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Somapacitan in children born small for gestational age: 4-year results from phase 2. 出生时小于胎龄儿童的Somapacitan: 4年的第二阶段结果。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag017
Anders Juul, Michael Højby, Masanobu Kawai, Agnès Linglart, Jun Mori, Nehama Zuckerman-Levin, Philippe Backeljauw

Objective: Evaluate long-term efficacy, safety, and tolerability of once-weekly somapacitan, a long-acting growth hormone (GH) derivative, in children born small for gestational age (SGA) with short stature, including after switching from daily GH.

Design: REAL5 (NCT03878446) is a global, randomized, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension I, and an ongoing 4-year extension II.

Methods: Sixty-two children born SGA with short stature were recruited at 38 clinics across 12 countries and randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day) until week 52 (inclusive main phase and extension I). Sixty participants entered extension II. Forty-eight participants switched to somapacitan 0.24 mg/kg/week from cohorts randomized to daily GH or lower somapacitan doses. Fifty-five children completed 208 weeks of treatment. Novel safety and efficacy results from week 52 to 208 are presented here.

Results: Across all treatment arms, continuous increases in height standard deviation scores were observed from week 52 to week 208, including after switch to somapacitan 0.24 mg/kg/week. The safety and tolerability profile for somapacitan 0.24 mg/kg/week was similar to the well-established safety and tolerability profile for daily GH in SGA. Patient preference questionnaire results indicate that most respondents (87%) prefer somapacitan over daily GH. Most respondents (80%) answered that they expect to be more adherent to treatment with somapacitan.

Conclusions: These results support long-term continuous efficacy, safety, and tolerability of GH therapy with somapacitan 0.24 mg/kg/week for up to 4 years in children born SGA, including after switching from daily GH.

Clinicaltrials.gov: NCT03878446.

目的:评估每周一次的长效生长激素衍生物somapacitan在出生时小于胎龄(SGA)且身材矮小的儿童(包括从每日生长激素转换后)的长期疗效、安全性和耐受性。设计:REAL5 (NCT03878446)是一项全球性、随机、开放标签、对照的2期研究,包括26周的主期、26周的延长期和正在进行的4年延长期。方法:在12个国家的38个诊所招募了62名身高矮小的SGA儿童,随机(1:1:1:1:1)接受somapacitan(0.16、0.20或0.24 mg/kg/周)或每日GH(0.035或0.067 mg/kg/天)治疗,直到第52周(包括主要阶段和延长期I)。60名与会者参加延期二。48名参与者从随机分配到每日GH或较低剂量的somapacitan的队列中切换到每周0.24 mg/kg的somapacitan。55名儿童完成了208周的治疗。从第52周到第208周,新的安全性和有效性结果在这里展示。结果:在所有治疗组中,从第52周到第208周,包括改用somapacitan 0.24 mg/kg/周后,观察到身高标准差评分持续增加。每周0.24 mg/kg的somapacitan的安全性和耐受性与SGA中每日GH的安全性和耐受性相似。患者偏好问卷调查结果显示,大多数受访者(87%)更喜欢somapacitan而不是每日GH。大多数受访者(80%)回答说,他们希望更坚持使用somapacitan治疗。结论:这些结果支持生长激素治疗在SGA出生的儿童中使用0.24 mg/kg/周的somapacitan治疗长达4年的长期持续有效性、安全性和耐受性,包括从每日生长激素转换后。
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引用次数: 0
Adrenal histologic and genetic characteristics of primary aldosteronism in late adulthood. 成年晚期原发性醛固酮增多症的肾上腺组织学和遗传特征。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag022
Amy R Blinder, Dina Sapiro, Jessica E Baker, Zhaoping Qin, Irina Bancos, Melanie L Lyden, William F Young, Heather Wachtel, Debbie L Cohen, Lydia Kürzinger, Martin Fassnacht, James M Luther, Tracy Ann Williams, Martin Reincke, Adina F Turcu, Tobias Else, Thomas J Giordano, Aaron M Udager, William E Rainey, Kazutaka Nanba

Objective: Recent studies suggest a unique disease profile in elderly patients with primary aldosteronism (PA), who have a high prevalence of comorbidities and low clinical cure rate post-adrenalectomy. This study aims to investigate histopathology and genetic characteristics of PA in late adulthood.

Methods: Formalin-fixed, paraffin-embedded adrenal tissue sections from 114 patients with PA who underwent unilateral adrenalectomy at age 60 or older were used. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed for histopathologic analysis. Somatic DNA variants were identified in aldosterone-producing tissue following CYP11B2 IHC-guided sequencing.

Results: Histopathologic analysis revealed that 56 adrenals contained an aldosterone-producing nodule (APN) (49%), 44 contained an aldosterone-producing adenoma (APA) (39%), 7 contained multiple APN (6%), and 7 contained only non-functioning adenomas [NFA, of which 6 had at least one aldosterone-producing micronodule (APM) in the adjacent tissue] (6%). NFAs were also identified alongside APN/APA in 24 cases. An APN was the most common histologic subtype in men (51/88, 58%), while APA was predominant in women (18/26, 69%). Of 67 APNs with successful sequencing, the majority had variants in CACNA1D (40/67, 60%). KCNJ5 variants were the most common alteration in APA (14/44, 32%).

Conclusions: Older individuals with lateralized PA exhibit distinct genetic and histologic causes of disease with sex differences in mutation prevalence and adrenal histopathology. In APN, the most frequently altered gene is CACNA1D, while KCNJ5 variants are most common in APA. Unlike young patients with PA, the presence of NFA is a frequent observation in late adulthood individuals with PA.

