| BackgroundThe thyroid is the endocrine organ of a human body, which mainly regulates the secretion of thyroid hormone to affect the metabolism of a human body and the growth and development of an organism. Due to the influence of heredity, immunization and infection, the incidence of autoimmune thyroid diseases in a crowd is on the rise. Hyperthyroidism is referred to as hyperthyroidism. Eighty percent of patients suffer from Grave’s disease (abbreviated as GD). Grave’s disease is one of organ specific autoimmune diseases. Hypothyroidism is abbreviated as hypothyroidism, the most common of which is autoimmune thyroiditis caused by Hashimoto’s thyroiditis. The thyroid endocrine dysfunction can significantly affect pregnant women and their offsprings. The incidence of pregnant women with thyroid diseases is only next to that of pregnant women with diabetes, which is a common endocrine system disease. According to reports, the incidence of pregnant women with hyperthyroidism (referred to as hyperthyroidism) is about 0.1% to 0.4%, mainly as Grave’s disease. The incidence of pregnant women with hypothyroidism is about 0.05%, and the common primary cause of hypothyroidism is Hashimoto’s disease. Pregnancy with thyroid diseases can cause miscarriage, stillbirth, premature delivery, neonatal asphyxia and other diseases, and can also cause neonatal thyroid disease, mental development and growth disabilities. There are multiple kinds of autoimmune thyroid diseases, most notable of which are thyroid peroxidase antibodies (thyroperosidase antibody, TPOAb), thyroglobulin antibody (TgAb), and TSH receptor antibody (TRAb). Recent studies have confirmed that thyroid autoantibodies and habitual abortion, pregnancy, postpartum thyroiditis, hypothyroidism and other diseases are closely related. Iodine is the main constituent of the thyroid hormone in a human body, which is an essential element for the synthesis of thyroid hormone. The thyroid gland is the strongest tissue to absorb iodine, and 70% to 80% of the iodine in a human body is in the thyroid gland. Iodine not only involves itself in the synthesis and release of the thyroid hormone, but also regulates the synthesis and release of the thyroid hormone. When iodine concentration in the thyroid gland is high, iodine would inhibit peroxidase activity, reduce tyrosine generation and inhibit the synthesis of thyroid hormone. The excessive iodine in a thyroid gland can inhibit the release of lysosome in thyroid follicular, suppress hydrolysis of thyroid from thyroglobulin, inhibit the release of thyroid hormone in follicular, thereby, and in turn quickly reduce the level of circulating thyroid hormone (Wolff-Chaikoff effect is known as the effect of iodine retarded). Pregnancy is a complex physiological process when many changes would occur to the metabolism in the body. To go through her pregnancy cycle smoothly, a pregnant woman not only needs to ingest plenty of protein, folic acid and other nutrients, but she also need to take some essential trace elements (iodine, iron, etc.). Iodine deficiency is one of the main known reasons for mental retardation in human. However, excessive iodine can cause damage at varying degrees to human. Long-term excessive intake of iodine by a pregnant woman can inhibit the secretion of thyroid hormone, and even cause congenital hypothyroidism dysplasia and thyroid dysfunction in her fetus. The newborn may suffer from high iodine goiter or even suffocation. Oxidative stress refers to a body subjected to various harmful stimuli produces highly reactive molecules in vivo such as reactive oxygen species (ROS) and reactive nitrogen radical (or reactive nitrogen species, RNS), whose quantities are beyond the removal capacities of the antioxidant system and lead to imbalance between the oxide and antioxidant systems and consequently tissue damage. As the required starting material in the synthesis of thyroid hormones, iodine is also involved in the synthesis of thyroid hormone, which is an active response of the production of ROS. Therefore, iodine is closely related to the oxidative damage of thyroid. When iodine is in deficiency, the persistently elevated TSH will stimulate the thyroid gland to produce and cumulate excessive H2O2 and other oxygen radicals beyond the scavenging ability of the antioxidant of the defense system and cause damage to the structure of cell membranes. Experimental studies have found that in the development of diseases of low iodine, the thyroid follicular epithelial cells are in a state with unbalanced compensation and decompensation. And if low iodine is sustained, this imbalance will gradually be enhanced. As a result, antioxidant capacity will be lower, radicals will be more and cells will be further damaged. The mechanism of thyroid gland damage caused by excessive iodine is also associated with the Wolff- Chaikoff effect. However, this blocking effect is temporary. Whenever the body has adapted itself to the situation, the blocking effect will disappear, which is called the escape phenomenon. The mechanism of thyroid gland damage caused by excessive iodine is associated with