Pediatric endocrinology reviews : PER最新文献

英文中文

Osteoclasts in Health and Disease. 健康与疾病中的破骨细胞

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-12-01 DOI: 10.17458/per.vol17.2019.l.osteoclastshealthdisease

U. Lerner

Osteoclasts are multinucleated, giant cells originating from myeloid hematopoetic stem cells. These are the only cells in nature which can resorb bone. Differentiation of mononucleated osteoclast progenitor cells requires stimulation with M-CSF (macrophage colony-stimulating factor) for the cells to proliferate and survive and with RANKL (receptor activator of nuclear factor kappa B ligand) for differentiation along the osteoclastic lineage to cells which eventually fuse to the mature, multinucleated osteoclasts. Therefore, most hormones and cytokines stimulating osteoclastogenesis do so indirectly by regulating the expression in osteoblasts of RANKL and its inhibitory decoy receptor OPG. Antibodies neutralizing RANKL is a common therapy to inhibit excessive osteoclast formation in diseases such as osteoporosis and malignant tumors with skeletal metastasis. Mature osteoclasts resorb bone by stimulating acid release into the resorption lacunae, followed by proteolytic degradation of bone matrix proteins. Loss-of-function mutations of proteins involved in acidification and proteolysis cause osteopetrosis, a disease with sclerotic bone due to non-functional osteoclasts. Osteoclasts are important for a healthy skeleton by removing damaged bone during remodeling of the skeleton, but are also important for modeling of bone, calcium homeostasis and tooth eruption, and possibly also for glucose and fat metabolism. Loss of bone in inflammatory disease, metastasizing tumors and osteoporosis is due to increased RANKL expression and enhanced osteoclast formation. The present overview aims to summarize how osteoclasts are formed and resorb bone in health and disease.

破骨细胞是起源于髓系造血干细胞的多核巨细胞。这些细胞是自然界中唯一能吸收骨头的细胞。单核破骨细胞祖细胞的分化需要M-CSF(巨噬细胞集落刺激因子)的刺激才能增殖和存活，需要RANKL(核因子κ B配体受体激活因子)的刺激才能沿着破骨细胞谱系分化为最终融合为成熟的多核破骨细胞。因此，大多数刺激破骨细胞形成的激素和细胞因子是通过间接调节RANKL及其抑制诱饵受体OPG在成骨细胞中的表达来实现的。抗体中和RANKL是抑制骨质疏松症和伴有骨骼转移的恶性肿瘤等疾病中过度破骨细胞形成的常用疗法。成熟的破骨细胞通过刺激酸释放到吸收腔隙来吸收骨，随后是骨基质蛋白的蛋白水解降解。参与酸化和蛋白水解的蛋白质的功能缺失突变导致骨质疏松症，这是一种由无功能破骨细胞引起的骨质硬化疾病。破骨细胞在骨骼重塑过程中清除受损骨骼，对骨骼健康至关重要，但对骨骼建模、钙稳态和牙齿萌出也很重要，可能对葡萄糖和脂肪代谢也很重要。炎症性疾病、转移性肿瘤和骨质疏松症的骨质流失是由于RANKL表达增加和破骨细胞形成增强。本综述旨在总结破骨细胞在健康和疾病中是如何形成和吸收骨的。

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引用次数: 8

Endocrine Management of Ovotesticular DSD, an Index Case and Review of the Literature. 卵睾丸DSD的内分泌管理，一个指标病例及文献复习。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-12-01 DOI: 10.17458/per.vol17.2019.kmv.endocrineovotesticulardsd

Marissa J Kilberg, M. McLoughlin, L. Pyle, M. Vogiatzi

Ovotesticular Differences in Sexual Development (OT-DSD) is a rare subset of DSD with great phenotypic variability characterized by the presence of both testicular and ovarian tissue in the same individual. Here, we describe the case of 46,XX, SRY-negative baby with ambiguous genitalia and ovotestis discovered during laparoscopy. As the family decided on female gender of rearing, the testicular component of the ovotestis was removed while the ovarian component was preserved. Stemming from this case, we review the clinical presentation of OT-DSD throughout ages, the role of genetics and risk for gonadal tumors when making decisions about prophylactic gonadectomy. Finally, we summarize the most recent information of the spontaneous endocrine function, with or without conservative therapy, and fertility potential of people with OT-DSD.

