may alleviate anxiety for these patients. Aim: To explore the patients’ experience related to discovery of a pituitary adenoma and pilot a patient education intervention to address peri-diagnostic anxiety. Method: This mixed-methods pilot study evaluated the acceptability and effectiveness of an education intervention for adults diagnosed with PA (nonfunctioning PA or prolactinoma). At their first endocrine appointment, patients were given disease-specific information verbally, reinforced with printed material. Anxiety [Generalized Anxiety Disorder (GAD)-7 and Visual Analogue Scale for Anxiety (VAS-A)], patient satisfaction (Likert 1–5), patient knowledge of pituitary tumors [patient knowledge questionnaire (PKQ)] and need for information (Likert 1–5) was measured prior, immediately after, and 1 month following appointment. Patients participated in a semi-structured phone interview designed to explore patient diagnostic experiences pre-and post- intervention and to elicit patient evaluation of the intervention. Interviews were tape-recorded, transcribed, and analyzed using qualitative methods. Results: Seventeen patients participated in the study; 15 of these completed the interview. Baseline need for information was high (4.6± 0.6). Anxiety level by VAS-A [median (IQR) was 50 (35–71) prior, 47 (21–68) immediately after and 1 month later 31 (14–44)] and GAD-7 [median value before 9 (4–13), immediately after 7 (3–13) and 1 month later 5 (3–8)] improved significantly (P &lt; 0.01). PKQ was high at baseline (15 ± 0.4 /18) and increased (after 15.9 ± 0.4 and 1 month 15.8 ± 0.4, P=0.045). Patient satisfaction significantly improved (2.8 vs 4.6, P &lt; 0.01). Analysis of the semi-structured interviews identified 3 main themes: (1) Communication, (2) Need for information; and (3) Impact of the diagnosis on patient experience. Patient experience in relation to each theme was reported negatively prior to the intervention and positively post-intervention. Conclusion: The diagnostic experience is challenging for patients with newly diagnosed PA and is associated with high levels of anxiety despite most patients being notified of the benign diagnosis. Although patients desire more information, patients scored highly on the baseline PKQ. The delivery of information had a significant positive impact on patient satisfaction and led to a reduction in anxiety. While these observations are not controlled, the themes identified have important clinical implications. They suggest that patient experience can be improved by a timely, streamlined diagnostic process with readily accessible information.

Abstract Introduction: Transsphenoidal surgery is recommended as first line therapy in the vast majority of patients with acromegaly. Successful surgical intervention is determined by normalization of insulin like-growth factor (IGF) - 1 and adequate suppression of growth hormone (GH) during glucose GH suppression test or random GH levels &lt;1.0 ng/mL. Given the long half-life of IGF-1, evolution of IGF-1 and GH assays and limitations of GH suppression test, clinicians remain reliant on IGF-1 results 3–6 months following surgery to assess disease remission following surgical intervention. This can lead to delayed treatment of patients with persistent disease and significantly increase patient anxiety. Aim: To determine if IGF-1 levels at 6 weeks were equally predictive of surgical outcomes when compared to IGF-1 levels at 3–6 months postoperative. Methods: Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2010–2019 and had post-operative IGF-1 level measured at 6 weeks and 3–6 months. IGF-1 was measured using the Siemens Immulite assay until 2016 when it was replaced by a LC-MS/MS assay. IGF-1 measurements at 6 weeks are obtained based on clinician discretion. Results: 69 patients (mean age 49 ± 14.8, female 31/69, 44.9%) with acromegaly had surgery and IGF-1 follow-up measurements at 6 weeks and 3–6 months. Persistent acromegaly was noted in 45/69 at 3–6 months. The median IGF-1 pre-operative was 701 ng/ mL (289–1600), 6 weeks postoperative was 286 ng/ mL (109–1038) and at 3–6 months was 267 ng/ mL (77–996). The median pre-operative IGF-1 was significantly higher than the median IGF-1 level at 6 weeks and 3–6 months (P=&lt;0.001). Although a statistically significant difference was seen between IGF-1 levels at 6 weeks and 3–6 months, the mean difference between these time points was small (20 ng/mL, P=&lt;0.001). There was a greater percent reduction in IGF-1 at 6 weeks following surgery in those who had a normal IGF-1 at 3–6 months compared to those who did not (63% vs 35%, P=&lt;0.01). Among patients who were deemed in remission at 3–6 months (24/69, 35%), 3/24 patients (all male with macroadenoma and no cavernous sinus invasion) had mildly elevated IGF-1 levels at 6 weeks (≤1.12 upper limit of normal) which subsequently normalized. In all of these patients, GH was &lt;1 ng/mL post-op. In 1 male (macroadenoma and cavernous sinus invasion), IGF-1 levels increased from normal at 6 weeks to abnormal when measured at 3–6 months. Conclusion: In the vast majority of patients, 6 weeks post-operative IGF-1 can be used to assess response to surgery avoiding a delay in treatment. However, we would recommend repeating IGF-1 levels at 3–6 months in those who have marginally elevated IGF-1 above normal (≤ 1.12), without cavernous sinus invasion and a post-operative GH of &lt;1 ng/mL prior to intervening if the IGF-1 is elevated 6 weeks as the IGF-1 may normalize.

Abstract Background: Patients with primary adrenal insufficiency (PAI) and secondary adrenal insufficiency (SAI) report impaired quality of life. Predictors of adverse outcomes include duration of disease, supraphysiologic glucocorticoid (GC) use, and presence of other comorbidities. There is limited evidence to suggest that quality of life is disproportionately affected in one subtype of adrenal insufficiency. Objective: To identify determinants of quality of life in patients with PAI vs SAI. Method: Survey study of patients with the diagnosis of AI between 2015 and 2019 was evaluated at two large tertiary medical centers in the United States. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being. Patients with AI due to exogenous glucocorticoid use were excluded. Results: Patients with PAI (n=310, 65% women) were diagnosed at a younger age (37 ± 19 vs 48 ± 16 years, p&lt;.01) than patients with SAI (n=255, 57% women). Patients with SAI were more likely not to understand their diagnosis (13% vs 4% in PAI, p&lt;.01), or to report a discordant diagnosis (16% vs 9% in PAI, p=.02). Patients with PAI were on a higher dose of daily GC (23.8 mg vs 18.5 mg hydrocortisone (HC) equivalent, p &lt;.01), with higher number of patients on HC&gt; 25 mg/day (33% vs 15%, p&lt;.01). Patients with PAI reported a higher compliance with wearing medical alert ID (79% vs 64%, p=.01) and higher availability of injectable GC (74% vs 58%, p&lt;.01). Patients with PAI reported a higher frequency of at least one adrenal crisis within the last 12 months that required self- injectable GC (32% vs 16%, p&lt;.01), or prompted ER visits (56% vs 29%, p&lt;.01) compared to those with SAI. Nevertheless, patients with PAI were more likely to report good general health (78% vs 65% in SAI, p&lt;.01). When adjusted for current age, sex, duration of disease, supraphysiologic GC use, number of current symptoms and recent adrenal crises, patients with SAI had HR of 2.6 (CI 95% 1.5-4.3) for poor health, 1.6 (CI 95% 0.95-2.8) for physical limitations, 1.7 (CI 95% 1.1-2.7) for fatigue, and 2.7 (CI 95% 1.5-4.9) for social limitations compared to those with PAI. Conclusions: Patients with PAI receive higher daily GC and experience a higher number of adrenal crises when compared to patients with SAI. However, patients with PAI report a better general perception of health, possibly due to a more robust knowledge of their disease and higher comfort level managing AI. More effort is needed to ensure patients with AI are appropriately educated regarding their medical condition and therapy.

