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Mental disorders in children and adolescents with type 1 diabetes before and during the COVID-19 pandemic: results from the DPV registry. COVID-19 大流行之前和期间 1 型糖尿病儿童和青少年的精神障碍:DPV 登记的结果。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-21 Print Date: 2024-07-26 DOI: 10.1515/jpem-2024-0129
Esther Müller-Godeffroy, Stefanie Schmid, Christina Reinauer, Angela Galler, Dörte Hilgard, Louise Marshall, Thomas Kapellen, Eggert Lilienthal, Kirsten Mönkemöller, Burkhard Brosig, Christine Prchla, Reinhard W Holl

Objectives: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic.

Methods: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included. Multivariable regression models were applied to compare newly diagnosed comorbid mental disorders, adjusted for demographic and clinical variables, among them the number of medical visits, during the pre-pandemic period (09/2017-02/2020) and the COVID-19 pandemic period (03/2020-08/2022).

Results: Analysing both sexes together, there were no differences in the incidence rates of overall mental disorders between the pandemic and the pre-pandemic period. However, girls showed an increased incidence rate (odds ratio 1.2, CI 1.1-1.3) during the pandemic. Adolescent girls also displayed higher incidence rates of depression, eating disorders, and self-harm. Substance misuse declined overall during the pandemic (odds ratio 0.8, CI 0.7-0.9).

Conclusions: During the COVID-19 pandemic, we found higher incidence rates of overall mental disorders in girls, but not in boys and not in the total study population of children and adolescents with type 1 diabetes. Adolescent girls displayed increased incidence rates of depression, eating disorders, and self-harm. Substance misuse declined substantially. Clinicians should be aware of the high-risk group of adolescent girls during times of increased strain.

目标:COVID-19 大流行影响了普通人群中儿童和青少年的心理健康,但其对患有慢性疾病的儿童和青少年的影响却相对未知。本研究旨在比较大流行之前和期间患有1型糖尿病的儿童和青少年合并精神障碍和药物滥用的发生率:研究共纳入了多中心 DPV(糖尿病前瞻性随访)登记处的 42975 名 6-18 岁患者。采用多变量回归模型对大流行前(2017 年 9 月至 2020 年 2 月)和 COVID-19 大流行期间(2020 年 3 月至 2022 年 8 月)新诊断出的合并精神障碍进行比较,并对人口统计学和临床变量(其中包括就诊次数)进行调整:结果:对男女两性进行综合分析后发现,大流行期间与大流行前期间的总体精神障碍发病率没有差异。然而,在大流行期间,女孩的发病率有所上升(几率比 1.2,CI 1.1-1.3)。少女抑郁、饮食失调和自残的发病率也较高。在大流行期间,滥用药物的情况总体上有所减少(几率比0.8,CI 0.7-0.9):结论:在 COVID-19 大流行期间,我们发现女孩的总体精神障碍发病率较高,但男孩和所有 1 型糖尿病儿童和青少年患者中的发病率并不高。少女抑郁症、进食障碍和自残的发病率有所上升。药物滥用率则大幅下降。临床医生应在压力增加时注意青春期女孩这一高风险群体。
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引用次数: 0
Growth hormone therapy does not impact the development of intracranial hypertension in children with Chiari malformation. 生长激素治疗不会影响Chiari畸形患儿颅内高压的发展。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-24 Print Date: 2024-07-26 DOI: 10.1515/jpem-2024-0064
Matthew D Krasnow, Liam McGuirk, Alice Alexandrov, Monica Naparst, Tara Patale, Shilpa Mehta, Richard Noto

Objectives: Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT.

Methods: The database of a pediatric endocrinology center was queried for patients with CM who received GHT from 2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature of symptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated.

Results: GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS.