卵睾丸性发育差异(OT-DSD)是一种罕见的DSD亚型，具有很大的表型变异性，其特征是在同一个体中存在睾丸和卵巢组织。在这里，我们描述了一例46,XX, sry阴性婴儿，在腹腔镜检查中发现生殖器和卵睾丸模糊。当家庭决定雌性饲养时，卵睾丸的睾丸部分被移除，卵巢部分被保留。基于这一病例，我们回顾了OT-DSD在各个年龄段的临床表现，在决定是否进行预防性性腺切除术时，遗传和性腺肿瘤风险的作用。最后，我们总结了OT-DSD患者在接受或不接受保守治疗时自发性内分泌功能和生育潜力的最新信息。

引用次数: 7

Growth Hormone Deficiency and Excessive Sleepiness: A Case Report and Review of the Literature. 生长激素缺乏与嗜睡:1例报告及文献复习。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.ge.ghdeficiencyandsleepiness

Anisha Gohil, E. Eugster

The somatotropic axis is intricately involved in normal sleep, as evidenced by the fact that hypothalamic growth hormone-releasing hormone (GHRH) has sleep promoting effects and pituitary growth hormone (GH) release is strongly associated with slow-wave sleep (SWS). Abnormalities in the somatotropic axis, such as GH deficiency of hypothalamic or pituitary origin, result in an alteration of normal sleep patterns which may explain the fatigue reported in these individuals. Sleep disorders such as narcolepsy, in which individuals abnormally enter rapid eye movement (REM) sleep at sleep onset are also associated with an altered GHRH circadian rhythm and abnormal GH secretion. While few studies are available, this review explores what is known about sleep abnormalities in GH deficiency, the effect of treatment on sleep in patients with GH deficiency, and GH secretion in narcolepsy. Emerging evidence suggests a hypothalamic link between narcolepsy and GH secretion. We also describe the unique constellation of isolated idiopathic GH deficiency and severe excessive sleepiness in adopted Nicaraguan siblings, one of which has narcolepsy and the other idiopathic hypersomnia.

下丘脑生长激素释放激素(GHRH)具有促进睡眠的作用，垂体生长激素(GH)的释放与慢波睡眠(SWS)密切相关，这一事实证明，促生长轴与正常睡眠有着复杂的关系。体强性轴的异常，如下丘脑或垂体源的生长激素缺乏，导致正常睡眠模式的改变，这可能解释了这些人报告的疲劳。睡眠障碍，如嗜睡症，患者在睡眠开始时异常进入快速眼动(REM)睡眠，也与GHRH昼夜节律改变和生长激素分泌异常有关。虽然很少有研究可用，但这篇综述探讨了生长激素缺乏症患者的睡眠异常，治疗对生长激素缺乏症患者睡眠的影响，以及发作性睡病患者的生长激素分泌。新出现的证据表明，发作性睡病与生长激素分泌之间存在下丘脑联系。我们还描述了尼加拉瓜收养的兄弟姐妹中孤立的特发性生长激素缺乏和严重过度嗜睡的独特组合，其中一个患有发作性睡病，另一个患有特发性嗜睡症。

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引用次数: 8

Meeting Report: 2019 Annual Meeting of the Pediatric Endocrine Society: Selected Highlights Baltimore, MD, April 26-29, 2019. 会议报告:2019年儿科内分泌学会年会:精选亮点巴尔的摩，马里兰州，2019年4月26日至29日。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.gkg.mr.2019annualmeetingbaltimore

Danielle Guiffre, Grace Kim, Meenal Gupta

引用次数: 0

Emerging Mechanisms of GH-Induced Lipolysis and Insulin Resistance. gh诱导的脂肪分解和胰岛素抵抗的新机制。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.s.ghlipolysisandinsulinresistance

V. Sharma

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.