oxidative stress because iodine and H2O2 are related to tyrosine residues. In the presence of H2O2 and TPO, I-is first oxidized to I+, and then I+ reacts with the excessive I- to generate I2. Reaction between H2O2 and I2 can generate a variety of oxygen free radicals. Meanwhile I2 itself is also a highly reactive molecule that can react with proteins, lipids and nucleic acids to generate various iodide lipid compounds accompanying with the generation of reactive oxygen species and lipid peroxidation, which leads to the loss of integrity of cell membrane and mitochondrial membrane structures. Iodine overdose may also activate the body’s defense mechanisms. Studies found that the blood supply of thyroid is very sufficient when low iodine is ingested, With the increase of iodine intake, the blood supply of thyroid is significantly reduced, this may be the protective or adaptive response of the body to excessive iodine in order to avoid thyroid follicular epithelial cell injury caused by high iodine concentration. Iodine deficiency is a common phenomenon in the special physiological state of pregnancy, but the presence of excessive iodine cannot be completely ruled out. High or low level of iodine nutrition is closely related to the occurrence of oxidative stress and thyroid diseases. Therefore, iodine nutrition surveillance shall not be overlooked in the dietary of pregnant women.Oxidative stress plays a major role in the occurrence and development of thyroid diseases. The study of Zarkovic M showed that when a body is in a hyperthyroidism state, oxidative stress and antioxidant balance disorders occur. Oxygen free radicals are involved in the reaction process of autoimmune thyroid diseases. The study of Ademoglu found that the level of malondialdehyde in the plasma of patients with GD is significantly higher than that in the control group, while the total level of thiol is significantly reduced. The former is an enhanced reflection of oxidation in vivo, while the latter is a non-enzymatic antioxidant. The level change of both sides indicates that there is oxidative stress in patients with GD. The study of Bednarek found that the content of oxidation reaction product in patients with GD is significantly higher than that in normal controls, and that the activity of antioxidants such as SOD is also significantly increased compared to the control. Erdamr conducted studies on the newly diagnosed hypothyroidism patients of HT and hyperthyroidism patients of GD. The results showed that the generation of ROS is increased and the antioxidant system is in dysfunction in the experimental group, which is more apparent in the HT hypothyroidism group. Thus, there is a close relationship between oxidative stress and thyroid diseases. There are an antioxidant enzyme system and a nonenzymatic antioxidant system in a body. Superoxide dismutase (SOD) as an important part of the enzyme antioxidant system plays an irreplaceable role in the oxidative stress process. It is the only enzyme that can specifically remove superoxide radicals. It is the most effective antioxidant and free radical scavenger. The oxidative stress of placent happens in trimester, but as some antioxidants such as superoxide dismutase, catalase and glutathione peroxidase enzymes are increased at this time, the reactive oxygen can be timely removed from the placent to avoid oxidative stress damage and pregnancy can be maintained. An antioxidant system with its functions hindered may lead to adverse pregnancy outcomes such as miscarriage, premature rupture of membranes and others.In summary, the abnormal function of the autoimmune system in pregnant women can cause harm to the matrix and the fetus. As thyroid diseases can take on various forms, further studies on the impact of the various thyroid malfunctions during pregnancy on the matrix and the fetus are needed. The pathogenesis of thyroid diseases during pregnancy is very complex. There are studies found that iodine, oxidative stress and thyroid function are related to autoimmune abnormalities. In this study, we investigate the level of iodine nutrition, oxidative stress in pregnant women to analyze the relationship between iodine and oxidative stress during pregnancy and their impact on thyroid function and autoimmunity to provide the basis for prevention and treatment of thyroid diseases during pregnancy to reduce the pregnancy incidences and adverse neonatal outcomes.Objective1. To find out the relationship between the iodine nutrition level at different pregnant stages and the thyroid hormone level by studying pregnant women with thyroid diseases.2. To study the superoxide dismutase in pregnant women with thyroid disease.3. To study how iodine and superoxide dismutase affect thyroid function in pregnant women so as to provide the basis for the prevention and treatment of thyroid disease during pregnancy.Subjects and Methods1. Research subjectA total of 442 women aged from 17 to 44 (27±4 on average) and in singleton pregnancies were chosen from the Chancheng District Center Hospital to participate in this study between June 2013 and November 2014.1.1 Subject selection criteriaNo