The Journal of clinical endocrinology and metabolism最新文献

{"title":"Functional Hypothalamic Amenorrhea Phenotype and Cardiovascular Disease Risk.","authors":"Chrisandra L Shufelt, Jennifer J Stuart, Jana Karam, Xiaoyu Che, JoAnn E Manson, Karen K Miller, Kathy Rexrode, Stephanie Faubion, Sarah Berga, C Noel Bairey Merz, Janet W Rich-Edwards","doi":"10.1210/clinem/dgag405","DOIUrl":"https://doi.org/10.1210/clinem/dgag405","url":null,"abstract":"<p><strong>Context: </strong>Menstrual irregularities have been associated with cardiovascular disease (CVD) risk, but underlying etiologies may confer distinct risk profiles. Functional hypothalamic amenorrhea (FHA) has not been evaluated as a separate risk phenotype.</p><p><strong>Objective: </strong>To assess the association between FHA phenotype and incident CVD and cardiometabolic risk factors.</p><p><strong>Design: </strong>Prospective cohort study with biennial follow-up from 1993 to 2019.</p><p><strong>Setting: </strong>Nurses' Health Study II cohort.</p><p><strong>Participants: </strong>The sample included 52,655 premenopausal women free of CVD in 1993. FHA phenotype was defined as irregular or absent cycles without PCOS traits combined with low body mass index and/or high physical activity.</p><p><strong>Intervention: </strong>None.</p><p><strong>Main outcome measures: </strong>Incident CVD (coronary heart disease [CHD; myocardial infarction or coronary revascularization] and stroke) and incident elevated cholesterol, hypertension, and type 2 diabetes (T2DM).</p><p><strong>Results: </strong>During up to 26 years of follow-up, 1,007 CVD events occurred. Among women who developed CVD, the median time to the first CVD event was 17.0 years (IQR, 11.3-21.0). FHA phenotype in mid-adulthood was associated with a 62% higher risk of CVD (95% confidence interval [CI]: 1.01-2.59), driven by an almost two-fold higher risk of CHD (hazard ratio [HR] = 1.91; 95% CI: 1.11-3.27), compared with women with regular cycles. FHA was also associated with T2DM (HR = 1.86; 95% CI: 1.41-2.47), but not hypertension or elevated cholesterol. Non-FHA menstrual irregularity was associated with elevated cholesterol, hypertension, and T2DM, but not CVD. FHA in early adulthood was not associated with outcomes.</p><p><strong>Conclusions: </strong>FHA phenotype in mid-adulthood was associated with increased CHD risk independent of traditional risk factors. Menstrual history may serve as an early marker of cardiometabolic risk.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approach to the pregnant patient with prolactinoma.","authors":"Zuleyha Karaca, Fahrettin Kelestimur","doi":"10.1210/clinem/dgag408","DOIUrl":"https://doi.org/10.1210/clinem/dgag408","url":null,"abstract":"<p><p>Prolactinomas account for approximately half of the pituitary adenomas and predominantly affect women of reproductive age. Hyperprolactinemia commonly causes infertility by suppressing hypothalamic gonadotropin-releasing hormone (GnRH) secretion and impairing gonadal function. Because dopamine agonist therapy can rapidly restore fertility, clinicians caring for women with prolactinomas should be qualified to manage problems that may arise during pregnancy. Pregnancy is characterized by physiological enlargement of the anterior pituitary gland and progressive hyperprolactinemia, primarily driven by increased placental estrogen secretion. Therefore, the management of prolactinoma during preconception, pregnancy, and the postpartum period requires an individualized, multidisciplinary approach by an experienced team. The principal challenges are symptomatic tumor enlargement and, rarely, pituitary apoplexy. If clinically significant tumor growth occurs during pregnancy, dopamine agonist therapy can be safely restarted. Both bromocriptine and cabergoline may be used safely during gestation, but cabergoline is increasingly preferred because of its greater efficacy and better tolerability. In patients with pituitary apoplexy, management may include close observation, dopamine agonist therapy, glucocorticoid replacement when indicated, or transsphenoidal surgery, depending on the severity of clinical and neuro-ophthalmological findings. Breastfeeding can generally be permitted in women with prolactinomas; therefore, dopamine agonist therapy should be withheld during lactation unless treatment is clinically necessary. This review discusses the practical aspects of recognizing, and managing prolactinoma-related problems before, during, and after pregnancy.