Journal of the Endocrine Society最新文献

{"title":"Growth Response to Weekly Somapacitan Therapy in Children With GH Deficiency Is Related to GH Thresholds in GH Stimulation Testing.","authors":"Philippe F Backeljauw, Claudia Boettcher, Michael Højby, Nicky Kelepouris, Mathias Lerbech Jeppesen, Jun Mori, Alberto Pietropoli, Bradley S Miller","doi":"10.1210/jendso/bvaf038","DOIUrl":"10.1210/jendso/bvaf038","url":null,"abstract":"<p><strong>Context: </strong>The lack of a severity definition and standardized GH cutoff level for GH deficiency (GHD) diagnosis in children leads to ambiguity in the interpretation of GH stimulation tests and treatment recommendations.</p><p><strong>Objective: </strong>To investigate treatment response differences among children with GHD treated with daily GH (somatropin) (year 1) or once-weekly somapacitan (years 1 and 2) based on GH peak concentrations assessed at diagnosis.</p><p><strong>Methods: </strong>This was a subgroup analysis of 200 patients with GHD aged ≥2.5 years participating in the REAL4 randomized, phase 3 trial. Height velocity (HV; cm/year) and changes in height SD score (SDS) and IGF-I SDS from baseline were compared for 3 GH peak groups: ≤ 3, >3 to <7, and ≥7 to ≤10 μg/L.</p><p><strong>Results: </strong>The ≤3 μg/L GH peak concentration group had the greatest HV at weeks 52 and 104. Mean change in height SDS ranged from 1.89 to 1.59, 1.17 to 1.06, and 0.92 to 1.07 at week 52 and 2.79 to 2.30, 1.64 to 1.54, and 1.33 to 1.51 at week 104 for the 2 treatment groups across the 3 GH peak concentrations, respectively. Mean change in IGF-I SDS ranged from 3.13 to 3.01, 2.11 to 1.96, and 1.87 to 2.26 at week 52 and from 2.81 to 2.11, 1.85 to 1.62, and 1.28 to 1.71 at week 104 for the 3 GH peak concentrations.</p><p><strong>Conclusion: </strong>Patients with GHD in the ≤3 μg/L GH peak concentration group had greater HV and greater changes in height SDS and IGF-I SDS from baseline.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf038"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657609","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":"Composite Pheochromocytoma-Paraganglioma With Ganglioneuroma: A Dual-Center Clinical Experience.","authors":"Shubham Agarwal, Hussam Alkaissi, Karel Pacak, Jorge Esteban Mosquera Izurieta, Alan P Dackiw, Sarah C Oltmann, Fiemu Nwariaku, Liwei Jia, Mary Grace Roden, Oksana Hamidi","doi":"10.1210/jendso/bvaf036","DOIUrl":"10.1210/jendso/bvaf036","url":null,"abstract":"<p><strong>Context: </strong>Cells derived from neural crest populate several organs. A particular precursor cell, sympathogonia, gives rise to pheochromoblasts and neuroblasts. Due to common origin, tumors originating from pheochromoblasts, such as pheochromocytoma (PHEO) and paraganglioma (PGL), may rarely coexist with ganglioneuroma (GN).</p><p><strong>Objective: </strong>We evaluated clinical, biochemical, and radiological characteristics of patients with composite PHEO/PGL and GN (PPGL-GN) and compared them to patients with PHEO.</p><p><strong>Methods: </strong>In this retrospective, dual-center, observational, case-control study, we identified patients with PPGL-GN. Similarly, we identified a control group of patients with PHEO who underwent laparoscopic adrenalectomy. All diagnoses were confirmed on histology. Descriptive statistics were used to summarize demographic and clinical data.</p><p><strong>Results: </strong>We identified 19 consecutive patients with PPGL-GN and 86 patients with PHEO. Patients with PPGL-GN, compared to those with PHEO, were younger (aged 46.0 vs 50.8 years; <i>P</i> = .03), had higher rate of underlying genetic disorders (47.4% vs 23.2%; <i>P</i> = .03), and had fewer functioning tumors (89.5% vs 100%; <i>P</i> = .002). There was no difference in the median radiological tumor size or the precontrast computed tomography density. Disease recurrence (at another site) was noted in 15.8% of PPGL-GN patients who had a median follow up of 14.6 months, as opposed to no disease recurrence in patients with PHEO. There was no documented recurrence at the tumor bed and no metastasis in both groups.</p><p><strong>Conclusion: </strong>Patients with PPGL-GN were younger and had a higher occurrence of underlying genetic disorders compared to PHEO. However, PPGL-GN was radiologically indistinguishable from PHEO. The higher observed disease recurrence of PPGL-GN reinforces vigilant postoperative follow-up.