Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Unraveling a Subgroup of Men With Unexplained Male Infertility-Men With Normogonadotropic Nonobstructive Azoospermia.","authors":"Vanessa Schwarzkopf, Joachim Wistuba, Reinhild Sandhowe-Klaverkamp, Sabine Kliesch, Jörg Gromoll, Maria Schubert","doi":"10.1210/clinem/dgaf200","DOIUrl":"10.1210/clinem/dgaf200","url":null,"abstract":"<p><strong>Context: </strong>Nonobstructive azoospermia (NOA) constitutes male infertility with complete absence of sperm in the ejaculate. NOA can originate in testicular malfunction or in endocrine dysregulation. Elevated follicle-stimulating hormone (FSH) levels are diagnostically valuable for NOA.</p><p><strong>Objective: </strong>An azoospermic patient cohort comprising 79 men and exhibiting no obstruction but normal FSH levels was identified. Focusing on this normogonadotropic nonobstructive azoospermic (NNOA) group, the study aimed to characterize these patients in depth.</p><p><strong>Methods: </strong>Whether the missing FSH upregulation in patients with NNOA is due to testicular or pituitary/hypothalamic malfunctions was examined by analyzing somatic, endocrine, and testicular parameters compared with 87 men with hypergonadotropic NOA and 88 normozoospermic men.</p><p><strong>Results: </strong>Testicular phenotypes of patients with NNOA and NOA were compared in histologically stratified subgroups (most advanced germ cell type). Using flow cytometry, the samples were evaluated for testicular cell composition by ploidy analysis. Concerning the distinct histological classification (hypospermatogenesis, spermatogenic arrest, Sertoli cell only, tubular atrophy) NNOA men produced more elongated spermatids and showed higher sperm retrieval. Testicular tissue composition between patients with NNOA and patients with NOA only differed after meiosis.</p><p><strong>Conclusion: </strong>The missing FSH upregulation in NNOA might be due to a testicular malfunction, as both FSH and testosterone were normal and NNOA spermatogenesis differed only after meiosis. Two explanations are possible: NNOA represents a phenotype in which spermatogenesis fails-different from NOA-only at the postmeiotic level, leaving FSH regulation unaffected, or the same mechanism underlies both NNOA and NOA, but the groups are at different stages of progression of the same disorder.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3400-3411"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediabetes and Risk of All-Cause and Cause-Specific Mortality: A Prospective Study of 114 062 Adults in Mexico City.","authors":"Carlos Alberto Fermín-Martínez, Omar Yaxmehen Bello-Chavolla, César Daniel Paz-Cabrera, Daniel Ramírez-García, Jerónimo Perezalonso-Espinosa, Luisa Fernández-Chirino, Arsenio Vargas-Vázquez, Juan Pablo Díaz-Sánchez, Padme Nailea Méndez-Labra, Alejandra Núñez-Luna, Martín Roberto Basile-Alvarez, Paulina Sánchez-Castro, Fiona Bragg, Louisa Gnatiuc Friedrichs, Diego Aguilar-Ramírez, Jonathan R Emberson, Jaime Berumen, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jesus Alegre-Díaz, Jacqueline A Seiglie, Neftali Eduardo Antonio-Villa","doi":"10.1210/clinem/dgaf225","DOIUrl":"10.1210/clinem/dgaf225","url":null,"abstract":"<p><strong>Background: </strong>Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations.</p><p><strong>Methods: </strong>We analyzed data from 114 062 adults without diabetes (diagnosed or undiagnosed) from the Mexico City Prospective Study. Participants were followed until January 1, 2021, for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA; HbA1c ≥ 5.7% to <6.5%) and the International Expert Committee (IEC; HbA1c ≥ 6.0 to <6.5%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) for deaths occurring at ages 35 to 74 years associated with prediabetes.