Abstract While long term fasting is reported to augment the corticotropic function, effect of short term (overnight) fasting on ACTH-cortisol coordinated release pattern and potential effect(s) of nutrient intake is not fully defined. Eleven healthy men (age: 33-70 yrs, BMI 20.4-31.5 kg-m2) were studied after overnight fast on 4 separate days, involving oral ingestion of 300 ml of either water, dextrose, protein, or lipid solutions. Test meals were isocaloric (400 kcal). Sessions were 6.5 h long, starting at 0800-0900 hrs. Blood was collected at 10-min intervals for ACTH (pg per mL), and cortisol (µg per dL) measurements. Linear regression, cross-correlation, deconvolution, and ApEn were used for data analyses. ACTH and cortisol concentration time series during short-term fast (water day) were found not to be chronologically coupled per linear regression (r2= 0.0014, P=0.82), and cross-correlation (r= - 0.156, lag=150 min) statistics. Oral intake of the 3 macronutrients improved the temporal relationship between ACTH and cortisol concentrations, verified by linear regression (r2:P- dextrose 0.54:0.0001, protein 0.65: 0.0001, lipid 0.42:0.0001), and cross-correlation (r:lag in min- dextrose 0.8:10, protein 0.77:10, lipid 0.78:20). Oral ingestion of either macronutrient did not significantly alter mean ACTH and cortisol concentrations and their respective secretion pattern (total, pulsatile, basal) over the period of 6.5 hr. However compared to the control (water) session, dextrose ingestion evoked less frequent and larger ACTH secretory bursts, and more regular ACTH and cortisol secretory patterns. In this study, we have observed lack of concordance between ACTH and cortisol after overnight fasting, which is restored with oral intake of macronutrients. This effect appears to be uniform among the 3 macronutrients, except for less frequent and lager ACTH bursts and more regular ACTH and cortisol release events after dextrose intake. These findings and the specific role of nutrients being direct or via physiologic nutrient-induced hormonal adaptation warrants future investigation.

Abstract BACKGROUND At the initial presentation of autoimmune adrenal insufficiency, most patients present with hormonal deficiencies from all three layers of adrenal cortex. However, isolated aldosterone deficiency causing a true partial adrenal insufficiency in the setting of autoimmune adrenalitis remains underrecognized. CASE REPORT A 67-year old female patient with a known history of diabetes mellitus type 1 since the age of 13 and morphea, presented with progressively worsening symptoms of confusion and hallucinations, fatigue, and loss of appetite over the past 5 years. During this time, she has had frequent and recurrent episodes of mild intermittent hyponatremia with hyperkalemia requiring intravenous fluids and ingested salt tablets, especially when she felt more symptomatic. On her initial evaluation here, she presented with hyponatremia (125 mmol/l, n: 135-145 mmol/l), low osmolality (264 mOsm/kg, n: 275-295 mOsm/kg), and normal potassium level (3.6 mmol/l, n: 3.6-5.2 mmol/l). Further investigations drawn at the same time revealed a low aldosterone (&lt;4 ng/dL), normal renin (5.3 ng/mL/hr, ref 2.9-10.8), normal serum cortisol level (and normal response to Cortrosyn stimulation), though all in the setting of positive antibodies against 21-hydroxylase. Pan-imaging revealed no evidence of malignancy that can be causing ectopic SIADH production. Additional testing showed presence of auto antibodies contributing to pernicious anemia and thyroid disease. Treatment was started with fludrocortisone 0.1 mg tablet daily and she was advised to take the salt tablets only if she has any symptoms. The patient’s symptoms have resolved 8 months since this diagnosis, with normalized sodium and potassium levels. CONCLUSION Autoimmune primary adrenal insufficiency usually affects all three layers of the adrenal cortex, where patients present with deficiencies in cortisol and aldosterone. Isolated hypoaldosteronism has rarely been reported, however because it can cause life-threatening hyponatremia, it is an important entity to recognize. It is important to work up in such patients as they may be in the initial stages of autoimmune Addison’s disease and can progress to developing cortisol deficiency, though the time course to this progression is not well known.