Clinical Endocrinology最新文献

{"title":"Hypogonadotropic Hypogonadism Before and After Transsphenoidal Surgery for Non-Functioning Pituitary Adenoma","authors":"Victor Hantelius,&nbsp;Gudmundur Johannsson,&nbsp;Sofie Jakobsson,&nbsp;Erik Thurin,&nbsp;Tobias Hallen,&nbsp;Thomas Skoglund,&nbsp;Oskar Ragnarsson","doi":"10.1111/cen.70139","DOIUrl":"10.1111/cen.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The effect of transsphenoidal surgery (TSS) on the hypothalamic-pituitary-gonadal (HPG) axis in patients with non-functioning pituitary adenomas (NFPA) is underexplored, especially in women. Our aim was to investigate the HPG axis function before and after TSS, its association with quality of life (QoL), and to identify factors that predict its recovery after TSS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>This was a prospective cohort study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>One hundred twenty-two consecutive patients, 73 men and 49 women, with NFPA planned for TSS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Endocrine function and QoL were assessed before and 12 months after TSS. Psychological well-being was evaluated using the Psychological General Well-Being index (PGWBi).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Before surgery, 50 of 73 (68%) men had hypogonadotropic hypogonadism (HH), of whom four (8%) recovered. Eight of 13 (62%) women of reproductive age had preoperative HH, of whom 5 (63%) regained regular menstrual cycles. Preoperative central hypothyroidism (<i>p</i> = 0.046) and male sex (<i>p</i> = 0.027) were predictors of persistent HH.</p>\u0000 \u0000 <p>The median total PGWBi score increased in both men and women following surgery (<i>p</i> &lt; 0.001). Comparing psychological well-being within subgroups in patients with preoperative HH, categorised by sex (men or women of reproductive age) and postoperative recovery status, only women of reproductive age who recovered their HPG axis experienced improved psychological well-being.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HH is frequent in men and women with NFPA planned for TSS. Postoperative HPG axis recovery rate is higher in women and is associated with improved QoL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"442-451"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignancy in Pediatric Hyperfunctioning Thyroid Nodules: A Case Report and Literature Review","authors":"Cristina Clausi,&nbsp;Simona Censi,&nbsp;Jacopo Maria Arnone,&nbsp;Giulia Messina,&nbsp;Ilaria Piva,&nbsp;Fausto Cortese,&nbsp;Loris Bertazza,&nbsp;Susi Barollo,&nbsp;Francesca Galuppini,&nbsp;Marco Zarantonello,&nbsp;Maurizio Iacobone,&nbsp;Gianmaria Pennelli,&nbsp;Caterina Mian","doi":"10.1111/cen.70165","DOIUrl":"10.1111/cen.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Thyroid nodules are rare in children but carry a markedly higher risk of malignancy compared to adults (20%–26% vs. 5%). Hyperfunctioning thyroid nodules are exceptionally uncommon in the pediatric population and are typically benign. We describe a rare case of a hyperfunctioning thyroid nodule in a prepubertal child that was ultimately diagnosed as an angioinvasive encapsulated follicular carcinoma, arising in the context of the WHO entity ‘follicular adenoma showing papillary architecture’. In addition, we provide a comprehensive review of published pediatric cases of hyperfunctioning thyroid nodules with malignant histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 12-year-old boy presented with a left-sided thyroid nodule detected on ultrasound after cervical swelling. Laboratory evaluation revealed suppressed thyroid-stimulating hormone (TSH), with free thyroxine (fT4) and free triiodothyronine (fT3) within the reference range. Serial ultrasound examinations revealed a progressively enlarging mildly hypoechoic nodule, autonomously functioning on thyroid scintigraphy. Fine-needle aspiration cytology (FNAC) was classified as TIR2. Surgical excision showed a follicular-patterned neoplasm showing papillary features, focal capsular and vascular invasion and no lymph node metastases. Comprehensive molecular analysis identified a pathogenic somatic variant in the <i>GNAS</i> gene, whereas no alterations were detected in <i>TSHR</i>, <i>BRAF</i>, <i>RAS</i> genes, the <i>TERT</i> promoter, or <i>DICER1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case highlights the importance of an integrated evaluation in pediatric thyroid nodules, particularly when hyperfunction coexists with indeterminate or suspicious imaging features. Follicular-patterned thyroid neoplasms showing papillary architecture pose diagnostic challenges in children, and molecular analysis may assist risk stratification and elucidate pathogenetic mechanisms linking autonomous function and malignant transformation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"474-485"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Parathyroid Localization in Real Life: The Role of Expert-Performed Ultrasonography","authors":"Tzahi Yamin,&nbsp;Nir Battat,&nbsp;Annat Blank,&nbsp;Shmuel Meirsdorf,&nbsp;Bar Sara Zigdon,&nbsp;Oded Cohen,&nbsp;Avi Khafif","doi":"10.1111/cen.70154","DOIUrl":"10.1111/cen.