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Selenium Supplementation in the Treatment of Hashimoto's Thyroiditis: A Systematic Review and a Meta-analysis
Abstract
Evidence suggests that selenium (Se) supplementation could be useful as an adjunctive therapy to levothyroxine (LT₄) in the treatment of Hashimoto's thyroiditis (HT). To summarize evidence regarding its effect on thyroid autoantibodies' titers, demands in LT₄ replacement therapy, ultrasonographic thyroid morphology, and mood in patients with HT under LT₄ treatment, a systematic review and meta-analysis of relevant literature were performed.
Systematic review of prospective studies involving patients with HT under LT₄ treatment and meta-analysis of studies on randomized, placebo-controlled, blinded trials were performed.
Patients with HT assigned to Se supplementation for 3 months demonstrated significantly lower thyroid peroxidase autoantibodies (TPOab) titers (four studies, random effects weighted mean difference: −271.09, 95% confidence interval: −421.98 to −120.19, p< 10⁻⁴) and a significantly higher chance of reporting an improvement in well-being and/or mood (three studies, random effects risk ratio: 2.79, 95% confidence interval: 1.21-6.47, p= 0.016) when compared with controls. Demands in LT₄ replacement therapy and ultrasonographic thyroid morphology were found either unaltered or underreported.
On the basis of the best available evidence, Se supplementation is associated with a significant decrease in TPOab titers at 3 months and with improvement in mood and/or general well-being. Evidence suggests a different pattern of response to Se supplementation in HT relative to baseline TPOab titers, and this, if confirmed, could be used to identify which patients would benefit most from treatment. An improvement in thyroid function and morphology should be demonstrated before Se routine supplementation can be recommended in the treatment of HT.
... So, even mild selenium deficiency may lead to progression and survival of autoimmune thyroid diseases. [13] In various studies, the effect of selenium on reducing inflammatory activities of thyroid and reducing the titer of anti-TPO Ab, [3,12,[14][15][16][17][18] as well as its potential impact on improving echostructure thyroid ultrasound, [8,19] is shown. It seems that selenium as an adjunctive treatment with LT4 is effective in autoimmune thyroiditis. ...
... On the other hand, FT3 and FT4 levels in both groups fell to the same level. In other words, it can be concluded that the increase in serum levels of selenium have significantly reduced the levels of anti-thyroid hormone antibodies and our study confirms the hypothesis that selenium has inhibitory effect on the activity of anti-thyroid hormone antibodies although studies conducted by van Zuuren et al., Krysiak and Okopien and Negro et al., also revealed the effect of selenium on reducing inflammatory activity of the thyroid and anti-TPO titer, [3,12,[14][15][16][17][18] and the potential impact of increased serum levels of selenium on the improvement of thyroid echostructure has been demonstrated in studies of Onal et al., and Duntas during ultrasound. [8,19] It has been shown that selenium as an adjunctive treatment with LT4 is effective in autoimmune thyroiditis. ...
... [19] Leonidas in his study concluded that the use of selenium containing supplements is efficient in the prevention of thyroid diseases. [8] The study of Toulis et al., indicated that a significant reduction can occur in the level of anti-TPO due to the selenium prescription for 3 months in patients with Hashimoto's thyroiditis [15] in the study of Anastasilakis et al., the selenium prescription for 3 months in patients with hypothyroidism autoimmune had no significant effect on anti-TPO level but anti-TG level significantly reduced 3 months after treatment. [21] Considering the results of this study and other studies, the overall conclusion is that selenium supplementation in patients with autoimmune hypothyroidism may be helpful in reducing the levels of antibodies however, due to limitations of the present study, including the number of samples and the follow-up time still evidences are inadequate to support the efficacy of selenium supplementation in patients with autoimmune hypothyroidism [3] and also the exact impact of TPO-Ab and duration of the disease is not clear on the effect of selenium. ...
Background:
In the subclinical hypothyroidism, T4 or T3 levels are normal and thyroid-stimulating hormone (TSH) is slightly high. Selenium deficiency can lead to thyroid dysfunction. The present study aims to investigate the effect of selenium supplementation on the thyroid hormone and anti-thyroid peroxidase antibody (anti-TPO AB) levels.
Materials and methods:
In this double-blinded, randomized, placebo-controlled clinical trial, 42 patients with subclinical hypothyroidism were randomly assigned to receive 200 μg selenium or placebo for 8 weeks. In the both groups, the serum TSH and anti-TPO antibody levels were measured and assessed before and after the intervention.
Results:
After the interventions, the mean serum TSH reduction in the intervention and placebo groups was -10.98 ± 33.31 and -3.20 ± 38.36, respectively, which were not statistically significant. However, the mean serum anti-TPO Ab concentration increased in the intervention and placebo groups (109.81 ± 51.49% vs. 173.17 ± 96.26%), between which the difference was not statistically significant (P >0.05) despite a slight increase in the mean anti-TPO level in the intervention group.
Conclusion:
The results of the current study indicated that selenium supplementation has no significant effect on serum anti-TPO Ab and TSH levels in the patients with subclinical hypothyroidism. Studies with larger sample size and with different doses of selenium are needed to reach more precise results.
... T-cell activation is suppressed by the production of CTLA-4 on the surface of T cells, which is produced by T-cell receptor activation. CTLA-4 gene polymorphisms may lower CTLA-4 antigen expression or function, resulting in less suppression of T-cell proliferation and, as a result, increased susceptibility to autoimmune responses [11]. Several variants of the CTLA-4 gene have been examined in HT patients in the past. ...
... A 49A/G single nucleotide polymorphism (SNP) in exon 1 that results in threonine to alanine substitution has been linked to HT, but other investigations have not verified this association. A major meta-analysis of 866 HT patients found a substantial link with 49A/G, using both published and unpublished data [11]. ...
... Thyroid autoimmunity is the most common pathologic causing thyroid dysfunction in women of reproductive age. When compared to the general population, infertile women have a higher prevalence of thyroid autoimmune dysfunction [11]. However, there is a lack of evidence on the direct influence of TAA positivity on IVF success, particularly in the community of infertile, euthyroid TAA positive women. ...
Hashimoto thyroiditis, also known as chronic autoimmune thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune illness in which thyroid cells are damaged by immunological mechanisms involving cells and antibodies. Thyroid peroxidase and/or thyroglobulin autoantibodies in the serum are biochemical indicators of the condition, with females having a higher incidence than males and increasing with age. It's the leading cause of hypothyroidism in affluent countries. Inadequate dietary iodine intake, on the other hand, is the most common cause of hypothyroidism worldwide. The development of antithyroid antibodies that target the thyroid tissue, causing gradual fibrosis, is the pathogenesis of Hashimoto thyroiditis. The diagnosis can be difficult, and as a result, the problem is frequently not detected until late in the disease process. The most prevalent laboratory findings are raised TSH and low thyroxine (T4) levels, as well as enhanced antithyroid peroxidase (anti-TPO) antibodies. The pathogenesis, diagnosis, and management of Hashimoto thyroiditis are discussed in this article.
... Thyroid autoimmunity is the most common pathologic causing thyroid dysfunction in women of reproductive age. When compared to the general population, infertile women have a higher prevalence of thyroid autoimmune dysfunction (Toulis et al., 2010). However, there is a lack of evidence on the direct influence of TAA positivity on IVF success, particularly in the community of infertile, euthyroid TAA positive women. ...
... on the surface of T cells, which is produced by T-cell receptor activation. CTLA-4 gene polymorphisms may lower CTLA-4 antigen expression or function, resulting in less suppression of T-cell proliferation and, as a result, increased susceptibility to autoimmune responses(Toulis et al., 2010). Several variants of the CTLA-4 gene have been examined in HT patients in the past.Among them, the (AT)n microsatellite CTLA-4 polymorphism in the untranslated region (UTR) was linked to HT in Caucasian and Japanese patients, but not in Italians. ...
... A 49A/G single nucleotide polymorphism (SNP) in exon 1 that results in threonine to alanine substitution has been linked to HT, but other investigations have not verified this association. A major meta-analysis of 866 HT patients found a substantial link with 49A/G, using both published and unpublished data(Toulis et al., 2010). Preprints (www.preprints.org) ...
Hashimoto thyroiditis, also known as chronic autoimmune thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune illness in which thyroid cells are damaged by immunological mechanisms involving cells and antibodies. Thyroid peroxidase and/or thyroglobulin autoantibodies in the serum are biochemical indicators of the condition, with females having a higher incidence than males and increasing with age. It's the leading cause of hypothyroidism in affluent countries. Inadequate dietary iodine intake, on the other hand, is the most common cause of hypothyroidism worldwide. The development of antithyroid antibodies that target the thyroid tissue, causing gradual fibrosis, is the pathogenesis of Hashimoto thyroiditis. The diagnosis can be difficult, and as a result, the problem is frequently not detected until late in the disease process. The most prevalent laboratory findings are raised TSH and low thyroxine (T4) levels, as well as enhanced antithyroid peroxidase (anti-TPO) antibodies. The pathogenesis, diagnosis, and management of Hashimoto thyroiditis are discussed in this article.
... Furthermore, Se is a cofactor of iodothyronine deiodinase, which converts thyroxine (T4) to triiodothyronine (T3) , and plays a critical role in the regulation of thyroid hormone synthesis. Selenium has been suggested to act as a cofactor for glutathione reductase and glutathione peroxidase, which protect the thyroid gland against oxidative stress [5]. Zinc has been reported to be essential for the optimal thyroid function [6], which is essential in the normal conversion of thyroid hormones [7]. ...
... Studies were included in the final analysis if they: (1) had a case-control or cross-sectional design; (2) conducted investigations on adults (age > 18 years) with hypothyroidism and healthy controls; and (3) reported at least the mean and standard deviation of one of the trace elements (Zn, Se, Fe, Cu, Mn, Pb) and Mg in serum or plasma. Studies were excluded if they: (1) were trials, animal studies, case reports, conference papers, letters, editorial, or review studies; (2) did not have adequate information to extract the required endpoints for the purposes of the present study; (3) were conducted on children or pregnant women; (4) were uncontrolled studies or conducted on non-healthy controls; and (5) reported the levels of trace elements in erythrocytes. All studies were separately assessed by two investigators (H.M. and S.T.) to determine adherence to the selection criteria. ...
... These studies reported that there is an association between Se status and thyroid hormone metabolism; in addition, Se levels were reduced in autoimmune thyroid disorders [11,32]. The results of previous meta-analyses [5,43,44] indicated that Se supplementation may improve Hashimoto's thyroiditis health outcomes; specifically, Se decreased antibody levels and dosage of levothyroxine. Moreover, evidence from animal studies [45,46] revealed that a Se-deficient diet is linked to reduced T 3 and elevated T 4 concentrations. ...
The relationship between thyroid hormones metabolism and trace element levels has biological plausibility; however, previous reports that compared trace element levels in patients with hypothyroidism and healthy individuals yielded conflicting results. Therefore, the aim of this meta-analysis was to investigate the association between selected trace elements (i.e., selenium (Se), zinc (Zn), iron (Fe), manganese (Mn), copper (Cu), lead (Pb)), and magnesium (Mg) concentrations in patients with hypothyroidism and healthy controls. Electronic databases, including PubMed, Scopus, Embase, and Science Direct, were searched systematically until September 2019. Thirty-two observational studies were included in the final analyses. Hedges’ g tests were used to estimate effect sizes, as trace element concentrations were reported using different measurement units across the studies. Selenium (Hedges’ g = − 0.52; 95% CI = [− 1.05, − 0.002]; P = 0.049) and Zn (Hedges’ g = − 0.86; 95% CI = [− 1.66, − 0.06]; P = 0.035) concentrations were significantly lower, whereas Pb concentrations were significantly higher (Hedges’ g = 0.34; 95% CI = [0.10, 0.59]; P = 0.006) in patients with hypothyroidism compared with healthy controls. There were no differences in the concentrations of Fe, Cu, Mn, and Mg between the groups. Patients with hypothyroidism exhibited lower Se and Zn and increased Pb concentrations compared with healthy controls. High-quality studies with larger sample sizes are required to explicate the link between trace element status and hypothyroidism.