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Plasma Metabolites Associated with Subsequent Response to Lifestyle Intervention in People with Prediabetes.","authors":"Peace Asuzu, Frankie Stentz, Chi-Yang Chiu, Jim Wan, Nawajes Mandal, Samuel Dagogo-Jack","doi":"10.1210/clinem/dgag403","DOIUrl":"https://doi.org/10.1210/clinem/dgag403","url":null,"abstract":"<p><strong>Context: </strong>Plasma metabolites have been associated with the development of type 2 diabetes (T2D) and prediabetes.</p><p><strong>Objective: </strong>To test the hypothesis that baseline metabolites predict response to lifestyle intervention (LI) in people with prediabetes.</p><p><strong>Design: </strong>Longitudinal cohort study.</p><p><strong>Setting: </strong>Academic health center.</p><p><strong>Participants: </strong>Adults with prediabetes enrolled in the 5-year Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study.</p><p><strong>Interventions: </strong>PROP-ABC participants received LI for 5 years. Assessments included anthropometry, fasting and 2-hr plasma glucose (FPG, 2hrPG), insulin sensitivity and secretion, and plasma metabolites (18 amino acids, 45 acylcarnitines, 54 sphingolipids) measured with liquid chromatography tandem mass spectrometry.</p><p><strong>Main outcome measure: </strong>The primary outcome was glycemic response during 5 years of LI. The present report assessed baseline metabolites as predictors of persistent prediabetes versus reversion to normal glucose regulation (NGR) (10 subjects with T2D were excluded).</p><p><strong>Results: </strong>Participants with persistent prediabetes or NGR post-LI showed significant baseline differences in specific metabolites. In logistic regression models, the odds ratio per 1-SD [95% confidence intervals] for persistent prediabetes were 2.405 [1.341-4.312], P = 0.0032 for 2hrPG and 1.850 [1.047- 3.271], P = 0.034 for ceramide C18:0/C18:1 ratio, adjusted for age, sex, race, adiposity, insulin sensitivity and secretion, and percentage changes in weight and waist circumference.</p><p><strong>Conclusions: </strong>Out of 117 metabolites examined in adults with prediabetes, higher baseline levels of 2hrPG and the saturated/monounsaturated ratio of stearic acid ceramide (C18:0/C18:1) emerged as potential candidate biomarkers for the outcome of persistent prediabetes versus reversion to normoglycemia in response to lifestyle intervention.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nadir Prolactin-guided Individualized Cabergoline Therapy Achieves Durable Remission and Safe Pregnancy in Prolactinomas.","authors":"Nobuhiro Miki, Masami Ono, Shun-Ichiro Izumi, Tomokatsu Hori, Kayoko Abe, Takakazu Kawamata","doi":"10.1210/clinem/dgag406","DOIUrl":"https://doi.org/10.1210/clinem/dgag406","url":null,"abstract":"<p><strong>Context: </strong>Achieving durable prolactinoma remission while preserving safe pregnancy remains a central unmet goal of cabergoline therapy.</p><p><strong>Objective: </strong>To prospectively evaluate individualized-dose cabergoline therapy for safe pregnancy, remission, and dosing optimization.</p><p><strong>Methods: </strong>Women with 310 prolactinomas comprised 97 bromocriptine (BC)-resistant, 93 BC-intolerant, and 120 naïve patients, harboring 56 large macroprolactinomas (≥20 mm), 80 small macroprolactinomas (≥10 mm), and 174 microprolactinomas. Cabergoline dosing was individualized to maintain nadir prolactin within the lowest achievable normal range. In 129 macroprolactinomas and 19 microprolactinomas at risk of gestational enlargement, medical debulking prophylactically restored the optic-pituitary (O-P) distance to >5.0 mm before conception. Cabergoline was discontinued immediately after conception.