High Iodine Intake Research Articles

Risks of papillary and follicular thyroid cancer among immigrants to Sweden

Previous studies have indicated that ionizing radiation, particularly during childhood, is the main established risk factor for thyroid cancer. History of benign nodules/adenoma, goiter, iodine deficiency or high-iodine intake might be other associated factors. We wanted to define the histology-specific thyroid cancer risk in the first-generation immigrants to Sweden. We used the 2010 update of the nation-wide Swedish Family-Cancer Database (>12 million individuals; 1.8 million immigrants; histology code in force since 1958) to calculate standardized incidence ratios (SIRs) for histology-specific thyroid cancer among immigrants compared to the native Swedes. The patient series covered 2,604 male and 6,406 female Swedes, and 247 and 863 immigrants. The median age at immigration was 29 years, and the median age at thyroid cancer diagnosis was 46 years. Increased risks for female papillary carcinoma were observed for Finns (SIR = 1.63), former Yugoslavians (2.36), Russians (2.34), other East Europeans (2.14), Turks (3.16), Iranians (2.68), Iraqis (2.77), East and Southeast Asians (2.92), other Asians (1.69) and South Americans (2.23). Male Iranians (2.85), East and Southeast Asians (3.57) and other Asians (2.26) had an increased risk for papillary carcinoma. Only male East and Southeast Asians (2.93) had an increased risk for follicular carcinoma. The data might suggest that immigrant populations in Sweden from areas of low or high-iodine intake are at risk of papillary carcinoma, implicating iodine imbalance as a contributing factor to our findings. The increased risk of thyroid cancer among Asian immigrants may confirm the role of childhood-ionizing radiation on thyroid cancer risk.

Correlation Between Iodine Intake and Thyroid Function in Subjects with Normal Thyroid Function

Excessive iodine intake is known to induce hypothyroidism in people who have underlying thyroid disorders. However, few studies have been performed on subjects with normal thyroid function without a history of autoimmune thyroid disease. We hypothesized that high iodine intake may cause a subtle change in thyroid function even in subjects with normal thyroid function. We analyzed 337 subjects (64 men and 273 women; mean age, 49years) who showed normal levels of thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibodies (Tg-Ab) by measuring the urinary iodine excretion, free T4 (FT4), and thyroid-stimulating hormone (TSH). The results showed urinary iodine excretion had negative correlation with FT4 (γ = -0.11, p = 0.043) and showed a positive trend with TSH (γ = 0.10, p = 0.068). We found that 61.7% of subjects had circulating TPO-Ab within normal reference range. In all subjects, TPO-Ab levels were negatively correlated with FT4 (γ = -0.17, p = 0.002) and positively with TSH (γ = 0.13, p = 0.021). In conclusion, high iodine intake can negatively affect thyroid hormone levels in subjects with normal thyroid function. Population-based study will be helpful for further clarification.

Diagnostic Value of a Chimeric TSH Receptor (Mc4)-Based Bioassay for Graves' Disease

Background/AimsGraves' disease (GD) is caused by thyroid-stimulating hormone receptor (TSHR) and thyroid-stimulating immunoglobulin (TSI). We used a recently introduced, technically enhanced TSI bioassay to assess its diagnostic value and determine the cut-off in patients in high iodine intake area.MethodsIn a cross-sectional setting, we collected serum from 67 patients with untreated GD, 130 with GD under treatment, 22 with GD in remission, 42 with Hashimoto's thyroiditis, 12 with subacute thyroiditis, 20 with postpartum thyroiditis, and 93 euthyroid controls. TSI was measured using the Thyretain™ bioassay, which is based on Chinese hamster ovary cells transfected with chimeric TSHR (Mc4). TSI levels are reported as a specimen-to-reference ratio percentage (SRR%).ResultsThe TSI levels in patients with GD (either treated or not) were significantly higher than those of the remaining patients (p < 0.05). The new bioassay showed a sensitivity of 97.0% and a specificity of 95.9% with a cut-off value of 123.0 SRR% for GD. A weak correlation was found between TSI and thyrotropin-binding inhibiting immunoglobulin (TBII) (rs = 0.259, p = 0.03), but no correlation was found between TSI and tri-iodothyronine or free thyroxine.ConclusionsThe Mc4-CHO bioassay showed comparable diagnostic value for GD with the conventional TBII assay. We propose a cut-off of 123.0 SRR% in areas where iodine intake is high.

