Baretić Maja, Balić Stjepan, Gudelj Goran
Department of Endocrinology, University Department of Medicine, Zagreb University Hospital Center, Zagreb, Croatia.
Acta Clin Croat. 2010 Mar;49(1):67-71.
Myasthenia gravis and Graves' disease are two autoimmune diseases with a similar mechanism, both having circulating organ autoantibodies and cell specific autoantibodies. It is not unusual for these diseases to occur together. There is a large body of data proving that antithyroid drugs such as methimazole and propylthiouracil have an immunomodulatory effect in addition to their thyrosuppressant action. This case report describes a 34-year-old woman hospitalized for just diagnosed myasthenic crisis (Osserman IV). She had a prior history of hyperthyroidism and treatment with methimazole was initiated. However, improvement in thyroid disease led to the burst of myasthenia. The phenomenon described as worsening of one disease while improving the other, the so-called 'see-saw' relationship, occurred in this case. The question is whether antithyroid drugs improve hyperthyroidism while unveiling or worsening myasthenia. Is the 'see-saw' relationship actually a therapeutic side effect of antithyroid drug? The proposed mechanism of methimazole action is intracellular: it lowers the level of proliferating cell nuclear antigen (PCNA). PCNA promotes selective apoptosis in some T lymphocyte clones. In this way, CD4+CD25+ regulatory T cells might 'skip' immune self-tolerance and autoantibodies against acetylcholine receptor may occur. Do antithyroid drugs actually create an immune 'thymic surrounding'?
重症肌无力和格雷夫斯病是两种机制相似的自身免疫性疾病,均存在循环器官自身抗体和细胞特异性自身抗体。这些疾病同时发生并不罕见。有大量数据证明,甲巯咪唑和丙硫氧嘧啶等抗甲状腺药物除具有甲状腺抑制作用外,还具有免疫调节作用。本病例报告描述了一名34岁女性,因刚诊断出的重症肌无力危象( Osserman IV型)住院。她既往有甲状腺功能亢进病史,已开始使用甲巯咪唑治疗。然而,甲状腺疾病的改善导致了重症肌无力的发作。在该病例中出现了一种疾病改善而另一种疾病恶化的现象,即所谓的“跷跷板”关系。问题在于抗甲状腺药物在改善甲状腺功能亢进的同时,是否会引发或加重重症肌无力。这种“跷跷板”关系实际上是抗甲状腺药物的治疗副作用吗?甲巯咪唑的作用机制是在细胞内:它降低增殖细胞核抗原(PCNA)的水平。PCNA促进某些T淋巴细胞克隆的选择性凋亡。通过这种方式,CD4 + CD25 +调节性T细胞可能会“跳过”免疫自身耐受性,从而可能产生针对乙酰胆碱受体的自身抗体。抗甲状腺药物实际上会造成免疫“胸腺环境”吗?