After the industrial revolution, the earth's atmosphere started to be contaminated with the gas production of fossil fuels consumption. Different air pollutants with particulate matter (PM) with a diameter of ≤ 2.5 µm (PM2.5), such as CO, SOx, and NOx have affected the health of all living creatures on earth and human beings in different aspects [23]. Mainly, we focused on the effect of air pollutants on the thyroid in this study. With regard to the applied meta-analysis, maternal hypothyroxinemia was associated with PM2.5 exposure, while no positive relationship was found with NO2 exposure. Additionally, PM2.5 exposure could significantly affect congenital hypothyroxinemia.
Hypothyroxinemia is an essential widespread issue in pregnant women due to its effects on fetal brain development [24]. Thus, the association of air pollutants with maternal thyroid function is a concern in the industrial world. Some articles have found that maternal PM2.5 and NO2 exposure had inverse associations with FT4 levels, while maternal or neonatal TSH levels had no association with this exposure [23, 25, 26]. During the first trimester, higher exposure to PM2.5 could decrease maternal FT4 concentrations [23]. Also, another research mentioned that PM2.5 and NO2 affect the mother in the second and first trimesters of pregnancy, respectively [25]. Therefore, in the first-trimester pregnant woman's thyroid is more susceptible to PM2.5 exposure, and the second trimester is a harmful period to the maternal thyroid for the same exposure [23, 25]. Nevertheless, the exact pathophysiological mechanism is still unclear, but different studies reported a dose-dependent association between PM2.5 exposure and thyroid hormone levels, especially TSH [23, 27]. Others suggested that TPO antibody positive women are more vulnerable to side effects of air pollutants [25]. Moreover, air pollutants toxicity, mutagenicity, and increment of oxidative stress and inflammation can have roles in the mechanism [27].
Followed by air pollutants' effects on maternal thyroid hormones, it is essential to evaluate their impact on neonatal hypothyroidism due to the crucial role of thyroid hormones in the metabolisms, growth, and neurodevelopment of the fetus. In several studies, exposure to PM2.5 in the third trimester of pregnancy could affect thyroid hormone levels and reduce birth weight due to decreased FT4 levels in cord blood and increased congenital hypothyroidism (CHT) [28–31]. This effect was highly consistent with our meta-analysis findings. This study suggested that PM2.5 exposure may be inversely associated with TSH levels and the FT4/FT3 ratio in cord blood, showing the effective conversion of T4 into T3 [28]. However, in another study, PM2.5 exposure during pregnancy was associated with increased TSH levels in both the mother and the newborn [32]. Also, PM2.5 could positively affect T4 levels in newborns, while no association was found between NO2 and T4 levels [33].
In contrast, another study conducted by Cuifang Qi et al. has mentioned that O3 and NO2 exposure in the mother possibly influences CHT [34]. If air pollution increases the thyroxine-binding globulin (TBG) levels, neonatal T4 concentration could increase while neonatal FT4 could decrease [15, 29]. Li Shang et al. commented that if the average PM2.5 concentration is less than 58.500 µg/m3, the effects of PM2.5 on thyroid gland development would not be harmful [31]. The most vulnerable windows for prenatal PM2.5 exposure have been the first trimester, third trimester, or last month of pregnancy [33]. The suggested mechanism for the PM2.5 effect might contribute to oxidative stress, leading to DNA damage and a decrease in oxygen and nutrient exchange between the placenta and fetus [31].
Another concern about air pollution is creating a favorable environment for cancer progression and increasing cancer risks. A study in São Paulo demonstrated that PM10 air pollution could increase the incidence and mortality of some cancers [35]. This study associated thyroid cancer incidence with PM10 [35]. In another investigation, the mixture of industrial waste gas and not just one air pollutant was related to the elevation of the incidence of thyroid cancer [36]. Some research specifically studied the effect of air pollution on thyroid cancers. At least two years of exposure to PM2.5 increases the risk of papillary thyroid carcinoma (PTC) [20]. Moreover, by increasing the concentration of PM2.5 and duration of exposure, the risk will be higher due to potential genomic instability and mutations in proto-oncogenes [20]. Additionally, Hg highly affects the hypothalamic-pituitary-thyroid axis, which leads to decrease levels of T3 and T4 and elevated levels of TSH. Hence, the thyroid gland is prone to hyperplasia and neoplasia [37]. Nevertheless, the effect of air pollutants on thyroid malignancies needs further investigations to figure out the mechanism and approaches to control it better.
There were studies about air pollution's effects on thyroid function in the general population. In a study in China, after air pollution exposure, FT4 concentration lowered due to possible acceleration of T4 removal, while FT3 concentration elevated, and as a result, the FT4/FT3 decreased [38]. PM2.5 exposure did not significantly influence TSH levels in the study [38]. Another research conducted by Hyun-Jin Kim in South Korea indicated that thyroid function in elderly or obese people is more susceptible to air pollution, especially NO2 and CO, and lowered FT4 levels and elevated TSH levels were observed [39]. Additionally, people living near the Petrochemical Complex are at higher risk of anti-thyroid antibodies, thyroiditis, and primary hypothyroidism due to the immunotoxicity mechanisms of compounds in petrochemical plants [6, 40].
One of the limitations of our study was the lack of studies in some fields related to thyroid abnormalities, such as hypothyroidism in the general population. Therefore, a meta-analysis could not be performed for these categories. On the other hand, the heterogenicity of some articles was more than expected, and they were not qualified for meta-analysis, for instance, the thyroid cancer subgroup. As a result, we just discussed their results without pooling their data.
In conclusion, air pollution could influence thyroid function, especially in pregnant women and newborns. These groups are prone to hypothyroidism. This study and similar investigations provide evidence of air pollution toxicity for healthcare systems. Preventive policies should be considered to keep air pollutants concentration below the harmful threshold.