目的:最近的研究表明,老年原发性醛固酮增多症(PA)患者具有独特的疾病特征,其肾上腺切除术后的合并症患病率高,临床治愈率低。本研究旨在探讨成年晚期PA的组织病理学和遗传特征。方法:114例60岁及以上行单侧肾上腺切除术的PA患者,采用福尔马林固定石蜡包埋肾上腺组织切片。采用醛固酮合成酶(CYP11B2)免疫组化(IHC)进行组织病理学分析。通过CYP11B2 ihc引导测序,在醛固酮产生组织中鉴定出体细胞DNA变异。结果:组织病理学分析显示56例肾上腺含有醛固酮生成结节(APN)(49%), 44例肾上腺含有醛固酮生成腺瘤(APA)(39%), 7例肾上腺含有多发APN(6%), 7例肾上腺仅含有无功能腺瘤[NFA,其中6例相邻组织中至少有一个醛固酮生成微结节(APM)](6%)。在24例中,NFA与APN/APA同时被发现。APN是男性最常见的组织学亚型(51/88,58%),而APA在女性中占主导地位(18/26,69%)。在测序成功的67例APN中,大多数存在CACNA1D变异(40/ 66,60 %)。KCNJ5变异是APA中最常见的变异(14/44,32%)。结论:老年侧PA患者表现出不同的遗传和组织学原因,在突变发生率和肾上腺组织病理学上存在性别差异。在APN中,最常见的改变基因是CACNA1D,而KCNJ5变异在APA中最常见。与年轻PA患者不同,成年晚期PA患者常出现NFA。
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引用次数: 0
Endocrine and metabolic late effects in childhood cancer survivors in Germany: the VersKiK study. 德国儿童癌症幸存者的内分泌和代谢晚期效应:VersKiK研究
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 Epub Date: 2026-01-19 DOI: 10.1093/ejendo/lvag010
Pietro Trocchi, Enno Swart, Ekaterina Aleshchenko, Hiltrud Merzenich, Cecile Ronckers, Katja Baust, Gabriele Calaminus, Thorsten Langer, Peter Ihle, Jutta Küpper-Nybelen, Christian Lüpkes, Patrik Dröge, Thomas Ruhnke, Dirk Horenkamp-Sonntag, Ursula Marschall, Melanie Klein, Claudia Spix, Christian Apfelbacher, Judith Gebauer

Objective: Endocrine and metabolic diseases are known to be common late effects in childhood cancer survivors (CCS). We assessed the prevalence of these diseases in a large German CCS cohort, and a matched comparison population, using health claims data.

Design: The cohort study was based on record linkage between the nationwide German Childhood Cancer Registry and claims data from 13 major German statutory health insurances.

Methods: The monitored insurance period covered the years 2017-2021. We assessed the frequencies of endocrine and metabolic diseases among 11 863 five-year CCS, diagnosed 1991-2021, with continuous insurance coverage and a matched comparison group of 35 589 insured persons without a history of childhood cancer. We present prevalence and prevalence ratios (PR) with corresponding 95% confidence intervals (95% CI).

Results: At least one endocrine or metabolic disease was recorded in 31.3% of survivors (n = 3716) and in 16.4% of the comparison group (n = 5819, PR = 1.9; 95% CI: 1.8-2.0). The frequency of diseases was higher among females than among males in both groups. The PR was 2.4 (95% CI: 2.3-2.5) for males and 1.6 (95% CI: 1.5-1.7) for females. The frequency of at least one disease increased with increasing attained age. The disease with the highest frequency among CCS was hypothyroidism (15.85%), and the highest PR was estimated for patients with primary thyroid cancer (43.5; 95% CI: 24.2-78.1).

Conclusions: Our study highlights the increased vulnerability of CCS to endocrine and metabolic diseases compared to the general population and underscores the need for risk-adapted surveillance during the whole survivorship trajectory.

目的:已知内分泌和代谢性疾病是儿童癌症幸存者(CCS)常见的晚期效应。我们使用健康声明数据评估了这些疾病在大型德国CCS队列和匹配的比较人群中的患病率。设计:队列研究基于德国全国儿童癌症登记处和13个主要德国法定健康保险索赔数据之间的记录联系。方法:监测保险期为2017-2021年。我们评估了11,863名1991-2021年诊断为连续保险的5年期CCS患者的内分泌和代谢疾病的频率,以及35,589名没有儿童癌症史的参保人员的匹配对照组。我们给出了患病率和患病率比(PR)以及相应的95%置信区间(95% CI)。结果:31.3%的幸存者(n = 3716)和16.4%的对照组(n = 5819, PR = 1.9; 95% CI: 1.8-2.0)至少有一种内分泌或代谢性疾病。在两组中,女性患病的频率都高于男性。男性的PR为2.4 (95% CI: 2.3-2.5),女性的PR为1.6 (95% CI: 1.5-1.7)。至少有一种疾病的发生频率随着年龄的增长而增加。CCS中发病率最高的疾病是甲状腺功能减退症(15.85%),估计原发性甲状腺癌患者的PR最高(43.5;95% CI: 24.2-78.1)。结论:我们的研究强调了与一般人群相比,CCS对内分泌和代谢疾病的易感性增加,并强调了在整个生存轨迹中进行风险适应监测的必要性。
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引用次数: 0
Adrenal androgens as predictors of growth characteristics in premature pubarche. 肾上腺雄激素作为早产婴儿生长特征的预测因子。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag024
Mehmet Eltan, Zehra Yavas Abali, Aylin Tugba Canbaz, Tarik Kirkgoz, Sare Betul Kaygusuz, Busra Gurpinar Tosun, Tuba Seven Menevse, Didem Helvacioglu, Ali Yaman, Goncagul Haklar, Serap Turan, Abdullah Bereket, Tulay Guran

Background: Premature pubarche (PP) is characterized by the early onset of pubic or axillary hair, body odor, or mild acne, most commonly reflected by elevated plasma dehydroepiandrosterone-sulfate (DHEA-S) concentrations. However, recent evidence suggests that 11-oxygenated adrenal androgens [11β-hydroxyandrostenedione (11OHA4), 11β-hydroxytestosterone (11OHT)] may better represent true androgenic activity.

