Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Changes in A1C Versus GMI Across Glycemic Categories in Clinical Trials of Type 1 Diabetes.","authors":"Eslam Montaser, Sebastián E Abad, Viral N Shah","doi":"10.1210/clinem/dgaf211","DOIUrl":"10.1210/clinem/dgaf211","url":null,"abstract":"<p><strong>Context: </strong>The glucose management indicator (GMI) is an estimated glycated hemoglobin (A1C) derived from sensor glucose. Though it is being used to approximate A1C in clinical trials, there are no data on direction and magnitude of change in GMI vs A1C after an intervention.</p><p><strong>Objective: </strong>To evaluate the magnitude and direction of changes in A1C compared to GMI across different baseline glycemic categories in type 1 diabetes (T1D) clinical trials.</p><p><strong>Methods: </strong>Baseline and 3-month central laboratory-measured A1C and estimated GMI from sensor glucose were collected from T1D clinical trials (DCLP3, DCLP5, and WISDM), encompassing children, adolescents, adults, and older adults. Magnitude and direction of changes (baseline-3 months) in A1C vs GMI were compared overall across the studies and by stratified baseline A1C (<7%, 7%-9%, >9%).</p><p><strong>Results: </strong>A modest correlation was found between changes in A1C and GMI (r = 0.34). Participants with baseline A1C > 9% had larger reductions in A1C compared to GMI (-1.2 [-2.1 to -0.6] vs -0.6 [-0.94 to 0], P < .01). Those with baseline A1C between 7% and 9% showed a greater decline in A1C than GMI (-0.4 [-0.9 to -0.1] vs -0.12 [-0.49 to 0.21], P < .01). No significant difference was observed for baseline A1C < 7%.</p><p><strong>Conclusion: </strong>Change in GMI is influenced by the baseline A1C of the participants and it underestimates the true change in A1C. Use of GMI as an endpoint in clinical trials may not reliably capture efficacy of an intervention in T1D trials or real-world studies.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4182-e4187"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765734","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":"Testosterone Effects on Short-term Physical, Hormonal, and Neurodevelopmental Outcomes (TESTO) in Infants With 47,XXY.","authors":"Shanlee M Davis, Susan Howell, Jennifer Janusz, Najiba Lahlou, Regina Reynolds, Talia Thompson, Karli Swenson, Rebecca Wilson, Judith L Ross, Philip S Zeitler, Nicole R Tartaglia","doi":"10.1210/clinem/dgaf217","DOIUrl":"10.1210/clinem/dgaf217","url":null,"abstract":"<p><strong>Context: </strong>47,XXY/Klinefelter syndrome (XXY) is associated with impaired testicular function and differences in physical growth, metabolism, and neurodevelopment. Clinical features of XXY may be influenced by testosterone during the minipuberty period of infancy.</p><p><strong>Objective: </strong>We tested the hypothesis that exogenous testosterone treatment positively affects short-term physical, hormonal, and neurodevelopmental outcomes in infants with XXY.</p><p><strong>Design: </strong>Double-blind randomized controlled trial, 2017-2021.</p><p><strong>Setting: </strong>US tertiary care pediatric hospital.</p><p><strong>Patients: </strong>Infants 30 to 90 days of age with prenatally identified, nonmosaic 47,XXY (n = 71).</p><p><strong>Intervention: </strong>Testosterone cypionate 25 mg IM injections every 4 weeks for 3 doses.</p><p><strong>Main outcome measures: </strong>The a priori primary outcomes were change in percent fat mass z-scores and change in the total composite percentile on Alberta Infant Motor Scales assessment from baseline to 12 weeks.</p><p><strong>Results: </strong>The between-group difference in change in percent fat mass z-scores was -0.57 (95% CI, -1.1 to -0.06; P = .03), secondary to greater increases in lean mass in the testosterone-treated group (1.5 ± 0.4 kg vs 1.2 ± 0.4; P = .001). Testosterone suppressed gonadotropins and inhibin B (P < .001 for all). In contrast, there were no significant group differences in short-term motor, cognitive, or language outcomes (P > .15 for all).</p><p><strong>Conclusions: </strong>In this double-blind randomized controlled trial in infants with XXY, testosterone injections resulted in physical effects attributable to systemic androgen exposure; however, this dose suppressed the hypothalamic-pituitary-gonadal axis. Neurodevelopment outcomes were not impacted by treatment. These results do not support routine testosterone treatment in infants with XXY; however, long-term follow-up on physical health, neurodevelopment, and testicular function is needed.