生长激素(GH)是一种多效性激素，协调一系列生理过程，包括生长和代谢。生长激素促进除脂肪外的所有组织的合成代谢作用，在脂肪中，它分解代谢储存的脂肪，释放能量，促进其他组织的生长。然而，生长激素对脂肪分解的慢性刺激导致游离脂肪酸(FFAs)进入体循环的通量增加。因此，高水平生长激素的持续释放通过拮抗胰岛素的抗脂溶作用而显著促进胰岛素抵抗的发展。然而，与生长激素在脂肪组织中的脂溶作用相关的分子途径仍然难以捉摸。最近的研究提供了gh诱导的脂肪分解和胰岛素信号损伤的分子见解。本文讨论了GH对脂肪组织的生理和代谢作用，以及GH介导的FSP27-PPARγ轴的失调，这种失调改变了脂肪组织的稳态，并有助于胰岛素抵抗和2型糖尿病的发展。

引用次数: 4

FGF23 and Associated Disorders of Phosphate Wasting. FGF23与磷酸盐消耗相关疾病。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.gi.fgf23anddisordersphosphate

Anisha Gohil, Erik A Imel

Fibroblast growth factor 23 (FGF23), one of the endocrine fibroblast growth factors, is a principal regulator in the maintenance of serum phosphorus concentration. Binding to its cofactor αKlotho and a fibroblast growth factor receptor is essential for its activity. Its regulation and interaction with other factors in the bone-parathyroid-kidney axis is complex. FGF23 reduces serum phosphorus concentration through decreased reabsorption of phosphorus in the kidney and by decreasing 1,25 dihydroxyvitamin D (1,25(OH)2D) concentrations. Various FGF23-mediated disorders of renal phosphate wasting share similar clinical and biochemical features. The most common of these is X-linked hypophosphatemia (XLH). Additional disorders of FGF23 excess include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, and tumor-induced osteomalacia. Treatment is challenging, requiring careful monitoring and titration of dosages to optimize effectiveness and to balance side effects. Conventional therapy for XLH and other disorders of FGF23-mediated hypophosphatemia involves multiple daily doses of oral phosphate salts and active vitamin D analogs, such as calcitriol or alfacalcidol. Additional treatments may be used to help address side effects of conventional therapy such as thiazides to address hypercalciuria or nephrocalcinosis, and calcimimetics to manage hyperparathyroidism. The recent development and approval of an anti-FGF23 antibody, burosumab, for use in XLH provides a novel treatment option.

成纤维细胞生长因子23 (FGF23)是一种内分泌成纤维细胞生长因子，是维持血清磷浓度的主要调节因子。结合其辅因子α - klotho和成纤维细胞生长因子受体对其活性至关重要。它与骨-甲状旁腺-肾轴的其他因子的调节和相互作用是复杂的。FGF23通过降低磷在肾脏中的重吸收和降低1,25二羟基维生素D (1,25(OH)2D)浓度来降低血清磷浓度。各种fgf23介导的肾磷消耗紊乱具有相似的临床和生化特征。最常见的是x连锁低磷血症(XLH)。FGF23过量的其他疾病包括常染色体显性低磷血症佝偻病、常染色体隐性低磷血症佝偻病、纤维发育不良和肿瘤诱导的骨软化症。治疗是具有挑战性的，需要仔细监测和滴定剂量，以优化效果和平衡副作用。XLH和其他fgf23介导的低磷血症疾病的常规治疗包括每日多次剂量的口服磷酸盐和活性维生素D类似物，如骨化三醇或阿法骨化醇。额外的治疗可以用来帮助解决常规治疗的副作用，如噻嗪类药物治疗高钙尿症或肾钙化症，和钙化剂治疗甲状旁腺功能亢进。最近开发和批准的抗fgf23抗体burrosumab用于XLH提供了一种新的治疗选择。

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引用次数: 36

Are We Aware that Hyperphosphatemia Affects Mortality and Morbidity as much as Hypophosphatemia in Pediatric Intensive Care Patients? 我们是否意识到高磷血症对儿童重症患者的死亡率和发病率的影响与低磷血症一样大?

