Journal of Clinical and Translational Endocrinology最新文献_第4页

Corrigendum to “False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology” [J. Clin. Translat. Endocrinol. 40 (2025) 100396] “ThyGeNEXT®+ThyraMIR®检测与甲状腺切除术后组织病理学的假阴性率和一致性”的更正[J]。中国。诠释。内分泌，40 (2025)100396 [j]

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI: 10.1016/j.jcte.2025.100397

Sobrina S. Mohammed , Daniel Mettman , Mariana Garcia-Touza , Betty Drees , Maricel Ridella

引用次数: 0

Testicular function and fertility outcomes in males with CF: A multi center retrospective study of men with congenital bilateral absence of the vas deferens based on CFTR mutation status CF男性的睾丸功能和生育结局：基于CFTR突变状态的先天性双侧输精管缺失男性的多中心回顾性研究

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1016/j.jcte.2025.100388

Rossella Cannarella , Danielle Velez Leitner , Marissa Weiss , Sarah C. Vij

Background

Modern cystic fibrosis (CF) treatments, particularly CFTR modulators, have allowed males with CF (MwCF) to live longer, healthier lives and pursue parenthood. Approximately 98% of MwCF have congenital bilateral absence of the vas deferens (CBAVD). While research shows MwCF experience spermatogenic dysfunction alongside obstructive azoospermia, understanding male reproductive health in MwCF remains limited. This study retrospectively examines testicular function and intracytoplasmic sperm injection outcomes of the partners of males with CBAVD, stratified by CF mutation status (CF, CF carriers, no known mutation).

Subjects and Methods

This multicenter, retrospective study assessed sperm retrieval outcomes and testicular function in males with CBAVD. Participants were categorized into three groups: MwCF (Group 1), CFTR gene mutation carriers (CFTR carriers, Group 2), and CBAVD males without CFTR mutations (Group 3). We collected data on genetic testing, testicular hormone levels (FSH, LH, total testosterone), sperm retrieval methods, and reproductive outcomes. Statistical analysis was used to assess intergroup differences.

Results

Thirty subjects were included (Group 1: 14, Group 2: 11, Group 3: 5). No significant differences in demographic, anthropometric, or reproductive characteristics were found across groups. Hormone levels (LH, FSH, and testosterone) were similar among groups. In Group 1, 42 % had elevated FSH levels. The prevalence of hypogonadism was 16.7 % in Group 1. Group 3 had a significantly lower fertilization rate (p < 0.01), but no differences were found in blastocyst formation, pregnancy, miscarriage, or live birth rates.

Conclusions

Our data support the presence of primary spermatogenic dysfunction in some MwCF. However, reproductive outcomes were similar across all groups.

背景现代囊性纤维化（CF）治疗方法，尤其是 CFTR 调节剂，让男性囊性纤维化患者（MwCF）活得更长、更健康，并能为人父母。约 98% 的男性囊性纤维化患者患有先天性双侧输精管缺失 (CBAVD)。研究表明，MwCF 在患有梗阻性无精子症的同时还存在生精功能障碍，但对 MwCF 男性生殖健康的了解仍然有限。本研究对CBAVD男性患者伴侣的睾丸功能和卵胞浆内单精子注射结果进行了回顾性研究，并根据CF突变状态（CF、CF携带者、未知突变）进行了分层。参与者分为三组：MwCF（第 1 组）、CFTR 基因突变携带者（CFTR 携带者，第 2 组）和无 CFTR 突变的 CBAVD 男性（第 3 组）。我们收集了有关基因检测、睾丸激素水平（FSH、LH、总睾酮）、取精方法和生殖结果的数据。结果纳入了 30 名受试者（第 1 组：14 人，第 2 组：11 人，第 3 组：5 人）。各组在人口统计学、人体测量和生殖特征方面均无明显差异。各组的激素水平（LH、FSH 和睾酮）相似。第一组中有 42% 的人 FSH 水平升高。第 3 组的受精率显著较低（p < 0.01），但在囊胚形成、妊娠、流产或活产率方面未发现差异。结论：我们的数据证实了部分 MwCF 存在原发性生精功能障碍，但各组的生殖结果相似。