Conclusions: Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

目的:Chiari畸形(CM)患者容易出现各种神经系统后遗症,包括良性颅内高压(BIH)。在这些患者中,良性颅内高压是由于后窝解剖异常导致脑脊液(CSF)流动受阻所致。偶尔,CM 患者可能需要生长激素治疗(GHT),这可以增加 CSF 的分泌。据认为,接受生长激素治疗的 CM 患者出现 BIH 相关症状(BIHAS)的风险很高。我们描述了 34 例 CM 患者在接受 GHT 治疗前和治疗期间神经系统症状的发生率:我们在一家儿科内分泌中心的数据库中查询了 2010-22 年间接受 GHT 治疗的 CM 患者。对不良事件记录进行了审查。收集并分析了人口统计学和放射学数据。排除了患有肿瘤性疾病、活动性炎症或急性创伤的患者。CM诊断由神经放射科独立完成。根据 GHT 前和 GHT 期间症状的存在和性质对患者进行分组。评估了起始剂量/体重指数与 BIHAS/所有 GHT 相关症状发生率之间的关系:结果:在 34 名 CM 患者中,33 人的 GHT 与新发或原有 BIHAS 的恶化无关。五名复杂的患者继续存在原有的 BIHAS,但并未恶化。在接受 GHT 治疗期间出现新发 BIHAS 的四名患者中,有三名患者的症状是由其他疾病引起的。没有患者因 BIHAS 而永久停止 GHT:结论:生长激素治疗对于Chiari畸形患者可能是一种安全的治疗方法,不太可能导致BIHAS。
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引用次数: 0
Familial dysalbuminemic hyperthyroxinemia (FDH) due to Arg242 His variant in ALB gene in Turkish children. 土耳其儿童因 ALB 基因 Arg242 His 变异而患家族性白蛋白血症性高甲状腺素血症 (FDH)。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-14 Print Date: 2024-06-25 DOI: 10.1515/jpem-2023-0506
Doga Turkkahraman, Merve Gullu, Suat Tekin, Tarkan Kalkan

Objectives: To investigate albumin (ALB) gene variations in patients suspected from familial dysalbuminemic hyperthyroxinemia (FDH).

Methods: Eight Turkish patients were included into the study. Clinical and laboratory characteristics of the subjects and their parents were evaluated and genetic analysis were performed.

Results: In genetic analysis, a previously reported heterozygous, c.725G>A variant was detected in exon seven of the ALB gene.

Conclusions: FDH is an asymptomatic condition however there is still a risk of misdiagnosis and unnecessary treatment. Therefore, if FDH is considered, initial ALB hotspot sequencing as a rapid and simple method is recommended instead of complex and expensive laboratory and imaging techniques.

目的调查家族性白蛋白异常性高甲状腺素血症(FDH)疑似患者的 ALB 基因变异:研究纳入了 8 名土耳其患者。对受试者及其父母的临床和实验室特征进行了评估,并进行了基因分析:结果:在基因分析中,在 ALB 基因第七外显子中检测到了一个之前报道过的 c.725G>A 杂合子变异:结论:FDH 是一种无症状疾病,但仍存在误诊和不必要治疗的风险。因此,如果考虑到 FDH,建议采用快速、简单的 ALB 热点测序初步方法,而不是复杂、昂贵的实验室和成像技术。
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引用次数: 0
Post hoc subgroup analysis of Asian children with paediatric GHD from the global phase 3 efficacy and safety study of once-weekly somatrogon vs. once-daily somatropin. 每周一次索马特罗贡与每日一次索马特罗苹的全球第三阶段疗效和安全性研究中,对患有小儿GHD的亚洲儿童进行的事后分组分析。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-09 Print Date: 2024-06-25 DOI: 10.1515/jpem-2023-0512
Roy Gomez, Vaman Khadilkar, Jayashri Shembalkar, Der-Ming Chu, Cheol Woo Ko, Michael P Wajnrajch, Ronnie Wang

Objectives: Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD.

Methods: Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS.

Results: This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children.

Conclusions: This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004.