Pathologic features of polycystic thyroid disease: Comparison with benign nodular goiter

Polycystic thyroid disease (PCTD) is characterized by multiple thyroid cysts detected by ultrasonography, the absence of thyroid autoantibodies, and susceptibility to the development of hypothyroidism due to a high iodine intake. It is necessary to obtain histopathological information on PCTD in order to clarify the cause of hypothyroidism. We retrospectively reviewed three patients with PCTD and small papillary thyroid cancer who underwent thyroidectomy. We observed the thyroid tissues pathologically in areas with and without multiple cysts, and compared them with those of multinodular goiter with cysts. In the patients with PCTD, there were multiple enlarged follicles that resembled enlarged normal follicles and differed from those found in multinodular goiter in terms of their shape. Huge follicles corresponded to the cysts that were detected by ultrasonography. Each follicle contained colloid. Follicular cells in enlarged follicles comprised low cuboidal epithelium that appeared normal. These findings were common in the 3 patients with PCTD. In Conclusion the PCTD patients had multiple enlarged follicles that seemed to decrease the total number of follicular cells, and may be a cause of hypothyroidism. We believe that PCTD is a new entity of thyroid disease based on the pathological findings.

The Prevalence of Polycystic Thyroid Disease in Hypothyroid Patients with Negative Thyroid Autoantibodies

We previously reported that multiple thyroid cysts may be a cause of hypothyroidism in patients with a relatively high iodine intake and we termed it polycystic thyroid disease (PCTD). The aim of this study was to investigate the prevalence of PCTD in patients who visited our thyroid center. We hypothesized that patients with PCTD are not rare in a region with a high iodine intake. We retrospectively studied the cause of hypothyroidism based on medical histories and ultrasonography in new patients to our hospital from April 2008 to March 2009 whose serum tests for antithyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were negative. Serum thyroid hormones, thyrotropin (TSH), TgAb, and TPOAb were measured in 8243 patients. Patients with four or more thyroid cysts, negative tests for TgAb and TPOAb, no evidence for thyroid diseases other than their thyroid cysts, and no exposure to thyroid-perturbing influences were defined as having PCTD. Three hundred seven patients had overt hypothyroidism (TSH level above 10.0 μU/mL and free thyroxine level below 0.7 ng/dL), of whom 71 patients were both TgAb and TPOAb negative. There were 546 patients with subclinical hypothyroidism (TSH level above 5.0 μU/mL and normal free thyroxine), of whom 193 patients were both TgAb and TPOAb negative. There were 24 patients with overt hypothyroidism and PCTD, accounting for 7.8% (24/307) of all causes of overt hypothyroidism. There were 42 patients with subclinical hypothyroidism and PCTD, accounting for 7.7% (42/543) of all causes of subclinical hypothyroidism. PCTD was more common among elderly people than young people. PCTD appears to be a minor but not negligible cause of hypothyroidism, at least in iodine-rich regions. PCTD with hypothyroidism may have been misdiagnosed as thyroid antibody-negative Hashimoto's thyroiditis in many reports.

Estimating the impact of mandatory fortification of bread with iodine on pregnant and post-partum women

BackgroundIodine deficiency has re-emerged in Australia. Pregnant and breastfeeding women need higher iodine intakes (estimated average requirements: 160 μg/day and 190 μg/day) than non-pregnant women (100 μg/day) because iodine is...

The Impact of Dietary Iodine Intake on Lipid Metabolism in Mice

The present study has been designed to investigate the impact of dietary iodine intake on lipid metabolism in mice, including iodine deficiency and iodine excess. Different amounts of iodine mixed in the drinking water were continuously administered to mice. The body weights and the levels of urinary iodine were measured 8months after the treatment. Thyroid hormones in the serum were detected by chemiluminescence immunoassay. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C) were determined enzymatically by automatic analyzer. Results showed that the urine iodine concentrations paralleled the amounts of iodine intakes. No statistical differences of body weights among different groups were found. The levels of thyroid hormones were dramatically decreased in iodine deficiency while no significant differences were found between iodine excess groups and normal iodine group. In iodine deficiency groups, the levels of TG, TC, and LDL were increased at varying degrees. In iodine excess groups, the levels of TG in the male mice and the levels of TC in the female mice were much lower than normal iodine group. In conclusion, dietary iodine intake may affect the metabolism of serum lipids. Hypothyroid function induced by iodine deficiency may be responsible for the changes of lipids. Higher iodine intake might benefit lipid metabolism.