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引用次数: 0

Effect of GIP and GLP-1 infusion on bone resorption in glucose intolerant, pancreatic insufficient cystic fibrosis GIP和GLP-1输注对糖不耐受胰不全囊性纤维化患者骨吸收的影响

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-07 DOI: 10.1016/j.jcte.2025.100392

Wang Shin Lei , XianYan Chen , Lingyu Zhao , Tanicia Daley , Bradley Phillips , Michael R. Rickels , Andrea Kelly , Joseph M. Kindler

Context

Diabetes and bone disease are common in cystic fibrosis (CF) and primarily occur alongside exocrine pancreatic insufficiency (PI). “Incretins,” glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), augment insulin secretion and regulate bone metabolism. In CF, PI dampens the incretin response. Loss of the insulinotropic effect of GIP in CF was recently identified, but effects on bone are unknown.

Objective

Determine effects of incretins on bone resorption markers in adults with PI-CF.

Design

Secondary analysis of a mechanistic double-blinded randomized placebo-controlled crossover trial including adults ages 18–40 years with PI-CF (n = 25).

Intervention

Adults with PI-CF received either GIP (4 pmol/kg/min) or GLP-1 (1.5 pmol/kg/min) infusion, followed by double-blind randomization to either incretin or placebo infusion. Non-CF healthy controls received double-blind GIP (4 pmol/kg/min) or placebo. Serum C-terminal telopeptide (CTX), a bone resorption marker, was assessed during the infusion over 80 (GIP) or 60 (GLP-1) minutes.

Main Outcome Measures

CTX (mg/dL) concentrations.

Results

In PI-CF, CTX decreased during GIP infusion, but not during placebo (time-by-treatment interaction P < 0.01). GLP-1 did not affect CTX. In non-CF healthy controls, time-by-treatment interaction was not significant (P = 0.23), but CTX decreased during GIP (P = 0.02) but not placebo (P = 0.47).

Conclusions

GIP evokes a bone anti-resorptive effect in people with PI-CF. Since the incretin response is perturbed in PI-CF, and an infusion of GIP lowers bone resorption, the “gut-bone axis” in CF-related bone disease requires attention.

背景糖尿病和骨病是囊性纤维化（CF）的常见病，主要与胰腺外分泌功能不全（PI）同时发生。"胰岛素"、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽 1（GLP-1）可促进胰岛素分泌并调节骨代谢。在 CF 中，PI 会抑制增量素反应。最近发现 GIP 在 CF 中失去了促胰岛素作用，但对骨骼的影响尚不清楚。目的确定增量素对 PI-CF 成人骨吸收标志物的影响。干预患有 PI-CF 的成人接受 GIP（4 pmol/kg/min）或 GLP-1（1.5 pmol/kg/min）输注，然后双盲随机输注增量素或安慰剂。非中风健康对照组接受双盲 GIP（4 pmol/kg/min）或安慰剂输注。在输注 80 分钟（GIP）或 60 分钟（GLP-1）期间，评估血清 C 端端肽（CTX）（一种骨吸收标志物）。GLP-1 不影响 CTX。在非 CF 健康对照组中，时间与治疗的交互作用不显著（P = 0.23），但在注射 GIP 期间 CTX 下降（P = 0.02），而安慰剂期间 CTX 不下降（P = 0.47）。由于 PI-CF 患者的增量素反应受到干扰，而 GIP 的输注可降低骨吸收，因此 CF 相关骨病中的 "肠-骨轴 "需要引起关注。

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引用次数: 0

Treatment of hypothyroidism with the combination of levothyroxine and slow-release triiodothyronine: a randomized clinical trial 左甲状腺素联合缓释三碘甲状腺原氨酸治疗甲状腺功能减退：一项随机临床试验