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf036"},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605547","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":"Marrow Adiposity Content and Composition Are Not Associated With Incident Fragility Fractures in Postmenopausal Women: The ADIMOS Fracture Study.","authors":"Cécile Philippoteaux, Sammy Badr, Daniela Lombardo, Emeline Cailliau, Stefan Ruschke, Dimitrios C Karampinos, Anne Cotten, Julien Paccou","doi":"10.1210/jendso/bvaf033","DOIUrl":"10.1210/jendso/bvaf033","url":null,"abstract":"<p><strong>Context: </strong>Noninvasive measurement of bone marrow adipose tissue using magnetic resonance imaging and proton density fat fraction (PDFF) may enhance clinical fractures prediction in postmenopausal women.</p><p><strong>Objective: </strong>This study aimed to assess the association between PDFF measurements and clinical fracture incidence.</p><p><strong>Methods: </strong>A longitudinal study was conducted. Postmenopausal women with recent osteoporotic fractures (<12 months) and with osteoarthritis without fractures were included. Lumbar spine and proximal femur PDFFs were measured at baseline using water-fat imaging (WFI) and dual-energy x-ray absorptiometry scans. Clinical fractures were recorded during follow-up.</p><p><strong>Results: </strong>Among 195 participants (mean age 67.4 ± 10.0 years, body mass index 27.2 ± 5.9 kg/m²), the PDFF (WFI-based) was higher at the proximal femur, particularly at the femoral head (90.0% ± 4.9%), compared to the lumbar spine (57.8% ± 9.6%). Over a mean follow-up period of 37.2 ± 11.6 months, 7 participants died, 29 (14.9%) experienced incident clinical fractures, and 1 was lost to follow-up. The lack of an association between WFI-based PDFFs and the incidence of clinical fractures was demonstrated regardless of the region of measurement (hazard ratio [HR] = 0.95 [95% CI 0.67-1.35], <i>P</i> = 0.77 at the lumbar spine, HR = 1.07 [95% CI 0.71-1.63], <i>P</i> = 0.74 at the femoral neck). Stepwise regression analysis did not alter these findings, and the variable \"recent osteoporotic fractures\" was found to be significantly associated with incident clinical fractures.</p><p><strong>Conclusion: </strong>This study found no evidence of a relationship between PDFF and clinical fracture incidence in postmenopausal women. Further studies are necessary involving larger cohorts and longer follow-up periods.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf033"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605549","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":"Resting Energy Expenditure and Metabolic Features in Children With Septo-Optic Dysplasia.","authors":"David J Cullingford, Jacqueline A Curran, Mary B Abraham, Aris Siafarikas, A Marie Blackmore, Jenny Downs, Catherine S Y Choong","doi":"10.1210/jendso/bvaf031","DOIUrl":"10.1210/jendso/bvaf031","url":null,"abstract":"<p><strong>Context: </strong>Septo-optic dysplasia (SOD) is a major cause of congenital hypopituitarism and is known to be associated with overweight and obesity in up to 44% of children. Given the role of the hypothalamus in hormonal regulation, we sought to assess the association of resting energy expenditure (REE), appetite and physical activity with SOD.</p><p><strong>Objective: </strong>To characterize REE and other metabolic features in patients with SOD and evaluate relationships with elevated body mass index (BMI).</p><p><strong>Methods: </strong>Children with SOD above 5 years of age attending Perth Children's Hospital participated. A CosMED Q-NRG indirect calorimeter was used to calculate mean measure REE (mREE). This was compared with predictive REE (pREE) based on the Schofield equation to determine mREE/pREE quotient. A BMI z-score >1 was considered elevated. Parents/carers completed a questionnaire about pituitary function, the Hyperphagia Questionnaire and the Sleep Disturbances Scale for Children (SDSC).</p><p><strong>Results: </strong>Twenty-six participants underwent testing (9 female, mean age 12.1 years) with 11 having elevated BMI and 15 with pituitary hormone deficiencies. Mean mREE was 1309 kcal/day (838-1732), mREE/pREE quotient was 88.8% ± 10.1. mREE/pREE quotient was similar in those with elevated BMI compared with normal BMI (83.3% ± 12.5 vs 92.1% ± 7.2, <i>P</i> = .068). Those with midline defects had a higher mREE/pREE quotient (91.8% ± 8.1 vs 80.4% ± 11.3, <i>P</i> = .026). Hyperphagia and SDSC scores were similar between BMI groups. Hyperphagia domain scores were higher in children with multiple hypopituitarism, pituitary structural defects, and normal septum pellucidum (<i>P</i> = .044, .042, and .033, respectively).</p><p><strong>Conclusion: </strong>Children with SOD had lower mREE than predicted and hyperphagia scores were higher in those with biochemical or structural pituitary changes, suggesting that hypothalamic dysfunction could drive BMI elevation in SOD. Indirect calorimetry may be used to guide the management of overweight and obesity in SOD.