Journal of the Endocrine Society最新文献

{"title":"Clinical burden of classic congenital adrenal hyperplasia and glucocorticoid-related complications: a claims analysis.","authors":"Hyunwoo Kim, Vivian H Lin, Ron S Newfield, Andrew Dauber, Michelle Luo, Samantha Cicero, Michael Li, Cecilia Zhao, Henry Kim Cheng","doi":"10.1210/jendso/bvag112","DOIUrl":"10.1210/jendso/bvag112","url":null,"abstract":"<p><strong>Context: </strong>Classic congenital adrenal hyperplasia (CAH) is a rare genetic condition characterized by impaired cortisol and aldosterone synthesis. Historical management required glucocorticoid (GC) therapy to replace cortisol and, often, to suppress excess ACTH and adrenal androgens. However, supraphysiologic GC doses can lead to substantial complications.</p><p><strong>Objective: </strong>This study aimed to characterize the clinical burden associated with CAH and quantify the degree to which CAH- and/or GC-related complications manifest.</p><p><strong>Methods: </strong>Retrospective cohort analyses were conducted using administrative claims data from MarketScan® Research Databases (1/1/2020-12/31/2022) to quantify the burden of CAH- and/or GC-related complications among insured patients with CAH in the United States compared with a matched cohort.</p><p><strong>Results: </strong>A total of 719 patients with CAH receiving GC therapy were matched 1:5 with 3595 individuals based on age, sex, payer, region, and enrollment duration. Patients with CAH had significantly higher rates of predominantly GC-related complications, including cardiovascular/circulatory diseases, type 2 diabetes, hypertension, hyperglycemia, metabolic complications, obesity, and osteoporosis (all <i>P</i> < .05). Patients with CAH demonstrated significantly higher rates and risks of nearly all CAH-related complications compared with matched controls (<i>P</i> < .05). Rates and risks of nearly all complications categorized as both CAH- and GC-related were significantly higher among patients with CAH (<i>P</i> < .05). Rates were consistently higher in adults than pediatric patients, underscoring the progressive and cumulative nature of CAH- and GC-related morbidity.</p><p><strong>Conclusion: </strong>Individuals with CAH experience higher rates and risks of CAH- and/or GC-related complications, highlighting the considerable burden associated with CAH and supraphysiologic GC treatment. Higher complication rates in adults emphasize the need for early and effective management of CAH. Novel non-GC therapies may enable GC dose reduction while maintaining androgen control, potentially mitigating these complications.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag112"},"PeriodicalIF":4.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277906","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":"A cautionary tale of neurodevelopment gone wrong: roundup the zebra(fish).","authors":"Neruja Loganathan, Denise D Belsham","doi":"10.1210/jendso/bvag105","DOIUrl":"10.1210/jendso/bvag105","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag105"},"PeriodicalIF":4.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016096","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":"Evaluation and management of worsening virilization in a postmenopausal woman diagnosed with PCOS.","authors":"Matthew F Osborne, William B Horton, Arthur J Pesch, Richard J Santen","doi":"10.1210/jendso/bvag110","DOIUrl":"10.1210/jendso/bvag110","url":null,"abstract":"<p><p>The manifestations of common disorders can infrequently obscure the presence of very rare conditions that share similar clinical findings. Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism, ovulatory dysfunction, and/or polycystic ovarian morphologic features. A key component of the Rotterdam PCOS diagnostic criteria is the exclusion of other conditions that can mimic the signs and symptoms of PCOS. Compared to PCOS, androgen-producing tumors are rare neoplasms that originate in either the ovaries or adrenals and appear in only about 0.2% of people with hyperandrogenism. Ovarian steroid cell tumors (OSCTs) are an exceptionally rare subset of this class that represents less than 0.1% of all ovarian neoplasms. OSCTs are often hormonally active and classically cause the sudden and severe onset of secondary virilizing characteristics. In the case presented here, we describe a postmenopausal patient who was referred for management of PCOS but ultimately found to have an OSCT. A detailed history elicited a worsening of symptoms after menopause that raised the suspicion of a virilizing tumor; however, the clinical challenge was to determine whether the patient had both PCOS and an OSCT or whether the OSCT had been \"causing\" PCOS all along. This required careful scrutiny of the patient's 24-year clinical course and a comprehensive literature review in an effort to distinguish the manifestations of an OSCT from those of PCOS.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag110"},"PeriodicalIF":4.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982250","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":"Psychiatric morbidity following liothyronine exposure in autoimmune hypothyroidism: a Swedish nationwide cohort study.","authors":"Fredric Hedberg, Jonatan D Lindh, Buster Mannheimer, Tereza Planck, Jakob Skov, Henrik Falhammar, Jan Calissendorff","doi":"10.1210/jendso/bvag107","DOIUrl":"10.1210/jendso/bvag107","url":null,"abstract":"<p><strong>Context: </strong>Levothyroxine (LT4) is the primary treatment of hypothyroidism. Despite adequate LT4 substitution some patients experience symptoms and the use of adjunct liothyronine (LT3) has increased. Several trials show no clear advantage of LT4 + LT3, and observational studies report conflicting results.</p><p><strong>Objective: </strong>We aimed to assess the relationship between initiation of LT3 treatment and psychiatric morbidity in patients with autoimmune hypothyroidism.</p><p><strong>Methods: </strong>All adults in Sweden with autoimmune hypothyroidism without prior psychiatric morbidity initiated on thyroid hormone replacement between 2006 and 2020 were included. Data were obtained from the National Patient Register and the National Prescribed Drug Register. The risk of any psychiatric morbidity after LT4 vs LT4 + LT3 therapy was estimated using Cox regression models with multivariable adjustments and LT3 as a time-dependent covariate.</p><p><strong>Results: </strong>The total cohort comprised 184 266 individuals. During follow-up, 5346 (2.9%) were exposed to LT3. Median follow-up on LT4 + LT3 was 2.7 years (IQR 1.1-4.4) and 3.8 years (IQR 1.5-7.3) on LT4. Exposure to LT3 was associated with higher risk of any psychiatric morbidity (aHR 1.43, 95% CI 1.34-1.53, <i>P</i> < .001). An association was also found with affective or anxiety morbidity (aHR 1.44, 95% CI 1.35-1.54, <i>P</i> < .001) and with psychotic morbidity (aHR 1.46, 95% CI 1.11-1.92, <i>P</i> = .0067) after multivariable adjustment.</p><p><strong>Conclusion: </strong>In autoimmune hypothyroidism LT4 + LT3 treatment was associated with increased risk of psychiatric morbidity. This may reflect a potential LT3 effect or an underlying vulnerability among LT3 users, underscoring the need for further studies to clarify any causal relationship.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag107"},"PeriodicalIF":4.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199477","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":"Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.","authors":"Lukas Plachy, Petra Dusatkova, Lukas Kavciak, Shenali Anne Amaratunga, Matvei Slavenko, Jana Drabova, Klara Maratova, Vit Neuman, Barbora Obermannova, Stanislava Kolouskova, Marta Snajderova, Zdenek Sumnik, Jan Lebl, Stepanka Pruhova","doi":"10.1210/jendso/bvag106","DOIUrl":"10.1210/jendso/bvag106","url":null,"abstract":"<p><strong>Context: </strong>Growth hormone (GH) stimulation tests have limited reliability and may lead to false-positive results.