Endocrine Connections最新文献

{"title":"Incidence and risk factors of venous thromboembolism in an adrenocortical carcinoma patient cohort.","authors":"Nienke Visser, Isabelle Holscher, C Willemien Menke-van der Houven van Oordt, Anton F Engelsman, Els J M Nieveen van Dijkum, Alberto M Pereira, Koen M A Dreijerink","doi":"10.1530/EC-25-0445","DOIUrl":"https://doi.org/10.1530/EC-25-0445","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy. Venous thromboembolic events (VTE) have been reported in ACC patients. ACC is often associated with endogenous hypercortisolism, which is linked to increased VTE risk. The primary objective of this retrospective study in patients who received treatment for ACC in Amsterdam UMC between 2003-2024 was to determine the total incidence of VTE. Secondary objectives included the incidence of VTE after adrenalectomy and to identify risk factors for VTE. Patients were categorized into VTE and non-VTE groups. Mann-Whitney U tests, unpaired t-tests and Chi-square or Fisher's exacts were used in order to assess differences. Seventy-four patients were included, of whom 10 (13.5%) had experienced a VTE during the observation period, amounting to 29 VTEs (CI 13-58) per 1000 patient years. All VTEs were pulmonary embolisms. 64 patients underwent adrenalectomy. 50 (98%) patients of whom data was available used peri-operative thromboprophylaxis or anticoagulant therapy. The median duration of peri-operative thromboprophylaxis was 5 days (IQR 4-11, range 0-90). Two patients experienced a VTE within six months after surgery (3,3%). Four patients with a VTE (40%) had cortisol producing ACC (p=0.83). We conclude that the overall incidence of VTE in ACC patients is high. The incidence of post-operative VTE after adrenalectomy for ACC was lower in this cohort compared with the literature. No risk factors for VTE were identified, most notably hypercortisolism was not associated with increased VTE incidence. Our findings expand the literature addressing this issue and re-affirm the importance of the use of peri-operative thromboprophylaxis in ACC patients undergoing adrenalectomy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198603","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":"BUROSUMAB PREVENTS FURTHER HEIGHT DEFICIT IN TODDLERS AFFECTED BY XLH.","authors":"Elisa Sala, Jugurtha Berkenou, Anya Rothenbuhler, Anne-Sophie Lambert, Christelle Audrain, Barbara Girerd, Marco Pitea, Stefano Mora, Agnès Linglart, Diana-Alexandra Ertl","doi":"10.1530/EC-25-0435","DOIUrl":"https://doi.org/10.1530/EC-25-0435","url":null,"abstract":"<p><strong>Background: </strong>X-linked hypophosphatemia (XLH) is a rare disease caused by PHEX variants. Besides rickets, XLH leads to disproportionately short stature which develops during the first months of life. Burosumab afforded minimal improvement of growth in children above the age of four years. No data are available on growth, including body mass index, of XLH children who started burosumab at a very young age, i.e., between one and four years.</p><p><strong>Methods: </strong>We performed a prospective follow-up of growth and other XLH-related outcomes in XLH children who started burosumab before the age of four years. We compared these children 1:2 with a historical cohort of XLH children who started vitamin D analogs and phosphate supplements before the age of four years.</p><p><strong>Results: </strong>We included 15 children treated with burosumab and 31 children treated with vitamin D analogs and phosphate supplements. In the burosumab-treated group, mean± SD for age at therapy baseline was 2.1± 0.7 (range: 1-2.9 years old). They were treated with oral phosphate and active vitamin D for 1.7±0.8 years before switching to burosumab. From birth to burosumab start, they presented a decline in height standard deviation score (SDS) from -0.3±0.7 to -1.4±0.8 (mean± SD), respectively, p<0.001. On burosumab, height SDS did not decline further during the first two years of treatment: mean± SD 0.1±0.6 (range: -0.7- 1.3 SDS) after one year (p=0.16) and 0.0±0.7 SD (range: -0.6- 1.4 SDS) after two years (p=0.54). Burosumab did not correct the acquired height deficit as children had a difference in height SDS of -1.5 SDS after two years of therapy when compared to birth length SDS (p=0.04). BMI SDS did not significantly change during the first two years on burosumab. Children treated with vitamin D analogs and phosphate supplements started treatment at a mean± SD age of 1.3±0.7 (range: 0.1-3.0 years old) and presented a continuous decline in height SDS of 0.7±0.9 SDS (range: -2.6- 1) during the first two years of therapy (p<0.001) and up to four years of age (-1.8 ± 0.9 SDS, to -1.9 ± 0.9, respectively). BMI SDS increased by 0.5±0.9 SDS (range: -0.6- 1.9) during the same period (p=0.006).