Citations

Abstract Disclosure: D.S. Ali: None. Z. Chung: None. L. Kamel: None. S. Björnsdottir: Shire. B.L. Clarke: Shire, Takeda, Ascendis, Calcilytix. S. Hahner: None. L.C. Hofbauer: Amgen Inc, Ascendis, UCB, Ascendis, Amolyte. P. Houillier: None. S.W. Ing: Amgen Inc, Radius Health, Inc, Takeda, AscendAlexion, Amolyt, Ascendis, Calcilytix, Kyowa Kirin. M.A. Levine: Takeda, Amolyt, Calcilytix. M. Mannstadt: Takeda, Amolyt, Calcilytix. L. Rejnmark: Takeda, Amolyt, Ascendis, Calcilytix. D.M. Shoback: Amolyt, Ascendis, member of the advisory board (PARADIGHM). M. Brandi: Takeda, Eli Lilly & Company, Calcilytix, Kyowa Kirin, UCB, Abiogen, Alexion, Amolyt, Amorphical, Bruno Farmaceutici, CoGeDi, Echolight. A.A. Khan: Takeda, Amgen Inc, Alexion, Ascendis, Amolyt, Calcilytix. Background: Hypoparathyroidism (HypoPT) is a rare endocrine disorder that requires close evaluation and follow up during pregnancy to minimize maternal and fetal complications. The primary objectives of this study are to evaluate the use of rhPTH (1-84) during pregnancy by analyzing data from the PARADIGHM disease registry, and to compare maternal and neonatal outcomes among patients who continued PTH therapy during pregnancy versus those on conventional therapy (CT). Methods: We performed a retrospective analysis of data in the PARADIGHM registry. Maternal and neonatal outcomes in women treated with rhPTH (1-84) were compared to women who received CT. Results: We analyzed 39 pregnancies of 32 women. Of those, 4 women (6 pregnancies) used rhPTH (1-84) either before or during pregnancy and 28 women (33 pregnancies) continued CT during pregnancy. The mean (SD) maternal age at enrollment was 31.7 (5.6) years. Postsurgical HypoPT was the most common etiology (68.8%). The mean gestational age at delivery was 36 (2.4) weeks (PTH-treated) vs 38.3 (3.3) weeks (CT) (p=0.162). Preterm delivery rates were higher in the PTH-treated group (50% vs. 27%, p=0.591), but this was not statistically significant. Two women had pre-eclampsia, one in each group (PTH-treated and CT). In the PTH-treated group, one pregnancy resulted in a stillbirth, and one infant was born with congenital anomalies (16.7% each). Conclusions: The safety of rhPTH (1-84) use in pregnancy cannot be determined at this time. The PTH-treated group exhibited trends towards higher rates of preterm delivery, but the rates of stillbirth, and congenital anomalies were low and comparable in both groups of women. Larger studies are necessary to determine the optimal approach to manage women with HypoPT during pregnancy. Presentation: Sunday, July 13, 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: 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: A. Riaz: None. R. Haider: None. F. Naseer: None. S. Fatima: None. A. Khan: None. M. Mal: None. A. Qadeer: None. INTRODUCTION: Giant mastauxe is a rare neonatal condition characterized by excessive breast enlargement, with a breast bud diameter exceeding 3 cm. It is an exaggerated form of common neonatal breast enlargement (1 to 2 cm) that typically resolves within six months. This condition results from maternal estrogen withdrawal, which triggers prolactin release and breast tissue proliferation. Its pronounced presentation raises parental concern and requires clinical evaluation to exclude pathological causes. Very few reports exist in literature on it. Here we report a rare case of giant mastauxe, highlighting its presentation and management. CASE PRESENTATION: A 1-month-20-day-old male infant came with bilateral breast enlargement and milky discharge since birth. There was no history of trauma or redness. He was born at 39 weeks via vaginal delivery, weighing 3100g, with APGAR scores of 8 and 9 at 1 and 5 minutes, respectively. Mother had no history of antenatal infections or drug intake, except for iron, calcium, and folic acid supplements during antenatal visits.On examination, the respiratory rate was 54 breaths/min, heart rate 140 beats/min, temperature 98.5°F, and oxygen saturation 99%. Bilateral, non-tender, non-erythematous breast swelling with soft consistency and milky discharge was noted (right: 5.1×3.2 cm; left: 3.8×3.0 cm), with retracted nipples and no skin changes.Laboratory tests showed normal leukocytes and CRP. Ultrasonography revealed enlarged breasts with dilated ducts/cysts. Diagnosed as Giant mastauxe, malignancy and inflammation were ruled out. Treatment included Miconazole gel, Miconazole nitrate, Hydrocortisone cream, Iron polymaltose complex, Vitamin B complex, Vitamin C, and Lysine.After 3 weeks, follow-up showed reduced breast size with retracted nipples and no infection. DISCUSSION: Giant Mastauxe is breast bud enlargement more than 3 cm. Postnatally, falling maternal estrogen triggers prolactin secretion in the newborn’s pituitary, leading to breast stimulation and milk secretion in 5-20% of infants. The breast's engorgement correlates with plasma prolactin, implying the infant’s prolactin drives the response. The cause of exaggerated hormonal response in neonatal mastauxe is unclear but may involve heightened sensitivity to estrogen or prolactin. increasing the risk of malignancy later. Ultrasound typically shows hypoechoic tissue for diagnosis. The condition resolves on its own, and requires simple follow-up every two months. Presentation: Saturday, July 12, 2025