</p><p><strong>Objective: </strong>This work aimed to evaluate genetic causes of short stature in children clinically diagnosed with GH deficiency (GHD) and assess genotype-phenotype correlations.</p><p><strong>Methods: </strong>A retrospective single-center study was conducted including 233 children with clinically diagnosed primary GHD treated with GH for 5 years or more. Genetic testing was performed using a targeted next-generation sequencing panel of 398 growth-associated genes.</p><p><strong>Results: </strong>A genetic cause was identified in 39 of 233 (17%) children. Only 13 of 39 (33%) findings confirmed GHD (genes <i>CHD7</i>, <i>GH1, GHSR</i>, <i>GLI2</i>, <i>GNAO1</i>, <i>KMT2D</i>, <i>OTX2</i> [3], <i>POU1F1</i>, <i>PROP1</i>, <i>SALL4</i>, <i>TBX3</i>). The remaining 26 of 39 (67%) revealed alternative etiologies of growth failure: RASopathies (13/39; genes <i>NF1</i> [2], <i>PTPN11</i> [7], <i>RAF1</i>, <i>SOS1</i> [2], <i>SPRED1</i>), growth plate disorders (8/39; genes <i>ACAN</i>, <i>COL2A1</i>, <i>EXT2</i>, <i>FGFR3</i> [2], <i>NPR2</i> [3]), and miscellaneous conditions (5/39; genes <i>CDC42</i>, <i>LMNA</i>, <i>HMGA2</i>, <i>PMM2</i>, <i>RAI1</i>). Genetically confirmed GHD patients presented with lower peak GH (median 1.8 vs 4.8 [alternative genetic etiology] and 5.9 μg/L [no genetic etiology]; <i>P</i> = .017), more frequent combined pituitary hormone deficiency (46% vs 4% and 12%; <i>P</i> = .001) and magnetic resonance imaging midbrain abnormalities (73% vs 14% vs 32%; <i>P</i> = .003). Conversely, the alternative etiology group demonstrated the least robust 5-year GH therapy response (median height gain 1.4 vs 2.3 [GHD group] and 1.8 [no genetic etiology]; <i>P</i> = .001).</p><p><strong>Conclusion: </strong>The population of children clinically diagnosed with GHD is genetically heterogeneous. A statistically significant proportion harbors defects in RAS-MAPK signaling or growth plate disorders, highlighting the limitations of current methods of GHD diagnostics.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag106"},"PeriodicalIF":4.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016167","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":"Feasibility, reproducibility, and cold-induced energy expenditure using whole-room calorimetry in adults and children.","authors":"Paige Cheveldayoff, Bader Alamri, Dongdong Wang, Rogelio Cruz Gonzalez, Aaron C Q Thomas, Norm Konyer, Michael D Noseworthy, Hertzel C Gerstein, Zubin Punthakee, Gregory R Steinberg, Katherine M Morrison","doi":"10.1210/jendso/bvag102","DOIUrl":"10.1210/jendso/bvag102","url":null,"abstract":"<p><strong>Context: </strong>To understand energy balance, whole-room indirect calorimetry (WRIC) allows for accurate measurement of energy expenditure (EE).</p><p><strong>Objective: </strong>To examine the relationship between cold-induced resting EE and brown adipose tissue (BAT) activity measured by magnetic resonance imaging (MRI) and to evaluate WRIC system (WRICS) performance and feasibility of use in children and adults.</p><p><strong>Methods: </strong>The WRICS was equipped with a Promethion High-Definition Room Calorimetry System. Technical validation utilized nitrogen (N₂) and carbon dioxide (CO₂) gas infusions. Healthy adults (n = 21) and children aged 8-17 years (n = 17) attended two 4-hour WRIC visits (one week apart) and one MRI visit. Resting EE at 25 °C (REE₂₅) was compared between visits and to REE at 18 °C (REE₁₈). Recruitment and completion rates were examined. BAT activity was assessed by MRI as the decline in supraclavicular proton density fat fraction during 18 °C cold exposure.</p><p><strong>Results: </strong>Gas infusion testing confirmed high accuracy (respiratory exchange ratio [RER] = 0.99; 95% CI 0.991-0.996). Study completion rates were high (adults: 20/21; children: 17/18). REE₂₅ over a 10-minute period was consistent between visits (adults: 1.68 ± 0.462 vs 1.66 ± 0.301 kcal/min, <i>P</i> = 0.77; children: 1.50 ± 0.358 vs 1.58 ± 0.348 kcal/min, <i>P</i> = .25). Cold exposure increased fasting EE by 0.21 kcal/min (adults) and 0.14 kcal/min (children). BAT activity was correlated with REE₁₈ in adults (<i>r</i> = 0.49, <i>P</i> = .04).