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Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 ( n  = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 μg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 μg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly ( p  < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p  < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 μg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter ( p  < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p  < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

To evaluate the relationship between smoking and both antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) positivity in subjects from Panshan, Zhangwu, and Huanghua with mildly deficient, more than adequate, and excessive iodine intake, respectively. Smoking-related data were collected by questionnaire, and laboratory measurements of TPOAb, TgAb, and thyrotropin (TSH) were determined at baseline and follow-up. (1) A 1.48-fold increased risk of TPOAb positivity was found in smokers than in non-smokers after adjusting for confounders (age, sex, and areas) (OR[95% CI] = 1.48[1.12-1.95], p = 0.01). (2) Among female subjects, the prevalence of thyroid autoantibodies in smokers was increased than that in non-smokers in Panshan, Zhangwu, and Huanghua (TPOAb): 16.79 vs. 8.89%, 14.14 vs. 11.09%, 19.53 vs. 9.57%; TgAb 15.32 vs. 9.29%, 12.79 vs. 11.94%, 17.19 vs. 10.55%, respectively). The difference was significant in Panshan after adjusting for age. (3) Female long-term smokers (> 20 years) had an increased frequency of thyroid autoantibody positivity than non-smokers after adjusting for confounders (TPOAb OR[95% CI] = 1.60[1.10-2.34]; TgAb OR[95% CI] = 1.31[0.88-1.94]). (4) There was no difference in the incidence of thyroid autoantibodies among non-smokers, new smokers, and long-term smokers at follow-up. (5) TSH was greater in TPOAb-positive subjects than in seronegative smokers (1.56 vs. 1.20 mU/L, p < 0.001) and non-smokers (1.97 vs. 1.58 mU/L, p < 0.001). However, TSH was also greater in non-smokers than in smokers, regardless of whether subjects were positive (1.97 vs. 1.56 mU/L, p = 0.04) or negative (1.58 vs. 1.20 mU/L, p < 0.001) for TPOAb. Long-term smoking could increase the prevalence of thyroid autoantibodies in a population with mildly deficient iodine intake. TSH levels were lesser in smokers than in non-smokers and greater in subjects with thyroid autoantibody positivity than in seronegative subjects. The influence of smoking on TSH levels was independent of thyroid autoantibody levels.

Many studies focused on the association between thyroid disease and pregnancy outcomes. The present study explored the effect of iodine nutrition during the first trimester on pregnancy outcomes. One thousand five hundred sixty-nine pregnant, euthyroid women at ≤12 weeks of gestation in an iodine-sufficient area in China were recruited. According to the World Health Organization (WHO) criteria for iodine nutrition during pregnancy, participants were divided into four groups: adequate iodine (median urinary iodine concentration (UIC), 150-249 μg/L), mild deficiency (UIC, 100-150 μg/L), moderate and severe deficiency (UIC, <100 μg/L), and more than adequate and excessive (UIC, ≥250 μg/L) groups. Pregnancy outcomes, including abortion, gestational hypertension, pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, placental abruption, preterm labor, low birth weight infants, macrosomia, breech presentation, and cord entanglement, were obtained during follow-up. The results showed that there was no significant difference in general characteristics, including age, body mass index, abdominal circumference, systolic blood pressure, diastolic blood pressure, heart rate, smoking rate, and drinking rate, among the four groups. In the more than adequate and excessive group, thyroid-stimulating hormone (TSH) was greater and free thyroxine (FT4) was lower than any other groups but still within normal range. The thyroglobulin (Tg) level was greater in the moderate and severe deficiency group. The incidence of GDM was significantly greater in women with mild iodine deficiency than in women with adequate iodine nutriture (18.38 vs. 13.70%, p < 0.05). Compared with the adequate group, incidence of macrosomia was significantly greater in the more than adequate and excessive group (12.42 vs. 9.79%, p < 0.05). Mild iodine deficiency was an independent risk factor for GDM (odds ratio = 1.566, 95% confidence interval = 1.060-2.313, p = 0.024); more than adequate and excessive iodine was an independent risk factor for macrosomia (OR = 1.917, CI = 1.128-3.256, p = 0.016). In summary, during 1st trimester, both mild iodine deficiency and excessive iodine intake had adverse impacts on pregnancy outcomes in an iodine-sufficient area.

