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Hypothalamic-pituitary-adrenal axis plasticity across life-history stages of a free-living subtropical finch, Amandava amandava amandava. 自由生活的亚热带雀科鸟类 Amandava amandava 的下丘脑-垂体-肾上腺轴在不同生活史阶段的可塑性。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-30 DOI: 10.1111/jne.13459
Banalata Mohanty

The alterations of phenotypic traits (morphology, endocrine physiology, and behavior) in response to predictable environmental cues across life-history stages in seasonally breeding birds enable successful culmination of reproduction. The present study elucidated the plasticity of the hypothalamic-pituitary-adrenal (HPA) axis in a subtropical free-living finch, Amandava amandava amandava, and suggests the crucial role of the baseline corticosterone (CORT) to coordinate energetic readiness across life-history stages. Birds were captured monthly from an area (25.1337° N 82.5644° E) in Uttar Pradesh, India, from June 2014 to May 2015. Only male birds were included in this study corresponding to different life-history stages (6/life-history stage; 2/month): pre-breeding (June-August), breeding (September-November), post-breeding (December-February), and quiescent phases (March-May). The pituitary expression of adrenocorticotropic hormone (ACTH), adrenal interrenal cell morphometry, and plasma level of the CORT showed varied patterns across life-history stages. The density and immunointensity of the ACTH-immunoreactive corticotropes and the interrenal cell number increased along with the significant plasma CORT elevation during the breeding cycle (both pre-breeding and breeding phases). CORT might facilitate the energy demand for the display of sexual behavior (nest-building, courtship), testicular recrudescence, and foraging of food for offspring during the breeding cycle. On the contrary, plasma CORT decrease in the post-breeding and quiescent phases might enable the bird to molt avoiding the protein catabolic effect of the hormone. Given the complexity involved in the study of baseline CORT in free-living birds, more studies are needed to better understand the crucial role of the HPA axis in the modulation of life-history stages in this and other subtropical avian species.

在季节性繁殖的鸟类中,表型特征(形态、内分泌生理和行为)的改变是对各生命史阶段可预测的环境线索的反应,从而使繁殖成功达到高潮。本研究阐明了一种亚热带自由生活雀类(Amandava amandava amandava)的下丘脑-垂体-肾上腺(HPA)轴的可塑性,并提出了基线皮质酮(CORT)在协调各生活史阶段的能量准备方面的关键作用。2014年6月至2015年5月期间,每月从印度北方邦的一个地区(北纬25.1337°,东经82.5644°)捕获鸟类。只有雄性鸟类被纳入本研究,它们分别处于不同的生命史阶段(6只/生命史阶段;2只/月):繁殖前(6月-8月)、繁殖期(9月-11月)、繁殖后(12月-2月)和静止期(3月-5月)。垂体促肾上腺皮质激素(ACTH)的表达、肾上腺间质细胞形态学和血浆 CORT 水平在不同生活史阶段表现出不同的模式。在繁殖周期(包括繁殖前和繁殖期),促肾上腺皮质激素免疫反应性肾上腺皮质细胞的密度和免疫点密度以及肾间质细胞数量增加,血浆 CORT 也显著升高。CORT可能有助于繁殖周期中的性行为(筑巢、求偶)、睾丸再萌发和为后代觅食所需的能量需求。相反,鸟类在繁殖后和静止期血浆 CORT 的减少可能会使鸟类在蜕皮时避免激素的蛋白质分解作用。鉴于研究自由生活鸟类的基线 CORT 所涉及的复杂性,需要进行更多的研究,以更好地了解 HPA 轴在调节该鸟类和其他亚热带鸟类的生命史阶段中的关键作用。
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引用次数: 0
Cognitive decline in Cushing's syndrome: A systematic review. 库欣综合征的认知能力下降:系统综述。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-11-06 DOI: 10.1111/jne.13466
Anila Katragadda, Jessica Kunadia, Polly Kirsch, Brenda Dorcely, Shruti Shah, Zachary Henig, Asha Job, Richard A Feelders, Nidhi Agrawal