目的:索马曲贡(Somatrogon)是一种长效重组人生长激素,用于治疗小儿生长激素缺乏症(pGHD)患者。这项全球性三期研究比较了生长激素缺乏症儿童每周一次索马曲贡和每天一次索马托品的疗效和安全性:青春期前的患者按 1:1 随机分配到每周一次的索马曲贡(0.66 毫克/千克/周)或每日一次的索马托品(0.24 毫克/千克/周),为期 12 个月。主要终点是第12个月时的身高速度(HV);次要终点包括第6个月时的身高速度、第6个月和第12个月时的身高标准差评分(SDS)变化以及胰岛素样生长因子1(IGF-1)SDS:这项事后分组分析专门针对八个国家的亚洲儿童(索马特罗琼:24 人,平均年龄 7.76 岁;索马特罗苹:21 人,平均年龄 8.10 岁)。第 12 个月时的平均 HV 值为 10.95 厘米/年(索马特罗贡)和 9.58 厘米/年(索马特罗苹);索马特罗贡的治疗差异为 1.38 厘米/年。治疗差异(索马特罗贡-索马托品)的双侧 95% CI 下限为-0.20,与总体研究人群(-0.24)相似。与索马托品组相比,索马曲康组在第6个月时的身高体重数值更高(8.31厘米/年对11.23厘米/年);在第6个月和第12个月时,身高SDS和IGF-1 SDS也观察到类似趋势。各治疗组之间的安全性和耐受性相似;83%接受过索马曲贡治疗的儿童和76%接受过索马托品治疗的儿童发生了不良事件:该亚组分析表明,索马曲贡在亚洲儿童中的疗效和安全性与总体研究结果一致,即每周一次的索马曲贡疗效不劣于每日一次的索马托品。Clinicaltrials.gov:NCT02968004。
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引用次数: 0
Comprehensive analyses of phenylalanine hydroxylase variants and phenotypic characteristics of patients in the eastern region of Türkiye. 综合分析土耳其东部地区苯丙氨酸羟化酶变体和患者的表型特征。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-07 Print Date: 2024-06-25 DOI: 10.1515/jpem-2024-0091
Ceren Alavanda, Emine İpek Ceylan, Sebile Kılavuz, Kısmet Çıkı

Objectives: Phenylalanine hydroxylase (PAH) is predominantly a hepatic enzyme that catalyzes phenylalanine (Phe) into tyrosine, which is the rate-limiting step in Phe catabolism. Biallelic variants in the PAH gene cause PAH enzyme deficiency. Phenylketonuria (PKU) is an autosomal recessive disorder that causes neurologic, behavioral, and dermatological findings. PKU could be divided clinically into three types based on the blood Phe levels: classic phenylketonuria (cPKU), mild-moderate phenylketonuria (mPKU), and mild hyperphenylalaninemia (MHP). This study aimed to determine the phenotypic and genotypic characteristics of Turkish PKU patients in the eastern region of Türkiye.

Methods: Demographic characteristics, serum Phe levels, treatments, and PAH variants of 163 patients with PKU and hyperphenylalaninemia (HPA) were retrospectively evaluated. Blood Phe levels of the patients were analyzed with the high-performance liquid chromatography method. For PAH gene analysis, next-generation sequencing was performed.

Results: Of the 163 patients included in the study, 38 (23.3 %) had cPKU, 16 (9.8 %) had mPKU, and 109 (66.9 %) had MHP. Homozygous variants in the PAH gene were detected in 66 (40.5 %) of the patients, while compound heterozygous variants were detected in 97 (59.5 %) patients. Two novel and 35 recurrent variants in the PAH gene were detected. Of the two novel variants, one was missense (p.Phe351Leu) and the other was frameshift (p.Met276Cysfs*65). The most frequently detected variants were p.Thr380Met (18 %), p.Arg261Gln (16.8 %), and p.Ala300Ser (12.8 %). All patients with the homozygous c.1066-11G>A variant exhibited cPKU phenotype. The c.898G>T (p.Ala300Ser), c.1139C>T (p.Thr380Met), and c.1208C>T (p.Ala403Val) variants were statistically related to mild phenotype. On the other hand, c.592_613del (p.Tyr198Serfs*136), c.1028A>G (p.Tyr343Cys), and c.782G>A (p.Arg261Gln) variants were more frequently detected in the cPKU group.

Conclusions: Our study, conducted with patients from the eastern region of Türkiye, demonstrates the genetic heterogeneity in the Turkish population. Simultaneously, our research contributes to genotype-phenotype correlation and expands the genotypic spectrum by identifying novel variants.