Aim: This study aims to evaluate the predictive value of adrenal androgens in determining growth characteristics among girls with PP.

Subjects and methods: A prospective study was conducted to evaluate anthropometric and clinical features and to quantify plasma adrenal androgens-including DHEA, DHEA-S, androstenedione (A4), androsterone, 11OHA4, and 11OHT-using liquid chromatography-mass spectrometry in 53 girls with isolated PP at presentation and during follow-up. Thirty-six age-matched girls without PP served as the control group.

Results: The height, body mass index-standard deviation score (SDS), DHEA, DHEA-S, A4, androsterone, and 17OH-pregnenolone concentrations were higher (P < .0001), whereas no difference in 11OHA4 and 11OHT concentrations was observed in the PP group compared with controls. There was no correlation of adrenal androgen concentrations with height, corrected height, and growth velocity at baseline or during follow-up of 2.7 years. Corrected height SDS was positively correlated with baseline corrected height SDS (r = .63, P < .0001), baseline bone age (BA)/chronological age ratio (r = .31, P = .02), and baseline BA SDS (r = .32, P = .01) but not with hormone concentrations.

Conclusion: Isolated idiopathic PP appears to be a benign variant of normal development. In this setting, adrenal androgen concentrations are not associated with adverse linear growth outcomes and are unlikely to influence clinical management, supporting a conservative approach after exclusion of pathological causes.

背景:阴毛早发(PP)的特征是阴毛或腋毛早发、体臭或轻度痤疮,最常见的表现是血浆脱氢表雄酮硫酸(DHEA-S)浓度升高。然而,最近的证据表明,11-氧合肾上腺雄激素(11β-羟基雄烯二酮(11OHA4), 11β-羟基睾酮(11OHT))可能更好地代表真正的雄激素活性。目的:本研究旨在评估肾上腺雄激素在确定PP女孩生长特征方面的预测价值。对象和方法:采用液相色谱-质谱联用(LC-MS/MS)对53例分离性PP女孩进行了一项前瞻性研究,以评估人体测量学和临床特征,并定量血浆肾上腺雄激素-包括DHEA、DHEA- s、雄烯二酮(A4)、雄酮、11OHA4和11oht。36例年龄匹配的无PP女孩作为对照组。结果:身高、BMI-SDS、DHEA、DHEA- s、A4、雄酮、17oh -孕烯醇酮浓度均较高(p)。结论:分离性特发性早毛是正常发育的一种良性变异。在这种情况下,肾上腺雄激素浓度与不良的线性生长结果无关,也不太可能影响临床管理,支持在排除病理原因后采用保守方法。
{"title":"Adrenal androgens as predictors of growth characteristics in premature pubarche.","authors":"Mehmet Eltan, Zehra Yavas Abali, Aylin Tugba Canbaz, Tarik Kirkgoz, Sare Betul Kaygusuz, Busra Gurpinar Tosun, Tuba Seven Menevse, Didem Helvacioglu, Ali Yaman, Goncagul Haklar, Serap Turan, Abdullah Bereket, Tulay Guran","doi":"10.1093/ejendo/lvag024","DOIUrl":"10.1093/ejendo/lvag024","url":null,"abstract":"<p><strong>Background: </strong>Premature pubarche (PP) is characterized by the early onset of pubic or axillary hair, body odor, or mild acne, most commonly reflected by elevated plasma dehydroepiandrosterone-sulfate (DHEA-S) concentrations. However, recent evidence suggests that 11-oxygenated adrenal androgens [11β-hydroxyandrostenedione (11OHA4), 11β-hydroxytestosterone (11OHT)] may better represent true androgenic activity.</p><p><strong>Aim: </strong>This study aims to evaluate the predictive value of adrenal androgens in determining growth characteristics among girls with PP.</p><p><strong>Subjects and methods: </strong>A prospective study was conducted to evaluate anthropometric and clinical features and to quantify plasma adrenal androgens-including DHEA, DHEA-S, androstenedione (A4), androsterone, 11OHA4, and 11OHT-using liquid chromatography-mass spectrometry in 53 girls with isolated PP at presentation and during follow-up. Thirty-six age-matched girls without PP served as the control group.</p><p><strong>Results: </strong>The height, body mass index-standard deviation score (SDS), DHEA, DHEA-S, A4, androsterone, and 17OH-pregnenolone concentrations were higher (P < .0001), whereas no difference in 11OHA4 and 11OHT concentrations was observed in the PP group compared with controls. There was no correlation of adrenal androgen concentrations with height, corrected height, and growth velocity at baseline or during follow-up of 2.7 years. Corrected height SDS was positively correlated with baseline corrected height SDS (r = .63, P < .0001), baseline bone age (BA)/chronological age ratio (r = .31, P = .02), and baseline BA SDS (r = .32, P = .01) but not with hormone concentrations.</p><p><strong>Conclusion: </strong>Isolated idiopathic PP appears to be a benign variant of normal development. In this setting, adrenal androgen concentrations are not associated with adverse linear growth outcomes and are unlikely to influence clinical management, supporting a conservative approach after exclusion of pathological causes.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"225-232"},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association between body image and well-being in polycystic ovary syndrome: a mixed-methods study. 多囊卵巢综合征身体形象与幸福感之间的关系:一项混合方法研究。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag023
Sophie Broughton, Eleni Armeni, Agatha Chu, Amanda Ling Jie Yee, Aspasia Manta, Shams Ali Baig, Ella Blendis, Punith Kempegowda

Objective: To examine body image (BI) concerns in women with polycystic ovary syndrome (PCOS) by comparing perceptions with normative data, assessing links with psychological distress, clinical features, disordered eating, and quality of life (QoL), and identifying body image cut-offs that predict psychological risk.

