【作者】 桑仲娜；

【导师】 张万起； 吴蕴棠；

【作者基本信息】 天津医科大学 ， 营养与食品卫生学， 2006， 硕士

【摘要】 碘是人体必需的微量元素,它是合成甲状腺激素重要的原料。碘是通过甲状腺激素发挥代谢和发育（体格发育和脑发育）的调节作用。长期碘摄入不足会造成以脑发育障碍为主要特征的碘缺乏病（Iodine Deficiency Disorders,IDD）。碘是具有毒性的,长期碘摄入过量也会导致碘过多病（Iodine Excess Disorders,IED）。为防治IDD,中国政府从1996年起在全国范围内实行全民普遍食盐加碘（Universal Salt Iodization,USI）,IDD得到了有效的控制。但随着中国居民碘摄入量的增加,居民碘营养水平的提高,部分地区临床甲状腺疾病的发病率呈现显并增加的趋势。中国目前一些地区（3000～5000万人口）由于生存环境中碘过多,居民摄入的碘过多,已构成公共卫生问题。所以在防治IDD的今天,我们要有一个适宜的补碘剂量,在提高人口素质的同时,避免造成人群的高碘摄入及其可能诱发的危害。对于高碘所造成的公共卫生问题其预防和控制策略是限制人群的高碘摄入。而采取防治措施的首要问题就是在碘摄入量达到何种水平会引起人体的功能变化,即碘的可耐受的最高摄入量（Tolerable upper intake levels,UL）。本课题从探讨解决上述问题的角度出发,选择健康志愿者,随机分为7组,每组分别接受不同剂量的碘。通过7组人群甲状腺激素水平等相关指标的比较,观察不同碘补充水平对甲状腺功能的影响,探讨成人安全的碘接触水平。方法本研究中征集了240名志愿者,对其进行甲状腺过氧化物酶抗体（thyroidpcroxidase antibody,TPOAb）和甲状腺球蛋白抗体（thyroglobulin antibody,TGAb）)的检查,排除了16名抗体阳性者。对剩余人群进行血清甲状腺激素水平,敏感促甲状腺激素（sensitive thyroid stimulating hormone sTSH）以及尿碘（urinary idoine,UI）的测定。依据上述检查结果,最终确定161名甲状腺功能正常的健康成人作为调查对象,年龄在22.54±2.65岁。其中男性85人,女性76人。将被调查者随机分为7组,采取连续4周口服补充碘剂,每组口服不同剂量水平的碘剂。即A组500μg、B组750μg、C组1000μg、D组1250μg,E组1500μg,F组1750μg,G组2000μg。于实验前、实验第2周以及实验结束时分别采集志愿者空腹血、尿。采用化学发光法检测血清中各种激素水平(游离T₃（free T₃.FT3）、游离T₄（free T₄.FT4）、sTSH;采用放免法（immunoradiometriassay,IRMA）测定激素水平和抗体水平（三碘甲腺原氨酸（triiodothyronine,T3）、四碘甲腺原氨酸（thyroxine,T4）、甲状腺过氧化物酶抗体（thyroidperoxidase antibody,TPOAb）和甲状腺球蛋白抗体（thyroglobulin antibody,TGAb））;采用砷铈氧化还原法测定尿碘水平。测定志愿者的甲状腺体积。对被调查者进行为期7天的膳食调查。采集天津市市售食物、饮用水样品以及食盐样品,测定其碘含量。调查结果及实验室数据全部输入数据库,采用SPSS软件进行统计分析。结果1.被调查人群碘营养充足,尿碘中位数在272.25μg/L;人均膳食碘日摄入量在338.78～351.30μg范围内:各组人群的甲状腺激素水平、甲状腺体积均在正常值范围内:TPOAb和TGAb均为阴性。2.与补充碘剂前相比,补碘后各组人群尿碘水平明显增加（p＜0.05）:甲状腺体积减小,女性减小比较明显（p＜0.05）;血清FT4呈轻度下降趋势,至1500μg剂量组时,血清FT4在正常值范围内明显下降（p＜0.05）;血清FT3在正常值范围内呈现下降趋势,但变化不明显（p＞0.05）。各组人群在补充碘剂2周后血清sTSH明显上升,与补碘前相比增加近1倍多,至4周后增加近2倍多。补碘前后有统计学差异（p＜0.05）。各剂量组间血清sTSH变化幅度相同（p＞0.05）。在补充500μg碘剂量组,人群甲状腺激素水平在正常值范围内的情况下,血清sTSH水平升高。部分人群（15%）血清sTSH水平超出正常值上限,出现了亚临床甲状腺功能减退。3.正常人群补充500～2000μg碘剂2周后,各组人群中均发现抗体阳性者。4周后,500μg、750μg剂量组人群TPOAb阳性率保持不变,TPOAb的阳性率在1750μg剂量组稍有下降,部分人群恢复正常,其余各组的阳性率升高。补充碘剂4周后各剂量组抗体阳性者的血清FT4、血清FT3水平均在正常值范围内。500μg～1250μg四组血清sTSH水平明显升高,抗体阳性人群中血清sTSH＞5.0UI/ml的发生率分别为10.74%、11.74%、9.86%、12.86%。4.正常人群补充500μg～2000μg剂量的碘2周后会出现亚临床甲减的发生。500μg剂量组人群亚临床甲减的发病率较低（15.00%）且稳定不变,1750μg组4周后的发病率下降,部分人群甲状腺功能恢复正常。其余各组的亚临床甲减的发病率随着补充碘剂时间的延长,人群呈现发病率上升的趋势。各剂量组的发病率在28.00%～47.37%之间。各剂量组未见临床甲减患者。5.在停止补碘3个月后,复查各组部分亚甲减病人,其甲状腺激素、抗体水平及sTSH水平均恢复正常结论1.被调查人群尿碘中位数为272.25μg/L,人群碘营养充足,说明现行碘盐浓度是安全的。2.血清FT4对高剂量碘敏感,正常人群在补充1500μg以上碘剂时,其他激素水平无明显变化,血清FT4水平下降明显,是高碘的效应表现。3.正常人群在接触500～2000μg碘摄入量时主要造成以亚临床甲状腺功能减退为主（血清sTSH＞5μUI/ml,血清FT4＞10.3pmol/L）的甲状腺功能异常,但未见临床甲减。4.碘营养充足人群在接触高剂量碘补充剂时引发自身免疫性甲状腺疾病的危险性增加。5.甲状腺抗体阳性者可能造成甲状腺功能异常。6.人群中存在着具有自身免疫遗传倾向但TPOAb为阴性者,高剂量的碘摄入可以使其抗体转变为阳性,提示TPOAb并非此类人群的特异性指标。7.正常人群补充500μg/d的碘即可引起亚临床甲状腺功能减退。生活在碘营养充足地区的人群每日碘的补充剂量不宜超过500μg。我们建议碘的UL的上限值应低于900μg安全的。8.正常人群在短期内（一个月）补充大剂量的碘,仅出现亚临床甲状腺功能减退,未发现甲状腺临床的损伤。3个月后复查,人群甲状腺功能恢复正常。更多还原