... To the best of our knowledge, the reviews or meta-analyses conducted so far have focused on the importance of selected nutrients in Hashimoto's disease, i.e., selenium, vitamin D, iodine, gluten, zinc, iron, and goitrogens [8,10,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. However, current clinical evidence of the effect of the dietary factors on HT is still scanty and inconclusive. ...
... A significant association was also observed between elevated anti-TPO (p = 0.001) and obesity, but no relationship was found between a positive anti-TG result and obesity. According to three meta-analyses, selenium supplementation leads to a reduction in antibodies, although, as the authors indicate, the quality of the included evidence is low [13,14,21]. According to the meta-analyses, Nigella sativa reduces body weight [51,52]. ...
Diet can be a complementary treatment for Hashimoto's disease by affecting thyroid function and anti-inflammatory properties. It is still unclear which dietary strategy would be the most beneficial. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody and thyroid hormones levels) and characteristic symptoms in the course of Hashimoto's thyroiditis. This systematic review was prepared based on PRISMA guidelines. Articles in PubMed and Scopus databases published up to November 2022 were searched. As a result of the selection, out of 1350 publications , 9 were included for further analysis. The nutritional interventions included the following: elimination of gluten (3 articles) or lactose (1 article), energy restriction with or without excluding selected foods (n = 2), consumption of Nigella sativa (n = 2), or dietary iodine restriction (n = 1). The intervention duration ranged from 21 days to 12 months and included individuals with various thyroid function. Of the nine studies, three studies were female only. An improvement was observed during an energy deficit and after the elimination of selected ingredients (e.g., gluten, lactose, or goitrogens), as well as after the intervention of Nigella sativa. These interventions improved antibody levels against peroxidase (anti-TPO), (thyrotropin) TSH, and free thyroxine (fT4). No improvement was seen on the iodine-restricted diet. Varied outcomes of analyzed dietary interventions may be due to the heterogeneous thyroid condition, high variability between patients, and differences in habitual intake of critical nutrients (e.g., iodine, selenium, and iron) in different populations. Therefore, there is a great need for further experimental studies to determine whether any nutritional interventions are beneficial in Hashimoto's disease.
... Selenium is often prescribed in the treatment of AIT, while the effects of selenium supplementation on AIT were controversial. Some reports have confirmed a suppressive effect of selenium supplementation on serum TPOAb and TGAb levels in AIT patients [12,13]. However, an RCT study concluded that selenite supplementation had no effect on serum TPOAb and TSH levels in euthyroid TPOAb-positive women [14]. ...
... e effects of selenium supplementation on AIT were debated. Some meta-analyses have confirmed a suppressive effect of selenium supplementation on serum TPOAb and TGAb levels in AIT patients [12,13]. However, other studies demonstrated the opposite results. ...
Methods:
45 healthy and adult female SD rats were randomly divided into three groups: normal control group, EAT model group, and selenium yeast supplement EAT group. The EAT model rats were induced by subcutaneous injection of porcine thyroglobulin and fed with high iodine water. The concentrations of serum thyroid-stimulating hormone (TSH), TGAb, TPOAb, and B cell activating factor (BAFF) were detected in each group by enzyme-linked immunosorbent assay (ELISA), and the expression of interleukin-10 (IL-10) in thyroid tissue was detected by immunohistochemistry. B cells and regulatory B cells (Bregs) ratios in the spleen of rats were analyzed by flow cytometry.
Results:
In contrast with the EAT model group, the levels of serum TSH, TGAB, TPOAb, and BAFF were decreased, while IL-10 expression was increased in thyroid tissue, and Bregs ratio was upregulated in the spleen (all p < 0.05) in the selenium yeast supplement EAT group.
Conclusion:
Selenium yeast supplement could partially attenuate immune imbalance in EAT rats, which may be related to the mechanism of modulating B lymphocyte activity.
... In populations not receiving LT4, there was a decrease in TPOAb levels after 3 and 6 months and TgAb levels at 3 months. To summarize the results of our study and previous reviews, selenium supplementation could decrease TPOAb levels in AIT patients [3,7,38]. TPOAb levels seemed to be influenced by a polymorphism (r25191g/a, otherwise known as rs7579) within the human SEPP1 (SELENOP) gene [2]. ...
... However, when performing subgroup analysis on the included studies, a small amount of evidence was pooled, and thus the results should be viewed dialectically. Toulis et al. also found a decrease in TPOAb levels following 3 months of selenomethionine administration relative to sodium selenite administration in a subgroup analysis [38]. Ultrasound echogenicity is of some importance in defining disease status, and a significant difference in the change in echogenicity was reached in our meta-analysis after synthesizing the contradictory results. ...
Background
This study critically reappraises the documentation on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (AIT) with the goal of improving the normalization of the treatment of this disease.MethodsA literature search was performed in the Medline, Embase, and Cochrane Library databases. Twenty-three trials conducted in adults with AIT comparing the efficacy of selenium with or without levothyroxine (LT4) versus placebo and/or LT4 were eligible. The assessed outcomes were primarily pooled using a random- or fixed effects model based on the results of the heterogeneity test. The quality of evidence was assessed per outcome.ResultsIn LT4-treated populations, patients receiving selenium demonstrated lower thyroid peroxidase antibody (TPOAb) levels at 3 months (mean difference [MD], −236.88; 95% confidence interval [CI], −353.35 to −120.41; p < 0.0001), 6 months (MD, −407.17; 95% CI, −623.60 to −190.73; p = 0.0002), and 12 months (MD, −327.03; 95% CI, −613.78 to −40.28; p = 0.0254), while thyroglobulin antibody (TgAb) levels only decreased at 12 months. In non-LT4-treated population, the selenium group demonstrated significantly lower TPOAb levels after 3 months (MD, −203.07; 95% CI, −395.44 to −10.70; p = 0.0385) and 6 months (MD, −322.27; 95% CI, −597.50 to −47.04; p = 0.0217) but not after 12 months, while TgAb levels only decreased at 3 months. There was no significant change in thyroid stimulating hormone (TSH) levels. Lower thyroid echogenicity was observed in all patients receiving selenium at 3, 6, and 12 months. However, these participants had a significantly higher risk of reported adverse effects.Conclusions
Current evidence does not justify the emerging use of selenium supplementation in the treatment of AIT, despite it resulting in a decrease in autoantibody levels.
... This shows the potential for selenium effects to protect the progression of the disease in selenomethionine supplementation. 56 Other studies showed a significant reduction in TPOAb levels after 3 months supplementation of 200 mcg selenomethionine/day. 57 Chemokine CXCL-9 levels decreased significantly after 12 months supplementation of 80 mcg of selenomethionine/day, whereas with supplementation 160 mcg selenomethionine/day, a significant decrease was seen in the 6 month and remain stable. CXCL-10 levels decreased significantly after 12 months of supplementation both in the group that given selenomethionine 80 mcg and 160 mcg. ...
... The results of that study showed a positive effect of selenomethionine as an immunomodulator by reducing some cytokine regulation. 56 Study by Farias et al. 52 showed a decrease in TPOAb by giving selenium supplementation for 3 months that occurred after 6 months. Low selenium levels are associated with poor immune function, and it has been hypothesized that mild selenium deficiency may promote the progression of thyroid autoimmunity. ...
Introduction: Thyroid gland has the highest selenium content compare with other endocrine organs. Enzyme that catalyzing thyroid hormone activation, iodothyronine deiodinases, were identified as selenocysteine-containing proteins. Selenium levels in soil and rice consumed in Indonesia were lower than in several other countries, which can increase the risk of selenium deficiency.Methods: This is an article review of the current literatures published up to November 2018 about the role of selenium in hyperthyroid.Result: Several studies have shown that selenium supplementation can be beneficial in patients with Graves disease and autoimmune thyroiditis. Selenium has an important immunomodulatory effect, but the effects of selenium supplementation in hyperthyroid has not been conclude. Data regarding selenium intake, prevalence of deficiency, and the relationship between selenium and thyroid disease in Indonesia are limited. Various studies of selenium supplementation in thyroid disease provide controversial results, so there are no guidelines that include selenium as standard therapy hyperthyroid. Selenium supplementation can enhance the restoration of biochemical euthyroidism in Graves disease and was associated with a significant decrease in the levels of thyroid peroxidase antibodies in autoimmune thyroiditis.Conclusions: Micronutrients that play a role in thyroid hormone synthesis and maintain thyroid function in addition to selenium are iodine, iron, zinc, and vitamin A. By correcting the deficit of selenium, and meeting other micronutrient requirements may provide health benefits in patient with hyperthyroid.
... Многие исследователи считают, что эти антитела менее специфичны для аутоиммунного тиреоидита [8]. Роль оценки их уровня для анализа патогенеза диагностики аутоиммунного тиреоидита не определена, что подтверждено нашим наблюдением [3,9]. ...
... Одним из представителей класса иммуноглобулинов, роль которого в аутоиммунных процессах в последнее время активно изучается, служит IgА [9,12]. Как видно из табл. ...
The authors studied the effect of selenium on the dynamics of immune system indicators in children with autoimmune thyroiditis. They examined 31 children (average age of 11.16 ± 0.59 years). Group I included 17 children who took selenium (100 μg per day for 6 months) along with the basic treatment. Group II (n=14) took L-thyroxin. The control group included 15 healthy children of the same age. The average level of selenium in children of Group I and II was 69.23 ± 1.52 μg / l at the beginning of the study, in the control group it was 114.8 ± 3.18 μg / l. Before treatment, children in Group I and II had T-cell suppression, the average level of all cytokines (especially TNF-α and IL-6) was significantly higher than in practically healthy children. The study demonstrated that the level of the thyroid tissue antibodies decreased significantly (p=0.001) with an increase in the level of selenium in the blood serum. By the end of the study the content of IgA (p=0.012) and IgG (p=0.044) in Group I, as well as the number of lymphocytes CD3 + (p=0.008), CD4 + (p=0.015), CD16 + / 56 + (p=0.010) significantly increased. The authors observed statistically significant decrease in the levels of TNF-α (p=0.028), IL-6 (p=0.002) and IL-1β (p=0.009) in children who took selenium in addition to the main treatment. Thus, the results of the study suggest that selenium in the complex therapy of autoimmune thyroiditis significantly reduces the titer of antithyroid antibodies and positively affects a number of important indicators of immune homeostasis in children.
... Многие исследователи считают, что эти антитела менее специфичны для аутоиммунного тиреоидита [8]. Роль оценки их уровня для анализа патогенеза диагностики аутоиммунного тиреоидита не определена, что подтверждено нашим наблюдением [3,9]. ...
... Одним из представителей класса иммуноглобулинов, роль которого в аутоиммунных процессах в последнее время активно изучается, служит IgА [9,12]. Как видно из табл. ...
The authors studied the effect of selenium on the dynamics of immune system indicators in children with autoimmune thyroiditis. They examined 31 children (average age of 11.16 ± 0.59 years). Group I included 17 children who took selenium (100 μg per day for 6 months) along with the basic treatment. Group II (n=14) took L-thyroxin. The control group included 15 healthy children of the same age. The average level of selenium in children of Group I and II was 69.23 ± 1.52 μg / l at the beginning of the study, in the control group it was 114.8 ± 3.18 μg / l. Before treatment, children in Group I and II had T-cell suppression, the average level of all cytokines (especially TNF-α and IL-6) was significantly higher than in practically healthy children. The study demonstrated that the level of the thyroid tissue antibodies decreased significantly (p=0.001) with an increase in the level of selenium in the blood serum. By the end of the study the content of IgA (p=0.012) and IgG (p=0.044) in Group I, as well as the number of lymphocytes CD3 + (p=0.008), CD4 + (p=0.015), CD16 + / 56 + (p=0.010) significantly increased. The authors observed statistically significant decrease in the levels of TNF-α (p=0.028), IL-6 (p=0.002) and IL-1β (p=0.009) in children who took selenium in addition to the main treatment. Thus, the results of the study suggest that selenium in the complex therapy of autoimmune thyroiditis significantly reduces the titer of antithyroid antibodies and positively affects a number of important indicators of immune homeostasis in children.