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

库欣综合征(CS)对神经认知和精神的影响已得到公认,并对生活质量产生负面影响。本系统综述旨在比较库欣病(CD)/CS 患者和非功能性垂体腺瘤(NFPA)患者在手术治疗前后的神经认知疾病、精神症状和脑结构变化,并与健康对照组进行比较。我们强调了CS患者持续神经认知症状和生活质量下降的可能预测因素。我们查阅了截至 2021 年发表在 Medline/Pubmed 上的英文文献,以确定符合条件的研究。本系统综述在 Prospero 上注册,并按照 PRISMA 声明指南进行报告。最初的文献检索结果为 1772 篇文章,去除重复文章后剩余 1096 篇。在排除病例报告、动物研究、叙事性综述、比较性综述和非英语文章后,有 86 篇文章进行了全文审阅。符合纳入条件的研究符合以下标准:(1) 描述 CD/CS 患者;(2) 报告精神症状;(3) 以英语撰写或提供英语翻译;(4) 发表在同行评审期刊上。全文审阅过程确定了 40 项符合条件的研究。这 40 项研究共纳入了 2603 名 CD 或 CS 患者,其中 45.2% 的患者患有 CD。大多数研究都是病例对照研究,并使用了经过验证的问卷,如贝克抑郁指数(Beck's Depression Index)、寻路测试(Trail Making Test)、医院焦虑抑郁量表(Hospital Anxiety and Depression Scale)和库欣生活质量(Cushing Quality of Life)进行筛查。与 NFPA 对照组相比,基线血清皮质醇水平较高的 CD 患者认知功能较差,即使在手术缓解后也是如此。这表明,CS 患者基线皮质醇水平较高与认知功能持续受损之间可能存在关联。不受控制的CS持续时间越长,认知功能越差;但是,缓解时间的长短与记忆力之间没有关联。与活动性疾病相比,CD 缓解期患者的总体脑容量有所增加。然而,颞叶和额叶体积并未恢复到正常体积。CS患者会出现神经认知功能障碍、精神障碍和生活质量下降,治愈性手术后症状可能会持续存在。我们发现有几个因素与 CS 患者的持续认知和神经精神症状有关,包括术前皮质醇分泌基线较高、病程较长、额叶和颞叶萎缩以及基线时存在认知和神经精神症状。需要进行更大规模的前瞻性研究来验证这些发现。
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引用次数: 0
Adolescent social stress alters the role of orexin innervation in the hindbrain in male hamsters. 青春期社会压力改变了雄性仓鼠后脑中奥曲肽神经支配的作用
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-27 DOI: 10.1111/jne.13457
Kevin M Moran, Ava Elana Enstrom, Leah Jarrell, Misheel Khashchuluun, Anna Tran, Yvon Delville

Juvenile male hamsters exposed to chronic social stress eat more, gain weight, and have larger fat pads. The purpose of the present study was to address possible changes in food hoarding and orexin/hypocretin innervation in response to social stress. Male hamsters in early adolescence were exposed to a resident-intruder social stress paradigm or control condition daily for 2 weeks. Metabolism-related physiological measures and behaviors were tracked, and brains were immunocytochemically labeled for orexin-A. Our data confirm our previous observations on appetite, weight gain, and obesity, and showed a strong trend toward enhanced food hoarding as in prior studies. In addition, there were no statistically significant differences in orexin innervation in any brain area analyzed. However, unique correlation patterns were observed between orexin innervation and appetite or metabolic outcome. In particular, opposite correlations were observed between groups within the dorsal raphe nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These opposite patterns of correlations suggest chronic social stress causes site-specific alterations in synaptic activity in relation with these behaviors.

