Endocrine Connections最新文献

{"title":"Later Menopause Confers No Additional Protection Against Osteoporosis in Older Women.","authors":"Zhiyi Zhou, Hao Li, Zhaojun Lu, Jiarui Chen, Jiang Xue, Siqing Song, Dequan Liu, Yufan Xu, Xinli Zhan, Chong Liu","doi":"10.1530/EC-26-0078","DOIUrl":"https://doi.org/10.1530/EC-26-0078","url":null,"abstract":"<p><strong>Background: </strong>Previous studies may have overestimated the effect of age at menopause when assessing osteoporosis risk and may have overlooked women with late menopause as a high-risk group. Therefore, we aim to clarify the association between age at menopause and osteoporosis risk, as well as to identify key characteristics of individuals with osteoporosis.</p><p><strong>Methods: </strong>This study utilized a nationally representative cross-sectional sample, including 5,804 postmenopausal women aged 55-79 years. Weighted multivariate linear regression and logistic regression models were used to assess the association between age at menopause and femoral neck BMD and osteoporosis. Core characteristics of the osteoporosis population were identified by calculating standardized coefficients and applying SHapley additive interpretation (SHAP) analysis. Restricted cubic spline (RCS) analysis and subgroup analysis were conducted on these core characteristics.</p><p><strong>Results: </strong>The age at menopause showed no significant association with osteoporosis risk in any model (P > 0.05). the two primary modifiable factors associated with reduced osteoporosis risk were BMI(OR = 0.84, 95% CI: 0.80-0.88) and hormone-use history (OR = 0.50, 95% CI: 0.33-0.74). Furthermore, RCS analyses revealed significant nonlinear relationships between age at menopause and both BMI (P < 0.001) and hormone-use history (P < 0.001). Subgroup analyses indicated that the compensatory effects of these two factors varied across different specific subgroups.</p><p><strong>Conclusion: </strong>This study reveals that the initial protective advantage in reducing osteoporosis risk conferred by a later age at menopause diminishes in later life. Maintaining a higher BMI and appropriate hormone therapy can effectively compensate for the initial risk disadvantage.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835139","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":"'Glucocorticoids, Cushing's syndrome and cellular senescence: a mechanistic link to metabolic ageing'.","authors":"Cintia M Santillan, Maha Abbas, Salvador Macip, Felicia A Hanzu","doi":"10.1530/EC-26-0197","DOIUrl":"10.1530/EC-26-0197","url":null,"abstract":"<p><p>Glucocorticoids are key regulators of immune, stress, and inflammatory responses, as well as of multiple metabolic pathways throughout life, and they play an anabolic role in tissue and organ development. Chronic glucocorticoid excess, whether due to endogenous Cushing's syndrome, long-term pharmacological treatment, or persistent stress, induces tissue-specific alterations that closely resemble those seen during physiological ageing. These shared changes include loss of tissue regenerative capacity, altered body composition, impaired glucose and lipid homeostasis, and increased cardiovascular and neuropsychiatric vulnerability. Emerging evidence indicates that glucocorticoid excess can promote cellular senescence, amplify pro-inflammatory signalling, and disrupt inter-organ communication, thereby accelerating a state of metabolic ageing. This review synthesises current clinical and experimental data linking glucocorticoid excess with cellular senescence in key metabolic organs and systems, including adipose tissue, skeletal muscle, liver, bone, the cardiovascular system, and the brain. Particular emphasis is placed on chronic neoplastic hypercortisolism as a human model, while also considering prolonged pharmacological glucocorticoid exposure and sustained stress as more prevalent, subclinical sources of hormonal overload. By integrating these lines of evidence, we outline the emerging concept of glucocorticoid-driven metabolic ageing and highlight potential mechanistic targets along the glucocorticoid axis and within senescence pathways. A better understanding of these mechanisms may inform strategies to prevent or mitigate age-related metabolic and cardiovascular complications in patients with Cushing's syndrome, in individuals exposed to long-term glucocorticoid therapy, and in the broader ageing population.