Journal of the Endocrine Society最新文献

{"title":"Recombinant TSH Performs as Well as Thyroid Hormone Withdrawal for Iodine-131 Therapy With Dosimetry for Thyroid Cancer.","authors":"Anupam Kotwal, Abbey Fingeret, Jarod Hamsa, Dana Awad, Craig Johnson, Frank Rutar, Carrie Carson, Anery Patel, Whitney Goldner","doi":"10.1210/jendso/bvaf050","DOIUrl":"10.1210/jendso/bvaf050","url":null,"abstract":"<p><strong>Introduction: </strong>Dosimetry helps calculate the optimal iodine-131 (I-131) dose for treating metastatic differentiated thyroid cancer (DTC). We aimed to evaluate if recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) are equivalent methods of preparation for dosimetry-guided I-131 therapy in metastatic DTC.</p><p><strong>Methods: </strong>We performed a retrospective cohort study of 51 adults with metastatic DTC who received I-131 with dosimetry from 2010 through 2022. Gamma camera and blood activity measurements were taken following the pretherapeutic I-131 dose. Statistical analysis compared rhTSH and THW groups; <i>P</i> < .05 was considered significant.</p><p><strong>Results: </strong>Fifty-one adults undergoing 55 I-131 dosimetry-guided treatments were included: 22 by rhTSH and 33 by THW. The median age was lower (<i>P</i> = .0008), and the proportion of stage IV (<i>P</i> = .009) was higher in rhTSH compared to the THW group. The terminal effective half-life at 24 to 48 hours in the whole body was longer in rhTSH compared to THW group (21.9 vs 17.1 hours; <i>P</i> = .014), but this difference was less significant when limited to the n = 37 metastatic cases (<i>P</i> = .046) and not different for red marrow effective half-life. The calculated allowed I-131 dose was lower in rhTSH compared to THW group (187.5 mCi vs 259.9 mCi; <i>P</i> = .0000). Thyroglobulin was higher during treatment in the rhTSH group (<i>P</i> = .031), whereas its reduction at 3 months was not different after adjusting for age and stage.</p><p><strong>Conclusion: </strong>rhTSH is noninferior to THW in preparation for I-131 dosimetry. Compared to THW, rhTSH results in lower calculated allowed I-131 dose after dosimetry, which could translate to fewer side effects or impact on quality of life.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf050"},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780370","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":"Predicting Glycemic Control in Patients With Impaired Fasting Glucose With Fasting Respiratory Exchange Ratio.","authors":"Andrea Foppiani, Federica Sileo, Francesca Menichetti, Giorgia Pozzi, Silvia Gallosti, Ramona De Amicis, Alessandro Leone, Simona Bertoli, Alberto Battezzati","doi":"10.1210/jendso/bvaf047","DOIUrl":"10.1210/jendso/bvaf047","url":null,"abstract":"<p><strong>Context: </strong>Impaired metabolic flexibility is associated with prediabetes. However, its assessment with reference methods is impractical in routine clinical practice.</p><p><strong>Objective: </strong>This study investigates the relationship between fasting respiratory exchange ratio (RER), measured through indirect calorimetry, and glucose metabolism in individuals with prediabetes.</p><p><strong>Methods: </strong>The study involved 2 cohorts: (1) a cross-sectional cohort of 10 176 individuals to assess the association between fasting RER and glucose metabolism parameters, and (2) a matched longitudinal cohort of 86 patients with impaired fasting glucose, categorized into fat oxidation (RER < 0.775) and glucose oxidation (RER > 0.925) groups, to evaluate the impact of fasting RER on impaired fasting glucose resolution and fasting glucose after a 1-year lifestyle intervention.</p><p><strong>Results: </strong>In the cross-sectional cohort, a higher fasting RER was associated with higher fasting glucose, insulin, and Homeostatic Model Assessment for Insulin Resistance. In the longitudinal cohort, the fat oxidation group showed a greater reduction in fasting glucose (+5.9; 95% CI 1.4, 10; <i>P</i> = .011) and a higher probability of achieving normal fasting glycemia (log(odds ratio) -0.89; 95% CI -1.8, -0.03; <i>P</i> = .046) after the intervention, despite similar weight loss between groups.</p><p><strong>Conclusion: </strong>Our findings suggest that fasting RER, a readily accessible clinical measure, can provide valuable insights into glucose metabolism and impaired fasting glucose resolution. A lower fasting RER, indicative of a greater capacity for fat oxidation, is associated with improved glycemic control after a lifestyle intervention.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf047"},"PeriodicalIF":3.