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-23 DOI: 10.1016/j.jcte.2025.100395

F. Azizi , A.S. Moeini , L. Mehran , S. Masoumi , H. Abdi , S.M. Foroutan , A.E. Saghafinia , A. Amouzegar

Background

Some patients with hypothyroidism lack satisfaction with levothyroxine (LT4) monotherapy, which may be related to lower serum triiodothyronine (T3) and T3/T4 ratios compared to control individuals. This study aimed to evaluate the efficacy and safety of a combination therapy of slow-release T3 (SRT3) and LT4 in patients with primary hypothyroidism compared with LT4 monotherapy.

Methods

Thirty-two hypothyroid women were randomized into two groups of SRT3 + LT4 combination and LT4 monotherapy. Group one received a combination of 15 µg SRT3 and 75 µg LT4, and group two received 100 µg LT4 daily for 8 weeks. Clinical and biochemical measurements were performed at baseline and 4 to 8 weeks after intervention.

Results

There were no significant changes in serum levels of fT4, T3, TSH, and T3/fT4 ratio in the LT4 group at the end of 4 to 8 weeks of study. A statistically significant decrease in fT4 and TSH, and an increase in serum T3 and the T3/fT4 ratio, were observed in the SRT3 + LT4 group. The T3/fT4 ratio reached comparable values to those in normal subjects, 93.63 ± 23.25 vs 95.06 ± 19.44 ng/ng, respectively. The rise in the T3/fT4 ratio 8 weeks after SRT3 + LT4 treatment was between 21 % and 90 % in 10 patients and 1 % and 13 % in 5 patients, with no change in one patient.

Conclusion

The novel combination of SRT3 + LT4 therapy resulted in a significant increase in serum T3 and the T3/fT4 ratio in hypothyroid patients compared to those receiving LT4 monotherapy. The rise in the T3/fT4 ratio was ≥ 21 % in two-thirds of patients; the lack of a significant increase in the T3/fT4 ratio in some patients during SRT3-LT4 combination therapy demands further investigation.

一些甲状腺功能减退患者对左旋甲状腺素（LT4）单药治疗缺乏满意度，这可能与血清三碘甲状腺原氨酸（T3）和T3/T4比值较对照组低有关。本研究旨在评价缓释T3 （SRT3）和LT4联合治疗原发性甲状腺功能减退患者与LT4单药治疗的疗效和安全性。方法32例甲状腺功能低下妇女随机分为SRT3 + LT4联合治疗组和LT4单药治疗组。第一组每天给予15µg SRT3和75µg LT4，第二组每天给予100µg LT4，连续8周。在基线和干预后4至8周进行临床和生化测量。结果在4 ~ 8周的研究结束时，LT4组患者血清fT4、T3、TSH水平及T3/fT4比值无明显变化。SRT3 + LT4组fT4、TSH水平明显降低，血清T3、T3/fT4比值明显升高。T3/fT4比值达到与正常受试者相当的值，分别为93.63±23.25和95.06±19.44 ng/ng。SRT3 + LT4治疗8周后，T3/fT4比值上升的10例患者为21% - 90%，5例患者为1% - 13%，1例患者无变化。结论与单纯LT4治疗相比，SRT3 + LT4联合治疗可显著提高甲状腺功能减退患者的血清T3水平和T3/fT4比值。三分之二的患者T3/fT4比值升高≥21%；在SRT3-LT4联合治疗期间，一些患者的T3/fT4比值缺乏显著增加，这需要进一步的研究。

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引用次数: 0

Faculty perspectives on supervising endocrinology residents in the longitudinal clinic setting 在纵向临床环境中监督内分泌科住院医师的教师观点

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-02-28 DOI: 10.1016/j.jcte.2025.100385

Isabella Albanese , Katherine Drummond , Vanessa Tardio , Diana Dolmans

Introduction

Longitudinal clinic supervision is complex but key to training residents, such as endocrinology residents. Supervisors report difficulties providing learners with the right balance of supervision and autonomy. Cognitive apprenticeship theory applies to teaching in workplace-based settings, such as the endocrinology longitudinal clinic. While this theory identifies effective strategies for supervising medical students in longitudinal settings, little is known about how and why supervisors adapt their strategies when offering longitudinal supervision to endocrinology residents.