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3493-3504"},"PeriodicalIF":5.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774668","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":"Distinct Luteinization Profiles of Cultured Human Granulosa Cells From Small Antral and Preovulatory Follicles.","authors":"Lea Bejstrup Jensen, Cristina Subiran Adrados, Jane Alrø Bøtkjær, Jesús Cadenas, Sivanandane Sittadjody, Emmanuel Opara, Pernille Landbæk Sørensen, Kirsten Tryde Macklon, Anette Tønnes Pedersen, Stine Gry Kristensen","doi":"10.1210/clinem/dgaf218","DOIUrl":"10.1210/clinem/dgaf218","url":null,"abstract":"<p><strong>Context: </strong>The transformation of follicular granulosa cells into luteal cells of the corpus luteum remains poorly understood in the human ovary.</p><p><strong>Objective: </strong>To investigate the luteinization process and steroidogenic differences between granulosa cells from small antral and preovulatory follicles in vitro.</p><p><strong>Methods: </strong>At the University Hospital of Copenhagen, Denmark, and Wake Forest Institute for Regenerative Medicine, USA, granulosa-lutein cells were obtained from 12 women undergoing IVF treatment, while follicular granulosa cells from unstimulated small antral follicles and corpus luteum were collected from 18 women undergoing ovarian tissue cryopreservation. Cells were cultured for up to 96 hours or 12 days with or without androstenedione or testosterone supplementation and analyzed using RT-qPCR and steroid hormone assays.</p><p><strong>Results: </strong>In follicular granulosa cells, luteinization markers (CYP11A1, P < .05; STAR, P < .001) increased within 24 to 48 hours, while granulosa markers (HSD17β1, P < .001; CYP19A1, P < .05) decreased within 6 to 12 hours. Luteinizing hormone/choriogonadotropin receptor remained unchanged. By 48 hours, gene expression resembled that of the corpus luteum. In contrast, granulosa-lutein cells exhibited highly luteinized profiles from day 0, with significantly higher progesterone/(17)estradiol ratios. Androgen supplementation and long-term follicle-stimulating hormone exposure did not alter luteinization.</p><p><strong>Conclusion: </strong>This study uniquely demonstrates that unstimulated follicular granulosa cells undergo a gradual, intrinsic luteinization process, independent of external hormonal triggers. In contrast, granulosa-lutein cells are already highly luteinized upon aspiration. These findings challenge conventional views on luteinization and highlight intrinsic cellular programming as a key driver, offering new insights into ovarian physiology and potential therapeutic targets for reproductive disorders.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3470-3481"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789172","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":"Navigating Transition to Adult Care in Youth-Onset Type 2 Diabetes: Facilitators, Attitudes, Barriers, and Behaviors.","authors":"Sophia Beth Glaros, Sydney Annemarie Dixon, Noemi Malandrino, Faith Suzanne Davis, Aruba Chowdhury, Ila Nikki Kacker, Natalie Ann Macheret, Samson Levy Cantor, Geethika Thota, Lilian Mabundo, Catherine Mason Gordon, Marissa Lightbourne, Doris Elizabeth Estrada, Maureen Monaghan, Stephanie Therese Chung","doi":"10.1210/clinem/dgaf239","DOIUrl":"10.1210/clinem/dgaf239","url":null,"abstract":"<p><strong>Context: </strong>Transitioning from pediatric to adult-centered diabetes care may be challenging, especially for young individuals at risk for and with youth-onset type 2 diabetes (Y-T2D) who have a high disease burden and rapidly progressive disease. However, the scope of transition readiness, range of psychosocial factors, and perceived barriers among Y-T2D are understudied.</p><p><strong>Objective: </strong>In Y-T2D attending an adult diabetes transition clinic, our objectives were to (1) characterize attitudes toward transition readiness, (2) examine relationships among depressive and anxiety-related symptoms and transition readiness, and (3) identify perceived barriers and facilitators of diabetes self-care.</p><p><strong>Methods: </strong>Transition readiness was assessed with the Endocrine Society \"Self-assessment of Worries, Concerns, and Burdens Related to Diabetes and Preparation for Transitioning,\" and mood symptoms with the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaire. Logistic regression analyses evaluated the response to transition readiness by mood symptoms. Qualitative analysis identified themes of diabetes self-care in a subset of Y-T2D.