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780361","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":"The Role of Estrogen and ER Stress in Glycemic Regulation in the Sexually Dimorphic TALLYHO/JngJ Mouse Model of Diabetes.","authors":"Monica De Paoli, Zinal Patel, Susanna Fang, Geoff H Werstuck","doi":"10.1210/jendso/bvaf048","DOIUrl":"10.1210/jendso/bvaf048","url":null,"abstract":"<p><p>The global incidence of diabetes mellitus is increasing, causing a heavy burden on health care management and costs. Sex differences in the incidence and prevalence of diabetes mellitus do exist, with premenopausal women being protected from developing this disease, compared to men or postmenopausal women. The mechanisms underlying these differences are not yet known and experimental animal models can significantly advance our understanding of these processes. In this study we characterized a mouse model of polygenic type 2 diabetes, the TALLYHO/JngJ mouse, which shows sexual dimorphism in blood glucose regulation. Male TALLYHO/JngJ mice develop chronic hyperglycemia by 5 weeks of age, while females remain normoglycemic. We analyzed the role of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) in the development of hyperglycemia in this mouse model. Additionally, we evaluated the effect of estrogen depletion in female TALLYHO/JngJ mice through ovariectomies. Ovariectomized female mice and males become chronically hyperglycemic (fasting blood glucose threshold >15 mM) and show significantly increased expression of GRP78/GRP94, markers of the adaptive unfolded protein response (UPR). GADD153/CHOP, a marker of the apoptotic UPR, is significantly increased in ovariectomized female mice. Treatment with a chemical chaperone 4-PBA, an ER stress alleviator, improves but does not normalize blood glucose levels in male and ovariectomized female TALLYHO/JngJ mice. Together, these findings support a protective role for estrogen and identify the UPR as a pathway through which estrogen may maintain pancreatic beta cell health.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf048"},"PeriodicalIF":3.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795951","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":"Osilodrostat Treatment of Cushing Syndrome in Real-World Clinical Practice: Findings From the ILLUSTRATE study.","authors":"Maria Fleseriu, Richard J Auchus, Wenyu Huang, Joanna L Spencer-Segal, Kevin C J Yuen, Kelley C Dacus, Julianne Padgett, Elizabeth K Babler, Ashis K Das, Cynthia Campos, Michael S Broder, Adriana G Ioachimescu","doi":"10.1210/jendso/bvaf046","DOIUrl":"https://doi.org/10.1210/jendso/bvaf046","url":null,"abstract":"<p><strong>Context: </strong>In clinical trials, osilodrostat (11β-hydroxylase inhibitor) effectively reduced cortisol levels in patients with endogenous Cushing syndrome (CS).</p><p><strong>Objectives: </strong>A real-world study (ILLUSTRATE) was conducted evaluating osilodrostat use in patients with various etiologies of CS in the United States.</p><p><strong>Methods: </strong>A retrospective chart-review study was conducted of adults with CS treated with osilodrostat between May 1, 2020, and October 29, 2021.</p><p><strong>Results: </strong>A total of 42 patients (Cushing disease, n = 34; CS due to adrenal adenoma, n = 5; ectopic adrenocorticotropin syndrome [EAS], n = 3) were included. Starting doses were 2 mg twice daily in 27/42 patients (64.3%), maintenance doses were 2 mg twice daily in 6 of 9 patients (66.7%) attaining them. During osilodrostat treatment, urinary free cortisol (UFC) decreased below the upper limit of normal (ULN) in 14 of 20 patients (70.0%) with pretreatment UFC greater than the ULN. Osilodrostat response was observed across a range of doses (2-20 mg/day). In Cushing disease, median UFC and late-night salivary cortisol decreased from 3.03 and 2.39 × ULN, respectively, to 0.71 and 1.13 × ULN at last assessment in those with available data (n = 17 and 8, respectively). UFC decreased in all patients with adrenal CS or EAS with available data (n = 2 each). There were no unexpected safety signals; the most common adverse events (incidence ≥20%) were fatigue, nausea, and lower-extremity edema. Glucocorticoid withdrawal syndrome and/or adrenal insufficiency were reported in 12 of 42 patients (28.6%) after osilodrostat initiation, resulting in treatment discontinuation in 4.</p><p><strong>Conclusion: </strong>In routine practice with dosing individualized according to clinical condition, response, and tolerability, osilodrostat was effective and well tolerated regardless of CS etiology and severity.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf046"},"PeriodicalIF":3.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031939","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":"First Trimester Hematological Indices in Gestational Diabetes Mellitus: A Meta-Analysis.","authors":"Faegheh Firouzi, Fahimeh Ramezani Tehrani, Hojat Shaharki, Maryam Mousavi, Nahid Moradi, Marzieh Saei Ghare Naz","doi":"10.1210/jendso/bvaf043","DOIUrl":"10.1210/jendso/bvaf043","url":null,"abstract":"<p><strong>Context: </strong>The association between blood parameters and gestational diabetes (GDM) is of renewed interest. Some blood cell parameters are assumed to be associated with GDM.</p><p><strong>Objective: </strong>This meta-analysis was performed to assess the association of hematological indices in the first trimester of pregnancy and later development of GDM.</p><p><strong>Methods: </strong>A comprehensive database search, including PubMed, Web of Science, Epistemonikos, Scopus, Scientific Information Database, and Magiran, was conducted to identify potential peer-reviewed publications. The PECO framework was applied to evaluate the eligibility of all included studies. Standardized mean differences (95% CI), were calculated. Additionally, pooled odds ratios, summary estimates of sensitivity and specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) were determined.