目的:苯丙氨酸羟化酶(PAH)主要是一种肝脏酶,可催化苯丙氨酸(Phe)转化为酪氨酸,这是 Phe 分解代谢的限速步骤。PAH 基因的双叶变体会导致 PAH 酶缺乏症。苯丙酮尿症(PKU)是一种常染色体隐性遗传疾病,可导致神经、行为和皮肤病。根据血液中 Phe 的水平,PKU 临床上可分为三种类型:典型苯丙酮尿症(cPKU)、轻中度苯丙酮尿症(mPKU)和轻度高苯丙氨酸血症(MHP)。本研究旨在确定土耳其东部地区 PKU 患者的表型和基因型特征:方法:对163名PKU和高苯丙氨酸血症(HPA)患者的人口统计学特征、血清Phe水平、治疗方法和PAH变体进行了回顾性评估。采用高效液相色谱法分析了患者的血Phe水平。为了分析 PAH 基因,进行了新一代测序:在纳入研究的 163 名患者中,38 人(23.3%)患有 cPKU,16 人(9.8%)患有 mPKU,109 人(66.9%)患有 MHP。在 66 例(40.5%)患者中检测到 PAH 基因的同源杂合变异,而在 97 例(59.5%)患者中检测到复合杂合变异。PAH 基因中检测到 2 个新变异和 35 个复发性变异。在这两个新变异中,一个是错义变异(p.Phe351Leu),另一个是框架移位变异(p.Met276Cysfs*65)。最常检测到的变异是 p.Thr380Met(18%)、p.Arg261Gln(16.8%)和 p.Ala300Ser(12.8%)。所有具有同源 c.1066-11G>A 变异的患者都表现出 cPKU 表型。c.898G>T(p.Ala300Ser)、c.1139C>T(p.Thr380Met)和c.1208C>T(p.Ala403Val)变异与轻度表型有统计学关系。另一方面,c.592_613del(p.Tyr198Serfs*136)、c.1028A>G(p.Tyr343Cys)和c.782G>A(p.Arg261Gln)变异在cPKU组中更常被检测到:我们的研究以土耳其东部地区的患者为对象,显示了土耳其人群的遗传异质性。同时,我们的研究还有助于基因型与表型之间的相关性,并通过识别新型变体扩大了基因型谱。
{"title":"Comprehensive analyses of phenylalanine hydroxylase variants and phenotypic characteristics of patients in the eastern region of Türkiye.","authors":"Ceren Alavanda, Emine İpek Ceylan, Sebile Kılavuz, Kısmet Çıkı","doi":"10.1515/jpem-2024-0091","DOIUrl":"10.1515/jpem-2024-0091","url":null,"abstract":"<p><strong>Objectives: </strong>Phenylalanine hydroxylase (PAH) is predominantly a hepatic enzyme that catalyzes phenylalanine (Phe) into tyrosine, which is the rate-limiting step in Phe catabolism. Biallelic variants in the <i>PAH</i> gene cause PAH enzyme deficiency. Phenylketonuria (PKU) is an autosomal recessive disorder that causes neurologic, behavioral, and dermatological findings. PKU could be divided clinically into three types based on the blood Phe levels: classic phenylketonuria (cPKU), mild-moderate phenylketonuria (mPKU), and mild hyperphenylalaninemia (MHP). This study aimed to determine the phenotypic and genotypic characteristics of Turkish PKU patients in the eastern region of Türkiye.</p><p><strong>Methods: </strong>Demographic characteristics, serum Phe levels, treatments, and <i>PAH</i> variants of 163 patients with PKU and hyperphenylalaninemia (HPA) were retrospectively evaluated. Blood Phe levels of the patients were analyzed with the high-performance liquid chromatography method. For <i>PAH</i> gene analysis, next-generation sequencing was performed.</p><p><strong>Results: </strong>Of the 163 patients included in the study, 38 (23.3 %) had cPKU, 16 (9.8 %) had mPKU, and 109 (66.9 %) had MHP. Homozygous variants in the <i>PAH</i> gene were detected in 66 (40.5 %) of the patients, while compound heterozygous variants were detected in 97 (59.5 %) patients. Two novel and 35 recurrent variants in the <i>PAH</i> gene were detected. Of the two novel variants, one was missense (p.Phe351Leu) and the other was frameshift (p.Met276Cysfs*65). The most frequently detected variants were p.Thr380Met (18 %), p.Arg261Gln (16.8 %), and p.Ala300Ser (12.8 %). All patients with the homozygous c.1066-11G>A variant exhibited cPKU phenotype. The c.898G>T (p.Ala300Ser), c.1139C>T (p.Thr380Met), and c.1208C>T (p.Ala403Val) variants were statistically related to mild phenotype. On the other hand, c.592_613del (p.Tyr198Serfs*136), c.1028A>G (p.Tyr343Cys), and c.782G>A (p.Arg261Gln) variants were more frequently detected in the cPKU group.</p><p><strong>Conclusions: </strong>Our study, conducted with patients from the eastern region of Türkiye, demonstrates the genetic heterogeneity in the Turkish population. Simultaneously, our research contributes to genotype-phenotype correlation and expands the genotypic spectrum by identifying novel variants.</p>","PeriodicalId":50096,"journal":{"name":"Journal of Pediatric Endocrinology & Metabolism","volume":" ","pages":"543-552"},"PeriodicalIF":1.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Diurnal 11-ketotestosterone and 17-hydroxyprogesterone saliva profiles in paediatric classical congenital adrenal hyperplasia. 小儿典型先天性肾上腺皮质增生症患者唾液中 11-酮睾酮和 17-羟孕酮的昼夜变化情况。
IF 1.4 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-02 Print Date: 2024-05-27 DOI: 10.1515/jpem-2024-0027
Ilja Dubinski, Susanne Bechtold-Dalla Pozza, Martin Bidlingmaier, James Hawley, Brian Keevil, Sonja Kunz, Hannah Franziska Nowotny, Nicole Reisch, Katharina Schiergens, Lea Tschaidse, Heinrich Schmidt