Abstract Disclosure: R. Haider: None. M. Waqas: None. S. Khan: None. A. Ullah: None. M. Khawar: None. A. Qadeer: None. M. Talha: None. A. Batool: None. A. Khan: None. M.Z. Haider: None. R.W. Kirchoff: None. Background: Hypothyroidism and heart failure (HF) contribute significantly to mortality among older adults. Understanding mortality trends, including demographic, geographic, and socio-economic disparities, is crucial to inform healthcare policies and resource allocation. Methods: This study analyzed age adjusted mortality rates (AAMRs) from 1999 to 2022 for adults aged 55-85+ years. Age adjusted mortality rates (AMRs) per 1,000,000 population were stratified by gender, race, geographic location, and urbanicity. Trends were evaluated using Average Annual Percentage Change (APC) with 95% confidence intervals (CI), examining periods of decline and increase. Results: Between 1999 and 2022, 105,008 deaths were recorded among older adults (55-85+ years) due to hypothyroidism and heart failure (HF). The age-adjusted mortality rate (AAMR) initially declined from 1999 to 2016, marked by a significant drop between 2005 and 2008 (APC = -6.0, 95% CI: -7.6 to -3.0). However, mortality trends reversed post-2016, with a sharp increase (APC = 6.7, 95% CI: 5.5 to 8.4). Age-specific trends revealed declining crude mortality rates (CMR) across all groups until 2016, followed by increases, particularly in the 65-74 and 75-84 age brackets, with APCs of 14.1 (95% CI: 7.8 to 27.8) and 8.9 (95% CI: 3.8 to 21.8), respectively. Gender disparities showed men and women had similar trends, with declines until 2015-2016 followed by surges, with APCs of 6.8 (95% CI: 5.2 to 9.1) and 6.6 (95% CI: 4.6 to 11.1), respectively. Racial disparities highlighted steady declines until 2016, followed by increases in non-Hispanic Whites (APC = 10.4, 95% CI: 5.2 to 23.2) and Hispanics (APC = 7.5, 95% CI: 6.0 to 10.1). Geographically, the Midwest exhibited the highest AAMR (71.1), while the Northeast showed the lowest (51.4). State-level disparities revealed North Dakota with the highest AAMR (129.5), contrasting with Nevada, which had the lowest (20.4). Urban-rural differences showed similar trends, with notable AAMR increases in both settings post-2016. These results underscore significant demographic and regional disparities in hypothyroidism and HF-related mortality. Conclusion: While mortality from hypothyroidism and HF among older adults declined until 2016, trends have since reversed across all demographic and geographic strata. Addressing these rising rates require targeted interventions focusing on high-risk groups and areas. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. F. Saleem: None. M.H. Alsaadi: None. H. Jawad: None. A.Z. Khan: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. M.F. Hemida: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Background: Globally, pediatric endocrine anomalies are a significant cause of early mortality. This study examines the discrepancies of paediatric endocrine abnormalities 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 for the vulnerable demographics. Methods: Adhering to STROBES criteria, we extracted the mortality statistics due to endocrine disorders in the paediatric population from 1999-2020 from the Centre for Disease Control and Prevention-Wide Ranging Online Data for Epidemiologic research (CDC-WONDER). We calculated Age-Adjusted mortality rates (AAMRs) per 100,000 individuals. We calculated the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC) to assess trends stratified by age, gender, urbanization, race, census region, and states. Joinpoint regression model was used for analysis. Results: Between 1999 and 2020, 5161 deaths among children less than 1 year to 14 years of age in the United States were related to endocrine-related disorders. Most occurred due to thyroid disorders, diabetes mellitus, and other miscellaneous disorders related to glucose regulation and pancreatic internal secretion. The overall AAPC for endocrine-related mortality in the pediatric population increased from 1.4866 in 2008 to 2.4982 in 2020, with an AAPC of 0.1346 (95% CI: -3.1216 to -3.5003, p > 0.000001). The male population had higher AAPCs than the female population (women: -0.9938; men: 0.7223). There were notable racial differences: The Hispanic or Latino population had the highest AAPC (0.15), followed by the Black population (-0.195) and then the White population with the lowest AAPC (-0.166). According to the age group stratification, the age group with the highest AAPC was the 5-14 age group (2.03) and the lowest the less than 1 year age group, with AAPC (-2.007). There was a significant decrease in deaths in the less than 1 year age group from 1999 to 2020 (p value < 0.05) with APC (-2.0) (95% CI: -3.0191 to -0.9861) and for the 5-14 age group from 2010 to 2020 with APC (10.8861) (95% CI: 3.4843 to 18.8). Depending on the urban-rural categorization, metro areas had a higher AAPC (0.1508) compared to the non-metro areas with an AAPC (-0.4467). Conclusion: The overall decline in endocrine-related deaths in the pediatric population from 1999 to 2020 hails an improvement in efforts made to manage these disorders. However, the recent uptick in the Hispanic-Latino population emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities as well as in children 1-4 years of age, depicting the increased vulnerability and need for added care in this age group. Presentation: Saturday, July 12, 2025