Design: Mixed-methods observational study conducted in the United Kingdom (June 2023-October 2024).

Methods: Women with PCOS (n = 171) completed validated questionnaires assessing BI (Multidimensional Body-Self Relations Questionnaire-Appearance Scale), depression, anxiety, disordered eating, and QoL; 41 also participated in semi-structured interviews. Moderation by ethnicity and socioeconomic status (SES) was examined.

Results: Women with PCOS reported greater BI-distress than normative data, driven by elevated body mass index (BMI) and hirsutism. Poorer BI was linked to higher depression, anxiety, disordered eating, and reduced QoL. ROC-analyses identified self-classified weight scores (SW) ≥ 4.25 as the cut-off for depression and overweight preoccupation (OP) ≥ 2.88 for anxiety. In adjusted models, higher SW scores predicted nearly 5-fold greater depression risk, while elevated OP scores conferred a 4-fold higher anxiety risk and doubled disordered eating risk. Together with BMI, OP and SW predicted most PCOS-QoL domains, with the strongest effects in weight-related QoL. Socioeconomic deprivation amplified OP effects on disordered eating, while ethnicity showed minimal influence. Qualitative findings echoed these results, with weight gain, hirsutism, negative diagnostic experiences, and social withdrawal emerging as key distress drivers.

Conclusion: BI concerns are central to psychological morbidity and reduced QoL in PCOS. Establishing OP and SW cut-offs enables early risk stratification, while acknowledging that SES influences may support equitable, patient-centred care.

目的:通过比较多囊卵巢综合征(PCOS)女性身体形象(BI)的认知与规范数据,评估其与心理困扰、临床特征、饮食失调和生活质量(QoL)的联系,并确定预测心理风险的身体形象截断值,探讨多囊卵巢综合征(PCOS)女性身体形象(BI)的担忧。设计:在英国进行的混合方法观察研究(2023年6月- 2024年10月)。方法:171名多囊卵巢综合征(PCOS)女性完成有效问卷,评估BI(多维身体自我关系问卷-外貌量表)、抑郁、焦虑、饮食失调和生活质量;41人还参加了半结构化访谈。研究了种族和社会经济地位(SES)的适度性。结果:由于体重指数(BMI)升高和多毛症,多囊卵巢综合征(PCOS)女性报告的bi窘迫程度高于标准数据。较差的BI与较高的抑郁、焦虑、饮食失调和较低的生活质量有关。roc分析确定自分类体重评分(SW)≥4.25为抑郁的截止值,超重关注(OP)≥2.88为焦虑的截止值。在调整后的模型中,较高的SW分数预示着抑郁风险增加近5倍,而较高的OP分数则预示着焦虑风险增加4倍,饮食失调风险增加一倍。OP和SW与BMI一起预测了大多数PCOS-QoL结构域,其中对体重相关QoL的影响最大。社会经济剥夺放大了OP对饮食失调的影响,而种族的影响微乎其微。定性研究结果与这些结果相呼应,体重增加、多毛、负面诊断经历和社交退缩成为主要的困扰因素。结论:BI是PCOS患者心理发病和生活质量下降的主要原因。建立OP和SW的界限可以实现早期风险分层,同时承认SES的影响可能支持公平的、以患者为中心的护理。
{"title":"The association between body image and well-being in polycystic ovary syndrome: a mixed-methods study.","authors":"Sophie Broughton, Eleni Armeni, Agatha Chu, Amanda Ling Jie Yee, Aspasia Manta, Shams Ali Baig, Ella Blendis, Punith Kempegowda","doi":"10.1093/ejendo/lvag023","DOIUrl":"10.1093/ejendo/lvag023","url":null,"abstract":"<p><strong>Objective: </strong>To examine body image (BI) concerns in women with polycystic ovary syndrome (PCOS) by comparing perceptions with normative data, assessing links with psychological distress, clinical features, disordered eating, and quality of life (QoL), and identifying body image cut-offs that predict psychological risk.</p><p><strong>Design: </strong>Mixed-methods observational study conducted in the United Kingdom (June 2023-October 2024).</p><p><strong>Methods: </strong>Women with PCOS (n = 171) completed validated questionnaires assessing BI (Multidimensional Body-Self Relations Questionnaire-Appearance Scale), depression, anxiety, disordered eating, and QoL; 41 also participated in semi-structured interviews. Moderation by ethnicity and socioeconomic status (SES) was examined.</p><p><strong>Results: </strong>Women with PCOS reported greater BI-distress than normative data, driven by elevated body mass index (BMI) and hirsutism. Poorer BI was linked to higher depression, anxiety, disordered eating, and reduced QoL. ROC-analyses identified self-classified weight scores (SW) ≥ 4.25 as the cut-off for depression and overweight preoccupation (OP) ≥ 2.88 for anxiety. In adjusted models, higher SW scores predicted nearly 5-fold greater depression risk, while elevated OP scores conferred a 4-fold higher anxiety risk and doubled disordered eating risk. Together with BMI, OP and SW predicted most PCOS-QoL domains, with the strongest effects in weight-related QoL. Socioeconomic deprivation amplified OP effects on disordered eating, while ethnicity showed minimal influence. Qualitative findings echoed these results, with weight gain, hirsutism, negative diagnostic experiences, and social withdrawal emerging as key distress drivers.</p><p><strong>Conclusion: </strong>BI concerns are central to psychological morbidity and reduced QoL in PCOS. Establishing OP and SW cut-offs enables early risk stratification, while acknowledging that SES influences may support equitable, patient-centred care.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"233-241"},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
European Society for Paediatric Endocrinology (ESPE) and European Society of Endocrinology (ESE) joint clinical practice guidance for healthcare transition from paediatric to adult endocrine care. 欧洲儿科内分泌学会(ESPE)和欧洲内分泌学会(ESE)联合临床实践指导医疗保健从儿科过渡到成人内分泌护理。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag020
Enora Le Roux, Kirstine Stochholm, Martin Fassnacht, Imelda Coyne, Philippe Touraine, Krystallenia I Alexandraki, Malgorzata Wasniewska, Judith P van Eck, Victoria Di Guisto, Amanda Helm, Elena Valassi, Joke Marlier, Martine Cools, Rasha T Hamza, Tommaso Aversa, Andrea M Isidori, Anders Juul, Charlotte Verroken, Marie Juul Ornstrup, Lina Zabuliene, Kirsten Davidse, Stefano Cianfarani, Sebastian J C M M Neggers

