Endocrine Connections最新文献

{"title":"Mitochondrial gene expression-based model for the prediction of thyroid cancer prognosis.","authors":"Weina Zha, Jingwu Li, Yufeng Li, Hanchen Li, Xiaolin Yang, Ying Liu, Chen Wang, Yi Xu, Xingchen Li, Xue Wang, Geling Liu","doi":"10.1530/EC-26-0245","DOIUrl":"10.1530/EC-26-0245","url":null,"abstract":"<p><p>The roles of mitochondrial genes in the development of thyroid cancer (TC) and the associated tumor microenvironment remain to be elucidated. Based on 64 dysregulated mitochondrial genes, unsupervised consensus clustering analysis was performed using TC datasets from The Cancer Genome Atlas and integrated gene expression databases. A dysregulated mitochondrial-based prognostic model was constructed using machine learning. Fourteen prognostic genes were identified, and the correlation between semaphorin 7A (SEMA7A) and immune cell infiltration was validated. The functions of SEMA7A were investigated through plate cloning, scratch wound healing, and Transwell invasion assays. This study constructed a prognostic model for predicting overall survival by identifying 14 mitochondrial dysregulated-based prognostic genes (APOD, ATP2C2, FAM111B, GJB4, GZMA, HHIPL2, IFIT3, IL18, MCEMP1, PRRT4, RGS16, SEMA7A, SLC2A3, and TDRD9). Its effectiveness was validated in an independent cohort. The model accurately predicted OS across cancer stages. SEMA7A expression was significantly upregulated in papillary thyroid carcinoma (PTC) tissues and PTC cell lines. Functional experiments showed that SEMA7A promoted TC progression, including cell proliferation, migration, and invasion. Compared with the SEMA7A low-expression group, the high-expression group showed a larger FOXP3+ regulatory T cell (Treg) population. Although a higher ratio of SEMA7A + CD8-positive cells/SEMA7A + FOXP3-positive cells was observed, increased Treg abundance is known to shift the immune context toward a less cytotoxic and more exhausted state. Thus, oncogenic SEMA7A in TC promotes malignant functions in TC cells and may play an important role in shaping the immunosuppressive microenvironment. Consequently, our mitochondrial dysregulation-based prognostic risk model for TC may offer good clinical application value.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445124","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":"Periconceptional use of GLP-1 receptor agonists and the risk of major congenital malformations: a systematic review and meta-analysis.","authors":"Xiangxian Liu, Beijia Xiong, Rui Yang, Haining Wang, Ye Liu","doi":"10.1530/EC-26-0280","DOIUrl":"10.1530/EC-26-0280","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic diseases, but their reproductive safety remains controversial. We assessed the impact of periconceptional GLP-1RA exposure on birth outcomes to inform their use in reproductive-aged women. PubMed, Embase, Web of Science (through December 2025) were searched for randomized controlled trials (RCTs)/cohorts reporting offspring or pregnancy outcomes in women exposed to GLP-1RAs within three months before conception or during pregnancy. The primary outcome was major congenital malformations (MCMs), compared between neonates with or without maternal GLP-1RA exposure. Secondary outcomes were spontaneous abortion, stillbirth, preterm birth, large for gestational age (LGA), and small for gestational age (SGA). One prospective and five retrospective studies involving 286,599 women (43,577 exposed and 243,022 unexposed to GLP-1RAs) were included. Meta-analysis showed no significant difference in MCM risk in the GLP-1RA exposure group, compared with the non-exposure group (relative risk (RR): 1.02, 95% CI: 0.96-1.08). Risks of preterm birth (RR: 1.09, 95% CI: 0.80-1.49), LGA (RR: 2.31, 95% CI: 0.56-9.44), SGA (RR: 0.71, 95% CI: 0.39-1.27), and stillbirth (RR: 1.16, 95% CI: 0.24-5.69) were not significantly elevated. The incidence of spontaneous abortion was comparable between the two groups in one study. Evidence suggests that periconceptional GLP-1RA exposure in women is not associated with an increased risk of MCMs or other adverse birth outcomes. However, given the observational design and limited exposed pregnancies, these findings should not be interpreted as proof of safety. Large