Objectives: The most suitable biochemical markers for therapy adjustment in patients with congenital adrenal hyperplasia are controversial. 11-Oxygenated androgens are a promising new approach. The objective of this study was to investigate the diurnal rhythm of 11-ketotestosterone in children and adolescents in saliva and to correlate it with salivary 17-hydroxyprogesterone.

Methods: Fifty-one samples of steroid day-profiles from 17 patients were additionally analysed for 11-ketotestosterone, retrospectively. All patients were treated in our university outpatient clinic for paediatric endocrinology between 2020 and 2022. Steroid day-profiles of 17 patients could be examined. The cohort showed a balanced sex ratio. The median age was 13 years. The measurements for 17-hydroxyprogesterone were carried out during routine care by immunoassay. The measurements of 11-ketotestosterone were performed from frozen saliva samples using an implemented in-house protocol for liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most important outcome were the absolute values for 11-ketotestosterone, their diurnal rhythmicity and the correlation with 17-hydroxyprogesterone.

Results: Both steroids show a circadian diurnal rhythm. 17-hydroxyprogesterone and 11-ketotestosterone correlate significantly. 11-Ketotestosterone showed a positive correlation with BMI at all times of the day.

Conclusions: 11-Ketotestosterone shows circadian rhythmicity in our cohort and correlates with 17-hydroxyprogesterone. These findings serve as an important basis for prospective research into 11-oxygenated androgens as therapeutic markers in paediatrics. However, 11-ketotestosterone appears to be very dependent on BMI.

目的:先天性肾上腺皮质增生症患者的治疗调整最合适的生化指标还存在争议。11-氧代雄激素是一种很有前景的新方法。本研究的目的是调查儿童和青少年唾液中 11-酮睾酮的昼夜节律,并将其与唾液中 17-羟孕酮联系起来:方法:对 17 名患者的 51 份类固醇日概况样本进行了额外的 11-酮睾酮回顾性分析。所有患者均于 2020 年至 2022 年期间在我校儿科内分泌门诊接受治疗。17名患者的类固醇日档案可以进行检查。患者性别比例均衡。年龄中位数为 13 岁。17-羟孕酮的测量是在常规护理期间通过免疫测定法进行的。对 11-酮睾酮的测量则是通过内部实施的液相色谱-串联质谱法(LC-MS/MS)对冷冻唾液样本进行的。最重要的结果是 11-酮睾酮的绝对值、其昼夜节律性以及与 17-羟孕酮的相关性:结果:两种类固醇都显示出昼夜节律。17-羟基黄体酮和 11-酮睾酮有明显的相关性。11-酮睾酮在一天中的任何时间都与体重指数呈正相关:结论:在我们的人群中,11-酮睾酮显示出昼夜节律性,并与 17-羟孕酮相关。这些发现为将 11-氧代雄激素作为儿科治疗标志物进行前瞻性研究提供了重要依据。不过,11-酮睾酮似乎与体重指数有很大关系。
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引用次数: 0
Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology. 解决沙特阿拉伯生长激素治疗的获取和支付障碍:沙特儿科内分泌学工作组共识声明。
IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-29 Print Date: 2024-05-27 DOI: 10.1515/jpem-2024-0021
Najya Attia, Khairya Moussa, Abdulaziz Altwaim, Abdulmoein Eid Al-Agha, Ashraf A Amir, Aseel Almuhareb

