碘过量对不同人群甲状腺功能影响及成人碘安全摄入量的研究
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摘要
目的1.通过对高碘和适碘地区的成人、儿童、孕妇及新生儿碘营养状况及甲状腺功能的调查,明确碘过量对目标人群甲状腺功能及甲状腺自身免疫功能的影响。2.探讨我国成人的碘的安全摄入量,为修订国人碘可耐受最高摄入量(UL)提供数据参考。
方法1.根据纳入标准选择高碘和适碘地区的成人、儿童、孕妇及新生儿为研究对象,采集调查对象空腹中段晨尿、空腹静脉血,新生儿采集出生时脐带血,将血样静置离心后收集血清。采集被调查地区饮用水及食盐样品。2.招募甲状腺功能正常的健康志愿者共95人(男55人,女40人)。将95名志愿者按性别、年龄分层后随机分为5组,连续服用碘补充剂4周,每组每人每天分别服用碘补充齐(?)0μg/d、100μg/d、200μg/d、300μg/d、400μg/d。于实验初期(第0周)、实验中期(第2周末)、实验末期(第4周末)分别采集志愿者晨尿、空腹晨血并测量志愿者甲状腺体积。实验结束后3个月(3m)及9个月(9m)时对部分志愿者进行随访。采用24小时回顾法对所有志愿者进行7日膳食调查。采集志愿者饮用水水样、食盐样品及部分膳食样品。采用化学免疫发光法测定血清游离三碘甲腺原氨酸(Free Triiodothyronine, FT3)、游离甲状腺素(Free Thyroxine, FT4)及灵敏促甲状腺激素(Sensitive thyroid Stimulating Hormone, sTSH)水平；采用放射免疫法测定血清甲状腺过氧化物酶抗体(Thyroid Peroxidase Antibody, TPOAb)和甲状腺球蛋白抗体(Thyroglobulin Antibody, TGAb);采用砷铈催化分光光度法测定尿碘、水碘浓度。采用直接滴定法测定食盐碘浓度。采用电位滴定法测定膳食食盐含量。
结果1.碘过量地区成人、儿童及孕妇的尿碘中位数均高于适碘地区的相应人群(1152.01vs185.20μg/L;1034.06vs120.95μg/L;1240.70vs217.06μg/L;P<0.05)。2.碘过量地区成人、儿童及孕妇的甲状腺疾病的患病率均高于适碘地区的相应人群(20.6%vs10.3%；11.9%vs1.3%；22.9%vs2.3%；P<0.05)。亚临床甲状腺功能减退(亚甲减)为碘过量地区成人、儿童及孕妇甲状腺疾病的主要形式(13.6%,6.5%,20%)。高碘地区新生儿sTSH>10μIU/ml的比率(21%)及>20μIU/ml的比率(7.6%)明显高于适碘地区新生儿(1.1%,1.1%)(P<0.05)。3.除碘过量地区儿童的TGAb阳性率和TPOAb阳性率均高于适碘地区(χ21=5.097,P1=0.024；χ22=10.063,P2=0.002)外,两地区成人、孕妇及新生儿TGAb阳性率和TPOAb阳性率均无差异。但成人和儿童中女性的甲状腺自身抗体的阳性率高于男性。(成人：TGAb:χ21=19.174,P1=0.000;χ22=11.616,P2=0.001；TPOAb:χ21=10.015, P1=0.002;χ22=6.651,P2=0.010.儿童：TGAb:χ21=4.592,P1=0.032;χ22=4.620, P2=0.032；TPOAb:χ211=1.510,P1=0.219;χ22=7.468,P2=0.006)。4.高碘地区甲状腺功能正常的成人、儿童血清sTSH水平高于适碘地区的成人和儿童(P<0.05)。5.两地区患有甲状腺疾病的成人和儿童的甲状腺自身抗体的阳性率大于甲状腺功能正常者(P<0.05)。高碘时患有亚甲减的儿童抗体较甲功正常的儿童升高明显(TPOAb:25%vs5.2%;TGAb:20.8%vs5.2%)(P<0.05),且儿童甲状腺自身抗体阳性时血清TSH水平大于阴性。适碘地区成人亚甲减的抗体水平高于高碘地区(TPOAb:57.1%vs15.4%;TGAb:42.9%vs12.8%)(P<0.05).6.高碘地区TGAb阳性的孕妇血清sTSH水平高于适碘地区(3.96μIU/ml Vs1.10μIU/ml)(P<0.05)。7.高碘和适碘地区孕妇与新生儿血清sTSH水平正相关(r=0.278,P=0.000；r=0.202,P=0.008),孕妇与新生儿的甲状腺自身抗体正相关。8.患高碘地区有亚甲减的孕妇,新生儿TSH>10μIU/ml (?)匕例大于适碘地区(P<0.05)。甲状腺自身抗体有升高的趋势,但无统计学差异(P>0.05)。9.高碘地区甲状腺自身抗体阳性的孕妇,新生儿血清TSH水平大于适碘地区(TPOAb:7.53μIU/ml vs5.09μIU/ml;TGAb:8.38μIU/ml vs5.86μIU/ml)(P<0.05)。10.与补碘前相比,各组志愿者补碘4周后血清FT4、FT3及sTSH水平有所升高(P<0.05),血清FT4、FT3水平始终处于正常值范围。300μg/d、400μg/d组各出现一名亚甲减患者,发病率为5.3%。补碘结束3个月后进行随访,300μg/d组亚甲减患者甲状腺功能恢复正常,停止高碘暴露9个月后对志愿者进行随访,400μg/d亚甲减患者血清sTSH水平降至临界值。11.补碘前后所有志愿者血清TGAb、TPOAb差异均无统计学意义(P>0.05)。