【Abstract】 Iodine is one of human body’s necessary micronutrients.It is one of raw materials for synthesis of thyroid hormone which plays an important role in metabolism and development(both mental and physical) of human body.Lack of iodine in our body can lead to iodine deficiency disorders(IDD),which is characterized by retarded mental and physical development.Mean while,long absorbed iodine may result in iodine excess disorders(lED).Today,after implementing Universal Salt Iodization(USI) for many years,IDD has got the valid control.With the inhabitants’ iodine level was enhanced,and it seems that the incident of thyroid diseases increases dramatically.Currently in some area(about thirty million to fifty million people) in China the existence environment iodine is excessive,and the residents are under iodine excess.It has already led to the public hygiene problem.At the time of raising the population character we want to get an adequate iodine intake to avoid the high iodine intake in the crowd and the harm of iodine excess during the process of amending iodine deficiency.The prevented form and strategy is to limit the excessive iodine intake in the people.The important problem of the prevention is to assure what is the iodine intake level that can lead to thyroid dysfunction. The level is called tolerable upper intake level(UL) of iodine.In order to solve the question we choose the healthy volunteers who were divided into seven groups,each group accepted a quantity of iodine respectively. We took advantage of the advanced diagnostic assays to screen for the thyroid hormone and related index to comprise the changes at each group and studied the safe iodine intake level in adults.MethodsAt the result of the physical examination,the thyroid gland antibody examination and urine examination we adopted one hundred and sixty-one people as the objects who were randomly divided in to seven groups.Each group was randomly assigned to receive 500, 750,1000,1250,1500,and 2000 micrograms iodide oral doses/day for four weeks.Blood and urine samples during morning fast were obtained on weeks 0,2 and 4.We used CLIA to measure sTSH,FT3,FT4 and used IRMA to measure T3,T4,TPOAb and TGAb.Urinary iodine was evaluated.Thyroid ultrasounds were also done to the volunteers.The dietary survey was done by recording method to collect food consumption data for 7 days.We also measured the iodine amount in the drinking water,food and iodinized salt.All the investigation data and examination data were input into the database,and used SPSS software to analysis them.Results1.The iodine intake of volunteers was sufficient.MUI was 272.25μg/L.The dietary iodine intake was 338.78～351.30μg/d.The thyroid hormone level and the thyroid volume were normal.Both TPOAb and TGAb were negative.2.We found all the iodide supplemented groups responded in the same way with a significant rise in urinary iodide excretion(p＜0.05) and in serum sTSH levels(p＜0.05),with a small decline in serum free T4 concentration at normal range(p＜0.05).No changes in FT3 were observed(p＞0.05).After 2 weeks each the iodide supplemented groups increased nearly more than one multiple in serum sTSH levels,and nearly more than two multiple after 4 weeks.No significant changes in sTSH were observed(p＞0.05) among groups.The volume of the thyroid gland became significantly decreased after 4 