Clinical Endocrinology最新文献_第4页

Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1 来自 C-CAT 数据库的综合基因组图谱显示，无性甲状腺癌中 80% 以上存在致癌驱动因子，包括 BRAF、RAS 家族、NF1 和 FGFR1。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-06-09 DOI: 10.1111/cen.15098

Yuki Saito, Hidenori Kage, Kenya Kobayashi, Teru Kamogashira, Osamu Fukuoka, Koji Yamamura, Satoshi Yamashita, Masahiko Tanabe, Katsutoshi Oda, Kenji Kondo

Objective

Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications.

Design, Patients and Mesurement

A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ² tests, were employed for survival analysis and gene mutation comparisons.

Results

Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data.

Conclusions

Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.

目的：甲状腺无节细胞癌（ATC）被认为是一种侵袭性很强的癌症，治疗策略难以奏效。本研究探讨了包括BRAF V600E突变在内的ATC基因组改变情况及其临床意义：本研究利用日本癌症基因组学与先进治疗中心（Center for Cancer Genomics and Advanced Therapeutics，C-CAT）收集的 102 例 ATC 病例的综合基因组图谱数据，开展了一项回顾性观察研究。此外，还分析了 267 个病例的 AACR-GENIE 数据以进行验证。统计方法包括条件Kendall tau统计和χ2检验，用于生存分析和基因突变比较：在 102 例 ATC 中，83 例（81.2%）发现了 BRAF、RAS 和其他驱动基因突变。BRAF V600E基因突变的发生率高达60%。共突变分析在 BRAF、RAS 和野生型组中发现了不同的基因组特征。尽管分子背景各不相同，但在临床变量和总生存率方面没有观察到显著差异。考虑到左侧截肢的分析表明，RAS突变的预后较差。在BRAF/RAS野生型组中，FGFR1和NF1被确定为驱动突变，拷贝数变异累积，TERT启动子突变较少。AACR-GENIE数据也支持这一分子亚组划分：结论：对日本 ATC 进行的全面基因组分析揭示了不同的分子亚群，突出了 BRAF V600E 突变（尤其是 V600E）作为潜在治疗靶点的重要性，并提示了基于基因组图谱的定制治疗策略的相关性。

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引用次数: 0

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus 2 型糖尿病患者低镁血症与白蛋白尿之间的关系。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-06-04 DOI: 10.1111/cen.15094

Edibe S. Eker, Hayriye E. Ataoğlu

Objective

Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM).

Design, Patients and Measurements

This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia.

Results

The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = −.117, r = −.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76–7.52, p = .001).

Conclusion

Albuminuria is more frequently observed in patients with hypomagnesemia.

目的：糖尿病肾病是全球慢性肾病的一个普遍病因。镁在胰岛素抵抗中起着关键作用，而胰岛素反过来又调节镁的水平。我们旨在研究 2 型糖尿病（T2DM）患者低镁血症与白蛋白尿之间的关系：这项回顾性单中心研究涵盖了2019年1月至2020年8月期间在我院门诊就诊的1178名18岁及以上的T2DM患者。白蛋白尿水平根据肾脏疾病结果质量倡议指南进行分类。在文献中，当研究低镁血症的临界值时，发现研究通常使用医院的正常水平作为参考点。低镁血症的定义是镁水平低于 1.6 毫克/分升，并与正常镁血症（镁水平在 1.6 至 2.4 毫克/分升之间）进行了比较。首要目标是探讨镁水平对白蛋白尿的影响，次要目标是确定低镁血症的患病率。根据年龄、性别（男性）、HbA1c和是否存在低镁血症进行了多变量逻辑回归分析：参与者的平均年龄为 58.7 ± 12.2 岁，男性占 44%。5.3%的患者存在低镁血症。高龄和女性在低镁血症患者中更为常见（p = .001）。镁水平与 HbA1c 和空腹血糖呈负相关，与肌酐水平呈正相关（r = -.117, r = -.131, r = .117, p 结论：低镁血症患者更易出现白蛋白尿。

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引用次数: 0

Early identification of postoperative remission for thyrotropin-secreting adenomas 甲状腺素分泌腺瘤术后缓解的早期识别。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-05-31 DOI: 10.1111/cen.15066

Linling Fan, Zhihong Wang, Wanwan Sun, Qiaoli Cui, Wei Wu, Boni Xiang, Zengyi Ma, Yue Wu, Yongfei Wang, Zhaoyun Zhang, Yiming Li, Min He, Hongying Ye

Objective

Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission.