结论1.碘过量导致人群甲状腺疾病发病的危险性增加,尤其以亚甲减最为明显。高碘地区亚甲减的发病原因可能是高碘和甲状腺自身免疫损伤的联合作用,适碘地区甲状腺自身免疫损伤可能是导致亚甲减发病的主要原因。2.长期高碘暴露人群其甲状腺自身免疫增强,但由高碘导致的孕妇甲状腺免疫增强对自身和所产新生儿甲状腺功能的影响较大。3.甲状腺功能正常的成人和儿童长期高碘摄入,会导致其sTSH水平向高位偏移,甲状腺自身免疫增强。4.甲状腺自身免疫损伤女性较为明显。5.孕妇和新生儿的甲状腺自身免疫水平密切相关,孕妇的甲状腺功能对新生儿的甲功有直接影响。6.短期(1个月)碘过量摄入会导致甲状腺功能正常的成人出现亚甲减,停止碘暴露后,甲状腺功能逐渐恢复。7.对于甲状腺功能正常的成人来说,碘安全摄入量低于700μg/d是安全的。
Objective1.To determine the effect of iodine excess on thyroid function and autoimmune thyroid function by the survey of the iodine nutritional status and thyroid function of adults, children, pregnant women and newborn.2.To explore the safety iodine intake of adult and provide data reference for iodine UL.
Method1.According to the inclusion criteria adults, children, pregnant women and newborns were selected from excessive iodine intake area and sufficient iodine intake area. Morning urine and blood samples were obtained from all the subjects. Serum was stored at-80℃until assayed. Water and salt samples were collected to determine the iodine content.2.95healthy volunteers (man55, woman40) were divided into5groups with varying iodine supplement doses ranging from0to400μg for4weeks. Fasting blood and urine samples were obtained in the morning on weeks0,2, and4, and the blood samples were stored at-80℃until they were analyzed. Thyroid ultrasounds utilizing a7.5MHz/40mm probe were performed by trained specialists. A part of subjects were followed up at third month and ninth month after iodine withdrawal. A seven consecutive24-hour dietary recall was used to record food they consumed for all subjects.Drinking water and salt samples were collected to determine the iodine content. Serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and sensitive thyroid stimulating hormone (sTSH) were measured in all subjects with automated chemiluminescent immunoassay, the diagnostic kits from the Bayer Company. Serum levels of Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were measured with RIA. Urinary iodine and water iodine content were determined with the use of the colorimetric coercion-arsenious acid ash method. Salt iodine was determined with Direct titration; salt in food with Electric potential titration.