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.ake.hyperphosphatemiaaffectsmortality

Y. Akbaş, A. Koker, N. Erkek

OBJECTIVEHypophosphatemia was previously shown to affect the duration of admission, mechanical ventilator requirements, mortality and morbidity during pediatric intensive care. Different from previous studies, our study was planned with the aim of showing whether hyperphosphatemia affects morbidity and mortality in pediatric intensive care patients as much as hypophosphatemia.METHODPatients' ages, genders, reason for admission, underlying diseases, phosphorus levels examined on admission and on the 1-4th and 5-10th-days, duration on mechanical ventilation, duration of admission, final status and PRISM and PELOD scores calculated in the first 24 hours of admission were recorded.RESULTSMortality was distinctly higher for those who were hypophosphatemic and hyperphosphatemic compared to those who were normophosphatemic. The highest mortality was identified in those who were hyperphosphatemic on the 5-10th-days. PELOD scores were only significantly different according to admission phosphorus levels (p:0.04).CONCLUSIONIn our study, we identified that hyperphosphatemia is a serious problem as hypophosphatemia for patients who admitted to the PICU. Patients identified to be hyperphosphatemic on admission had a significantly higher PELOD score. The significant difference of hyperphosphatemia in terms of PELOD score is one of the important points shown in our study. It should not be forgotten that like hypophosphatemia, hyperphosphatemia may cause serious problems in pediatric intensive care patients.

目的:低磷血症先前被证明会影响儿科重症监护期间的入院时间、机械呼吸机需求、死亡率和发病率。与以往的研究不同，我们的研究旨在揭示高磷血症是否与低磷血症一样影响儿科重症患者的发病率和死亡率。方法记录患者的年龄、性别、入院原因、基础疾病、入院时、1-4天、5-10天检查的磷水平、机械通气时间、住院时间、最终状态及入院前24 h计算的PRISM和PELOD评分。结果低磷血症和高磷血症患者的死亡率明显高于正常磷血症患者。死亡率最高的是那些在5-10天出现高磷血症的患者。入院时各组患者的PELOD评分差异有统计学意义(p:0.04)。结论:在我们的研究中，我们发现高磷血症与低磷血症对于入住PICU的患者来说是一个严重的问题。入院时确诊为高磷血症的患者PELOD评分明显较高。高磷血症在PELOD评分上的显著差异是我们研究的重点之一。不应忘记，像低磷血症一样，高磷血症可能会对儿科重症监护患者造成严重问题。

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引用次数: 2

Letter to the Editor: Central Nervous System Complications in Diabetic Ketoacidosis. 致编辑的信:糖尿病酮症酸中毒的中枢神经系统并发症。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-09-01 DOI: 10.17458/per.vol17.2019.le.bwwmwc.nervouscomplicationsdiabetic

Marta Baszyńska-Wilk, M. Wysocka-Mincewicz, Małgorzata Wajda-Cuszlag, A. Świercz, M. Szalecki

引用次数: 3

Height SDS Changes (ΔhSDS) in Healthy Children from Birth to 18 Years, with Correction Factors for Measurement Intervals of Less than One Year. 健康儿童从出生到18岁的身高SDS变化(ΔhSDS)，测量间隔小于一年的校正因子。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-06-01 DOI: 10.17458/per.vol16.2019.hmr.heightsdschanges

Michael Hermanussen, Rebekka Mumm, Aileen Rintisch, Janina Tutkuviene, Andrej Suchomlinov, Kálmán Joubert, Angel Ferrandez Longas, Christiane Scheffler

Background: Growth is volatile and non-linear. Assessing the instantaneous speed of growth (momentary height velocity) depends on the precision and the number of measurements and the duration of the observation period. Measurements at short intervals reflect both the non-linearity of growth and the technical error of measurements (TEM).

Material: We reanalyzed longitudinal measurements of body length at age 0, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months, from 1879 healthy infants (956 girls, 923 boys) from France (180 girls, 173 boys), Vilnius, Lithuania (507 girls, 507 boys), Lublin, Poland (67 girls, 56 boys), Zürich, Switzerland (94 girls, 102 boys) and Spain (108 girls, 95 boys); and longitudinal measurements of annual body height from age 2 to 18 years from 1528 healthy children and adolescents (774 girls, 754 boys) from France (41 girls, 47 boys), Vilnius, Lithuania (23 girls, 27 boys), Lublin, Poland (70 girls, 58 boys), Zürich, Switzerland (111 girls, 120 boys), Spain (94 girls, 74 boys), the Czech Republic (65 girls, 69 boys), Hungary (316 girls, 320 boys), and Berkeley, USA (54 girls, 39 boys).