</p><p><strong>Results: </strong>Survey response rate was 89%; n = 65; age: 19.6 ± 2.0 years (mean ± SD); 85% Y-T2D; 15% prediabetes; 57% female; 78% Black; body mass index: 38.0 ± 8.2; and hemoglobin A1c: 7.6 ± 2.7%. Perceived challenges were reported in 95% of participants, and 54% reported worrying about their future. Mild or greater depressive and anxiety-related symptoms were associated with higher odds of reporting social, emotional, and cognitive challenges. Stress, socioeconomic difficulties, and challenges with organizational cognitive functioning were reported barriers to diabetes self-care.</p><p><strong>Conclusion: </strong>Mood symptoms and difficulties with organizational cognitive functioning were commonly reported in Y-T2D during the transitioning period. Interventions are needed to successfully address these psychosocial factors.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3412-3419"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037081","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":"Increased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling.","authors":"Carrie Malcom, Ozlem Guzeloglu-Kayisli, Burak Un, Erika New, Busra Cetinkaya-Un, Xiaofang Guo, Emad Mikhail, Anthony Imudia, Charles Lockwood, Umit Kayisli","doi":"10.1210/clinem/dgaf255","DOIUrl":"10.1210/clinem/dgaf255","url":null,"abstract":"<p><strong>Context: </strong>FK506-binding-protein-51 (FKBP51) is a glucocorticoid-induced co-chaperone protein previously shown to bind glucocorticoid receptor (GR), inhibiting its transcriptional activity. We previously found increased FKBP51 levels in uterine leiomyoma vs paired myometrium.</p><p><strong>Objective: </strong>To test the hypothesis that elevated FKBP51 levels contribute to leiomyoma pathogenesis by altering GR signaling.</p><p><strong>Design: </strong>RNA-sequencing was performed in leiomyoma cell cultures transfected with scramble or FKBP5-siRNA for 48 hours, then treated with vehicle or dexamethasone (DEX) for 24 hours. Differentially expressed genes, including HSD11B1, CNN1, and LAMA2 were analyzed by quantitative polymerase chain reaction. Hydroxysteroid 11-β dehydrogenase 1 (HSD11β1) expression was analyzed in leiomyoma, leiomyoma-adjacent paired myometrium, myometrium from patients without leiomyoma, and human endometrial stromal cells by quantitative polymerase chain reaction and immunohistochemistry.</p><p><strong>Setting: </strong>University research institution.</p><p><strong>Patients: </strong>Women with or without uterine leiomyoma.</p><p><strong>Main outcome measures: </strong>HSD11B1 mRNA and protein levels in leiomyoma, paired myometrium, and normal myometrium.</p><p><strong>Results: </strong>HSD11β1 expression was higher in paired myometrial and leiomyoma tissues vs normal myometrium (P < .02). DEX treatment increased HSD11B1 transcription in normal myometrial and human endometrial stromal cell cultures, but to a significantly greater extent in leiomyoma (P < .001). However, FKBP5-silencing blunted this DEX-induced HSD11B1 upregulation. DEX-treatment reduced LAMA2 and increased CNN1 levels (coding for extracellular matrix and smooth muscle proteins, respectively) in FKBP5-silenced vs scramble siRNA-transfected leiomyoma cultures.</p><p><strong>Conclusion: </strong>FKBP51 not only inhibits but can augment GR-mediated transcription. Importantly, FKBP51-GR interactions increase HSD11B1 levels in leiomyoma cells, generating a pathological FKBP51-GR-HSD11β1 circle, altering transcription of downstream extracellular matrix and smooth muscle genes to induce a myofibroblast phenotype, thereby possibly contributing to leiomyoma pathogenesis.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3370-3379"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038738","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":"Assessing the Cardiovascular Effects of Levothyroxine Use in an Ageing United Kingdom Population (ACEL-UK): Cohort Study.","authors":"Mia Holley, Salman Razvi, Ian Maxwell, Rosie Dew, Scott Wilkes","doi":"10.1210/clinem/dgaf208","DOIUrl":"10.1210/clinem/dgaf208","url":null,"abstract":"<p><strong>Context: </strong>Thyrotropin (TSH) levels tend to rise with age, but standard reference intervals do not reflect this, potentially leading to overdiagnosis of subclinical hypothyroidism (SCH) and excessive levothyroxine (LT4) prescriptions in older adults.</p><p><strong>Objective: </strong>This work aimed to compare outcomes in adults older than 50 years with SCH who were either prescribed or not prescribed LT4.