Objective

To understand supervisors’ perspectives on supervision of endocrinology residents over time in the longitudinal clinic.

Methods

This is a qualitative study set in the endocrinology division of a Canadian multi-site academic centre in 2023–2024 using semi-structured interviews of endocrinology longitudinal clinic supervisors. Transcripts were analyzed using inductive and deductive thematic analysis, with cognitive apprenticeship theory as a sensitizing concept.

Results

Five main themes were identified articulating how participants perceive their supervision and its changes over time. These include supervisors treating residents as colleagues and making clinic experiences reflect real life when possible. Supervisors also tailor clinic experiences to resident needs and career goals. They provide residents with support but also autonomy to execute their own management plans even if discordant with that of supervisors provided that patient safety is maintained. Similarly, supervisors encourage residents to take patient ownership. Together, these strategies enable supervisors to support resident development into independent professional endocrinologists.

Conclusion

Overall, supervisors try to encourage residents to self-regulate their learning, but also offer support and autonomy to enhance their longitudinal growth and development.

纵向临床监督是一项复杂而又关键的住院医师培训工作，如内分泌科住院医师。导师们报告说，很难让学习者在监督和自主之间取得适当的平衡。认知学徒理论适用于以工作场所为基础的教学环境，如内分泌纵向诊所。虽然这一理论确定了在纵向环境中监督医学生的有效策略，但很少有人知道主管如何以及为什么在向内分泌科住院医生提供纵向监督时调整他们的策略。目的了解督导医师对纵向门诊内分泌科住院医师长期监护的看法。方法采用半结构化访谈法，对2023-2024年在加拿大某多中心学术中心内分泌科进行定性研究。以认知学徒理论为增敏概念，采用归纳和演绎主题分析对文本进行分析。结果确定了五个主要主题，阐明了参与者如何看待他们的监督及其随时间的变化。这些措施包括主管将住院医生视为同事，并尽可能使诊所经验反映真实生活。主管还会根据住院医生的需求和职业目标量身定制诊所经验。他们为住院医生提供支持，也为他们提供自主权，让他们执行自己的管理计划，即使与主管的计划不一致，前提是要维护病人的安全。同样，主管也鼓励住院医生承担病人的责任。总之，这些策略使主管能够支持住院医生发展成为独立的专业内分泌学家。结论总体而言，导师在鼓励住院医师自我调节学习的同时，也提供了支持和自主权，以促进住院医师的纵向成长和发展。