prospective cohorts and RCTs are needed to confirm the safety of GLP-1RA usage before pregnancy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445087","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":"Maternal methyl-donor supplementation and hypothalamic methylation stability.","authors":"Thomas Gerhard Brune, Bettina Schloesser, Marianne Volleth, Martin Zenker","doi":"10.1530/EC-25-0790","DOIUrl":"10.1530/EC-25-0790","url":null,"abstract":"<p><strong>Background: </strong>Maternal nutrition can shape fetal epigenetic programming with long-term health effects. This study tested whether central and peripheral tissues differ in responsiveness to maternal methyl-donor supplementation.</p><p><strong>Methods: </strong>C57BL/6 dams received either standard chow (control) or a methyl-donor-enriched diet during pregnancy. Offspring were allocated to three groups: i) control (mother and offspring on standard chow), ii) prenatal exposure (mother on methyl-donor diet during pregnancy, offspring on standard chow thereafter), and iii) combined exposure (mother on methyl-donor diet during pregnancy and lactation, offspring continued methyl-donor diet postnatally). Global DNA methylation was measured by ELISA in the brain and hypothalamus (n = 10) and in the liver, spleen, and heart (n = 5). Exploratory hypothalamic gene expression analysis compared the prenatal exposure group vs controls (n = 4).</p><p><strong>Results: </strong>Prenatal supplementation was associated with increased global 5-methylcytosine levels in the brain and hypothalamus (both P < 0.01). In the hypothalamus, this elevation persisted irrespective of later diet, whereas peripheral organs displayed ongoing plasticity and responded strongly to postnatal exposure. Microarray analysis identified 36 differentially expressed hypothalamic transcripts, including genes previously linked to methylation-related pathways.</p><p><strong>Conclusion: </strong>Maternal methyl-donor supplementation is associated with a stable hypothalamic methylation profile established during intrauterine life, while peripheral organs remain epigenetically adaptable. These findings reveal an organ-specific divergence in developmental programming, with exploratory gene expression suggesting functional consequences.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053442","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":"Baxdrostat versus osilodrostat: steroid biosynthesis in human adrenocortical cells.","authors":"Yuki Taki, Takashi Kono, Ikki Sakuma, Naoko Hashimoto, Masataka Yokoyama, Eiryo Kawakami, Takashi Miki, Hironobu Sasano, Yasuhiro Nakamura, Tomoaki Tanaka","doi":"10.1530/EC-25-0807","DOIUrl":"10.1530/EC-25-0807","url":null,"abstract":"<p><p>To compare the functional selectivity of baxdrostat versus osilodrostat in primary human adrenocortical cells, focusing on aldosterone suppression while preserving cortisol biosynthesis, we conducted an experimental ex vivo study using primary cells derived from aldosterone-producing adenomas, cortisol-producing tumors, and normal adrenal cortex. Cells were stimulated with the adrenocorticotropic hormone (10 nM) and exposed for 72 h to baxdrostat, osilodrostat, or metyrapone (0-10 μM). Outcomes included geometric mean (GM) IC50 values for aldosterone and cortisol, LC-MS/MS steroid profiling, and molecular docking to CYP11B2/CYP11B1. In aldosterone-producing adenoma cells, baxdrostat selectively inhibited aldosterone (GM IC50 = 0.041 μM) and did not achieve 50% cortisol suppression in cortisol-producing tumor or normal adrenal cortex within 0-10 μM. Osilodrostat inhibited aldosterone (GM IC50 = 0.0022 μM) and cortisol (GM IC50 = 0.196 μM). Steroid profiling showed a modest, selective rise in 11-deoxycorticosterone with baxdrostat (+3.76-fold), whereas osilodrostat produced larger increases in 11-deoxycorticosterone (+25.4-fold) together with androgen elevations. Docking supported the mechanism: baxdrostat showed stronger predicted binding to CYP11B2 (-11.5 kcal/mol) than osilodrostat (-8.7 kcal/mol) with limited engagement of CYP11B1. Baxdrostat demonstrated greater functional selectivity for CYP11B2, with minimal cortisol axis impact and smaller upstream precursor accumulation than osilodrostat. These human-tissue data inform dose selection and safety monitoring strategies for selective aldosterone synthase inhibition in aldosterone-mediated and treatment-resistant hypertension.