长期处于社会压力下的幼年雄性仓鼠食量更大、体重增加、脂肪垫更大。本研究的目的是探讨囤积食物和奥曲肽/甲状腺素神经支配在应对社会压力时可能发生的变化。研究人员将处于青春期早期的雄性仓鼠置于居民-入侵者社会应激范式或对照组条件下,每天进行为期两周的观察。对与代谢相关的生理指标和行为进行了追踪,并对大脑进行了奥曲肽-A的免疫细胞化学标记。我们的数据证实了我们以前在食欲、体重增加和肥胖方面的观察结果,并显示出与以前的研究一样,囤积食物的现象有明显增强的趋势。此外,在所分析的大脑区域中,奥曲肽神经支配在统计学上没有显著差异。不过,在奥曲肽支配与食欲或代谢结果之间观察到了独特的相关模式。特别是,在背侧剑突核、外侧腮旁核和孤束核中观察到了组间相反的相关性。这些相反的相关模式表明,慢性社会压力会导致与这些行为相关的突触活动发生特定部位的改变。
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引用次数: 0
Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence. 神经内分泌肿瘤与妊娠:来自欧洲神经内分泌肿瘤卓越中心的真实世界数据。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-11-06 DOI: 10.1111/jne.13465
Gowri M Ratnayake, Kalyan Mansukhbhai Shekhda, Thomas Glover, Yasser Al-Obudi, Aimee Hayes, Panagiotis Armonis, Dalvinder Mandair, Bernard Khoo, TuVinh Luong, Christos Toumpanakis, Ashley Grossman, Martyn Caplin
<p><p>Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross-sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre- and post-pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) - 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 - Date 1 + 1)/30.44. Tumour growth rate pre-conception (TGRpc) and tumour growth rate post-partum (TGRpp) were calculated for each patient. In a sub-group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post-partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid-gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was -0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre-conception and post-pregnancy scans showed an increase in TGRpp com
神经内分泌肿瘤(NENs)产生于弥漫性内分泌系统,一直被认为是罕见肿瘤。然而,近年来这类肿瘤的发病率和流行率都在上升,而且患者越来越年轻,包括育龄妇女。由于数据匮乏,在妊娠期管理此类肿瘤的诊断和治疗策略对主治医生和患者来说都具有挑战性。本文介绍了欧洲神经内分泌肿瘤协会(ENETS)卓越中心在治疗妊娠合并神经内分泌肿瘤孕妇方面的经验和结果。在这项回顾性分析中,我们评估了皇家自由医院ENETS卓越中心对18名同时诊断为NEN的孕妇的22次妊娠情况。这些孕妇是从 2015 年至 2023 年间 3500 名 NEN 患者的肿瘤登记册中确定的。每位患者怀孕前后的横断面成像(计算机断层扫描(CT)/磁共振成像(MRI))均由经验丰富的放射科医生进行审查。肿瘤生长率(TGR)的计算公式为TGR = 100 × [exp (TG) - 1]; TG.[3 × log (D2/D1)]/时间(月),其中 D1 为日期 1 时的肿瘤大小;D2 为日期 2 时的肿瘤大小;时间(月)= (Date 2 - Date 1 + 1)/30.44。计算每位患者孕前肿瘤生长率(TGRpc)和产后肿瘤生长率(TGRpp)。在一部分患者中,我们分析了肿瘤组织中雌激素和孕激素受体的阳性率,以评估这些受体的存在是否会影响妊娠期间肿瘤的进展。我们还回顾了在怀孕期间接受过体生长激素类似物治疗的患者的妊娠结局。我们分析了 18 名妇女共 22 次妊娠的数据:15 次妊娠(68%)在确诊 NEN 之前,而在妊娠期间或产后确诊 NEN 的分别有 5 次(23%)和 2 次(9%)。8 名患者(44%)被诊断为胰腺 NEN,5 名患者(28%)被诊断为中肠 NEN,另有 5 名患者被诊断为其他部位的 NEN。大多数患者(12 人,67%)在确诊时已有转移性疾病的证据。大多数患者的妊娠结果都很成功(19 人,86%),但有 3 名患者(14%)在妊娠头三个月流产。在 6 次妊娠中,有 5 名患者在妊娠期间接受了体生长抑素类似物单药治疗,所有患者在妊娠后病情均趋于稳定。所有患者都生下了健康的婴儿,没有因治疗而出现任何副作用或并发症。TGRpc的平均值为-0.8%(5例),TGRpp的平均值为+0.96%(6例)。此外,在孕前和孕后扫描的 4 名患者中,有 2 人的 TGRpp 比 TGRpc 有所上升。妊娠期营养不良症的治疗应该是多学科的,并针对每位患者采取个性化的治疗方法。体生长抑素类似物在妊娠期间似乎是安全的,但还需要进一步的可靠研究。妊娠本身可能会加速肿瘤的进展,因此应就这一可能性向患者提供咨询。
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引用次数: 0
Developmental expression patterns of gonadal hormone receptors in arcuate kisspeptin and GABA neurons of the postnatal female mouse. 出生后雌鼠弓状吻肽和 GABA 神经元中性腺激素受体的发育表达模式
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1111/jne.13477
Yugo Watanabe, Lorryn Fisher, Rebecca E Campbell, Christine L Jasoni
<p><p>The arcuate nucleus of the hypothalamus (ARC) is central in the neuronal regulation of fertility and reproduction through translating gonadal steroid hormone cues into the GnRH signaling pathway in the brain. Evidence suggests that circulating gonadal steroids play an important role in modulating female reproduction via kisspeptin and γ-aminobutyric acid (GABA) neurons in the ARC in both development and adulthood. However, the temporal onset of these ARC neurons' sensitivity to gonadal steroids is unknown. Using RNAscope® in situ hybridization, we localized androgen receptor (Ar), estrogen receptor alpha (Esr1), and progesterone receptor (Pgr) expression in ARC kisspeptin or GABA neurons of female mice at postnatal day (P)4, P8, P12, P20, and P60. A probe that binds to kiss1 mRNA or vGat mRNA was used to produce signal in kisspeptin or GABA neurons, respectively. In adult, we identified that the vast majority of kisspeptin neurons coexpressed Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increased from P4 (24%) to P20 (59%). These results suggest that while ARC GABA neurons can respond to circulating estrogen and progesterone from early postnatal ages, this same population may become more sensitive to androgens during later postnatal life. Our findings identified the expression patterns of Ar, Esr1, and Pgr by ARC kisspeptin and GABA neurons during early postnatal life. These data provide the understanding for the hormone sensitivity of these populations during early postnatal life, the critical time for the formation and regulation of female reproductive physiology.Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increas
下丘脑弓状核(ARC)通过将性腺类固醇激素线索转化为大脑中的 GnRH 信号通路,在生育和生殖的神经元调控中起着核心作用。有证据表明,在发育期和成年期,循环中的性腺类固醇通过 ARC 中的吻肽和γ-氨基丁酸(GABA)神经元在调节雌性生殖方面发挥着重要作用。然而,这些 ARC 神经元对性腺类固醇的敏感性在何时开始尚不清楚。我们使用 RNAscope® 原位杂交技术定位了出生后第 4 天、第 8 天、第 12 天、第 20 天和第 60 天雌性小鼠 ARC 吻抑素或 GABA 神经元中雄激素受体 (Ar)、雌激素受体 alpha (Esr1) 和孕酮受体 (Pgr) 的表达。使用与kiss1 mRNA或vGat mRNA结合的探针分别在kisspeptin或GABA神经元中产生信号。在成体中,我们发现绝大多数的kisspeptin神经元共表达Esr1(95%)和Pgr(93%),而小部分共表达Ar(66%)。从 P4 开始,Ar 或 Esr1 阳性的吻肽素神经元比例相似,这表明吻肽素神经元在出生后早期就对雄激素和雌激素产生了类似成人的敏感性。与此相反,生命早期 Pgr 阳性的吻肽素细胞比例明显低于成年期,这表明随着时间的推移,ARC 吻肽素群体对黄体酮的敏感性会逐渐发展。成年后,ARC GABA神经元也与Ar(70%)、Esr1(64%)或Pgr(85%)共定位。GABA 神经元从出生后阶段到成年期持续表达 Esr1 或 Pgr,而 Ar 阳性 GABA 神经元的比例则从 P4(24%)逐渐增加到 P20(59%)。这些结果表明,虽然 ARC GABA 神经元从出生后早期就能对循环中的雌激素和孕激素做出反应,但在出生后晚期,这部分神经元可能会对雄激素变得更加敏感。我们的研究结果确定了 ARC 吻肽和 GABA 神经元在出生后早期的 Ar、Esr1 和 Pgr 表达模式。这些数据有助于了解这些神经元在出生后早期对激素的敏感性,而出生后早期正是女性生殖生理形成和调节的关键时期。从P4开始,Ar-或Esr1阳性的吻肽素神经元比例相似,这表明吻肽素神经元在出生后早期就对雄激素和雌激素产生了类似成人的敏感性。与此相反,生命早期 Pgr 阳性的吻肽素细胞比例明显低于成年期,这表明随着时间的推移,ARC 吻肽素群体对黄体酮的敏感性会逐渐发展。成年后,ARC GABA神经元也与Ar(70%)、Esr1(64%)或Pgr(85%)共定位。GABA 神经元从出生后阶段到成年期持续表达 Esr1 或 Pgr,而 Ar 阳性 GABA 神经元的比例则从 P4(24%)逐渐增加到 P20(59%)。这些结果表明,虽然 ARC GABA 神经元从出生后早期就能对循环中的雌激素和孕激素做出反应,但在出生后晚期,这部分神经元可能会对雄激素变得更加敏感。我们的研究结果确定了 ARC 吻肽和 GABA 神经元在出生后早期的 Ar、Esr1 和 Pgr 表达模式。这些数据有助于了解这些神经元在出生后早期对激素的敏感性,而出生后早期正是女性生殖生理形成和调节的关键时期。
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引用次数: 0
Nomogram for predicting diabetes insipidus following endoscopic transsphenoidal surgery in pituitary adenomas. 预测垂体腺瘤经蝶腔手术后尿崩症的Nomogram。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1111/jne.13475
Xinming Yu, Guangming Xu, Peng Qiu

