Journal of the Endocrine Society最新文献

{"title":"<i>FLCN</i> Variants in Parathyroid Carcinoma and Atypical Parathyroid Tumors.","authors":"Callie Shea Burke, Justin Bellizzi, Jessica Costa-Guda, Andrew Arnold","doi":"10.1210/jendso/bvaf009","DOIUrl":"10.1210/jendso/bvaf009","url":null,"abstract":"<p><p>Parathyroid carcinoma (PC) and atypical parathyroid tumors (APT) are incompletely understood and pose challenges in definitive diagnosis. <i>FLCN</i> sequence variants have recently been linked to PC and APT. Inactivating mutations in the ubiquitously expressed <i>FLCN</i> tumor suppressor gene, encoding folliculin, cause Birt-Hogg-Dubé syndrome (BHD), a rare tumor predisposition syndrome. Germline inactivating <i>FLCN</i> variants, accompanied by somatic allelic loss, were reported in 2 unrelated patents with PC, both with clinical features, but no diagnosis, of BHD. Somatic frameshift variants of likely pathogenicity were reported in 1 patient with PC and 1 with APT. On the other hand, neither PC nor APT has been reported in sizeable BHD series. To better understand the frequency of <i>FLCN</i> variants in PC and APT, we analyzed a series of 10 patients with sporadic PC and 14 with APT by direct Sanger DNA sequencing. We identified no inactivating <i>FLCN</i> mutations in any of the PC or APT samples examined. A germline missense variant (p.Gly325Val), predicted as benign/tolerated, was seen in 1 PC and a synonymous variant in 1 APT. The absence of pathogenic mutations detected in our series of PC and APT further suggests that <i>FLCN</i> variants are rare in these tumors. Nevertheless, the potential roles of <i>FLCN</i> in the pathogenesis of PC and APT merits further consideration and study.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf009"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Among Fragility Fractures and the Overall Cardiovascular Burden in Endogenous Cushing Syndrome.","authors":"Giacomo Voltan, Pierluigi Mazzeo, Michele Cannito, Silvia Pinelli, Mattia Barbot, Carla Scaroni, Filippo Ceccato, Valentina Camozzi","doi":"10.1210/jendso/bvaf008","DOIUrl":"10.1210/jendso/bvaf008","url":null,"abstract":"<p><strong>Context: </strong>Patients with endogenous Cushing syndrome (CS), in addition to significant cardiovascular morbidity, are burdened by a high prevalence of fragility fractures. Bone mineral density (BMD) alone poorly predicts the risk of fracture, and the implementation of trabecular bone score (TBS) is supported only by scant evidence. Indeed, reliable predictors of fractures in endogenous CS are still lacking.</p><p><strong>Objective: </strong>This work aimed to analyze the prevalence and the potential predictors of fragility fractures in our patients with CS.</p><p><strong>Methods: </strong>A monocentric, retrospective, cross-sectional study. A total of 51 patients with overt CS were enrolled. Main outcome measures included biochemical evaluation, BMD measurement, TBS evaluation, fracture presence, body composition evaluation, and arterial intima-media thickness (IMT) assessment.</p><p><strong>Results: </strong>Fragility fractures were found in 62.7% of patients at diagnosis. Fractured patients exhibited lower spine T-score (<i>P</i> = .03), longer disease duration (<i>P</i> = .025), higher waist circumference (<i>P</i> = .006), and predominantly male sex (<i>P</i> = .008). Increased serum uric acid levels (<i>P</i> = .001), greater IMT (<i>P</i> = .017), and higher prevalence of venous thromboembolism events (31.3% vs 5.3%, <i>P</i> = .037) and atherosclerotic plaques (47% vs 5.3%, <i>P</i> = .002) were described in the fracture group.Multivariable logistic regression identified the presence of atherosclerosis (OR 13.35; 95% CI 1.154-154.34, <i>P</i> = .038) and osteoporosis (OR 11.30; 95% CI 1.55-82.56, <i>P</i> = .017) as independent predictors. TBS values were inversely correlated with body mass index, fat and lean mass, and serum uric acid, and positively correlated with high-density lipoprotein cholesterol.</p><p><strong>Conclusion: </strong>CS patients with higher overall burden of cardiovascular morbidity are more prone to experience fragility fractures.