Results1. The median urinary iodine of adults, children and pregnant women in excessive iodine areas were higher than the corresponding people in adequate iodine areas.(1152.01vsl85.20μg/L;1034.06vs120.95μg/L;1240.70vs217.06μg/L; P<0.05).2.The prevalence of thyroid diseases among the adults, children and pregnant women in iodine excess area were higher than the corresponding population iodine adequate areas (20.6%vs10.3%;11.9%vsl.3%;22.9%vs2.3%; P<0.05) Subclinical hypothyroidism was the main form of thyroid diseases among adults, children and pregnant women in excessive iodine areas(13.6%,6.5%,20%). The rate of sTSH>10μIU/ml (21%) and>20μIU/ml rate (7.6%) of neonate in excessive iodine areas were higher than the corresponding people in adequate iodine areas (1.1%,1.1%)(P <0.05).3. In addition to TGAb and TPOAb positive rate of children in excessive iodine areas were higher than iodine adequate regions (P<0.05), there were no differences in positive rate of TPOAb and TGAb of adults, pregnant women and newborns between the two areas. However, female adults and children in the thyroid antibodies positive rate were higher than in men(P<0.05).4. The serum sTSH concentration of adults and children with normal thyroid function in excessive iodine areas was higher than the corresponding people in adequate iodine areas(P<0.05).5.In the two areas the positive thyroid autoimmune antibodies rate of adults and children with thyroid disease were higher than the corresponding people with normal thyroid function(P<0.05). In excessive iodine areas the positive thyroid autoimmune antibodies rate of the children with subclinical hypothyroidism increased significantly than those who with normal thyroid function (TPOAb:25%vs5.2%; TGAb:20.8%vs5.2%)(P<0.05), and the serum TSH concentration of children with positive thyroid autoimmune antibodies was higher than children with negative thyroid autoimmune antibodies. In adequate iodine areas the positive thyroid autoimmune antibodies rate of adults with subclinical hypothyroidism was higher than the corresponding people in excessive iodine areas (TPOAb:57.1%vs15.4%; TGAb:42.9%vs12.8%)(P <0.05).6.The serum sTSH concentration of pregnant women with positive TGAb in excessive iodine areas was higher than the corresponding people in adequate iodine areas (3.96μIU/ml vs1.10μIU/ml)(P<0.05).7.In the two areas the serum sTSH concentration showed positive correlation between the pregnant women and neonate(r=0.278, P=0.000; r=0.202, P=0.008), thyroid autoimmune antibodies showed the same change correlation between the pregnant women and neonate.8. In excessive iodine areas the rate of serum sTSH>10μIU/ml of pregnant women with subclinical hypothyroidism was higher than the corresponding people in adequate iodine areas (P<0.05), thyroid autoimmune antibodies of pregnant women with subclinical hypothyroidism had increased tendency, but no significant difference (P>0.05).9. The serum sTSH concentration of neonate whose mother with positive thyroid antibodies was higher than the corresponding people in adequate iodine areas (TPOAb:7.53μIU/mlvs5.09μIU/ml;TGAb:8.38μIU/mlvs5.86μIU/ml)(P<0.05).10.The re was a increase in FT4, FT3and sTSH concentrations but serum FT4, FT3remained within normal range. One person displayed subclinical hypothyroidism in group400μg and300μg at the4th week (5.3%,5.3%). One additional subject in group300μg had subclinical hypothyroidism at week2, but it disappeared at the end of the trial. After9month, the patient's sTSH in group400μg/d decreased to critical value.11. TGAb and TPOAb had no significant change during iodine asministration.
Conclusions1. Iodine excess increased the risk of thyroid diseases; the subclinical hypothyroidism was most obvious. In excessive iodine areas the main reason of subclinical hypothyroidism were the combined effects of high iodine and thyroid autoimmunity injury, however, in adequate areas thyroid autoimmunity damage may led to the subclinical hypothyroidism.2. The thyroid autoimmunity increased among the people with long-term high iodine exposure.It was greater effect of neonate whose mother with positive thyroid antibodies than the corresponding people in adequate iodine areas.3. Long-term excessive iodine intake of adults and children with normal thyroid function led to high sTSH concentration, and enhanced thyroid autoimmunity.
