Studies of Thyroid Function in Health and Disease

健康和疾病中的甲状腺功能研究

基本信息

项目摘要

Autoimmune thyroid disorders such as Graves disease might be associated with extrathyroidal manifestations - orbitopathy, dermopathy, and acropachy (periosteal changes and clubbing of fingers and toes). Severe forms of Graves dermopathy, such as nodular dermopathy or elephantiasis nostras verrucosa, can cause significant morbidity. The pathophysiology of Graves dermopathy is poorly understood. A combination of factors may contribute to its development, including immunologic factors, such as infiltration of T and B lymphocytes, cytokine production, interactions between serum thyroid-stimulating hormone receptor antibodies (TRAbs) and thyroid-stimulating hormone and insulin-like growth factor I receptors in dermal tissues; cellular factors, such as glycosaminoglycan production from fibroblasts; and other factors, such as smoking, local trauma, and dependent edema. Many agents have been used to treat this condition, including monotherapy with glucocorticoids, thalidomide, cyclophosphamide, intravenous immunoglobulins, infliximab, pentoxifylline, rituximab, and rituximab plus plasmapheresis, but all have produced limited and variable responses. The efficacy of combined immunosuppressive therapy for Graves dermopathy is unknown. We have successfully used combined immunosuppressive therapy to treat a patient with severe, refractory Graves dermopathy. Case Report: We provided care for a 55-year-old man with severe, disabling dermopathy, acropachy, and elephantiasis that developed gradually over 20 years. We started combined immunosuppressive therapy with a single course of rituximab, dexamethasone, and oral cyclophosphamide At 12 months, the physical examination found resolution of Graves dermopathy of the upper extremities and marked improvement in the appearance and function of the lower extremities, including the ability of the patient to wear shoes. An MRI scan documented a substantial reduction in soft tissue swelling of the patient's extremities. His quality-of-life score, as measured by the Short Form-36 questionnaire, increased from 425.8 to 582.5 points (maximum achievable score, 800; mean score in the general population, 584). Serum autoantibodies levels (TRABs) decreased from greater than 40 to 1.12 IU/L (normal, 0 to 1.75 IU/L), as documented by immunoassay and by the luciferase immunoprecipitation system assay. Combined immunosuppressive therapy appears to be a safe and effective option for the management of severe Graves dermopathy. We also performed a pilot study, using mass spectrometry analysis of steroid and thyroid hormone profiles in patients 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. We found about 17.7% of TSH values being low, up to 52.8% of TT4 and 69.4% of TT3 values being low, while 52.8% of rT3 values were elevated. This biochemical pattern of low TT4 and TT3, elevated rT3, and low to normal TSH is suggestive of non-thyroidal systemic illness syndrome commonly associated with COVID19.
自身免疫性甲状腺疾病,如Graves病,可能与甲状腺外表现-眼眶病变、皮肤病和肢端肥厚(骨膜改变和手指和脚趾棍棒)有关。严重形式的Graves皮肤病,如结节性皮肤病或疣状象皮病,可导致显著的发病率。Graves皮肤病的病理生理学还知之甚少。可能是多种因素共同作用的结果,包括免疫因素,如T和B淋巴细胞的渗透,细胞因子的产生,血清促甲状腺激素受体抗体(TRABS)与促甲状腺激素和真皮组织中的胰岛素样生长因子I受体之间的相互作用;细胞因素,如成纤维细胞产生的糖胺聚糖;以及其他因素,如吸烟,局部创伤和依赖性水肿。许多药物已经被用于治疗这种疾病,包括糖皮质激素、沙利度胺、环磷酰胺、静脉免疫球蛋白、英夫利昔单抗、己酮可可碱、利妥昔单抗和利妥昔单抗加血浆置换,但都产生了有限和可变的反应。联合免疫抑制疗法治疗Graves皮肤病的疗效尚不清楚。 我们已经成功地使用联合免疫抑制疗法治疗了一例严重的难治性Graves皮肤病。 病例报告:我们为一位55岁的男性患者提供护理,他患有严重的致残性皮肤病、肢端肥厚和象皮病,这些症状在20年内逐渐发展。我们在12个月时开始单疗程联合免疫抑制治疗,服用利妥昔单抗、地塞米松和口服环磷酰胺,体检发现上肢Graves皮肤病消失,下肢外观和功能明显改善,包括患者穿鞋的能力。核磁共振扫描显示,患者四肢软组织肿胀显著减少。他的生活质量得分,根据简短的表格-36问卷,从425.8分增加到582.5分(最高可达到得分,800分;普通人群的平均得分,584分)。免疫分析和荧光素酶免疫沉淀系统检测表明,血清自身抗体水平(TRAB)从40以上降至1.12IU/L(正常,0至1.75IU/L)。联合免疫抑制疗法似乎是治疗重症Graves皮肤病的一种安全有效的选择。 我们还进行了一项先导性研究,在两个第三转诊中心对SARS-CoV-2住院患者的类固醇和甲状腺激素谱进行了质谱仪分析。对肾上腺皮质类固醇激素孕酮、皮质酮、17-羟孕酮、11-脱氧皮质醇、脱氢表雄酮(DHEA)、雄烯二酮、睾酮、总甲状腺素(TT4)、总三碘甲腺原氨酸(TT3)、反三碘甲腺原氨酸(RT3)、促肾上腺皮质激素(ACTH)、促甲状腺激素(TSH)、黄体生成素和卵泡刺激素以及醛固酮进行了免疫分析。发现约17.7%的TSH值偏低,高达52.8%的TT4和69.4%的TT3值偏低,而52.8%的RT3值偏高。TT4和TT3降低,rT3升高,TSH降低到正常的这种生化模式提示非甲状腺系统疾病综合征通常与COVID19相关。

