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Effects of high fluoride and iodine combined exposure on thyroid nodules and goiter in school-age children in Jiangsu, China.Abstract
Introduction
With advancements in detection equipment and an increase in the frequency of examinations, thyroid nodules and goiter in children have garnered attention.
Objective
This study aims to determine the effects of high iodine and fluoride exposure on thyroid nodules and goiter in school-aged children.
Methods
We recruited children aged 8 to 12 from rural Jiangsu, China, based on the concentrations of iodine and fluoride in local drinking water and urine. Participants were divided into four groups: a group with high fluoride and iodine (HFHI), a group with high fluoride (HF), a group with high iodine (HI), and a control group (CONTROL). Fluoride levels in both drinking water and urine samples were measured using the ion-selective electrode method. Urinary iodine (UI) was assessed using inductively coupled plasma mass spectrometry, and children’s thyroids were examined with portable ultrasound equipment equipped with a linear 7.5-MHz probe.
Results
The detection rates of thyroid nodules in the HFHI, HF, HI, and CONTROL groups were 10.4 %, 6.5 %, 7.7 %, and 2.8 %, respectively. The goiter detection rates were 3.8 %, 2.9 %, 3.8 %, and 1.1 %, respectively. In the HFHI group, statistically significant correlations were found between urinary fluoride (UF) and thyroid nodules (P = 0.011, adjusted OR and 95 % CIs were 2.29 [1.21, 4.32]), as well as between UI and thyroid nodules (P = 0.038, adjusted OR and 95 % CIs were 1.58 [1.04, 2.40]), and between UI and goiter (P = 0.014, adjusted OR and 95 % CI were 2.31 [1.19, 4.48]). In the HI group, there was a statistically significant link between UI and goiter (P = 0.005, adjusted OR and 95 % CI were 2.45 [1.31, 4.58]).
Conclusions
Combined high iodine and fluoride exposure may have an adverse effect on thyroid nodules in school-age children.
EXCERPTS:
4 Discussion
The simultaneous exposure of school-age children to both high iodine and fluoride levels in rural areas of northern Jiangsu has been associated with an increase of thyroid nodules compared to exposure to high fluoride or high iodine. However, this dual exposure did not result in a significant increase in the goiter rate. In the HFHI group, a positive association was observed between urinary fluoride levels and thyroid nodules, as well as between urinary iodine and thyroid nodules. Additionally, an increase in urinary iodine concentration correlated with a higher detection rate of goiter in both the HFHI and HI groups.
Thyroid nodules are less prevalent in children and adolescents compared to adults, with an incidence of detectable thyroid nodules ranging from 1.5% to 13 % [32–34]. Our study found that the detection rate of thyroid nodules in children was intermediate [35]. Literature reports indicate that the incidence of goiter ranges from 1.9 % to 16 %, with women around 50 years old being the most commonly affected group [36]. Research on goiter prevalence in children is limited. In our study, the goiter rate was less than 5 % across all groups and subjects.
Research has also shown that elevated levels of iodine and fluoride can impact children’s cognitive abilities, as well as their iodine and fluorine metabolism [37]. Urinary fluoride is commonly used as a diagnostic test for fluoride poisoning [38]. We collected urine samples from the participating children. Studies conducted in Canada and Mexico have demonstrated that internal fluoride exposure correlates with external exposure, as evidenced by the correlation between fluoride levels and water fluoride concentrations in the HFHI and HF groups [39–41]. Both the HFHI and HF groups exhibited similar urinary fluoride levels, and a correlation was found between urinary fluoride and thyroid nodules. However, the detection rates of thyroid nodules differed, possibly due to the addition of high iodine exposure. Conversely, the HFHI group showed an association between urinary iodine and thyroid nodules, while the HI group did not exhibit such an association, suggesting a potential relationship influenced by the presence of high fluoride.
High fluoride exposure has been shown to lower the concentration of antioxidants in the human body, thereby increasing sensitivity to fluoride [42]. One study demonstrated that excessive ingestion of fluoride by rats damages the structure of the thyroid gland [43]. Another animal study reported that fluoride exposure inhibited the sodium-iodine symporter [44], suggesting that fluoride exposure hampers iodine absorption and metabolism. This indicates a potential biological interaction between fluorine and iodine. However, the specific mechanism remains unclear. Furthermore, population studies have suggested that fluoride exposure may disrupt thyroid function. Our research results may suggest a potential synergy between high levels of fluoride and iodine in thyroid nodules, but further investigations are necessary to clarify the precise mechanism involved.
The iodine concentration in water is the primary factor influencing geographical variations in iodine consumption [45,46]. As urine iodine indicators are highly sensitive, the median urinary iodine level in a cohort of more than 100 individuals [47] serves as a useful biomarker for assessing iodine intake. In our study, iodine nutrition levels were found to be excessive in both the HFHI and HF groups. This aligns with existing knowledge that external environmental exposure to high iodine can result in excessive iodine intake. Additionally, the impact of excessive iodine exposure on thyroid nodules may differ by gender [48]. In our study, we also observed this difference in overall analysis. However, when we conducted subgroup analyses, no significant gender difference was detected within each group. The varying influences of iodine and fluoride or the sample size may account for these observations.
Some studies have shown that combined exposure to high fluoride and high iodine is a risk factor for goiter [49,50]. Our study also indicated that the rate of thyroid swelling in the HFHI and HI groups was higher than that in the HF and CONTROL groups, but the difference was not statistically significant. Notably, the median urinary iodine levels in the HFHI and HI groups were both greater than 300 ?g/L, which may be related to the low overall detection rate of goiter across all groups. A study conducted in China suggested that excess iodine in household water was likely the cause of endemic goiter and elevated urinary iodine levels in that region [51]. Our findings also showed an association between urinary iodine and goiter in the HFHI and HI groups. Furthermore, a study from Turkey found that the prevalence of goiter was higher among individuals with a high BMI [52]. In Chinese women, BMI has been significantly associated with goiter [53], and obesity is recognized as an independent risk factor for the development of large nodular goiter [54]. Our study found a statistically significant association between BMI and goiter. After conducting regression analysis across all groups, we discovered a correlation between obesity and goiter, specifically in the HFHI group.
In China, dental fluorosis is likely the most prevalent form of fluorosis, affecting both children and adults [55]. The results of our study indicated that nodules were more likely to occur in children with dental fluorosis. The occurrence of dental fluorosis suggests that fluoride accumulation or its effect within the body have reached a certain threshold. Typically, the urinary fluoride concentration of patients is higher than that in those without it [31,56]. Therefore, the increased rate of thyroid nodules in children with dental fluorosis aligns with the findings from our regression analysis.
We must interpret our findings cautiously. Our study relies on the analysis of individual urinary iodine levels, and most indicators recommend the median to assess iodine nutrition. Thus, although our results show a link between urinary fluoride, urinary iodine, and thyroid nodules in the HFHI group, further research is needed, incorporating additional towns with varying levels of water fluoride and water iodine to obtain more comprehensive and robust evidence.
5 Conclusion
Our study suggests that combined exposure to high levels of iodine and fluoride may have an adverse effect on the development of thyroid nodules in school-age children. Furthermore, future studies should focus on elucidating the interaction mechanisms of fluorine and iodine within human metabolic processes.
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