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638188","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":"Pattern of height and weight development in a large cohort of underage Chinese pseudohypoparathyroidism patients from a single center.","authors":"Yi Yang, An Song, Hanze Du, Yan Jiang, Mei Li, Weibo Xia, Xiaoping Xing, Ou Wang, Hui Pan","doi":"10.1530/EC-25-0865","DOIUrl":"https://doi.org/10.1530/EC-25-0865","url":null,"abstract":"<p><strong>Objective: </strong>Pseudohypoparathyroidism (PHP) is a rare disorder characterized by hypocalcemia and elevated PTH. Although short stature is a key feature, especially in PHP type 1 (PHP1), growth data in Chinese patients remain limited.</p><p><strong>Methods: </strong>Clinical data, including height, age, and biochemical indices, were retrospectively collected from PHP1 patients at Peking Union Medical College Hospital. Molecular diagnosis was performed using MS-MLPA, Sanger sequencing, and WES. Growth charts for height, weight, and BMI in underage patients were constructed.</p><p><strong>Results: </strong>A total of 92 PHP1 patients (58 males, 34 females) including 32 pseudohypoparathyroidism type 1A (PHP-1A), 49 sporadic pseudohypoparathyroidism type 1B (PHP-S1B), and 11 autosomal dominant pseudohypoparathyroidism type 1B (PHP-AD1B) were recruited. Growth velocity peaked at 12 years in males and 5 years in females, with height plateau at 14 and 13 years. Adult height was 166.6 cm (SDS -1.04) in males and 155.0 cm (SDS -0.52) in females. PHP-1A patients had significantly shorter adult height than PHP-1B (male: 157.0±6.9 vs. 171.9±8.9, P=0.004; female: 146.8±10.2 vs. 156.2±4.9, P=0.007). PHP-1A showed early-onset weight gain from age 1, persisting into adulthood. Adult Wt-SDS was 1.67 vs. 1.55 in males and 2.00 vs. 3.10 in females (PHP-1A vs. PHP-1B). Weight curves exceeded population P50 in most groups, with no significant differences in adult weight, Wt-SDS, BMI, or obesity prevalence between subtypes.</p><p><strong>Conclusions: </strong>Chinese PHP1 patients show early growth plateau and short stature, more severe in PHP-1A. Obesity varies by subtype and sex, with earlier and more persistent weight gain in PHP-1A. These growth charts may aid clinical management.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835137","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":"Exploring the relationship between microplastic exposure and bone health.","authors":"Apostolos I Gogakos, Stergios A Polyzos, Dimitrios A Anastasilakis, Athanasios D Anastasilakis","doi":"10.1530/EC-26-0187","DOIUrl":"10.1530/EC-26-0187","url":null,"abstract":"<p><p>The ubiquity of microplastics and nanoplastics (or microplastic and nanoplastic particles, collectively MNPs) in the modern environment has led to the detection of polymer particles and polymer-associated chemicals repeatedly within human tissues and fluids, inevitably raising concern for long-term effects on organ systems, including the skeleton. Accumulated evidence over the past decade implicates MNPs and plastic-associated endocrine-disrupting chemicals (EDCs), such as phthalates and bisphenols, in pathways central to bone homeostasis and in direct cellular toxicity to bone cells. Epidemiological data that directly link MNP burden to osteoporosis or fractures in humans remain scarce; by contrast, multiple human biomonitoring studies of phthalates, bisphenol analogs, and other EDCs report associations with lower bone mineral density or with surrogate markers of bone turnover. Preclinical studies suggest plausible causal routes by which MNPs could affect bone strength. This narrative review synthesizes current human-relevant data on exposure, tissue presence, epidemiology, and mechanisms; highlights critical gaps; and proposes priorities for research and clinical surveillance.