</p><p><strong>In conclusion: </strong>we present data from the largest pediatric XLH cohort of very young children treated with burosumab over a follow-up period of two years. Our data suggest that, in contrast to the combination of vitamin D analogs and phosphate supplements, burosumab prevents further height deficit in XLH children, even at a period of life associated with a high growth velocity. In addition, burosumab prevents the early and excessive weight gain associated with the development of XLH in children.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198871","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":"Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions.","authors":"Wenjing Hu, Huijuan Zhu, Fengying Gong","doi":"10.1530/EC-25-0521","DOIUrl":"10.1530/EC-25-0521","url":null,"abstract":"<p><p>Leptin, a key adipokine regulating energy homeostasis, has been extensively studied for its potential in the management of obesity. However, its therapeutic efficacy is often limited due to leptin resistance. This review synthesizes animal and clinical evidence on leptin's role in obesity, focusing on models such as genetically deficient mice (e.g., ob/ob, db/db), diet-induced obesity mice, and clinical conditions such as congenital leptin deficiency (CLD), leptin receptor deficiency (LRD), lipodystrophy, and common obesity. The mechanisms underlying leptin resistance are summarized, including hyperleptinemia, impaired JAK2-STAT3 signaling, reduced blood-brain barrier permeability, defective autophagy, endoplasmic reticulum stress, inflammation, decreased leptin receptor expression, leptin signaling pathway dysfunction, increased mTOR activity, and peripheral leptin resistance. Due to these leptin receptor and/or post-receptor signaling pathway defects, leptin or its analogs usually fail to produce the expected weight-loss effect in individuals with overweight or obesity, although they remain highly effective in individuals with CLD and lipodystrophy, as well as in ob/ob mice. Alternative strategies, such as melanocortin-4 receptor (MC4R) agonists (e.g., setmelanotide) for LRD treatment, are very promising. Future directions include enhancing leptin sensitization, combining leptin with other drugs, and exploring partial leptin reduction to mitigate compensatory responses during weight loss. The review emphasizes the complexity of leptin resistance and the necessity of targeted approaches in obesity therapy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032863","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":"Reduced serum sestrin 2 levels in Hashimoto's disease: a cross-sectional study on a potential pathophysiological and diagnostic role.","authors":"Merve Ates, Mesut Ates, Murat Alisik, Ozgur Mehmet Yis","doi":"10.1530/EC-25-0546","DOIUrl":"10.1530/EC-25-0546","url":null,"abstract":"<p><strong>Objective: </strong>Expression of mammalian target of rapamycin (mTOR), which plays a key role in coordinating the balance between cell growth and autophagy, is elevated in thyroid tissues of patients with Hashimoto's disease. Sestrins are an evolutionarily conserved, stress-inducible protein family that reduces oxidative stress and regulates the adenosine monophosphate-dependent protein kinase (AMPK)-mTOR signaling pathway. The aim of this study was to investigate the potential role and significance of sestrin 2 (SESN2), a member of the sestrin family, in Hashimoto's disease.</p><p><strong>Methods: </strong>This cross-sectional study included patients with Hashimoto's disease and healthy volunteers. Thyroid autoantibodies, free T4, TSH, and sestrin 2 were measured from blood samples. Sestrin 2 was analyzed by an ELISA kit.</p><p><strong>Results: </strong>One hundred ten patients and 64 healthy volunteers were included in the study. Median SESN2 levels in the patient group (1.36 ng/mL (1.10-2.03)) were significantly lower than in the control group (1.83 ng/mL (1.34-2.64)) (P = 0.002). There was no significant difference in SESN2 levels between euthyroid and subclinical hypothyroidism subgroups of patients (P > 0.05).</p><p><strong>Conclusion: </strong>In this study, serum SESN2 levels were found to be lower in patients with Hashimoto's disease than in healthy adults, suggesting that SESN2 may have a role in the pathophysiology of Hashimoto's disease. These results indicate that further research is needed to better understand the effect of regulation of SESN2 in Hashimoto's disease on the course and pathological processes of the disease.