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263836","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":"Vertebral fracture risk in patients with differentiated thyroid cancer receiving TSH-suppressive therapy.","authors":"Dilek Gogas Yavuz, Ceyda Dincer Yazan, Zeliha Hekimsoy, Kadriye Aydin, Naile Gokkaya, Canan Ersoy, Berna İmge Aydoğan, Aysen Akalin, Ömercan Topaloğlu, Esra Nur Ademoglu Dilekci, Guven Baris Cansu, Bulent Can, Kagan Gungor, Mehtap Evran, Lezzan Keskin, Ziynet Alphan, Özlem Turhan İyidir, Levent Ozsari, Tayfun Garip, Gulsah Elbuken, Meral Mert, Zafer Pekkolay, Zeynep Cantürk, Can Ilgin, Onur Buğdaycı, Nilufer Ozdemir, Goknur Yorulmaz, Ahmet Toygar Kalkan, Yasemin Aydogan Unsal, Adnan Yay, Baris Karagun, Evin Bozkur","doi":"10.1530/EC-26-0103","DOIUrl":"10.1530/EC-26-0103","url":null,"abstract":"<p><strong>Background: </strong>Suppression of thyroid-stimulating hormone (TSH) can adversely affect bone tissue in individuals with differentiated thyroid cancer (DTC). This study aims to examine bone mineral density (BMD) and vertebral fractures (VFs) in DTC patients receiving levothyroxine (LT4) suppression therapy.</p><p><strong>Methods: </strong>A total of 990 patients with DTC who had undergone total thyroidectomy and received levothyroxine suppression therapy for a minimum of one year were included in the study. Clinical and laboratory data obtained at the most recent visit were extracted from patient records. BMD measurements of the lumbar spine and femoral regions, assessed by dual-energy X-ray absorptiometry (DXA) within the preceding year, were recorded. When available, lateral vertebral radiographs were also evaluated.</p><p><strong>Results: </strong>The study included 990 patients with DTC. According to DXA results, 545 (55.2%) had normal BMD, 363 (36.6%) had osteopenia, and 82 (8.2%) had osteoporosis. Osteoporotic patients were older and had lower BMI (P = 0.001 for both), while TSH levels were similar across groups. Among 476 patients with vertebral radiographs, 131 (27.5%) had moderate-to-severe VFs. Fracture rates were significantly higher in patients with severe TSH suppression compared with other groups (P = 0.013). Patients with VFs were older and had lower femoral neck and L1-L4 BMD (P = 0.001). Regression analysis showed that disease duration, FT4 levels, and femoral neck BMD were associated with fracture risk (P = 0.001). Multivariate analysis identified age, femoral neck BMD, L1-L4 BMD, and osteocalcin as independent predictors of osteoporosis (P = 0.001). TSH subgroups showed no differences in BMD values.</p><p><strong>Conclusion: </strong>Findings suggest that DTC patients undergoing TSH suppression have a significant risk of VFs. Assessments of VFs should be integrated into routine care for DTC survivors to ensure long-term skeletal safety.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445168","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":"External validation of the PASO prediction score for primary aldosteronism.","authors":"Alaa Abdelsalam, Mohammad Mahmoud Rajab Eddama, Virginia Rozalen-Garcia, Teng-Teng Chung, Umasuthan Srirangalingam, Gerard S Conway, Steven Hurel, Bernard Khoo, Stephanie E Baldeweg, Tom R Kurzawinski, Tarek E Abdel-Aziz","doi":"10.1530/EC-26-0255","DOIUrl":"10.1530/EC-26-0255","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong></p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445102","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":"Preconception thyroid function optimization and pregnancy outcomes in women with recurrent pregnancy loss: a real-world cohort study.","authors":"Heze Xu, Zhijiao Wang, Yijia Liu, Shanwei Xing, Hang Zhen, Jiapo Li, Chong Qiao","doi":"10.1530/EC-26-0215","DOIUrl":"10.1530/EC-26-0215","url":null,"abstract":"<p><strong>Background: </strong>The management of subclinical hypothyroidism with thyroid-stimulating hormone (TSH) levels between 2.5 and 4.0 mIU/L in women with recurrent pregnancy loss (RPL) remains controversial, as guidelines derived from general populations conflict. While a recent randomized trial confirmed the benefit of initiating levothyroxine (LT4) during early pregnancy, whether a more proactive strategy of preconception thyroid optimization improves outcomes in this high-risk group remains unknown.