Background: The transition from paediatric to adult healthcare is a critical period for young individuals with endocrine conditions. Despite numerous published recommendations, Europe still lacks recent, comprehensive, evidence-based, and practically applicable guidelines for endocrine healthcare transition.

Objective: To develop European consensus guidance for transition from paediatric to adult care in endocrine conditions through a structured, evidence-based approach.

Methods: A systematic literature review identified 351 recommendations from 55 articles (2011-2023). Articles were included if they provided recommendations on transition from paediatric to adult care for patients with endocrine diseases or general (non-disease-specific) transition guidance. The guidance was developed by a core multidisciplinary group (n = 7) and refined through focus groups with 18 experts from 10 European countries, representing both paediatric and adult care settings. Patient representatives have reviewed and approved it.

Results: The guidance includes recommendations across 11 domains: structure of transition service, patient empowerment, patient-professional relationship, multidisciplinary team organization, healthcare provider education, timing and planning, care coordination, management of non-attendance, psychological support, parents/caregivers role, and readiness tools. Each recommendation was rated as either "recommend" (strong) or "suggest" (conditional) based on expert consensus and available evidence.

Conclusion: This ESE-ESPE guidance provides a comprehensive, practical framework for endocrine healthcare transition, applicable across different European healthcare settings. The recommendations emphasise structured programs, care coordination, and patient-centred approaches to optimize transition outcomes.

背景:从儿科过渡到成人医疗保健是一个关键时期的年轻人与内分泌条件。尽管发表了许多建议,但欧洲仍然缺乏最新的、全面的、以证据为基础的、实际适用的内分泌保健过渡指南。目的:通过结构化的、基于证据的方法,制定从儿科到成人内分泌疾病护理过渡的欧洲共识指南。方法:系统文献综述从55篇文章(2011-2023)中筛选出351条建议。如果文章提供了关于内分泌疾病患者从儿科转向成人护理的建议或一般(非疾病特异性)过渡指导,则纳入。该指南由一个核心多学科小组(n = 7)制定,并通过来自10个欧洲国家的18名专家(代表儿科和成人护理机构)组成的焦点小组进行了完善。患者代表已经审核通过了。结果:该指南包括11个领域的建议:过渡服务结构、患者授权、患者-专业关系、多学科团队组织、医疗保健提供者教育、时间安排和计划、护理协调、缺勤管理、心理支持、父母/照顾者角色和准备工具。根据专家共识和现有证据,每个建议被评为“推荐”(强烈)或“建议”(有条件)。结论:本espe指南为内分泌保健转型提供了一个全面、实用的框架,适用于不同的欧洲医疗保健环境。这些建议强调结构化方案、护理协调和以患者为中心的方法,以优化过渡结果。
{"title":"European Society for Paediatric Endocrinology (ESPE) and European Society of Endocrinology (ESE) joint clinical practice guidance for healthcare transition from paediatric to adult endocrine care.","authors":"Enora Le Roux, Kirstine Stochholm, Martin Fassnacht, Imelda Coyne, Philippe Touraine, Krystallenia I Alexandraki, Malgorzata Wasniewska, Judith P van Eck, Victoria Di Guisto, Amanda Helm, Elena Valassi, Joke Marlier, Martine Cools, Rasha T Hamza, Tommaso Aversa, Andrea M Isidori, Anders Juul, Charlotte Verroken, Marie Juul Ornstrup, Lina Zabuliene, Kirsten Davidse, Stefano Cianfarani, Sebastian J C M M Neggers","doi":"10.1093/ejendo/lvag020","DOIUrl":"https://doi.org/10.1093/ejendo/lvag020","url":null,"abstract":"<p><strong>Background: </strong>The transition from paediatric to adult healthcare is a critical period for young individuals with endocrine conditions. Despite numerous published recommendations, Europe still lacks recent, comprehensive, evidence-based, and practically applicable guidelines for endocrine healthcare transition.</p><p><strong>Objective: </strong>To develop European consensus guidance for transition from paediatric to adult care in endocrine conditions through a structured, evidence-based approach.</p><p><strong>Methods: </strong>A systematic literature review identified 351 recommendations from 55 articles (2011-2023). Articles were included if they provided recommendations on transition from paediatric to adult care for patients with endocrine diseases or general (non-disease-specific) transition guidance. The guidance was developed by a core multidisciplinary group (n = 7) and refined through focus groups with 18 experts from 10 European countries, representing both paediatric and adult care settings. Patient representatives have reviewed and approved it.</p><p><strong>Results: </strong>The guidance includes recommendations across 11 domains: structure of transition service, patient empowerment, patient-professional relationship, multidisciplinary team organization, healthcare provider education, timing and planning, care coordination, management of non-attendance, psychological support, parents/caregivers role, and readiness tools. Each recommendation was rated as either \"recommend\" (strong) or \"suggest\" (conditional) based on expert consensus and available evidence.</p><p><strong>Conclusion: </strong>This ESE-ESPE guidance provides a comprehensive, practical framework for endocrine healthcare transition, applicable across different European healthcare settings. The recommendations emphasise structured programs, care coordination, and patient-centred approaches to optimize transition outcomes.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"194 2","pages":"G1-G10"},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of increased cortical thickness and cognitive impairment in patients with Kallmann syndrome. Kallmann综合征患者皮质厚度增加与认知障碍的关系
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag019
Yan Fu, Xueying Wang, Jinfan Zhang, Feifei Wu, Han Wu, Yafang He, Haimiao Huang, Meichao Men, Wenzhen Zhu, Yuanchao Zhang, Alessandro Grecucci, Xiaoping Yi, Bihong T Chen