</p><p><strong>Results: </strong>Treatment achieved 100% biochemical normalization; 84-100% prepregnancy tumor debulking; 365 uneventful pregnancies in 294 patients (95%); no symptomatic tumor enlargement during pregnancy; and 72% postpartum remission overall (naïve 82%, BC-resistant 70%, BC-intolerant 61%; microprolactinomas 73%, macroprolactinomas 72%). Responder frequency was subtype-specific across 0.25-9.0 mg/week doses with distinct ED50 values ranging from 0.66 in BC-intolerant to 3.71 in BC-resistant patients. AIC-based multivariate analysis identified nadir prolactin-markedly lower in nonvisible than residual prolactinomas-as the dominant determinant of tumor disappearance. No cardiac valvulopathy or impulse control disorders were observed on longitudinal follow-up.</p><p><strong>Conclusion: </strong>Despite marked ED50 heterogeneity, nadir prolactin-guided individualized-dose cabergoline therapy safely achieved durable remission with excellent pregnancy outcomes. These findings establish a clinically actionable, outcome-directed framework that prospectively integrates endocrine normalization, anatomical risk reduction, and tumor eradication, rendering durable remission and safe pregnancy realistically achievable therapeutic objectives in prolactinomas.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic and psychosocial outcomes of automated insulin delivery in older and high-risk populations with type 1 diabetes: a systematic review and meta-analysis.","authors":"Puguh Oktavian, Citrawati Dyah Kencono Wungu, Indah Mohd Amin, Sony Wibisono Mudjanarko","doi":"10.1210/clinem/dgag344","DOIUrl":"https://doi.org/10.1210/clinem/dgag344","url":null,"abstract":"<p><strong>Background: </strong>Automated insulin delivery (AID) has revolutionized care for people with type 1 diabetes. However, its efficacy and safety in older adults (≥60 years) and high-risk populations, including those with impaired awareness of hypoglycemia, or cognitive or functional impairment, have not been systematically evaluated.</p><p><strong>Materials and methods: </strong>CENTRAL, PubMed, Web of Science, Scopus, and ClinicalTrials.gov from inception to March 10, 2026. Studies on automated insulin delivery in older and high-risk individuals with type 1 diabetes were included. The primary outcome was time in range (3.9-10.0 mmol/L [70-180 mg/dL]). Secondary outcomes included time above range, time below range, psychosocial well-being (Gold, Clarke, and Hypoglycemia Fear Survey score), and serious adverse events. Pooled effect sizes were estimated with random-effects models (PROSPERO, CRD420251273526).</p><p><strong>Results: </strong>Twenty-three studies involving 967 participants (11 randomized controlled trials, 3 single-arm, and 9 cohort studies) were included. Automated insulin delivery increased time in range by 11.38% (95% CI: 8.07-14.70; I2 = 70%; P < .0001; very low certainty; equivalent to 2.7 hours/day). Time in range improvement was observed during the day (8.70%; 95% CI 5.18-12.22%) and overnight (13.35%; 95% CI 11.07-15.62%). Favorable improvement was also comparable among commercial and noncommercial systems. Automated insulin delivery reduced the time spent in hyperglycemia (-7.89%) and hypoglycemia (-1.16%). No significant differences in psychosocial well-being were observed. Diabetic ketoacidosis and severe hypoglycemia events were not significant.</p><p><strong>Conclusion: </strong>Automated insulin delivery exhibits favorable glycemic outcomes and safety profiles in older and high-risk individuals with type 1 diabetes, suggesting potential benefits for populations traditionally considered vulnerable, although no significant improvements were observed in psychosocial outcomes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Yield of Laboratory-Based Screening for Hypophosphatasia Among Chinese Children With Low Alkaline Phosphatase.","authors":"Dandan Zhang, Xueqian Wang, Lijun Zhou, Qunfei Li, Haiying Wu, Bingyu Yang, Rongrong Xie, Fengyun Wang, Xiuli Chen, Linqi Chen, Yaoshuang Li, Qing Wang, Xiaoyan Wang, Hui Sun, Hongying Wang, Jie Huang, Xiuzhi Ren, ZhenLin Zhang, Ting Chen","doi":"10.1210/clinem/dgag400","DOIUrl":"https://doi.org/10.1210/clinem/dgag400","url":null,"abstract":"<p><strong>Context: </strong>Hypophosphatasia (HPP) is a rare metabolic bone disease caused by pathogenic variants in ALPL gene. Due to its marked phenotypic heterogeneity, milder pediatric forms are frequently underdiagnosed, and systematic, laboratory-based screening strategies remain poorly defined.