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the accuracy of expert-performed ultrasonography (US) for preoperative localization in minimally invasive parathyroidectomy (MIP) compared with community US and other imaging modalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design</h3>\u0000 \u0000 <p>Retrospective cohort study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Setting</h3>\u0000 \u0000 <p>Tertiary referral center for endocrine surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective, single-center diagnostic accuracy study of 227 patients with primary hyperparathyroidism who underwent surgery and pre-operative imaging by a dedicated neck radiologist (expert US). Sensitivity, specificity, and positive predictive value (PPV) were calculated, and were compared to other imaging modalities including community US, 99mTc-MIBI, SPECT-CT and 4DCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Expert US showed high sensitivity (89%), specificity (98%), and PPV (95%), correctly localizing adenomas in 89% of cases. It outperformed the sensitivity and specificity of community US (50%/95%), MIBI (75%/95%), SPECT-CT (82%/96%) and 4D-CT (52%/94%), respectively, particularly in atypical cases like ectopic adenomas (25% prevalence) and multiglandular disease (6% prevalence).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Expert-performed US should be considered the primary imaging modality for guiding MIP. Surgeons should consider referring patients to an expert ultrasonographer in cases of suspected ectopic adenoma, presence of multiglandular disease, before referring to 4D-CT scans or when considering bilateral neck explorations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"386-394"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid Carcinoma Revisited: Clinical and Pathological Insights From Two Decades of Experience","authors":"Ayushi Singhal,&nbsp;Subhash Chandra Yadav,&nbsp;Ayushi Chak,&nbsp;Anjali Mishra,&nbsp;Ayush Gupta,&nbsp;Preeti Dabadghao,&nbsp;Shivendra Verma,&nbsp;Ambica Tandon,&nbsp;Bibhuti Bhusan Mohanta","doi":"10.1111/cen.70194","DOIUrl":"10.1111/cen.70194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parathyroid carcinoma is a rare endocrine malignancy (&lt; 1% of primary hyperparathyroidism and 0.005% of all cancers) that often mimics a benign adenoma, leading to diagnosis only after surgery, unless invasion or metastasis is present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To identify distinguishing clinical, biochemical and pathological features of parathyroid carcinoma in comparison with primary parathyroid adenoma and atypical parathyroid tumor and to determine its perioperative predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis compared 16 histopathologically confirmed parathyroid carcinoma cases with 378 primary parathyroid adenoma and 11 atypical parathyroid tumors, evaluating and contrasting their clinical and laboratory features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant differences in age or gender were observed across groups. Parathyroid carcinoma was significantly associated with hoarseness, hypercalcaemic crisis, palpable neck mass (all <i>p</i> &lt; 0.001), pancreatitis, and concomitant bone/kidney involvement (both <i>p</i> &lt; 0.05). Ridge-penalized logistic regression identified hoarseness, palpable neck mass and an involved parathyroid gland weight ≥ 3 grams (g) as significant perioperative predictors of parathyroid carcinoma while adenoma diameter, serum calcium levels and intact parathyroid hormone (iPTH) were not statistically significant. ROC analysis showed parathyroid adenoma weight of ≥ 7.5 g had the highest diagnostic accuracy (75% sensitivity, 86% specificity), whereas serum calcium and iPTH exhibited only moderate diagnostic performance. Recurrence was observed in 31% of cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Parathyroid carcinoma exhibits more severe clinical and biochemical features and greater gland weight than benign lesions. The high recurrence rate necessitates rigorous long-term surveillance. While offering a framework