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）
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.
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
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.
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.
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.
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.
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.
The research protocols were approved by the medical ethics committee of China Medical University (serial number: IRB34). All subjects provided written in-formed consent.
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).