bluuebunny/crossref_metadata_2025_split huggingface dataset:
5165 Cushing’s Disease And Primary Aldosteronism Confounded By A Non-functioning Solitary Adrenal Incidentaloma
Authors: Friedman Jared G , Huang Wenyu 
Published: October 2024

Abstract
Disclosure: J.G. Friedman: None. W. Huang: None.
Background: Adrenal incidentalomas are common, affecting ∼2% of the general population. The presence of adrenal incidentaloma necessitates biochemical testing for hypersecretion, however hypercortisolism and/or hyperaldosteronism may not necessarily originate from the nodule that prompted the initial workup. Clinical Case: A 53-year-old man with a history of obesity and hypertension was referred for workup of a 2.4 x 1.4 cm R adrenal nodule that was incidentally discovered on an abdominal CT to rule out pancreatitis. He was noted on examination to have some Cushingoid features. He was on three antihypertensives (amlodipine 10 mg, carvedilol 50 mg, and spironolactone 50 mg) with adequate blood pressure control and no hypokalemia. He denied spells nor exogenous steroid exposure. Initial testing for hypersecretion showed an elevated cortisol 8.7 ug/dL (&lt;1.8) after 1 mg dexamethasone with adequate dexamethasone level, aldosterone concentration (PAC) 9 ng/dL (3-16), plasma renin activity (PRA) 0.7 ng/mL/h (0.25-5.82), potassium of 3.8 mmol/L (3.5-5.1), and normal plasma metanephrines. Further testing revealed elevated 24-hour urinary free cortisol 81.3 mcg/24h (4-50) and elevated late night salivary cortisol 0.10 and 0.13 mg/dL (&lt;0.09). Baseline 8 AM ACTH was not suppressed 16.3 pg/mL (7.2-63.6). DDAVP stimulation resulted in an increase in cortisol and ACTH suggestive of Cushing’s disease, which was confirmed by inferior petrosal sinus sampling (IPSS). Pituitary MRI showed a 3.6 mm L-sided microadenoma. He underwent transsphenoidal resection with pathology consistent with an ACTH-staining pituitary adenoma. Immediate post-op cortisol nadir was 4.9 ug/dL. A few weeks after surgery, he underwent retesting for primary aldosteronism notable for PAC 14 ng/dL, PRA 0.58 ng/mL/h, and K 4.0 mmol/L. After oral salt loading, 24-hour urine aldosterone was 14.4 mcg/24h (&lt;12) with urine sodium 247 mmol/L/24h (&gt;200). He completed AVS which lateralized to the L adrenal gland despite a R adrenal nodule. He underwent L adrenalectomy with significant improvement in blood pressure which is now well-controlled on carvedilol monotherapy with normalization of PRA to 1.94 ng/ml/h. The R adrenal nodule remains stable in size and appearance on follow up imaging. Conclusion: The presence of an adrenal adenoma with concomitant biochemical evidence of hormonal excess cannot inherently be attributed to nodular autonomous function without further workup. Other hormonal assessment including ACTH level and localization studies are necessary prior to any surgical procedure to avoid missed diagnoses of Cushing’s disease and contralateral primary aldosteronism in the presence of a non-functioning adrenal nodule.
Presentation: 6/1/2024
7828 First Trimester Serum 11-Deoxycorticosterone Predicts Extreme Premature Childbirth
Authors: Ronde Salminen Emma K , Schoenmakers Sam , van Zelst Bertrand D , van den Berg Sjoerd A A 
Published: October 2024

Abstract
Disclosure: E.K. Ronde Salminen: None. S. Schoenmakers: None. B.D. van Zelst: None. S.A. van den Berg: None.
