原创中华医学会内分泌学分会02-08 00:36

摘要: 参与的一项中国碘营养状况和甲状腺疾病患病率、甲状腺疾病谱变化的研究在《Thyroid》发布。


编者按

2016年7月22日,由中华医学会内分泌学分会组织,中国医科大学第一附属医院牵头,北京大学第一附属医院、上海瑞金医院、西安交大第一附属医院、山东省立医院、江苏省人民医院、中山大学第三附属医院、四川华西医院、华中科技大学附属协和医院、贵阳医学院附属医院参与的一项中国碘营养状况和甲状腺疾病患病率、甲状腺疾病谱变化的研究在《Thyroid》发布。


文中最新报告了我国甲状腺疾病患病率,其结果与既往常用的2010年CSE年会报告数据具有差异,与1999年数据相比,临床及亚临床甲亢患病率均较前下降,但亚甲减明显上升,临床甲减患病率无显著变化,甲结节患病率较前亦明显增加。


摘要

中国在过去的16年间推行全民食盐加碘计划,成功消除了碘缺乏的现象。因此,中国摄碘量被认为已超过所需水平。本研究旨在调查中国当前碘营养状况以及增加碘摄入量对甲状腺疾病谱和患病率的影响。

研究对象为来自中国东部和中部10个城市的 15008位成年人。测量指标包括血清促甲状腺素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)和尿碘浓度(UIC)以及甲状腺超声检查。若血清TSH超出正常范围,还会测量游离甲状腺素(fT4)和游离三碘甲状腺原氨酸(fT3)水平。


研究根据UIC中位数来评估摄碘情况(UIC中位数在学龄儿童是197μg/L,在整体人群中是205μg/L),六个城市被列入碘充足(AII)地区,四个城市为碘过量(MTAII)地区。


结果显示, MTAII地区的临床甲减、亚临床甲减的患病率,甲状腺抗体阳性率显著高于AII地区。此外,MTAII地区临床甲亢(1.1% VS. 0.8%,P=0.033)和Graves疾病(甲状腺机能亢进,0.8% VS. 0.5%,P=0.019)的患病率也显著增加。相较于1999年开展的五年前瞻性研究,甲状腺肿的患病率显著降低(2.9% VS. 5.02%,P=0.001),但是甲状腺结节的患病率显著增加(12.8% VS. 2.73%,P=0.001)。亚临床甲减(16.7% VS. 3.22%)的患病率,TPOAb阳性率(11.5% VS. 9.81%)和TgAb阳性率(12.6% VS. 9.09%)显著增加,但临床甲亢、亚临床甲亢及Graves病的患病率有所下降。


甲状腺疾病患病率的比较(1999 vs. 2011)


总之,消除碘缺乏这一目标已经在中国成功实现。但是,甲状腺疾病患病率和疾病谱的改变反映出碘摄入过量可能产生的负面影响。


原文摘录

Iodine Status and Prevalence of Thyroid Disorders After Introduction of Mandatory Universal Salt Iodization for 16 Years in China: A Cross-Sectional Study in 10 Cities


ZhongyanShan,1 Lulu Chen,2 Xiaolan Lian,3Chao Liu,4 Bingyin Shi,5 Lixin Shi,6Nanwei Tong,7Shu Wang,8 Jianping Weng,9Jiajun Zhao,10 Xiaochun Teng,1 Xiaohui Yu,1Yaxin Lai,1 Weiwei Wang,1 Chenyan Li,1Jinyuan Mao,1 Yongze Li,1 Chenling Fan,1and Weiping Teng1


Background: The goal of eliminating iodine deficiency worldwide was successfully achieved in China after the implementation of a mandatory universal salt iodization program for the last 16 years. Thus, China has been assessed as a country with more than adequate iodine levels. This survey aimed to investigate the current iodine status in China and the effects of an increased iodine intake on the spectrum and prevalence of thyroid disorders.


 Methods: A total of 15,008 adult subjects from 10 cities in eastern and central China were investigated. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and urine iodine concentration (UIC) were measured, and an ultrasonography of the thyroid was performed in all subjects. Free thyroxine (fT4) and free triiodothyronine (fT3) levels were only measured if the serum TSH was outside the normal range.


Results: The median UIC values were 197 lg/L in school-age children (SAC) and 205 lg/L in a cohort popu-lation. Six cities were classified as regions with adequate iodine intake (AII), and four cities as regions with more than adequate iodine intake (MTAII), according to median SAC UIC. The prevalence of clinical hypothyroidism, subclinical hypothyroidism, and positive thyroid antibodies was significantly higher in MTAII cities than it was in AII cities. Moreover, the prevalence of clinical hyperthyroidism (1.1% vs. 0.8%, p = 0.033) and Graves’ disease (0.8% vs. 0.5%, p = 0.019) also significantly increased in MTAII cities. Compared with a five-year prospective study conducted in 1999, the prevalence of goiter significantly decreased (2.9% vs. 5.02%, p = 0.001), but there was a significant increase in thyroid nodules (12.8% vs. 2.78%, p = 0.001). The prevalence of subclinical hypo-thyroidism (16.7% vs. 3.22%), positive TPOAb (11.5% vs. 9.81%), and positive TgAb (12.6% vs. 9.09%) significantly increased, while no changes were seen in clinical hyperthyroidism, subclinical hyperthyroidism, or Graves’ disease.