Design, Patients and Measurements

We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission.

Results

The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff.

Conclusions

Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

目的：促甲状腺激素分泌腺瘤（TSHoma）是一种罕见的垂体腺瘤：促甲状腺激素分泌腺瘤（TSHoma）是一种罕见的垂体腺瘤，发病率为百万分之一。人们对促甲状腺激素瘤知之甚少。我们根据单中心的经验总结了促肾上腺皮质激素瘤的人口统计学、临床和激素特征。此外，我们还探讨了术后甲状腺功能对长期缓解的预测价值：我们回顾性分析了2015年1月至2021年6月在本院确诊为TSHoma并接受手术治疗的63名患者。分析术前临床特征，并在缓解组和非缓解组之间进行比较。在术后1天、1个月、3个月、6个月、12个月及12个月后测量甲状腺功能，以确定它们是否能预测长期缓解：TSHoma 的男女比例为 1.25。确诊时的平均年龄为 45 ± 12 岁。临床表现多种多样，主要表现为甲状腺功能亢进（68.25%）、占位效应（15.87%）、闭经（占女性患者的 7.14%）和无症状（22.22%）。88.14%的患者术后内分泌缓解。肿瘤体积较大、肿瘤侵犯海绵窦和星状上皮并压迫椎弓根是内分泌缓解率较低的有力预测因素。术后3个月的甲状腺功能是术后缓解的可行诊断预测指标，尤其是FT4水平，其临界值为20.65 pmol/L：结论：肿瘤大小和范围是缓解的主要预后因素。术后3个月的甲状腺功能可作为长期内分泌缓解的临床预测工具。

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引用次数: 0

18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly 持续性肢端肥大症患者的 18F- 氟-乙基-酪氨酸 PET 与核磁共振成像联合登记。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-05-31 DOI: 10.1111/cen.15079

Leontine E. H. Bakker, Marco J. T. Verstegen, Diandra C. Manole, Huangling Lu, Thomas J. M. Decramer, Iris C. M. Pelsma, Mark C. Kruit, Berit M. Verbist, Annenienke van de Ven, Mark Gurnell, Idris Ghariq, Wouter R. van Furth, Nienke R. Biermasz, Lenka M. Pereira Arias-Bouda

Objective

To report our experience with ¹⁸F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI^CR) in the care trajectory for persistent acromegaly.

Design

Prospective case series.

Patients

Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.

Measurements

FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.

Results

FET-PET/MRI^CR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI^CR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI^CR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI^CR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.

Conclusions

In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI^CR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.

目的报告我们在顽固性肢端肥大症的治疗过程中使用18F-氟-乙基酪氨酸（FET）正电子发射断层扫描-计算机断层扫描（PET-CT）和磁共振成像（MRI）（FET-PET/MRICR）的经验：前瞻性病例系列：十名肢端肥大症控制不佳的患者转诊至我们的团队，以评估手术方案：如果仅靠磁共振成像和多学科团队评估无法充分明确手术方案，则使用 FET-PET/MRICR 辅助决策：所有患者的 FET-PET/MRICR 均显示可疑的（副）蝶窦示踪剂摄取。五名患者的 FET-PET/MRICR 与传统磁共振成像完全吻合，一名患者部分吻合。FET-PET/MRICR 在另外四名患者中发现了提示性新病灶。九名患者进行了手术再探查（目的是全切除（6 例）、清扫（2 例）、诊断（1 例）），一名患者接受了放射治疗。9 名手术患者中有 7 人（78%）的 FET-PET/MRICR 结果在术中得到证实，6 人（67%）的结果也在组织学上得到证实。八名患者（89%）的 IGF-1 明显下降。所有患者的临床症状均有所改善。三例患者（预计可进行全切除手术的 50%）的生化指标完全缓解。五名患者的生化指标有所改善，一名患者的生化指标没有变化。没有出现永久性并发症。6个月后，6名患者（67%）达到了最佳治疗效果（达到术前预期目标，无永久性并发症），另外3名患者达到了中等治疗效果（未达到目标，但无并发症）：对于磁共振成像没有明确手术目标的持续性肢端肥大症患者，FET-PET/MRICR是一种新的示踪剂，可提供额外信息，帮助多学科垂体小组做出决策。