... In addition to pharmacological interventions, some caregivers have equally found nutritional therapy and food supplements to be helpful. [41]. It has also been emphasized that compliance with nutritional guidelines may help thyroiditis of Hashimoto (TH) patients to reduce the need for medicines [42]. ...
... Tiroid fonksiyon bozukluğu gösteren çeşitli hastalıklarda selenyum takviyesinin antioksidan enzim olan glutatyonperoksidaz ve diğer selenoproteinlerin aktivitesini artırdığını bildiren çalışmalar mevcuttur (6). Diffüz veya nodüler guatr ile karakterize, ötiroid, subklinik hipotiroi-dizm ve kalıcı hipotiroidizm ile seyreden önemli bir tiroid hastalığı olan Hashimoto tiroditinde selenyum takviyesinin levotiroksine destekleyici olarak kullanılmasının faydalı olduğuna dair kanıtlar vardır (7). Ayrıca gebeliği süresince ve doğum sonrası dönemde selenyum takviyesi alan hastalarda otoimmun tiroid hastalığının ve hipotiroidi gelişiminin daha az görüldüğü bildirilmiştir (8). ...
OBJECTIVE: Selenium is an essential component of important metabolic pathways of the human body. Proteins in which selenium is added to the active site in the form of selenocysteine are defined as selenoproteins and they require selenium to fulfill their functions. Glutathioneperoxidase (GPXs) is found in such selenoproteins as Thioredoxinreductase (TRs) and Iodothyroninedeiodinase (ID). Selenoproteins contribute to thyroid hormone biosynthesis and metabolism and the control of the antioxidant defence system. In our study, we aimed to reveal how often patients with subclinical hypothyroidism and autoimmune thyroiditis are accompanied by low serum selenium level and the effects of oral selenium replacement on Tiroit Stimulating Hormone (TSH) in patients with low selenium.MATERIAL AND METHODS: In our study, we evaluated 69 patients who were with asymptomatic subclinical hypothyroidism and aged older than 18 and who applied admitted to our outpatient/out-patient clinic between December 2019 and July 2020. Patients with serum selenium levels lower than 80 μg / L were given 83 mcg of selenomethionine in a soft gel capsule for 3 months. No other treatment was applied. At the end of the third month, serum thyroid hormone profile and selenium levels were measured in all patients. Changes in TSH levels were observed in patients with autoimmune thyroiditis with subclinical hypothyroidism after oral selenium replacement by using percentiles.RESULTS: In our study, 69 patients with asymptomatic subclinical hypothyroidism diagnosed in our outpatient clinic between December 2019 and July 2020 were evaluated. Serum selenium level was identified as normal in 12 (28%) of 43 patients, and serum selenium level was identified as low (<80 μg / L) in 31 (72%) patients. TSH values were found as regressed within normal limits (0,5mIU/L 10.00 mIU / L) in 3 (10%) patients, the TSH value was identified as still in the range of 4.26 mIU / L-10.00 mIU / L in 9 (29%) patients and levothyroxine treatment was started in these patients.CONCLUSIONS: In our study, we evaluated the short-term effects of oral selenium replacement in asymptomatic autoimmune subclinical hypothyroid patients with selenium deficiency, on serum TSH values and we observed that 61% of patients were euthyroid within 3 months. Replacing selenium deficiency has positive effects on the inflammatory and oxidative damage processes of all autoimmune diseases, especially autoimmune thyroiditis. However, we think that experimental and clinical comprehensive studies, which are detailed in sub-groups, should be conducted on this subject.
... This has led to numerous studies investigating the relationship between thyroid functions and selenium (20)(21)(22). In a previous study, the use of selenium has been reported to be effective in Hashimoto's thyroiditis, a common autoimmune thyroid disease ( 23 ). Another study has reported low selenium in newly diagnosed HT and Graves' disease patients ( 24 ).Various selenium levels have been reported in TM patients ( 3 , 7 , 25 ). ...
Introduction
Previous studies have measured selenium levels and glutathione peroxidase 3 (GPX3) activity in patients with thalassemia major (TM). However, Selenoprotein P (SEPP), which is responsible for the storage and transport of selenium, has not been studied in thalassemia patients. This study aims to correlate thyroid functions of TM patients with their SEPP and GPX3 levels.
Materials and Methods
Eighty subjects (40 controls, 40 TM patients) were included in this study. GPX3 and SEPP concentrations were measured in all subjects using sandwich ELISA. Iron, ferritin, urinary iodine, thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), anti-thyroid peroxidase (anti-TPO), and anti-human thyroglobulin (anti-hTG) concentrations were also measured.
Results
Mean SEPP concentration was higher in the TM group compared to the control group. A slight elevation in GPX3 levels was also observed in thalassemia patients, yet it was not statistically significant. In both TM patients and controls, ferritin was inversely correlated with free T4 concentration and GPX3 was inversely correlated with free T4 and T3 concentrations. There was also a negative correlation between SEPP and TSH concentrations in healthy subjects.
Conclusion
This is the first study, which has measured SEPP concentrations in thalassemia patients. SEPP levels were higher in TM patients compared to controls. Correlations between thyroid hormones and selenoproteins may indicate that selenium is necessary for thyroid function. Detailed studies are required to elaborate the role of SEPP in thyroid metabolism in thalassemia patients.
... But, there were also diverse results showing that selenium supplementation may reduce levels of antithyroid antibodies, improve thyroid structure, autoimmune thyroid diseases and interleukin levels, improve thyroid metabolism, and clinical symptoms (30)(31)(32). ...
Context. Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective. The study aimed to determine Hashimoto's thyroiditis (HT) clinical course in adults and the factors that could affect it. Design. The study was in a retrospective manner between 2010-2018. Subjects and Methods. 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results. No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a "Gaussian distribution" in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions. Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.
... But, there were also diverse results showing that selenium supplementation may reduce levels of antithyroid antibodies, improve thyroid structure, autoimmune thyroid diseases and interleukin levels, improve thyroid metabolism, and clinical symptoms (30)(31)(32). ...
Context:
Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium.
Objective:
The study aimed to determine Hashimoto's thyroiditis (HT) clinical course in adults and the factors that could affect it.
Design:
The study was in a retrospective manner between 2010-2018.
Subjects and methods:
101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course.
Results:
No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a "Gaussian distribution" in all patients at the diagnosis and at the end, independent of levothyroxine treatment.
Conclusions:
Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.
... 26 There are data suggesting that decreased selenium intake may activate HT, but selenium administration has not shown any improvement in the disease course although a reduction in thyroid peroxidase (TPO) autoantibody titers was observed. 27,28 Because of an association between HT and celiac disease, a low gluten diet has been suggested as potentially modulating HT. In a prospective study of patients with celiac disease compared with controls without celiac disease, a low-gluten diet was associated with decreased thyroid volume only in the patients with celiac disease, although antibodies against thyroid peroxidase (TPOAbs) were unaffected. ...
Hashimoto thyroiditis (HT) is a common autoimmune disorder, affecting women 7-10 times more often than men, that develops because of genetic susceptibility, X-chromosome inactivation patterns, modulated by environmental factors as well as microbiome composition, and leading to an imbalance in the self-tolerance mechanisms. The consequential thyroid infiltration by the lymphocytes, potentiated by antibody-mediated autoimmune response through the antibodies against thyroid peroxidase (TPOAbs), leads to a destruction of thyrocytes. The presence of TPOAbs is associated with a two to fourfold increase in the risk of recurrent miscarriages and preterm birth in pregnant women. The clinical presentation of HT includes: (A) thyrotoxicosis, when stored thyroid hormones are released to circulation from destroyed thyroid follicles; (B) euthyroidism, when preserved thyroid tissue compensates for destroyed thyrocytes; and (C) hypothyroidism, when thyroid hormone production by the affected thyroid gland is insufficient. The management of Hashitoxicosis is based on symptoms control usually with β-blockers, euthyroidism requires periodical thyroid stimulating hormone measurements to assess for progression to hypothyroidism, and hypothyroidism is treated with thyroid hormone replacement therapy. The dose of levothyroxine (LT4) used for treatment is based on the degree of preserved thyroid functionality and lean body mass and usually ranges from 1.4-1.8 mcg/kg/day. There is insufficient evidence to recommend for or against therapy with triiodothyronine (T3), apart from in pregnancy when only levothyroxine is indicated, as T3 does not sufficiently cross fetal blood-brain barrier. HT is associated with 1.6 times higher risk of papillary thyroid cancer and 60 times higher risk of thyroid lymphoma than in general population.
... Selenium-dependent health effects in thyroiditis-and especially Hashimoto's thyroiditis (HT)-are described only in females as are the associations between selenium status with thyroid volume, goiter, and thyroid nodules [334][335][336][337]. For cardiovascular disease, results are currently conflicting. ...
Selenium is an essential microelement required for a number of biological functions. Selenium—and more specifically the amino acid selenocysteine—is present in at least 25 human selenoproteins involved in a wide variety of essential biological functions, ranging from the regulation of reactive oxygen species (ROS) concentration to the biosynthesis of hormones. These processes also play a central role in preventing and modulating the clinical outcome of several diseases, including cancer, diabetes, Alzheimer’s disease, mental disorders, cardiovascular disorders, fertility impairments, inflammation, and infections (including SARS-CoV-2). Over the past years, a number of studies focusing on the relationship between selenium and such pathologies have been reported. Generally, an adequate selenium nutritional state—and in some cases selenium supplementation—have been related to improved prognostic outcome and reduced risk of developing several diseases. On the other hand, supra-nutritional levels might have adverse effects. The results of recent studies focusing on these topics are summarized and discussed in this review, with particular emphasis on advances achieved in the last decade.
... Three trials reported successful reductions in TPO autoantibodies titers and/or improvement of mood and well-being (114)(115)(116)(117). As no consistent adverse events were observed, routine selenium supplementation in patients with Hashimoto's thyroiditis was considered as a promising adjuvant treatment option (118). It is worth noting that experiences with subjects deficient in both iodine and selenium, and displaying increased disease symptoms when Se supplementation was initiated without at the same time raising iodine supply (so called myxedematous cretinism). ...
Consistent activation and functioning of thyroid hormones are essential to the human body as a whole, especially in controlling the metabolic rate of all organs and systems. Impaired sensitivity to thyroid hormones describes any process that interferes with the effectiveness of thyroid hormones. The genetic origin of inherited thyroid hormone defects and the investigation of genetic defects upon the processing of thyroid hormones are of utmost importance. Impaired sensitivity to thyroid hormone can be categorized into three conditions: thyroid hormone cell membrane transport defect (THCMTD), thyroid hormone metabolism defect (THMD), and thyroid hormone action defect (THAD). THMD is caused by defects in the synthesis and processing of deiodinases that convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). Deiodinase, a selenoprotein, requires unique translation machinery that is collectively composed of the selenocysteine (Sec) insertion sequence (SECIS) elements, Sec-insertion sequence-binding protein 2 (SECISBP2), Sec-specific eukaryotic elongation factor (EEFSEC), and Sec-specific tRNA (TRU-TCA1-1), which leads to the recognition of the UGA codon as a Sec codon for translation into the growing polypeptide. In addition, THMD could be expanded to the defects of enzymes that are involved in thyroid hormone conjugation, such as glucuronidation and sulphation. Paucity of inherited disorders in this category leaves them beyond the scope of this review. This review attempts to specifically explore the genomic causes and effects that result in a significant deficiency of T3 hormones due to inadequate function of deiodinases. Moreover, along with SECISBP2, TRU-TCA1-1, and deiodinase type-1 (DIO1) mutations, this review describes the variants in DIO2 single nucleotide polymorphism (SNP) and thyroid stimulating hormone receptor (TSHR) that result in the reduced activity of DIO2 and subsequent abnormal conversion of T3 from T4. Finally, this review provides additional insight into the general functionality of selenium supplementation and T3/T4 combination treatment in patients with hypothyroidism, suggesting the steps that need to be taken in the future.