Results: We calculated age - and sex-specific mean values for height and SD for height separately for each country. In addition, we defined the instantaneous speed of growth by the difference of two measures of hSDS Formulas References A1 , or in the case of multiple measurements, by the slope of the linear regression (βhSDS(t)). Based on the longitudinal measurements of body length, we present reference values for annual growth velocity given in the form of SD of annual hSDS changes (ΔhSDS), from birth to maturity. Correction factors are added for validating measurements obtained at intervals of less than one year. The correction factors depend on number of measurements, and duration of the observation period.

背景:增长是不稳定和非线性的。评估瞬时增长速度(瞬时高度速度)取决于测量的精度和次数以及观察期的持续时间。短时间间隔的测量反映了生长的非线性和测量的技术误差(TEM)。资料:我们重新分析了1879名来自法国(180名女孩，173名男孩)、立陶宛维尔纽斯(507名女孩，507名男孩)、波兰卢布林(67名女孩，56名男孩)、瑞士z rich(94名女孩，102名男孩)和西班牙(108名女孩，95名男孩)的健康婴儿(956名女孩，923名男孩)0、3个月、6个月、9个月、12个月、18个月和24个月时的体长纵向测量数据;并对来自法国(41名女孩，47名男孩)、立陶宛维尔纽斯(23名女孩，27名男孩)、波兰卢布林(70名女孩，58名男孩)、瑞士z里希(111名女孩，120名男孩)、西班牙(94名女孩，74名男孩)、捷克共和国(65名女孩，69名男孩)、匈牙利(316名女孩，320名男孩)和美国伯克利(54名女孩，39名男孩)的1528名健康儿童和青少年(774名女孩，754名男孩)从2岁到18岁的年身高进行纵向测量。结果:我们分别计算了每个国家不同年龄和性别的身高平均值和身高标准差。此外，我们通过hSDS的两个测量值的差来定义瞬时生长速度，或者在多次测量的情况下，通过线性回归的斜率(βhSDS(t))来定义瞬时生长速度。根据体长的纵向测量，我们给出了从出生到成熟的年生长速度的参考值，以年hSDS变化的SD形式给出(ΔhSDS)。为验证间隔小于一年的测量结果，增加了校正因子。校正因子取决于测量次数和观察期的持续时间。

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引用次数: 0

For Debate: Testicular Volume Development along Ages: Evaluation by Different Methods. 辩论:睾丸体积随年龄的发展:不同方法的评估。

4区医学 Q2 Medicine

Pediatric endocrinology reviews : PER

Pub Date : 2019-06-01 DOI: 10.17458/per.vol16.2019.dsm.fd.testicularvolume

Vincenzo De Sanctis, Ashraf T Soliman, Salvatore Di Maio, Giuseppe Millimaggi, Christos Kattamis

In the last five decades an increasing number of studies and clinical reports demonstrated the importance of testicular volume assessment in pediatric and adolescent population. Reliable and accurate determination of testicular volume (TV) through infancy and adolescence is of great importance for assessing normal pubertal development to diagnose disturbances in development and to suspect certain genetic and endocrine diseases. Various approaches are available for the assessment of TV, including orchidometry, rulers, callipers, and ultrasonography (USG). Our report focuses on the importance of the evolution of TV from birth to adulthood and debates the main factors influencing the accuracy of different TV measurements. We endorse that any method for the evaluation of TV must satisfy certain criteria: a. be applicable to persons of all ages from pre-adolescence, through the pubertal spurt to full maturity, b. be simple to use, c. be free from observer error as possible, and d. have a high degree of correlation with other observable developmental characteristics.

在过去的五十年中，越来越多的研究和临床报告证明了睾丸体积评估在儿科和青少年人群中的重要性。在婴儿期和青春期可靠、准确地测定睾丸体积(TV)对于评估青春期正常发育、诊断发育障碍和怀疑某些遗传和内分泌疾病具有重要意义。有多种方法可用于评估电视，包括兰花测量，尺子，卡尺，和超声检查(USG)。我们的报告侧重于电视从出生到成年演变的重要性，并讨论了影响不同电视测量精度的主要因素。我们赞同任何评估电视的方法都必须满足以下标准:a.适用于从青春期前到青春期爆发到完全成熟的所有年龄段的人;b.使用简单;c.尽可能避免观察者误差;d.与其他可观察到的发展特征高度相关。

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引用次数: 1

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