</p><p><strong>Results: </strong>After median 18.4 (IQR 17.6-19.7) years of follow-up, individuals with prediabetes had higher risk of all-cause mortality at ages 35 to 74 compared to those without prediabetes (RR 1.13 [1.07-1.20] for ADA-defined and 1.27 [1.17-1.38] for IEC-defined prediabetes), as well as higher risk of cardiovascular (RR 1.23 [1.11-1.37] and 1.44 [1.24-1.67], respectively), renal (RR 1.33 [1.06-1.66] and 1.62 [1.18-2.23], respectively), and acute diabetic deaths (RR 2.62 [1.75-3.93] and 3.42 [2.09-5.61], respectively). The absolute excess risk associated with ADA-defined prediabetes at ages 35 to 74 accounted for 7% of cardiovascular, 9% of renal, and 31% of acute diabetic deaths. IEC-defined prediabetes accounted for 4%, 5% and 14% of cardiovascular, renal, and acute diabetic deaths. Prediabetes-associated excess mortality risks were, at least in part, explained by adiposity.</p><p><strong>Conclusion: </strong>Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Early identification and timely management of prediabetes among individuals at risk of this condition could reduce premature mortality in this population.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3451-3460"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Validation of ATA Risk Score for Papillary Thyroid Microcarcinoma: An ITCO Real-World Study.","authors":"Simone De Leo, Giulia Brigante, Silvia D'Elia, Simona Censi, Bruno Madeo, Silvia Morelli, Alice Nervo, Andrea Repaci, Clotilde Sparano, Ilaria Stramazzo, Camilla Virili, Francesco Bertagna, Francesco Dondi, Efisio Puxeddu, Edoardo Talpacci, Maria Chiara Zatelli, Maria Rosaria Ambrosio, Francesco Felicetti, Alessandro Piovesan, Luisa Petrone, Virginia Adornato, Matteo Trevisan, Laura Fugazzola, Chiara Mele, Marco Zavattaro, Erica Solaroli, Nicola Salituro, Mattia Rossi, Loredana Pagano, Alessandra Colapinto, Cristina Basso, Graziano Ceresini, Michela Marina, Umberto Crocetti, Michela Massa, Maurilio Deandrea, Francesca Retta, Giovanna Spiazzi, Nicoletta Rolli, Rocco Bruno, Antonella Carbone, Mario Rotondi, Flavia Magri, Poupak Fallahi, Maria Grazia Chiofalo, Maria Giulia Santaguida, Salvatore Monti, Tommaso Porcelli, Roberto Castello, Alfonso Sagnella, Cristina Clausi, Giulia Di Dalmazi, Dario Tumino, Andrea Palermo, Antonio Brunetti, Andrea Lania, Andrea Liverani, Cosimo Durante, Umberto Ferraro Petrillo, Marco Alfo', Sebastiano Filetti, Giorgio Grani","doi":"10.1210/clinem/dgaf190","DOIUrl":"10.1210/clinem/dgaf190","url":null,"abstract":"<p><strong>Context: </strong>The risk of recurrence of papillary thyroid carcinoma (PTC) smaller than 1 cm (microPTC) is low. Predictors of disease persistence in microPTC are still unclear.</p><p><strong>Objective: </strong>To compare the clinical and pathological characteristics of microPTCs with macrocarcinomas (PTC > 1 cm), identifying the predictors of biochemical and structural incomplete response 1 year after initial treatment in microPTC.</p><p><strong>Methods: </strong>We included patients consecutively enrolled in the Italian Thyroid Cancer Observatory (NCT04031339), and selected patients with a histological diagnosis of PTC for whom complete pathological, clinical, treatment information, and results at the 1-year follow-up visits were available.</p><p><strong>Results: </strong>Among 5038 patients in the cohort, 2345 (46.5%) had a microPTC. Patients with microPTCs had tumors with more indolent pathological features: only 3% of patients were classified as high risk according to the American Thyroid Association (ATA) risk stratification system for persistent or recurrent disease and 1% had distant metastases at diagnosis. MicroPTCs had a significantly better outcome: only 5% had a biochemical response and 2.3% a structural incomplete (SIR) response. Distant metastases at diagnosis were the best predictor of SIR in microPTCs (OR 5.13, 95% CI 1.11-23.73, P = .04). In a subgroup of 925 patients treated by total thyroidectomy and radioiodine treatment, the best predictor of SIR was the ATA high risk (OR 5.47, 95% CI 1.42-21.04, P = .01).</p><p><strong>Conclusion: </strong>Our study confirms the favorable initial outcome of microPTC in a large series. We demonstrate that the ATA risk classification is reliable in predicting biochemical and structural persistence in patients with microPTC. Distant metastases, although rare, remain the best predictor of structural persistence at 1-year follow-up. These findings underscore the importance of tailored management strategies based on comprehensive risk stratification, rather than solely on tumor size.