Does chronic thyroid inflammation explain persistent symptoms in Hashimoto thyroiditis?

慢性甲状腺炎症是否可以解释桥本甲状腺炎的持续症状？

• 批准号: MR/Z503617/1
• 负责人: Simon Pearce
• 金额: $ 165.32万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FZ503617%2F1
• 关键词: Does; chronic; thyroid; inflammation; explain

Around 10% of the female population have Hashimoto thyroiditis as judged by positive thyroid peroxidase antibodies in their blood, and approximately 50% of these people progress to thyroid failure, manifest as thyroid underactivity (hypothyroidism) over several decades. When seen under a microscope, there is progressive destruction of the thyroid cells by inflammatory lymphocyte white blood cells, which are targeted to destroy the thyroid hormone producing cells. Once thyroid underactivity is recognised, the standard treatment is thyroid hormone replacement using levothyroxine tablets. However, about 10% of patients remain dissatisfied with standard levothyroxine treatment, typically leaving fatigue, muscle aches and cognitive symptoms often referred to as 'brain fog'. Multiple randomised clinical trials have shown that improvement in the blood thyroid hormone levels or adding tri-ioidothyronine (T3, the active thyroid hormone) does not help these people. This raises the possibility that the thyroid inflammation itself rather than the consequent hormonal deficiency is responsible for the residual symptoms in hypothyroid patients. We will perform a double blind, randomised controlled trial of an immunosuppressant/ anti-inflammatory drug called mycophenolate, which will kill off the lymphocytes in the thyroid and reduce the thyroid inflammation. Forty-eight women with Hashimoto thyroiditis will be in the trial for 16 weeks, with thirty taking the active mycophenolate and eighteen taking placebo. The primary outcome measurement will be the change in the number of inflammatory lymphocytes in thyroid samples taken before and after the experimental treatment by fine-needle aspiration. We will also perform a multimodal investigation including fatigue, other symptom and quality of life questionnaires, cognitive tests, blood 'acute-phase' inflammation markers, cytokine assays and functional imaging of the activity of inflammatory cells in the thyroid by FDG-PET. This will demonstrate whether thyroid inflammation can be reduced by mycophenolate and whether this will improve the persistent symptoms and poor QoL for these patients. Mycophenolate is now an inexpensive drug and if successful, this treatment could improve the health of around 100,000 working-age women in the UK who have Hashimoto thyroiditis and who have persistent symptoms during conventional levothyroxine treatment.

根据血液中甲状腺过氧化物酶抗体阳性判断，约10%的女性患有桥本甲状腺炎，其中约50%的人进展为甲状腺功能衰竭，表现为甲状腺功能减退（甲状腺功能减退）数十年。当在显微镜下观察时，炎症淋巴细胞白色血细胞对甲状腺细胞进行性破坏，其目标是破坏甲状腺激素产生细胞。一旦确认甲状腺功能低下，标准治疗是使用左旋甲状腺素片进行甲状腺激素替代。然而，大约10%的患者仍然不满意标准的左旋甲状腺素治疗，通常会留下疲劳，肌肉疼痛和认知症状，通常被称为“脑雾”。多项随机临床试验表明，改善血液甲状腺激素水平或添加三碘甲状腺原氨酸（T3，活性甲状腺激素）对这些人没有帮助。这就提出了甲状腺炎症本身而不是随之而来的激素缺乏是甲状腺功能减退患者残留症状的原因的可能性。我们将对一种名为麦考酚酸的免疫抑制剂/抗炎药进行双盲、随机对照试验，该药物将杀死甲状腺中的淋巴细胞并减轻甲状腺炎症。48名患有桥本甲状腺炎的妇女将参加为期16周的试验，其中30名服用活性麦考酚酯，18名服用安慰剂。主要结果测量将是通过细针抽吸在实验性治疗前后采集的甲状腺样品中炎性淋巴细胞数量的变化。我们还将进行多模式调查，包括疲劳，其他症状和生活质量问卷，认知测试，血液“急性期”炎症标志物，细胞因子测定和FDG-PET甲状腺炎症细胞活性的功能成像。这将证明麦考酚酯是否可以减轻甲状腺炎症，以及这是否会改善这些患者的持续症状和不良生活质量。霉酚酸酯现在是一种廉价的药物，如果成功，这种治疗可以改善英国约10万名患有桥本甲状腺炎的工作年龄妇女的健康，这些妇女在常规左旋甲状腺素治疗期间症状持续存在。