Studies of Thyroid Function in Health and Disease

健康和疾病中的甲状腺功能研究

• 批准号: 10931304
• 负责人: Joanna Klubo-Gwiezdzinska
• 金额: $ 9.17万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10931304
• 关键词: 2019-nCoV; Acute; Adrenal Glands; Affect; Age; Aldosterone; Androstenedione; Biological; Blood; Board Certification; Body Composition; Clinical; Corticosterone; Corticotropin; Cortisone; Cortodoxone; Data; Diagnosis; Diagnostic Procedure; Differentiation and Growth; Discipline of Nuclear Medicine; Disease; Endocrine; Endocrinology; Energy Metabolism; Enrollment; Extracorporeal Membrane Oxygenation; Family history of; Female; Follicle Stimulating Hormone; Functional disorder; Genetic; Health; Hospitalization; Hydrocortisone; Hydroxyprogesterone; Hyperthyroidism; Hypothyroidism; Immunoassay; Laboratory Study; Literature; Luteinization; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measurement; Metabolism; Patients; Physical Examination; Plasma; Progesterone; Protocols documentation; Public Health; Radioactive Iodine; Recording of previous events; SARS-CoV-2 infection; Sampling; Scanning; Severity of illness; Steroids; Symptoms; Technetium; Testing; Testosterone; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Training; Training Programs; Triiodothyronine; United States National Institutes of Health; Urine; X-Ray Computed Tomography; biomedical referral center; cell growth; dehydroepiandrosterone; imaging study; liquid chromatography mass spectrometry; male; participant enrollment; patient screening; profiles in patients; research study; severe COVID-19; sex; steroid hormone; uptake

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with adrenal and thyroid dysfunction. However, the current literature is based on immunoassay measurements, which are subject to several interfering factors. In this preliminary study, we performed mass spectrometry analysis of steroid and thyroid hormone profiles in patients (18 years) hospitalized with SARS-CoV-2 at two tertiary referral centers. Liquid chromatography-mass spectrometry analysis of adrenocortical steroids progesterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, total thyroxine (TT4), total triiodothyronine (TT3), reverse triiodothyronine (rT3), and immunoassay analysis of adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), luteinizing and follicle-stimulating hormones, and aldosterone were performed. Data were dichotomized based on extracorporeal membrane oxygenation (ECMO) and survival status. Plasma analysis of a total of 63 plasma samples from ten patients (four females; median age: 41.5 years) revealed a median 11-deoxycortisol elevation up to 38-fold in male ECMO patients compared to non-ECMO patients, and up to 20-fold among female ECMO patients who died from SARS-CoV-2 compared to non-ECMO surviving patients. The 11-deoxycortisol elevations were more profound and out of proportion to corresponding cortisol levels. Significantly higher levels were noted in plasma DHEA in male non-survivors, androstenedione in females with severe SARS-CoV-2, corticosterone, and aldosterone in male/female non-survivors. Median TT4, TT3, and rT3 levels were significantly lower in patients on ECMO and among non-survivors. In conclusion, the adrenal and thyroid axes can be affected during acute SARS-CoV-2 and the degree of disruption may be associated with disease severity, sex, and ECMO status.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染与肾上腺和甲状腺功能障碍有关。然而，当前的文献是基于免疫测定的，这会受到多种干扰因素的影响。在这项初步研究中，我们对两个三级转诊中心的SARS-CoV-2住院患者（18岁）的类固醇和甲状腺激素谱进行了质谱分析。肾上腺皮质类固醇孕酮、皮质酮、17-羟孕酮、11-脱氧皮质醇、皮质醇、可的松、脱氢表雄酮（DHEA）、雄烯二酮、睾酮、总甲状腺素（TT 4）、总三碘甲状腺原氨酸（TT 3）、反三碘甲状腺原氨酸（rT 3）的液相色谱-质谱分析，促肾上腺皮质激素（ACTH）、促甲状腺激素（TSH）、促黄体生成激素、促卵泡激素和醛固酮。根据体外膜肺氧合（ECMO）和生存状态对数据进行二分。对来自10名患者（4名女性;中位年龄：41.5岁）的总共63份血浆样本的血浆分析显示，与非ECMO患者相比，男性ECMO患者的11-脱氧皮质醇中位数升高高达38倍，与非ECMO存活患者相比，死于SARS-CoV-2的女性ECMO患者的11-脱氧皮质醇中位数升高高达20倍。11-脱氧皮质醇的升高更为严重，与相应的皮质醇水平不成比例。男性死亡者血浆DHEA、严重SARS-CoV-2女性患者血浆雄烯二酮、男性/女性死亡者血浆皮质酮和醛固酮水平显著较高。ECMO患者和非幸存者的中位TT 4、TT 3和rT 3水平显著较低。总之，肾上腺和甲状腺轴可以在急性SARS-CoV-2期间受到影响，并且破坏程度可能与疾病严重程度、性别和ECMO状态相关。

项目成果

Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study.

• DOI: 10.2337/dc18-0884
• 发表时间: 2018-11
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Klubo-Gwiezdzinska J;Lange M;Cochran E;Semple RK;Gewert C;Brown RJ;Gorden P
• 通讯作者: Gorden P

The -258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH.

人类 2 型脱碘酶基因的 -258A/G (SNP rs12885300) 多态性与 TRH 诱导的 TSH 急剧升高后甲状腺激素分泌模式的转变有关。

• DOI: 10.1530/eje-11-1073
• 发表时间: 2012
• 期刊: European journal of endocrinology
• 影响因子: 5.8
• 作者: Peltsverger,MayaY;Butler,PeterW;Alberobello,AnnaTeresa;Smith,Sheila;Guevara,Yanina;Dubaz,OrnellaM;Luzon,JavierA;Linderman,Joyce;Celi,FrancescoS
• 通讯作者: Celi,FrancescoS

Graves' Autoantibodies Exhibit Different Stimulating Activities in Cultures of Thyrocytes and Orbital Fibroblasts Not Reflected by Clinical Assays.

格雷夫斯自身抗体在甲状腺细胞和眼眶成纤维细胞培养物中表现出不同的刺激活性，但临床检测并未反映出这一点。

• DOI: 10.1089/thy.2021.0326
• 发表时间: 2022
• 期刊: Thyroid : official journal of the American Thyroid Association
• 作者: Krieger,ChristineC;Kahaly,GeorgeJ;Azam,Asma;Klubo-Gwiezdzinska,Joanna;Neumann,Susanne;Gershengorn,MarvinC
• 通讯作者: Gershengorn,MarvinC

Catecholamine physiology and its implications in patients with COVID-19.

• DOI: 10.1016/s2213-8587(20)30342-9
• 发表时间: 2020-12
• 期刊: The lancet. Diabetes & endocrinology
• 作者: Gubbi S;Nazari MA;Taieb D;Klubo-Gwiezdzinska J;Pacak K
• 通讯作者: Pacak K

Thyrotropin regulation of differentiated gene transcription in adult human thyrocytes in primary culture.

• DOI: 10.1016/j.mce.2020.111032
• 发表时间: 2020-12-01
• 期刊: Molecular and cellular endocrinology
• 影响因子: 4.1
• 作者: Jang D;Marcus-Samuels B;Morgan SJ;Klubo-Gwiezdzinska J;Neumann S;Gershengorn MC
• 通讯作者: Gershengorn MC