for preoperative risk stratification, these retrospective findings require prospective validation in larger cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"395-407"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Comparative Analysis of Incidental and Non-Incidental Papillary Thyroid Microcarcinoma Outcomes: Implications on Management Recommendations’","authors":"Jingyi Zheng,&nbsp;Jun Zhang","doi":"10.1111/cen.70191","DOIUrl":"10.1111/cen.70191","url":null,"abstract":"","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"519-520"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal–Neonatal Metabolic Continuity and Early Postnatal HPG Axis Activity in Healthy Term Neonates","authors":"Merve Koca,&nbsp;Murat Karaoglan,&nbsp;Neslihan Bayramoglu Tepe,&nbsp;Elif Isbilen,&nbsp;Mehmet Hamdi Sahan,&nbsp;Umut Disibuyuk","doi":"10.1111/cen.70193","DOIUrl":"10.1111/cen.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Leptin integrates metabolic and reproductive signaling later in life; however, whether maternal metabolic cues influence early neonatal hypothalamic–pituitary–gonadal (HPG) axis activity remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate associations between maternal metabolic markers and early neonatal reproductive hormone activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty healthy term neonates (20 males) were prospectively evaluated. Maternal venous blood samples were collected at delivery, and neonatal blood samples were obtained within the first 24 h after birth. Maternal and neonatal adipokines and reproductive hormones were analyzed using correlation and simplified multivariable regression analyses. False discovery rate (FDR) correction using the Benjamini–Hochberg procedure was applied for multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Maternal leptin was positively associated with neonatal leptin concentrations (<i>r</i> = 0.52, <i>p</i> = 0.001; adjusted <i>β</i> = 0.47, <i>p</i> = 0.001), supporting maternal–neonatal metabolic continuity. However, maternal leptin was not significantly associated with neonatal LH concentrations (<i>β</i> = 0.00009, <i>p</i> = 0.347). Sex remained the strongest independent predictor of neonatal LH levels (<i>β</i> = 1.21, <i>p</i> = 0.011). Neonatal leptin was positively associated with triceps skinfold thickness (<i>β</i> = 1503.14, <i>p</i> = 0.034). Most exploratory associations did not remain statistically significant after FDR correction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Maternal metabolic markers were associated with neonatal metabolic parameters but were not strongly associated with early neonatal gonadotropin levels in this cohort. Larger longitudinal studies are required to clarify potential interactions between metabolic and reproductive pathways during later phases of mini-puberty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"432-441"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Osilodrostat on Health-Related Quality of Life in Cushing's Disease: Analysis of Patient-Reported Outcomes From the Phase III LINC 3 and LINC 4 Clinical Trials","authors":"John Newell-Price,&nbsp;Beverly M. K. Biller,&nbsp;Maria Fleseriu,&nbsp;Beatrice Gueron,&nbsp;Grzegorz Binowski,&nbsp;Anna Paćkowska,&nbsp;Mônica R. Gadelha","doi":"10.1111/cen.70166","DOIUrl":"10.1111/cen.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Evaluate the effects of osilodrostat short- and long-term treatment on health-related quality of life (HRQoL) in Cushing's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>LINC 3 and LINC 4 studies (pooled analysis).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>185 patients (mean baseline total scores: Cushing's Quality of Life [CushingQoL], 44.0; Beck Depression Inventory II [BDI-II], 15.6; EuroQol Five Dimensions Five Levels [EQ-­5D-5L], 0.7).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Changes from baseline in CushingQoL, BDI-­II and EQ-5D-5L scores. CushingQoL and EuroQol Five Dimensions Three Levels (EQ-5D-3L) scores were assessed in analyses of hypocortisolism-related adverse events (HAEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean CushingQoL score improved (all <i>p</i> &lt; 0.001) by +7.72 (Week [W]12), +11.45 (W26; achieving minimal clinically important difference [MCID]) and +15.32 (W72). Mean BDI-II score improved (all <i>p</i> &lt; 0.001) by −19.0% (W12; achieving MCID) and −41.2% (W72). EQ-5D-5L utility score improved over W26–72 (<i>p</i> &lt; 0.01), reaching the MCID range at W26. All items/domains in the HRQoL questionnaires significantly improved over time (<i>p</i> &lt; 0.001; ordinal mixed-effects regression), except