Dysregulated DNA methylation in lymphocytes has been linked to various autoimmune disorders. Excessive iodine intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT) flares in humans and animals. However, whether excessive iodine modifies the DNA methylation status in lymphocytes is unknown. Twenty NOD.H-2 h4 mice and 20 Kunming mice were randomly divided into high iodine and control groups. We scored lymphatic infiltration in the thyroid by hematoxylin and eosin (H&E) staining and assayed serum thyroglobulin antibody (TgAb) levels by an indirect enzyme-linked immunosorbent assay. CD3 + T cells and CD19 + B cells were separated by flow cytometry. Global DNA methylation levels were examined by absorptiometry. Methylation of long interspersed nucleotide element-1 (LINE-1) repeats was detected with bisulfite sequencing PCR. Expression of DNA methyltransferase (DNMT) 1, DNMT3a and DNMT3b mRNA and protein were determined by real-time PCR and Western blot, respectively. We observed evident thyroiditis in the high‑iodine-treated NOD.H-2 h4 mice, while mice in the other three groups did not develop thyroiditis. No differences were found in the global methylation levels and methylation status of LINE-1 repeats in T and B lymphocytes from high‑iodine-treated NOD.H-2 h4 mice and Kunming mice compared with those from normal‑iodine-supplemented controls. We did not find obvious changes in DNMT mRNA and protein expression levels in T and B lymphocytes among the studied groups. In conclusion, we showed for the first time that excess iodine did not affect the global methylation status or DNMT expression in T and B lymphocytes in NOD.H-2 h4 and Kunming mice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To describe the changes in thyroglobulin (Tg) based upon gestational and postpartum concentrations in healthy pregnant women from an iodine-sufficient region in China, and to evaluate the use of Tg as a biomarker for iodine-sufficient pregnant women., Design: A longitudinal study of Tg change in normal pregnant women from an iodine-sufficient region., Patients and Measurements: Blood and urine samples were obtained from 133 pregnant women. Urinary iodine concentration (UIC) was measured using an ammonium persulfate method. Serum iodine concentration was required by inductively coupled plasma mass spectrometry (ICP-MS). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), antithyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and Tg were measured using an electrochemiluminescence immunoassay., Results: Thyroglobulin concentrations were higher in early pregnancy (pregnancy at 8 weeks vs nonpregnancy: 11·42 ng/ml vs 8·8 ng/ml, P < 0·01) and maintained a stable level, and then increased greatly at the 36th week. After delivery, Tg decreased to nonpregnant levels. During pregnancy, maternal Tg was not correlated with thyroid function, UIC or urine iodine-creatinine ratio (UI/Cr). Cord blood Tg was much higher compared to maternal Tg levels at the 36w (57·34 vs 14·86 ng/ml, P < 0·001) and correlated positively with cord FT4 (r = 0·256, P < 0·05), cord TT4 (r = 0·263, P < 0·05) and maternal UI/Cr at 36w (r = -0·214, P < 0·05)., Conclusions: Our work demonstrates that Tg is elevated during pregnancy, and the effect of pregnancy should be taken into consideration when Tg is used as a biomarker for the iodine status. Cord blood Tg is much higher than maternal Tg levels at the 36w and is correlated with maternal iodine status., (© 2016 John Wiley & Sons Ltd.)

The purpose of this study is to determine the effect of prolonged iodine overdose on type 2 iodothyronine deiodinase (D2) ubiquitination-related enzymes. Male Wistar rats were fed different doses of iodine and were then euthanized at the 4, 8, 12, or 24 weeks (4w, 8w, 12w, or 24w) after iodine administration. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), total thyroxine (TT4), and total triiodothyronine (TT3) were determined. Real-time quantitative RT-PCR and Western blot were used to measure mRNA and protein expression levels of pituitary D2 as well as two D2-specific ubiquitin ligases [WD repeat and SOCS box-containing protein 1 (WSB-1), membrane-associated ring finger (C3HC4) 6 (MARCH6 or TEB4)] and two D2-specific deubiquitinating enzymes [ubiquitin-specific peptidase 20 (USP20) and ubiquitin-specific peptidase 33 (USP33)]. The mRNA and protein expression levels of USP19, a TEB4-specific deubiquitinating enzyme, were also measured. Prolonged high iodine intake significantly increased TSH expression. At 12w, TSH was 1.57-, 1.44-, and 2.11-fold of NI group in 6HI, 10HI, and 50HI groups, respectively. At 24w, TSH had increased to 2.11-fold in the 50HI group. The pituitary D2 protein level decreased at 12w and 24w; though the mRNA level did not change. Prolonged iodine intake increased mRNA and protein expression levels of pituitary WSB-1 and TEB4. High iodine intake had no discernible effects on USP20. Temporary increases in USP33 and USP19 mRNA levels were observed. The enzymes related to D2 ubiquitination change with prolonged high iodine intake. Increased D2 ubiquitination suppresses the activity of D2, causing a decrease in negative feedback of the hypothalamic-pituitary-thyroid axis.