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766085","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":"Androgenetic Alopecia in Polycystic Ovary Syndrome: A Cutaneous Marker of Systemic Metabo-inflammatory and Endocrine Dysfunction: A Narrative Review.","authors":"Farzaneh Motafeghi, Marzieh Saei Ghare Naz, Fahimeh Ramezani Tehrani, Samira Behboudi Gandevani","doi":"10.1530/EC-25-0728","DOIUrl":"https://doi.org/10.1530/EC-25-0728","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine-metabolic disorder in which androgenetic alopecia (AGA) serves as a prominent clinical marker of profound systemic dysregulation, extending beyond simple hyperandrogenism. This condition imposes a significant psychosocial burden on affected women, yet its complete pathophysiology remains incompletely understood, leading to therapeutic plateaus. This review advances the central hypothesis that alopecia in PCOS results from a synergistic failure of local follicular metabolic signaling and genetic predisposition. This framework posits that the hair follicle in susceptible individuals is a site of intrinsic vulnerability where systemic insults, principally insulin resistance and chronic low-grade inflammation, converge with specific gene polymorphisms. This local pathology both amplifies, and is amplified by, systemic hyperandrogenism, rendering androgen action a necessary but insufficient component of the complete pathophysiological cascade. This integrated perspective recontextualizes the roles of insulin, inflammatory mediators, and genetic variants as direct effectors of follicular distress, not merely as upstream triggers of androgen excess. We critically synthesize the evidence supporting this model, examining the intricate intersections of systemic hormone bioavailability, local androgen conversion, follicular bioenergetics, and genetic susceptibility. Furthermore, we provide an evidence-based, mechanistically organized framework for the management of PCOS-associated alopecia, evaluating therapeutic modalities based on their targeted action within this complex network. A deeper, systems-level understanding of this interplay is essential for moving beyond current therapeutic limitations and developing personalized management strategies that address the complete pathophysiological axis, ultimately improving both cutaneous and long-term systemic health outcomes for women with PCOS.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835048","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":"Nrf2 mRNA in the First Trimester as a Predictive Biomarker for Gestational Diabetes Mellitus.","authors":"Xinli Zhong, Si Li, Xingya Liu, Qian Li, Ping Shen","doi":"10.1530/EC-26-0077","DOIUrl":"https://doi.org/10.1530/EC-26-0077","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the role of the nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE)/heme oxygenase-1 (HO-1) signaling pathway in the development of GDM during the first trimester and to evaluate its potential as an early predictor biomarker.</p><p><strong>Methods: </strong>A prospective nested case-control study including 97 matched pairs of GDM patients and healthy controls was conducted. Peripheral blood collected between gestational weeks 8 and 12 was analyzed for mRNA levels of Nrf2, Keap1, and HO-1 using quantitative real-time PCR (qRT-PCR) analysis.</p><p><strong>Results: </strong>During the first trimester, the GDM group showed significantly higher levels of Nrf2 and HO-1 mRNA, while Keap1 expression was comparable to controls. Elevated Nrf2 mRNA levels were associated with a higher GDM risk (odds ratio (OR) = 2.369, 95% confidence interval (CI): 1.700-3.302, p < 0.001), with increased Nrf2 mRNA levels being positively linked to GDM development. Receiver operating characteristic (ROC) curve analysis indicated that first-trimester Nrf2 mRNA expression could predict mid-gestation GDM diagnosis with an area under curve (AUC) of 0.770 (95%CI: 0.704-0.827).</p><p><strong>Conclusions: </strong>In the early trimester of pregnancy, individuals with GDM show a significant increase in the mRNA expression of Nrf2 and HO-1. Nrf2 mRNA serves as an independent predictor of GDM development, supporting its possible role in pathogenesis and potential utility for early screening.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835060","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":"Spectrum and genotype-phenotype correlation of NR5A1 variants in 46,XY DSD: a systematic review and meta-analysis.","authors":"Renata T Dallago, Rafael Loch Batista, Sorahia Domenice, Vania Dos Santos Nunes-Nogueira, Berenice Bilharinho Mendonca","doi":"10.1530/EC-25-0783","DOIUrl":"10.1530/EC-25-0783","url":null,"abstract":"<p><strong>Context: </strong>NR5A1 encodes steroidogenic factor 1, a master regulator of adrenal and gonadal development. Pathogenic NR5A1 variants are among the most common genetic findings in 46,XY differences of sex development (DSD), yet the broad phenotypic spectrum remains incompletely defined.