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074634","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":"Relationship between Meteorin-like protein and type 2 diabetes mellitus: an update and meta-analysis.","authors":"Jing Xie, Yanhua Jiang, Jiayi Yao, Bin Feng, Xin Sun","doi":"10.1530/EC-25-0452","DOIUrl":"10.1530/EC-25-0452","url":null,"abstract":"<p><strong>Background: </strong>Meteorin-like protein (Metrnl) is considered a novel adipokine, which plays an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). In a previous meta-analysis, no significant difference in circulating Metrnl levels was found between T2DM patients and normal glucose tolerance individuals. However, these meta-analyses included limited studies, and more studies about Metrnl and T2DM were published recently. Therefore, the association between Metrnl and T2DM remains uncertain.</p><p><strong>Aim: </strong>This study aimed to systematically and comprehensively update the relationship between circulating Metrnl levels and T2DM.</p><p><strong>Methods: </strong>A systematic search was conducted on the Web of Science, Wiley Online Library, PubMed, and Ovid databases using the terms 'type 2 diabetes mellitus' in combination with 'Metrnl'. Meta-analysis results were reported as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs).</p><p><strong>Results: </strong>In total, 17 studies, including 649 patients with T2DM and 396 healthy controls, were included in the meta-analysis. We found that circulating Metrnl levels were lower in patients with T2DM than in healthy individuals (SMD: -0.47, 95% CI: (-0.98, 0.05); prediction interval: (-3.66, 2.73)). Moreover, serum Metrnl levels in patients with T2DM were significantly lower than in healthy individuals (SMD: -0.91, 95% CI: (-1.60, -0.22); prediction interval: (-5.03, 3.21)).</p><p><strong>Conclusions: </strong>This study aimed to systematically and comprehensively update the relationship between circulating Metrnl levels and T2DM. A clearer understanding of the role of Metrnl in T2DM could facilitate the development of effective treatments.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074637","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":"Loss of MBD2 is associated with tumor growth in small intestinal neuroendocrine tumors.","authors":"Elham Barazeghi, Samuel Backman, Per Hellman, Olov Norlén, Peter Stålberg","doi":"10.1530/EC-25-0169","DOIUrl":"10.1530/EC-25-0169","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumors (SI-NETs) represent the most frequent neoplasms of the small intestine, with loss of chromosome 18 as the most common genetic aberration. To date, no highly frequently mutated genes have been identified on chromosome 18 or elsewhere. This study aimed to explore the potential role of methyl-CpG binding domain protein 2 (MBD2), located at 18q21.2, as a tumor suppressor gene in SI-NETs. By immunohistochemistry, we found undetectable or very low levels of MBD2 expression in 64% of the analyzed SI-NETs, and overall, very low levels of mRNA and protein expression were observed. Overexpression of MBD2 in the SI-NET cell line, GOT1, reduced cell growth and induced apoptosis, though cell migration remained unaffected. In addition, MBD2 expression decreased cell proliferation and migration capacity of the neuroendocrine cells NCI-H727 but showed no effect on apoptosis. Furthermore, MBD2 expression in both cell lines was found to upregulate E-cadherin but downregulate the levels of N-cadherin and vimentin in GOT1 and NCI-H72, respectively, as determined by western blot analysis. These results suggest that MBD2 plays a role in inhibiting the epithelial-mesenchymal transition process and may function as a potential tumor suppressor gene in SI-NETs. Future studies to elucidate the underlying mechanisms are warranted.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039420","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":"Genomic features of the methylosome protein MEP50 and its implications in hormone signaling and cancer.","authors":"Gareth Pollin, Young-In Chi, Raul Urrutia, Gwen Lomberk","doi":"10.1530/EC-25-0444","DOIUrl":"10.1530/EC-25-0444","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Dysfunction of several WD40 family proteins causes diverse endocrine diseases. Until recently, MEP50, a WD40 protein, was considered a gene of unknown significance because no inherited disease had been linked to its function. However, genetic inactivation of MEP50 in mouse models or somatic mutations in humans drives oncogenesis in several endocrine-related cancers, including those of the prostate, breast, and uterus. In this study, we generate new knowledge through a