Conclusion: The goal of eliminating iodine deficiency has been successfully achieved in China. However, the prevalence and spectrum of thyroid disorders has increased, reflecting possible adverse effects of increased iodine intake.


Introduction

China used to be an iodine-deficient country, with a high prevalence of iodine deficiency disorders (IDD).


According to reports in the 1970s, 4.25 hundred million people lived in iodine-deficient regions, 35 million had en-demic goiter, and 250,000 had cretinism (1). A mandatory universal salt iodization (USI) program was introduced in 1996, and had been in place for 16 years at the time of our study (2011–2012). The National Monitoring Center for Io-dine Status reported in 2011 that the median urine iodine concentration (UIC) in school-age children (SAC) was 238.6 lg/L and the prevalence of goiter was 2.4%, with 98% coverage of iodized salt at the household level (2). As such, the international authorities declared that China has elimi-nated IDD, and its iodine status was more than adequate (3). China experienced excessive iodine intake (EII; defined as median UIC values ?300 lg/L) for six years, and more than adequate iodine intake (MTAII; defined as median UIC values 200–299 lg/L) for 10 years, which led to a great change in the prevalence and spectrum of thyroid disorders. Between 1999 and 2004, a five-year prospective study was completed in three communities with different iodine intakes(4). In 2011–2012, another cross-sectional study was per-formed in several cities with similar iodine intake: six with adequate iodine intake (AII; median UIC values 100–199 lg/ L), and four with MTAII located in the eastern and central part of China. The aim of the current study is to understand the iodine status and prevalence of thyroid disorders after the implementation of mandatory USI for 16 years.


Materials and Methods


Cities


Ten cities were chosen according to their historical median UIC in SAC that was representative of AII and MAII status. They were located in the eastern and central parts of China, which have a collective total population of 60 million and include Shenyang (SY), Beijing (BJ), Jinan ( JN), Xi’an (XA), Chengdu (CD), Nanjing (NJ), Shanghai (SH), Wuhan (WH), Guiyang (GY) and Guangzhou (GZ; Fig. 1).

FIG. 1.    The distribution of 10 cities investigated in China.


Subjects


One or two communities were randomly chosen from each city. The designed cohort included 1500 individuals from each city, giving a total of 15,008 participants across the 10 cities. To avoid recruitment bias, the inhabitants in the com-munity were screened according to their household regis-ters. The participants were enrolled in the cohort in line with the designed age composition. The average participant age was 45.5 years (standard deviation [SD] = 14.9; range 15–92 years). The sample was stratified by age to reflect the age range of the Chinese population (National Bureau of Statis-tics in China in 2008). Thus, the age groups 15–29, 30–39, 40–49, 50–59, 60–69, and ?70 comprised 17.1%, 22.3%, 22.4%, 19.6%, 10.3%, and 8.3% of the total study population, respectively. The ratio of men to women was 1:1.4, since fewer men lived at home.


The 10 city cohorts were similar in age and sex, but dif-fered in iodine intake. Exclusion criteria included residing in the city for <10 years, age <15 years, pregnant or lactating, or any medical regimen affecting thyroid function such as an-tithyroid drugs, thyroid hormones, glucocorticoids, dopa-mine, or amiodarone. A reference population was selected according to Guideline 22 of the National Academy of Clinical Biochemistry, that is, without medications, detectable thyroid autoantibodies, a personal or family history of thyroid dys-function, and goiter or nodules on thyroid ultrasonography(5). The 60 urine samples from SAC in each community were measured for UIC, and 10 samples of household salt and drinking water (tap water) in each community were measured for iodine concentration.


Survey protocols


Participants were visited at home, and an oral question-naire was administered as previously described (4), which collected personal information and data on the economic status of the family, eating habits, type of salt used, smok-ing status, and personal or family history of thyroid disease. Fasting blood and urine samples were collected between 8:00am and 10:00am. All samples were stored at -20LC and transferred within one month of collection to the laboratory in the project center for centralized measurements. Physicians who had received centralized training performed all thy-roid ultrasonography evaluations using a portable instrument (LOGIQ a50, 7.5 MHz; GE Healthcare). Table 1 shows the diagnostic criteria for thyroid disorders used in this study.