</p><p><strong>Results: </strong>The meta-analysis encompassed 33 studies involving a total of 247 107 pregnant women. Compared to control groups, GDM groups exhibited statistically significantly higher hemoglobin levels (standard mean difference: 0.50, 95% CI: 0.39-0.62), red blood cell (RBC) (0.23, 0.15-0.32), and hematocrit (0.44, 0.34-0.55). The pooled adjusted estimate (aOR:1.02, 1.006-1.03) indicated that the hemoglobin levels were significantly associated with an increased risk of GDM. GDM groups had significantly higher platelet count (0.280, 0.16-0.39) and white blood cells (WBC) counts, as well as (0.482, 0.377-0.58), lymphocytes (0.12, 0.025-0.22), neutrophils (0.541:0.404-0.679), and neutrophil-lymphocyte ratio (0.31, 0.20-0.43). In distinguishing women with GDM from the control group, the DOR was found to be 3.21 for the hemoglobin and 2.94 for the mean platelet volume.</p><p><strong>Conclusion: </strong>Higher levels of RBC, platelet, and WBC counts during the first trimester of pregnancy were observed in women who subsequently developed GDM compared to control groups.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf043"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764266","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":"Response to Letter to the Editor From Luis Del Carpio-Orantes: [Impact of Surreptitious Glucocorticoids in Over-the-counter Arthritis Supplements].","authors":"Kevin S Wei, Carolina R Hurtado, Trevor E Angell","doi":"10.1210/jendso/bvaf045","DOIUrl":"10.1210/jendso/bvaf045","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf045"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013364","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":"Recognition of Reviewers.","authors":"","doi":"10.1210/jendso/bvaf010","DOIUrl":"https://doi.org/10.1210/jendso/bvaf010","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf010"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605550","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":"Recognition of Reviewers.","authors":"","doi":"10.1210/jendso/bvaf010","DOIUrl":"https://doi.org/10.1210/jendso/bvaf010","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 4","pages":"bvaf010"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031935","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":"Real-world Outcome of Vosoritide Treatment in Children With Achondroplasia: A 12-month Retrospective Observational Study.","authors":"Susanna Reincke, Oliver Semler, Shino Junghänel-Welzing, Stefanie Stasek, Mirko Rehberg, Eva Pfeiffer, Heike Hoyer-Kuhn","doi":"10.1210/jendso/bvaf041","DOIUrl":"10.1210/jendso/bvaf041","url":null,"abstract":"<p><strong>Context: </strong>Vosoritide is the first approved targeted therapy for achondroplasia (ACH) based on increased annualized growth velocity in clinical trials. The aim of our project was an assessment of the real-world setting and treatment with vosoritide.</p><p><strong>Design: </strong>This was a 12-month, retrospective observational study on an inception cohort of 34 patients with ACH treated with vosoritide.</p><p><strong>Patients and methods: </strong>Thirty-four patients with ACH (22 males; aged 2.8 to 15.3 years at treatment initiation) who received vosoritide treatment for at least 12 months at a specialized clinic for skeletal dysplasia in childhood were included in the analysis. Auxological measurements at baseline and after 12 months of therapy were converted into disease-specific (ACH) and general population [Centers for Disease Control and Prevention (CDC)] z-scores. Physical function assessed by a 6-minute walk test was converted into z-scores and compared to an unaffected reference cohort.</p><p><strong>Results: </strong>After 12 months of treatment, both ACH and CDC height z-scores showed significant increases, with mean changes (mean ± SD) of 0.52 ± 0.35 and 0.38 ± 0.44, respectively (both <i>P</i> < .0001). The annualized growth velocity exceeded reference values for untreated children with ACH. No significant changes were observed in body mass index, upper to lower body segment ratio (sitting height/height), or head circumference. The 6-minute walking distance improved, with z-scores increasing from -2.00 ± 1.12 to -1.39 ± 1.23 (<i>P</i> = .0215).</p><p><strong>Conclusion: </strong>In a real-world setting, children with ACH showed significant improvements in growth and physical function after 12 months of treatment with vosoritide.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf041"},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710391","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-Acting Growth Hormone for Pediatric Growth Hormone Deficiency.","authors":"Norbert Albers, Sarah Cadarette, Ben Feakins, María Arregui, Stephen Ebohon, Pamela Lai, Subhara Raveendran, Mads Kjelgaard-Hansen, Christine Andersen, Carol Zhao, Alden Smith, Mitchell Geffner","doi":"10.1210/jendso/bvaf040","DOIUrl":"10.1210/jendso/bvaf040","url":null,"abstract":"<p><p>Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"9 5","pages":"bvaf040"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719909","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}