... The other food component, the heavy metal selenium a component of thyroid hormones biosynthetic enzymes play crucial role in thyroid function [25] . It is clear from the studies that selenium rich foods such as tuna fish, lobster, crab and Brazil nuts are increasing the selenium levels and corrects the thyroid dysfunctions [26] . ...
Thyroid disorders are common overwhelming health conditions reported worldwide. The prevalence of thyroid disorders such as hypothyroidism and hyperthyroidism is increasing in developed and developing countries including India. This is due to change in traditional foods to Besides low/insufficient iodine intake, smoking, ageing, genetic susceptibility, lifestyle, usage of new medicine, endocrine disrupting chemicals and immune status of an individual are the key determinants for thyroid disorders. This review emphasizes the various disorders of thyroid gland and, its epidemiology and treatment methods.
... GPx and therefore protects human against oxidative damage [1], inflammation [2], cancer [3], and Keshan disease [4,5]. As the continuous increase in health awareness and healthcare, it is widely concerned to obtain selenium-functionalized supplementation for maintaining the health [6][7][8]. In the traditional cultivation, Se-functionalized nutrients are mainly in the form of selenide protein deriving from wheat [9][10][11], rice [12][13][14], potato [15,16], etc. Due to the low protein content in these crops and the complex and long growth period of plant, the selenium content is unstable in targeted products. ...
Selenium-functionalized starch (Se-starch80) is one of the main functional foods used for selenium supplementation. In traditional agriculture, Se-starch has some deficiencies such as long growth cycle and unstable selenium content that prevent its antioxidant performance. In this study, Se-starch was prepared by the nucleophilic addition between NaSeH and carbon-carbon double bond of octenyl succinic anhydride waxy corn starch ester (OSA starch). Some techniques such as 1HNMR, XPS, SEM-EDS, XRD and FT-IR were used to characterize the relevant samples and the results showed that the modification did not destroy the starch framework significantly and the catalytic center (negative divalent selenium) was anchored on the starch framework. The intensive distribution of catalytic center on the starch surface and the hydrophobic microenvironments derived from the OSA chains furnished the Se-starch80 with a high GPx-like catalytic activity (initial reaction rate = 3.64 μM/min). This value was about 1.5 × 105 times higher than that of a typical small-molecule GPx mimic (PhSeSePh). In addition, the Se-starch80, without any cytotoxicity, showed a saturated kinetic catalytic behavior that is similar to a typical enzyme. This work exemplifies a biodegradable selenium-functionalized polymer platform for the high-performing GPx mimic.
... Se plays a crucial role as a cofactor of iodothyronine deiodinase by converting thyroxine (T4) into triiodothyronine (T3), which helps in thyroid hormone synthesis. It is also suggested that selenium is a cofactor for glutathione peroxidase and reductase, which are antioxidant enzymes and save the thyroid gland from oxidative stress damages [36]. Zinc has been reported to be indispensable for thyroid function, as it is essential for the normal conversion of thyroid hormones [34,37]. ...
Lead (Pb) is a prevalent environmental toxic metal that may harmfully affect the function of the thyroid gland. Our information about the effects of lead on thyroid function in lead poisoning is limited. The present study aimed to evaluate thyroid function in lead-poisoned patients compared with the healthy group. In this study, two groups of lead poisoning subjects (lead concentrations ≥ 25 μg/dL) (n = 56) (HBLC group) and randomly selected age and gender-matched healthy individuals with lower blood lead concentrations (BLC < 10 μg/dL) (n = 58) (LBLC group) were included. Thyroid function tests, including thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentration, were measured for each patient in both groups (for the HBLC group, it was taken on admission). The linear regression model was used to investigate the effects of lead poisoning on thyroid function tests. A p-value of less than 0.05 was considered significant. Our study showed no significant difference between the two groups in terms of age and gender. The mean concentration of T3 and TSH in the HBLC group was significantly lower than the LBLC group, but the mean levels of T4 were significantly higher in the HBLC group (p < 0.05). Based on the linear regression model results, the T3 and TSH levels in the LBLC group were significantly higher by 13.86 and 0.43 units than the HBLC group, respectively. The current study results showed that lead poisoning affects thyroid function, reduces TSH, and increases T4.
... The highest concentration of Se is found in the thyroid gland in the form of glutathione peroxidase 3 (GPX3) that protects thyroid cells from hydrogen peroxide in thyrocytes and the follicular lumen. 2 Several systematic reviews and meta-analyses have revealed that Se supplementation could reduce thyroidperoxidase autoantibody concentrations in patients with autoimmune thyroiditis. [5][6][7] Graves' orbitopathy (GO) is a multifactorial autoimmune disease. It is characterised by the initial reaction against autoantigens present in orbital fibroblasts and thyroid epithelial cells. ...
Background/aims
Selenium (Se), an antioxidant agent, is effective in preventing mild Graves’ orbitopathy (GO) deterioration. However, the significant risk of low serum Se concentration for GO progression has not been identified. Here, we aimed to investigate the risk of relative Se insufficiency and to identify its optimal cut-off value in the development of disease severity in patients with GO.
Methods
Serum Se levels were prospectively measured in 100 consecutive patients with GO. The patients were classified into groups with mild and severe GO (logistic regression analysis outcome). A receiver operating characteristic (ROC) curve and the minimum p value corresponding to χ ² statistics were analysed to select the optimal cut-off Se level for the diagnosis of severe orbitopathy.
Results
Thirty-two patients (32%) had mild GO and 68 (68%) had severe GO. The ROC revealed a cut-off Se level of 93 µg/L. Se levels ≤93 µg/L were observed in 48.5% and 12.5% of the patients in the severe and mild (p<0.001) groups, respectively. The risk estimate (OR) for an Se level ≤93 µg/L was 8.14 (95% CI 2.39 to 27.75). It remained a significant risk factor after adjusting for age, sex, thyroid status, smoking status, thyroidectomy and radioactive iodine.
Conclusion
Relative Se insufficiency (≤93 µg/L) is a potential risk factor for severe GO development. An evaluation of Se status is recommended in patients with GO for predicting disease progression and guiding supplementation therapy.
... Selenium supplementation may also protect against autoimmune thyroiditis, but the results have been ambiguous. The first meta-analysis by Toulis et al. [28] involving HT patients under L-T4 treatment and concluded that Se supplementation is a promising adjuvant therapy for HT. A subsequent meta-analysis by Wichman et al. [29] concluded that Se supplementation decreased TPOAb levels after 3, 6, and 12 months in LT4-treated AIT population, and after 3 months in LT4-untreated population. ...
Selenium is an essential trace element in human. Recent studies of selenium (Se) supplementation on the effect of Hashimoto thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of selenium (Se) treatment in HT patients, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized‑controlled study was performed in HT patients assigned to two groups. Se‐treated group (n=43) received Se‐yeast for 6 months, while no treatment in control group (n=47). The primary outcome is the changement of thyroid antibody (TPOAb or TGAb). Secondly, thyroid function, urinary iodine (UI), Se, Glutathione peroxidase3 (GPx3) and Selenoprotein P1 (SePP1) levels were measured during the treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs (rTregs) and secreting Tregs (sTregs), as well as Helios and PD‐1 expression on these cells were also detected. The results showed that Se supplementation significantly decreased thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3 and SePP1, compared with control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in Se group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.
... It is a constituent of selenoproteins many of which are engaged in protection against oxidative stress [2], and a cofactor of many enzymes involved in several major metabolic pathways [3][4][5][6]. It is involved in thyroid metabolism as a cofactor of the glutathione peroxidase (GPx), protecting the thyroid gland against oxidative stress, and iodothyronin deiodinase enzymes, converting thyroxine (T4) to triiodothyronine (T3) [4,[6][7][8][9]. Being so important in human organism, the deficiency of Se can endanger human health and lead to misbalance of many biochemical processes further resulting in disease [10,11]. ...
Selenium (Se) is essential micronutrient involved in several physiological processes. In many regions around the world, a suboptimal intake of Se has been reported in several health conditions, also in pediatric age. Studies on association between Se level and diseases in children reported contrasting results. We took an aim to perform a systematic review of literature and provide evidence-based conclusion on the magnitude of Se deficit in endocrine diseases in children. PubMed, ISI WoS, and Scopus databases were searched to identify eligible studies, published until July 25, 2019. Methodological quality was assessed using Newcastle-Ottawa Scale. After careful selection, 13 eligible studies were included. Majority were conducted in Turkey (n=5) and Iran (n=5), and sample size varied from 61 to 628 children, with a mean (±SD) age of cases from 5.1±1.6 months up to 13.8±4.5 years. Eleven studies focused on different thyroid diseases, and two on children with type 1 diabetes mellitus (T1DM). In goitrous patients, Se level ranged from mean (±SD), 25.71±20.68 μg/L to 114.9±34.1 μg/L, while in patients with T1DM was 20.9±12.9 μg/mL and mean (95% CI)=58.4 μg/L (55.0-63.09). We may conclude that goiter and thyroid dysfunction are prominent signs of Se deficiency in children. Although deficiency of iodine and selenium are usually combined in some area, our systematic review showed that Se deficiency is important goitrogenic factor in school children. Further randomized controlled trials are needed to adequately explore the role of Se in endocrine disorders in children, across different populations and regions.
... Currently, inadequate dietary Se intake affects up to 1 in 7 people globally with the associated risk of developing several chronic degenerative diseases (Fordyce, 2013;James et al., 1989;Rayman, 2000). To overcome this issue, Se supplementation has been extensively used (e.g. to control Keshan disease in China, and as adjunctive therapy in the treatment of Hashimoto's thyroiditis (Chen, 2012;Daniels, 1996;Toulis et al., 2010). Food derived from plants is a natural source of Se since plants can transform inorganic Se species present in soil into organic Se ones (e.g. ...
An appropriate selenium intake can be beneficial for human health. Se-biofortified food in Se-deficient regions is becoming an increasingly common practice but there are still issues to be addressed regarding the observed Se-induced toxicity to the plant. In this respect, plant biostimulants are used to enhance nutrition efficiency, abiotic stress tolerance and crop quality. In this work, the efficacy of a plant biostimulant to counteract the Se-induced stress in wheat plants is experimentally assessed. The co-application of different Se-biofortification treatments and the biostimulant at different growth stages (tillering or heading stage) was investigated. The use of micro focused X-ray spectroscopy allows us to confirm organic Se species to be the main Se species found in wheat grain and that the proportion of organic Se species is only slightly affected by the Se application stage. Our study proves that the biostimulant had a key role in the enhancement of both the amount of grains produced per spike and their dry biomass without hindering Se enrichment process, neither diminishing the Se concentration nor massively disrupting the Se species present. This information will be useful to minimize both plant toxicity and economic cost towards a more effective and plant healthy selenium supplementation.
... Increased expression of GPX1 and TXNRD1 is involved in this effect [77]. While selenium enhances T cell response when needed, it prevents the uncontrolled activation of immune system in autoimmune diseases [78,79]. The latter might be performed via T reg cells, which increase after selenium supplementation [80]. ...