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using data from UK Primary Care patients from the Health Improvement Network. The primary outcome was cardiovascular (CV) events (angina, myocardial infarction, peripheral vascular disease, stent procedures, or stroke). Secondary outcomes included bone events (fragility fractures or osteoporosis) and all-cause mortality. Time-varying hazard ratios (HRs) adjusted for relevant factors were estimated.</p><p><strong>Results: </strong>This study included 53 899 patients (baseline median age 67 years (interquartile range [IQR]: 59-76 years); 68.5% female; median TSH 4.6 mU/L (IQR: 4.1-5.4 mU/L). Median follow-up duration was 10 years (IQR: 5.5-10.0 years). Of these, 19 952 (37%) received LT4 and 33 947 (63%) did not. LT4 therapy showed a protective effect against CV events (HR: 0.91; 95% CI, 0.87-0.97; P < .001) but increased risk of bone events (HR: 1.21; 95% CI, 1.14-1.28; P < .001) and all-cause mortality (HR: 1.17; 95% CI, 1.13-1.22; P < .001).</p><p><strong>Conclusion: </strong>Our data suggest that LT4 therapy in older individuals with SCH is associated with a trade-off between the potentially beneficial effect on CV risk and the deleterious relationship with bone health and mortality risk. These risks need to be considered, mitigated, and discussed when LT4 therapy is being deliberated in older patients with SCH.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4137-e4143"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781303","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":"The Importance of Clinical Categorization for a Successful Etiologic Diagnosis of Monogenic Disorders in 46,XY DSD.","authors":"Sofía Suco Valle, Rodolfo A Rey","doi":"10.1210/clinem/dgaf054","DOIUrl":"10.1210/clinem/dgaf054","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4236-e4237"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411390","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":"Melatonin as a Possible Stimulus to Unmask an Oxytocin-Deficient State in Hypopituitarism and Hypothalamic Damage.","authors":"Queralt Asla, Maite Garrido, Eulàlia Urgell, Sílvia Terzan, Alicia Santos, Nimmy Varghese, Cihan Atila, Betina Biagetti, Franziska Plessow, Mirjam Christ-Crain, Anne Eckert, Susan M Webb, Elizabeth A Lawson, Anna Aulinas","doi":"10.1210/clinem/dgaf201","DOIUrl":"10.1210/clinem/dgaf201","url":null,"abstract":"<p><strong>Context: </strong>Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in hypopituitarism and hypothalamic damage (HHD). Identifying an applicable and reliable test to diagnose OXT-D is an unmet need. Melatonin (MEL) might be a candidate for such a test as it regulates OXT release in animals.</p><p><strong>Objective: </strong>This work aimed to examine the effects of melatonin on OXT release in HHD compared to healthy controls (HCs) and to describe the psychopathology, sexual function, and quality of life (QoL) and their associations with OXT.</p><p><strong>Methods: </strong>This proof-of-concept study (NCT05319301) included 20 participants with HHD (11 women) and 20 HCs (11 women). Blood samples were collected over 120 minutes to assess plasma OXT. A linear mixed-effects regression model was used to evaluate the change in OXT in response to MEL in HHD compared to HCs.</p><p><strong>Results: </strong>MEL significantly increased OXT at T90 vs T0 in HCs compared to the HHD group (difference 14.57 pg/mL 26% increase; 95% CI, 1.90-27.23; P = .02). The HHD group had more depression symptoms, alexithymia, impaired sexual function, and worse QoL compared to HCs. The mean percentage change in OXT from T0 to T90 was negatively associated with depressive and alexithymia symptoms in the HHD group and anxiety in both groups.</p><p><strong>Conclusion: </strong>The reduced OXT response after MEL in HHD supports the existence of an impaired OXT response at least in a subset of patients with HHD. The associations between OXT changes and psychopathology suggest its role in mood and QoL. These findings support further investigation into MEL's role as a diagnostic tool to address OXT-D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4205-e4214"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755615","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":"Effectiveness of the Dual GIP/GLP1-Agonist Tirzepatide in 2 Cases of Alström Syndrome, a Rare Obesity Syndrome.","authors":"Moritz Ferch, Isabel Peitsch, Alexandra Kautzky-Willer, Susanne Greber-Platzer, Albert Friedrich Stättermayer, Michael Krebs, Thomas Scherer","doi":"10.1210/clinem/dgaf258","DOIUrl":"10.1210/clinem/dgaf258","url":null,"abstract":"<p><strong>Context: </strong>Tirzepatide, a dual glucose-dependent insulinotropic peptide/glucagon-like peptide 1 (GIP/GLP1) receptor agonist, was recently approved for type 2 diabetes and weight management. Alström syndrome (AS) is a rare, genetic, multisystemic disorder, characterized by cone-rod dystrophy, progressive hearing loss, obesity, and diabetes with profound insulin resistance due to marked hyperphagia.