Objectives: To characterize whole-brain cortical thickness alteration in Kallmann syndrome (KS), assess its correlation with cognitive impairment, and explore the genetic association and extrapolated transcriptional underpinning.

Methods: We prospectively recruited 100 patients with KS and 100 age- and sex-matched healthy controls. All participants underwent high-resolution structural MRI and a comprehensive neuropsychological assessment targeting global cognition (Montreal Cognitive Assessment, MoCA), executive function and inhibitory control (Stroop Color and Word Test, SCWT), cognitive flexibility (Trail Making Test, TMT), working memory (Digit Span Test, DST), and visuospatial memory (Visual Reproduction task, VR). Cortical thickness and subcortical volumes were quantified using FreeSurfer. In the KS cohort, we examined brain-cognition correlations, performed exploratory genetic association analysis using whole-exome sequencing, and conducted extrapolated neuroimaging-transcription analysis using the Allen Human Brain Atlas (http://human.brain-map.org/) to identify underlying biological pathways.

Results: Compared to the healthy controls, patients with KS exhibited significant cognitive deficits, with 36% MoCA scoring below the clinical cutoff for cognitive impairment. Domain-specific analysis revealed impairments in SCWT-C, DST-Backward, TMT-B, and VR (all P-value < .05). Structurally, patients showed bilateral increased cortical thickness predominantly in the fronto-limbic circuit (orbitofrontal and subgenual cingulate cortices) and default mode network (voxel P-value < .001, cluster random field theory corrected P-value < .05), alongside bilateral hippocampal enlargement (P-FDR = .048). Crucially, the cortical thickness in these fronto-limbic regions was negatively correlated with SCWT-C and DST. Exploratory genetic analysis linked variants in genes such as OTUD4 and FGFR1 to cognitive variability (TMT-A and VR). Furthermore, the spatial pattern of cortical thickening was significantly associated with extrapolated gene expression profiles enriched for neurodevelopment, neuronal migration, and synaptic function.

Conclusions: This study identified cortical thickening involved in fronto-limbic and default mode network as key neuroanatomical signatures of the patients with KS, which was associated with cognitive impairment. Specific genetic variants may further modulate the structural alterations and cognitive functioning in patients with KS.