personal or familial thyroid diseases,No touched thyromegaly,No history of taking drugs containing iodine or antithyroid for the last three months,No unhealthy habits, such as excessive drinking, smoking and so on,No hereditary diseases, autoimmune diseases, organ dysfunction, psychiatric history and so on.1.2 Sample selectionOf the 442 subjects,145 (32.81%) were in early pregnancy (≤12 weeks),146 (33.03%) were in mid-pregnancy (13 to 27 weeks), and 151 (34.16%) were in late pregnancy(≥28 weeks).2. Research Methods and Procedures2.1 Subject history inquisition and general inspectionAll selected research subjects were requested to accept the subject history inquisition and physical examination, and risk factors were recorded.2.2 Laboratory examinationThe levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were determined using the method of electrochemiluminescence with E170 automated chemiluminescence analyzer. The urinary iodine content in pregnant women was measured by its catalytic effect on the As-Ce reaction. The superoxide dismutase (SOD) was determined using the method of pyrogallol autoxidation.2.3 Pregnancy outcomeAll results of the research subjects were tracked childbirth. The termination of pregnancy and the situation of childbirth were recorded.3. Research design3.1 Research subjectSubjects were chosen from the pregnant women going to the hospital for routine check.3.2 Diagnostic criteria of thyroid disease during pregnancy.The diagnostic criteria of thyroid disease were referred to the diagnosis and treatment guidelines of pregnancy and postpartum thyroid diseases of China in 2012. The reference values of FT4 and TSH in pregnant women were referred to reference ranges established by the First Affiliated Hospital of China Medical University (Shenyang), Tianjin Medical University General Hospital and the Affiliated International Peace Maternity and Child Health Hospital of Shanghai Jiaotong University. The reference range of FT4 is 9.12 to 22.35 mIU/L, the reference range of TSH is 0.05 to 6.84 mIU/L. The reference range of thyroid autoantibodies is provided by the reagent manufacturer. FT3 and thyroid autoantibodies reference ranges are also provided by the reagent manufacturer as:FT3,3.1-6.8 pmol/1; A-TPO,<34 IU/ml; TRAb,<1.75 IU/L; TgAb,<115 IU/ml.3.3 The diagnostic criteria of urinary iodineRefer to the standard of iodine nutrition during gestational period and lactation suggested by the WHO in 2007.3.4 The division of gestational weeks and pregnancy outcomeThe gestational weeks were divided into early gestation, mid gestation and late gestation, and pregnancy outcomes were generally classified as low birth weight new born, neonatal asphyxia, fetal distress, premature delivery, miscarriage, dead fetus and so on.3.5 Analysis of the prevalence of thyroid disease during gestational period3.6 Analysis of the relation of thyroid disease together with pregnancy and neonatal complications3.7 Analysis of the level of iodine nutrition of pregnant women and the iodine nutritional status of pregnant women in different gestational weeks3.8 Analysis of the relationship between the level of iodine nutrition of pregnant women and different gestational weeks with different thyroid diseases3.9 Analysis of the relationship between the SOD of different levels of iodine nutrition and gestational weeks (plotting)3.10 Analysis of the relationship between the superoxide dismutase in peripheral blood of pregnant women and thyroid diseases4. Statistical analysisFor data with normal distribution, differences were tested using t-test. For data with skewness distribution, differences were tested using the nonparametric Mann-Whitney U test. Count data were analyzed usingχ2 test. For all tests, a significant level of P< 0.05 was used.Results1. General situation of the research subjectA total of 442 pregnant women aged from 17 to 44 (27±4 on average) and with gestational weeks of 8 to 36 were chosen in this study. Of the 442 subjects,145 (32.81%) were in early pregnancy,146 (33.03%) were in mid pregnancy, and 151 (34.16%) were in late pregnancy.All results of the research subject were tracked until childbirth, and the termination of pregnancy and the situation of childbirth were recorded.All the pregnant women were tracked until the end of their pregnancy (the latest on November 30,2014).395 (89.37%) pregnant women gave full-term births,20 (4.52%) went through premature delivery,22 (4.98%) were subjected to abortion, and 5 (1.13%) gave stillbirth.2. The prevalence of thyroid disease during gestational periodThere were 11 cases (2.49%) of hyperthyroidism,24 cases (5.43%) of subclinical hyperthyroidism,14 cases (3.17%) of hypothyroidism,28 cases (6.33%) of subclinical hypothyroidism,12 cases (2.71%) of low FT4 hyperlipidemia and 32 cases (7.24%) of thyroid function normal antibody which was positive.3. The relationship between thyroid disease during gestational period and pregnancy outcomeThe rate of bad pregnancy outcome of euthyroid women during gestational period was significantly lower (P<0.05) than that of women of thyroid diseases during gestational period.4. The relationship