</p><p><strong>Objective: </strong>This study aims to establish pooled estimates of key clinical outcomes and to clarify whether variant type predicts phenotype, pubertal course, or gender transition in NR5A1-related 46,XY DSD.</p><p><strong>Methodology: </strong>MEDLINE, Embase, and HGMD were systematically searched. Two reviewers independently screened, extracted, and appraised studies following the methodology of the Joanna Briggs Institute. Ninety-eight studies (312 individuals) were included; 35 series with ≥3 cases entered meta-analysis. Across studies, 85% presented atypical external genitalia and 15% female-like genitalia; sex of rearing was female in 54%. Spontaneous puberty occurred in 82% (95% CI: 45-96), and adrenal insufficiency in only 1.6%. All reported gender transitions were female to male (10%, 95% CI: 5-21). Missense variants represented 54%. Meta-regressions revealed no association between variant class and genital phenotype (odds ratio (OR): 1.25) or between phenotype and gender transition (OR: 0.46).</p><p><strong>Conclusion: </strong>NR5A1-related 46,XY DSD is a dynamic condition with high rates of spontaneous virilisation (82%) and minimal adrenal involvement (1.6%). The absence of clear genotype-phenotype correlations and the occurrence of female-to-male gender reassignment support a conservative, longitudinal, patient-centred model of care. Given the unpredictability of individual outcomes, the quantitative estimates from this review support a shift towards evidence-based, longitudinal care that prioritises patient autonomy by deferring irreversible decisions.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688752","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":"Development and external validation of a parsimonious endocrine-metabolic model for 12-month pregnancy prediction in women with polycystic ovary syndrome (PCOS).","authors":"Sifu Ha, Lina Liu, Jian Li, Haixin Yu, Hong Liu, Lin Ma, Xin Liu","doi":"10.1530/EC-26-0049","DOIUrl":"10.1530/EC-26-0049","url":null,"abstract":"<p><strong>Background: </strong>Women with polycystic ovary syndrome (PCOS) exhibit diverse reproductive and metabolic phenotypes, complicating short-term pregnancy counseling. We developed and externally validated a pragmatic model to predict clinical pregnancy within 12 months.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from Center A (development) and Center B (validation). Predictors included routinely available anthropometric, reproductive endocrine, metabolic, and treatment markers. We developed a multivariable logistic regression model, evaluating discrimination (AUC and precision-recall), calibration (decile-based plots), and clinical utility via decision curve analysis (DCA). Clinical pregnancy, confirmed by ultrasonography, served as the reference standard. A web-based calculator was created for bedside risk estimation.</p><p><strong>Results: </strong>In the development cohort (n = 315; 167 pregnancies), the final model retained age, anti-Müllerian hormone (AMH), LH/FSH ratio, assisted reproductive treatment, HOMA-IR, and homocysteine. The model demonstrated good discrimination (AUC = 0.813) and remained robust after internal validation (AUC = 0.800; AUPRC = 0.823). Calibration showed strong agreement between predicted and observed probabilities, despite minor deviations at higher risk levels. DCA indicated higher net benefit compared to 'treat-all' or 'treat-none' strategies across relevant thresholds. External validation confirmed acceptable discrimination (AUC = 0.759), with modest calibration attenuation (slope = 0.681; intercept = -0.019).</p><p><strong>Conclusion: </strong>This endocrine-metabolic model provides individualized 12-month pregnancy predictions for women with PCOS, demonstrating validated discrimination and decision-analytic utility. While the web calculator facilitates clinical implementation, local recalibration is recommended to ensure accuracy across different populations.