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4196-e4204"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Prevalence of the Major Thyroid Cancer-Associated Syndromes.","authors":"Samantha Lee White, Taylor Jamil, Caitlin Bell, Lauren Fishbein, Bryan Roland Haugen, Christopher Raymond Gignoux, Nikita Pozdeyev","doi":"10.1210/clinem/dgaf236","DOIUrl":"10.1210/clinem/dgaf236","url":null,"abstract":"<p><strong>Context: </strong>Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.</p><p><strong>Objective: </strong>To estimate the prevalence of the major thyroid cancer-associated syndromes in the United States using data from the All of Us Research Program (All of Us) and the UK Biobank.</p><p><strong>Methods: </strong>In this cross-sectional study, we identified pathogenic and likely pathogenic (P/LP) variants from the ClinVar database in 245 394 All of Us and 469 558 UK Biobank participants. We calculated the prevalence of thyroid cancer-associated syndromes defined by the presence of P/LP variants.</p><p><strong>Results: </strong>Using logistic regression, we found that 3 hereditary syndromes, multiple endocrine neoplasia type 2 (MEN2, RET gene, P = 3.23e-20), PTEN hamartoma tumor syndrome (PHTS, PTEN gene, P = 2.59e-15), and familial adenomatous polyposis type 1 (FAP, APC gene, P = 2.73e-10) were significantly associated with thyroid cancer. The prevalence of thyroid cancer-associated syndromes in the All of Us was 1:2172, 1:8764, and 1:8461, and in the UK Biobank, it was 1:2348, 1:13 043, and 1:8238 for MEN2, PHTS, and FAP, respectively. Three pathogenic RET variants that cause 2 amino acid substitutions, V804M and V804L, constitute 65% of all MEN2 variants in the All of Us, and none of these carriers were diagnosed with thyroid cancer.</p><p><strong>Conclusion: </strong>The prevalence of MEN2 and PHTS is ∼10 to 20 times higher than is currently estimated for the general population. Most affected individuals are not diagnosed with thyroid cancer. Our findings may change the clinical approach to patients with moderate-risk RET mutations.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4049-e4054"},"PeriodicalIF":5.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal Concentrations of Perfluoroalkyl Substances and Maternal Beta Cell Function at 7 to 9 Years of Follow-Up.","authors":"Jana Palaniyandi, Jennifer E Bruin, Mandy Fisher, Michael M Borghese, Myriam P Hoyeck, Constadina Panagiotopoulos, Jillian Ashley-Martin","doi":"10.1210/clinem/dgaf143","DOIUrl":"10.1210/clinem/dgaf143","url":null,"abstract":"<p><strong>Context: </strong>Epidemiological evidence regarding prenatal per- and polyfluoroalkyl substance (PFAS) exposure and long-term maternal metabolic health outcomes is lacking.</p><p><strong>Objective: </strong>Quantify associations between prenatal PFAS concentrations and maternal metabolic biomarkers of glucose homeostasis 7 to 9 years later.</p><p><strong>Methods: </strong>We measured second trimester plasma concentrations of 9 PFAS in participants enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We measured individual biomarkers of glucose homeostasis (fasting intact proinsulin, C-peptide, insulin, glucose, and hemoglobin A1C levels) in samples collected 7 to 9 years after the MIREC pregnancy (n = 258) and derived indicators of pancreatic beta cell function (proinsulin to insulin [PI:INS], proinsulin to C-peptide [PI:CP] ratios) and insulin resistance (homeostatic model assessment for insulin resistance [HOMA-IR], triglyceride-glucose index). Using multivariable linear regression models, we quantified the percent change in each outcome per doubling of individual PFAS concentrations. We used quantile g-computation and weighted quantile sum regression to evaluate the mixture of PFAS.</p><p><strong>Results: </strong>Prenatal perfluorononanoic acid and perfluorodecanoic acid concentrations were associated with 13.9% (95% CI: 0.8, 28.8) and 10.5% (95% CI: -1.0, 23.4) higher HOMA-IR values as well as 11.9% (95% CI: 0.1, 25.1) and 8.9% (95% CI: -1.5, 20.3) higher fasting insulin concentrations, respectively. A doubling of perfluorooctanoic acid concentrations was associated with increases in intact proinsulin concentrations (12.8% [95% CI: -3.5, 31.8]) and beta cell function ratios (PI:INS: 11.5% [95% CI: -4.4, 30.1]; PI:CP: 13.5% [95% CI: -2.4, 32.0]).