{"title":"Faculty perspectives on supervising endocrinology residents in the longitudinal clinic setting","authors":"Isabella Albanese , Katherine Drummond , Vanessa Tardio , Diana Dolmans","doi":"10.1016/j.jcte.2025.100385","DOIUrl":"10.1016/j.jcte.2025.100385","url":null,"abstract":"<div><h3>Introduction</h3><div>Longitudinal clinic supervision is complex but key to training residents, such as endocrinology residents. Supervisors report difficulties providing learners with the right balance of supervision and autonomy. Cognitive apprenticeship theory applies to teaching in workplace-based settings, such as the endocrinology longitudinal clinic. While this theory identifies effective strategies for supervising medical students in longitudinal settings, little is known about how and why supervisors adapt their strategies when offering longitudinal supervision to endocrinology residents.</div></div><div><h3>Objective</h3><div>To understand supervisors’ perspectives on supervision of endocrinology residents over time in the longitudinal clinic.</div></div><div><h3>Methods</h3><div>This is a qualitative study set in the endocrinology division of a Canadian multi-site academic centre in 2023–2024 using semi-structured interviews of endocrinology longitudinal clinic supervisors. Transcripts were analyzed using inductive and deductive thematic analysis, with cognitive apprenticeship theory as a sensitizing concept.</div></div><div><h3>Results</h3><div>Five main themes were identified articulating how participants perceive their supervision and its changes over time. These include supervisors treating residents as colleagues and making clinic experiences reflect real life when possible. Supervisors also tailor clinic experiences to resident needs and career goals. They provide residents with support but also autonomy to execute their own management plans even if discordant with that of supervisors provided that patient safety is maintained. Similarly, supervisors encourage residents to take patient ownership. Together, these strategies enable supervisors to support resident development into independent professional endocrinologists.</div></div><div><h3>Conclusion</h3><div>Overall, supervisors try to encourage residents to self-regulate their learning, but also offer support and autonomy to enhance their longitudinal growth and development.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"40 ","pages":"Article 100385"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Prediction of BRAF and TERT status in PTCs by machine learning-based ultrasound radiomics methods: A multicenter study” [J. Clin. Translat. Endocrinol. 40 (2025) 100390] “基于机器学习的超声放射组学方法预测ptc的BRAF和TERT状态：一项多中心研究”[J]。中国。诠释。内分泌，40 (2025)100390 [j]

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-14 DOI: 10.1016/j.jcte.2025.100394

Hui Shi , Ke Ding , Xue Ting Yang , Ting Fan Wu , Jia Yi Zheng , Li Fan Wang , Bo Yang Zhou , Li Ping Sun , Yi Feng Zhang , Chong Ke Zhao , Hui Xiong Xu

引用次数: 0

Cholesterol and triglyceride concentrations following 12–18 months of clinically prescribed elexacaftor-tezacaftor-ivacaftor—PROMISE sub-study 12-18个月临床处方的elexaftor - tezactor -ivacaftor - promise亚研究后的胆固醇和甘油三酯浓度

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-02 DOI: 10.1016/j.jcte.2025.100391

Rosara Bass , Michael Stalvey , George Solomon , Steven Rowe , David Nichols , Sarah Jane Schwarzenberg , Steven Freedman , Rachel Walega , Andrea Kelly

Background/Aims

People with CF (PwCF) have low total, high, and low density lipoprotein cholesterol (TC, HDL-C and LDL-C) and historically have had low prevalence of cardiovascular disease. More recently, cases of acute myocardial infarction are reported in PwCF. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on cholesterol and triglyceride (TG) concentrations, traditional cardiometabolic risk factors, is unknown.

Methods/Results

TC, LDL-C, HDL-C, and TG concentrations were analyzed from participants enrolled in the observational PROMISE study of clinically prescribed ETI prior to and 12–18 months after initiation. Pre-ETI and follow-up concentrations were compared, and relationships between TC, LDL-C, HDL-C and TG and clinical factors were tested using linear mixed-effect models.

Fasting samples were available for 51 participants (25 M/26F, median age 17.4 y) with pancreatic exocrine insufficiency at baseline and 12–18 months after ETI initiation. TC and HDL-C were higher after 12–18 mo ETI in an unadjusted model, but with adjustment for BMI-Z, only HDL-C remained significantly higher at follow up (p < 0.05). Low HDL-C was the most common abnormality (>50 %), but prevalence of participants meeting criteria for low HDL-C did not differ between timepoints.

Conclusions

In a population of youth and young adults with CF, TC and HDL-C were higher after 12–18 months of ETI, but differences in TC were attenuated with adjustment for BMI-Z. Prevalence of low HDL-C was high at both timepoints.