Effect of Long Term Excessive Iodine Intake on Thyroid Function and Oxidative Stress in Euthyroid and Hypothyroid Rats

Background and aim of work: The aim of the current study was to investigate theeffects of long term excessive iodine intake on gene expression of thyroidal sodiumiodide symporter (NIS), D1 deiodinase and thyroid peroxidase (TPO), thyroidhormones, oxidative injury and anti-oxidative ability of euthyroid and hypothyroidSprague Dawley rats. Materials and Methods: Ninety rats were divided intoeuthyroid and hypothyroid (thiocyanate induced) groups with or withoutadministration of excess iodine (3000 or 6000 μg/l) for 4 weeks. Serum thyroxine (T4),triiodothyronine (T3), TSH, thyroid antioxidants ((glutathione S transferase, catalase,superoxide dismutase enzymes, nitric oxide and total antioxidants), lipid peroxide(malondialdehyde, MDA) were measured. RT-PCR gene expression for thyroidal NIS,D1 deiodinase and TPO were performed. Results: Thiocyanate significantlydecreased thyroid hormones (T3, T4), increased lipid peroxides and antioxidants,increased gene expression of NIS, D1 deiodinase, TPO. High iodine intake tohypothyroid rats significantly decreased NIS, D1 deiodinase and TPO genesexpression. Excess iodine significantly increased MDA and antioxidants in euthyroidand hypothyroid rats. Despite the increase in T4 in euthyroid rats administered excessiodine, T3 decreased whereas in hypothyroid rats, both of them were increased. NIS,and D1 deiodinase genes expression in euthyroid rats administered excess iodinewere decreased but TPO was non-significantly increased. Conclusion:Hypothyroidism increased gene expression of NIS, TPO, and induces an oxidativestress. High iodine intake decreased NIS and D1 deiodinase gene expression ineuthyroid and hypothyroid rats. Moreover, excess iodine increase thyroid hormones,lipid peroxides and antioxidants in cases of euthyroid and hypothyroid rats.Therefore, screening of thyroid function and assessment of prooxidant/antioxidantstatus in subjects treated with drugs containing iodine and after investigations withcontrast media are recommended.

Lower Incidence of Anaplastic Carcinoma After Higher Iodination of Salt in Slovenia

Anaplastic thyroid carcinoma (ATC) may arise de novo or from a preexistent differentiated carcinoma. It is well known that higher iodine intake in the diet causes higher frequency of papillary thyroid carcinoma, but decreases the frequency of follicular thyroid carcinoma. However, it is not known how the change in iodine intake influences the frequency of ATC. The aim of our study was to compare the incidence of ATC during the periods when the intake of potassium iodide in salt was 10 and 25 mg/kg. A total of 205 patients with ATC (140 women, 65 men; median, 69 years) were treated in the Republic of Slovenia between 1972 and 2008. In Slovenia, a country with a population of 2 million people, the salt was iodinated with 10 mg of potassium iodide/kg from 1972 to 1997. From 1998 to 2008 the degree of iodination of salt was increased to 25 mg of potassium iodide/kg. The frequency of ATC during the two periods and the characteristics of the patients during these periods were compared. The mean incidences of ATC during 1972-1997 and 1998-2008 was 6.2 (range, 3-12) and 4 (range, 2-10) patients per year, respectively. During the period 1972-1997 and 1998-2008, the mean age of patients was 66.7 and 72.2 years (p = 0.02), and the mean tumor diameter was 9.6 and 8.6 cm (p = 0.21), respectively. However, the median survival of patients in both periods was 3 months. The incidence of ATC decreased after higher iodination of salt. The patients with ATC during the period of higher iodination of salt were older than those from the period with lower iodination of salt.

Iodine content of thyroglobulin in NOD.H2h4 mice developing iodine-accelerated autoimmune thyroiditis

In NOD.H2h4 mice, high dietary iodine intake has been known to cause iodine-accelerated spontaneous autoimmune thyroiditis (ISAT) via an unknown mechanism. The aim of the study was to examine whether the NOD.H2h4 genetic background predisposes to enhanced iodine organification in thyroglobulin (Tg), a target autoantigen in ISAT. To avoid issues associated with an ongoing anti-Tg antibody response, we assessed Tg iodination levels in iodine-fed, B-cell deficient NOD.H2h4 mice. Additionally, we tested whether humoral or cellular immune responses of iodine-fed NOD.H2h4 mice are preferentially directed to Tg with increased iodine content (I-Tg) or known pathogenic Tg peptides that contained iodine. The iodine content of Tg was not significantly different between control (9.0 +/- 2.7 I atoms per monomer) and iodine-fed mice (10.9 +/- 0.3 I atoms per monomer). Furthermore, in iodine-fed NOD.H2h4 mice developing ISAT, strong but equivalent serum IgG responses were detected to both Tg or I-Tg, whereas their lymphoid cells were stimulated weakly but equally well by Tg or I-Tg in vitro and did not show reactivity against a panel of five pathogenic Tg peptides that contained iodine. The results suggest that development of ISAT in NOD.H2h4 mice is not associated with enhanced iodine organification or differential B- or T-cell responses to iodinated determinants in Tg.