</p><p><strong>Conclusion: </strong>WRICS use was feasible in adults and children. Changes in EE during cold (ie, cold-induced thermogenesis) were measurable and related to BAT activity, supporting the usefulness of this system in the assessment of EE in response to interventions in adults and children.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag102"},"PeriodicalIF":4.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218273","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":"Association of insulin resistance and fracture risk in the Osteoporotic Fractures in Men (MrOS) cohort.","authors":"Jeonghoon Ha, Li-Yung Lui, Kristine Ensrud, Qian Xiao, Andrew R Hoffman, Joy Y Wu","doi":"10.1210/jendso/bvag101","DOIUrl":"10.1210/jendso/bvag101","url":null,"abstract":"<p><strong>Context: </strong>Insulin resistance (IR) is more prevalent in men than in women, but evidence directly linking IR to fracture risk in older men remains limited.</p><p><strong>Objective: </strong>To evaluate the association between insulin resistance (IR), estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the triglyceride-glucose (TyG) index, and fracture risk in older men.</p><p><strong>Methods: </strong>Data from 5994 men (≥65 years) in the MrOS cohort were analyzed. A total of 5416 participants were included in the HOMA-IR analysis and 5384 in the TyG index analysis. Fractures were self-reported and confirmed radiographically. Participants were grouped into quartiles based on IR indices, and fracture outcomes were evaluated during a mean follow-up of 12.2-13.6 years using Cox models.</p><p><strong>Results: </strong>A U-shaped association was observed in the HOMA-IR analysis, with Q3 vs Q1 showing a lower hazard ratio (HR) for any fracture (HR 0.82, 95% CI 0.70-0.97). Similarly, in the TyG index analysis, Q3 vs Q1 was associated with lower risks of any fracture (HR 0.84, 95% CI 0.72-0.98) and major osteoporotic fracture (MOF) (HR 0.80, 95% CI 0.65-0.99). No associations were found for hip or vertebral fractures, and results were unchanged in sensitivity analyses excluding T2DM.</p><p><strong>Conclusion: </strong>Older community-dwelling men in Q3 of HOMA-IR and TyG had modestly lower risks of any clinical fracture and MOF, but associations were inconsistent across quartiles and fracture types. Further studies in other populations are needed to confirm these findings.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag101"},"PeriodicalIF":4.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157116","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":"Adrenal crises and quality of life after bilateral adrenalectomy vs primary autoimmune adrenal insufficiency.","authors":"Alexandra N Bancos, Raul Gregg-Garcia, Natalia Genere, Sanan Mahrokhian, Sara J Achenbach, Elizabeth J Atkinson, Anand Vaidya, Irina Bancos","doi":"10.1210/jendso/bvag104","DOIUrl":"10.1210/jendso/bvag104","url":null,"abstract":"<p><strong>Context: </strong>Bilateral adrenalectomy (BLA) and autoimmune adrenal insufficiency (AAI) are 2 major causes of primary adrenal insufficiency (PAI). Comparative data between etiologies are limited.</p><p><strong>Objective: </strong>To compare management, quality of life (QoL), and frequency of adrenal crises between participants post-BLA vs AAI.</p><p><strong>Methods: </strong>We conducted a dual-center, cross-sectional study of adults with AAI or BLA between 2018 and 2025. All participants completed questionnaires on management, adrenal crises, and the Addison Disease-specific QoL Questionnaire (AddiQoL).