Introduction The primary goal of thyroid nodule evaluation is detecting malignancy. Due to the low prevalence and typically indolent nature of thyroid cancer, American Thyroid Association (ATA) guidelines emphasize reducing overdiagnosis and avoiding unnecessary surgery. Some studies suggest that cancer outcomes in Hispanic Americans are worse than in non-Hispanic Americans, raising concerns regarding whether current thyroid nodule evaluation guidelines are appropriate across ethnic groups. Objective To characterize the demographic, clinical, radiological, and pathological features of thyroid nodules in Hispanic Americans and compare findings with published general population data to assess whether intensified diagnostic evaluation is warranted Methods We created an ongoing, prospective registry of Hispanic Americans aged ≥18 years with diagnosed thyroid nodules. From January 2023 to January 2025, 211 subjects were enrolled. Cosmetic and ThyPRO-39 scores were calculated. Statistical analyses included descriptive statistics, unadjusted linear and ordinal regression, and the Kruskal-Wallis and Fisher Exact tests (p < 0.01). The registry is continuously updated. Results Among 211 subjects, median age was 59 years, and median BMI was 29 kg/m2. Most were female (92.4%) and referred for incidental imaging findings (73.0%), with only 1.0% reporting symptoms. FNA was performed in 102 subjects (48.3%), yielding Bethesda Categories II (69.6%), III (21.6%), I (5.9%), IV (2.0%), and V (1.0%). There were no Category VI results. Among 22 Category III nodules, 4 had molecular results suggesting high risk for malignancy. Pathology confirmed one follicular variant papillary thyroid carcinoma, one Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features, one oncocytic adenoma, and one papillary thyroid carcinoma. Thus, thyroid cancer was diagnosed in 2 of 211 subjects (0.9%). Conclusion The overall malignancy rate in this Hispanic American cohort was 0.9%, which is lower than the malignancy prevalence commonly reported in the general thyroid nodule population. When restricted to subjects undergoing fine-needle aspiration, the malignancy rate was 2.0%, more comparable to biopsy-selected cohorts. These findings support the continued use of current thyroid nodule evaluation and management guidelines in this population, without the need for more intensive screening approaches.

BACKGROUND: Curcumin, a natural compound found in turmeric (Curcuma longa), demonstrates anticancer properties; however, it is characterized by poor bioavailability and stability. This study investigates the stability, antioxidant activity, and anticancer effects of two monocarbonyl analogs of curcumin (MACs), C66 and B2BrBC, in in vitro breast cancer models. METHODS: Stability and antioxidant activity of C66 and B2BrBC were assessed using spectrophotometric assays. Their effects on breast cancer cells (MCF-7, BT-474, MDA-MB-231) were evaluated through MTT assay, wound-healing assay, and caspase-3 fluorescence microscopy. EMT modulation was examined via RT-qPCR, Western blot, and immunofluorescence analyses. A MILLIPLEX protein assay was used to analyze cancer metastasis-related protein expression. RESULTS: C66 and B2BrBC demonstrated enhanced stability compared to curcumin. Both compounds significantly reduced breast cancer cell viability and migration, with B2BrBC showing higher potency. They effectively suppressed EMT, reversing EMT-inducer effects on epithelial and mesenchymal markers. C66 and B2BrBC modulated the expression of several metastasis-related proteins, including DKK1, OPG, and GDF15, in a cell line-dependent manner. CONCLUSIONS: C66 and B2BrBC exhibit improved stability and potent anticancer effects in breast cancer cells, effectively inhibiting cell viability, migration, and EMT. These compounds show promise as potential therapeutic agents for breast cancer, warranting further investigation in in vivo models.

Curcumin is a polyphenolic bio-compound derived from the rhizomes of the turmeric plant (Curcuma longa) that has proven anti-carcinogenic properties but poor bioavailability. By modifying its chemical structure, the monocarbonyl analogs of curcumin (MACs) possess improved stability, resorption, and circulation. This dataset presents RT-qPCR array analysis of 84 genes associated with Epithelial to Mesenchymal Transition (EMT), a key early event in cancer progression and metastasis, in human MCF-7 breast cancer cells. Cells were stimulated toward EMT reprogramming by treatment with a combination of EMT-inducing factors and co-treated with two experimental MACs, C66 or B2BrBC. Gene expression was measured using the human EMT QIAGEN RT2 Profiler kit, and results were obtained from three independent experiments. Gene expression changes are presented as both fold regulation and fold change values, with statistical significance determined by Student’s t-test (p < 0.05). This comprehensive dataset enables investigation into how MACs modulate the EMT transcriptome in breast cancer cells, with potential applications for understanding EMT mechanisms. The raw and processed data are publicly available and can be used for comparative analyses, validation studies, and bioinformatic analyses of EMT-related signaling pathways.