Management of IBD (inflammatory bowel disease) has always been a challenge for physicians. Current treatment protocols may cause numerous adverse effects. Selenium is known for its putative anti-inflammatory properties. Selenium is needed for the biosynthesis of enzymatically active selenoproteins, which contribute to antioxidative defence, and effective function of immune systems. Several studies showed that IBD patients have a lower selenium level compared to healthy subjects. Hence, experimental studies mimicking ulcerative colitis and Crohn's disease investigated the effect of selenium supplementation on IBD.
Previous studies indicated that: i) Selenoproteins can curb the inflammatory response and attenuate oxidative stress. This anti-inflammatory property caused remission in animal models of colitis. ii) Selenium supports protective gut microbiota which indirectly improves management of IBD. iii) Selenium may block some of the predominant tumorigenesis pathways proposed in colitis-associated colorectal cancer. iv) Selenium supplementation showed promising results in preliminary clinical studies particularly in patients with selenium deficiency.
While selenium supplementation seems to be beneficial for IBD, clinical studies remained too preliminary in this regard. Randomized clinical trials are needed to measure the short-term and long-term effects of selenium on both active and quiescent IBD particularly in IBD patients whom have documented selenium deficiency.
... It is known [21] that they enhance the assimilation of each other; however, a high content of vitamin E (2.4 and 3.8 at a daily rate of 2 mg) will correct the predicted consequences due to increased assimilation of B vitamins. This synergism of substances is described and experimentally confirmed in [22]. ...
... Selenium plays a key role in the physiology of thyroid cells and is functional in the molecular structure of thyroid enzymes [7]. One of these enzymes is glutathione peroxidase, which protects the thyroid from oxidation induced by enzymatic production of hydrogen peroxide deriving from the synthesis of thyroid hormone [8]. ...
Autoimmune thyroiditis (AT) is a disease whose incidence has increased dramatically over the
past few decades [1]. In iodine sufficient areas, this pathological condition affects up to 5% of the
general population [1]. The higher incidence of AT observed in areas of the world with low-selenium (Se) soils appears to be
the consequence of reduced activity of the intracellular Se-dependent glutathione peroxidase activity [2]. Se is involved,
through selenoproteins, in the regulation of intracellular antioxidant, redox and anti-inflammatory processes [3]. As a component of selenoproteins, Se exerts various structural and enzymatic functions [3]. A low Se/high fat diet can cause selenoprotein
changes and promote the expression of pro-inflammatory factors [4]. In particular, it has been well recognized as an antioxidant
and trace element catalyst essential in the production of thyroid hormone [2, 5]. Selenium is important for the functioning of the
immune system. The recommended daily dose for adults is 55 µg [6].
... Selenium intake in Europe showed a decrease of 50% in the last 30 years. Nevertheless, the administration of selenium supplements did not show an improvement in thyroid morphology but only a reduction in levels of TPO autoantibodies, as demonstrated in recent meta-analysis [45]. ...
Hashimoto's thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully elucidated, Hashimoto's thyroiditis is related to an interaction among genetic elements, environmental factors and epigenetic influences. Cellular and humoral immunity play a key role in the development of the disease; thus, a T and B cells inflammatory infiltration is frequently found. Histopathologic feature of the disease includes lymphoplasmacytic infiltration, lymphoid follicle formation with germinal centers, and parenchymal atrophy. Moreover, the occurrence of large follicular cells and oxyphilic or Askanazy cells is frequently associated to Hashimoto's thyroiditis. Clinically, Hashimoto's thyroiditis is characterized mainly by systemic manifestations due to the damage of the thyroid gland, developing a primary hypothyroidism. Diagnosis of Hashimoto's thyroiditis is clinical and based on clinical characteristics, positivity to serum antibodies against thyroid antigens (thyroid peroxidase and thyroglobulin), and lymphocytic infiltration on cytological examination. The mainstream of treatment is based on the management of the hypothyroidism with a substitution therapy. A relationship between Hashimoto's thyroiditis and a possible malignant transformation has been proposed in several studies and involves immunological/hormonal pathogenic links although specific correlation is still debated and needs to be further investigated with prospective studies.
... However, no conclusive results from randomized controlled trials are available to date in HT. Hence, the current evidence does not support the use of Se supplementation in HT treatment [10,[24][25][26]. Se supplementation in patients with HT has been investigated also in combination with Myo-I. ...
Previous reports indicate that selenium supplementation may be useful to reduce cell oxidative stress. In particular, selenium may decrease the level of thyroid autoantibodies in patients with Hashimoto’s thyroiditis (HT). Recent studies also indicate that myo-inositol may have beneficial effects on thyroid function in patients with HT. Hence, the aim of the present study is to evaluate whether myo-inositol may enhance the protective effect of selenium on HT progression to hypothyroidism. The study was designed as observational and retrospective. Thyroid hormones were evaluated in patients with HT who were either euthyroid or subclinically hypothyroid. These patients were subdivided into three groups: untreated, treated with selenomethionine alone (Se-meth: 83 μg/day) and treated with Se-meth plus myo-inositol (Se-meth + Myo-I: 83 μg/day + 600 mg/day). Outcome evaluation was performed at baseline and after 6 and 12 months of treatment. High-resolution ultrasound of the thyroid gland was performed to evaluate changes in thyroid echoic pattern during the study. Compared to baseline, levels of thyroid-stimulating hormone (TSH) increased significantly in untreated patients but decreased by 31% and 38%, respectively, in those treated with Se-meth and Se-meth + Myo-I. Moreover, in the latter group the TSH reduction was observed earlier than in the Se-meth-treated group. Densitometric analysis of thyroid ultrasonography showed an echoic pattern improvement in both treated groups compared to untreated patients, although this difference was not statistically significant. Thus, Se-meth treatment is effective in patients with HT and its effect may be improved in combination with Myo-I through earlier achievement of TSH levels closer to physiological concentrations.
... Patients with HT who have normal thyroid function and no obvious symptoms of oppression should be followed up and monitored thyroid function regularly. [38] Current therapeutic strategies for HT with normal thyroid function in the early stages include Se supplementation, glucocorticoids, and vitamin D. [39][40][41] However, the available data on beneficial effects of Se on thyroid autoimmune parameters are limited. [42] On the other hand, caution should be taken when long-term selenium supplementation, the increased risk of type 2 diabetes was observed in a randomized clinical trial. ...
Background:
Hashimoto thyroiditis (HT) is highly prevalent among reproductive-aged women and has a substantial negative impact on fertility. Currently, there is no specific treatment for Hashimoto thyroiditis. We hypothesize that acupuncture can halt or delay the progression of HT and improve fertility in child-bearing period female. We therefore designed a randomized controlled trial to test this hypothesis by comparing the therapeutic effect of acupuncture vs sham acupuncture in patients with Hashimoto thyroiditis.
Methods:
In this randomized controlled study, a total of 284 eligible patients will be assigned to acupuncture group (n = 142) or sham acupuncture group (n = 142) in a 1:1 ratio. All patients will receive 36 sessions in total for 12 consecutive weeks with the same acupoint prescription (RN23, ST9, RN17, RN4, RN6, ST36, SP6, KI6). The primary assessment is the titers of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TGAb). Secondary outcomes include the thyroid function, ovarian function, the rate of primary ovarian insufficiency, and pregnancy outcome. The thyroid function and thyroid antibodies tests will be measured at weeks 0, 4, 8, and 12 after randomization. The ovarian function will be examined on the 2nd to 4th day of the menstrual period in the 1st month, 2nd month and 3rd month compared with baseline. Both the pregnancy outcome and the rate of primary ovarian insufficiency will be evaluated 1 year after treatment.
Discussion:
This will be the first large-scale trial specifically evaluating acupuncture therapy in child-bearing period female with Hashimoto thyroiditis. If the study confirms the effectiveness of acupuncture treatment, more consistent acupuncture therapy can be set up for clinical practice.
Trial registration:
Chinese Clinical Trials Register identifier, ChiCTR2000031320, registered on 27 March 2020.
... Selenium intake in Europe showed a decrease of 50% in the last 30 years. Nevertheless, the administration of selenium supplements did not show an improvement in thyroid morphology but only a reduction in levels of TPO autoantibodies, as demonstrated in recent meta-analysis [45]. ...
Hashimoto’s thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully elucidated, Hashimoto’s thyroiditis is related to an interaction among genetic elements, environmental factors and epigenetic influences. Cellular and humoral immunity play a key role in the development of the disease; thus, a T and B cells inflammatory infiltration is frequently found. Histopathologic feature of the disease includes lymphoplasmacytic infiltration, lymphoid follicle formation with germinal centers, and parenchymal atrophy. Moreover, the occurrence of large follicular cells and oxyphilic or Askanazy cells is frequently associated to Hashimoto’s thyroiditis. Clinically, Hashimoto’s thyroiditis is characterized mainly by systemic manifestations due to the damage of the thyroid gland, developing a primary hypothyroidism. Diagnosis of Hashimoto’s thyroiditis is clinical and based on clinical characteristics, positivity to serum antibodies against thyroid antigens (thyroid peroxidase and thyroglobulin), and lymphocytic infiltration on cytological examination. The mainstream of treatment is based on the management of the hypothyroidism with a substitution therapy. A relationship between Hashimoto’s thyroiditis and a possible malignant transformation has been proposed in several studies and involves immunological/hormonal pathogenic links although specific correlation is still debated and needs to be further investigated with prospective studies.
... Selenium-rich sources include nuts, meat, cereals, fish and shellfish [4]. Selenomethionine and sodium selenite are the two most common oral forms of selenium supplementation that are available in variable dosages (100 and 200 μg/day) [5]. Selenium plays a key role in thyroid cell physiology, it is incorporated in the molecular structure of several enzymes in the thyroid gland [6,7]. ...
The essential mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system. An elevated selenium intake may be associated with reduced cancer risk [1,2]. Selenium is an trace element that is required for the correct functioning of the immune system with a recommended daily intake for adults of 55 μg [3]. Selenium-rich sources include nuts, meat, cereals, fish and shellfish [4]. Selenomethionine and sodium selenite are the two most common oral forms of selenium supplementation that are available in variable dosages (100 and 200 μg/day) [5]. Selenium plays a key role in thyroid cell physiology, it is incorporated in the molecular structure of several enzymes in the thyroid gland [6,7]. One of these enzymes, glutathione peroxidase, is critically involved in protecting the gland against oxidative damage. Thyroid peroxidase uses hydrogen peroxide (H 2 O 2), a free radical capable of inflicting oxidative damage, as a substrate in catalyzing the iodination and coupling of tyrosyl residues in thyroglobulin to produce thyroid hormone. The tri-iodothyronine (T3), is produced by de-iodination of the hormone T4 by type I and type II iodothyronine de-iodinases in, a two-substrate, along with degradation of H 2 O 2 to water by glutathione peroxi-dase. Iodothyronine de-iodinases are also selenoproteins, as is glutathione peroxidase. If there is selenium deficiency, these two enzymes cannot function properly, which results in both ineffective production of T3 and inefficient protection against free radicals, the latter facilitating cell damage and autoimmune destruction of the gland [6-8]. Autoimmune thyroiditis is one of the most prevalent autoimmune diseases and affects more than 10% of females and 2% of males. Cellular destruction by CD4 cell-mediated autoimmune attacks results in permanent hypothyroidism in more patients [9]. More than one-third of the patients have other autoimmune diseases. In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium is strongly involved, via the variable selenoproteins, in antioxidant, redox, and anti-inflammatory processes. Selenium enhances CD4+/CD25 FOXP3 and T regulatory cells activity while suppressing cytokine secretion, thus preventing apoptosis of the follicular cells and providing protection from thyroiditis. Environmental factors, such as iodine intake, immunotherapeutic agents or viral infections, can also trigger the disease. Sele-nium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other autoimmune diseases [9]. Low selenium status is associated with an increased risk of overall mortality, a reduced immune response and a decline of cognitive functions [10]. On the other hand, dietary selenium supplementation has shown to exert antiviral effects [11], improves male and female reproduction [12] and lower the risk of autoimmune diseases [13]. Furthermore, several clinical studies have highlighted a significant association between higher selenium status and reduced risk of prostate, lung, colorectal and bladder cancer. However, other clinical observations failed to demonstrate such correlation. In this scenario,
... A further issue to discuss is the timing of evaluation of the effect of Se on the circulating levels of chemokines, which has been reported by others to be significantly reduced for serum CXCL9, CXCL10 and CXCL11 after 12 months of Se supplementation, 8 while, in this study, after 4 months of Se administration, this lowering effect was limited to CXCL9. ...