The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors.A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L.The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg.In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L., Competing Interests: The authors have no conflicts of interest to declare.

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 μg/L in school-age children (SAC) and 205 μg/L in a cohort population. 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 hypothyroidism (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.

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P<0.01), which were associated with age, sex, the rate of positive TgAb, abnormal thyroid volume, abnormal TSH, and positive personal history of thyroid diseases. The data from 1856 subjects with normal range of thyroid parameters but no personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. Among these three regions, the serum Tg levels were substantially different in both 1999 and 2004, with a similar pattern for increased Tg (ΔTg) (3.1μg/L, 2.5μg/L and 3.5μg/L respectively, P<0.01). The general linear model analysis revealed that age, Tg, and baseline TSH levels were the determinants of ΔTg besides iodine intake. In conclusion, serum Tg in adults, resulting from a time-accumulative effect of iodine exposure, is a useful biomarker of regional iodine intake.

Context: The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥ 500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak., Objective: We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China., Method: Seven thousand one hundred ninety pregnant women at 4-8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured., Results: The prevalence of overt hypothyroidism was lowest in the group with UIC 150-249 μg/L, which corresponded to the lowest serum Tg concentration (10.18 μg/L). Prevalences of subclinical hypothyroidism (2.4%) and isolated hypothyroxinemia (1.7%) were lower in the group with UIC 150-249 μg/L. Multivariate logistic regression indicated that more-than-adequate iodine intake (UIC 250-499 μg/L) and excessive iodine intake (UIC ≥ 500 μg/L) were associated with a 1.72-fold and a 2.17-fold increased risk of subclinical hypothyroidism, respectively. Meanwhile, excessive iodine intake was associated with a 2.85-fold increased risk of isolated hypothyroxinemia. Moreover, the prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess., Conclusion: The upper limit of iodine intake during early pregnancy in an iodine-sufficient region should not exceed UIC 250 μg/L, because this is associated with a significantly high risk of subclinical hypothyroidism, and a UIC of 500 μg/L should not be exceeded, as it is associated with a significantly high risk of isolated hypothyroxinemia.

Background: Iodine deficiency and iodine excess are both associated with adverse health consequences. Iodine deficiency during pregnancy leads to insufficient maternal thyroid hormone, subsequently causing irreversible adverse effects on the neurological and cognitive functions of the offspring. The results of our previous epidemiological study suggested that mild iodine excess might increase the prevalence of subclinical hypothyroidism. In the present study, female Wistar rats maintained on low-iodine grain were randomly assigned to three groups based on iodated water concentration: low iodine (LI, 1.2 μg/d), normal iodine (NI, 5-6 μg/d), and 3-fold high iodine (3HI, 15-16 μg/d). The present study investigated whether higher-than-normal iodine intake (3HI) by rats from before pregnancy until breastfeeding affects the postnatal (PN) neurodevelopment (PN7 and PN45) of their offspring during particularly sensitive periods in brain development., Results: After 12 weeks of treatment (before pregnancy), iodine concentrations in urine and thyroid tissue and circulating thyroxine of adult females correlated with iodine intake. Brain-derived neurotrophic factor (BDNF) expression in the hippocampi of pups on PN7 and PN45 was decreased in 3HI group compared to the NI controls (P < 0.05, all) On PN7 and PN45, the BDNF levels of the 3HI pups were 83.5% and 88.8%, respectively, that of the NI pups. In addition, the 3HI group had a higher neuroendocrine-specific protein A (NSP-A) level than the NI controls on PN7 (P < 0.05). NSP-A levels of the 3HI pups were 117.0% that of the NI pups. No significant difference was observed in the expressions of c-Fos or c-Jun in the hippocampal CA1 region of the 3HI group compared to the controls (P > 0.05). Results from the Morris water maze test revealed that pups of the 3HI group had mild learning and spatial memory deficits., Conclusions: The neurodevelopmental and cognitive deficits of the 3HI pups were mild and temporary, likely related to the changes in hippocampal protein expressions of BDNF and NSP-A.