{"title":"18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly","authors":"Leontine E. H. Bakker, Marco J. T. Verstegen, Diandra C. Manole, Huangling Lu, Thomas J. M. Decramer, Iris C. M. Pelsma, Mark C. Kruit, Berit M. Verbist, Annenienke van de Ven, Mark Gurnell, Idris Ghariq, Wouter R. van Furth, Nienke R. Biermasz, Lenka M. Pereira Arias-Bouda","doi":"10.1111/cen.15079","DOIUrl":"10.1111/cen.15079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To report our experience with <sup>18</sup>F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI<sup>CR</sup>) in the care trajectory for persistent acromegaly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Prospective case series.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FET-PET/MRI<sup>CR</sup> showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI<sup>CR</sup> was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI<sup>CR</sup> identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI<sup>CR</sup> findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI<sup>CR</sup> is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fertility and pregnancy outcomes in women with Turner syndrome: A single centre experience 特纳综合征妇女的生育能力和妊娠结局：一个单一中心的经验。

IF 3.2 3区医学 Q2 Medicine

Clinical Endocrinology

Pub Date : 2024-05-27 DOI: 10.1111/cen.15078

Elizabeth Burt, Melanie C. Davies, Ephia Yasmin, Antoinette Cameron-Pimblett, Vikram Talaulikar, Clementina La Rosa, Sophie A. Clarke, Gerard S. Conway

Objective

Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators.

Design

A retrospective single-centre cross-sectional study.

Patients and Measurements

Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS.

Results

In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6−10.8, p = .003) and SGA (OR: 2.92, 95% CI: 1.02−8.38, p = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34−0.84, p = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, p = .04).

Conclusions

We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.

目的：许多患有特纳综合征（TS）的妇女都会考虑生育和怀孕的选择。我们希望通过大型单中心队列研究接受卵母细胞捐献（OD）治疗或自然怀孕的 TS 妇女的生育和妊娠结局。一般人群参考数据或特发性卵巢早衰患者的数据被用作比较对象：设计：回顾性单中心横断面研究：74名TS女性接受了卵巢早衰治疗，共妊娠105次，31名TS女性自然受孕71次。生育结果包括临床妊娠和活产率。妊娠结局包括流产率、高血压发病率、妊娠糖尿病、下段剖腹产（LSCS）、胎龄小（SGA）、早产和 TS 垂直传播：在 TS 患者中，与自然妊娠相比，OD 妊娠与 LSCS 和 SGA 的发生率增加有关；LSCS（OR：4.19，95% CI：1.6-10.8，p = .003）和 SGA（OR：2.92，95% CI：1.02-8.38，p = .04）。没有记录到心脏事件，但发现了 5 例（17.2%）女儿垂直传播 TS 的病例。与 POI 妇女相比，TS 妇女的 OD 与每个周期开始时较低的活产率（OR：0.53，95% CI：0.34-0.84，p = .008）和较高的流产率（40% vs. 26.2%，p = .04）有关：我们的研究表明，患有TS的妇女怀孕，无论是OD还是自然受孕，都存在产科风险，因此，考虑怀孕的TS妇女应接受全面的孕前咨询和最佳产科护理。

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引用次数: 0

Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency 重新定义雅培平台的 ITT 皮质醇阈值，防止肾上腺功能不全的误诊。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-05-27 DOI: 10.1111/cen.15074

Katharine Lazarus, Annabel Hayes, Kavita Narula, Debbie Papadopolou, Tricia M.-M. Tan, Karim Meeran, Sirazum Choudhury

Background

Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk.

Design, Patients and Measurements

This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre.

Results

Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%.

Conclusion

This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.