multi-tier integration of evolutionary genomics, sequence and structural analyses, molecular mechanic calculations, and dynamic simulations of wild-type and cancer-mutated MEP50 proteins. Indeed, we find that a conserved splicing event across evolution generates an alternative MEP50 isoform, which is smaller than the canonical MEP50 and lacks the final β-sheet of the first WD40 domain, the entirety of the second WD40 domain, and the first β-sheet of the third WD40 domain. Notably, we find that this novel, short MEP50 (s-MEP50) transcript encodes a 278 amino acid protein that retains aspects of the key regulatory and interaction sites, including those critical for androgen receptor and PRMT5 binding. Finally, we analyze the mutational landscape of MEP50 in endocrine-regulated cancers and use molecular mechanic calculations and dynamic simulations to reveal that cancer-associated mutations disrupt conserved bonding networks and induce widespread structural destabilization within the WD40 domain architecture. Thus, by combining evolutionary, structural, and biophysical approaches, we advance the understanding of MEP50 genomics, providing significant mechanistic and clinically relevant insights into endocrine-regulated tissues and their cancers.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014184","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":"The association between sleep quality and cognitive function in patients with non-functioning pituitary adenoma.","authors":"M Brown, I L Ross, W Nkoana, M Henry","doi":"10.1530/EC-25-0082","DOIUrl":"10.1530/EC-25-0082","url":null,"abstract":"<p><strong>Background: </strong>Cortisol and growth hormone are important for sleep regulation and cognition. Sleep is critical for cognitive functioning and memory consolidation. Patients with pituitary disease experience hormonal dysregulation, impaired sleep quality, and cognitive dysfunction. We wished to examine the relationship between objective sleep and cognitive functioning in patients with pituitary adenomas.</p><p><strong>Methods: </strong>Ten patients with non-functioning pituitary adenomas (NFPA) and ten healthy controls were assessed using a crossover design. Each participant was administered standardised neuropsychological tests (Wechsler logical memory test (LMT) and finger tapping task (FTT)) assessing declarative and procedural memory performance after a period of sleep and after an equivalent period of wakefulness. Objective sleep data were elicited, and the Pittsburgh Sleep Diary captured self-reported sleep data.</p><p><strong>Results: </strong>Controls performed better than patients with NFPA on retention on the LMT (P = 0.027). Objective measures of sleep quality revealed no between-group differences, whereas controls reported better subjective sleep quality (P = 0.016) and being more alert when awake (P = 0.015) than patients. Generally, sleep was not related to cognition in either group.</p><p><strong>Conclusions: </strong>Patients demonstrated poorer performance on declarative memory tasks, but not poorer sleep. Interventions for memory rehabilitation may assist their capacity to complete other important daily activities.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023094","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":"The Combined Diagnostic and Therapeutic Value of Ultrasound and X-ray Bone Age Index in Girls with Idiopathic Central Precocious Puberty.","authors":"Linli Kan, Deng He, Wensheng Yue","doi":"10.1530/EC-25-0354","DOIUrl":"https://doi.org/10.1530/EC-25-0354","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The objectives of this study are threefold: firstly, to evaluate the diagnostic utility of ultrasound in combination with radiographic bone age assessments for identifying idiopathic central precocious puberty (ICPP) in girls; secondly, to determine the efficacy of treatment; and thirdly, to establish comprehensive models for both diagnosis and therapeutic evaluation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Female patients diagnosed with 96 cases of idiopathic central precocious puberty (ICPP) in our hospital from January 2022 to February 2024 were assigned to the research group, while 94 girls with premature thelarche (PT) from the same period were designated as the control group.Both groups underwent ultrasound examinations (of the uterus, ovaries, and breasts) and X-ray bone age evaluations, and their serum endocrine hormone levels (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) were measured. Differences in ultrasound parameters, bone age indices, and hormone levels were analyzed between the research and control groups. Univariate and