Postoperative diabetes insipidus (DI) frequently complicates endoscopic transsphenoidal surgery (TSS) in pituitary adenoma (PA) patients, yet reliable predictive methods for DI risk remain lacking. This study aims to identify risk factors associated with DI following endoscopic transsphenoidal resection of PA and to develop a predictive nomogram for assessing postoperative DI risk. This study involved 600 PA patients underwent endoscopic TSS at Shandong Provincial Hospital from 2021 to 2023. Among these patients, 82 developed postoperative DI while 518 did not. The cohort was randomly divided into training (n = 360) and validation (n = 240) groups at 6:4 ratios by R software. Clinical parameters and radiographic features were evaluated using univariable and multivariable logistic regression to construct a predictive nomogram for post-endoscopic TSS DI risk. Model performance was assessed using ROC curves, calibration plots, and decision curve analysis. Subgroup analysis was used to evaluate the model's ability to discriminate between transient and permanent DI. Univariable and multivariable logistic regression analyses on the training group identified several independent risk factors for post-endoscopic TSS DI, including maximum tumor diameter, Knosp grade, Esposito grade, recurrent PA, and pituitary stalk deviation angle. A nomogram was developed based on these factors, demonstrating robust predictive accuracy with ROC areas under curve of 0.840 for the training group and 0.815 for the validation group. Calibration plots indicated excellent agreement between predicted and observed probabilities of postoperative DI. DCA curves highlighted the nomogram's efficacy in guiding clinical decision-making. Subgroup analysis showed that the model was able to discriminate between transient and permanent DI, and the AUC was 0.652 (95% CI 0.525-0.794). This study presents a nomogram designed to predict postoperative DI risk in patients undergoing endoscopic TSS for PA. Internal and external validations underscored the model's high accuracy, calibration, and clinical utility. Simultaneously, the model can also assess the development risk of permanent DI. This predictive tool offers clinicians valuable support in identifying high-risk DI patients, optimizing postoperative care strategies, and tailoring treatment plans to improve patient outcomes.

