碘营养现状及对甲状腺疾病的影响
我国自1996年实行全民食盐加碘(Universal Salt Iodization, USI),2005年达到了碘缺乏病(IDD)完全消除的目标,至今保持IDD持续消除。在此过程中经历了6年的碘过量和13年的碘超足量,并且因存在高碘水源地区,面临着碘摄入量过高带来的风险。碘过量对甲状腺功能的影响,一方面是过量的碘带来的氧化应激造成了甲状腺细胞的损伤,另一方面是碘对甲状腺细胞的抑制作用。因此碘营养水平长期处于超足量或过量,会增加自身免疫性甲状腺疾病(AITD)的患病风险和临床甲减与亚临床甲减风险。滕卫平课题组调查我国轻度碘缺乏(88μg/L)、碘超足量(214μg/L)、碘过量(634μg/L)的3个地区3 761名常住居民甲状腺患病情况,并进行了5年随访。结果显示3个地区AITD的患病率分别为0.5%、1.7%和2.8%,累积发病率为0.2%、1.0%和1.3%。碘超足量、碘过量人群与轻度碘缺乏人群相比,患病率和发病率显著升高且具有统计学意义。碘超足量与碘过量地区人群在随访中TSH异常升高的风险增加3~4倍,亚临床甲减持续不缓解的风险是轻度碘缺乏地区的8~10倍[66]。丹麦的研究中84.4%的甲减可归因于自发,其中又有95%是自身免疫导致。美国Surks等报道40~49岁的人群甲功减退归因于自身免疫的比例是67.4%,80岁以上的人群为40.5%[67]。但我国的流行病学调查却不支持自身免疫来解释大多数临床/亚临床甲减的增加,横断面调查发现,亚临床甲减患者的抗体阳性率仅有29%~40%,且临床/亚临床甲减与TSH正常人群的抗体阳性率无显著差异。在水源性高碘地区发现临床甲减患者抗体阳性率为85.71%,亚临床甲减仅有29.23%[68]。因此中国人碘致TSH升高的机制有待更多的研究,可能与易感个体对Wolff-Chaikoff效应逃逸失败、过量碘对下丘脑2型脱碘酶活性的直接抑制作用等相关。
长期的碘超足量或碘过量没有增加甲亢风险的可靠证据。但在既往碘缺乏地区补碘,会带来一过性的甲亢患病率和发病率增加。甲亢患者增加的现象在既往缺碘严重、补碘起始剂量大的地区更加明显。补碘诱发的甲亢类型,在老年人中以自主功能性甲状腺腺瘤/结节为主,在青壮年以Graves病为主。瑞士研究补碘的长期效应,发现甲亢的患病率在补碘后前2年增加了12%,但在此后4年降至补碘前的25%并维持稳定。我国甲亢发病率在补碘当年马上开始增加,2~3年达到高峰,此后6~7年下降至补碘前水平。因此提出如果食盐加碘浓度缓慢增加,虽然甲亢发病率一过性增加,从长远看可以降低发病率。有学者认为,这一现象的机制是长期碘缺乏导致甲状腺滤泡上皮细胞发生基因原位突变,形成自主功能腺瘤/结节,在碘充足时不受中枢调控,甲状腺激素合成与释放增加。
单纯甲状腺肿的患病率和发病率随尿碘浓度增加呈U形曲线变化,即碘缺乏与碘过量都增加甲状腺肿的风险,但对结节性甲状腺肿的影响还有待更多证据支持[69]。Zhao等[70]对我国实行食盐加碘政策前后的结节性甲状腺肿患病率进行Meta分析后得出结论,食盐加碘后结节性甲状腺肿的患病率有所升高。但Peterson等系统综述了21篇研究饮食与甲状腺结节相关性的文献,对2项病例对照和3项生态学研究的结果进行Meta分析,统计结果支持食盐加碘不增加甲状腺结节的发病率(RR值0.49~1.6)[69]。
目前已有大量文献探讨高碘是否增加甲状腺癌的风险,但由于混杂因素较多,使甲状腺癌患病率的可比性很低。美国、中国等地区,报告补碘后MUI增加,甲状腺癌患病率也增加[71]。丹麦和冰岛则发现MUI稳定的条件下,甲状腺癌患病率也有所增加,这可能是检测手段敏感性增加导致的。Zimmermann[72]对4项研究碘营养水平与甲状腺癌风险的病例对照研究进行Meta分析,发现高碘组的甲状腺癌风险降低(OR=0.77,P=0.068)。但是这项Meta分析纳入的研究仅以饮食估计碘营养水平,缺乏尿碘的数据。另外一个纳入31项研究碘营养水平与隐匿性甲状腺癌(Occult Thyroid Carcinoma,OTC)发生率的Meta分析,发现OTC发生率随尿碘水平升高而降低,碘过量组(3.3%)显著低于碘缺乏组(5.6%)和碘适量组(6.0%)。但这项Meta分析未纳入日本对碘过量人群的研究,在日本高碘人群中OTC发现率高达22.4%。甲状腺癌的死亡率由于早诊断、早治疗和放射碘清甲的应用有所降低,也给研究碘对甲状腺癌死亡率的影响带来了偏倚。高碘使甲状腺恶性肿瘤的类型发生改变,乳头状癌的发病率和比例均增加。甲状腺乳头状癌的风险和BRAFV600E突变相关,而BRAFV600E突变是可受碘摄入量等环境因素影响的,Guan[73]等检测不同碘营养水平的1 032名甲状腺乳头状癌患者BRAF突变的发生率,发现碘超足量地区发生BRAF突变的风险是碘适量地区的1.97倍。Zimmerman等综述10项对比补碘前后乳头状癌与滤泡癌比值的研究,发现在碘适量地区这个比值为1.6~3.7,在高碘地区则上升至3.4~6.5。
少数个体会发生含碘造影剂或海鲜食品过敏的情况,因此人群中会产生这些个体是对碘本身过敏碘误解,甚至认为海鲜过敏是由于海鲜富含碘元素。但事实上没有任何证据表明过敏源是碘元素,怀疑碘元素或单纯碘盐导致过敏也缺乏理论依据。对多种食物过敏、有哮喘等过敏病史的个体,对含碘造影剂更易发生过敏[74]。
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