</p><p><strong>Objective: </strong>Here we highlight the potential of tirzepatide as a novel therapeutic option for improving glycemic outcomes, metabolic dysfunction-associated steatotic liver disease (MASLD), and effectively reducing body weight in individuals with AS.</p><p><strong>Methods: </strong>We present the first 2 reported cases of people living with AS treated with tirzepatide.</p><p><strong>Results: </strong>Two individuals with AS, previously treated with semaglutide, received tirzepatide at our clinic. The first, a 23-year-old man with 18 months of treatment, experienced a weight loss of -28 kg (113.6 to 83 kg, -26.9%); glycated hemoglobin A1c decreased by -0.4% (6.7% to 6.3%), with considerable reductions in daily insulin doses of -96 IU/day (-83%; 58 to 20 IU insulin glargine and 58 to 0 IU prandial insulin), while maintaining oral antidiabetics. Hepatic steatosis, with a previous fat fraction of 20%, resolved as confirmed by magnetic resonance imaging (MRI). The second, a 20-year-old man with previously well-controlled diabetes, was followed up for 9 months and showed a weight reduction of -9.5 kg (132 kg to 122.5 kg; -7.2%) with a reduction of hepatic lipid content from 21% at the latest MRI to 11% after approximately 3 months of therapy.</p><p><strong>Conclusion: </strong>Tirzepatide shows great effectiveness with regard to body weight, MASLD, and insulin resistance in AS. Follow-up studies with larger cohorts have to be performed to confirm these findings.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3364-3369"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12623033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058851","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":"Aromatase Inhibitors Treatment Alone or With GH Increases Final Height in Short-statured Pubertal Boys-Real-world Data.","authors":"Michal Yackobovitch-Gavan, Ariel Tenenbaum, Moshe Phillip, Liora Lazar, Tal Oron","doi":"10.1210/clinem/dgaf224","DOIUrl":"10.1210/clinem/dgaf224","url":null,"abstract":"<p><strong>Context: </strong>Short-statured midpubertal boys with predicted adult height (PAHt) below the third percentile are a therapeutic challenge. Aromatase inhibitors (AI) delay estrogen-driven epiphyseal fusion and possibly enhance adult height (AHt).</p><p><strong>Objective: </strong>To assess the efficacy of AI treatment on AHt in midpubertal boys with a short PAHt due to advanced bone age (BA) or idiopathic short stature (ISS).</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Setting: </strong>Tertiary pediatric endocrine referral center.</p><p><strong>Patients and methods: </strong>Two groups of midpubertal boys treated with AI were studied: 27 boys with fast puberty compared to matched untreated controls and 16 boys with ISS treated with GH and AI (GH&AI) compared to those treated with GH only. Anthropometric measurements, BA and PAHt, were tracked. AHt was compared across groups.</p><p><strong>Main outcome measures: </strong>Achieved AHt in AI-treated boys vs controls and the PAHt.</p><p><strong>Results: </strong>The median duration of AI treatment was 2.8 years for the AI-only group and 2 years for the GH&AI group. Throughout treatment, AI-treated groups gained height similarly to controls and showed a decrease in BA SD score (AI only: P = .009; GH&AI: P = .029) and an improvement in PAHt (AI only: P = .003; GH&AI: P = .037). Compared to controls, AI-treated children achieved greater AHt (AI only: 166.6 ± 3.1 cm vs 163.4 ± 1.3 cm, P = .003; GH&AI: 167.3 ± 6.1 cm vs 164.9 ± 3.5 cm, P = .194). The difference between AHt and PAHt at baseline was more pronounced in the AI-treated groups (AI only: 3.8 ± 3.5 cm vs -0.3 ± 5.0 cm, P = .001; GH&AI: 7.5 ± 5.2 cm vs 4.3 ± 3.6 cm, P = .050).</p><p><strong>Conclusion: </strong>AI treatment extends the growth period, resulting in an AHt surpassing initial predictions. Our findings underscore the potential of AI treatment in midpubertal boys with a short PAHt due to advanced BA and in those treated with GH for ISS.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e4129-e4136"},"PeriodicalIF":5.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804696","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}