</p><p><strong>Conclusion: </strong>Prenatal exposure to PFAS may impact long-term maternal insulin resistance and beta cell function, key risk factors for type 2 diabetes. These associations differ by specific PFAS.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4221-e4231"},"PeriodicalIF":5.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine-Vasopressin Dynamics in Relation to Food Intake and 8-Week Intranasal Oxytocin Treatment in Adults With Obesity.","authors":"Anna Aulinas, Francesca Galbiati, Marie-Louis Wronski, Carol Sue Carter, Shawn Nazarloo, Katherine Holman, Emily Rose Golden, Maged Muhammed, Natalia Hadaway, Elisa Asanza, Sarah Elizabeth Smith, Franziska Plessow, Elizabeth Austen Lawson","doi":"10.1210/clinem/dgaf237","DOIUrl":"10.1210/clinem/dgaf237","url":null,"abstract":"<p><strong>Context: </strong>Oxytocin (OXT) and arginine-vasopressin (AVP) are structurally similar hypothalamic-pituitary peptides with broad physiologic actions including regulation of caloric intake and metabolism. While OXT is under investigation as an antiobesity therapeutic, there are no data on endogenous AVP levels in relation to eating behavior in humans. Further, the effects of exogenous OXT on AVP dynamics, which could affect safety of treatment given AVP effects on water balance, are not well understood.</p><p><strong>Objective: </strong>This work aimed to define secretory dynamics of circulating AVP around a standardized meal and in response to 8 weeks (W) intranasal (IN) OXT vs placebo in adults with obesity.</p><p><strong>Methods: </strong>Cross-sectional and longitudinal data were used from an 8-W randomized clinical trial at a tertiary academic center. Participants included 63 adults with obesity (56% women, age 33.7 ± 6.3 years) of whom 61 were randomly assigned 1:1 to 8-W IN OXT (24 IU) 4 times daily or placebo. Intervention included a standardized meal, IN OXT vs placebo. Main outcome measure was AVP levels before and 30, 60, and 120 minutes after a standardized meal at baseline, and W4, 6, and 8 after starting OXT or placebo.</p><p><strong>Results: </strong>In response to food intake, AVP levels decreased at 60 minutes (adjusted mean ± SE = 68.55 ± 9.64 pg/mL) compared to fasting (80.99 ± 11.22 pg/mL; P = .022). AVP levels did not significantly change over the course of 8-W IN OXT treatment vs placebo (P ≥ .544). There was no effect of body mass index (P ≥ .615) or sex (P ≥ .498) on AVP levels.</p><p><strong>Conclusion: </strong>AVP levels decreased after food intake in adults with obesity, indicating a potential disruption in AVP signaling and possibly underlying obesity pathophysiology. Chronic IN OXT administration did not alter AVP levels, supporting safety of OXT-based therapeutics.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3972-e3979"},"PeriodicalIF":5.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid Use and Long-Term Changes in Weight and Waist Circumference: The Lifelines Cohort Study.","authors":"Mostafa Mohseni, Eline S van der Valk, Maartje J B Van der Hurk, Mesut Savas, Mariëtte R Boon, Elisabeth F C van Rossum","doi":"10.1210/clinem/dgaf166","DOIUrl":"10.1210/clinem/dgaf166","url":null,"abstract":"<p><strong>Context: </strong>The use of corticosteroids (CS) has been associated with higher body mass index (BMI) and waist circumference (WC) in cross-sectional studies. However, longitudinal data are scarce, particularly for locally administered forms.</p><p><strong>Design: </strong>We analyzed weight and waist circumference changes in 81 361 Lifelines Cohort Study participants (mean age 46.3 years, mean BMI 26.0 kg/m2, 41% male, mean follow-up 3.9 years) via linear regression. Sensitivity analyses included stratification by sex and BMI. Short-term weight changes post-start were assessed in a subset using linear mixed-effect models.