First Trimester Serum 11-Deoxycorticosterone Predicts Extreme Premature Childbirth Background: Preterm birth is the leading cause of perinatal mortality and morbidity worldwide. Unfortunately, the prediction of preterm birth remains challenging, causing unnecessary hospital admittance and overexposure to medication. Studies have shown that metabolites of progesterone can influence uterine contractility[1] and serum levels of 11-deoxycorticosterone have been shown to correlate with an increased risk of preterm birth before 32 weeks of gestation2. The aim of this prospective study was to determine whether first trimester measurement of the progesterone metabolites 11-deoxycorticosterone (11-DOC) and 16-alpha hydroxyprogesterone (16-OHP) could be used as a predictive marker for preterm birth. Methods and results: A cohort of 386 pregnant women were included at 12 weeks of gestation between 2014-2016. Their obstetric histories and comorbidities were noted and their plasma was frozen. Of these women, n=26 delivered prior to 32 weeks of gestation and n=286 delivered at term. 11-DOC and 16-OHP were determined using LC-MS/MS. Mann-Whitney U test was used to statistically analyze differences between the groups. There was a highly significant difference in the level of 11-DOC between women delivering prior to 32 weeks of gestation in comparison to women delivering after 37 weeks of gestation (p=0.007). 16-OHP levels tended to be different between the two groups, but this did not reach statistical significance (p=0.062). No difference was found in the ratio 16-alpha hydroxyprogesterone/11-deoxycorticosterone between the two groups (p=0.916). Conclusion: Plasma levels of progesterone metabolites collected late in the first trimester of pregnancy predicts preterm birth prior to 32 weeks of pregnancy. References: 1.Patil AS, Swamy GK, Murtha AP et al, Progesterone metabolites produced by cytochrome P450 3A modulate uterine contractility in a murine model, Reprod Sci, 2015 Dec 22(12):1577-1586 2.Patil AS, Gaikwad NW, Grotegut CA et al, Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery, Hum Reprod Open, 2020 Apr 6;2020(2):hoaa007
Presentation: 6/1/2024
7830 Gender-Affirming Hormone Therapy Improves Levels of Depression in Transgender Individuals Within the First Year of Treatment
Authors: Godar Cassandra M , De La Torre Sebastian C , Shakir Mohamed K M , Hoang Thanh D 
Published: October 2024

Abstract
Disclosure: C.M. Godar: None. S.C. De La Torre: None. M.K. Shakir: None. T.D. Hoang: None.
Introduction: High rates of depression and suicidality are known threats to the health of transgender individuals in the United States. Epidemiologic studies report depression rates as high as 69% of the transgender population. Nearly 40% of the trans population has a history of suicide attempt, which is 8 times that of the general US population. Initiation of gender-affirming hormone therapy (GAHT) is a life-saving intervention that improves gender dysphoria and the overall health status of patients who choose this therapy. In this study we apply a validated metric, the Beck Depression Inventory (BDI), to demonstrate the mental health benefits of GAHT in transgender people. Methods: A prospective study of 31 transgender patients was approved by IRB at an academic medical center. 18 transgender females and 13 transgender males completed the BDI prior to initiation of GAHT and again after one year of GAHT use. The BDI is a 21-item self-reported questionnaire that is scored to identify levels of depression. Depression levels are stratified as normal (1-10 levels), mild mood disturbance (11-16 levels), borderline clinical depression (17-20 levels), moderate depression (21-30 levels), severe depression (31-40 levels), or extreme depression (&gt;40 levels). Median scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: In the total study population, an average BDI score of 11 at baseline (range 0-32) improved to average score of 8 after 1 year of GAHT (range 0-28). Average BDI for transgender females was at 10.5 at baseline and 7.4 at 1 year. Average BDI for transgender males was 10.7 at baseline and 7.7 at 1 year. Transgender females reported increased crying (question 10), and transgender males reported increased irritability (question 11) at 1 year. Both genders report increased satisfaction with life, interest in others, physical appearance, and sleep quality. Both genders report slight decrease of suicidal ideation (average BDI 0.9 decreased to 0.1 for question 9) though with no decrease in median BDI score. Discussion: Uninterrupted access to GAHT is critical to the well-being of transgender individuals. GAHT use improves depression by about 3 levels as demonstrated above and is one component of a holistic treatment approach to include behavioral health therapy, gender-affirming surgeries, and speech therapy to improve gender dysphoria and overall quality of life. Regular behavioral health follow-up is important to support at-risk patients through gender transition. BDI is a simple, open-access tool to screen for depression and expedite behavioral health treatment for this vulnerable population.
Presentation: 6/2/2024
12334 Harnessing Protective Diets: Phytoestrogens As A Strategy To Alleviate Estradiol-driven Progression And Symptomatology In Endometriosis
Authors: Strong A D , Andrisse S , Antani D 
Published: October 2024

Abstract
Disclosure: A.D. Strong: None. S. Andrisse: None. D. Antani: None.