4. Women showed more apparent in thyroid autoimmunity injury than men.5.There was a closed relation of thyroid autoimmunity between pregnant women and newborns, thyroid function of newborns was impacted directly by mothers.6. People with normal thyroid function appeared subclinical hypothyroidism with short-term (1month) excessive iodine intake, and the people returned to be normal after withdraw iodine supplement.7. For95%people the daily intake should not exceed700p,g/day.
方法1.根据纳入标准选择高碘和适碘地区的成人、儿童、孕妇及新生儿为研究对象,采集调查对象空腹中段晨尿、空腹静脉血,新生儿采集出生时脐带血,将血样静置离心后收集血清。采集被调查地区饮用水及食盐样品。2.招募甲状腺功能正常的健康志愿者共95人(男55人,女40人)。将95名志愿者按性别、年龄分层后随机分为5组,连续服用碘补充剂4周,每组每人每天分别服用碘补充齐(?)0μg/d、100μg/d、200μg/d、300μg/d、400μg/d。于实验初期(第0周)、实验中期(第2周末)、实验末期(第4周末)分别采集志愿者晨尿、空腹晨血并测量志愿者甲状腺体积。实验结束后3个月(3m)及9个月(9m)时对部分志愿者进行随访。采用24小时回顾法对所有志愿者进行7日膳食调查。采集志愿者饮用水水样、食盐样品及部分膳食样品。采用化学免疫发光法测定血清游离三碘甲腺原氨酸(Free Triiodothyronine, FT3)、游离甲状腺素(Free Thyroxine, FT4)及灵敏促甲状腺激素(Sensitive thyroid Stimulating Hormone, sTSH)水平；采用放射免疫法测定血清甲状腺过氧化物酶抗体(Thyroid Peroxidase Antibody, TPOAb)和甲状腺球蛋白抗体(Thyroglobulin Antibody, TGAb);采用砷铈催化分光光度法测定尿碘、水碘浓度。采用直接滴定法测定食盐碘浓度。采用电位滴定法测定膳食食盐含量。
结果1.碘过量地区成人、儿童及孕妇的尿碘中位数均高于适碘地区的相应人群(1152.01vs185.20μg/L;1034.06vs120.95μg/L;1240.70vs217.06μg/L;P<0.05)。2.碘过量地区成人、儿童及孕妇的甲状腺疾病的患病率均高于适碘地区的相应人群(20.6%vs10.3%；11.9%vs1.3%；22.9%vs2.3%；P<0.05)。亚临床甲状腺功能减退(亚甲减)为碘过量地区成人、儿童及孕妇甲状腺疾病的主要形式(13.6%,6.5%,20%)。高碘地区新生儿sTSH>10μIU/ml的比率(21%)及>20μIU/ml的比率(7.6%)明显高于适碘地区新生儿(1.1%,1.1%)(P<0.05)。3.除碘过量地区儿童的TGAb阳性率和TPOAb阳性率均高于适碘地区(χ21=5.097,P1=0.024；χ22=10.063,P2=0.002)外,两地区成人、孕妇及新生儿TGAb阳性率和TPOAb阳性率均无差异。但成人和儿童中女性的甲状腺自身抗体的阳性率高于男性。(成人：TGAb:χ21=19.174,P1=0.000;χ22=11.616,P2=0.001；TPOAb:χ21=10.015, P1=0.002;χ22=6.651,P2=0.010.儿童：TGAb:χ21=4.592,P1=0.032;χ22=4.620, P2=0.032；TPOAb:χ211=1.510,P1=0.219;χ22=7.468,P2=0.006)。4.高碘地区甲状腺功能正常的成人、儿童血清sTSH水平高于适碘地区的成人和儿童(P<0.05)。5.两地区患有甲状腺疾病的成人和儿童的甲状腺自身抗体的阳性率大于甲状腺功能正常者(P<0.05)。高碘时患有亚甲减的儿童抗体较甲功正常的儿童升高明显(TPOAb:25%vs5.2%;TGAb:20.8%vs5.2%)(P<0.05),且儿童甲状腺自身抗体阳性时血清TSH水平大于阴性。适碘地区成人亚甲减的抗体水平高于高碘地区(TPOAb:57.1%vs15.4%;TGAb:42.9%vs12.8%)(P<0.05).6.高碘地区TGAb阳性的孕妇血清sTSH水平高于适碘地区(3.96μIU/ml Vs1.10μIU/ml)(P<0.05)。7.高碘和适碘地区孕妇与新生儿血清sTSH水平正相关(r=0.278,P=0.000；r=0.202,P=0.008),孕妇与新生儿的甲状腺自身抗体正相关。8.患高碘地区有亚甲减的孕妇,新生儿TSH>10μIU/ml (?)匕例大于适碘地区(P<0.05)。甲状腺自身抗体有升高的趋势,但无统计学差异(P>0.05)。9.高碘地区甲状腺自身抗体阳性的孕妇,新生儿血清TSH水平大于适碘地区(TPOAb:7.53μIU/ml vs5.09μIU/ml;TGAb:8.38μIU/ml vs5.86μIU/ml)(P<0.05)。10.与补碘前相比,各组志愿者补碘4周后血清FT4、FT3及sTSH水平有所升高(P<0.05),血清FT4、FT3水平始终处于正常值范围。300μg/d、400μg/d组各出现一名亚甲减患者,发病率为5.3%。补碘结束3个月后进行随访,300μg/d组亚甲减患者甲状腺功能恢复正常,停止高碘暴露9个月后对志愿者进行随访,400μg/d亚甲减患者血清sTSH水平降至临界值。11.补碘前后所有志愿者血清TGAb、TPOAb差异均无统计学意义(P>0.05)。