背景/目的CF （PwCF）患者有低总、高、低密度脂蛋白胆固醇（TC、HDL-C和LDL-C），历史上心血管疾病的患病率较低。最近，急性心肌梗死的病例被报道在PwCF。对胆固醇和甘油三酯（TG）浓度（传统的心脏代谢危险因素）的影响尚不清楚。方法/结果在临床处方ETI开始前和开始后12-18个月的观察性PROMISE研究中，对参与者的stc、LDL-C、HDL-C和TG浓度进行分析。比较eti前和随访浓度，采用线性混合效应模型检验TC、LDL-C、HDL-C和TG与临床因素的关系。51名参与者（25 M/26F，中位年龄17.4岁）在基线和ETI开始后12-18个月存在胰腺外分泌功能不全。在未调整的模型中，12-18个月ETI后TC和HDL-C较高，但在调整BMI-Z后，只有HDL-C在随访时仍显着升高(p <；0.05)。低HDL-C是最常见的异常（50%），但符合低HDL-C标准的参与者的患病率在时间点之间没有差异。结论在青年和青壮年CF患者中，ETI治疗12-18个月后TC和HDL-C升高，但调整BMI-Z后TC的差异减弱。低HDL-C的患病率在两个时间点都很高。

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引用次数: 0

Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis 年轻发病的散发性垂体大腺瘤的种系遗传变异：多基因面板分析

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-04 DOI: 10.1016/j.jcte.2025.100389

Leonor M. Gaspar , Catarina I. Gonçalves , Ema L. Nobre , Fernando Fonseca , Cláudia Amaral , João S. Duarte , Luísa Raimundo , Catarina Saraiva , Luísa Cortez , Olinda Marques , Manuel C. Lemos

Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic pituitary adenomas (i.e. with no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations in these genes, especially in young patients with larger tumours. The aim of this study was to determine the frequency of germline mutations in patients with young-onset sporadic pituitary macroadenomas. A cohort of 225 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years was studied by whole exome sequencing (WES) followed by the analysis of a virtual panel of 29 genes that have been associated with predisposition to pituitary adenomas. Pathogenic and likely pathogenic variants were identified in 16 (7.1 %) of patients. The affected genes were AIP (n = 4), PMS2 (n = 4), MEN1 (n = 2), VHL (n = 2), CDH23 (n = 1), MSH2 (n = 1), SDHB (n = 1), and TP53 (n = 1). In patients diagnosed under the ages of 30 and 18 years, the frequency of pathogenic and likely pathogenic variants increased to 9.0 % and 12.0 %, respectively. This is so far the largest multigene analysis of patients with young-onset sporadic pituitary macroadenomas. We confirmed the AIP as the most frequently involved gene, but also uncovered rarer genetic causes of pituitary adenomas. The results may contribute to a better understanding of the genetic landscape of these tumours and help to decide which genes to include in the genetic screening of patients with young-onset pituitary macroadenomas.

一些基因的突变与家族性垂体腺瘤有关。散发的垂体腺瘤（即没有家族史或共存的内分泌肿瘤）也偶尔被发现是由这些基因的种系突变引起的，特别是在肿瘤较大的年轻患者中。本研究的目的是确定年轻发病的散发性垂体大腺瘤患者种系突变的频率。通过全外显子组测序（WES）对年龄在40岁之前诊断为散发性垂体大腺瘤的225名葡萄牙患者进行队列研究，随后对与垂体腺瘤易感性相关的29个基因进行虚拟面板分析。在16例（7.1%）患者中发现致病性和可能致病性变异。影响基因为AIP （n = 4）、PMS2 （n = 4）、MEN1 （n = 2）、VHL （n = 2）、CDH23 （n = 1）、MSH2 （n = 1）、SDHB （n = 1）、TP53 （n = 1）。在30岁以下和18岁以下的患者中，致病性变异和可能致病性变异的频率分别增加到9.0%和12.0%。这是迄今为止对年轻发病的散发性垂体大腺瘤患者进行的最大的多基因分析。我们证实AIP是最常见的基因，但也发现了罕见的垂体腺瘤的遗传原因。结果可能有助于更好地了解这些肿瘤的遗传景观，并有助于决定哪些基因包括在年轻发病的垂体大腺瘤患者的遗传筛查中。

