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Spurious Serum Hormone Immunoassay Results: Causes, Recognition, Management. 假血清激素免疫分析结果:原因,识别,处理。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.141
Glenn D Braunstein

For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and other analytical components. Despite the differences between commercial products, these assays provide important clinical information about hormone levels in patients. However, inaccurate results can occur because of technical issues, as well as patient-specific factors that can interfere with immunoassay hormone measurements. The latter include excessive normal blood or serum components, the presence of cross-reacting substances, extremely high levels of hormones leading to the high-dose hook effect, and interference from a variety of endogenous factors such as human antibodies that interact with the assay components or high levels of biotin in the serum from exogenous ingestion. This article briefly reviews the sources and recognition of endogenous interference, and describes methods to determine the correct serum hormone concentration.

50多年来,免疫测定法被广泛用于定量血液、其他液体和组织中的激素。每种分析方法都有自己的敏感性、特异性和其他分析成分。尽管商业产品之间存在差异,但这些检测提供了关于患者激素水平的重要临床信息。然而,由于技术问题以及可能干扰免疫测定激素测量的患者特异性因素,结果可能不准确。后者包括过量的正常血液或血清成分,交叉反应物质的存在,导致高剂量钩效应的极高水平的激素,以及各种内源性因素的干扰,如与测定成分相互作用的人抗体或外源性摄入的血清中高水平的生物素。本文简要综述了内源性干扰的来源和识别方法,并介绍了正确测定血清激素浓度的方法。
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引用次数: 2
Review of the Function of the Hypothalamic-Pituitary-Gonadal Axis in Children and Adolescents with Cancer. 儿童和青少年癌症患者下丘脑-垂体-性腺轴功能的研究进展。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.122
Jimena Lopez Dacal, Romina P Grinspon, Rodolfo A Rey

The most common malignancies in childhood are leukaemias, brain tumours, lymphomas, neuroblastomas, soft tissue sarcomas and kidney tumours. At present, about 80% of childhood cancers can be treated successfully, which has significantly increased long-term survival. Concomitantly, adult gonadal function in childhood cancer survivors has become a concern. However, the immediate effect of cancer and its management on the reproductive axis function has received less attention. We conducted a review of the effects of malignancies and their treatments on the gonadal axis during childhood and adolescence. Some results are controversial, probably because the analyses do not distinguish between the malignancy types, their treatments and/or the age at treatment. However, there is agreement that cancer can partially affect gonadal function before treatment, as revealed by low circulating levels of inhibin B and anti-Müllerian hormone. Subsequently, chemotherapy transiently impairs the somatic component of the gonads (i.e. testicular Sertoli cells and ovarian granulosa cells) with normalization after treatment ends. The impact of chemotherapy may persist through adulthood after more intensive chemotherapy regimens, radiotherapy and conditioning for haematopoietic stem cell transplantation, when there is a severe impairment of the somatic component of the gonads or of the stem germ cells.

儿童时期最常见的恶性肿瘤是白血病、脑肿瘤、淋巴瘤、神经母细胞瘤、软组织肉瘤和肾肿瘤。目前,约80%的儿童癌症可以成功治疗,这大大提高了长期生存率。与此同时,儿童癌症幸存者的成人性腺功能已成为一个关注的问题。然而,癌症的直接影响及其管理对生殖轴功能的关注较少。我们对儿童和青少年时期恶性肿瘤及其治疗对性腺轴的影响进行了综述。一些结果是有争议的,可能是因为分析没有区分恶性肿瘤类型、治疗方法和/或治疗年龄。然而,人们一致认为癌症在治疗前可以部分影响性腺功能,如低循环水平的抑制素B和抗勒氏激素。随后,化疗短暂地损害性腺的体细胞成分(即睾丸支持细胞和卵巢颗粒细胞),治疗结束后恢复正常。化疗的影响可能持续到成年后,在更密集的化疗方案,放疗和调节造血干细胞移植,当性腺或干细胞的体细胞成分严重受损。
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引用次数: 1
Macimorelin Acetate for the Diagnosis of Childhood-onset Growth Hormone Deficiency. 醋酸马西莫瑞林对儿童期生长激素缺乏症的诊断价值。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.84
Rohan K Henry

Growth hormone provocation testing forms the cornerstone of the diagnosis of childhood growth hormone deficiency in clinical practice. Despite the widespread use of these tests, various criticisms have been levelled against them, such as the labour-intensive nature of the tests, their potential for serious adverse effects and their questionable reproducibility. Macimorelin acetate, a ghrelin mimetic approved for the diagnosis of adult growth hormone deficiency, could serve an unmet need in the diagnosis of childhood-onset growth hormone deficiency based on its good tolerability and benign side effect profile.