Multiple Thyroid Cysts May Be a Cause of Hypothyroidism in Patients with Relatively High Iodine Intake

Multiple cysts of the thyroid gland have not been recognized as one of the causes of hypothyroidism. Here we present six patients from a region with relatively high iodine intake in whom multiple cysts of the thyroid were associated with hypothyroidism or the development of hypothyroidism. All patients were women and ranged in age from 49 to 71. Their thyroids were mildly enlarged, tests for thyroid autoantibodies were negative, and multiple cysts were detected in the thyroid by ultrasonography. By dietary questionnaire their iodine intake was estimated to range from 2 to 10 mg of iodine daily. Otherwise, there was no evidence for disorders or factors associated with hypothyroidism. All four patients who agreed to dietary iodine restriction became euthyroid at approximately 1 month after a low-iodine diet (less than 0.5 mg iodine per day) was started. Although these patients were from a region with high-iodine intake and had a relatively high intake compared with most regions of the world, this amount of iodine intake is not associated with hypothyroidism in otherwise healthy persons. Therefore, we propose that multiple thyroid cysts, which we have termed polycystic goiter, is probably a cause of hypothyroidism in patients with a relatively high iodine intake.

Iodine intake as a determinant of thyroid disorders in populations

Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most serious association between disease and the level of iodine intake in a population. In less severe iodine deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range. However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function. In populations with mild and moderate iodine deficiency, such multifocal autonomous thyroid function is a common cause of hyperthyroidism in elderly people, and the prevalence of thyroid enlargement and nodularity is high. The average serum TSH tends to decrease with age in such populations caused by the high frequency of autonomous thyroid hormone production. On the other hand, epidemiological studies have shown that hypothyroidism is more prevalent in populations with a high iodine intake. Probably, this is also a complication to thyroid adaptation to iodine intake. Many thyroid processes are inhibited when iodine intake becomes high, and the frequency of apoptosis of follicular cells becomes higher. Abnormal inhibition of thyroid function by high levels of iodine is especially common in people affected by thyroid autoimmunity (Hashimoto's thyroiditis). In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Caucasian populations with a genetically determined high tendency to thyroid autoimmunity. A small tendency to higher serum TSH may be observed already when iodine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality. Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine.

Iodine excess

Several mechanisms are involved in the maintenance of normal thyroid hormone secretion, even when iodine intake exceeds physiologic needs by a factor of 100. The sodium-iodide symporter system contributes most to this stability. Faced with an iodine excess, it throttles the transport of iodide into the thyroid cells, the rate-limiting step of hormone synthesis. Even before the iodine symporter reacts, a sudden iodine overload paradoxically blocks the second step of hormone synthesis, the organification of iodide. This so-called Wolff-Chaikoff effect requires a high (>or=10(-3) molar) intracellular concentration of iodide. The block does not last long, because after a while the sodium-iodide symporter shuts down; this allows intracellular iodide to drop below 10(-3) molar and the near-normal secretion to resume. In some susceptible individuals (e.g., after radio-iodine treatment of Graves' disease or in autoimmune thyroiditis), the sodium-iodide symporter fails to shut down, the intracellular concentration of iodide remains high and chronic hypothyroidism ensues. To complicate matters, iodine excess may also cause hyperthyroidism. The current explanation is that this happens in persons with goitres, for example, after long-standing iodine deficiency. These goitres may contain nodules carrying a somatic mutation that confers a 'constitutive' activation of the TSH receptor. Being no more under pituitary control, these nodules overproduce thyroid hormone and cause iodine-induced hyperthyroidism, when they are presented with sufficient iodine. These autonomous nodules gradually disappear from the population after iodine deficiency has been properly corrected. More recent studies suggest that chronic high iodine intake furthers classical thyroid autoimmunity (hypothyroidism and thyroiditis) and that iodine-induced hyperthyroidism may also have an autoimmune pathogenesis.