Disclosure: R.G. Dsouza: None. J. Lee: None. E.P. Liao: None. A. Sanchez: None. K. Ziskovich: None. T. Leung: None. K. Daniel: None. L. Poretsky: None. J.E. Sanchez: None. Objective: The goal of this study is to determine the characteristics and natural history of benign thyroid nodules (TN) in Hispanic Americans living in an urban area. Methods: We examined 212 Hispanic Americans, (January 2024 - January 2025). Participants were aged 18+, self-identified as LatinX, and with diagnosed TN. A chart review was conducted for demographic, medical, and thyroid function data. LUMP score, cosmetic score, and ThyPRO symptom score were assessed. As part of a long-term prospective registry, statistical analyses using descriptive statistics, linear/ordinal regression models, Kruskal-Wallis and Fisher's tests, with a significance level of p < 0.01 were performed. Results: The median age was 59 years, a median BMI of 29 kg/m2. Participants were 92% female. Common comorbidities included diabetes (30%), hypertension (30%), and hyperlipidemia (27%). Other conditions included asthma (5%), chronic obstructive pulmonary disease (0.5%), cancer (1%), coronary artery disease (5%), and thyroid disease (17%). 15% of nodules were left-sided, 18% right-sided, and 60% were bilateral. The median number of nodules per patient was 3, with a median total nodule volume of 1.52 cm3. 74% of patients were referred due to imaging findings, followed by other reasons (19%), abnormal lab tests (4%), and symptomatic presentations (1%). The majority (98%) reported no symptoms. 1% reported one symptom, 0.5% reported three symptoms. There was a significant association between total nodule volume and cosmetic score (p=0.0007). Age was associated with both total nodule volume (p=0.0045) and the total number of nodules (p<0.0001), with older patients exhibiting larger nodule volumes and a higher number of nodules. Among 26 patients with total nodule volume measurements at baseline and 6 months, the median change in volume was -0.02 cm3. Of these, 58% showed a decrease, while 30% experienced an increase in nodule volume. After adjusting for age, no significant change in total nodule volume over time was observed. No significant changes were found in LUMP score, cosmetic score, or ThyPRO score. Age was significantly associated with the change in total nodule volume (p=0.0058), with a 3% increase in nodule volume for every year of age. No significant associations were observed between BMI, diabetes, hypertension, or hyperlipidemia and changes in total nodule volume. Conclusion: In conclusion, this study found that age was significantly associated with an increase in total nodule volume. No significant associations were observed between volume change and factors such as BMI, diabetes, hypertension, or hyperlipidemia over a 6-month timeframe. Additionally, there were no significant changes in LUMP score, cosmetic score, or ThyPRO score. Active recruitment for the registry is ongoing and we will continue to evaluate for changes every 6 months. Presentation: Monday, July 14, 2025

Background/Synopsis Research exploring the cardiovascular health (CVH) of transgender and nonbinary individuals remains limited, and there is evidence that gender affirming hormone therapy (GAHT) may impact CVH. Moreover, the Gender Minority Stress and Resilience Model highlights the mental and physical health consequences of unique stressors that affect these individuals. Together, these factors place an ever-increasing importance on the role of CVH risk assessment within this population. Objective/Purpose To characterize behavioral risk factors and biomarkers of CVH among transgender and nonbinary individuals and to assess the role of mental health in modulating these risk factors. Methods Individuals ages 18 or older who identify as transgender male/female (TGM/TGF) or nonbinary (NB) were recruited. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) were used to assess symptoms of depression and anxiety. Self-reported intake of specific food groups was converted to a score of 0-16, with higher diet scores reflecting larger quantities of potato chips, butter, fast-food, and soda and fewer quantities of fruits, vegetables, and beans. Weekly exercise was assessed using the International Physical Activity Questionnaire and converted to Metabolic Equivalent Tasks (METs). Diet scores, weekly METs, Body Mass Index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), and low-density lipoprotein (LDL) levels were compared between those who screened positive on both the PHQ-2 and GAD-2 and those who screened negative. Unadjusted Mann-Whitney and Chi-square tests were performed; a p-value of under 0.05 was considered statistically significant. Results Seventy-eight participants were included: 24 TGM, 42 TGF, and 12 NB. Ages ranged from 18-69. 77% (n=60) of participants were on GAHT. Twenty-eight participants screened positive on both the PHQ-2 and GAD-2, and 34 participants screened negative for both. Participants who screened positive had less healthy diets than those who screened negative (average diet score 7.3 vs 6.0; p=0.0456). These participants also tended to be less likely to surpass the American Heart Association's recommended 600 weekly METs (57% of participants (n=16) vs 79% of participants (n=29); p=0.0584) and less likely to attain recommended levels of CVH biomarkers (Figure 1). Conclusions Our data highlight an important trend in which participants with symptoms of anxiety and depression had less healthy diets and were less likely to meet exercise and biomarker goals. With less than 50% of either group attaining target BMI or LDL levels, our data also underscore the significant overall CVH risk in this population.

