更新于：2024-11-01

Cushing Syndrome

库欣综合征

更新于：2024-11-01

基本信息

别名

CUSHING、CUSHING SYNDROME、CUSHING'S SYNDROME

+ [32]

简介

A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.

关联

项与库欣综合征相关的药物

Levoketoconazole

左旋酮康唑

靶点

CYP11B1 x CYP17A1 x CYP21A2

作用机制

CYP11B1抑制剂 [+2]

在研机构

Cortendo AB [+1]

原研机构

Strongbridge Biopharma Plc

在研适应症

内源性库欣综合征

非在研适应症

2型糖尿病

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2021-12-30

Osilodrostat Phosphate

磷酸奥唑司他

靶点

CYP11B1

作用机制

CYP11B1抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2020-01-09

Pasireotide Diaspartate

门冬氨酸帕瑞肽

靶点

SSTR1 x SSTR2 x SSTR3 x SSTR5

作用机制

SSTR1激动剂 [+3]

在研机构

Novartis Pharmaceuticals Corp. [+5]

原研机构

Novartis Pharma AG

在研适应症

生长激素过多 [+8]

非在研适应症

晚期肝细胞癌 [+32]

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2012-04-24

164

项与库欣综合征相关的临床试验

NCT06635629 / Not yet recruiting临床2期IIT

Phase II Prospective Evaluation of Desmopressin Stimulation Test Performance in ACTH-dependent Cushing s Syndrome

Background:
Cushing syndrome (CS) is a set of diseases that develop when the body produces too much adrenocorticotropic hormone (ACTH). ACTH stimulates the production of a hormone called cortisol. Excess cortisol can cause serious issues, such as diabetes, high blood pressure, weight gain, and mood changes. Diagnosing CS early can be difficult. One test used to diagnose CS, the desmopressin (Desmo) stimulation test (DesmoST), has not been studied in enough people to know how accurate it is.
Objective:
To find ways to improve the DesmoST. Researchers especially want to learn more about how well the DesmoST identifies people with specific ACTH CSs: Cushing disease (CD) and ectopic ACTH syndrome (EAS).
Eligibility:
People aged 18 to 70 years who have or may have CS, especially CD or EAS. Healthy volunteers are also needed.
Design:
Participants with CS will have 3 DesmoSTs at least 48 hours apart. The procedure for each is as follows:
They will limit their fluid intake the day before each test. They will have nothing to eat or drink for 12 hours before the test.
For 1 of the tests, they will take a pill that contains a hormone (dexamethasone). They will take it around 11 pm the day before the test.
Desmo is given through a tube attached to a needle inserted into a vein.
Blood will be drawn a total of 6 times before and after the desmo is given.
Healthy volunteers will have 4 DesmoSTs. These will be 2 to 14 days apart.
All participants will have follow-up visits 3 to 5 days after each test. These visits may be by phone.

开始日期2024-11-05

申办/合作机构

National Institute of Diabetes & Digestive & Kidney Diseases

NCT06246357 / Recruiting临床2期IIT

Phase 2 Study Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism

Background:
The adrenal glands are 2 small organs that sit on top of each kidney. They release hormones; these are chemicals that control how the body works. Tumors on or outside the adrenal glands are called functional if they release hormones; they are called nonfunctional if they do not. Doctors who treat adrenal tumors need to know which type a person has. Researchers want to find better ways to learn whether an adrenal tumor is functional.
Objective:
To see if a new radioactive tracer ([68Ga]Ga-PentixaFor) can make it easier to identify functional adrenal tumors with positron emission tomography (PET) scans.
Eligibility:
People aged 18 years and older with 1 or more adrenal tumors. They must have increased levels of the hormones aldosterone or cortisol. They must also be enrolled in at least 1 other related NIH study (protocols 19-DK-0066, 18-CH-0031, or 09-C-0242).
Design:
Participants will be screened. They may have imaging scans. Their ability to perform normal activities will be reviewed.
Participants will have one PET scan with the study tracer.
The tracer will be given through a tube attached to a needle inserted into a vein. Participants will receive the tracer 1 hour before the scan. They will lie still on a bed while a machine captures images of the inside of their body. The scan will take 45 to 90 minutes.
Participants heart rate, blood pressure, and rate of breathing will be checked before, during, and after the scan.
Participants will have a follow-up visit 3 days after their scan. This visit can be by phone, email, or in person.