Measuring thyroglobulin autoantibodies by sensitive assay is important for assessing the presence of thyroid autoimmunity in areas with high iodine intake

There is some debate over the clinical utility of measuring serum TgAb to assess the presence of thyroid autoimmunity. To clarify the relationship between TgAb levels and thyroid autoimmunity, a histological examination of thyroid tissue was carried out on unselected living individuals with detectable serum TgAb. 146 patients with a pathological diagnosis of follicular adenoma were selected as subjects. Focal lymphocytic infiltration (FLI) was defined as lymphocytic aggregates of more than 200 in number. A thyroid gland in which 0-1 FLI was observed in a few visual fields of low magnification (20 x 4) in thyroid tissue adjacent to a tumor was judged to be normal and a thyroid gland in which 2 or more FLI were observed was diagnosed as focal lymphocytic thyroiditis (FLT). Serum levels of TgAb and TPOAb were measured by radioimmunoassay. Out of the 146 patients, 18 had detectable serum TgAb and 16 had detectable serum TPOAb. All but one (i.e. 94%) of the 18 TgAb positive patients had FLT and 14 out of the 16 TPOAb positive patients had FLT. The sensitivity (17/32; 53.1%) and specificity (113/114; 99.1%) of TgAb for detecting FLT were higher than those (14/32; 43.7% and 112/114; 98.2%) of TPOAb, but the differences were not significant. In 9 patients who were TgAb positive (but TPOAb negative), 8 (88.9%) had FLT. These results throw doubt on the Laboratory medicine practice guidelines published in Thyroid 2003, in which measuring TgAb is not usually necessary for detecting autoimmune thyroid disease. At least measuring TgAb by sensitive assay is useful for assessing the presence of thyroid autoimmunity in Japan, an area with high iodine intakes.

Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

Exploratory study on the association between high iodine intake and lipid

To explore the association between excessive iodine intake and lipid disorder in human bodies. Based on the NTTST sample survey on water iodine in Suining of Jiangsu province, this study involved 81 residents whose drinking water containing excessive iodine and 101 residents who drank water with normal iodine content. Blood samples were tested and compared on lipids (TG, TC, HDL-C, LDL-C, apoA1, apoB) between the two groups, after adjusting the influences of age and gender. The study also compared the abnormal rate of each lipid indicator between the two groups. Corresponding RR values and 95% confidence interval were calculated. Correlation between iodine content in drinking water and blood lipid was also studied. apoA1 in the group with excessive iodine intake was significantly lower than that in the normal iodine group, while there were no significant differences between the two groups in other lipid indicators. The abnormal rate of HDL-C of excess iodine group (16.88%) was significantly higher than the rate of normal iodine group (7.22%) while there were no significant differences between the two groups in other lipid indicators. Both apoA1 and HDL-C in the excess iodine group had a negative correlation with water iodine, while the other indicators of two groups had no correlation with water iodine. Drinking water with excess iodine might increase the risk of lipid disorder.

Iodine content of mother’s milk – Hungarian representative survey, 2006

In Hungary, except for some small area, iodine content of soil, cultivated crops and potable water is low; therefore the iodine intake of Hungarian population is lower than the amount recommended by international organizations. The high iodine intake for pregnant and nursing women is important to ensure the appropriate iodine intake of fetus and nursing babies, as well. The objective of the study was to get a comprehensive picture of iodine content of mother's milk and to make recommendation for the level of iodine supplementation for pregnant and nursing women. Following a country-wide sampling, iodine content of 72 human milk samples were analyzed by inductively coupled plasma-mass spectrometry. Iodine intake in 42 percent of babies is lower than the recommended amount which could remarkably influence the physical and mental development of infants. Iodine supplementation and consumption of food with high iodine content is highly recommended during pregnancy and nursing.