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 3","pages":"bvaf008"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pros and Cons of Inpatient SGLT2i Use for Hyperglycemia and Heart Failure.","authors":"Hayley Fried, Yael Tobi Harris, Rifka Schulman-Rosenbaum","doi":"10.1210/jendso/bvae229","DOIUrl":"10.1210/jendso/bvae229","url":null,"abstract":"<p><p>Sodium-glucose cotransporter 2 inhibitors (SGLT2is), originally approved by the US Food and Drug Administration for glycemic control in type 2 diabetes mellitus (DM2), have shown substantial cardiovascular and renal benefits, leading to their expanded use in managing heart failure (HF) and chronic kidney disease in the outpatient setting. Despite these benefits, their use for inpatient hyperglycemia management is not universally endorsed due to safety concerns and inadequate data. However, emerging evidence suggests potential advantages of initiating SGLT2i treatment for patients during hospitalization in the setting of HF. While SGLT2is are not recommended for managing inpatient hyperglycemia, initiation during hospitalization for HF provides significant benefits. We review the current literature on the pros and cons of using SGLT2is in hospitalized DM2 and HF patients and provide guidance on careful patient selection and risk mitigation for inpatient use.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvae229"},"PeriodicalIF":3.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Cell-Free DNA in Metabolic Diseases.","authors":"Alessio Pollastri, Peter Kovacs, Maria Keller","doi":"10.1210/jendso/bvaf006","DOIUrl":"10.1210/jendso/bvaf006","url":null,"abstract":"<p><p>Metabolic diseases affect a consistent part of the human population, leading to rising mortality rates. This raises the need for diagnostic tools to monitor the progress of these diseases. Lately, circulating cell-free DNA (cfDNA) has emerged as a promising biomarker for various metabolic diseases, including obesity, type 2 diabetes, and metabolic-associated fatty liver disease. CfDNA is released from apoptotic and necrotic cells into the bloodstream and other body fluids, and it retains various molecular signatures of its tissue of origin. Thus, cfDNA load and composition can reflect tissue pathologies and systemic metabolic dysfunctions. In addition to its potential as a diagnostic biomarker, interest in cfDNA derives from its recently discovered role in adipose tissue inflammation in obesity. This review discusses detection methods and clinical significance of cfDNA in metabolic diseases.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf006"},"PeriodicalIF":3.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF-1 Assessment During Weekly Somatrogon Treatment in Pediatric Patients With GH Deficiency.","authors":"Satyaprakash Nayak, Michael P Wajnrajch, Joan Korth-Bradley, Carrie Turich Taylor, Marc Thomas, Aristides Maniatis, Cheri L Deal, Ron G Rosenfeld, José F Cara, Patanjali Ravva","doi":"10.1210/jendso/bvaf001","DOIUrl":"10.1210/jendso/bvaf001","url":null,"abstract":"<p><strong>Context: </strong>In patients with GH deficiency (GHD) receiving GH treatment, IGF-1 concentrations are used by physicians to monitor treatment safety and efficacy and guide dosing decisions. Somatrogon is a long-acting GH approved as a once-weekly treatment for pediatric GHD. Somatrogon administration results in characteristic changes in the IGF-1 profile, with values measured at 96 hours postdose representing mean IGF-1 concentrations that best reflect overall somatrogon exposure.</p><p><strong>Objective: </strong>To develop a simple method to enable physicians to predict mean IGF-1 concentrations following somatrogon dosing, based on a single IGF-1 measurement taken at any point during the 7-day dosing interval.</p><p><strong>Methods: </strong>Data from phase 2 and phase 3 somatrogon studies were used to develop a 2-compartment pharmacokinetic model with delayed first-order absorption. An indirect-response pharmacokinetic/pharmacodynamic model was applied to the predicted somatrogon concentrations, and model simulations were used to predict IGF-1 and IGF-1 SD score (SDS) levels for participants in both studies.</p><p><strong>Results: </strong>A total of 16,213 dosing records (from 42 and 109 participants in the phase 2 and 3 studies, respectively) were used for the simulations, generating predicted values for IGF-1 and IGF-1 SDS. Predicted values were scaled against the respective values at 96 hours (day 4). These values were used to create a table showing the adjustments required to predict mean IGF-1 and IGF-1 SDS values depending on time after dose.