Laboratory methods


Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were mea-sured in all participants. Free thyroxin (fT4) and free triio-dothyronine (fT3) levels were only measured if TSH was outside the reference range. The laboratory reference ranges provided by the manufacturer were used in this study: TSH 0.27–4.2 mIU/L, fT4 12–22 pmol/L, fT3 3.1–6.8 pmol/L, TPOAb 0–34 IU/L, and TgAb 0–115 IU/L. Measurements were done using electrochemiluminescence immunoassays on a Cobas 601 analyzer (Roche Diagnostics). The functional sensitivity of serum TSH was 0.002 mIU/L. The intra-assay coefficients of variation (CV) of serum TSH, fT4, fT3, TPOAb, and TgAb were 1.1–6.3%, and the inter-assay CV values were 1.9–9.5%. UIC was determined in all participants by the am-monium persulfate method based on the Sandell–Kolthoff reaction (6). The reference range of the certified reference material (GBW09109) from the Center for Disease Control (CDC) in China was 138 – 10 lg/L, and the result measured by the central laboratory was 134.3 – 6.2 lg/L. The intra- and inter-assay coefficients of variation for UIC were 3–4% and 4–6% at 66 lg/L and 2–5% and 3–6% at 230 lg/L.


Statistical analysis


All statistical analyses were performed using SPSS Statistics for Windows v17.0 (SPSS, Inc.), and values of p < 0.05 were considered significant. The data were tested for normality using the Kolmogorov–Smirnov test. UIC was not normally dis-tributed, therefore the median and interquartile ranges are re-ported. The chi-square test was used to compare the prevalence of thyroid disorders between different regions and years.


Medical ethics


The research protocols were approved by the medical ethics committee of China Medical University (serial number: IRB[2008]34). All subjects provided written in-formed consent.


Results


As shown in Table 2, the median UIC values were 197 lg/L in SAC and 205 lg/L in the total cohort population. According to the median UIC of SAC, six cities (SY, BJ, JN, CD, SH, and GZ) were classified as AII regions (median UIC 172.8 lg/L in SAC), and four cities (GY, NJ, WH, and XA) as MTAII regions (me-dian UIC 239.5 lg/L in SAC). The average iodine concentra-tions in the drinking water were 6.55 lg/L in AII and 3.18 lg/L in MTAII. The average iodine concentration in household salt was 29.1 mg/kg in AII and 28.4 mg/kg in MTAII.


Table 3 shows the proportion of UIC in the cohort population. The percentages of the populations with UIC <50 lg/L and <100 lg/L were 3.23% and 16.04% in AII and 1.49% and 8.26% in MTAII, respectively. In the whole cohort, the percentages of the populations with UIC <50 lg/L and <100 lg/L were 2.78% and 12.23%, respectively. In women of child-bearing age (20–45 years), median UIC (MUI) was 215.43 lg/L, with 2.78% UIC <50 lg/L and 24.55% UIC <150 lg/L.


Table 4 shows the significantly higher prevalence of thy-roid disorders in MTAII cities than in AII cities, including overt hyperthyroidism (1.1% vs. 0.8%, p = 0.33), overt hy-pothyroidism (1.3% vs. 1.0%, p = 0.033), subclinical hypo-thyroidism (22.6% vs. 12.7%, p < 0.001), Graves’ disease (0.8% vs. 0.5%, p = 0.019), positive TPOAb (12.4% vs. 10.9%,p = 0.004), and positive TgAb (13.4% vs. 12.0%, p = 0.04), except for subclinical hyperthyroidism (0.8% vs. 0.8%, p = 0.095). However, the prevalence of goiter was significantly lower (1.0% vs. 4.3%, p < 0.001) and the prevalence of thyroid nodules was significantly higher (14.5 vs. 10.4%, p < 0.001) in MTAIII cities than it was in AII cities.

A remarkable change was found in the prevalence of subclinical hypothyroidism (TSH >4.2 mIU/L), which was unexpectedly higher in both regions (12.7% in AII and 22.6% in MTAII). Of the individuals with subclinical hypothy-roidism, 20.6% were TPOAb positive and 21.2% were TgAb positive. On the contrary, the prevalence of subclinical hy-pothyroidism in individuals with TPOAb positivity was 36%, while that of TgAb positivity was 33.8%. The prevalence of TPOAb and TgAb positivity in the whole cohort population was 11.5% and 12.0%, respectively, with a higher prevalence in women than in men (14.8% vs. 7.0%, p < 0.001; TgAb 18.1% vs. 5.1%, p < 0.001).


Table 5 shows the prevalence of thyroid disorders found in this study compared with the results reported in 1999 (5). As reported by most studies, the prevalence of the hyperthy-roidism and Graves’ disease decreased significantly (0.89% vs. 1.68%, p = 0.001 for hyperthyroidism; 0.61% vs. 1.25%, p = 0.001 for Graves’ disease). An increased prevalence was found in subclinical hypothyroidism (16.7% vs. 3.22%, p = 0.001) without a change in clinical hypothyroidism (1.03% vs. 1.11%, p = 0.69). The prevalence of TPOAb and TgAb positivity also increased significantly (11.5% vs. 9.81%, p = 0.003 for TPOAb; 12.6% vs. 9.09%, p = 0.001 for TgAb). The prevalence of goiter in this study decreased significantly (2.9% vs. 5.02%, p = 0.001), but the prevalence of thyroid nodules increased (12.8% vs. 2.78%, p = 0.001).

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