生长激素激发试验是临床诊断儿童生长激素缺乏症的基础。尽管这些测试被广泛使用,但对它们提出了各种批评,例如测试的劳动密集性、可能产生严重不利影响以及可重复性值得怀疑。醋酸马西莫瑞林(Macimorelin acetate)是一种被批准用于诊断成人生长激素缺乏症的促生长素仿物,由于其良好的耐受性和良性副作用,可以满足儿童发病生长激素缺乏症的诊断需求。
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引用次数: 0
A New Medical Therapy for Multiple Endocrine Neoplasia Type 1? 1型多发性内分泌肿瘤的新疗法?
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.86
Hessa Boharoon, Ashley Grossman

Pancreatic neuroendocrine tumours (pNETs) are a major manifestation of multiple endocrine neoplasia type 1 (MEN1), and the most significant cause of morbidity and mortality in this disorder. There is some evidence that the early use of somatostatin analogues can retard progression, especially of small non-functioning tumours, but there are no other prophylactic therapies for patients, and the treatment of metastatic disease is similar to that for sporadic pNETs. A recent study has shown that in cell line and animal models, MEN1 mutations lead to an upregulation of the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in increasing precursor metabolites for the synthesis of pyrimidines. In these studies, blockade of this pathway by various means, including the DHODH inhibitor leflunomide, attenuates cell growth and tumour progression, suggesting a critical dependence on DHODH specifically in MEN1-mutated tissue. Preliminary clinical studies in three patients with MEN1 and pNETs have indicated some therapeutic potential of this drug, which has previously been used for some years in patients with rheumatoid arthritis. It is suggested that further clinical trials of this re-purposed drug are indicated to evaluate its potential for the treatment of patients with MEN1 and pNETS. This article describes the clinical problem of MEN1 and pNETs, and reviews the recent publication reporting on these initial results.

胰腺神经内分泌肿瘤(pNETs)是多发性1型内分泌瘤(MEN1)的主要表现,是该疾病发病率和死亡率的最重要原因。有一些证据表明,早期使用生长抑素类似物可以延缓进展,特别是小的无功能肿瘤,但没有其他预防治疗的患者,转移性疾病的治疗与散发性pNETs相似。最近的一项研究表明,在细胞系和动物模型中,MEN1突变导致二氢酸脱氢酶(DHODH)的上调,该酶参与嘧啶合成的前体代谢物的增加。在这些研究中,通过各种手段(包括DHODH抑制剂来氟米特)阻断这一途径,可以减缓细胞生长和肿瘤进展,这表明men1突变组织特异性依赖DHODH。在3例MEN1和pNETs患者的初步临床研究表明,该药物具有一定的治疗潜力,该药物先前已用于类风湿关节炎患者数年。建议进一步的临床试验,以评估其治疗MEN1和pNETS患者的潜力。本文描述了MEN1和pNETs的临床问题,并回顾了最近关于这些初步结果的出版物报道。
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引用次数: 0
APOC3 Interference for Familial Chylomicronaemia Syndrome. 家族性乳糜小贫血综合征的APOC3干扰。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.82
Robert A Hegele

Patients with familial chylomicronaemia syndrome (FCS) have severe hypertriglyceridaemia due to genetically absent lipolytic capacity. They have a poor response to conventional therapies. To reduce the risk of potentially fatal pancreatitis, the management of FCS relies principally on a strict low-fat diet, which is difficult to follow and compromises quality of life. Targeted reduction of apolipoprotein C-III using new anti-APOC3 agents, such as the short interfering RNA ARO-APOC3, represents a promising approach to correct the severe biochemical disturbance in FCS.

家族性乳糜小血症综合征(FCS)患者有严重的高甘油三酯血症,这是由于遗传上缺乏溶脂能力。他们对传统疗法的反应很差。为了降低潜在致命性胰腺炎的风险,FCS的管理主要依赖于严格的低脂饮食,这很难遵循并影响生活质量。使用新的抗apoc3药物(如短干扰RNA ARO-APOC3)靶向减少载脂蛋白C-III,是纠正FCS严重生化干扰的一种有希望的方法。
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引用次数: 3
Statin-related Muscle Toxicity: An Evidence-based Review. 他汀类药物相关肌肉毒性:基于证据的综述。
Pub Date : 2022-11-01 Epub Date: 2022-11-21 DOI: 10.17925/EE.2022.18.2.89
Mohammad S Jeeyavudeen, Joseph M Pappachan, Ganesan Arunagirinathan

The efficacy of statins in the primary and secondary prevention of cardiovascular disease has been proven beyond doubt. The number needed to treat to prevent one cardiovascular event is 1 in 30 over 10 years, and the number needed to treat for secondary prevention is much lower. However, a recent study demonstrated that only 68% of eligible patients are on statin therapy. Moreover, there seems to be a reluctance to escalate statin doses due to the fear of adverse effects. The adverse effects that worries patients and their physicians most frequently are those related to muscular symptoms. N-of-1 trial evidence suggests that muscular symptoms attributed to statins are often caused by the nocebo effect. This article aims to provide a structured, evidence-based approach to suspected statin-related muscle toxicity.