垂体腺瘤(PA)患者术后尿崩症(DI)经常使内镜下经蝶窦手术(TSS)并发症,但仍缺乏可靠的尿崩症风险预测方法。本研究旨在确定内镜下经蝶窦切除PA后发生DI的相关危险因素,并开发评估术后DI风险的预测图。本研究纳入了2021年至2023年在山东省立医院接受内窥镜TSS治疗的600例PA患者。其中82例发生术后DI, 518例未发生。采用R软件按6:4的比例随机分为训练组(n = 360)和验证组(n = 240)。使用单变量和多变量logistic回归对临床参数和影像学特征进行评估,以构建内镜后TSS DI风险的预测图。采用ROC曲线、校正图和决策曲线分析评估模型性能。亚组分析用于评估模型区分暂时性和永久性DI的能力。对训练组进行单变量和多变量logistic回归分析,确定了内镜后TSS DI的几个独立危险因素,包括最大肿瘤直径、Knosp分级、Esposito分级、复发性PA和垂体柄偏离角。基于这些因素建立了一个nomogram,显示出稳健的预测准确性,训练组的ROC曲线下面积为0.840,验证组为0.815。校正图显示预测和观察到的术后DI概率非常吻合。DCA曲线突出了nomogram在指导临床决策中的作用。亚组分析表明,该模型能够区分暂时性和永久性DI, AUC为0.652 (95% CI为0.525-0.794)。本研究提出了一种nomogram预测内镜TSS治疗PA患者术后DI风险的方法。内部和外部验证强调了该模型的高精度、可校准性和临床实用性。同时,该模型还可以对永久性DI的发展风险进行评估。该预测工具为临床医生提供了有价值的支持,可以识别高风险DI患者,优化术后护理策略,定制治疗计划以改善患者预后。
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引用次数: 0
Earlier diagnosis of small intestine neuroendocrine tumours (SI-NETs) through transformation of the South Wales NET service. 小肠神经内分泌肿瘤(SI-NETs)的早期诊断通过改造南威尔士网络服务。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-26 DOI: 10.1111/jne.13486
Harriet L Gould, Kapish Amin, Thanos Karategos, Sarah Abbas, Susannah Olive, Mathoorika Sivananthan, Ayeesha Rela, Harriet Reed, Catherine Powell, Janu Navaratnam, Rwth Ellis-Owen, Patrick Fielding, Dipanjali Mondal, Steve Kihara, Gethin Williams, Carys Morgan, Justyna Witczak, Julie Cornish, Sarah Gwynne, James Horwood, Jared Torkington, Rachel Hargest, Adam Christian, Michael Davies, James Ansell, Mohid S Khan