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf031"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657535","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":"Disease-specific Mortality of Differentiated Thyroid Cancer With Distant Metastases.","authors":"Ali Howaidi, Anwar Alswailem, Abdulrhman Hakami, Afnan Hadadi, Deema Alturki, Fayha Abothenain, Lulu Alobaid, Najla Saleh Ewain, Avaniyapuram Kannan Murugan, Ali S Alzahrani","doi":"10.1210/jendso/bvaf034","DOIUrl":"10.1210/jendso/bvaf034","url":null,"abstract":"<p><strong>Overview: </strong>Distant metastases (DM) are the major cause of death in patients with differentiated thyroid cancer (DTC). This study aimed to investigate the predictors of DM-associated mortality.</p><p><strong>Patients and methods: </strong>We identified 154 thyroid cancer (TC) patients with DM from our institution's tumor registry. We excluded anaplastic (n = 21) and medullary TC (n = 32) and patients with inadequate data (n = 15). The remaining 86 patients with DTC were studied. These include 57 females (66.3%) and 29 males (33.7%) with a median age of 53.5 years [interquartile range (IQR) 45-65]. All patients underwent thyroidectomy; 58 (67.4%) had neck dissection, and 81 (94.2%) received radioactive iodine (I-131) ablation/therapy.</p><p><strong>Results: </strong>Lung metastases were the most common, occurring in 91.9%; skeletal metastases occurred in 58.1%, brain metastases in 9.3%, and multiple-organ DM in 58%. The management of DM included surgery, 1 or more doses of I-131, external beam radiotherapy, and multikinase inhibitors. Over a median follow-up of 84 months (IQR 35.5-118) for the whole cohort, 47 patients succumbed to their disease (disease-specific mortality 54.7%). Factors associated with mortality were increasing age (<i>P</i> = .001) and bone metastases (<i>P</i> < .0001). These factors remained significant in multivariate analyses [for age, <i>P</i> = .009, hazard ratio (HR) 1.030, 95% confidence interval (CI) 1.007-1.053] and for bone metastases (<i>P</i> = .017, HR 2.58, 95% CI 1.19-5.6).</p><p><strong>Conclusion: </strong>DM from DTC are associated with ∼ 55% mortality at a median survival of 47 months. Increasing age and skeletal metastases are predictors of an increased risk of mortality.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf034"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605548","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":"Adult Growth Hormone Deficiency (AGHD) and Outcomes (NordiNet and ANSWER).","authors":"John D Carmichael, Atil Y Kargi, Laura Dichtel, Nicky Kelepouris, Navid Nedjatian, Moshe Fridman, Matthias M Weber","doi":"10.1210/jendso/bvaf026","DOIUrl":"10.1210/jendso/bvaf026","url":null,"abstract":"<p><p>Adult growth hormone deficiency (AGHD) is a rare disease with both physiological and psychological effects for untreated patients. AGHD symptoms can improve over time with GH treatment. Here we have analyzed the long-term effectiveness and safety of short-acting GH replacement therapy (GHRT) in treatment naïve and nonnaïve patients with AGHD using real-world data from the NordiNet® International Outcome Study and American Norditropin® Studies: Web Enabled Research Program. Outcomes were compared between 3 age groups, comprised of patients aged 18 to 29 years, 30 to 39 years, and 40 to 59 years. The safety outcome was the incidence of nonserious and serious adverse reactions and serious adverse events by age group. Efficacy outcomes included mean GH exposure by age group alone, by sex and age group, or based on estrogen usage in female patients; IGF-I SD score (SDS) levels by sex and age group; mean glycated hemoglobin by sex and age group; and mean non-high-density lipoprotein cholesterol by sex and age group. The incidence rates of adverse events and reactions did not statistically differ between the 3 groups. Mean IGF-I SDS levels reached a normal range (-2 to 2) in ≥80% of patients from all groups in the effectiveness analysis set by year 2. Together with previous reports of older patients, these results support the real-world safety and efficacy of short-acting GHRT among all ages of patients with AGHD.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf026"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615726","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":"Clinical Features and Plasma Metabolites Analysis in Obese Chinese Children With Nonalcoholic Fatty Liver Disease.","authors":"Xiaoxiao Liu, Shifeng Ma, Jing Li, Mingkun Song, Yun Li, Yingyi Qi, Fei Liu, Zhongze Fang, Rongxiu Zheng","doi":"10.1210/jendso/bvaf032","DOIUrl":"10.1210/jendso/bvaf032","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the clinical characteristics and plasma metabolites of nonalcoholic fatty liver disease (NAFLD) in obese Chinese children and to develop machine learning-based NAFLD diagnostic models.