Abstract The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here, we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Our data reveal non-epistatic interactions between HELLS and PARP1 and suggest that HELLS functionally compensates for PARP1 deficiency in promoting cell survival in response to DNA alkylation damage. Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.

Metastatic meningioma exhibits diverse dissemination patterns across organ systems (lungs, bone, liver, soft tissue, etc), with molecular imaging—particularly gallium 68 DOTA Tyr3-octreotide PET/CT—playing a pivotal role in detection, characterization, and guiding management.

Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver cancers, represent a significant global health burden, with high prevalence and mortality rates driven by aging, lifestyle factors, and infections. Emerging research highlights the role of vitamin D in cancer biology, particularly its potential in the prevention and management of GI cancers. Through its active form, calcitriol, vitamin D regulates cell proliferation, apoptosis, angiogenesis, and immune responses via the vitamin D receptor (VDR). Epidemiological studies suggest an inverse association between vitamin D deficiency and cancer risk, while experimental models demonstrate its anti-tumor effects. Additionally, vitamin D influences gut microbiota composition and immune regulation, potentially enhancing cancer immunity and response to immunotherapy. Despite promising evidence, clinical trials have yielded mixed results, underscoring the need for further research to determine optimal supplementation strategies, individual responses, and genetic influences. This review explores vitamin D’s mechanisms, epidemiological evidence, and therapeutic potential in GI cancers, advocating for personalized approaches in cancer prevention and treatment.