Small intestine neuroendocrine tumours (SI-NETs) are often diagnosed late with a UK median of 3 years and high misdiagnosis rates. Previous studies, largely based on patient surveys, offer little data on improving diagnosis. In 2017, the South Wales NET service underwent a nationally commissioned, systematic transformation, aiming to improve diagnosis through the development of a gastroenterology and surgical referral network, and education of these specialities. This study aims to assess the impact of the transformation on SI-NET diagnosis times and misdiagnosis rates using accurate hospital data, along with the diagnostic routes and investigations used for SI-NETs. We retrospectively analysed the hospital records of 224 patients diagnosed with SI-NETs referred to the South Wales NET service (110 pre-transformation and 114 post-transformation). Following the service transformation, there was a significant reduction in diagnosis times from a median of 12.5-5.2 months (p < .05), at an earlier stage (cases with metastases reduced from 77% to 62%), and reduced misdiagnosis rates from 40% to 25%. Colonoscopy, used to investigate the presenting gastrointestinal symptoms in 42% of patients prior to diagnosis, identified an abnormality in only 28%, compared with 97% with computed tomography (CT) scans. A gastroenterology and surgical referral network across hospitals may improve diagnosis in SI-NETs, leading to earlier detection and reducing misdiagnosis rates. Further exploration of GP interactions is needed. Caution is needed following negative colonoscopy in patients with persistent lower gastrointestinal symptoms as this could lead to missed SI-NET diagnosis if further abdominal imaging is not undertaken.

小肠神经内分泌肿瘤(SI-NETs)通常诊断较晚,英国中位时间为3年,误诊率高。以前的研究主要基于对患者的调查,几乎没有提供改善诊断的数据。2017年,南威尔士网络服务进行了全国委托的系统改造,旨在通过发展胃肠病学和外科转诊网络以及这些专业的教育来改善诊断。本研究旨在利用准确的医院数据,以及SI-NETs的诊断途径和调查,评估SI-NET诊断时间和误诊率的转变的影响。我们回顾性分析了224名被诊断为SI-NETs的患者的医院记录,这些患者转到南威尔士NET服务(110名转化前和114名转化后)。在服务转型之后,诊断时间从12.5-5.2个月的中位数显著减少(p
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引用次数: 0
Impact of dyslipidemia and lipid-lowering therapy with statins in patients with neuroendocrine tumors. 他汀类药物对神经内分泌肿瘤患者血脂异常和降脂治疗的影响。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-26 DOI: 10.1111/jne.13485
Antongiulio Faggiano, Flaminia Russo, Virginia Zamponi, Franz Sesti, Giulia Puliani, Roberta Modica, Pasqualino Malandrino, Francesco Ferraù, Maria Rinzivillo, Marco Di Muzio, Emanuele Di Simone, Nicolò Panattoni, Pasquale Dolce, Rosa Lauretta, Gianfranco Di Iasi, Antonio Prinzi, Ylenia Alessi, Tiziana Feola, Rossella Mazzilli, Marialuisa Appetecchia, Elisa Giannetta, Francesco Panzuto, Annamaria Colao

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression-free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non-dyslipidemic patients, and 72 months in dyslipidemic patients (p = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; p = .024). Recurrence-free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non-dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs.