</p><p><strong>Methods: </strong>We conducted a retrospective cohort analysis of 896 women with RPL and elevated TSH (2.5-4.0 mIU/L) during pre-pregnancy, from the Recurrent Pregnancy Loss Cohort Study. Based on clinical records, participants were categorized into two groups: treated group (n = 636) and untreated group (n = 260). The primary outcome was miscarriage. Associations were assessed using Firth's penalized-likelihood regression to address small-sample bias, with propensity score matching as a sensitivity analysis.</p><p><strong>Results: </strong>After adjustment for antiphospholipid syndrome, degree of education, gravidity, and parity, LT4 treatment was associated with a significantly lower risk of miscarriage (adjusted odds ratio (aOR) = 0.33; 95% CI: 0.20, 0.54; P < 0.001). A reduced risk was also observed for threatened abortion (aOR = 0.49; 95% CI: 0.35, 0.71; P < 0.001). Results were robust in the propensity score-matched analysis.</p><p><strong>Conclusion: </strong>In women with RPL and elevated TSH (2.5-4.0 mIU/L), a clinical care pathway involving preconception LT4 treatment was significantly associated with a reduced risk of miscarriage. This finding provides real-world evidence supporting the potential value of proactive preconception thyroid optimization in RPL, highlighting it as a priority strategy worthy of prospective investigation versus post-conception treatment initiation.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445060","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":"Myopathy in endogenous Cushing's syndrome: type II muscle fiber atrophy and its association with age and circulating IGF-1.","authors":"Moritz Schrenk, Elisabeth Nowak, Frederick Vogel, Lucia Krüger, Isabel Stüfchen, Matthias Oettle, Tugce Apaydin, Malgorzata Bobrowicz, Martin Bidlingmaier, Natalia Garcia-Angarita, Susanna M Hofmann, Sophia M Dinges, Nicole Reisch, Georg Siebenbürger, Martin Halle, Martin Reincke, Benedikt Schoser","doi":"10.1530/EC-26-0355","DOIUrl":"10.1530/EC-26-0355","url":null,"abstract":"<p><strong>Context: </strong>Patients with endogenous Cushing's syndrome (CS) exhibit reduced muscle strength compared with healthy individuals and frequently experience a further postoperative decline despite remission.</p><p><strong>Objective: </strong>To evaluate the histological and immunohistochemical patterns underlying myopathy in patients with active and remitted CS.</p><p><strong>Patients and methods: </strong>We included nine patients with active CS and eight patients with CS in remission, prospectively enrolled at LMU Hospital. Patients in remission had curative tumor surgery and biochemical remission for ≥24 months. Biopsies of the vastus lateralis muscle were obtained surgically and analyzed by histology, immunohistochemistry and electron microscopy. IGF-1 concentrations were determined using an IDS-iSYS analyzer.</p><p><strong>Results: </strong>In active CS, the mean cross-sectional area of type II muscle fibers was reduced. Nicotinamide adenine dinucleotide staining revealed mild moth-eaten fiber patterns in four patients, accompanied by ultrastructural pathologies on electron microscopy, including increased subsarcolemmal mitochondrial aggregates that were also present in remitted CS. In active CS, circulating absolute IGF-1 concentrations positively (rs = 0.8, P = 0.014) and age inversely (rs = -0.77, P = 0.021) correlated with mean cross-sectional area of type II muscle fibers. In remission from CS, type II fiber atrophy was not present in most patients. No substantial associations were found between the severity of glucocorticoid excess and histological alterations during active or remitted disease.</p><p><strong>Conclusion: </strong>Active CS is characterized by type II fiber atrophy and is associated with circulating IGF-1 and age. In remission, type II fiber atrophy was not present, whereas mitochondrial ultrastructural alterations could be observed. These findings indicate sustained muscle alterations and highlight the need for mechanistic studies to guide targeted therapies.