one BDI-II item (past failure) and one EQ-5D-5L domain (self-care). CushingQoL total score improved in patients with mild (mean urinary free cortisol [mUFC] ≤ 2x upper limit of normal [ULN]), moderate (mUFC &gt; 2–5 × ULN) and severe (mUFC &gt; 5 × ULN) hypercortisolism. BDI-II and EQ-5D-5L total scores improved in patients with moderate and severe hypercortisolism. Grade 3 HAEs temporarily reduced CushingQoL and EQ-5D-3L scores during event weeks. In the multivariable models, longer treatment duration was associated with CushingQoL improvements; higher mUFC, higher body mass index, and occurrence of HAEs were associated with lower CushingQoL scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Osilodrostat improved HRQoL, with clinically meaningful, consistent improvements across HRQoL assessments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"452-463"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Therapy With Metformin, Inositol and Dietary Restriction Improves Insulin Resistance and Endocrine Outcomes in Women With Polyendocrine Metabolic Ovarian Syndrome: A Randomized Controlled Trial","authors":"Noor-ul-ain Irfan,&nbsp;Shemaila Saleem,&nbsp;Asma Irfan","doi":"10.1111/cen.70188","DOIUrl":"10.1111/cen.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine–metabolic disorder characterized by insulin resistance, hyperandrogenism and ovulatory dysfunction. Metformin, inositol supplementation and lifestyle modification are widely used treatments, but direct comparative evidence remains limited. Multimodal therapy combining metformin, inositol and dietary restriction produces greater metabolic and reproductive improvement than single-modality interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a 12-week randomized controlled trial in 192 women aged 18–35 years diagnosed with PMOS according to Rotterdam criteria. Participants were allocated to metformin (1500–2000 mg/day), inositol (myo-inositol 2 g plus <span>d</span>-chiro-inositol 50 mg twice daily), calorie-restricted diet (1200–1500 kcal/day), or combination therapy. Primary outcomes included changes in body mass index (BMI) and insulin resistance assessed by HOMA-IR. Secondary outcomes included testosterone, LH/FSH ratio and menstrual regularity. Analysis was performed using analysis of covariance (ANCOVA), with post-intervention values as dependent variables and corresponding baseline values as covariates. Categorical outcomes were compared using the Chi-square test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All interventions improved metabolic and endocrine parameters. Combination therapy resulted in the greatest reduction in HOMA-IR (− 2.64, 95% CI − 2.82 to −2.46, <i>p</i> &lt; 0.001) and BMI (− 2.8 kg/m², 95% CI − 3.05 to −2.55, <i>p</i> &lt; 0.001). Menstrual cyclicity improved across all groups, with the highest proportion of participants reporting cycle regularisation in the combination therapy group (85.4%), compared with dietary restriction (72.9%), inositol (64.6%), and metformin (39.6%) (<i>p</i> &lt; 0.001). Given the short follow-up duration, these findings reflect early improvements rather than sustained normalisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Multimodal therapy was associated with superior metabolic and reproductive outcomes compared with single-modality interventions in women with PMOS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical trial registration</h3>\u0000 \u0000 <p>ClinicalTrials. gov (NCT07380841)</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"505-513"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in Diagnosing Central Adrenal Insufficiency in Children: Cortisol-Stimulating Tests are Safe and Often Required","authors":"Mariana Peduti Halah,&nbsp;Ana Carolina Maia Teodózio,&nbsp;Davi Casale Aragon,&nbsp;Paula Conde Lamparelli Elias,&nbsp;Margaret de Castro,&nbsp;Ayrton Custodio Moreira,&nbsp;Sonir Rauber Antonini","doi":"10.1111/cen.70164","DOIUrl":"10.1111/cen.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The accuracy and safety of cortisol-stimulating tests (CSTs) for assessing hypothalamic–pituitary–adrenal (HPA) axis integrity, including the diagnosis of central adrenal insufficiency (CAI), in children remain uncertain. Although these tests can simultaneously evaluate cortisol and growth hormone secretion, the present study focuses exclusively on cortisol measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the diagnostic accuracy and safety profile of CST in pediatric patients submitted to insulin tolerance test (ITT) or glucagon-stimulation test (GST) in a tertiary center for 15 years in this retrospective cohort study. According to cortisol (F; nmol/L), we classified patients as having CAI (Fbasal &lt; 138 or Fpeak &lt; 414), indeterminate (Fbasal = 138−358.7 or Fpeak = 414−496.6), and normal (Fbasal &gt; 358.7 or Fpeak &gt; 496.6). Cutoffs were selected based on the literature and on our University Hospital protocol. Plasma cortisol was measured using a consistent radioimmunoassay (RIA) following extraction, with duplicate analyses. The assay had a detection limit of 33.11 nmol/L, with intra- and inter-assay coefficients of variation of 5% and 10.5%, respectively. We evaluated the sensitivity, specificity, likelihood ratios (LR), and clinicopathological variables associated with Fbasal and Fpeak.