开始日期2024-09-23

申办/合作机构

National Cancer Institute

NCT06430528 / RecruitingN/AIIT

A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement

The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach).
The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.

开始日期2024-07-19

申办/合作机构

University of Michigan

[+1]

100 项与库欣综合征相关的临床结果

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100 项与库欣综合征相关的转化医学

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0 项与库欣综合征相关的专利（医药）

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12,422

项与库欣综合征相关的文献（医药）

2024-12-31·Annals of Medicine

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing’s syndrome

Article

作者: He, Wen-Tao ; Yu, Xue-Feng ; Wu, Kun ; Yuan, Gang ; Zhang, Mu-Xun ; Ran, Chun-Qiong ; Su, Ying ; Liu, Zhe-Long ; Li, Jin ; Yang, Yan

BACKGROUNDCushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.METHODSA retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.RESULTSA total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm³ [125.67, 189.41] vs 90.55 cm³ [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm³ in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively.CONCLUSIONCS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

2024-12-31·Journal of Dermatological Treatment

Evaluation of psoriasis patients with long-term topical corticosteroids for their risk of developing adrenal insufficiency, Cushing’s syndrome and osteoporosis

Article

作者: Gonul, Muzeyyen ; Ozturk Unsal, Ilknur ; Erdem, Betul ; Ozdemir Sahingoz, Seyda

PURPOSEIn this study, we will investigate the possible side effects of psoriasis patients using long-term topical corticosteroids (TCS) such as adrenal insufficiency, Cushing's Syndrome (CS) and osteoporosis and determine how these side effects develop.MATERIAL AND METHODSForty-nine patients were included in the study. The patients were divided into two groups based on the potency of the topical steroid they took and the patients' ACTH, cortisol and bone densitometer values were evaluated.RESULTSThere was no significant difference between the two groups regarding the development of surrenal insufficiency, CS and osteoporosis. One patient in group 1 and 4 patients in group 2 were evaluated as iatrogenic CS. ACTH stimulation tests of these patients in group 2 showed consistent results with adrenal insufficiency, while no adrenal insufficiency was detected in the patient in Group 1. Patients who used more than 50g of superpotent topical steroids per week compared to patients who used 50g of superpotent topical steroids per week. It was identified that patients who used more than 50g of superpotent topical steroids had significantly lower cortisol levels, with a negatively significant correlation between cortisol level and the amount of topical steroid use (p < .01).Osteoporosis was detected in 3 patients in group 1 and 8 patients in Group 2. Because of the low number of patients between two groups, statistical analysis could not be performed to determine the risk factors.CONCLUSIONSOur study is the first study that we know of that investigated these three side effects. We have shown that the development of CS, adrenal insufficiency and osteoporosis in patients who use topical steroids for a long time depends on the weekly TCS dosage and the risk increases when it exceeds the threshold of 50 grams per week. therefore, our recommendation would be to avoid long-term use of superpotent steroids and to choose from the medium-potent group if it is to be used.

2024-12-01·Hormones

The molecular genetics of adrenal cushing

Review

作者: Vaduva, Patricia ; Bertherat, Jerome

Adrenal Cushing represents 20% of cases of endogenous hypercorticism. Unilateral cortisol-producing adenoma (CPA), a benign tumor, and adrenocortical carcinoma (ACC), a malignant tumor, are more frequent than bilateral adrenal nodular diseases (primary bilateral macronodular adrenal hyperplasia (PBMAH) and primary pigmented nodular adrenal disease (PPNAD)).In cortisol-producing adrenal tumors, the signaling pathways mainly altered are the protein kinase A and Wnt/β-catenin pathways. Studying components of these pathways and exploring syndromic and familial cases of these tumors has historically enabled identification of many of the predisposing genes. More recently, pangenomic sequencing revealed alterations in sporadic tumors.In ACC, mainly due to TP53 alterations causing Li-Fraumeni syndrome, germline predisposition is frequent in children, while it is rare in adults. Pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2, which cause Lynch syndrome or alterations of IGF2 and CDKN1C (11p15 locus) in Beckwith-Wiedemann syndrome, can also cause ACC. Rarely, ACC is described in other hereditary tumor syndromes due to germline pathogenic variants in MEN1 or APC and, in very rare cases, NF1, SDH, PRKAR1A, or BRCA2. Concerning ACC somatic alterations, TP53 and genetic or epigenetic alterations at the 11p15 locus are also frequently described, as well as CTNNB1 and ZNRF3 pathogenic variants.CPAs mainly harbor somatic pathogenic variants in PRKACA and CTNNB1 and, less frequently, PRKAR1A, PRKACB, or GNAS1 pathogenic variants. Isolated PBMAH is due to ARMC5 inactivating pathogenic variants in 20 to 25% of cases and to KDM1A pathogenic variants in food-dependent Cushing. Syndromic PBMAH may be due to germline pathogenic variants in MEN1, APC, or FH, causing type 1 multiple endocrine neoplasia, familial adenomatous polyposis, or hereditary leiomyomatosis-kidney cancer syndrome, respectively. PRKAR1A germline pathogenic variants are the main alteration causing PPNAD (isolated or part of Carney complex).

