胺碘酮诱发的甲状腺疾病
胺碘酮为临床治疗室上性心律失常特别有效的药物,除了对心脏的作用外,因其含碘量高和抑制外周T4向T3转化,还经常引起甲状腺功能异常:胺碘酮诱导甲状腺功能减退症(AIH)及甲状腺毒症(AIT)。AIH和AIT都可在正常甲状腺或甲状腺有潜在异常的情况下发生发展。发生甲状腺功能异常的类型,部分取决于碘的摄入量。在碘充足地区AIH发生率较高,在碘缺乏地区更容易发生AIT。
大多数甲状腺功能正常者,服用胺碘酮初期(通常200mg/d),即使较高剂量(400mg/d),甲状腺功能仍可保持正常。胺碘酮治疗者进行短期(≤3个月)和长期(>3个月)的甲状腺功能变化情况及机制见表18-2[42]。
1.AIH:在接受胺碘酮治疗的AIH患者中,有亚临床状态(血清TSH水平在参考值上限至10mU/L之间,FT4水平正常)和显性状态(血清TSH>10mU/L,FT4水平降低)两种,这两种状态的AIH患病率分别高达26%和5%。胺碘酮的每日或累积剂量与AIH的发生之间没有明确的相关性。临床AIH症状与其他来源的甲状腺功能减退症并没有区别。发生了AIH时,不需要停用胺碘酮。甲减症状明显者可用左甲状腺素钠替代治疗。考虑到心血管事件的潜在风险增加,亚临床甲状腺功能减退症患者在某些情况下可能是不需要治疗的,尤其是老年人,这时AIH可暂不需治疗。
表18-2 甲状腺功能正常者使用胺碘酮的甲状腺功能变化

2.AIT:AIT有两种主要类型。Ⅰ型AIT(AIT1)是碘诱导的一种甲状腺功能亢进类型,通过自主功能甲状腺组织对碘负荷的反应,导致了过度的、不受控制的甲状腺激素生物合成,在结节性甲状腺肿或者隐匿Graves病的患者中更容易发生AIT1。Ⅱ型AIT(AIT2)是一种破坏性甲状腺炎,为胺碘酮的直接毒性作用所致,通常发生于没有潜在甲状腺疾病的患者中。混合/不确定型也被认为是患者获得AIT两种类型重叠的情况,AIT2在碘充足的地区更为普遍,也是AIT最常见的类型。两种类型的甲亢治疗方法有所不同,AIT1应尽可能停用胺碘酮,当然,胺碘酮是否停用也要视心脏病情的允许,建议根据患者的风险分级,同时考虑个体化差异,由心血管专科医师和内分泌专科医生共同决定。AIT2需使用糖皮质激素治疗,如果甲状腺功能恢复正常,即可停药随访。
综上所述,急性碘过量,由于Wolff-Chaikoff效应,多数人不会出现甲状腺功能异常;长期慢性的碘过量会导致血清TSH的升高,增加临床/亚临床甲状腺功能减退的风险。血清高TSH通过对甲状腺细胞的刺激作用,有可能增加甲状腺结节发生、增大或恶变的风险。但高碘是否有增加甲状腺恶性肿瘤的风险,仍需要更深入的研究。USI后甲状腺癌的类型发生改变,乳头状甲状腺癌的发病率及占所有甲状腺癌的比例均增加。
TIDE研究再次证明MUI 100~300μg/L是普通人群补碘安全剂量范围。这个范围已经被国际防治碘缺乏病权威组织认可。碘缺乏(MUI<100μg/L)是大部分甲状腺疾病的危险因素,碘过量的危险显著低于碘缺乏。目前我国居民的碘营养在安全范围内,甲状腺疾病的发病率都处于合理的水平,所以补碘不仅能够治疗碘缺乏病,也是降低各种甲状腺疾病的发病率所必需的措施。我们认为,今天我国的适宜的碘营养是中华人民共和国成立以来多年防治碘缺乏病(包括20年的USI)的结果。我国碘缺乏的自然本底不可能在短期改变。所以我们必须坚持科学补碘的方针,继续坚持食盐加碘的国策,监测居民碘营养变化,既要防止碘缺乏病死灰复燃,也要避免碘过量的危害,为保护国民的甲状腺健康做出我们的贡献。
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