背景：肾上腺功能不全（AI）是一种危及生命的疾病，需要长期替代糖皮质激素。胰岛素耐量试验（ITT）是目前诊断继发性肾上腺功能不全的金标准试验，但皮质醇峰值小于 500 nmol/L 的临界值已被广泛接受，这意味着任何未达到该值的人都患有肾上腺功能不全，因此需要完全替代。用于诊断 AI 的临界值也是基于过时的检测方法。因此，在使用更特异的免疫测定法的时代，使用这一临界值有可能导致误诊，从而引起不必要的糖皮质激素暴露和相关不良反应，增加死亡风险：这项回顾性分析评估了一家三级中心在12年间（2010年8月至2022年1月）使用雅培Architect和Alinity分析仪平台对300名疑似AI患者的ITT皮质醇反应：由垂体和肾上腺专家组成的小组对患者从检测开始至今的电子病历进行了全面的临床审查，并根据审查结果对患者进行了人工流产与否的分类。使用当前机构设定的 500 nmol/L 临界值，接收器操作特征分析确定了 100.0% 的灵敏度和 43.6% 的特异性（曲线下面积为 0.979）。在雅培分析仪平台上使用较低的皮质醇临界值 416 nmol/L，灵敏度保持在 100.0%，特异性提高到 86.7%：这些数据支持将雅培分析仪的 ITT 皮质醇峰值阈值降至 416 nmol/L。本研究中有 104 人（34.7%）使用了这一改进的临界值，避免了不必要的糖皮质激素替代治疗。所有患者在糖皮质激素替代治疗至少 1 年的纵向随访中均保持良好状态。

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引用次数: 0

Severe adrenal insufficiency in six neonates with normal newborn screening for CAH 六名新生儿严重肾上腺功能不全，但新生儿 CAH 筛查结果正常

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-05-26 DOI: 10.1111/cen.15080

Ilknur Kurt, Metin Eser, Ahmet Kahveci, Ahmet Ucar, Derya Bulus, Bahar Ozcabi, Omer Guran, Selen Karagozlu, Aysenur Ersoy, Senol Demir, Bilge Geckinli, Tulay Guran

Background

Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI).

Patients and Methods

Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined.

Results

Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05−0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established.

Conclusion

Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a ‘normal’ screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.

背景新生儿筛查（NBS）可降低先天性肾上腺皮质增生症（CAH）的死亡风险，这主要是由于21-羟化酶缺乏引起的盐耗竭。关于非CAH原发性肾上腺功能不全（non-CAH PAI）的NBS结果，目前所知有限。患者和方法研究了2022年1月至12月期间被诊断为非CAH PAI的新生儿的临床和NBS数据。结果患者（n = 6，4 名女性）在出生 3 小时至 2 个月期间出现严重色素沉着（n = 6）、低血糖（n = 4）、低钠血症（n = 3）、高钾血症（n = 1）和呼吸窘迫综合征（n = 1）。所有患儿的 NBS 结果均正常。CAH NBS 中第一级 17- 羟孕酮（17OHP）浓度的中位数为 0.14 纳克/毫升（范围：0.05-0.85）。分子研究显示，MC2R（n = 4；3 个同源，1 个复合杂合）、MRAP（n = 1）和 STAR（n = 1）基因存在双偶合突变。结论患有非CAH PAI的新生儿由于17OHP持续偏低，NBS总是正常的，即使这些新生儿有严重的肾上腺功能不全症状。临床医生应警惕新生儿肾上腺功能不全的迹象，即使患者的 CAH 筛查结果 "正常"，以免延误诊断和治疗。尤其是在这些疾病比其他地方更为常见的国家，更应牢记这一点。

{"title":"Severe adrenal insufficiency in six neonates with normal newborn screening for CAH","authors":"Ilknur Kurt, Metin Eser, Ahmet Kahveci, Ahmet Ucar, Derya Bulus, Bahar Ozcabi, Omer Guran, Selen Karagozlu, Aysenur Ersoy, Senol Demir, Bilge Geckinli, Tulay Guran","doi":"10.1111/cen.15080","DOIUrl":"10.1111/cen.15080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients (<i>n</i> = 6, 4 females) were presented with severe hyperpigmentation (<i>n</i> = 6), hypoglycemia (<i>n</i> = 4), hyponatremia (<i>n</i> = 3), hyperkalemia (<i>n</i> = 1), respiratory distress syndrome (<i>n</i> = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05−0.85). Molecular studies revealed biallelic mutations in the <i>MC2R</i> (<i>n</i> = 4; 3 homozygous, 1 compound heterozygous), <i>MRAP</i> (<i>n</i> = 1) and <i>STAR</i> (<i>n</i> = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a ‘normal’ screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Diagnostic accuracy of morning serum cortisol concentration in confirming recovery of the hypothalamic-pituitary-adrenal axis in patients on chronic glucocorticoid therapy 晨间血清皮质醇浓度在确认慢性糖皮质激素治疗患者下丘脑-垂体-肾上腺轴恢复方面的诊断准确性。