</p><p><strong>Methods: </strong>We recruited 222 obese children aged 4 to 17 years and divided them into an obese control group and an obese NAFLD group based on liver ultrasonography. Mass spectrometry metabolomic analysis was used to measure 106 metabolites in plasma. Binary logistic regression was used to identify NAFLD-related clinical variables. NAFLD-specific metabolites were illustrated via volcano plots, cluster heatmaps, and metabolic network diagrams. Additionally, we applied 8 machine learning methods to construct 3 diagnostic models based on clinical variables, metabolites, and clinical variables combined with metabolites.</p><p><strong>Results: </strong>By evaluating clinical variables and plasma metabolites, we identified 16 clinical variables and 14 plasma metabolites closely associated with NAFLD. We discovered that the level of 18:0 to 22:6 phosphatidylethanolamines was positively correlated with the levels of total cholesterol, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio, whereas the level of glycocholic acid was positively correlated with the levels of alanine aminotransferase, gamma-glutamyl transferase, insulin, and the homeostasis model assessment of insulin resistance. Additionally, we successfully developed 3 NAFLD diagnostic models that showed excellent diagnostic performance (areas under the receiver operating characteristic curves of 0.917, 0.954, and 0.957, respectively).</p><p><strong>Conclusions: </strong>We identified 16 clinical variables and 14 plasma metabolites associated with NAFLD in obese Chinese children. Diagnostic models using these features showed excellent performance, indicating their potential for diagnosis.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf032"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657608","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":"Azoospermia/Oligozoospermia and Prostate Cancer Are Increased in Families of Women With Primary Ovarian Insufficiency.","authors":"Kristina Allen-Brady, Samantha Kodama, Lauren E Verrilli, Joemy M Ramsay, Erica B Johnstone, Joshua J Horns, Benjamin R Emery, Lisa Cannon-Albright, Kenneth I Aston, James M Hotaling, Corrine K Welt","doi":"10.1210/jendso/bvaf030","DOIUrl":"10.1210/jendso/bvaf030","url":null,"abstract":"<p><strong>Background: </strong>Nonobstructive azoospermia (NOA) and primary ovarian insufficiency (POI) have common genetics that may also predispose patients to cancer risk.</p><p><strong>Objectives: </strong>We hypothesized that NOA or severe oligozoospermia and the risk of male cancers would be higher in families of women with POI.</p><p><strong>Methods: </strong>Women with POI were identified using International Classification of Disease codes in electronic medical records (1995-2021) from 2 major healthcare systems in Utah and reviewed for accuracy. Using genealogy information in the Utah Population Database, women with POI (n = 392) and their relatives were included if there were at least 3 generations of ancestors available. Men with NOA or severe oligozoospermia (≤5 million/mL) from the Subfertility Health and Assisted Reproduction and the Environment Study were identified in these families and risk was calculated in relatives compared to population rates. The relative risk of prostate and testicular cancer was examined using the Utah Cancer Registry.</p><p><strong>Results: </strong>There was an increased risk of NOA/severe oligozoospermia in relatives of women with POI among first- (relative risk 2.8 [95% confidence interval 1.1, 6.7]; <i>P</i> = .03), second- (3.1 [1.1, 6.7]; <i>P</i> = .02), and third-degree relatives (1.8 [1.1, 3.1]; <i>P</i> = .03). In these families with POI and NOA/oligozoospermia (n = 21), prostate cancer risk was higher in first- (3.5 [1.1, 8.1]; <i>P</i> = .016) and second-degree relatives (3.1 [1.9, 4.8]; <i>P</i> = .000008).</p><p><strong>Conclusion: </strong>The data demonstrate excess familial clustering of severe spermatogenic impairment compared to matched population rates, along with higher prostate cancer risk in relatives of women with POI. These findings support a common genetic contribution to POI, spermatogenic impairment, and prostate cancer.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf030"},"PeriodicalIF":3.