</p><p><strong>Conclusion: </strong>We developed a simple method enabling physicians to predict mean weekly IGF-1 values using IGF-1 values measured at any point in the dosing interval.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf001"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Value of Peer Mentoring in Advancing Science Careers: Lessons Learned From NR Impact.","authors":"Zeynep Madak-Erdogan, Rebecca B Riggins, Matthew J Sikora","doi":"10.1210/jendso/bvaf005","DOIUrl":"10.1210/jendso/bvaf005","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf005"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central Downregulation of S-Resistin Alleviates Inflammation in EWAT and Liver and Prevents Adipocyte Hypertrophy.","authors":"María Rodríguez, Eduardo Moltó, Rosario Serrano, Jorge Diaz-Rullo, Iván Parralejo, Diego Muñoz, Rosa María Andreu, Jennifer Seco, Nilda Gallardo, Antonio Andrés, Carmen Arribas, Cristina Pintado","doi":"10.1210/jendso/bvae224","DOIUrl":"10.1210/jendso/bvae224","url":null,"abstract":"<p><p>The hypothalamus integrates peripheral signals and modulates food intake and energy expenditure by regulating the metabolic function of peripheral tissues, including the liver and adipose tissue. In a previous study, we demonstrated that s-resistin, an intracellular resistin isoform highly expressed in the hypothalamus and upregulated during aging, is important in the central control of energy homeostasis, affecting mainly the peripheral response to insulin by still unknown mechanisms. Herein, using an intracerebroventricular injection of a specific lentiviral RNAi against s-resistin, we assessed, in the Wistar rat, the effects of central s-resistin downregulation on the expression and phosphorylation levels of intermediates involved in insulin signaling and the inflammatory response in epididymal white adipose tissue (eWAT) and liver. Additionally, we studied the imbalance of eWAT hypertrophy/hyperplasia remodeling. Our results indicate that central downregulation of s-resistin regulates insulin signaling cascade in a tissue-specific manner, reduces the inflammatory status both in the liver and eWAT, and prevents eWAT hypertrophy. Taken together, our results highlight the pivotal role of central s-resistin in maintaining metabolic homeostasis in AT and the liver. This suggests a direct association between its function and the modulation of the inflammatory response in these tissues.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvae224"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancies Between Sex Prediction and Fetal Sex After Prenatal Noninvasive Cell-Free DNA Screening.","authors":"Selma F Witchel, Aleksandar Rajkovic, Svetlana A Yatsenko","doi":"10.1210/jendso/bvaf007","DOIUrl":"10.1210/jendso/bvaf007","url":null,"abstract":"<p><p>In the last 10 years the field of prenatal diagnosis has been significantly reshaped followed by the implementation of noninvasive prenatal cell-free DNA (cfDNA) testing methodologies in clinical practice. Based on a superior performance and higher sensitivity and specificity than the former practice of biochemical markers screening, the American College of Obstetricians and Gynecologists and American College of Medical Genetics and Genomics recommend noninvasive prenatal cfDNA screening for trisomy 21, 18, 13, and sex chromosome aneuploidy to all pregnant people. While cfDNA screening is helpful in risk assessment for the most common autosomal trisomies, cfDNA also provides information about fetal sex chromosomes. Prediction of fetal sex is highly desired by the parents and also useful to healthcare providers for management of pregnancies that are at-risk for X-linked conditions. In fact, utilization of cfDNA screening has resulted in a significant number of referrals to evaluate discordant results for cfDNA sex prediction and appearance of fetal genitalia by prenatal ultrasound scan or at birth raising concerns about the fetus/infant atypical sex development known as a difference in sex development (DSD). In this mini-review, we outline principles and limitations of cfDNA technology, summarize recent findings related to cfDNA test performance in prediction of sex chromosome abnormalities and DSD conditions, define the technical and biological causes of discrepant results, provide recommendations to consolidate efforts by prenatal and clinical management teams in challenging situations, and discuss ethical considerations associated with fetal sex prediction and prenatal DSD diagnosis.