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

及时诊断和早期治疗是优化生长激素缺乏症(GHD)患儿治疗效果并达到遗传学预期成人身高的关键目标。然而,一些障碍可能会阻碍生长激素缺乏症的及时诊断和治疗,其中包括与支付方相关的问题。据报道,在沙特阿拉伯,13.1% 和 11.7% 的健康男童和女童患有中度至重度身材矮小。在沙特阿拉伯,儿科内分泌专家在诊断和治疗 GHD 的过程中可能会遇到一些就医和付款方面的障碍。由于 GHD 和重组人生长激素 (rhGH) 的费用高昂且缺乏黄金标准,保险政策可能会限制 GHD 和重组人生长激素 (rhGH) 的诊断测试。有些保险政策可能会限制rhGH的治疗时间或每月承保的药量。这篇共识文章收集了沙特阿拉伯儿科内分泌专家的见解,以反映身材矮小儿童诊断测试和治疗方案的获取和支付方障碍。我们还讨论了目前内分泌科医生在对身材矮小儿童进行检查时所面临的与支付方相关的挑战。共识确定了克服这些挑战和优化患者管理的潜在策略。
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引用次数: 0
Medulloblastoma in a child with osteoma cutis - a rare association due to loss of GNAS expression. 一名患有切骨瘤的儿童髓母细胞瘤--因 GNAS 表达缺失而导致的罕见关联。
IF 1.4 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-27 Print Date: 2024-05-27 DOI: 10.1515/jpem-2023-0533
Jananie Suntharesan, Ekaterina Lyulcheva-Bennett, Rachel Hart, Barry Pizer, James Hayden, Renuka Ramakrishnan

Objectives: Inactivating GNAS mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline GNAS mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations.

Case presentation: A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating GNAS mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of GNAS in the tumor.

Conclusions: This case provides important insights into the role of GNAS as a tumor suppressor and the emerging association between inactivating GNAS variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating GNAS variants or associated phenotypes. Further work to establish genotype-phenotype correlations is needed to inform optimal management of these patients.

目的:GNAS 失活突变会导致不同的表型,这取决于父母的血统。母方遗传的突变通常会导致激素抵抗和阿尔布莱特遗传性骨营养不良症(AHO),其特征为身材矮小、圆脸、畸形和皮下骨化。父系遗传具有 AHO 或异位骨化的特征,但不伴有激素抵抗。本报告描述了一例患有切骨瘤和髓母细胞瘤的患儿。本报告旨在强调灭活生殖系GNAS突变与髓母细胞瘤之间新出现的关联,旨在阐明其对肿瘤生物学的影响,并促进未来有针对性的监测策略的发展,以改善具有这些突变的儿科患者的预后:一名 12 个月大的男孩出现多处斑块样皮肤损伤。活组织检查证实他患有骨瘤,并进行了基因检测,结果证实他患有杂合子失活GNAS突变。2.5 岁时,他出现神经系统症状,经核磁共振成像和组织学检查确诊为脱鳞结节性髓母细胞瘤,SHH 分子组。进一步分析表明,肿瘤中存在 GNAS 双复制缺失:本病例为了解 GNAS 作为肿瘤抑制因子的作用,以及失活 GNAS 变异与髓母细胞瘤发病之间新出现的关联提供了重要见解。该病例强调了对已知存在失活GNAS变异或相关表型的儿童进行仔细的神经评估和持续警惕的重要性。我们需要进一步研究基因型与表型之间的相关性,以便为这些患者的最佳治疗提供依据。
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引用次数: 0
Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients. 慢性肾病儿童继发性甲状旁腺功能亢进的手术治疗。19例患者的经验
IF 1.4 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-25 Print Date: 2024-04-25 DOI: 10.1515/jpem-2023-0492
Silvia Mercedes Gil, Mariana Aziz, Valeria De Dona, Laura Lopez, Maria Florencia Soto, Victor Ayarzabal, Marta Adragna, Alicia Belgorosky, Marta Ciaccio, Gisela Viterbo

Objectives: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT.

Methods: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy.

Results: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients.