目的:研究Kallmann综合征(KS)的全脑皮质厚度改变特征,评估其与认知障碍的相关性,并探讨其遗传关联和推断的转录基础。方法:我们前瞻性地招募了100例KS患者和100例年龄和性别匹配的健康对照。所有参与者都接受了高分辨率结构MRI和全面的神经心理学评估,包括全球认知(蒙特利尔认知评估,MoCA)、执行功能和抑制控制(Stroop Color and Word Test, SCWT)、认知灵活性(Trail Making Test, TMT)、工作记忆(Digit Span Test, DST)和视觉空间记忆(Visual Reproduction task, VR)。使用FreeSurfer对皮质厚度和皮质下体积进行量化。在KS队列中,我们检查了脑认知相关性,使用全外显子组测序进行了探索性遗传关联分析,并使用Allen人脑图谱(http://human.brain-map.org/)进行了外推神经成像转录分析,以确定潜在的生物学途径。结果:与健康对照相比,KS患者表现出明显的认知缺陷,36%的MoCA评分低于认知障碍的临床临界值。区域特异性分析显示SCWT-C、DST-Backward、TMT-B和VR受损(p值均< 0.05)。在结构上,患者双侧皮层厚度增加主要发生在额边缘回路(眶额和亚膝扣带皮层)和默认模式网络(体素p值< 0.001,聚类随机场理论校正的p值< 0.05),同时双侧海马增大(p-FDR = 0.048)。关键是,这些额边缘区域的皮质厚度与SCWT-C和DST呈负相关。探索性遗传分析将OTUD4和FGFR1等基因的变异与认知变异性(TMT-A和VR)联系起来。此外,皮质增厚的空间模式与外推的基因表达谱显著相关,这些基因表达谱丰富了神经发育、神经元迁移和突触功能。结论:本研究发现,涉及额边缘和默认模式网络的皮质增厚是KS患者的关键神经解剖学特征,与认知功能障碍有关。特定的基因变异可能会进一步调节KS患者的结构改变和认知功能。
{"title":"Association of increased cortical thickness and cognitive impairment in patients with Kallmann syndrome.","authors":"Yan Fu, Xueying Wang, Jinfan Zhang, Feifei Wu, Han Wu, Yafang He, Haimiao Huang, Meichao Men, Wenzhen Zhu, Yuanchao Zhang, Alessandro Grecucci, Xiaoping Yi, Bihong T Chen","doi":"10.1093/ejendo/lvag019","DOIUrl":"10.1093/ejendo/lvag019","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize whole-brain cortical thickness alteration in Kallmann syndrome (KS), assess its correlation with cognitive impairment, and explore the genetic association and extrapolated transcriptional underpinning.</p><p><strong>Methods: </strong>We prospectively recruited 100 patients with KS and 100 age- and sex-matched healthy controls. All participants underwent high-resolution structural MRI and a comprehensive neuropsychological assessment targeting global cognition (Montreal Cognitive Assessment, MoCA), executive function and inhibitory control (Stroop Color and Word Test, SCWT), cognitive flexibility (Trail Making Test, TMT), working memory (Digit Span Test, DST), and visuospatial memory (Visual Reproduction task, VR). Cortical thickness and subcortical volumes were quantified using FreeSurfer. In the KS cohort, we examined brain-cognition correlations, performed exploratory genetic association analysis using whole-exome sequencing, and conducted extrapolated neuroimaging-transcription analysis using the Allen Human Brain Atlas (http://human.brain-map.org/) to identify underlying biological pathways.</p><p><strong>Results: </strong>Compared to the healthy controls, patients with KS exhibited significant cognitive deficits, with 36% MoCA scoring below the clinical cutoff for cognitive impairment. Domain-specific analysis revealed impairments in SCWT-C, DST-Backward, TMT-B, and VR (all P-value < .05). Structurally, patients showed bilateral increased cortical thickness predominantly in the fronto-limbic circuit (orbitofrontal and subgenual cingulate cortices) and default mode network (voxel P-value < .001, cluster random field theory corrected P-value < .05), alongside bilateral hippocampal enlargement (P-FDR = .048). Crucially, the cortical thickness in these fronto-limbic regions was negatively correlated with SCWT-C and DST. Exploratory genetic analysis linked variants in genes such as OTUD4 and FGFR1 to cognitive variability (TMT-A and VR). Furthermore, the spatial pattern of cortical thickening was significantly associated with extrapolated gene expression profiles enriched for neurodevelopment, neuronal migration, and synaptic function.</p><p><strong>Conclusions: </strong>This study identified cortical thickening involved in fronto-limbic and default mode network as key neuroanatomical signatures of the patients with KS, which was associated with cognitive impairment. Specific genetic variants may further modulate the structural alterations and cognitive functioning in patients with KS.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"185-198"},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circadian rhythms, endogenous glucocorticoids and skeletal health. 昼夜节律、内源性糖皮质激素和骨骼健康。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag012
Eugenie Macfarlane, Hong Zhou, Markus J Seibel

Circadian rhythms are a hallmark of life. They are present in numerous physiological functions, including behavioural patterns such as sleep-wake cycles or feeding-fasting behaviour, hormonal secretion, core body temperature, cardiovascular and brain activity, cell regeneration and metabolic processes. Most organisms have developed evolutionarily conserved biological clock mechanisms that effectively react to cyclic changes in the photic environment to synchronize behaviour and physiological processes accordingly. These "pacemaker" like clocks are present in almost every cell and are intrinsically generated to maintain internal rhythms with a cycle frequency of approximately 24 hours. Chronic disruption of circadian rhythms, as in the case of shift work, frequent jet lag or sleep disorders, is increasingly being recognized as an important contributor to adverse health conditions such as cardiovascular disease, neurodegeneration, cancer, bone loss and joint degeneration. The effects of chronic disruption of circadian rhythms on musculoskeletal health are multifactorial, but endogenous glucocorticoids are likely to be involved given their critical role in numerous physiological processes, including bone and mineral homeostasis, systemic metabolism, and the inflammatory response. Of particular interest are the actions of endogenous glucocorticoids in the regulation of intrinsic circadian rhythms. It is well established that glucocorticoids act as a potent internal time signal to synchronize cell-autonomous clocks in peripheral tissues (such as bone and cartilage) with the central master clock in the suprachiasmatic nucleus. Furthermore, disruption to physiological glucocorticoid rhythms can disturb normal rhythms in gene expression, with deleterious effects on bone health. Understanding how glucocorticoids regulate skeletal molecular clocks and bone remodelling during disruption of circadian rhythms may provide opportunities to mitigate the effects of shift work on skeletal homeostasis. This review will focus on the interactions between circadian rhythms and glucocorticoid actions in bone and cartilage and their role in skeletal pathology.