170

项与库欣综合征相关的新闻（医药）

2024-10-23

·BioSpace

Corcept Therapeutics to Announce Third Quarter Financial Results, Provide Corporate Update and Host Conference Call

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Corcept Therapeutics Incorporated (NASDAQ: CORT) today announced it will report third quarter financial results and provide a corporate update on October 30, 2024. The company will also host a conference call that day at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). Conference Call Information Participants must register in advance of the conference call by clicking here . Upon registering, each participant will receive a dial-in number, and a unique access PIN. Each access PIN will accommodate one caller. Additionally, a listen-only webcast will be available by clicking here . A replay of the call will be available on the Investors / Events tab of Corcept.com. About Corcept Therapeutics For over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients with a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept is conducting advanced clinical trials in patients with hypercortisolism, solid tumors, amyotrophic lateral sclerosis (ALS) and liver disease. In February 2012, the company introduced Korlym ® , the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with Cushing’s syndrome. Corcept is headquartered in Redwood City, California. For more information, visit Corcept.com. Contacts Investor inquiries: ir@corcept.com Media inquiries: communications@corcept.com

上市批准财报

2024-10-15

·药智网

又一爆款，恒瑞HR19042纳入突破性疗法

10月14日晚，恒瑞医药发布公告，HR19042胶囊被国家药品监督管理局药品审评中心（以下简称“药审中心”）纳入突破性治疗品种名单。图片来源：企业公告 01 迫切的临床需求据公告内容显示，自身免疫性肝炎作为一种现阶段无法治愈的自免疾病，疾病负担重且危及生命，10年累计死亡率为26.4%，疾病进展的最终结果为肝硬化或终末期肝病，约1/3的患者在初诊时即为肝硬化表现，20%—25%的患者还表现为急性发作，急性重症AIH可迅速发展为急性肝衰竭，不进行肝移植生存率仅66%。现阶段临床一线治疗方式通常为糖皮质激素联合硫唑嘌呤，且治疗至少要维持2年，患者服药顺应性不足，约70%的患者在停药后复发。更关键的是，长期服用糖皮质激素伴随较多明显的不良反应，如库欣综合征、骨质疏松、股骨头坏死、2型糖尿病等，临床上迫切需要一系列不良反应小的激素类药物。 02 良好的竞争格局据悉，HR19042胶囊是由恒瑞医药自主研发并具有知识产权的改良型新药，拟用于治疗活动性自身免疫性肝炎。在“自身免疫性肝炎”上市新药方面，目前全球仅有GSK与田边三菱的“硫唑嘌呤”获批上市。在“自身免疫性肝炎”在研新药方面，布地奈德与伊利尤单抗在自身免疫性肝炎适应症下的全球临床进展较快，目前已进入了临床III期；其次有6款新药进入了临床II期，恒瑞HR-19042正是其中之一。并且，更值得一提的是，所有在研新药该适应症下，也仅有恒瑞HR-19042的具有中国临床进展。表1 部分“自身免疫性肝炎”新药数据来源：药智数据在“自身免疫性肝炎”的仿制药方面，国内获批用于该适应症的化药仅有“硫唑嘌呤”（雷公藤多苷片等中药不在范围内），根据药智数据上市数据库显示，国内该药共有6家企业进行仿制药生产，分别是上药信谊、诚意药业、浙北药业、嘉林药业与天方药业。国内“自身免疫肝炎”上市药品图片来源：药智数据综上所述，恒瑞医药这款HR19042胶囊拟纳入突破性治疗品种，意味着该产品也有望更快惠及患者。在目前我国尚无同类产品获批该适应症的情况下，恒瑞医药HR19042一旦成功上市，必将快速攻占市场，未来可期。声明：本文系整合内容，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。责任编辑 | 青霉素阅读原文，是受欢迎的文章哦