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf007"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing ChatGPT's Capability in Addressing Thyroid Cancer Patient Queries: A Comprehensive Mixed-Methods Evaluation.","authors":"Matthew A Gorris, Reese W Randle, Corey S Obermiller, Johnson Thomas, David Toro-Tobon, Sophie Y Dream, Oliver J Fackelmayer, T K Pandian, Sarah E Mayson","doi":"10.1210/jendso/bvaf003","DOIUrl":"10.1210/jendso/bvaf003","url":null,"abstract":"<p><strong>Context: </strong>Literature suggests patients with thyroid cancer have unmet informational needs in many aspects of care. Patients often turn to online resources for their health-related information, and generative artificial intelligence programs such as ChatGPT are an emerging and attractive resource for patients.</p><p><strong>Objective: </strong>To assess the quality of ChatGPT's responses to thyroid cancer-related questions.</p><p><strong>Methods: </strong>Four endocrinologists and 4 endocrine surgeons, all with expertise in thyroid cancer, evaluated the responses to 20 thyroid cancer-related questions. Responses were scored on a 7-point Likert scale in areas of accuracy, completeness, and overall satisfaction. Comments from the evaluators were aggregated and a qualitative analysis was performed.</p><p><strong>Results: </strong>Overall, only 57%, 56%, and 52% of the responses \"agreed\" or \"strongly agreed\" that ChatGPT's answers were accurate, complete, and satisfactory, respectively. One hundred ninety-eight free-text comments were included in the qualitative analysis. The majority of comments were critical in nature. Several themes emerged, which included overemphasis of diet and iodine intake and its role in thyroid cancer, and incomplete or inaccurate information on risks of both thyroid surgery and radioactive iodine therapy.</p><p><strong>Conclusion: </strong>Our study suggests that ChatGPT is not accurate or reliable enough at this time for unsupervised use as a patient information tool for thyroid cancer.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvaf003"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appetite-related Gut Hormone Responses to Feeding Across the Life Course.","authors":"Adrian Holliday, Katy Horner, Kelsie O Johnson, Aygul Dagbasi, Daniel R Crabtree","doi":"10.1210/jendso/bvae223","DOIUrl":"10.1210/jendso/bvae223","url":null,"abstract":"<p><p>Appetite-related hormones are secreted from the gut, signaling the presence of nutrients. Such signaling allows for cross-talk between the gut and the appetite-control regions of the brain, influencing appetite and food intake. As nutritional requirements change throughout the life course, it is perhaps unsurprising that appetite and eating behavior are not constant. Changes in appetite-related gut hormones may underpin these alterations in appetite and eating. In this article, we review evidence of how the release of appetite-related gut hormones changes throughout the life course and how this impacts appetite and eating behaviour. We focus on hormones for which there is the strongest evidence of impact on appetite, food intake, and body weight: the anorexigenic glucagon like peptide-1, peptide tyrosine tyrosine, and cholecystokinin, and the orexigenic ghrelin. We consider hormone concentrations, particularly in response to feeding, from the very early days of life, through childhood and adolescence, where responses may reflect energy requirements to support growth and development. We discuss the period of adulthood and midlife, with a particular focus on sex differences and the effect of menstruation, pregnancy, and menopause, as well as the potential influence of appetite-related gut hormones on body composition and weight status. We then discuss recent advancements in our understanding of how unfavorable changes in appetite-related gut hormone responses to feeding in later life may contribute to undernutrition and a detrimental aging trajectory. Finally, we briefly highlight priorities for future research.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 2","pages":"bvae223"},"PeriodicalIF":3.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}