</p><p><strong>Results: </strong>Of 343 participants, 203 had AAI (median age 54 years, 72% women) and 139 had BLA (median age 57 years, 76% women). AddiQoL scores were similar between participants with AAI and BLA (median 84 vs 83, <i>P</i> = .947), but better in participants post-BLA for pheochromocytoma versus hypercortisolism (median 88 vs 81, <i>P</i> = .031). Participants with AAI reported a higher number of adrenal crises within the past year than those post-BLA (25% vs 13%, <i>P</i> = .022). In multivariable analyses of age, sex, glucocorticoid dose and type, PAI type, AddiQoL score, and autoimmune comorbidities, only PAI type was associated with higher number of reported adrenal crisis within the last year (AAI vs BLA: odds ratios of 2.1-2.2, <i>P</i> < .05 for all models).</p><p><strong>Conclusion: </strong>QoL was comparable between participants with AAI and BLA, though patients post-BLA for pheochromocytoma reported better QoL than patients post-BLA for hypercortisolism. Adrenal crises were more common in participants with AAI than those post-BLA, a finding that was not explained by patients' glucocorticoid management, underscoring the need for tailored crisis prevention strategies.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag104"},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578964","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":"Diazoxide choline extended-release (DCCR) use in Prader-Willi syndrome: patient selection, dosing, and management.","authors":"Jennifer M Miller, Ashley H Shoemaker, Parisa Salehi, Jorge Mejia-Corletto","doi":"10.1210/jendso/bvag099","DOIUrl":"10.1210/jendso/bvag099","url":null,"abstract":"<p><p>Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag099"},"PeriodicalIF":4.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839698","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":"Natural history of a pediatric cohort with islet autoantibody positivity: a single-center retrospective cohort study.","authors":"Emilio Casalini, Donella Puliti, Barbara Piccini, Matteo Cerutti, Silvia Farina, Emanuela Laudani, Lorenzo Lenzi, Stefano Romano, Francesco Citera, Maria Moriondo, Salvatore De Masi, Sonia Toni","doi":"10.1210/jendso/bvag087","DOIUrl":"10.1210/jendso/bvag087","url":null,"abstract":"<p><strong>Context: </strong>Type 1 diabetes (T1D) progresses from genetic risk to metabolic disease. Anti-β-cell antibodies (AABs), alongside clinical features, define the stages of T1D and enable identification of presymptomatic individuals.</p><p><strong>Objective: </strong>To describe the natural history of patients with ≥1 positive AAB, analyzing progression to stage 3 T1D and clinical severity at diagnosis.</p><p><strong>Design: </strong>Single-center retrospective cohort study (February 2012-April 2025).</p><p><strong>Patients: </strong>One-hundred and six patients with ≥1 AAB-positive enrolled in a structured follow-up program.</p><p><strong>Main outcome measure: </strong>progression to stage 3 T1D and occurrence of diabetic ketoacidosis (DKA) at diagnosis.</p><p><strong>Results: </strong>During a median follow-up of 4 years, 19 of 106 AAB-positive patients progressed to stage 3 T1D, none of whom presented with DKA at diagnosis. The 5-year cumulative risk of progression was 16.6% (95% CI: 10.0%-26.9%). Patients with multiple AAB positivity at baseline had a significantly higher 5-year risk than those with a single positive AAB (40.4% vs 8.3%; <i>P</i> = .0002). Glutamic acid decarboxylase (GAD) autoantibody positivity was associated with an increased 5-year risk of progression (25.7% vs 2.8% in GAD-negative children; <i>P</i> = .0063) and remained independently associated with T1D onset in multivariable analysis.</p><p><strong>Conclusion: </strong>Persistent autoantibody positivity, particularly for GAD, is strongly associated with progression to stage 3 T1D. Children identified through AAB monitoring show a milder clinical presentation at diagnosis, with no cases of DKA. These data support screening and structured follow-up of at-risk children, which may help prevent DKA and facilitate identification of candidates for disease-modifying interventions.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag087"},"PeriodicalIF":4.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816779","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}