Effect of various iodine supplementations, rapeseed meal application and two different iodine species on the iodine status and iodine excretion of dairy cows

The aim of the present study was to investigate the impact of various feed iodine supplementations up to the permitted maximum level in the EU, the effect of applying rapeseed meal (RSM) compared to a glucosinolate (GSL) free ration and the impact of two different iodine species (iodide, iodate) on milk, urinary, faecal and blood serum iodine as well as on T 3 and T 4 levels of blood. The results of the milk iodine are not completely shown but partly discussed in this paper. The study was conducted with 32 dairy cows, divided into 4 groups with 8 animals each. In two groups the cows were fed distillers dried grains with solubles (DDGS) as main protein source (16.5% of ration DM), in the other groups rapeseed meal (3.5 mmol GSL/kg) was applied. In each case half of the animals received feed with iodine in the form of potassium iodide, the other half as calcium iodate. Iodine supplementations of 0, 0.5, 1, 2, 3, 4 and 5 mg/kg DM were tested in consecutive periods of 21 days each. The supplementary iodine increased iodine contents of serum, urine and faeces. RSM application resulted in consistently higher iodine contents in the mentioned matrices just displaying significant differences at high supplementation levels. When feeding DDGS, at high iodine supplementations iodide caused higher serum and faecal iodine than iodate. Besides, the iodine species showed no consistent impact on the tested parameters. At the highest tested iodine supplementation (5 mg/kg DM) in the experimental groups (DDGS/iodide, DDGS/iodate, RSM/iodide, RSM/iodate) the iodine concentration of serum amounted to 234, 157, 334 and 361 µg/l, of urine to 1134, 1020, 2341 and 2513 µg/l and of faeces to 673, 354, 715 and 790 µg/kg fresh matter. At the same supplementation level T 4 was significantly lowered. No impact was shown for the RSM application and the iodine species on T 3 and T 4. The results of the present study indicate that high iodine intakes not only cause strong increases in milk and urinary iodine but also lead to a considerable rise of iodine excretion via faeces. RSM in feed causes a shift of iodine normally excreted via milk to an excretion via urine and faeces accompanied by higher serum iodine.

The Impact of Iodine Excess on Thyroid Hormone Biosynthesis and Metabolism in Rats

Thyroid function ultimately depends on appropriate iodine supply to the gland. There is a complex series of checks and balances that the thyroid uses to control the orderly utilization of iodine for hormone synthesis. The aim of our study is to evaluate the mechanism underlying the effect of iodine excess on thyroid hormone metabolism. Based on the successful establishment of animal models of normal-iodine (NI) and different degrees of high-iodine (HI) intake in Wistar rats, the content of monoiodotyrosine (MIT), diiodotyrosine (DIT), T(4), and T(3) in thyroid tissues, the activity of thyroidal type 1 deiodinase (D1) and its (Dio1) mRNA expression level were measured. Results showed that, in the case of iodine excess, the biosynthesis of both MIT and DIT, especially DIT, was increased. There was an obvious tendency of decreasing in MIT/DIT ratio with increased doses of iodine intake. In addition, iodine excess greatly inhibited thyroidal D1 activity and mRNA expression. T(3) was greatly lower in the HI group, while there was no significant difference of T(4) compared with NI group. The T(3)/T(4) ratio was decreased in HI groups, antiparalleled with increased doses of iodine intakes. In conclusion, the increased biosyntheses of DIT relative to MIT and the inhibition of thyroidal Dio1 mRNA expression and D1 activity may be taken as an effective way to protect an organism from impairment caused by too much T(3). These observations provide new insights into the cellular regulation mechanism of thyroid hormones under physiological and pathological conditions.

Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

Epidemiological studies have indicated that high iodine intake might be a risk factor for papillary thyroid cancer (PTC), which commonly harbors the oncogenic T1799A BRAF mutation. The objective of the study was to investigate the relationship between BRAF mutation in PTC and iodine intake in patients. We analyzed and compared the prevalences of the T1799A BRAF mutation in classical PTC of 1032 patients from five regions in China that uniquely harbor different iodine contents in natural drinking water, ranging from normal (10-21 microg/liter) to high (104-287 microg/liter). The BRAF mutation was identified by direct DNA sequencing. The prevalence of BRAF mutation was significantly higher in any of the regions with high iodine content than any of the regions with normal iodine content. Overall, BRAF mutation was found in 387 of 559 PTC with high iodine content (69%) vs. 252 of 473 PTC with normal iodine content (53%), with an odds ratio of 1.97 (95% confidence interval 1.53-2.55) for the association of BRAF mutation with high iodine content (P < 0.0001). In addition, clinicopathological correlation analysis, the largest one of its type ever, showed that BRAF mutation was significantly associated with extrathyroidal invasion, lymph node metastasis, and advanced tumor stages of PTC. High iodine intake seems to be a significant risk factor for the occurrence of BRAF mutation in thyroid gland and may therefore be a risk factor for the development of PTC. This large study also confirmed the association of BRAF mutation with poorer clinicopathological outcomes of PTC.