Objective
The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis.
Patients and methods
Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83 mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end.
Results
50 patients (43/7 female/male, median age 43.9 ± 11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders).
There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid.
Conclusions
The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9.
... Selenium status has been shown to affect immune functions, e.g., T cell differentiation, and selenium deficiency has been associated with Th2 cells/markers, while higher selenium concentrations seem to favor an increased Th1 and Treg response [82]. These observations are thus in keeping with the suggestion of beneficial effects of selenium supplementation in autoimmune diseases of the thyroid [73,83]. Newly diagnosed autoimmune hyperthyroidism, Graves' disease, has been associated with low selenium concentrations [84], an observation which has fuelled several interventional treatment studies of selenium supplementation as adjunctive to antithyroid drugs in Graves' disease [85][86][87][88]. ...
In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology—these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol—some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.
... Selenomethionine (Se-met) is an organic form of Se and is suitable for nutritional Se supplementation [15]. Studies found that the decrease in thyroid antibody titration was particularly pronounced in subjects received 200 mg of Se-met daily, suggesting that the supplementation of Se-met enhanced the role of thyroid autoimmunity [16,17]. The effects of heavy metals on the environment and humans are well known. ...
Selenium (Se) is a trace element for human and animal health. Cadmium (Cd) is a known human carcinogen. The effects of Cd on the environment and humans are well known. Because chickens are at the top of the food chain, it is a good experimental animal model for assessing heavy metal toxicity and its potential threat to humans. Selenomethionine (Se-met) is a suitable form for nutritional Se supplementation. Therefore, the toxicity of Cd to the chicken liver and the antagonistic effects of Se-met on Cd were examined at the molecular level in the present study. The results showed that oxidative stress indicators (apoptosis-related genes, P13K/AKT pathway–related genes, and heat shock proteins (HSPs)–related genes) in the Cd group have changed significantly, indicating Cd induced hepatocyte stress and apoptosis. Interestingly, the changes in oxidative stress indicators (apoptosis-related genes, P13K/AKT pathway–related genes, and HSPs-related genes) in the Cd-Se-met group were mitigated compared with the control group. Our results indicated that Cd can induce hepatocyte apoptosis and stress in the chickens. Se-met has an ameliorative effect on Cd-induced apoptosis of chicken hepatocyte by regulating PI3K/AKT pathway. Our findings will provide a new insight for better understanding of the detoxification function of Se-met to heavy metals.
... По данным мета-анализа показано отсутствие влияния приема препаратов селена на функцию ЩЖ, улучшение общего самочувствия и качества жизни пациентов [42]. ...
В обзоре дана характеристика основных путей метаболизма селена в организме человека. Показано, что основной биологической ролью селена у эукариот является его участие в синтезе и регуляции активности ряда ферментов (глутатионпероксидаз, селензависимой пероксидазы, белков семейств селенопротеинов P и W,5`-йодотирониндейодиназ, тиоредоксинредуктазы). В последние годы эндокринологи Украины стали активно назначать препараты селена при любых проблемах со щитовидной железой. Мы не являемся сторонниками такого лечения, а считаем необходимым назначение селеносодержащих препаратов только при исходно низком содержании селена в организме человека. Правильность этого мнения находит свое подтверждение и в ряде статей зарубежной литературы. В обзоре авторы сделали попытку обобщить научно обоснованную информацию о том, когда нужно принимать селен, а когда нет, и почему возникла такая практика в принципе
An imbalance between pro-oxidative and antioxidative cellular mechanisms is oxidative stress (OxS) which may be systemic or organ-specific. Although OxS is a consequence of normal body and organ physiology, severely impaired oxidative homeostasis results in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells’ function and viability. The thyroid gland is an organ that exhibits both oxidative and antioxidative processes. In terms of OxS severity, the thyroid gland’s response could be physiological (i.e. hormone production and secretion) or pathological (i.e. development of diseases, such as goitre, thyroid cancer, or thyroiditis). Protective nutritional antioxidants may benefit defensive antioxidative systems in resolving pro-oxidative dominance and redox imbalance, preventing or delaying chronic thyroid diseases. This review provides information on nutritional antioxidants and their protective roles against impaired redox homeostasis in various thyroid pathologies. We also review novel findings related to the connection between the thyroid gland and gut microbiome and analyze the effects of probiotics with antioxidant properties on thyroid diseases.
Background
Increasingly, patients are asking their physicians about the benefits of dietary and alternative approaches to manage their diseases, including thyroid disease. We seek to review the evidence behind several of the vitamins, minerals, complementary medicines, and elimination diets which patients are most commonly using for the treatment of thyroid disorders.
Summary
Several trace elements are essential to normal thyroid function, and their supplementation has been studied in various capacities. Iodine supplementation has been implemented on national scales through universal salt iodization with great success in preventing severe thyroid disease, but can conversely cause thyroid disorders when given in excess. Selenium and zinc supplementation has been found to be beneficial in specific populations with otherwise limited generalizability. Other minerals, vitamin B12, low-dose naltrexone, and ashwagandha root extract have little to no evidence of any impact on thyroid disorders. Avoidance of gluten and dairy have positive impacts only in patients with concomitant sensitivities to those substances, likely by improving absorption of levothyroxine. Avoidance of cruciferous vegetables and soy has little proven benefit in patients with thyroid disorders.
Conclusion
While many patients are seeking to avoid conventional therapy and instead turn to alternative and dietary approaches to thyroid disease management, many of the most popular approaches have no proven benefit or have not been well-studied. It is our responsibility to educate our patients about the evidence for or against benefit, potential harms, or dearth of knowledge behind these strategies.
Background:
Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been published annually in various journals. However, to date, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric analysis on AIT to reveal the dynamic scientific developments and help researchers gain a global perspective while exploring the hotspots and development trends.
Methods:
AIT-related articles and reviews from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The following search terms were used to extract document data: TS= (" autoimmune thyroiditi*") OR TI= ("chronic lymphocytic thyroiditi*") OR TI=(hashimoto*) OR TI= ("postpartum thyroiditis"). We selected articles and reviews published in English from 2000 to 2022. Three software programs (VOSviewer, CiteSpace, Pajek) were employed to analyze the contribution and co-occurrence relationships of different references, countries/regions, institutes, journals and also keywords in this field.
Results:
This scientometric study included 2290 English papers published in 723 journals with 39661 co-cited references from 561 institutions in 120 countries/regions. Based on the reference and keyword analysis, researchers used to focus on "apoptosis", "insulin resistance", "encephalopathy", "IFN-γ" related to AIT during the past 20 years. However, with the development of other novel directions such as "papillary thyroid cancer" (2018-2022), "Vitamin D" (2016-2022), "oxidative stress" (2018-2022), "polymorphism" (2019-2022) and "association" (2020-2022), researchers are more interested in the relationship between papillary thyroid carcinoma and AIT, the effect of vitamin D supplementation on AIT, the oxidative stress in thyroid disease as well as the influence of polymorphism.
Conclusion:
Bibliometric analysis of the outputs of AIT shows an overview of the current status of the research on AIT. The associations between papillary thyroid carcinoma, vitamin D, oxidative stress, polymorphism and AIT are major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of AIT and quickly determine new directions for future research.
Hashimoto’s thyroiditis is a disease of the thyroid gland which affects the body in various ways leading to somatic complications. In addition to that, it affects the patient’s mental health. The extent of psychiatric diseases in patients with Hashimoto’s thyroiditis is not extensively explored. The primary objective of this study was to find the association between Hashimoto’s disease and depression in female patients aged 36-50 from North America/Central America. Questionnaires were designed to assess the extent of possible depression in those patients. We compared 115 cases to 188 controls. After analyzing results, we found that relative risk for developing depression in patients with hashimoto’s disease was 1.7202 (95% CI 1.4722- 2.0099, p value< 0.001). Thus, we concluded that Hashimoto’s disease is associated with increased risk of development of depression in a given sample.
The content of this chapter includes an introduction to three thyroiditis syndromes – Hashimoto, de Quervain, and Riedel. The clinical presentation and diagnostic features of each are discussed in detail. Medical management for each condition is reviewed. Surgical indications for each type of thyroiditis are discussed, with a focus on clinical outcomes. While surgery is not often indicated for thyroiditis alone, surgical treatment of coexistent thyroid nodules or malignancy is often warranted. The impact of inflammatory thyroid conditions on the diagnostic evaluation of nodules and malignancy is reviewed. This chapter begins with a case example and a series of multiple-choice questions and answers to strengthen the reader’s understanding.KeywordsThyroiditisInflammatory thyroid conditionsHashimoto’sChronic lymphocytic thyroiditisAutoimmune thyroiditisde QuervainSubacute thyroiditisRiedel
Introduction. Due to the many physiological functions of Selenium (Se), its deficiency is associated with a broad spectrum of adverse health effects. This review aims to analyze epidemiological data on the relation of selenium status to public health and the possibility of selenium-containing drugs usage. Material and methods. Based on the literature search in Pubmed, The Cochrane Library, and Google Scholar, epidemiological data on the association between Se status and population health and effects of Se supplementation were analyzed. Results. Meta-analyses indexed in the Cochrane Library demonstrated a significant association between Se status and many pathologies. Specifically, it has been shown that subjects with physiologically high Se body burden are characterized by a 24-31% lower risk of cancer and 36% lower risk of cancer-related mortality. It is also notable that Se supplementation in human immunodeficiency virus-infected women reduced the risk of maternal diarrhoea and low birth mass in offspring. Moreover, Se supplementation in premature newborns and critically low mass newborns significantly decreased the risk of sepsis. Many extensive epidemiological studies also demonstrated the efficiency of improvement in the Se status concerning coronary heart disease and sepsis mortality risk. At the same time, constant monitoring of Se body burden is essential for assessing Se supplementation efficiency and prevention of adverse health effects of Se overload. It is also noted that Se status is considered as the determinant of the efficiency of prevention of cardiovascular diseases and cancer under Se supplementation. Conclusion. Given the high incidence of Se deficiency in Russia (24-45% depending on the region), assessment and improvement of Se status may be considered a valuable tool for population health management.
Although several studies indicate that exposure to polybrominated diphenyl ethers (PBDEs) and metals may influence thyroid function, the evidence is limited and inconsistent in general population. The current study was conducted to determine the levels of plasma PBDEs and urinary metals and evaluate the associations of co-exposure to both with thyroid hormones (THs) among rural adult residents along the Yangtze River, China. A total of 329 subjects were included in current analyses, and 8 PBDEs congeners and 14 urinary metals were measured to reflect the levels of environmental exposure. Multiple linear regression models were used to evaluate the association between PBDEs, metals and THs levels. Bayesian Kernel Machine Regression (BKMR) was used to examine PBDEs and metals mixtures in relation to THs. The geometric mean (GM) and 95% confidence interval (CI) of total measured PBDEs was 65.10 (59.96, 70.68) ng/g lipid weights (lw). BDE-209 was the most abundant congener, with a GM (95% CI) of 47.91 (42.95, 53.26) ng/g lw, accounting for 73.6% of the total PBDEs. Free thyroxine (FT4) was significantly negatively associated with BDE-28, 47, 99, 100, 154, and 183, and urinary strontium [β (95% CI): -0.04 (-0.07, -0.02)], but positively associated with selenium [β (95% CI): 0.04 (0.02, 0.06)]. Free triiodothyronine (FT3) was negatively associated with BDE-28 [β (95% CI): -0.03 (-0.05, -0.01)] and urinary arsenic [β (95% CI): -0.01 (-0.02, -0.001)]. The current study did not observe a statistically significant association of thyroid-stimulating hormone (TSH) with PBDEs and urinary metals. BKMR analyses showed similar trends when these chemicals were taken into consideration simultaneously. We found no significant interaction in the association between individual chemical at the 25th versus 75th percentiles and THs estimates, comparing the results when other chemicals were set at their 10th, 50th, and 90th percentile levels. Further study is required to confirm these findings and determine potential mechanisms.