</p><p><strong>Objective: </strong>To establish a routine laboratory-based screening algorithm in a tertiary pediatric setting, characterize the ALPL genetic landscape in Chinese children, and delineate the milder clinical and neurobehavioral manifestations of HPP.</p><p><strong>Methods: </strong>We screened the laboratory records of 178,778 pediatric subjects at the Children's Hospital of Soochow University from September 2023 through August 2025 by means of daily surveillance. Individuals with persistently low serum alkaline phosphatase (ALP) levels (<2.5th percentile for age and sex) underwent ALPL next-generation sequencing and serum pyridoxal 5'-phosphate (PLP) measurement by UPLC-MS/MS. In vitro tissue-nonspecific ALP (TNSALP) functional assays were performed to adjudicate variants of uncertain significance (VUS).</p><p><strong>Results: </strong>Among 339 enrolled subjects, 73 clinically relevant ALPL variants were identified in 114 individuals, including 16 pathogenic and 30 likely pathogenic variants. Functional assays supported the reclassification of three VUS as likely pathogenic on the basis of significantly reduced TNSALP activity. Integrated clinical and genetic assessment confirmed HPP in 32 subjects and identified 25 suspected cases and 57 asymptomatic carriers. The predominant clinical features were dental abnormalities and impaired linear growth. Although classic severe complications were uncommon, neurobehavioral manifestations, including attention-deficit/hyperactivity disorder and tic disorders, were observed, broadening the recognized pediatric phenotype.</p><p><strong>Conclusion: </strong>A routine laboratory-based low-ALP screening algorithm can effectively identify previously unrecognized HPP in a pediatric population. Our findings demonstrate a high prevalence of mild HPP in Chinese children, highlight neurobehavioral manifestations, and provide a clinical framework for earlier diagnosis and timely intervention.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic status modifies skeletal response to active vitamin D: A post hoc analysis of the DPVD randomized trial.","authors":"Tetsuya Kawahara, Mikio Toda, Maiko Kanagawa, Nagahiro Toyama, Gen Suzuki, Tetsuya Inazu, Chie Kawahara","doi":"10.1210/clinem/dgag396","DOIUrl":"https://doi.org/10.1210/clinem/dgag396","url":null,"abstract":"<p><strong>Objective: </strong>Active vitamin D analogs increase bone mineral density (BMD), but inter-individual variability in skeletal response remains unexplained. Emerging evidence suggests skeletal remodeling is influenced by systemic metabolic status. Therefore, we examined whether metabolic state, defined by glycemic trajectory, modifies skeletal responsiveness to eldecalcitol.</p><p><strong>Methods: </strong>This post hoc cohort analysis used data from the Diabetes Prevention with Vitamin D (DPVD) randomized, placebo-controlled trial. Among 1,256 individuals with prediabetes, 1,164 participants with longitudinal BMD measurements were included. Longitudinal changes in lumbar spine BMD over three years were analyzed using a linear mixed-effects model including treatment group, glycemic trajectory (incident type 2 diabetes, persistent prediabetes, or regression to normoglycemia), time, and their interaction terms. Multivariable linear regression was used to identify baseline factors associated with the 3-year percentage change in lumbar spine BMD in the eldecalcitol group.