weeks of iodide intake, especially in female(p＜0.05).We found the thyroid hormone at the normal level and serum sTSH levels increased significantly at the 500 micrograms/day doses.Some individuals(15%) of the iodide supplemented subjects serum sTSH levels raised above the laboratory reference range and occured the subclinical hypothyroidism.3.We found some people appeared TPOAb positive in all the iodide supplemented groups after 2 weeks.After 4 weeks the TPOAb positive ratio kept the same level at the 500 micrograms/day and 750 micrograms/day doses,a small declined at the 1750 micrograms/day doses,and increased at the other iodine supplemented groups.The serum FT3,FT4 levels of the people with TPOAb positive were at the normal range.The serum sTSH levels of the people with TPOAb positive significantly increased at the 500 micrograms/day to 1250 micrograms/day doses.And the rate(sTSH＞5.0UI/ml) was respectively 10.74%、11.74%、9.86%、12.86%.4.The subclinical hypothyroidism appeared at the 500 micrograms/day to 2000 micrograms/day doses after 2 weeks.After 4 weeks the prevalence of subclinical hypothyroidism kept the same level at the 500 micrograms/day(15%),a small declined at the 1750 micrograms/day doses,and increased at the other iodine supplemented groups.The subclinical hypothyroidism prevalence at the 750～2000 micrograms/day doses was at the range of 28.00%～47.37%.No clinical hypothyroidism observed among the people during iodide administration.5.When iodide was discontinued after three months we found the thyroid hormone,sTSH and TPOAb returned to baseline levels for the subclinical hypothyroidism subjects.Conclusions1.The volunteers were under good iodine nutrition and MUI was 272.25μg/L.It showed the iodine amount in the iodinized salt was safe.2.Serum FT4 was sensitive to the excess iodine.Serum FT4 decreased significantly and other thyroid hormone at normal level at the 1500 micrograms/day doses and a further doses.3.The subclinical hypothyroidism(sTSH＞5UI/ml,FT4＞10.3pmol/L) is the main form of thyroid dysfunction at the 500～2000 micrograms/day doses.No clinical hypothyroidism observed among the people during iodide administration.4.The excessive iodine supplement can cause the risk of autoimmune thyroid disorders increased for the people with sufficient iodine nutrition. 5.Thyroid autoantibody may lead to thyroid dysfunction.6.The TPOAb of the people with the autoimmunity heredity tendency can be negative in the crowd;it can turn to be positive with high iodine intake.It hinted that TPOAb was not the particular sign of this kind of crowd.7.It can lead to subclinical hypothyroidism in the subjects at 500 micrograms/day doses.In iodine-sufficient area iodine supplemented dose was not appropriate to exceed 500 micrograms/day.We suggested The UL of iodine should below 900μg/d.8.The normal adults can’t lead to clinical thyroid dysfunction with exposure excessive iodine in short period(within 1 month).When iodide was discontinued after three months we found the thyroid function returned to baseline levels for the subclinical hypothyroidism subjects.更多还原