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology

Pub Date : 2024-05-19 DOI: 10.1111/cen.15077

Ella Sharma, Joe Berry, Bridget Griffiths, Alice Lorenzi, Ben Thompson, Chris Boot, Yaasir Mamoojee

Chronic glucocorticoid therapy (CGT) is widely used in a variety of medical specialities as an anti-inflammatory and immunosuppressive agent. The prevalence of oral CGT use can be as high as 3% in some populations, and as such CGT above physiological dosing and for a prolonged period of time invariably carries an increased risk of glucocorticoid-induced adrenal insufficiency (AI). In clinical practice, the oral dose of CGT is gradually reduced according to disease activity and to prevent flare, as well as allowing for recovery of the hypothalamic–pituitary–adrenal (HPA) axis.¹ Many centres undertake inappropriate 250 µg Synacthen tests (SST) in patients who may be on suppressive doses of prednisolone, especially those suffering from hypo-adrenal symptoms on tapering steroid doses (arthralgia/myalgia, lethargy, weakness, sleep disturbance and mood changes).

We previously reported that an early morning serum cortisol concentration of >237 nmol/L (>8.6 μg/dL) on the Cortisol-II assay (by Roche Diagnostics) has 100% specificity at confirming an intact HPA axis in a large cohort of patients at risk of secondary AI from pituitary disease.² Given that the pathophysiology of AI in CGT and pituitary disease is comparable and secondary to low/suppressed secretion of adrenocorticotropic hormone from the pituitary gland, we postulated that the same morning serum cortisol concentration cutoff can be applied as a screening test for patients on CGT. To validate this cutoff, we retrospectively reviewed SST results performed in patients on tapering doses of CGT, from our rheumatology department, over a 12-month period. This study was registered as a service evaluation within our institution.

All SSTs were performed in the morning (7 AM to 12 AM) after withholding CGT for 48 h. Peripheral blood was sampled for cortisol at baseline, 30 and 60 min. AI was defined as a peak serum cortisol concentration <420 nmol/L (<15.2 μg/dL) (Cortisol-II assay Roche Diagnostics), based on previously validated cutoff values from healthy control population.³ Data is expressed as mean (±SD) and percentages. Mann–Whitney test was used for statistical analyses between continuous variables.

Sixty SSTs were performed on 58 patients. The mean age of our cohort was 65( ± 15) years with a female predominance of 2:1. Mean duration of CGT was 63( ± 42) months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%). All patients were on prednisolone as CGT and the mean daily dose was 3.4 (±2.5) mg at the time of SST. 15% of our cohort had a failed SST. With our previously reported basal serum cortisol concentration of >237 nmol/L (>8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 out of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided. Receiver operating curve an