Endometriosis (EMS) is a prevalent gynecological disorder affecting 10% of reproductive-age women with up to 50% experiencing infertility. It is characterized by the presence of endometrial-like tissue outside the uterus, leading to symptoms such as pelvic pain and infertility. While the exact cause of EMS remains elusive, hormonal dysregulation and the succeeding inflammation play a crucial role in its pathogenesis. Phytoestrogens (PEs) are a diverse group of plant-derived compounds that exhibit structural and functional similarities to endogenous estrogens and have emerged as potential therapeutic agents due to their ability to modulate hormonal signaling and inflammatory pathways. This integrative review aimed to provide a summation of the current evidence on the mechanisms of action and potential therapeutic applications of PEs in the context of EMS. PEs exhibit weak estrogenic activity and can interact with estrogen receptors (ERs), influencing hormonal and molecular pathways relevant to the pathology. These compounds have shown promise in regulating estrogen levels, inhibiting cell proliferation, and modulating insulin-like growth factor 1 signaling, all of which are critical in developing and progressing the disease state. Notably, curcumin and resveratrol have demonstrated anti-proliferative effects on endometrial cells by targeting key pathways involved in cell growth and angiogenesis. Curcumin has been shown to downregulate inflammatory factors like COX-2 and TNF-α while reducing vascular endothelial growth factor expression associated with angiogenesis. Similarly, resveratrol has been found to suppress inflammatory responses in endometrial stromal cells through the sirtuin 1 pathway. Studies indicate PEs can enhance antioxidant defenses and counteract reactive oxygen species levels implicated in endometriotic pain and disease progression. By restoring antioxidant balance and mitigating oxidative damage, PEs may offer therapeutic benefits in managing EMS symptoms. In conclusion, their multifaceted effects on estrogen signaling, inflammation, and oxidative stress highlight their potential as adjunctive or alternative treatments for symptomatic women with active disease. Plausible evidence supports that certain dietary components can reduce or exacerbate inflammation associated with EMS symptoms and progression. Foods that are rich in phytoestrogens include soy, fruits, vegetables, spinach, sprouts, beans, cabbages, and grain. Specifically, curcumin is a primary component in turmeric and resveratrol is found in high amounts in black and red grapes, red wine, berries, and nuts. While more research is still needed to fully understand the relationship between diet and endometriosis, utilizing therapeutic dietary interventions appears to be a promising self-management strategy for improving quality of life and symptom management.
Presentation: 6/3/2024
12554 Human Sex Determination: SRY Length Regulates Its Cellular Stability And Hence The Robustness Of Testis Differentiation
Authors: Chen Yen-Shan , Thomson Ella , Pelosi Emanuele , Weiss Michael A 
Published: October 2024

Abstract
Disclosure: M.A. Weiss: None.
The abundance of transcription factors (TFs) mediated by the rates of degradation are subjected to be a robust to an appropriate level. This regulation via the proteasome is largely controlled by the stability of individual proteins and then could determine the direction of a gene-regulatory network. Insight is obtained through studies of bistable genetic circuits mediated by initiating transcription factors. A model is provided by SRY, a Y-encoded TF that initiates testicular differentiation. Known functions in human SRY (204 residues) majorly cluster in its high mobility group (HMG) box whereas the functions of the N- and C-terminal non-box segments are not well characterized. Here, we have used cell-based and mouse transgenic studies to measure the transcriptional threshold of SRY regulating the balance between development and dysgenesis. Our findings demonstrate a threshold length in the C-terminal domain of human SRY that determines the protein’s proteosome-enforced half-life. In a pre-Sertoli cell model, truncation of SRY resulted in the reduction of intracellular concentration and twofold attenuation of the male-specific GRN. Expression of the 1-164 fragment of human SRY in CRISPR-Cas9-edited XX mice failed to drive male differentiation whereas the 1-200 of SRY initiated male GRN development. This study provides insight into the robustness of human SRY and illustrates a powerful strategy to link biochemical properties in cultured cells and in vivo developmental outcomes. Our study reveals a checkpoint in a key TF initiating a sex-specific GRN, functioning as an experimental “control knob” in development. Our approach probes molecular determinants of cell fate and so promises to extend structure-function studies of SRY to the flanking and relatively obscure non-box domains. This result implies the balance between robustness and evolvability in metazoan is a game of numbers of initial transcription factor in the networks.