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445089","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":"Interpreting salivary cortisol thresholds in ectopic ACTH syndrome.","authors":"Omer Denizhan Tatar","doi":"10.1530/EC-26-0399","DOIUrl":"10.1530/EC-26-0399","url":null,"abstract":"<p><p>This Perspective comments on a recent national cohort study of ectopic ACTH syndrome that identified late-night salivary cortisol (LNSC) ≥ 130 nmol/L as an independent predictor of mortality. The finding is clinically important because it supports the prognostic relevance of biochemical severity. However, its numerical interpretation should remain method-specific. LNSC is sensitive to sampling conditions and analytical platform, and absolute values are not necessarily interchangeable across immunoassays or between immunoassays and liquid chromatography-tandem mass spectrometry. In addition, dichotomizing a continuous biomarker can reduce information and overstate apparent separation at a data-derived cut point. Building on the original authors' own assay caveat, the threshold is best viewed as a Roche ECLIA-context signal of severe hypercortisolism, pending prospective multicenter validation using continuous biomarker modeling, assay harmonization, and subgroup analyses by tumor context and treatment era.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344317","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":"Pharmacovigilance evaluation of somatrogon-associated adverse events in real-world databases.","authors":"Mengyuan Cai, Qian Guo, Huqiang Dong, Yabo Wang, Zhongyu Han, Ping Xu","doi":"10.1530/EC-26-0292","DOIUrl":"10.1530/EC-26-0292","url":null,"abstract":"<p><strong>Background: </strong>Somatrogon, a long-acting recombinant human growth hormone, is used in children with growth hormone deficiency. While clinical trials have shown its safety, real-world post-marketing data are limited, and uncommon or delayed adverse events (AEs) may not be fully recognized.</p><p><strong>Methods: </strong>We analyzed somatrogon-related AEs from the US FDA Adverse Event Reporting System (FAERS) (Q1 2004-Q2 2025) and the WHO global safety database via VigiAccess (up to Dec 2024). Disproportionality analyses were performed using four signal detection methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were assessed at both system organ class and preferred term (PT) levels. In FAERS, time to onset was examined to characterize the temporal pattern.</p><p><strong>Results: </strong>We identified 1,001 somatrogon-related reports in FAERS and 863 in VigiAccess. Most cases occurred in pediatric patients, with slightly more reports in males. At the SOC level, most AEs involved general disorders, administration site conditions, injuries, and product issues. At the PT level, recurring signals included injection-site reactions, device-related problems, and insulin-like growth factor abnormalities. Among 168 FAERS cases with valid onset data, 79.76% occurred within 30 days, with a median onset of 0 days.</p><p><strong>Conclusion: </strong>Somatrogon's real-world AE pattern shows early-onset injection-site reactions, device-related issues, and endocrine signals, highlighting the need for early treatment monitoring and ongoing post-marketing surveillance as its use grows globally.</p><p><strong>Key points: </strong>This dual-database pharmacovigilance study analyzed somatrogon-associated AE reports from FAERS and VigiAccess, providing a real-world overview of its post-marketing safety profile. Across both databases, the most consistent signal clusters were injection-site reactions, device- and product-related problems, and endocrine/laboratory abnormalities, particularly insulin-like growth factor disturbances. Among FAERS cases with valid onset data, 79.76% of reported events occurred within 30 days, with a median onset of 0 days, indicating that AEs tend to emerge early after treatment initiation. Serious outcomes were relatively uncommon, supporting the importance of early follow-up, injection-site assessment, device-use training, and IGF-1 monitoring in children receiving somatrogon.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263880","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}