昼夜节律是生命的标志。它们存在于许多生理功能中,包括睡眠-觉醒周期或进食-禁食行为等行为模式、激素分泌、核心体温、心血管和大脑活动、细胞再生和代谢过程。大多数生物已经发展出进化保守的生物钟机制,有效地对光环境的循环变化作出反应,从而相应地同步行为和生理过程。这些“起搏器”一样的时钟几乎存在于每个细胞中,它们的产生是为了维持内部节律,周期频率约为24小时。昼夜节律的慢性破坏,如倒班工作、频繁的时差反应或睡眠障碍,正日益被认为是心血管疾病、神经变性、癌症、骨质流失和关节变性等不良健康状况的重要因素。昼夜节律的慢性破坏对肌肉骨骼健康的影响是多因素的,但内源性糖皮质激素可能参与其中,因为它们在许多生理过程中起着关键作用,包括骨骼和矿物质稳态、全身代谢和炎症反应。特别感兴趣的是内源性糖皮质激素在调节内在昼夜节律中的作用。糖皮质激素作为一种有效的内部时间信号,使外周组织(如骨和软骨)中的细胞自主时钟与视交叉上核中的中央主时钟同步。此外,对生理糖皮质激素节律的破坏可以扰乱基因表达的正常节律,对骨骼健康产生有害影响。了解糖皮质激素在昼夜节律中断期间如何调节骨骼分子钟和骨骼重塑,可能为减轻轮班工作对骨骼稳态的影响提供机会。本文将重点讨论昼夜节律与骨和软骨中糖皮质激素作用的相互作用及其在骨骼病理中的作用。
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引用次数: 0
Histological evidence of familial GH-PitNET associated with germline MAX mutation. 家族性GH-PitNET与种系MAX突变相关的组织学证据。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag006
Laurence Salle, Alexandre Buffet, Gérald Raverot, Laure Cazabat, Chiara Villa, Theo Charnay, Mathilde Cane, Robin Mas, Damien Bresson, Pauline Romanet, Henri Salle
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引用次数: 0
Genetics and clinical characteristics of Korean patients with bilateral macronodular adrenocortical disease. 韩国双侧肾上腺皮质大结节病患者的遗传学和临床特点。
IF 5.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-04 DOI: 10.1093/ejendo/lvag014
Seung Shin Park, Jee-Soo Lee, Yunna Lee, Taek Min Kim, Young-Gon Kim, Su-Jin Kim, Kyu Eun Lee, Man Ho Choi, Moon-Woo Seong, Jung Hee Kim

Objective: Bilateral macronodular adrenocortical disease (BMAD) is a rare disorder characterized by bilateral adrenocortical nodules and variable cortisol excess. ARMC5 is a well-established genetic driver of BMAD, but data in East Asian populations are limited. We investigated the prevalence of pathogenic variants and genotype-phenotype correlations in Korean patients with BMAD.

Methods: A total of 69 patients with BMAD were retrospectively enrolled at Seoul National University Hospital (2009-2023). Whole-exome sequencing was performed for 35 patients. Clinical, biochemical, and imaging data were analyzed. Serum steroid profiling was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify 18 adrenal-derived steroids.

Results: The mean age of the cohort was 66.4 years, and 58% were male. Most had mild autonomous cortisol secretion (79.7%), and 15.9% had overt Cushing syndrome. Among the 35 patients who underwent genetic testing, 22.9% harbored pathogenic/likely pathogenic (P/LP) variants in ARMC5. P/LP ARMC5 variant carriers had lower BMI (25.0 vs 27.4 kg/m2), larger maximal tumor diameter (4.1 vs 2.7 cm), and greater total adrenal volume (19.8 vs 15.3 cm3). LC-MS/MS profiling revealed that P/LP ARMC5 carriers had significantly higher cortisol (153.1 vs 100.6 ng/mL), corticosterone (16.5 vs 1.3 ng/mL), and 18-hydroxycortisol concentrations (1.66 vs .66 ng/mL) (P < .05).

Conclusion: This study in a Korean cohort with BMAD showed that P/LP ARMC5 variants were present in 22.9% of the genetically investigated patients and were associated with more severe radiological and steroidogenic features. These findings underscore the importance of closely monitoring patients with BMAD who carry ARMC5 P/LP variants.

目的:双侧肾上腺皮质大结节病(BMAD)是一种以双侧肾上腺皮质结节和可变皮质醇过量为特征的罕见疾病。ARMC5是一个公认的BMAD遗传驱动因素,但东亚人群的数据有限。我们调查了韩国BMAD患者的致病变异患病率和基因型-表型相关性。方法:回顾性分析2009-2023年在首尔国立大学医院收治的69例BMAD患者。对35例患者进行全外显子组测序。分析临床、生化和影像学资料。采用液相色谱-串联质谱法(LC-MS/MS)对18种肾上腺源性类固醇进行定量分析。结果:队列的平均年龄为66.4岁,其中58%为男性。大多数有轻度自主皮质醇分泌(79.7%),15.9%有明显的库欣综合征。在接受基因检测的35名患者中,22.9%的人携带ARMC5致病性/可能致病性(P/LP)变异。P/LP ARMC5变异携带者BMI较低(25.0 vs 27.4 kg/m²),最大肿瘤直径较大(4.1 vs 2.7 cm),肾上腺总容量较大(19.8 vs 15.3 cm³)。LC-MS/MS分析显示,P/LP ARMC5携带者的皮质醇(153.1 vs 100.6 ng/mL)、皮质酮(16.5 vs 1.3 ng/mL)和18-羟基皮质醇浓度(1.66 vs 0.66 ng/mL)显著升高(结论:这项在韩国BMAD队列中的研究表明,在22.9%的遗传调查患者中存在P/LP ARMC5变异,并伴有更严重的放射学和类固醇性特征。这些发现强调了密切监测携带ARMC5 P/LP变异的BMAD患者的重要性。
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引用次数: 0
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European Journal of Endocrinology
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