上市批准突破性疗法临床3期

2024-10-14

·恒瑞医药

捷报！恒瑞HR19042胶囊自身免疫性肝炎适应症纳入突破性治疗品种名单

近日，恒瑞医药口服HR19042胶囊用于活动性自身免疫性肝炎（AIH）适应症被国家药品监督管理局药品审评中心纳入突破性治疗品种名单。自身免疫性肝炎（AIH）是一类无法治愈的自身免疫病，疾病负担重且危及生命。该疾病10年累计死亡率为26.4%[1]，早期如不进行临床干预，可迅速进展为肝硬化或终末期肝病，则难以逆转，且病死率和肝移植率显著上升[2]。约1/3的患者在初诊时即为肝硬化表现[3]，20-25%的患者还表现为急性发作，急性重症AIH可迅速发展为急性肝衰竭，不进行肝移植生存率仅66%[4]。《中国自身免疫性肝炎临床治疗指南》推荐，目前国内AIH的一线治疗为糖皮质激素联合硫唑嘌呤，且治疗应维持至少2年，70%的患者在尝试停药后复发[3]。但由于缺乏其他治疗选择，指南建议复发患者再次应用糖皮质激素和硫唑嘌呤[3]。长期使用传统糖皮质激素出现较多明显不良反应，包括库欣综合征（又称皮质醇过多综合征）、骨质疏松、股骨头坏死、2型糖尿病、白内障、高血压病、感染、精神疾病等，开发不良反应小的激素类药物需求迫切。 HR19042胶囊是由恒瑞医药自主研发并具有知识产权的改良型新药，为口服肠溶缓释胶囊，可选择性发挥肝脏抗炎作用。经查询，针对自身免疫性肝炎，国内尚无同类产品获批该适应症。目前除了AIH适应症外，HR19042胶囊还在原发性IgA肾病适应症中开展II/III期临床试验。什么是突破性疗法认定？为鼓励研究和创制具有明显临床优势的药物，国家药品监督管理局药品审评中心（CDE）发布了《国家药监局关于发布＜突破性治疗药物审评工作程序（试行）＞等三个文件的公告》（2020年第82号），明确了突破性疗法的纳入范围：药物临床试验期间，用于防治严重危及生命或者严重影响生存质量的疾病且尚无有效防治手段或者与现有治疗手段相比有足够证据表明具有明显临床优势的创新药或者改良型新药等。药审中心对纳入突破性治疗药物程序的药物优先配置资源进行沟通交流，加强指导并促进药物研发。参考文献： 1.中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗共识（2015）. 临床肝胆病杂志, 2016, 32(1): 9-22. 2.Wang G, Tanaka A, Zhao H, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatology International, 2021, 15(2): 223-257. 3.中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021). 中华内科杂志, 2021,60(12):1038-1049.4. 4.Mack C L, Adams D, Assis D N, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the study of liver diseases. Hepatology, 2020, 72(2): 671-722. 声明： 1. 本新闻旨在分享研发前沿资讯，仅供医疗卫生专业人士基于学术目的参阅，非广告用途。 2. 恒瑞医药不推荐任何未被批准的药品、适应症的使用。撰稿：姜文文排版：程梦真责编：王玲往期精选 | 研发创新 | 慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市恒瑞医药新突破！中国首个自研阿片类镇痛创新药富马酸泰吉利定获批上市 | 国际化 | 海外BD再传捷报！恒瑞医药GLP-1类创新药组合实现海外许可恒瑞医药与默克达成合作，携手推进癌症创新疗法 | 重磅奖项 | 喜报！恒瑞医药荣获2023年度国家科技进步奖恒瑞医药连续六年入选全球制药企业50强榜单！ | 社会公益 | “健康中国行·重走长征路”项目启动仪式圆满举行！恒瑞提供公益支持，助力健康中国恒瑞医药集团向中国扶贫基金会捐赠3000万设立“健康帮扶基金”

突破性疗法