</p><p><strong>Results: </strong>We found 23.8% CS users during the study period. Individuals reporting any new use of CS gained significantly more weight compared to nonusers at follow-up (β .034 kg/year, P = .021), particularly among those initiating local CS use (β .037 kg/year, P = .017). Use of new systemic CS was associated with increased WC (β .200 cm/year, P < .001). Discontinuation of CS led to decreased WC (β -.078 cm/year, P = .028). These effects were particularly observed in female participants and individuals with BMI ≥25 kg/m2, but not in male participants and those with BMI < 25 kg/m2. Short-term weight-inducing effects of CS were not observed in the weeks after initiation of CS use.</p><p><strong>Conclusion: </strong>This study demonstrates that CS use, including locally administered forms, is associated with long-term increases in weight and WC, notably in female individuals and those with overweight or obesity. Discontinuing CS was linked to reductions in WC. These findings underscore the need to carefully assess chronic systemic and local CS use, as discontinuation could benefit obesity-related outcomes in certain patients.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3989-e3997"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Levothyroxine Dosing Strategy for Immune Checkpoint Inhibitor-related Hypothyroidism: A Retrospective Study.","authors":"Ya Gao, Chunxia Du, Yan Xu, Xinqi Cheng, Haitao Zhao, Fang Jiang, Ninghai Cheng, Yang Xiang, Yuelun Zhang, Yuanmeng Li, He Liu, Xiaofeng Chai, Xiaolan Lian, Weigang Zhao, Naishi Li","doi":"10.1210/clinem/dgaf260","DOIUrl":"10.1210/clinem/dgaf260","url":null,"abstract":"<p><strong>Context: </strong>Immune checkpoint inhibitor (ICI)-related hypothyroidism is mostly irreversible and prompt thyroid hormone replacement therapy is crucial, especially for patients undergoing neoadjuvant immunotherapy.</p><p><strong>Objective: </strong>This study aimed to propose a novel titration strategy for ICI-related hypothyroidism, evaluate levothyroxine (LT4) dose differences between hypothyroidism patterns, and develop a predictive equation for the optimal LT4 dose.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Setting: </strong>Tertiary academic hospital.</p><p><strong>Patients: </strong>A total of 109 patients with ICI-related hypothyroidism.</p><p><strong>Interventions: </strong>Rapid vs conventional titration strategy.</p><p><strong>Main outcome measures: </strong>The time to achieve normal free thyroxine and TSH levels.</p><p><strong>Results: </strong>Patients with transient thyrotoxicosis followed by overt hypothyroidism required higher LT4 doses to achieve a euthyroid state compared to isolated overt hypothyroidism, with a mean difference of 0.23 μg/kg/day (95% CI, 0.08-0.38). In patients with ICI-related overt hypothyroidism and no cardiac disease, who had elevated TSH levels within 4 weeks of the last documented low or normal TSH, a rapid titration strategy was implemented. This strategy significantly improved the cumulative incidence of achieving normal free thyroxine and TSH levels compared to conventional titration strategy (hazard ratio, 4.44; 95% CI, 2.24-8.82; and hazard ratio, 4.11; 95% CI, 2.18-7.73, respectively), with a comparable safety profile. Predicted LT4 dose at euthyroid state (µg/kg/day) = (-0.016 × body weight) + (0.109 × baseline TSH level) + 2.661 for patients with thyrotoxicosis followed by overt hypothyroidism.</p><p><strong>Conclusion: </strong>LT4 requirements vary depending on the subtype of ICI-related hypothyroidism. The rapid titration strategy reduced the time to achieve a euthyroid state without a significant increase in adverse effects compared to conventional LT4 replacement therapy.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3342-3353"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occurrence of Newly Diagnosed Thyroid Cancer Is Not Increased After Radioactive Iodine Therapy for Graves' Disease.","authors":"Shigenori Hiruma, Natsuko Watanabe, Jaeduk Yoshimura Noh, Rei Hirose, Masakazu Koshibu, Masahiro Ichikawa, Akiko Sankoda, Hideyuki Imai, Yoshiyuki Saito, Nami Suzuki, Chie Masaki, Masako Matsumoto, Miho Fukushita, Ai Yoshihara, Kenichi Matsuzu, Hiroto Narimatsu, Michiko Matsuse, Norisato Mitsutake, Ryohei Katoh, Kiminori Sugino, Koichi Ito","doi":"10.1210/clinem/dgaf231","DOIUrl":"10.1210/clinem/dgaf231","url":null,"abstract":"<p><strong>Context: </strong>An analysis based on a large number of detailed patient data was performed to accurately assess the impact of radioiodine therapy (RAIT) for Graves' disease (GD) on thyroid cancer.