Iodine is an essential trace element for thyroid hormone synthesis and metabolism, either low or high intake may lead to thyroid disease, but the pathogenetic mechanisms by which iodine interacts with the thyroid autoimmune are poorly understood. We investigated the dynamic changes of CD4(+)CD25(+) regulatory T cells in NOD.H-2(h4) mice with iodine-induced autoimmune thyroiditis (AIT), and explore potential immune mechanism of AIT induced by iodine. NOD.H-2(h4) mice were randomly divided into two groups, and received plain water or water containing 0.005% sodium iodide. Eight weeks after iodine provision, the incidences of thyroiditis, relative weights of thyroids, and serum thyroglobulin antibody titers in the iodine-supplied groups were significantly increased compared to the control groups (p < 0.05). The AIT mice had fewer CD4(+)CD25(+)Foxp3(+) T cells and reduced Foxp3 mRNA expression in splenocytes compared with the controls (p < 0.01), and maintained relatively low levels during the development of thyroiditis. The changes described above aggravated gradually with the extension of iodine treatment. These data suggest that CD4(+)CD25(+) regulatory T cells may be involved in the pathogenesis and development of AIT induced by iodine.

Objective: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200-300 μg/l) or excessive iodine intake levels (MUI >300 μg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations., Design: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 μg/l; Chengshan, MUI 145 μg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant., Results: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P<0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, P=0.02; TgAb: 10.27 vs 7.93%, P=0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: ≥500 IU/ml) and low concentrations of TgAb (TgAb: 40-99 IU/ml) in Rongxing., Conclusions: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.

Acute and excessive iodine supplementation leads to iodine-induced thyroid cytotoxicity. Excessive oxidative stress has been suggested to be one of the underlying mechanisms in the development of thyroid cytotoxicity. The aim of this study was to investigate whether vitamin E (VE), an important antioxidant, could ameliorate iodine-induced thyroid cytotoxicity. A goiter was induced in rats by feeding a low-iodine (LI) diet for 12 weeks. Involution of hyperplasia was obtained by administering a twofold physiological dose of iodine in feeding water with/without the supplementation of 25-, 50-, or 100-fold physiological dose of VE in the LI diet for 4 weeks. In iodine-supplemented rats, thyroid epithelial cell ultrastructure injuries remained and were more severe. Relative weights of iodine-induced involuting glands were significantly reduced compared with the goiter, but still higher than control. Immunohistochemistry indicated that the expression of 4-hydroxynonenal, 8-hydroxyguanine, peroxiredoxin 5, and CD68 in thyroid increased (P<0.01), whereas thioredoxin reductase 1 decreased (P<0.01). VE supplementation attenuated thyroid cytotoxicity induced by iodine. A 50-fold VE dose was optimal in attenuating twofold iodine-induced thyroid cytotoxicity. However, VE supplementation did not reduce the weight or relative weight of the iodine-induced involuting gland. These results show that excess iodine leads to thyroid damage and VE supplementation can partly ameliorate iodine-induced thyroid cytotoxicity.

Iodine is an essential component of thyroid hormones; high intake may lead to thyroid disease. Epidemiologic researches have shown that exposure to iodine may be involved in the onset and development of autoimmune thyroiditis. Iodine may induce hypothyroidism in patients with autoimmune thyroiditis in a dose-dependent manner. The aim of the present study was to investigate the effects of dosages of iodine on thyroid autoimmunity, morphology, structure, and function in autoimmune-prone animals. NOD.H-2h4 mice were randomly divided into normal iodine, 5-fold, 10-fold, 100-fold, 1,000-fold iodine excess group, anesthetized by diethyl ether and bleed from eye socket vein at 4, 8, 16, and 24 weeks after the commencement of experiment. Iodine and thyroid hormone levels in the thyroid tissue and sera, serum thyroglobulin antibody levels, as well as thyroid gland histological appearance were measured. Excessive iodine caused thyroid goiter, and there was a positive correlation between the thyroid weight and the dosage of iodine (r = 0.64-0.92, P < 0.01). Iodine overdose ultrastructurally damaged thyroid epithelial cells in a dose-dependent manner. The incidence of thyroiditis, as well as the degree of lymphocytic infiltration in the thyroid gradually increased as the dosage increased (r = 0.87-0.98, P

Objective: The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline., Design: The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80.0%) participated in the 5-year follow-up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B-mode ultrasonography of the thyroid was performed., Results: In the reference population, there was a urinary iodine-related increment of serum TSH levels (r = 0.21, P = 0.000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1.15, 1.28 and 1.93 mIU/l, respectively (P = 0.000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0.3-4.8 mIU/l. TSH concentrations obtained in the follow-up study correlated well with those at baseline (r = 0.58, P = 0.000). A baseline serum TSH > 1.9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1.0 mIU/l was associated with an increased incidence of subnormal TSH development., Conclusions: Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1.0-1.9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.