Conclusions: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

目的:继发性甲状旁腺功能亢进症(sHPT)是慢性肾脏病(CKD)患儿骨病和心血管钙化的重要诱因。当保守治疗无效时,就需要进行甲状旁腺切除术。我们的研究旨在评估甲状旁腺次全切除术(sPTX)在儿童和青少年患者中的疗效和安全性,并为患有无法控制的甲状旁腺钙化症的 CKD 患者考虑这种积极治疗提供依据:我们回顾性分析了 2010 年至 2020 年期间在我院接受甲状旁腺切除术(sPTX)的 19 名接受透析治疗的难治性 sHPT 儿童 CKD 患者的病历。所有患者均有肾性骨营养不良的临床、放射学和生化症状:SPTX术后一年,甲状旁腺激素(PTH)水平(中位数和四分位间距(IQR))从2073(1339-2484)降至164(93-252)pg/mL(P=0.0001),碱性磷酸酶(ALP)水平从 1166(764-2373)降至 410(126-421)IU/L(p=0.002),平均(±SDS)钙磷酸盐(Ca*P)乘积从 51±11 降至 41±13 mg2/dL2 (p=0.07)。术后,所有患者都出现了严重的饿骨综合征(HBS),需要静脉和口服钙剂和钙三醇补充剂。没有人出现其他术后并发症。组织学检查结果与术前甲状旁腺超声成像(15例)和锝-99m (99mTc) sestamibi闪烁扫描(15例)的相关性分别为100%和86.6%。所有患者的骨病临床和放射学症状均有所改善:小儿 sPTX 可有效、安全地控制接受透析治疗的 CKD 儿童的 sHPT 和钙磷代谢,并可减轻不可逆的骨畸形和心血管疾病的进展。
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引用次数: 0
Early change of retinal nerve fiber layer in children with type 1 diabetes mellitus in northern China. 中国北方 1 型糖尿病患儿视网膜神经纤维层的早期变化。
IF 1.4 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-18 Print Date: 2024-04-25 DOI: 10.1515/jpem-2023-0446
Dejing Wu, Rongxiu Zheng, Xuan Kan, Liping Hao, Ying Wei, Jie Cao

Objectives: This study aimed to identify discrepancies in the retinal nerve fiber layer (RNFL) between type 1 diabetes mellitus (T1DM) children without retinopathy and healthy subjects in northern China.

Methods: This was a cross-sectional hospital-based study carried out from Jan 2019 until Jul 2021 at the department of pediatrics in Tianjin medical university general hospital. Children with T1DM but no retinal disease were screened. RNFL thickness was obtained via spectral domain optical coherence tomography. Disease duration, HbA1c, 25-hydroxyvitamin D level, insulin regimen, and diet control status were also collected.

Results: A total of 20 children with T1DM and 20 matched health participants were enrolled. The mean age in the T1DM group was 10.3 ± 2.8 years, and the median duration of diabetes was 1 (range 1-3) year. Children with T1DM had thinner average RNFL than control subjects (105 ± 6 vs. 110 ± 11 μm, p=0.008), especially in temporal and nasal parts. There was a significant negative association between HbA1c levels and the RNFL thickness in the T1DM group (B (95 % confidence interval): -4.313 (-7.055 to -1.571); p=0.005).

Conclusions: In our study, the decreased thickness of RNFL was negatively associated with elevated HbA1c in children with early stages of T1DM.

研究目的本研究旨在确定中国北方无视网膜病变的1型糖尿病(T1DM)儿童与健康受试者之间视网膜神经纤维层(RNFL)的差异:这是一项以医院为基础的横断面研究,于2019年1月至2021年7月在天津医科大学总医院儿科开展。对患有T1DM但无视网膜疾病的儿童进行筛查。通过光谱域光学相干断层扫描获得RNFL厚度。此外,还收集了病程、HbA1c、25-羟维生素D水平、胰岛素方案和饮食控制状况:结果:共招募了 20 名 T1DM 患儿和 20 名匹配的健康参与者。T1DM 组的平均年龄为 10.3±2.8 岁,中位糖尿病病程为 1 年(1-3 年不等)。与对照组相比,T1DM 患儿的平均 RNFL 更薄(105 ± 6 vs. 110 ± 11 μm,p=0.008),尤其是在颞部和鼻部。在 T1DM 组中,HbA1c 水平与 RNFL 厚度之间存在明显的负相关(B(95 % 置信区间):-4.313(-7.0 % 置信区间):-结论:在我们的研究中,T1DM 早期儿童的 RNFL 厚度下降与 HbA1c 升高呈负相关。
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引用次数: 0
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Journal of Pediatric Endocrinology & Metabolism
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