What is known and objective
Vitamin D administered together with selenomethionine has been reported to markedly reduce thyroid antibody titres in patients with autoimmune thyroiditis. Hyperprolactinaemia exerts a complex pro‐inflammatory effect. This study was aimed at investigating whether prolactin excess determines the effect of vitamin D/selenomethionine combination therapy on thyroid autoimmunity.
Methods
The study included two age‐, body mass index‐, hormone‐ and thyroid antibody‐matched groups of young euthyroid women with Hashimoto's thyroiditis: 19 women with mild‐to‐moderate hyperprolactinaemia and 19 individuals with prolactin levels within the reference range. All participants were then treated with vitamin D (4000 IU daily) and selenomethionine (200 µg daily). Serum titres of thyroid peroxidase and thyroglobulin (TgAb) antibodies, serum levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin and 25‐hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis, were determined at baseline and 6 months later.
Results and discussion
All women completed the study. With the exception of prolactin and 25‐hydroxyvitamin D levels, there were no differences between the study groups in the investigated parameters. In both study groups, vitamin D/selenomethionine combination therapy reduced thyroid peroxidase and TgAb antibody titres, decreased the free thyroxine:free triiodothyronine ratio and increased 25‐hydroxyvitamin D levels and SPINA‐GD. The decrease in antibody titres, as well as the improvement in vitamin D status, was more pronounced in subjects with prolactin levels within the reference range than in subjects with hyperprolactinaemia and was inversely correlated with prolactin levels. Moreover, only in normoprolactinaemic women, the treatment reduced thyrotropin levels and increased SPINA‐GT.
What is new and conclusion
The obtained results suggest that hyperprolactinaemia attenuates the impact of vitamin D/selenomethionine combination on thyroid autoimmunity.
The effects of selenium on human health are multiple and complex. This chapter provides a brief introduction to the chemistry and metabolism, sources and dietary intake, and the effects of deficiency and excess of selenium, followed by an overview of dietary recommendations set by different national and international agencies. We discuss the benefits and disadvantages of different biomarkers used for measuring selenium status and review the determinants of selenium status. The biological functions and potential health effects of selenoproteins are summarized. A comprehensive review of the relationship between selenium status and health effects, including mortality, cardiovascular disease, cancer, type 2 diabetes, thyroid function, stroke, and neurological diseases, and fertility and reproduction, based on results from observational studies and clinical trials, is presented. Finally, we discuss the key knowledge gaps for a more accurate determination of selenium status and dose-response relationships to clarify the optimal selenium status for preventing chronic disease.
In the 1990s, selenium was identified as a component of an enzyme that activates thyroid hormone; since this discovery, the relevance of selenium to thyroid health has been widely studied. Selenium, known primarily for the antioxidant properties of selenoenzymes, is obtained mainly from meat, seafood and grains. Intake levels vary across the world owing largely to differences in soil content and factors affecting its bioavailability to plants. Adverse health effects have been observed at both extremes of intake, with a narrow optimum range. Epidemiological studies have linked an increased risk of autoimmune thyroiditis, Graves disease and goitre to low selenium status. Trials of selenium supplementation in patients with chronic autoimmune thyroiditis have generally resulted in reduced thyroid autoantibody titre without apparent improvements in the clinical course of the disease. In Graves disease, selenium supplementation might lead to faster remission of hyperthyroidism and improved quality of life and eye involvement in patients with mild thyroid eye disease. Despite recommendations only extending to patients with Graves ophthalmopathy, selenium supplementation is widely used by clinicians for other thyroid phenotypes. Ongoing and future trials might help identify individuals who can benefit from selenium supplementation, based, for instance, on individual selenium status or genetic profile.
The trace element selenium (Se) occurs in the form of the amino acid selenocysteine in selenoproteins. Selenoproteins exerts multiple physiological effects in human health, many of which are related with regulation of reduction-oxidation processes. In fact, the selenoenzyme families of glutathione peroxidase (GPx) and thioredoxin reductase (TRx) display the ability to act as antioxidants, protecting cells from oxidative damage. Furthermore, another class of selenoproteins are the iodothyronine deiodinase enzymes (DIO), which catalyze the conversion of thyroxine (T4) in triiodothyronine (T3), then exerting a fine tuned control on thyroid hormones metabolism. Several studies have investigated the potential positive effects of Se supplementation in thyroid diseases, characterized by increased levels of hydrogen peroxide and free radicals, like autoimmune chronic thyroiditis. These studies have supplied evidences indicating that Se supplementation, maximizing the antioxidant enzymes activity, may reduce the thyroid inflammatory status. Then, it may be postulated that Se could play a therapeutical role in thyroid autoimmune diseases. Despite the fact that recent studies seem to be concordant about Se beneficial effects in decreasing thyroid peroxidase antibodies (TPOAb) titers and ameliorating the ultrasound echogenicity pattern, several doubts have to be still clarified, before advising Se supplementation in chronic autoimmune thyroiditis.
In the previous two articles1 2 we outlined the potentials and principles of meta-analysis and the practical steps in performing a meta-analysis. Now we will examine how to use meta-analysis to do more than simply combine the results from all the individual trials into a single effect estimate. Firstly, we discuss the advantages and disadvantages of performing subgroup analyses. Secondly, we consider the situation in which the differences in effects between individual trials are related in a graded way to an underlying phenomenon, such as the degree of mortality risk of the trial participants.
#### Summary points
Meta-analysis can be used to examine differences in treatment effects across trials; however, the fact that randomised trials are included in meta-analyses does not mean that comparisons between trials are also randomised comparisons
Meta-analytic subgroup analyses, like subgroup analyses within trials, are prone to bias and need to be interpreted with caution
A more reliable way of assessing differences in treatment effects is to relate outcome to some underlying patient characteristic on a continuous, or ordered, scale
The underlying level of risk is a key variable which is often related to a given treatment effect, with patients at higher risk receiving more benefit then low risk patients
Individual patient data, rather than published summary statistics, are often required for meaningful subgroup analyses
The main aim of a meta-analysis is to produce an estimate of the average effect seen in trials of a particular treatment. The direction and magnitude of this average effect is intended to guide decisions about clinical practice for a wide range of patients. Clinicians are thus being asked to treat their patients as though each one is well represented by the patients in the clinical trials included in the meta-analysis. This runs against doctors' concerns to use the specific characteristics of a …
In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.
To investigate the relationship between selenium status, thyroid Volume and gland echostructure.
Cross-sectional.
In 792 men (45-60 Years) and 1108 women (35-60 Years) from the SU.VI.MAX study, thyroid Volume and gland echostructure were determined ultrasonographically. At baseline, thyrotropin, free thyroxine, selenium, zinc, alpha-tocopherol, beta-carotene, retinol, urinary iodine and thiocyanate concentrations were measured. Alcohol consumption, smoking, and menopausal status were assessed by a questionnaire. A stepwise linear and a logistic regression model were used, adjusting for antioxidant vitamins, trace elements status and age.
In women, there was an inverse association between selenium status and thyroid Volume (P=0.003). A protective effect of selenium against goiter (odds ratio (OR)=0.07, 95% confidence interval (CI)=0.008-0.6) and thyroid tIssue damage (OR=0.2, 95% CI=0.06-0.7) was observed. There was no evidence of an association between menopausal status and other antioxidant elements, thyroid Volume or thyroid hypoechogenicity. Smoking, but not alcohol consumption, was associated with an increased risk of thyroid enlargement in women (OR=3.94, 95% CI=1.64-9.48). No association between thyroid Volume, thyroid structure or selenium was found in men.
Our findings suggest that selenium may protect against goiter. Selenium was related to thyroid echostructure, suggesting it may also protect against autoimmune thyroid disease.
Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyse the extrathyroidal production of tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and the autoimmune process. Therefore, we performed a randomised, placebo-controlled prospective study to investigate the effects of Se treatment on patients with autoimmune thyroiditis (AIT).
Sixty five patients aged 22-61 years (median age 48 years) with AIT were recruited into two groups. Group I (Gr I) (n=34) was treated with selenomethionine (Seme) 200 microg, plus L-thyroxine (LT(4)) to maintain TSH levels between 0.3-2.0 mU/l, whereas group II (Gr II) (n=31) received LT(4) plus placebo over a period of 6 months. Moreover, the pharmacokinetics of Seme were studied in 10 patients and eight volunteers at baseline and 2 h, 4 h, 6 h and 24 h after oral administration of a 200 microg tablet of Seme. Finally, Se levels were measured at the end of the study in some patients of both groups and their results were correlated with thyroid hormone levels.
In the pharmacokinetics study, basal serum concentration of Se (75+/-6 microg/l) was within the reference range (70-125 microg/l), it promptly increased at 2 h, peaked at 4 h (147+/-17 microg/l; P<0.0001) and it was abundant in serum at 24 h. In Gr I, antibodies against thyroid peroxidase (anti-TPO) levels showed an overall decrease of 46% at 3 months (from 1875+/-1039 U/l to 1013+/-382 U/l; P<0.0001) and of 55.5% at 6 months. In Gr II the overall decrease of anti-TPO amounted to 21% at 3 months and to 27% at 6 months (from 1758+/-917 U/l to 1284+/-410 U/l; P<0.005). There were no significant changes of antibodies against thyroglobulin levels between the groups. At the end of this study Se levels were found to be statistically significantly increased in Gr I (n = 9/34) compared with Gr II (n=11/31) (97+/-8.4 vs 79+/-8; P<0.01) but no correlation with thyroid hormone was found.
Seme is proven to be rapidly absorbed by the gastrointestinal tract. It appears to be useful as adjunctive therapy with LT(4) in the treatment of AIT. The exact mechanism(s) is not very well determined, it might enhance the activity of detoxifying enzymes and enforce the defense against oxidative stress.
Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
The trace element selenium (Se) is capable of exerting multiple actions on endocrine systems by modifying the expression of at least 30 selenoproteins, many of which have clearly defined functions. Well-characterized selenoenzymes are the families of glutathione peroxidases (GPXs), thioredoxin reductases (TRs) and iodothyronine deiodinases (Ds). These selenoenzymes are capable of modifying cell function by acting as antioxidants and modifying redox status and thyroid hormone metabolism. Se is also involved in cell growth, apoptosis and modifying the action of cell signalling systems and transcription factors. During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage. Thyroidal D1 in rats and both D1 and D2 in humans are also up-regulated to increase the production of bioactive 3,5,3'-tri-iodothyronine (T3). In the basal state, GPX3 is secreted into the follicular lumen where it may down-regulate thyroid hormone synthesis by decreasing hydrogen peroxide concentrations. The deiodinases are present in most tissues and provide a mechanism whereby individual tissues may control their exposure to T3. Se is also able to modify the immune response in patients with autoimmune thyroiditis. Low sperm production and poor sperm quality are consistent features of Se-deficient animals. The pivotal link between Se, sperm quality and male fertility is GPX4 since the enzyme is essential to allow the production of the correct architecture of the midpiece of spermatozoa. Se also has insulin-mimetic properties, an effect that is probably brought about by stimulating the tyrosine kinases involved in the insulin signalling cascade. Furthermore, in the diabetic rat, Se not only restores glycaemic control but it also prevents or alleviates the adverse effects that diabetes has on cardiac, renal and platelet function.