</p><p><strong>Results: </strong>Lumbar spine BMD trajectories differed according to treatment assignment and glycemic trajectory (treatment-by-trajectory-by-time interaction, P=0.0307). Among participants receiving eldecalcitol, 3-year BMD increases were progressively greater with more favorable glycemic trajectories (4.6% in those who progressed to type 2 diabetes, 7.3% in those with persistent prediabetes, and 9.2% in those who regressed to normoglycemia; trajectory-by-time interaction, P=0.0098), whereas no significant differences across glycemic trajectories were observed in the placebo group (P=0.772). In addition, a lower baseline HbA1c was independently associated with a greater 3-year increase in lumbar spine BMD (β = -5.15 percentage points per 1% higher HbA1c; 95% CI, -8.34 to -1.95; P = 0.002).</p><p><strong>Conclusion: </strong>These findings suggest that metabolic status influences skeletal response to active vitamin D therapy and support the concept of bone-metabolic coupling.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy Study of Morning Salivary Cortisone for Screening Adrenal Insufficiency in a Real-World Cohort.","authors":"Constantinos Televantos, Phillip J Monaghan, Maria Michaelidou, Lillian Ruiheng Chen, Mohammed Ahmed, Jan Hoong Ho, Shaishav Dhage, Claire Higham, Brian Keevil, Safwaan Adam","doi":"10.1210/clinem/dgag401","DOIUrl":"https://doi.org/10.1210/clinem/dgag401","url":null,"abstract":"<p><strong>Context: </strong>Morning serum cortisol is used to screen for adrenal insufficiency, but requires venepuncture, early morning clinic attendance, and may be affected by altered corticosteroid-binding globulin (CBG) levels. Salivary cortisone is a non-invasive, home-based alternative.</p><p><strong>Objective: </strong>To assess the diagnostic accuracy of morning salivary cortisone for screening adrenal insufficiency and establish clinically relevant thresholds.</p><p><strong>Design: </strong>Retrospective cross-sectional diagnostic accuracy study (2017 to 2024).</p><p><strong>Setting: </strong>Single tertiary oncology and endocrinology center in the United Kingdom.</p><p><strong>Participants: </strong>Consecutive patients undergoing adrenocorticotropin hormone (ACTH) stimulation test for suspected adrenal insufficiency.</p><p><strong>Intervention: </strong>Salivary sampling for cortisone and cortisol.</p><p><strong>Main outcome measures: </strong>Sensitivity and specificity of baseline salivary cortisone.</p><p><strong>Results: </strong>A total of 517 ACTH stimulation tests in 449 participants were included; adrenal insufficiency was confirmed in 104 tests (20.1%). Baseline salivary cortisone accurately predicted adrenal insufficiency (area under the receiver operating characteristic curve [AUC] 0.93, 95% CI [0.91-0.95]), similar to serum cortisol (0.93, 0.90-0.95; p = 0.67) and superior to salivary cortisol (0.87, 0.82-0.91; p = 0.00063). A baseline salivary cortisone rule-out threshold ≥703 ng/dL (19.5 nmol/L) (sensitivity 0.97 [95% CI 0.92-0.99]; specificity 0.59 [0.54-0.63]) and a rule-in threshold <180 ng/dL (5.0 nmol/L) (sensitivity 0.58 [0.48-0.67]; specificity 0.97 [0.95-0.98]) provided the highest net benefit. An intermediate threshold <389 ng/dL (10.8 nmol/L) (sensitivity 0.83 [0.74-0.89]; specificity 0.87 [0.83-0.90]) identified patients for whom glucocorticoid cover should be considered while awaiting confirmatory testing.</p><p><strong>Conclusion: </strong>Baseline morning salivary cortisone performs at least as well as serum cortisol for adrenal insufficiency screening.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An agentic, no-code artificial intelligence workflow for developing a thyroid nodule ultrasound malignancy classifier.","authors":"Johnson Thomas, Nikita Pozdeyev","doi":"10.1210/clinem/dgag351","DOIUrl":"https://doi.org/10.1210/clinem/dgag351","url":null,"abstract":"<p><strong>Background: </strong>Convolutional neural networks can classify thyroid nodules on ultrasound, yet published models are seldom available for independent testing, require machine learning expertise to develop and deploy, and are validated mostly on papillary thyroid carcinoma.