between the iodine nutrition in pregnant women and thyroid diseasesThe median urinary iodine (MUI) in 442 cases of pregnant women was 174 g/L. The percentages of the groups with UIC<50μg/L, UIC of 50-149 μg/L, UIC of 150-249 μg/L, and UIC≥250μg/L were 4.30%,29.86%,39.59% and 26.24%, respectively. The prevalence of thyroid disease in the group with UIC≥250 μg/L was significantly higher (P<0.05) than that of the groups with UIC<150 ug/L and UIC of 150-249 μg/L. The prevalence of thyroid disease in the group with UIC<150 μg/L was significantly higher (P<0.05) than that of the group with UIC of 150-249 μg/L. For the prevalence of hypothyroidism in pregnant women with three different levels of iodine nutrition (including hypothyroidism, subclinical hypothyroidism, low FT4 and simple thyroid autoantibodies which is positive), the prevalence of<150 μg/L group was significantly higher than that of the 150-249 μg/L group and the≥250 μg/L group. The prevalence of the ≥250 μg/L group is significantly higher (P<0.05) than that of the 150-249 μg/L group.The median urinary iodine at early, middle and late gestation was 164 μg/L,173 μg/L and 182 μg/L, respectively. This study showed that the level of iodine nutrition of pregnant women in different gestational periods was sufficient. The abnormal rate of the level of iodine nutrition in early, middle and late gestation was 72.41%, 45.89% and 62.91%, respectively. The incidence of thyroid diseases was 31.03%, 21.23% and 29.80%, respectively. The incidence of thyroid diseases in early gestation was significantly higher (P>0.05) than that in middle and late gestations.5. Comparison of the levels of FT3, FT4, TSH and SOD in different iodine nutrition groupsThe levels of FT3, FT4, TSH in the iodine-adequate group were lower than those in the iodine-deficient group and iodine-excessive groups. The level of SOD in the iodine-adequate group was higher than the other two groups. There was statistically significant (P<0.05) differences in the level of FT4 between the iodine-adequate group and the iodine-deficient group. There was statistically significant differences (P<0.05) in the level of TSH between the iodine-adequate group and the iodine-excessive group. In different gestational periods, the SOD activity in the group with normal iodine nutrition was significantly higher (P<0.05) than that in the group with abnormal iodine nutrition.6. SOD activity differences between gestational periods and different levels of iodine nutritionIn the group with normal iodine nutrition, the SOD level was higher in the second trimester of pregnancy than in early and late pregnancy. In the group with abnormal level of iodine nutrition, the SOD level was higher in early pregnancy than in the second and third trimesters. There was no significant differences (P>0.05) in SOD level between the normal and abnormal iodine nutrition groups in trimester or second trimester. The difference in SOD level between the normal and abnormal iodine nutrition groups was statistically significant (P<0.05) in late pregnancy.7. The relationship between the superoxide dismutase in peripheral blood of pregnant women and thyroid diseasesThe 442 pregnant women were tested for superoxide dismutase (SOD). The results showed that among the 442 cases,121 cases had thyroid diseases (including 11 cases of hyperthyroidism,24 cases of subclinical hyperthyroidism,14 cases of hypothyroidism,28 cases of subclinical hypothyroidism,12 cases of low FT4, and 32 cases of a reactive antibodies normal), and 348 cases had normal thyroid function. There were no statistically significant differences between age and gestational weeks in the two groups (P>0.05). The results also showed that SOD activity in the group with thyroid diseases was significantly lower (P<0.05) than that in the group with normal thyroid function.Conclusions1. The incidence of preterm birth by pregnant women is increased by thyroid diseases during pregnancy, and the risk of adverse pregnancy of pregnant women is significantly increased by thyroid autoantibodies. This suggests that pregnant women with autoimmune thyroid diseases are more likely to be suffered from adverse pregnancy outcomes and neonatal complications.2. The abnormal level of iodine nutrition is closely related to thyroid diseases, and there is a correlation between the level of iodine nutrition and superoxide dismutase, which suggests that the level of iodine nutrition plays a role in pregnant women with thyroid diseases and the state of oxidative stress.3. Relative to the mid gestation, the dysfunction of iodine nutrition and thyroid is more prone to occur in the early gestation and late gestation. The oxidation stress reaction in the early gestation and late gestation is stronger than that in the mid gestation, which suggests that the factor of adverse outcomes of pregnancy is prone to occur in the early gestation and late gestation.4. The oxidative stress is prone to occur in pregnant women with thyroid diseases, which suggests that oxidative damage may play an important role in the occurrence of thyroid diseases. |
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