Presentation: 6/1/2024
7667 Cushing’s Puzzle: Echinococcal Pituitary Cyst In A Rare Encounter
Authors: Sari Esra , Erenler Feyza 
Published: October 2024

Abstract
Disclosure: E. Sari: None. F. Erenler: None.
Introduction: Echinococcus is a rare parasitic infection endemic in the Mediterranean, Middle East, South America and Africa, which can cause cystic disease in several organs. Central nervous system involvement is known to comprise 1-2% of all cystic echinococcal disease. Hereby, we report a case of an opportunistic pituitary echinococcus infection in a patient with hypercortisolism due to adrenocortical adenoma with initial misdiagnosis of Cushing’s disease. Clinical Case: A 40-year-old South American female with poorly controlled T2DM on oral agents and hypertension presented to the ER with abdominal pain and subsequent CT of the abdomen with contrast showed a right adrenal mass measuring up to 2.8 cm. A follow up CT with adrenal protocol confirmed 3.3 cm right adrenal mass, 46 HU in precontrast images with &gt;50% washout. Review of records revealed that a recent MRI brain with contrast was performed for headache evaluation and showed an incidental 5x7x4 mm lesion in the pituitary gland. Endocrinology evaluation revealed 24-hour urine volume 1800 mL, elevated free cortisol levels 277.6 mcg/24hr (RR: 4.0-50.0 mcg/24hr), creatinine of 0.67g/24hr (RR: 0.50-2.15g/24hr). 1 mg dexamethasone suppression test showed AM cortisol of 28.7 mcg/dL. ACTH was elevated at 67 pg/mL (RR: 6-50 pg/mL). FSH, LH, and GH were normal. Presumed diagnosis of ACTH-dependent hypercortisolism was made and she underwent bilateral inferior petrosal sinus sampling with confirmed successful cannulation but this was inconclusive due to low ACTH levels. Follow-up MRI of the pituitary gland showed T1 bright, T2 isointense circumscribed lesion measuring 7x6x3 mm at anterior pituitary gland with a thin rim of peripheral enhancement consistent with cystic features. She underwent transsphenoidal resection of the pituitary lesion and the pathology specimen showed parasites consistent with echinococcosis. Infectious disease was consulted, and the patient started on albendazole. Post-operative laboratory evaluation was notable for persistently elevated AM cortisol, 24-hour urine free cortisol levels, and low ACTH levels, confirming ACTH independent hypercortisolism. She underwent right adrenal nodule resection and pathology was consistent with adrenocortical adenoma. Post-adrenalectomy AM cortisol levels were &lt; 2 mcg/dL, indicating the resolution of hypercortisolism along with substantiating the diagnosis of primary adrenocortical hyperfunction. Conclusion: To the best of our knowledge, this is the first case report of an opportunistic echinococcus infection presenting as a pituitary lesion in the setting of Cushing Syndrome. We would like to highlight the importance of recognizing opportunistic infections, including Echinococcus as a potential etiology in the setting of hypercortisolism, especially for patients from endemic regions.
Presentation: 6/2/2024
7820 Immune system adaptation during gender-affirming testosterone treatment
Authors: Lakshmikanth T , Consiglio C , Sardh F , Forlin R , Wang J , Tan Z , Barencilla H , Rodriguez L , Sugrue J , Noori P , Ivanchenko M , Piñero Páez L , Gonzalez L , Habimana Mugabo C , Johnsson A , Ryberg H , Hallgren Å , Pou C , Chen Y , Mikeš J , James A , Dahlqvist P M , Wahlberg Hughes J , Hagelin A , Holmberg M , Degerblad M , Isaksson M , Duffy D , Kampe O , Landegren N , Brodin P 
Published: October 2024

Abstract
Disclosure: T. Lakshmikanth: None. C. Consiglio: None. F. Sardh: None. R. Forlin: None. J. Wang: None. Z. Tan: None. H. Barencilla: None. L. Rodriguez: None. J. Sugrue: None. P. Noori: None. M. Ivanchenko: None. L. Piñero Páez: None. L. Gonzalez: None. C. Habimana Mugabo: None. A. Johnsson: None. H. Ryberg: None. Å. Hallgren: None. C. Pou: None. Y. Chen: None. J. Mikeš: None. A. James: None. P.M. Dahlqvist: None. J. Wahlberg Hughes: None. A. Hagelin: None. M. Holmberg: None. M. Degerblad: None. M. Isaksson: None. D. Duffy: None. O. Kampe: None. N. Landegren: None. P. Brodin: None.