multivariate LASSO regression were employed to screen imaging parameters, and a LASSO-Logistic regression model was established to create a combined predictive model. Receiver operating characteristic (ROC) curves were plotted to investigate the diagnostic efficacy of the individual and combined models in ICPP. The general clinical data and imaging parameters of the ICPP group were compared before and after treatment, with ultrasound and bone age indices used in combination to assess therapeutic efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The LASSO regression screened important predictive indicators, including the bone age index (BAI), mean bilateral breast thickness, uterine longitudinal diameter, uterine anteroposterior diameter, uterine transverse diameter, endometrial thickness, mean bilateral ovarian length, and the mean number of ovarian follicles with a diameter greater than 4 mm. These imaging parameters were incorporated into a logistic regression model, which demonstrated good discriminatory power with an AUC value of 0.895 (95% CI: 0.851, 0.938). The combined model outperformed the model using ultrasound alone (AUC: 0.869 [95% CI: 0.820, 0.918]) and the bone age index model (AUC: 0.758 [95% CI: 0.690, 0.826]), showing superior discrimination and calibration. In the follow-up evaluation of the ICPP group post-treatment, ultrasound parameters such as uterine anteroposterior diameter, mean bilateral ovarian length, mean number of ovarian follicles with a diameter greater than 4 mm, mean maximum follicular diameter, and mean bilateral ovarian volume showed good monitoring efficacy (AUC greater than 0.7). Additionally, the uterine longitudinal diameter and bone age index exhibited high specificity. Together, these indicators achieved a combined diagnostic AUC value of 0.877 with 75% sensitivity and 87% specificity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;To enhance diagnost","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124369","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":"Better growth outcomes in GH-deficient children treated younger than 2 years of age.","authors":"Tilman Robert Rohrer, Primož Kotnik, Bradley S Miller, Nicky Kelepouris, Anne Helene Olsen, Alberto Pietropoli, Michel Polak, Jo Blair","doi":"10.1530/EC-25-0493","DOIUrl":"10.1530/EC-25-0493","url":null,"abstract":"<p><strong>Background: </strong>Limited data are available on the growth response to growth hormone (GH) treatment in very young children with GH deficiency (GHD). In the present analysis, we compared clinical outcomes after GH treatment in children with GHD aged <2 and ≥2 years at the start of GH treatment.</p><p><strong>Methods: </strong>We analysed pooled data from two observational studies of paediatric patients who received Norditropin® treatment: NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905). Patients with GHD, who remained pre-pubertal after 1 year of treatment, were grouped by age at treatment start (<2 years; ≥2 years). The primary effectiveness outcome was change in height standard deviation score (SDS) after 1 and 10 years. We also investigated the frequency of non-serious adverse drug reactions (ADRs), serious ADRs and serious adverse events (SAEs).</p><p><strong>Results: </strong>In total, 507 and 7,486 children initiated treatment at <2 and ≥2 years of age, respectively. Height SDS (mean change (SD) from baseline) improved after 1 year of treatment in both groups and was greater in children initiating treatment at <2 years than in those initiating treatment at ≥2 years (1.4 (1.2) and 0.75 (0.5), respectively); these findings were sustained after 10 years of treatment (3.2 (1.7) and 2.2 (1.3), respectively). SAEs were more frequent in children initiating treatment at <2 years vs ≥ 2 years (3.3 vs 0.67%, respectively).</p><p><strong>Conclusions: </strong>Children aged <2 years at GH treatment initiation had better height outcomes, but more SAEs, after 1 and 10 years of GH treatment compared to children starting GH at age ≥2 years.</p><p><strong>Trial registration: </strong>NordiNet® IOS, ClinicalTrials.gov NCT00960128; ANSWER Program, ClinicalTrials.gov NCT01009905.</p><p><strong>Plain language summary: </strong>Data from two large studies showed that children with growth hormone deficiency (GHD) who began treatment with Norditropin® under 2 years of age had better growth than those first treated at or above 2 years of age, but also had more side effects. This highlights the value of early diagnosis, treatment and close monitoring of children with GHD.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014149","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}