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引用次数: 0

Prediction of BRAF and TERT status in PTCs by machine learning-based ultrasound radiomics methods: A multicenter study 基于机器学习的超声放射组学方法预测ptc的BRAF和TERT状态：一项多中心研究

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-03-30 DOI: 10.1016/j.jcte.2025.100390

Hui Shi , Ke Ding , Xue Ting Yang , Ting Fan Wu , Jia Yi Zheng , Li Fan Wang , Bo Yang Zhou , Li Ping Sun , Yi Feng Zhang , Chong Ke Zhao , Hui Xiong Xu

Background

Preoperative identification of genetic mutations is conducive to individualized treatment and management of papillary thyroid carcinoma (PTC) patients. Purpose: To investigate the predictive value of the machine learning (ML)-based ultrasound (US) radiomics approaches for BRAF V600E and TERT promoter status (individually and coexistence) in PTC.

Methods

This multicenter study retrospectively collected data of 1076 PTC patients underwent genetic testing detection for BRAF V600E and TERT promoter between March 2016 and December 2021. Radiomics features were extracted from routine grayscale ultrasound images, and gene status-related features were selected. Then these features were included to nine different ML models to predicting different mutations, and optimal models plus statistically significant clinical information were also conducted. The models underwent training and testing, and comparisons were performed.

Results

The Decision Tree-based US radiomics approach had superior prediction performance for the BRAF V600E mutation compared to the other eight ML models, with an area under the curve (AUC) of 0.767 versus 0.547–0.675 (p < 0.05). The US radiomics methodology employing Logistic Regression exhibited the highest accuracy in predicting TERT promoter mutations (AUC, 0.802 vs. 0.525–0.701, p < 0.001) and coexisting BRAF V600E and TERT promoter mutations (0.805 vs. 0.678–0.743, p < 0.001) within the test set. The incorporation of clinical factors enhanced predictive performances to 0.810 for BRAF V600E mutant, 0.897 for TERT promoter mutations, and 0.900 for dual mutations in PTCs.

Conclusion

The machine learning-based US radiomics methods, integrated with clinical characteristics, demonstrated effectiveness in predicting the BRAF V600E and TERT promoter mutations in PTCs.

背景术前基因突变的识别有助于个体化治疗和管理甲状腺乳头状癌（PTC）患者。目的：探讨基于机器学习（ML）的超声（US）放射组学方法对PTC中BRAF V600E和TERT启动子状态（单独和共存）的预测价值。方法本多中心研究回顾性收集了2016年3月至2021年12月期间接受BRAF V600E和TERT启动子基因检测的1076例PTC患者的数据。从常规灰度超声图像中提取放射组学特征，选择与基因状态相关的特征。然后将这些特征纳入9种不同的ML模型，预测不同的突变，并进行最优模型加上具有统计学意义的临床信息。模型经过了训练和测试，并进行了比较。结果与其他8种ML模型相比，基于决策树的美国放射组学方法对BRAF V600E突变的预测效果更好，曲线下面积（AUC）为0.767比0.547-0.675 (p <；0.05)。采用Logistic回归的美国放射组学方法在预测TERT启动子突变方面表现出最高的准确性(AUC, 0.802 vs. 0.525-0.701, p <；0.001)和BRAF V600E和TERT启动子共存突变(0.805 vs. 0.678-0.743, p <；0.001)。临床因素的结合将BRAF V600E突变的预测性能提高到0.810，TERT启动子突变的预测性能提高到0.897，ptc双突变的预测性能提高到0.900。结论基于机器学习的美国放射组学方法，结合临床特征，可有效预测ptc中BRAF V600E和TERT启动子突变。