Disclosure: R. Stojchevski: None. E. Sutanto: None. K. Dragarska: None. I. Todorovska: None. S. Velichkovikj: None. N. Hadzi-Petrushev: None. J. Bogdanov: None. M. Mladenov: None. L. Poretsky: None. D.B. Avtanski: None. Monocarbonyl analogs of curcumin (MACs) in recent years have emerged as promising candidates in breast cancer therapy, representing a strategic approach to improve curcumin's poor stability and pharmacological profile, thus paving the way for novel anticancer treatments. This study aimed to evaluate the stability of two MACs, C66 and B2BrBC, relative to curcumin and predict their absorption, distribution, metabolism, and excretion (ADME) properties, pharmacokinetic features, and estimated drug-likeness using SwissADME computational analysis. Additionally, the proapoptotic and antimetastatic potential of the analogs was investigated in two breast cancer cell lines, MCF-7 and BT-474. Our previous findings highlighted the potential therapeutic application of C66 and B2BrBC in mitigating breast cancer progression by modulating key markers for epithelial-to-mesenchymal transition. The results of the stability assay conducted under physiological conditions demonstrated that C66 and B2BrBC were significantly more stable than curcumin, which degraded by approximately 17% after 25 minutes, whereas the MACs showed only approximately 3% reduction. Moreover, the SwissADME analysis predicted favorable physicochemical properties for both compounds consistent with drug-likeness criteria and supported their potential as orally bioavailable drug candidates. Fluorescent microscopy using a caspase-3 dye confirmed the proapoptotic effects of C66 and B2BrBC, with B2BrBC inducing higher apoptotic activity in MCF-7 cells and C66 exhibiting higher caspase-3 activation in BT-474 cells. The MILLIPLEX assay conducted to measure the expression levels of various cancer metastasis biomarkers in cell culture media showed that both analogs significantly modulated key biomarkers associated with apoptotic pathways and bone metastasis, such as GDF-15, DKK-1, and OPG, underscoring their potential role in suppressing cancer progression. These findings highlight C66 and B2BrBC as stable, effective, and promising therapeutic agents against breast cancer, with notable effects on apoptosis and metastasis. Future studies should aim to further explore their clinical relevance and therapeutic applications. Presentation: Saturday, July 12, 2025

Transgender individuals are medically underserved in the United States. Based on the National Transgender Discrimination Survey, 19% transgender population were refused healthcare, 50% had providers with no knowledge of transgender care and 28% had to delay medical care because of discrimination based on the sexual orientation [1]. The Friedman Transgender Health and Wellness Program (FTHWP) was established in 2017 at Lenox Hill Hospital to provide clinical, legal and social services to transgender individuals. These services include pediatric and adult endocrinology services, primary care, mental health, gynecological services, HIV/AIDS testing and care, referrals for hair removal, vocal cord training and gender confirming surgery, legal services, specialty referrals and social work assistance. There were 10 participants at FTHWP in June 2017. The number of participants increased to 60 by September 2018. The patients’ ages range from 11 years to 80 years old. 32 are Caucasians (53%), 13 are African American (21%), 10 are Asian (16%) and 6 are Hispanic (10%). 29 patients are trans-male, 28 patients are trans-female, 4 patients are gender-fluid. 39 patients have received previous hormone therapy, while 22 patients initiated hormonal therapy in our program. From this limited initial experience we concluded that the demand for comprehensive transgender medical services exists and that the patients display diverse demographic and clinical characteristics. Endocrinologists are well positioned to establish transgender health centers because of their background in both internal medicine and hormone therapy. Reference: [1] Grant JM, Mottet LA, Tanis J, Harrison J, Herman JL, Keisling M. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. Washington, DC: National Center for Transgender Equality and National Gay and Lesbian Task Force; 2011.