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566636","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":"Secretagogin Is Highly Expressed in Enteroendocrine K Cells and Plays a Critical Role in Nutrient-Induced GIP Secretion.","authors":"Xinyu Liu, Xuan Liu, Yuanyuan Hu, Xin Wang, Xin Yang, Bin Yan, Yiting Zhou, Lingzhi Zhou, Gang Fan, Jing Yang","doi":"10.1210/jendso/bvaf022","DOIUrl":"10.1210/jendso/bvaf022","url":null,"abstract":"<p><strong>Context: </strong>Incretin hormones, primarily composed of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are secreted by enteroendocrine cells (EECs) and play crucial roles in maintaining blood glucose homeostasis. Notably, GIP accounts for two-thirds of the entire incretin effect. However, the secretion and function of GIP are impaired in individuals with type 2 diabetes mellitus (T2DM), and the regulatory mechanisms governing GIP secretion remain unclear.</p><p><strong>Objective: </strong>Our study aims to explore the role of an EEC-enriched protein, Secretagogin (SCGN), in the regulation of GIP secretion.</p><p><strong>Methods: </strong>We collected duodenal tissues from both humans and mice to observe the colocalization of SCGN and GIP in EECs. Additionally, we utilized human cohorts and gene-edited mouse models to investigate the effect of SCGN on GIP secretion. Our study included 128 subjects, comprising 64 individuals diagnosed with newly onset diabetes and 64 age- and sex-matched nondiabetic healthy controls. At the animal level, we employed leptin receptor-deficient (db/db) mice and <i>Scgn</i> knockout mice for our investigations.</p><p><strong>Results: </strong>Our findings indicate that SCGN is abundantly expressed in GIP-producing K cells within the intestinal epithelium of both humans and mice. We observed a positive correlation between SCGN and GIP levels in postprandial states among patients with T2DM, db/db mice, and their healthy controls. Notably, <i>Scgn</i> knockout mice exhibited decreased GIP and insulin secretion. However, SCGN deficiency did not affect K-cell number, GIP mRNA expression, or intestinal morphology.</p><p><strong>Conclusion: </strong>Collectively, these findings demonstrate that SCGN is a key regulator of nutrient-induced GIP secretion.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 3","pages":"bvaf022"},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515936","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":"Long-term Outcomes of Feminizing Genitoplasty in DSD: Genital Morphology, Sensitivity, Sexual Function, and Satisfaction.","authors":"Min Jeong Bag, Marlene Inacio, Tânia Aparecida Sartori Sanchez Bachega, Rafael Loch Batista, Guiomar Madureira, Elaine Maria Frade Costa, Sorahia Domenice, Berenice Bilharinho Mendonca, Francisco Tibor Dénes, Maria Helena Palma Sircili","doi":"10.1210/jendso/bvaf014","DOIUrl":"10.1210/jendso/bvaf014","url":null,"abstract":"<p><strong>Context: </strong>Understanding long-term outcomes and patient satisfaction with feminizing genitoplasty (FG) in patients with differences of sexual development (DSD) is crucial for optimizing treatment protocols.</p><p><strong>Objective: </strong>To evaluate long-term morphological and functional results and patients' satisfaction in a cohort of DSD patients submitted to FG.</p><p><strong>Design: </strong>Cross-sectional and retrospective cohort study conducted from 1965 to 2016 with follow-up assessments.</p><p><strong>Setting: </strong>Tertiary care center.</p><p><strong>Patients or other participants: </strong>Sixty DSD female patients, including 36 with congenital adrenal hyperplasia (CAH) and 24 with non-CAH DSD etiology, who underwent FG.</p><p><strong>Interventions: </strong>FG procedures were performed, and results were analyzed based on age at surgery and surgical techniques used.</p><p><strong>Main outcome measures: </strong>Surgical results, genital sensitivity, sexual function, and patient satisfaction.</p><p><strong>Results: </strong>Ninety-one percent of patients had normal clitoral size, and 85% had separated perineal orifices. Three patients with persistent urogenital sinus did not report symptoms. Genital sensitivity to mechanical and vibratory stimuli was similar to control groups. No CAH patients experienced overall sexual dysfunction, while 3 non-CAH patients and 4 control women reported reduced sexual desire and arousal. Eighty-nine percent of patients preferred surgery during childhood, and 97% were satisfied with their surgical outcomes.</p><p><strong>Conclusion: </strong>FG outcomes in this cohort were satisfactory, with no significant impact on genital sensitivity or sexual function. Most patients preferred early surgery and reported high satisfaction with the results. Further studies are needed to confirm these findings in broader populations.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 3","pages":"bvaf014"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458378","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}