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728639","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":"Predicting Time to Glycemic Stability in Hospitalized Type 2 Diabetes Patients Using Insulin Resistance Indices: A Nomogram Development and Validation Study.","authors":"Ying Ke, Shasha Shi, Nan Zhou, Hongyuan Shi, Ming Zhang, Yi He, Haixia Liu, Xiaoyun Liu, Jing Jiang, Cuicui Lv, Nan Zhao","doi":"10.1530/EC-26-0111","DOIUrl":"https://doi.org/10.1530/EC-26-0111","url":null,"abstract":"<p><strong>Background: </strong>Achieving rapid glycemic stability with intensive insulin therapy in hospitalized type 2 diabetes patients remains unpredictable. We hypothesized that underlying insulin resistance is a key determinant of this response. This exploratory study aimed to test this hypothesis and develop a predictive nomogram.</p><p><strong>Methods: </strong>We retrospectively analyzed 393 hospitalized patients initiating insulin pump therapy with continuous glucose monitoring. Stability was defined as Time in Range >70% for 24 consecutive hours. Collected data included body mass index, hemoglobin A1c (HbA1c), fasting glucose, fasting insulin, lipids, and calculated insulin resistance indices. Cox regression identified predictors of time to stability.</p><p><strong>Results: </strong>Analysis confirmed insulin resistance's significant role. Multivariate Cox regression identified older age, higher fasting insulin, elevated HbA1c, and a higher triglyceride-glucose (TyG) index as independent risk factors for prolonged time to stability (all P<0.05), with the TyG index interpreted as a marker of lipotoxic metabolic inflexibility rather than merely a surrogate of insulin resistance. A nomogram integrating these factors demonstrated good predictive accuracy, with a C-index of 0.801 (95% CI: 0.77-0.83). Calibration and decision curve analysis supported its clinical utility.</p><p><strong>Conclusion: </strong>Insulin resistance significantly influences time to glycemic stabilization. The developed nomogram, incorporating the TyG index, fasting insulin, age, and HbA1c, provides a practical tool for early risk stratification, potentially guiding more personalized inpatient diabetes management.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766141","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":"Association of basal thyroid function with clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-L1 inhibitor KL-A167: a multicenter post hoc analysis.","authors":"Keliang Chen, Haohan Fan, Shihong Xu, Jiacheng Li, Junyou Ge, Yan Qing, Youneng Wei, Yuping Xie, Xingchen Peng","doi":"10.1530/EC-26-0083","DOIUrl":"10.1530/EC-26-0083","url":null,"abstract":"<p><strong>Objective: </strong>While thyroid dysfunction during PD-L1 inhibitor therapy correlates with efficacy in recurrent/metastatic nasopharyngeal carcinoma, the prognostic value of basal thyroid function remains unclear. This study investigated the relationship between baseline serum thyroid-stimulating hormone (TSH) and clinical outcomes.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective analysis of 153 recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients from a prospective phase 2 trial of the PD-L1 inhibitor KL-A167. Patients were stratified by baseline TSH levels. Multivariate Cox and logistic regression models were used to analyze progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).</p><p><strong>Results: </strong>High basal TSH (n = 58) was independently associated with significantly prolonged OS (HR 0.56, 95% CI: 0.36-0.88; P = 0.011) and PFS (HR 0.60, 95% CI: 0.41-0.87; P = 0.008) compared to the low/normal TSH group (n = 95). Although ORR was numerically higher in the high TSH group (27.6 vs 17.9%), the difference was not statistically significant (P = 0.23). Subgroup analyses indicated consistent benefits across most clinical strata. Thyroid immune-related adverse events occurred in 32/153 (20.9%), similarly between groups (20.7 vs 21.1%, P = 0.957), and were not significantly associated with either OS (HR 0.65, 95% CI: 0.38-1.11, P = 0.117) or PFS (HR 0.88, 95% CI: 0.54-1.44, P = 0.613) by time-varying Cox regression.</p><p><strong>Conclusion: </strong>Elevated basal TSH levels are independently associated with improved survival in R/M NPC patients receiving KL-A167. Baseline TSH may serve as a simple, noninvasive biomarker for risk stratification and personalizing immunotherapy in this population.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697904","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}