慢性糖皮质激素疗法（CGT）作为一种抗炎和免疫抑制剂被广泛应用于各种医学专科。在某些人群中，口服 CGT 的比例可高达 3%，因此，超过生理剂量和长期使用 CGT 必然会增加糖皮质激素诱发肾上腺功能不全（AI）的风险。在临床实践中，CGT 的口服剂量会根据疾病活动情况逐渐减少，以防止复发，并使下丘脑-垂体-肾上腺（HPA）轴得以恢复。许多中心对可能正在使用泼尼松龙抑制剂的患者，尤其是在减少类固醇剂量时出现肾上腺功能减退症状（关节痛/肌痛、倦怠、虚弱、睡眠障碍和情绪变化）的患者，进行不适当的 250 微克辛纳坦试验（SST）。我们以前曾报道过，在一大群因垂体疾病而有继发性 AI 风险的患者中，用皮质醇-II 检测法检测清晨血清皮质醇浓度为 237 nmol/L（8.6 μg/dL）时，确认 HPA 轴完好的特异性为 100%。鉴于 CGT 和垂体疾病的 AI 病理生理学相似，都是继发于垂体促肾上腺皮质激素分泌过低/抑制，我们推测同样的晨间血清皮质醇浓度临界值可用作 CGT 患者的筛查试验。为了验证这一临界值，我们回顾性地检查了风湿病科在 12 个月内对正在减量服用 CGT 的患者进行的 SST 结果。所有 SST 均在停用 CGT 48 小时后的早晨（7 点至 12 点）进行。AI 的定义是血清皮质醇峰值浓度为 420 nmol/L（15.2 μg/dL）（Cortisol-II 检测法，罗氏诊断公司），以先前从健康对照人群中验证的临界值为依据。连续变量之间的统计分析采用 Mann-Whitney 检验。58 名患者共进行了 60 次 SST，平均年龄为 65（±15）岁，女性占 2:1。CGT的平均持续时间为63（± 42）个月，主要用于治疗巨细胞动脉炎/风湿性多肌痛（48%）和炎症性关节炎（18%）。所有患者都在使用泼尼松龙作为CGT，SST时的平均日剂量为3.4（±2.5）毫克。15% 的患者 SST 失败。如果我们之前报告的基础血清皮质醇浓度为 237 nmol/L（8.6 μg/dL），用于确认 HPA 轴是否完好，那么就不会漏掉任何 AI 患者，但会避免肾上腺素过多患者 51 次不必要 SST 中的 37 次（73%）。接收器操作曲线分析（见证明资料附录）显示，基础血清皮质醇浓度为 227 nmol/L 时，预测通过 SST 的特异性为 100%，而基础血清皮质醇浓度≤55 nmol/L 时，预测失败的灵敏度为 100%（曲线下面积：0.值得注意的是，AI 患者在 SST 时的平均每日泼尼松龙用量显著高于 SST 正常者（分别为 5.7 毫克对 2.9 毫克，P = .01）。Sagar 等人曾报告说，使用 ADVIA Centaur 皮质醇免疫分析仪（西门子）检测晨间皮质醇为 100 nmol/L（3.6 μg/dL）的慢性 CGT 患者 100%SST 不合格，而所有晨间皮质醇为 350 nmol/L （12.6 μg/dL）的患者均完全合格。此外，Sbardella 等人的研究表明，雅培 Architect i-2000 免疫测定法检测的清晨皮质醇≥336 nmol/L（≥12.1 μg/dL）对预测正常 SST 的特异性为 100%，而清晨皮质醇≤83 nmol/L（≤3 μg/dL）对 AI 的敏感性为 100%。我们的数据验证了罗氏诊断公司（Roche Diagnostics）的皮质醇-II测定法，早晨血清皮质醇浓度为237 nmol/L（8.6 μg/dL）时，预测服用减量CGT患者HPA轴恢复的特异性为100%。这为需要对 HPA 轴进行生化评估的患者提供了一种更快速、更方便、更经济的筛查方法，有可能在不对患者安全造成任何不利影响的情况下节省大量资源。在大多数中心，泼尼松龙减量治疗 GCA 非常成功，无需内分泌专家参与，例如，在几周内将剂量从 60 毫克减至 10 毫克，然后每月减量 1 毫克。

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引用次数: 0

Clinical outcomes from surgical management of primary aldosteronism based on inconclusive adrenal vein sampling 基于肾上腺静脉取样不确定的原发性醛固酮增多症手术治疗的临床效果。

IF 3.2 3区医学 Q2 Medicine

Clinical Endocrinology

Pub Date : 2024-05-19 DOI: 10.1111/cen.15076

Rachel Norman, Caitlin Carr-Knox, Chris Boot, Ralph Jackson, Muhammad Ramzan, Peter Truran, Jason Ramsingh, Richard Bliss, Andy James, Yaasir Mamoojee, RVI Endocrine Group

引用次数: 0

Liothyronine (LT3) prescribing in England: Are cost constraints inhibiting guideline implementation? 英格兰的甲状腺素（LT3）处方：成本限制是否阻碍了指南的实施？

IF 3.2 3区医学 Q2 Medicine

Clinical Endocrinology

Pub Date : 2024-05-16 DOI: 10.1111/cen.15061

Heald AH, Premawardhana LD, Taylor PN, Dasha Depesina, Nadia Chaudhury, Okosieme OE, Stedman M, Dayan CM

Background

Primary hypothyroidism affects about 3% of the general population in Europe. In most cases people with hypothyroidism are treated with levothyroxine. In the context of the 2023 British Thyroid Association guidance and the 2020 Competitions and Marketing Authority (CMA) ruling, we examined prescribing data for levothyroxine, Natural desiccated thyroid (NDT) and liothyronine by dose, regarding changes over the years 2016–2022.