他汀类药物在心血管疾病一级和二级预防中的疗效已被证明是毋庸置疑的。在 10 年内预防一次心血管事件所需的治疗人数为 30 分之 1,而二级预防所需的治疗人数要低得多。然而,最近的一项研究表明,只有 68% 的合格患者在接受他汀类药物治疗。此外,由于担心不良反应,人们似乎不愿意增加他汀类药物的剂量。最让患者及其医生担心的不良反应是与肌肉症状有关的不良反应。N-of-1试验证据表明,他汀类药物引起的肌肉症状通常是由 "预兆效应"(nocebo effect)引起的。本文旨在为怀疑他汀类药物相关的肌肉毒性提供一种结构化的循证方法。
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引用次数: 0
Advances and Emerging Therapies in the Treatment of Non-alcoholic Steatohepatitis. 非酒精性脂肪性肝炎治疗的进展和新疗法。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.148
Paul N Brennan, John F Dillon, Rory McCrimmon

Non-alcoholic steatohepatitis (NASH) now represents one of the most prevalent forms of cirrhosis and hepatocellular carcinoma. A number of treatment agents have undergone assessment in humans following promising results in animal models. Currently, about 50 therapeutic agents are in various stages of development. Recently, however, there have been a number of exciting and positive developments in this landscape, although there are inherent challenges ahead. In this article, we review the aetiological and pathological basis of NASH progression and describe putative targets for current therapies. We also discuss some of the likely future directions and difficulties around this complex and challenging disease paradigm.

非酒精性脂肪性肝炎(NASH)现在是肝硬化和肝细胞癌最常见的形式之一。在动物模型取得令人满意的结果后,一些治疗药物已在人类身上进行了评估。目前,大约有50种治疗药物处于不同的开发阶段。然而,最近在这方面出现了一些令人兴奋和积极的事态发展,尽管前面存在着固有的挑战。在本文中,我们回顾了NASH进展的病因和病理基础,并描述了当前治疗的假定靶点。我们还讨论了围绕这种复杂和具有挑战性的疾病范式的一些可能的未来方向和困难。
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引用次数: 1
Non-albuminuric Diabetic Kidney Disease Phenotype: Beyond Albuminuria. 非白蛋白尿糖尿病肾病的表型:超越白蛋白尿。
Pub Date : 2022-11-01 DOI: 10.17925/EE.2022.18.2.102
Luis D'Marco, Xavier Guerra-Torres, Iris Viejo, Luis Lopez-Romero, Alejandra Yugueros, Valmore Bermídez

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease worldwide. Its pathogenic mechanism is complex, and it can affect the entire structures of the kidneys such as the glomerulus, tubules and interstitium. Currently, the urinary albumin excretion rate and the estimated glomerular filtration rate are widely accepted as diagnostic criteria. However, some studies have reported a different or non-classical clinical course of DKD, with some patients showing declined kidney function with normal levels of albuminuria, known as the 'non-albuminuric DKD' phenotype. The pathogenesis of this phenotype remains unclear, but some clinical and pathological features have been postulated. This review explores the evidence regarding this topic.

糖尿病肾病(DKD)是世界范围内慢性和终末期肾病的主要原因。其致病机制复杂,可累及肾小球、肾小管、肾间质等整个肾脏结构。目前,尿白蛋白排泄率和估算的肾小球滤过率被广泛接受为诊断标准。然而,一些研究报道了不同的或非经典的DKD临床病程,一些患者表现出肾功能下降,蛋白尿水平正常,被称为“非蛋白尿DKD”表型。这种表型的发病机制尚不清楚,但一些临床和病理特征已被假设。这篇综述探讨了关于这一主题的证据。
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引用次数: 1
Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Sodium-Glucose Co-transporter-2 Inhibitors. 钠-葡萄糖共转运体-2 抑制剂对心血管和肾脏有益的临床证据和拟议机制。
Pub Date : 2022-11-01 Epub Date: 2022-11-29 DOI: 10.17925/EE.2022.18.2.106
Joshua J Neumiller, Fredrick J Lienhard, Radica Z Alicic, Katherine R Tuttle