血脂异常是神经内分泌肿瘤(NETs)的潜在不良预后因素;相反,他汀类药物被证明对NET细胞系具有抗增殖作用,对这些患者可能是一种有益的治疗策略。本观察性队列回顾性研究的主要目的是探讨血脂异常与NET进展之间的关系,并评估他汀类药物在此背景下的潜在影响。来自意大利6个中心的393例经组织学证实的胃肠胰或支气管肺NETs诊断和治疗的患者被纳入研究。该队列包括123例血脂异常患者,其中81例正在服用他汀类药物。收集临床病理数据,包括患者人口统计学、肿瘤特征、治疗细节以及患病率、血脂异常和低血脂治疗的时间。使用的主要结局指标是无进展生存期(PFS)。在393例患者中,123例(31.3%)患有血脂异常。81例(65.8%)血脂异常患者使用他汀类药物,主要是阿托伐他汀。中位PFS为87个月,非血脂异常患者为124个月,血脂异常患者为72个月(p = 0.268)。接受他汀类药物治疗的血脂异常患者的中位PFS(108个月)明显优于未接受他汀类药物治疗的患者(26个月;p = .024)。无复发生存(RFS)也进行了评估,但没有发现显著差异。综上所述,虽然血脂异常患者的PFS低于非血脂异常患者,但差异无统计学意义。他汀类药物治疗与血脂异常患者PFS改善相关,提示他汀类药物在NETs中具有潜在的抗增殖作用。这些发现值得进一步调查,以证实他汀类药物在NETs管理中的作用。
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引用次数: 0
Central regulation of drinking water in divergently selected high-water-efficient young broiler chickens: A minireview. 不同选择高效用水仔鸡饮水的中心调控:综述。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-26 DOI: 10.1111/jne.13488
Brooklee Roach, Elizabeth S Greene, Sami Dridi

Poultry production is confronting real challenges, including a lofty projected high demand for animal proteins to feed the future, and the need to adapt to planetary boundaries (global warming) with limited natural resources (land, energy, water). Among the most challenging stressors to poultry production sustainability are heat stress (HS) and water uncertainty, that need extensive fundamental and applied research to identify effective strategies. In that regard, our group has recently developed a high-water-efficient broiler (meat-type) chicken line using water conversion ratio (WCR) as a phenotypic trait and defined the hypothalamic molecular mechanisms controlling drinking water under heat stress conditions. In response to the invitation from the Organizing Committee of the 13th International Symposium on Avian Endocrinology (ISAE 2024), the present review summarizes these data and closes the chapter by asking questions for future investigations. Data showed that HS exposure increased core body temperature (CBT) of both lines, with higher degree in HWE than in LWE counterparts. Despite this increase in CBT, HWE line drank less water but had superior performance with better feed conversion ratio (FCR) and WCR than LWE line. Molecular analyses showed that hypothalamic drinking-related neuropeptides (arginine vasopressin system, aquaporin system, renin, and angiotensin system) are affected in line- and/or environmental-dependent manner. Together, our research outcome indicates that the divergent selection for water efficiency could be an effective strategy to preserve water while maintaining optimal growth performance and could be applied to other poultry species and livestock.