Design

Monthly primary care prescribing data for each British National Formulary code were analysed for levothyroxine, liothyronine and NDT.

Patients and Measurements

The rolling 12-month total/average of cost or prescribing volume was used to identify the moment of change. Results included number of prescriptions, the actual costs, and the cost/prescription/mcg of drug.

Results

Liothyronine: In 2016 94% of the total 74,500 prescriptions were of the 20 mcg dose. In 2020 the percentage prescribed in the 5 mcg and 10 mcg doses started to increase so that by 2022 each reached nearly 27% of total liothyronine prescribing. The average cost/prescription in 2016 of 20 mcg was £404/prescription and this fell by 80% to £101 in 2022; while the 10 mcg cost of £348/prescription fell by only 35% to £255 and the 5 mcg cost of £355/prescription fell by 38% to £242/prescription. The total prescriptions of liothyronine in 2016 were 74,605, falling by 30% up to 2019 when they started to grow again - most recently at 60,990−15% lower than the 2016 figure, with the result that total costs fell by 70% to £9 m/year.

Conclusions

Liothyronine costs fell after the CMA ruling but remain orders of magnitude higher than for levothyroxine. The remaining 0.2% of patients with liothyronine treated hypothyroidism are still absorbing 16% of medication costs. The lower liothyronine 5cmg and 10 mcg doses as recommended by BTA are 240% the costs of the 20 mcg dose. Thus, following latest BTA guidance which recommends the lower liothyronine doses still incurs substantial additional costs vs the prescribing liothyronine in the no longer recommended treatment regime. High drug price continues to impact clinical decisions, potentially limiting liothyronine therapy availability to a considerable number of patients who could benefit from this treatment.

<

背景：在欧洲，原发性甲状腺功能减退症患者约占总人口的 3%。在大多数情况下，甲减患者接受左甲状腺素治疗。在 2023 年英国甲状腺协会指南和 2020 年竞争与营销管理局（CMA）裁决的背景下，我们按剂量研究了 2016-2022 年间左甲状腺素、天然干燥甲状腺（NDT）和利甲氨酸的处方数据变化：对左旋甲状腺素、利甲氨酸和NDT的英国国家处方集各编码的每月初级保健处方数据进行分析：使用滚动的 12 个月总/平均成本或处方量来确定变化时刻。结果包括处方数量、实际成本以及成本/处方/毫克药物：甲状腺素：2016 年，7.45 万个处方中 94% 为 20 毫克剂量。2020 年，5 毫克和 10 毫克剂量的处方比例开始增加，到 2022 年，这两种剂量的处方占甲状腺氨酸处方总量的近 27%。2016 年，20 毫克的平均费用为 404 英镑/处方，到 2022 年，这一数字下降了 80% 至 101 英镑/处方；而 10 毫克的费用为 348 英镑/处方，仅下降了 35% 至 255 英镑/处方，5 毫克的费用为 355 英镑/处方，下降了 38% 至 242 英镑/处方。2016年，甲状腺素的总处方量为74605张，下降了30%，直到2019年，处方量又开始增长--最近的处方量为60990张，比2016年的数字下降了15%，结果总成本下降了70%，为900万英镑/年：在 CMA 作出裁决后，甲状腺素的成本有所下降，但仍比左甲状腺素高出几个数量级。剩下的 0.2% 甲减患者仍需承担 16% 的药费。根据 BTA 的建议，5 毫克和 10 毫克的低剂量利甲腺原氨酸的成本是 20 毫克剂量的 240%。因此，与按照不再推荐的治疗方案处方利甲腺原氨酸相比，按照英国治疗师协会的最新指导建议使用较低剂量的利甲腺原氨酸仍会产生大量额外费用。高昂的药价继续影响着临床决策，可能会限制大量本可从中受益的患者接受利甲腺原氨酸治疗。

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引用次数: 0

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