</p><p><strong>Objective: </strong>The purpose was to investigate whether the occurrence of newly diagnosed thyroid cancer is increased after RAIT for GD, and whether thyroid cancer following RAIT has poor prognosis.</p><p><strong>Methods: </strong>A total of 13 874 eligible patients diagnosed with untreated GD were retrospectively analyzed. The incidence rates of newly developed thyroid cancer by each treatment method for GD was evaluated using the person-year method. Among the 23 179 patients who underwent RAIT for GD, including those with recurrent GD or a history of prior treatment for GD, those who developed thyroid cancer after RAIT were analyzed. Logistic regression analysis was performed to investigate the risk factors for thyroid cancer.</p><p><strong>Results: </strong>A total of 2273 cases underwent RAIT, 287 underwent surgical treatment, and 11 314 were treated with medication only, and new-onset thyroid cancer was identified in 8 patients in the RAIT group and 39 in the medication-only group. A total of 107 218 person-years were observed, but no significant difference was observed in the incidence rate of thyroid cancer with treatment for GD. Of the 23 179 cases that underwent RAIT, 17 developed thyroid cancer. Sixteen were diagnosed with papillary thyroid carcinoma (PTC), of which 15 were microcarcinomas. Logistic regression analysis did not identify any significant risk factors for thyroid cancer development.</p><p><strong>Conclusion: </strong>In this study, the incidence of new thyroid cancer cases did not increase following RAIT for GD. Most thyroid cancers that developed after RAIT were micro-PTCs, with no evidence suggesting a poor prognosis.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3441-3450"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Healthcare Cost of Fractures in Patients With Type 1 Diabetes: A Population-Based Cohort Study in Denmark.","authors":"Annika Vestergaard Kvist, Morten Frost, Andrea M Burden, Peter Vestergaard, Adrian Martinez-De la Torre, Troels Kristensen","doi":"10.1210/clinem/dgaf199","DOIUrl":"10.1210/clinem/dgaf199","url":null,"abstract":"<p><strong>Context: </strong>Patients with type 1 diabetes (T1D) have increased risk of post-fracture complications, such as impaired healing and surgical complications compared to patients without diabetes. However, it is not known if this translates to higher healthcare costs.</p><p><strong>Objective: </strong>We aimed to compare the direct healthcare costs within the first year of hip, humerus, forearm, foot, and ankle fractures between patients with T1D and matched controls.</p><p><strong>Methods: </strong>Patients with hip, humerus, forearm, foot, and ankle fractures in the period 2011-2019 were identified from the Danish National Patient Register. Patients with T1D were matched 1:4 with patients without diabetes. Costs for hospitalizations, primary care physicians, physiotherapy, and medication within the first year after a fracture were calculated.</p><p><strong>Results: </strong>We identified 973 hip, 622 humerus, 1144 forearm, 945 foot, and 472 ankle fractures in patients with T1D. The direct healthcare cost within 1 year after fracture was significantly higher among patients with T1D compared to patients without diabetes for humerus (€726 vs €562), forearm (€441 vs €269), foot (€225 vs €123), and ankle fractures (€551 vs €367). By contrast, the direct healthcare cost of hip fractures was similar in patients with T1D and controls (€9463 vs €9429).</p><p><strong>Conclusion: </strong>While hip fractures were the most costly site, there were no differences in the 1-year post-fracture direct healthcare costs. However, the costs were significantly higher at all other fracture sites among patients with T1D. Increased uptake of fracture prevention strategies among T1D may help reduce fracture risk and subsequently costs.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4075-e4085"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}