家禽生产正面临着真正的挑战,包括对未来动物蛋白的高需求,以及在有限的自然资源(土地、能源、水)下适应地球边界(全球变暖)的需要。对家禽生产可持续性最具挑战性的压力因素是热应激(HS)和水的不确定性,这需要广泛的基础和应用研究来确定有效的策略。在这方面,我们小组最近以水分转化率(WCR)为表型性状,开发了一个高效用水的肉鸡(肉型)品系,并确定了热应激条件下下丘脑控制饮用水的分子机制。应第13届国际鸟类内分泌学研讨会(ISAE 2024)组委会的邀请,本文总结了这些数据,并对未来的研究提出了一些问题。数据显示,HS暴露增加了两种品系的核心体温(CBT), HWE组的升高程度高于LWE组。尽管CBT有所增加,但与LWE相比,HWE品系的饮水量更少,饲料系数(FCR)和WCR都更好。分子分析表明下丘脑饮酒相关的神经肽(精氨酸抗利尿激素系统、水通道蛋白系统、肾素和血管紧张素系统)以线性和/或环境依赖的方式受到影响。总之,我们的研究结果表明,水分效率的分歧选择可能是一种有效的策略,可以在保持最佳生长性能的同时保持水分,并且可以应用于其他家禽和牲畜。
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引用次数: 0
Lipopolysaccharide differentially alters systemic and brain glucocorticoid levels in neonatal and adult mice. 脂多糖不同地改变新生儿和成年小鼠的全身和脑糖皮质激素水平。
IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-18 DOI: 10.1111/jne.13481
Jordan E Hamden, Melody Salehzadeh, Hitasha Bajaj, Michael X Li, Kiran K Soma

Glucocorticoids (GCs) are secreted by the adrenal glands and increase in response to stressors (e.g., infection). The brain regulates local GC levels via GC synthesis, regeneration and/or metabolism. Little is known about local GC regulation within discrete brain regions at baseline or in response to stress. We treated male and female C57BL/6J mice at postnatal day 5 (PND5) or PND90 with lipopolysaccharide (LPS; 50 μg/kg bw i.p.) or vehicle and collected blood and brain after 4 h. We microdissected the prefrontal cortex, hippocampus, hypothalamus and amygdala. We measured seven steroids, including corticosterone, via liquid chromatography-tandem mass spectrometry and measured transcripts for key steroidogenic enzymes (Cyp11b1, Hsd11b1, Hsd11b2) via qPCR. At both ages, LPS increased GC levels in blood and all brain regions; however, the increases were much greater at PND90 than at PND5. Interestingly, PND5 corticosterone levels were lower in prefrontal cortex than in blood, but higher in amygdala than in blood. These changes in corticosterone levels align with local changes in steroidogenic enzyme expression, demonstrating robust regional heterogeneity and a possible mechanism for the region-specific effects of early-life stress. In contrast, PND90 corticosterone levels were lower in all brain regions than in blood and similar among regions, and steroidogenic enzyme mRNA levels were generally not affected by LPS. Together, these data indicate that local GC levels within discrete brain regions are more heterogeneous at baseline and in response to LPS at PND5 than at PND90, as a result of increased local GC production and metabolism in the neonatal brain.

糖皮质激素(GCs)由肾上腺分泌,并在应激源(如感染)的反应中增加。大脑通过GC合成、再生和/或代谢来调节局部GC水平。在基线或对压力的反应中,对分散的大脑区域的局部GC调节知之甚少。我们在出生后第5天(PND5)或PND90用脂多糖(LPS)治疗雄性和雌性C57BL/6J小鼠;50 μg/kg bw i.p)或载具,4 h后采集血液和脑组织。我们显微解剖了前额皮质、海马体、下丘脑和杏仁核。我们通过液相色谱-串联质谱法测量了七种类固醇,包括皮质酮,并通过qPCR测量了关键类固醇生成酶(Cyp11b1, Hsd11b1, Hsd11b2)的转录本。在两个年龄,LPS增加了血液和所有大脑区域的GC水平;然而,PND90的增幅远大于PND5。有趣的是,前额叶皮层中的PND5皮质酮水平低于血液,但杏仁核中的PND5皮质酮水平高于血液。皮质酮水平的这些变化与类固醇生成酶表达的局部变化一致,表明了强大的区域异质性和早期生活压力的区域特异性效应的可能机制。相比之下,PND90皮质酮水平在所有脑区都低于血液,且各区域之间相似,类固醇生成酶mRNA水平一般不受LPS的影响。综上所述,这些数据表明,由于新生儿大脑中局部GC产生和代谢增加,在PND5时,与PND90相比,在基线和LPS的反应中,离散脑区域内的局部GC水平更加不均匀。
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Journal of Neuroendocrinology
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