Objective: In a follow-up study, we determined the prevalence, incidence, and natural course of positive antithyroperoxidase antibodies (TPOAbs) and antithyroglobulin antibodies (TgAbs) in the general population and examined the influences of iodine intake., Design: The study was conducted in Panshan, Zhangwu, and Huanghua, regions with mildly deficient, more than adequate, and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 3018 participated in the 5-yr follow-up study. Serum TSH, TPOAb, and TgAb levels were measured., Results: Among subjects in Panshan, Zhangwu, and Huanghua, the prevalence of positive TPOAbs was 11.23, 11.83 and 12.02%, respectively, whereas 11.23, 11.17, and 11.26% of subjects were TgAb positive, respectively. In the older population (> or =45 yr), TgAb-positive individuals were more frequent in Huanghua than Panshan and Zhangwu (P < 0.05). The 5-yr cumulative incidence of positive TPOAb was 2.08, 3.84, and 2.84% in Panshan, Zhangwu, and Huanghua, respectively, whereas 2.91, 3.64, and 5.07% of subjects were TgAb positive, respectively (P < 0.05), corresponding to the increase in iodine intake. Subjects who were TPOAb and/or TgAb positive at baseline developed thyroid dysfunctions more frequently than those without antibodies (14.44 vs. 3.31%, P < 0.01); their incidence of elevated TSH levels was 1.32, 8.46, and 15.38% in Panshan, Zhangwu, and Huanghua, respectively (P < 0.05)., Conclusions: Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody-positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb.

Objective: An increasing incidence of hyperthyroidism has been observed when iodine supplementation has been introduced to an iodine-deficient population. Moreover, the influence of chronic more than adequate or excessive iodine intake on the epidemiological features of hyperthyroidism has not been widely and thoroughly described. To investigate the influences of different iodine intake levels on the incidence of hyperthyroidism, we conducted a prospective community-based survey in three communities with mild-deficient, more than adequate (previously mild deficient iodine intake), and excessive iodine intake., Subjects and Methods: In three rural Chinese communities, a total of 3761 unselected inhabitants aged above 13 years participated in the original investigation and 3018 of them received identical examinations after 5 years. Thyroid function, levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody and urinary iodine excretion were measured and thyroid ultrasound examination was also performed., Results: In three communities, median urinary iodine excretion was 88, 214, and 634 microg/l (P<0.05) respectively. The cumulative incidence of hyperthyroidism was 1.4, 0.9, and 0.8% (P>0.05) respectively. Autoimmune hyperthyroidism was predominant in thyroid hyperfunction in all the three cohorts. Either positive TPOAb (>50 U/ml) or goiter in original healthy participants was associated with the occurrence of unsuspected hyperthyroidism in 5 years (logistic regression, OR=4.2 (95% CI 1.7-8.8) for positive TPOAb, OR=3.1 (95% CI 1.4-6.8) for goiter)., Conclusion: Iodine supplementation may not induce an increase in hyperthyroidism in a previously mildly iodine-deficient population. Chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.

Background: Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 microg per liter), more than adequate (median, 243 microg per liter), and excessive (median, 651 microg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease., Methods: Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up., Results: Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function., Conclusions: More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis., (Copyright 2006 Massachusetts Medical Society.)

Iodine is an essential trace element for thyroid hormone synthesis and metabolism, either low or high intake may lead to thyroid disease, but the pathogenetic mechanisms by which iodine interacts with the thyroid autoimmune are poorly understood. We investigated the dynamic changes of CD4CD25 regulatory T cells in NOD.H-2 mice with iodine-induced autoimmune thyroiditis (AIT), and explore potential immune mechanism of AIT induced by iodine. NOD.H-2 mice were randomly divided into two groups, and received plain water or water containing 0.005% sodium iodide. Eight weeks after iodine provision, the incidences of thyroiditis, relative weights of thyroids, and serum thyroglobulin antibody titers in the iodine-supplied groups were significantly increased compared to the control groups ( p < 0.05). The AIT mice had fewer CD4CD25Foxp3 T cells and reduced Foxp3 mRNA expression in splenocytes compared with the controls ( p < 0.01), and maintained relatively low levels during the development of thyroiditis. The changes described above aggravated gradually with the extension of iodine treatment. These data suggest that CD4CD25 regulatory T cells may be involved in the pathogenesis and development of AIT induced by iodine. [ABSTRACT FROM AUTHOR]