结论1.碘过量导致人群甲状腺疾病发病的危险性增加,尤其以亚甲减最为明显。高碘地区亚甲减的发病原因可能是高碘和甲状腺自身免疫损伤的联合作用,适碘地区甲状腺自身免疫损伤可能是导致亚甲减发病的主要原因。2.长期高碘暴露人群其甲状腺自身免疫增强,但由高碘导致的孕妇甲状腺免疫增强对自身和所产新生儿甲状腺功能的影响较大。3.甲状腺功能正常的成人和儿童长期高碘摄入,会导致其sTSH水平向高位偏移,甲状腺自身免疫增强。4.甲状腺自身免疫损伤女性较为明显。5.孕妇和新生儿的甲状腺自身免疫水平密切相关,孕妇的甲状腺功能对新生儿的甲功有直接影响。6.短期(1个月)碘过量摄入会导致甲状腺功能正常的成人出现亚甲减,停止碘暴露后,甲状腺功能逐渐恢复。7.对于甲状腺功能正常的成人来说,碘安全摄入量低于700μg/d是安全的。
Objective1.To determine the effect of iodine excess on thyroid function and autoimmune thyroid function by the survey of the iodine nutritional status and thyroid function of adults, children, pregnant women and newborn.2.To explore the safety iodine intake of adult and provide data reference for iodine UL.
Method1.According to the inclusion criteria adults, children, pregnant women and newborns were selected from excessive iodine intake area and sufficient iodine intake area. Morning urine and blood samples were obtained from all the subjects. Serum was stored at-80℃until assayed. Water and salt samples were collected to determine the iodine content.2.95healthy volunteers (man55, woman40) were divided into5groups with varying iodine supplement doses ranging from0to400μg for4weeks. Fasting blood and urine samples were obtained in the morning on weeks0,2, and4, and the blood samples were stored at-80℃until they were analyzed. Thyroid ultrasounds utilizing a7.5MHz/40mm probe were performed by trained specialists. A part of subjects were followed up at third month and ninth month after iodine withdrawal. A seven consecutive24-hour dietary recall was used to record food they consumed for all subjects.Drinking water and salt samples were collected to determine the iodine content. Serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and sensitive thyroid stimulating hormone (sTSH) were measured in all subjects with automated chemiluminescent immunoassay, the diagnostic kits from the Bayer Company. Serum levels of Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were measured with RIA. Urinary iodine and water iodine content were determined with the use of the colorimetric coercion-arsenious acid ash method. Salt iodine was determined with Direct titration; salt in food with Electric potential titration.