项目成果

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Joanna Klubo-Gwiezdzinska其他文献

Joanna Klubo-Gwiezdzinska的其他文献

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{{ truncateString('Joanna Klubo-Gwiezdzinska', 18)}}的其他基金

Somatostatin receptors in the diagnosis and treatment of thyroid cancer
生长抑素受体在甲状腺癌诊断和治疗中的作用
  • 批准号:
    10700681
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Use of metformin in the treatment of thyroid cancer
二甲双胍在治疗甲状腺癌中的用途
  • 批准号:
    10011331
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
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:
    10011456
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Cross-talk between oncogene-driven signaling pathways and thyroid cancer metabolism
癌基因驱动的信号通路与甲状腺癌代谢之间的串扰
  • 批准号:
    10700683
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Somatostatin receptors in the diagnosis and treatment of thyroid cancer
生长抑素受体在甲状腺癌诊断和治疗中的作用
  • 批准号:
    9553303
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Cross-talk between oncogene-driven signaling pathways and thyroid cancer metabolism
癌基因驱动的信号通路与甲状腺癌代谢之间的串扰
  • 批准号:
    10931300
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Application of molecular diagnostics in thyroid cancer
分子诊断在甲状腺癌中的应用
  • 批准号:
    10255253
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Studies of Benign and Malignant Thyroid Disease
良性和恶性甲状腺疾病的研究
  • 批准号:
    10700666
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
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
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:
Somatostatin receptors in the diagnosis and treatment of thyroid cancer
生长抑素受体在甲状腺癌诊断和治疗中的作用
  • 批准号:
    10931298
  • 财政年份:
  • 资助金额:
    $ 8.27万
  • 项目类别:

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In vivo and ex vivo lessons from somatic adrenal mutations in cell adhesion molecule 1 for physiological and pathological production of aldosterone
细胞粘附分子 1 体细胞肾上腺突变对醛固酮生理和病理产生的体内和离体教训
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Creating therapeutic strategies targeting both aldosterone and AGEs-RAGE axis for stopping kidney diseases progression
制定针对醛固酮和 AGEs-RAGE 轴的治疗策略,以阻止肾脏疾病的进展
  • 批准号:
    23K15240
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    2023
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    $ 8.27万
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    Grant-in-Aid for Early-Career Scientists
Processivity and Catalytic Mechanism of Aldosterone Synthase
醛固酮合酶的持续合成能力和催化机制
  • 批准号:
    10600520
  • 财政年份:
    2023
  • 资助金额:
    $ 8.27万
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Aldosterone/mineralocorticoid receptor responses to biologic sex and salt intake: Role of Lysine Specific Demethylase 1 (LSD1)
醛固酮/盐皮质激素受体对生物性别和盐摄入量的反应:赖氨酸特异性脱甲基酶 1 (LSD1) 的作用
  • 批准号:
    10930190
  • 财政年份:
    2023
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Development of a CYP11B2 probe for imaging aldosterone-producing adenomas with high sensitivity.
开发用于高灵敏度对产生醛固酮的腺瘤进行成像的 CYP11B2 探针。
  • 批准号:
    23H02850
  • 财政年份:
    2023
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    $ 8.27万
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    Grant-in-Aid for Scientific Research (B)
Aldosterone blockade for Health Improvement Evaluation in End-stage kidney disease: Extension
醛固酮阻断用于终末期肾病健康改善评估:延伸
  • 批准号:
    461992
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    Operating Grants
Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure
利钠肽-肾素-血管紧张素-醛固酮系统节律轴与夜间血压
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    10545747
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    2022
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    $ 8.27万
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Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure
利钠肽-肾素-血管紧张素-醛固酮系统节律轴与夜间血压
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    10342142
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Role of Renin-Angiotensin-Aldosterone System during sarcoidosis granuloma formation
肾素-血管紧张素-醛固酮系统在结节病肉芽肿形成过程中的作用
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Association between excessive salt intake and brain renin-angiotensin-aldosterone system in obesity.
肥胖中过量盐摄入与脑肾素-血管紧张素-醛固酮系统之间的关联。
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