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 904 patients (60.1% males; median age 10.1 years [0.1−17.1]), CAI was confirmed in 79 (8.7%). Mild hypoglycemia (ITT), and nausea and vomiting (GST) occurred in 46% and 17.5%, respectively. No serious adverse events occurred. Fbasal classified 58% of patients as indeterminate. A Fbasal cutoff of 96.6 had a specificity of 99% and LR+ of 7.6, but low sensitivity (5.3%). In GST, a Fpeak of 303.5 had weak diagnostic accuracy (LR+ of 2.8) and low sensitivity (17%). Concomitant central hypothyroidism and a Fbasal &lt; 154.5 were associated with lower Fpeak, and pituitary stalk interruption was associated with lower Fbasal and Fpeak.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fbasal did not present good diagnostic accuracy. However, Fbasal &lt; 96.6 nmol/L predicted lower Fpeak. Therefore, many patients require CST to confirm or exclude CAI. ITT and GST are safe for young patients when performed in experienced centers in a controlled environment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"408-415"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the Luteinizing Hormone/Follicle-Stimulating Hormone Ratio in Polycystic Ovary Syndrome: Associations With a Possible Neuroendocrine and Anti-Müllerian Hormone-Related Phenotype","authors":"Mert Yesiladali,&nbsp;Melis Yazici,&nbsp;Zeynep Ece Utkan Korun,&nbsp;Rukset Attar,&nbsp;Erkut Attar,&nbsp;Fahrettin Kelestimur","doi":"10.1111/cen.70179","DOIUrl":"10.1111/cen.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To comprehensively reassess the clinical and metabolic significance of the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio in women with polycystic ovary syndrome (PCOS), and to investigate whether it is associated with a clinical and hormonal pattern consistent with a possible neuroendocrine-dominant subgroup, distinguishable from insulin-related metabolic presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Observational cross-sectional study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cross-sectional study included 316 women diagnosed with PCOS according to the Rotterdam criteria at a tertiary university hospital. Patients were categorised based on their LH:FSH ratio (using a cut-off of 2) and their PCOS phenotypes (Phenotypes A, B, C, and D). Clinical, hormonal, and metabolic parameters, including anti-Müllerian hormone (AMH) levels and ovarian volume, were compared across groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 316 patients, 18.35% had an LH:FSH ratio &gt;2. A strong positive correlation was found between LH:FSH ratio and AMH levels (<i>r</i> = 0.65, <i>p</i> &lt; 0.001), and a significant correlation was observed with ovarian volume (<i>r</i> = 0.20, <i>p</i> = 0.001) and polycystic ovarian morphology (mean LH:FSH 1.59 vs. 1.15, <i>p</i> &lt; 0.001). Patients with phenotype D (OA + PCOM, non-hyperandrogenic PCOS) exhibited the highest LH:FSH ratio (1.75 ± 0.87). Higher LH:FSH ratios were associated with oligo/amenorrhea (1.59 vs. 1.22, <i>p</i> &lt; 0.001), anovulation (1.66 vs. 1.16, <i>p</i> &lt; 0.001), and lower midluteal progesterone (ρ = −0.28, <i>p</i> &lt; 0.001), but not with serum androgens or Ferriman-Gallwey scores. Weak positive correlations were observed with insulin levels (ρ = 0.18, <i>p</i> = 0.022) and HOMA-IR (ρ = 0.18, <i>p</i> = 0.021), but no significant associations were found with BMI, glucose tolerance, or lipid profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A high LH:FSH ratio is associated with a clinical and hormonal pattern—including elevated AMH levels, prominent PCOM, and anovulation—that may be consistent with a neuroendocrine-dominant presentation of PCOS, rather than metabolic or androgenic disturbances. If confirmed by prospective studies, this association could inform more individualised therapeutic approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 4","pages":"493-504"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}