The number of people living with type 2 diabetes (T2D) and its complications worldwide is increasing at an alarming rate. Fortunately, our understanding of the benefits of glucose-lowering agents from the sodium-glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist classes on cardiovascular and kidney outcomes is advancing; this means we now have new options to mitigate the risks of these complications in patients with T2D. The SGLT2 inhibitors have consistently demonstrated benefits on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and heart failure (HF) events in dedicated outcome trials. Large guidelines groups now recommend SGLT2 inhibitors as a standard of care in patients with T2D and comorbid ASCVD, CKD and/ or HF. Evolving evidence additionally indicates kidney and HF benefits of SGLT2 inhibitors in populations without diabetes. These agents likely provide heart and kidney benefits through multiple mechanisms, as their impact on heart and kidney outcomes cannot be fully explained by their direct metabolic effects. On-going work to elucidate the beneficial mechanisms at play with SGLT2 inhibitors will help further optimize these life-saving therapies in patients with and without T2D.

全球 2 型糖尿病(T2D)患者及其并发症的人数正以惊人的速度增长。幸运的是,我们对钠-葡萄糖共转运体-2(SGLT2)抑制剂和胰高血糖素样肽-1(GLP-1)受体激动剂类降糖药物对心血管和肾脏功能的益处有了更深入的了解;这意味着我们现在有了新的选择来降低 T2D 患者出现这些并发症的风险。在专门的结果试验中,SGLT2 抑制剂已持续显示出对动脉粥样硬化性心血管疾病(ASCVD)、慢性肾脏疾病(CKD)和心力衰竭(HF)事件的益处。目前,大型指南小组推荐将 SGLT2 抑制剂作为并发 ASCVD、CKD 和/或 HF 的 T2D 患者的标准治疗方法。不断发展的证据还表明,SGLT2 抑制剂对无糖尿病人群的肾脏和心房颤动也有益处。这些药物可能通过多种机制为心脏和肾脏带来益处,因为它们对心脏和肾脏预后的影响不能完全通过其直接代谢作用来解释。目前正在进行的阐明 SGLT2 抑制剂获益机制的工作将有助于进一步优化这些拯救糖尿病患者和非糖尿病患者生命的疗法。
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引用次数: 0
Thyroid Function During and After COVID-19 Infection: A Review. COVID-19感染前后甲状腺功能的研究进展
Pub Date : 2022-06-01 Epub Date: 2022-06-13 DOI: 10.17925/EE.2022.18.1.58
Sabri Artun Çabuk, Ayşe Zeynep Cevher, Yaşar Küçükardalı

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to multiorgan dysfunction through pulmonary and systemic inflammation. Infection also affects the thyroid gland directly via cytopathological effects of the virus or indirectly through cytokines, complement systems and coagulation mechanisms. The thyroid gland regulates innate and adaptive immune systems by genomic and nongenomic pathways. During or after SARS-CoV-2 infection, Graves' disease and subacute thyroiditis might be triggered resulting in hyperthyroidism; alternatively, the effect of the virus on the hypophyseal.hypothalamic axis might cause central hypothyroidism. Severe cases of coronavirus disease 2019 (COVID-19) can present with hypoxia, which requires the use of dexamethasone. This can depress basal serum concentrations of 3,5,3'-triiodothyronine. Thyroid function should be monitored when using dexamethasone in patients with COVID-19. This article briefly reviews the direct and indirect effects of SARS-CoV-2 on the thyroid gland and function.

严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染可通过肺部和全身炎症导致多器官功能障碍。感染还通过病毒的细胞病理学作用直接影响甲状腺,或通过细胞因子、补体系统和凝血机制间接影响甲状腺。甲状腺通过基因组和非基因组途径调节先天和适应性免疫系统。在感染SARS-CoV-2期间或之后,可能引发Graves病和亚急性甲状腺炎,导致甲状腺功能亢进;或者,病毒对垂体的影响。下丘脑轴可能引起中枢性甲状腺功能减退。2019冠状病毒病(COVID-19)的严重病例可能出现缺氧,这需要使用地塞米松。这可以降低3,5,3'-三碘甲状腺原氨酸的基础血清浓度。COVID-19患者使用地塞米松时应监测甲状腺功能。本文就SARS-CoV-2对甲状腺及功能的直接和间接影响作一综述。
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引用次数: 5
期刊
TouchREVIEWS in endocrinology
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