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% 的人在几十年内进展为甲状腺功能衰竭，表现为甲状腺功能低下（甲状腺功能减退症）。在显微镜下观察时，甲状腺细胞被炎症淋巴细胞白细胞逐渐破坏，其目标是破坏甲状腺激素产生细胞。一旦发现甲状腺功能低下，标准治疗方法是使用左旋甲状腺素片替代甲状腺激素。然而，约 10% 的患者对标准左旋甲状腺素治疗仍不满意，通常会出现疲劳、肌肉疼痛和通常被称为“脑雾”的认知症状。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。这提出了一种可能性，即甲状腺炎症本身，而不是随之而来的激素缺乏，是导致甲状腺功能减退患者残留症状的原因。我们将对一种名为霉酚酸酯的免疫抑制剂/抗炎药物进行双盲、随机对照试验，该药物会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女性将接受为期 16 周的试验，其中 30 名服用活性霉酚酸酯，18 名服用安慰剂。主要结果测量是细针抽吸实验治疗前后采集的甲状腺样本中炎症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”炎症标记物、细胞因子测定以及通过 FDG-PET 对甲状腺炎症细胞活性进行功能成像。这将证明霉酚酸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较差的生活质量。麦考酚酯现在是一种廉价药物，如果成功，这种治疗可以改善英国约 100,000 名患有桥本甲状腺炎且在传统左甲状腺素治疗期间症状持续的工作年龄女性的健康。