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[抗甲状腺药物治疗的理论方面]

[Theoretical aspects of the treatment with antithyroid drugs].

作者信息

Orgiazzi J, Millot L

机构信息

Service de Médecine Interne, Centre Hospitalier Lyon Sud, Pierre Bénite.

出版信息

Ann Endocrinol (Paris). 1994;55(1):1-5.

PMID:7528484
Abstract

Antithyroid drugs (thionamides such as carbimazole and its active metabolite methimazole, and propyl thiouracile) are taken up by the thyroid gland just as the other anions similar to iodide (perchlorate, thiocyanate, pertechnetate). Their target is the thyroid peroxidase. They block the iodation of tyrosine residues and the coupling of iodotyrosines into iodothyronines. However, beyond the inhibition of thyroid hormone synthesis, antithyroid drugs appear to have the capacity of interfering with the immunological abnormalities involved in Graves' hyperthyroidism: they cure 50% of the patients provided they are maintained for at least 12 months and they significantly decrease the titers of antithyroid antibodies in most of the patients. Potential immunomodulatory effects of antithyroid drugs seem to involve thyroid depletion of iodine which might reduce antigen expression, and scavenging of reactive free radicals generated from oxygen and/or iodide during peroxidation. A direct toxic effect of thionamides on immuno-competent cells seems unlikely. Whatever the mechanisms, more accurate elucidation of the immunomodulatory action of antithyroid drugs might contribute to a better understanding of the thyroid-immune derangements involved in the initiation or perpetuation of Graves' hyperthyroidism.

摘要

抗甲状腺药物(如卡比马唑及其活性代谢产物甲巯咪唑等硫代酰胺类药物,以及丙硫氧嘧啶)与其他类似碘化物的阴离子(高氯酸盐、硫氰酸盐、锝酸盐)一样被甲状腺摄取。它们的作用靶点是甲状腺过氧化物酶。它们会阻断酪氨酸残基的碘化以及碘酪氨酸偶联形成甲状腺素。然而,除了抑制甲状腺激素合成外,抗甲状腺药物似乎还具有干扰格雷夫斯病甲亢所涉及的免疫异常的能力:如果持续用药至少12个月,它们能治愈50%的患者,并且能显著降低大多数患者的抗甲状腺抗体滴度。抗甲状腺药物潜在的免疫调节作用似乎涉及甲状腺碘的耗竭,这可能会减少抗原表达,以及清除过氧化过程中由氧和/或碘产生的活性自由基。硫代酰胺类药物对免疫活性细胞的直接毒性作用似乎不太可能。无论机制如何,更准确地阐明抗甲状腺药物的免疫调节作用可能有助于更好地理解格雷夫斯病甲亢发生或持续过程中涉及的甲状腺免疫紊乱。

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