Infectious, inflammatory and autoimmune conditions present differently in males and females. Following SARS-CoV-2 infection, male sex is associated with increased risk of death, while female sex is associated with increased risk of the postinfectious disorder, long COVID. Similar trends are seen in other infections. Female immune responses to vaccines are typically stronger, and adverse reactions are more frequent, like most autoimmune diseases. Immunological sex-differences stem from genetic, hormonal and behavioural factors but their relative importance is poorly understood. To understand the consequences of changing sex-hormones in vivo, we performed longitudinal, systems-level analyses in 22 adults, assigned female at birth, and undergoing gender-affirming testosterone treatment (trans-men). We find that sex hormones modulate a cross-regulation axis of type-I interferon (IFN-I) and TNFα in humans. This is mediated by a reduced frequency of plasmacytoid dendritic cells (pDC), and functional attenuation of IFN-I responses in both pDCs and monocytes. Conversely, testosterone potentiates monocyte responses to lipopolysaccharide (LPS) leading to increased TNFα, IL-6 and IL-15 production and downstream epigenetic opening of NFκB regulated genes and potentiation of IFNγ responses, primarily by NK cells. IFNγ in turn feeds back onto monocytes leading to upregulation of SLAMF7 and further enhanced TNFα responses by myeloid cells. These results are corroborated by sex-divergent responses in multiple public datasets and collectively illustrate the dynamic recalibration of human immune systems by sex hormones with implications for individuals undergoing gender-affirming hormone therapy, but also better understanding of divergent responses to infection, vaccines and self-antigens in cisgender individuals.
Presentation: 6/2/2024
7939 Impact of genetic background on chronic inflammation in a letrozole-induced mouse model of PCOS
Authors: Ujagar Naveena , De Robles Gabriela , Velez Leandro Martin , Seldin Marcus , Nicholas Dequina 
Published: October 2024

Abstract
Disclosure: N. Ujagar: None. G. De Robles: None. L.M. Velez: None. M. Seldin: None. D. Nicholas: None.
The etiology behind polycystic ovary syndrome (PCOS) is elusive due to the heterogeneity of its symptoms and varying severity in patients. There are a wide variety of factors associated with PCOS, like hyperinsulinemia, hyperandrogenism, endotoxemia and chronic inflammation that have been implicated as causal factors in the condition. However mechanisms of cause and effect are difficult to establish in human cohorts. Endotoxemia, observed in humans and mouse models of PCOS, is known to trigger chronic inflammation by activating immune cells. Although correlation of chronic inflammation with PCOS has been established, the type of inflammation in PCOS patients has not been defined, in part due to the genetic variance from person to person. Using a systems immunology approach to mimic human genetic diversity, combined with a letrozole-induced PCOS mouse model, we aim to distinguish the types of inflammation present in PCOS. We analyzed the immune cells from lymph nodes and spleens of 21 different strains of PCOS induced and control mice (130 mice in total), and found that based on genetic background the reproductive and metabolic phenotypes differed- similar to how PCOS presents clinically. We were able to categorize each letrozole-induced mouse strain into the sub-phenotypes of PCOS based on the current guidelines for diagnosing PCOS published in 2023 and extensive characterization of each strain. Splenocytes from these control and PCOS mice were activated in vitro to trigger T cell and myeloid cell cytokine secretion, which was measured via luminex. Clustering analysis of these multi-analyte cytokine measurements together with flow cytometry of the immune cells allowed us to identify T-helper 17 (Th17) cells as the prominent immune cell driving inflammation in letrozole-induce mouse model of PCOS independent of genetic background. This systems immunology approach has allowed us to define PCOS associated inflammation and will be the basis for integrating human inflammation in PCOS with mouse models that appropriately recapitulate disease. The discovery of Th17 cells as key inflammatory mediators provide targets for understanding the mechanisms linking chronic inflammation to reproductive and metabolic outcomes in PCOS, and will assist in future development of anti-inflammatory therapies.
Presentation: 6/2/2024