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引用次数: 0

Association of total and bioactive serum sclerostin levels with bone metabolism in type 2 diabetes mellitus 2型糖尿病患者总血清和生物活性血清硬化蛋白水平与骨代谢的关系

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology

Pub Date : 2025-06-01 Epub Date: 2025-04-08 DOI: 10.1016/j.jcte.2025.100393

Cyril Traechslin , Lilian Sewing , Sandra Baumann , Leticia Grize , Janina Vavanikunnel , Marius Kraenzlin , Christoph Henzen , Christian Meier

Background

Sclerostin has been associated with decreased bone turnover in patients with type 2 diabetes mellitus (T2DM). The relationship with bone turnover markers (BTMs) and bone mineral density (BMD) remains unclear. We investigate the relationship between total and bioactive sclerostin measured by three different assays with BTMs and BMD in patients with T2DM compared to healthy controls.

Methods

Baseline data from the cross-sectional multicenter DiabOS-study in Switzerland were analysed. Total and bioactive serum sclerostin levels were measured using three different ELISA-based sclerostin assays (Sclerostin Biomedica, Sclerostin bioactive Biomedica and Sclerostin hsTECO). Sclerostin levels in patients with T2DM and controls were correlated with BTMs and BMD.

Results

Data were analysed from 78 men and postmenopausal women with T2DM and 37 controls (aged 50–75 years). Serum sclerostin levels, adjusted for estimated glomerular filtration rate (eGFR), were higher in patients with T2DM compared to controls with all three assays. In a gender subgroup analysis, bioactive sclerostin levels remained significantly elevated in men with T2DM (T2DM, 106.8 ± 39.9 pmol/L; controls, 88.3 ± 21.3 pmol/L, p = 0.03).

Univariate analysis showed consistent significant correlations with all sclerostin assays for age, eGFR, glycated hemoglobin A1c and diabetes duration. However, in multivariate analysis, eGFR remained the only significant determinant of serum sclerostin levels. Sclerostin levels in patients with T2DM showed significant positive correlations with BMD but no significant correlations with BTMs.

Conclusions

We demonstrate a significant positive association of bioactive serum sclerostin with BMD at all measured sites in patients with T2DM, which may support its utility in the assessment of bone fragility in this population.

研究背景：在2型糖尿病（T2DM）患者中，硬化汀与骨转换减少有关。骨转换标志物（BTMs）和骨矿物质密度（BMD）之间的关系尚不清楚。我们研究了三种不同测定法测量的T2DM患者总硬化蛋白和生物活性硬化蛋白与btm和BMD之间的关系，并与健康对照进行了比较。方法对瑞士横断面多中心diabos研究的基线数据进行分析。采用三种不同的基于elisa的硬化蛋白测定法（sclerostin Biomedica、sclerostin生物活性Biomedica和sclerostin hsTECO）测定血清总硬化蛋白和生物活性硬化蛋白水平。T2DM患者和对照组的硬化蛋白水平与BTMs和BMD相关。结果分析了78名患有T2DM的男性和绝经后女性以及37名对照组（50-75岁）的数据。根据估计的肾小球滤过率（eGFR）调整后的血清硬化蛋白水平在T2DM患者中均高于对照组。在性别亚组分析中，男性T2DM患者的生物活性硬化蛋白水平仍显著升高(T2DM: 106.8±39.9 pmol/L；对照组为88.3±21.3 pmol/L, p = 0.03)。单因素分析显示，年龄、eGFR、糖化血红蛋白A1c和糖尿病病程与所有硬化蛋白检测结果具有一致的显著相关性。然而，在多变量分析中，eGFR仍然是血清硬化蛋白水平的唯一重要决定因素。T2DM患者的硬化蛋白水平与BMD呈显著正相关，而与BTMs无显著相关。结论：我们证明了生物活性血清硬化蛋白与T2DM患者所有测量部位的骨密度显著正相关，这可能支持其在评估该人群骨脆弱性方面的实用性。

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