</p><p><strong>Objective: </strong>To test whether an autonomous (\"agentic\"), no-code artificial intelligence (AI) agent can develop a calibrated thyroid nodule malignancy classifier and validate it internally and on an external cohort spanning multiple cancer histologies.</p><p><strong>Methods: </strong>This was a retrospective, computational diagnostic study. A no-code agent (Hugging Face ML-Intern) autonomously audited the data, selected and trained the model, and calibrated probabilities, using the open-source TN5000 dataset. The locked ResNet-18 model was externally validated on 232 nodules from the University of Colorado and benchmarked against a previously published classifier evaluated on the same source.</p><p><strong>Results: </strong>On the internal test set, the agentic model achieved an area under the receiver-operating-characteristic curve (AUROC) of 0.94 (95% CI, 0.92-0.95), sensitivity 0.90, and specificity 0.81. On external validation, the model achieved an AUROC of 0.90 (95% CI, 0.85-0.93); sensitivity was 0.92, specificity 0.68, positive predictive value 0.52, and negative predictive value 0.96, exceeding the performance of the benchmark model (AUROC 0.83; paired DeLong P = .03). Missed cancers clustered among follicular pattern tumors.</p><p><strong>Conclusion: </strong>An agentic, no-code AI workflow produced a calibrated, externally validated thyroid nodule classifier, supporting accessible, reproducible, and independently testable medical AI development. Prospective validation and local recalibration are required before clinical use.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic Fat and Stiffness Reflect Distinct Features of Pancreatic Remodeling and β-Cell Function.","authors":"Sara Sofia De Lucia, Gea Ciccarelli, Giulia Gliozzo, Gianfranco Di Giuseppe, Laura Soldovieri, Emanuele Gentile, Enza Genco, Lorenzo Gallo, Maria Assunta Zocco, Maria Elena Ainora, Giorgio Esposto, Paolo Sposato, Roberto Bizzotto, Alfredo Pontecorvi, Andrea Giaccari, Antonio Gasbarrini, Enrico Celestino Nista, Teresa Mezza","doi":"10.1210/clinem/dgag399","DOIUrl":"https://doi.org/10.1210/clinem/dgag399","url":null,"abstract":"<p><strong>Context: </strong>Fatty pancreas is associated with obesity and metabolic alterations and may coexist with pancreatic structural remodeling. However, its contribution to β-cell dysfunction remains unclear.</p><p><strong>Objective: </strong>We investigated the relationship between pancreatic fat, tissue remodeling, and β-cell function.</p><p><strong>Design: </strong>We conducted a cross-sectional study in individuals with ultrasound-detected pancreatic hyperechogenicity without prior diagnosis of diabetes. Pancreatic fat was quantified by MRI-derived proton density fat fraction (PDFF), while tissue stiffness was assessed by shear-wave elastography. Metabolic phenotyping was based on oral glucose tolerance test (OGTT).</p><p><strong>Participants: </strong>We recruited 29 individuals with ultrasound-detected fatty pancreas (F/M 16/13, age 54 ± 10.4 years) and assessed glucose tolerance with OGTT: 75.9% exhibited normal glucose tolerance (NGT; n=22), while 24.1% had impaired glucose tolerance (IGT; n=7).</p><p><strong>Results: </strong>MRI-derived pancreatic fat fraction was positively correlated with anthropometric measures (BMI ρ=0.43, p=0.02) and β-cell function (β-cell glucose sensitivity ρ=0.40, p=0.03). Pancreatic stiffness correlated negatively with body weight (ρ= -0.38, p=0.04), did not correlate with pancreatic fat fraction (ρ= -0.15, p= 0.44) and was correlated inversely with the potentiation factor ratio (PFR1; ρ= -0.44, p= 0.02), a measure of non-glucose-dependent amplification of insulin secretion.</p><p><strong>Conclusions: </strong>Intrapancreatic fat and pancreatic stiffness appear to reflect distinct pathophysiological processes, with potentially different relationships to systemic metabolic status and β-cell function. These findings support a more nuanced view of pancreatic structural alterations as heterogeneous markers of metabolic dysfunction.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}