Results1. The median urinary iodine of adults, children and pregnant women in excessive iodine areas were higher than the corresponding people in adequate iodine areas.(1152.01vsl85.20μg/L;1034.06vs120.95μg/L;1240.70vs217.06μg/L; P<0.05).2.The prevalence of thyroid diseases among the adults, children and pregnant women in iodine excess area were higher than the corresponding population iodine adequate areas (20.6%vs10.3%;11.9%vsl.3%;22.9%vs2.3%; P<0.05) Subclinical hypothyroidism was the main form of thyroid diseases among adults, children and pregnant women in excessive iodine areas(13.6%,6.5%,20%). The rate of sTSH>10μIU/ml (21%) and>20μIU/ml rate (7.6%) of neonate in excessive iodine areas were higher than the corresponding people in adequate iodine areas (1.1%,1.1%)(P <0.05).3. In addition to TGAb and TPOAb positive rate of children in excessive iodine areas were higher than iodine adequate regions (P<0.05), there were no differences in positive rate of TPOAb and TGAb of adults, pregnant women and newborns between the two areas. However, female adults and children in the thyroid antibodies positive rate were higher than in men(P<0.05).4. The serum sTSH concentration of adults and children with normal thyroid function in excessive iodine areas was higher than the corresponding people in adequate iodine areas(P<0.05).5.In the two areas the positive thyroid autoimmune antibodies rate of adults and children with thyroid disease were higher than the corresponding people with normal thyroid function(P<0.05). In excessive iodine areas the positive thyroid autoimmune antibodies rate of the children with subclinical hypothyroidism increased significantly than those who with normal thyroid function (TPOAb:25%vs5.2%; TGAb:20.8%vs5.2%)(P<0.05), and the serum TSH concentration of children with positive thyroid autoimmune antibodies was higher than children with negative thyroid autoimmune antibodies. In adequate iodine areas the positive thyroid autoimmune antibodies rate of adults with subclinical hypothyroidism was higher than the corresponding people in excessive iodine areas (TPOAb:57.1%vs15.4%; TGAb:42.9%vs12.8%)(P <0.05).6.The serum sTSH concentration of pregnant women with positive TGAb in excessive iodine areas was higher than the corresponding people in adequate iodine areas (3.96μIU/ml vs1.10μIU/ml)(P<0.05).7.In the two areas the serum sTSH concentration showed positive correlation between the pregnant women and neonate(r=0.278, P=0.000; r=0.202, P=0.008), thyroid autoimmune antibodies showed the same change correlation between the pregnant women and neonate.8. In excessive iodine areas the rate of serum sTSH>10μIU/ml of pregnant women with subclinical hypothyroidism was higher than the corresponding people in adequate iodine areas (P<0.05), thyroid autoimmune antibodies of pregnant women with subclinical hypothyroidism had increased tendency, but no significant difference (P>0.05).9. The serum sTSH concentration of neonate whose mother with positive thyroid antibodies was higher than the corresponding people in adequate iodine areas (TPOAb:7.53μIU/mlvs5.09μIU/ml;TGAb:8.38μIU/mlvs5.86μIU/ml)(P<0.05).10.The re was a increase in FT4, FT3and sTSH concentrations but serum FT4, FT3remained within normal range. One person displayed subclinical hypothyroidism in group400μg and300μg at the4th week (5.3%,5.3%). One additional subject in group300μg had subclinical hypothyroidism at week2, but it disappeared at the end of the trial. After9month, the patient's sTSH in group400μg/d decreased to critical value.11. TGAb and TPOAb had no significant change during iodine asministration.
Conclusions1. Iodine excess increased the risk of thyroid diseases; the subclinical hypothyroidism was most obvious. In excessive iodine areas the main reason of subclinical hypothyroidism were the combined effects of high iodine and thyroid autoimmunity injury, however, in adequate areas thyroid autoimmunity damage may led to the subclinical hypothyroidism.2. The thyroid autoimmunity increased among the people with long-term high iodine exposure.It was greater effect of neonate whose mother with positive thyroid antibodies than the corresponding people in adequate iodine areas.3. Long-term excessive iodine intake of adults and children with normal thyroid function led to high sTSH concentration, and enhanced thyroid autoimmunity.
4. Women showed more apparent in thyroid autoimmunity injury than men.5.There was a closed relation of thyroid autoimmunity between pregnant women and newborns, thyroid function of newborns was impacted directly by mothers.6. People with normal thyroid function appeared subclinical hypothyroidism with short-term (1month) excessive iodine intake, and the people returned to be normal after withdraw iodine supplement.7. For95%people the daily intake should not exceed700p,g/day.
引文
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