The aim of this study is to investigate the long-term (9 months) effects of variable doses (200/100 microg/day) of L-selenomethionine on autoimmune thyroiditis (AIT) and the parameters affecting the success rate of this therapy. The present study was designed in three steps: (1) 88 female patients with AIT (mean age = 40.1 +/- 13.3 years) were randomized into two groups according to their initial serum TSH, thyroid peroxidase antibody (TPOAb) concentrations, and age. All the patients were receiving L-thyroxine to keep serum TSH <or=2 mIU/l. Group S2 (n = 48, mean TPOAb = 803.9 +/- 483.8 IU/ml) received 200 microg L-selenomethionine per day, orally for 3 months, and group C (n = 40, mean TPOAb = 770.3 +/- 406.2 IU/ml) received placebo. (2) 40 volunteers of group S2 were randomized into two age- and TPOAb-matched groups. Group S22 (n = 20) went on taking L-selenomethionine 200 microg/day, while others (group S21) lowered the dose to 100 microg/day. (3) 12 patients of group S22 (group S222) went on taking L-selenomethionine 200 microg/day, while 12 patients of group S21 (S212) increased the dose to 200 microg/day. Serum titers of TPOAb decreased significantly in group S2 (26.2%, P < 0.001), group S22 (23.7%, P < 0.01) and group S212 (30.3%, P < 0.01). There were no significant changes in group C and group S222 (P > 0.05). TPOAb titers increased significantly in group S21 (38.1%, P < 0.01). A significant decrease in thyroglobulin antibody titers was only noted in group S2 (5.2%, P < 0.01). L-selenomethionine substitution suppresses serum concentrations of TPOAb in patients with AIT, but suppression requires doses higher than 100 microg/day which is sufficient to maximize glutathione peroxidase activities. The suppression rate decreases with time.
There is increasing evidence showing that apoptosis plays a role in the development of the autoimmune thyroid diseases-Hashimoto's (lymphocytic) thyroiditis (HT) and Graves' disease (GD). The immune pathogenesis of HT and GD is not yet fully understood, but evidence points toward several steps. A defect in CD4(+)CD25(+) T regulatory cells breaks the immunological tolerance of the host and induces an abnormal production of cytokines, which facilitates the initiation of apoptosis. Though apoptosis appears to play a role in the pathogenesis of both HT and GD, the mechanisms that mediate these processes appear different. The induction of apoptosis in HT results in the destruction of thyrocytes, while apoptosis in the GD leads to damage of thyroid-infiltrating lymphocytes. The differences in the apoptotic mechanisms produce two very different forms of thyroid autoimmune responses, eventually developing into HT and GD, respectively.
The present study was conducted to evaluate the serum copper, zinc, magnesium, and selenium levels in patients with subclinical hypothyroidism in the iodine-rich region of Ankara, Turkey. The effects of hormone replacement therapy on these elements were also studied in these patients. Basal levels of selenium and iron in patients were significantly lower than control group (67.7 +/- 10.4 vs. 83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03 microg/dl). Serum magnesium levels were significantly higher in patient group (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in patients with selenium levels <80 microg/l (n = 31) was significantly higher than hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0; 1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace elements have changed after euthyroidism in patients with SH when compared to pretreatment levels. Selenium deficiency may contribute to cardiovascular disease risk in these patients.
Selenium, a potential cancer prevention agent currently being tested against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), plays an integral role in thyroid metabolism. The effects of long-term selenium supplementation on thyroid hormone concentrations are unknown.
The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations.
Twenty-eight healthy adults took 200 microg selenomethionine/d for 28 mo. The thyroid hormones triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured in plasma for 4 mo before supplementation and quarterly during supplementation. The assay methods were changed midstudy; the results of the 2 methods were not comparable. Therefore, one analysis was conducted based on the results of the first method, and a second analysis was based on all of the data, adjusted for the change. Serial data collection permitted a test for trends rather than simply a difference between initial and final values.
By 9 mo, mean (+/-SEM) plasma selenium concentrations had increased from 1.78 +/- 0.07 micromol/L at baseline to 2.85 +/- 0.11 micromol/L for men and from 1.64 +/- 0.04 to 3.32 +/- 0.1.2 micromol/L for women. T3 concentrations in men increased 5% per year (P = 0.01). T4 and TSH concentrations were unchanged.
Selenium supplementation produced no clinically significant changes in thyroid hormone concentrations. A small but statistically significant increase in T3 concentrations was noted in men, with no corresponding decreases in TSH. A subset of SELECT subjects might be monitored periodically for changes during long-term selenium supplementation.
Autoimmune thyroid disorders (AITDs) are the result of a complex interplay between genetic and environmental factors, the former account for about 70-80% of liability to develop AITDs. However, at least 20-30% is contributed by environmental factors, which include certainly smoking (at least for Graves' disease and orbitopathy), probably stress, iodine and selenium intake, several drugs, irradiation, pollutants, viral and bacterial infections, allergy, pregnancy, and post-partum. Evidence for the intervention of these factors is often limited, and the mechanisms whereby environmental factors may concur to the onset of AITDs are in many instances unclear. Nevertheless, gene-environment interaction seems a fundamental process for the occurrence of AITDs.
Severe selenium deficiency has been documented in northern Zaïre, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases.
Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation.
Fifty-two healthy schoolchildren from northern Zaire.
Selenium status, thyroid function and urinary iodide were determined.
After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH.
Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.
Dioxygen (02) is required by most plants and animals (aerobes) for the oxidation of carbohydrates (glucose principally), protein (amino acids) and lipids (fatty acids) which serves as the terminal acceptor in mitochondria of both hydrogen and electrons in the formation of metabolic water. For aerobic metabolism dioxygen is essential. Other forms of life, the anaerobes, are viable only in the absence of dioxygen, for dioxygen is toxic to anaerobic organisms. Aerobic life has thus evolved in a dioxygen environment having developed the necessary cellular defenses to thwart dioxygen toxicity.
After in-vivo labeling with [75Se]selenite the Se-containing proteins present in rat tissues were investigated by means of SDS-polyacrylamide gel electrophoresis. Thirteen Se-containing proteins or protein subunits with relative molecular weights of 12,100, 15,600, 18,000, 19,700, 22,200, 23,700, 27,800, 33,300, 55,500, 59,900, 64,900, 70,100 and 75,400 were detected in the tissue homogenates. The protein with the molecular weight of 23,700 was the subunit of glutathione peroxidase, which is the only selenoprotein so far known to have biological functions in animals. Most of these proteins were found in all tissues investigated but one was only detected in the testes and the spermatozoa and one was present mainly in the thyroid. With inadequate selenium intake there was a priority supply of the element to the brain, the reproductive and the endocrine organs, and at a molecular level to Se-containing proteins other than glutathione peroxidase. The results suggest important biological functions of these selenoproteins, especially in the specific target tissues.
Selenium (Se) deficiency is said to contribute to the atrophy of the thyroid gland in certain endemic goiter areas in Africa. To test the hypothesis that, a low Se intake could protect against goiter development in autoimmune thyroiditis, we analysed the Se concentration in 20 patients with the atrophic variant of lymphocytic thyroiditis, 23 patients with Hashimoto's thyroiditis and 23 patients with non-toxic nodular (colloid) goiter. Twenty healthy females served as controls. We did not find any significant difference in serum selenium (S-Se) levels between the patients with the various thyroid disorders or between patients and controls. There was no difference in the S-Se concentration and the triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) or thyroglobulin concentrations in serum. Thus, the Se status had no impact on the development of goiter.
Selenium and cadmium concentrations were investigated in 60 autopsy tissue samples obtained from fetal life up to adulthood (defined in this study as 25-87 y of age) in Styria, a moderately industrialized region in Austria that has a low selenium supply. During the first 2 y after birth, median liver selenium concentrations were slightly lower (i.e., 1.5 nmol/g wet weight) than concentrations found in fetal life (i.e., 2.9 nmol/g) and adulthood (2.1 nmol/g). Whereas in the fetal period median selenium content in the kidney cortex (2.1 nmol/g) and the thyroid gland (1.6 nmol/g) was lower than that found in the liver, the reverse was true for adults (i.e., kidney, 5.5 nmol/g; thyroid, 4.3 nmol/g). Tissue cadmium concentrations approached 0 during gestation. Accumulation in the kidney and liver commenced immediately after birth. In the thyroid gland of adults, significantly higher concentrations of cadmium were found. Median concentrations in adults showed no statistical significant age dependency (i.e., liver, 7.6 nmol/g; kidney, 59.8 nmol/g; thyroid, 11.2 nmol/g). In summary, the data revealed very low tissue selenium concentrations and low cadmium burdens for the Styrian population that was not exposed occupationally.
Contempre B, Dumont JE, Denef J-F, Many M-C. Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. Eur J Endocrinol 1995;133:99–109. ISSN 0804–4643
It has been suggested that selenium deficiency is a co-factor to iodine deficiency in the pathogenesis of myxoedematous cretinism. The mechanism proposed is that the generation of hydrogen peroxide is greatly increased in iodine-deficient thyroid glands, and that selenium is involved in the control of hydrogen peroxide and its derived free radicals. This study was carried out to investigate the effect of the possibly impaired cellular defence mechanism associated with selenium deficiency on thyroid necrosis and tissue repair. For this purpose, we studied thyroid tissue from selenium- (SE–) and/or iodine-deficient (I–) rats before and after an acute toxic iodine overload. In I– thyroids, necrotic cells were numerous. Acute iodine administration increased this effect. Necrosis was associated with transient infiltration of inflammatory cells. In 1–SE+ thyroids the tissue resumed its normal appearance. In 1–SE– thyroid glands, the iodide toxicity was stronger, with greater necrosis and inflammatory reaction. The inflammation resolved but was replaced by fibrotic tissue. Fifteen days after the toxic overload, the connective tissue volume was twice the control value. Before iodide overload, the proportion of dividing cells was equal in 1–SE+ and 1–SE– thyroids. Three days after the iodide overload, this proportion was increased in 1–SE+ thyroids but reduced in the 1–SE– thyroids. Overall, the 1–SE– thyroids had four times fewer dividing cells than the 1–SE+ thyroids. In summary, selenium deficiency coupled to iodine deficiency increased necrosis, induced fibrosis and impeded compensatory epithelial cell proliferation. These results are compatible with histological and functional descriptions of thyroid tissue from myxoedematous cretins.
B Contempre, IRIBHN, C.P. 602, Free University of Brussels, Medicine Faculty, 808 route de Lennik, B-1070 Brussels, Belgium
Thyroid-cytotoxic antibodies (thyroid-cytotoxic Abs) have been described in patients with autoimmune thyroiditis, but their role in the development of hypothyroidism remains to be clarified. In this study, we evaluated the pathogenetic role of thyroid-cytotoxic Abs in 20 patients with atrophic thyroiditis (idiopathic myxedema; AT) and 94 patients with goitrous Hashimoto's thyroiditis (HT). Among patients with HT, 27 were euthyroid (HT-E), 27 had subclinical hypothyroidism (HT-SH), and 40 had overt hypothyroidism (HT-H). Seventeen normal subjects and 8 patients with nonthyroidal illnesses were used as controls (C). To detect thyroid-cytotoxic Abs, human thyroid cells expressing thyroid peroxidase (TPO) were labeled with 51Cr and challenged with the immunoglobulin G (IgG) fraction of serum plus rabbit complement. The cytotoxic effect of IgGs was calculated as the percent specific lysis (% SL), taking into account the lytic effect of complement alone and the maximal lysis produced by a detergent. Most C-IgGs decreased the cytotoxic effect of complement (median % SL, -3.3). IgGs from hypothyroid patients with thyroiditis had a greater cytotoxic effect than C-IgGs, either as a whole group (P < 0.001), or when subdivided according to clinical diagnosis: HT-SH (median % SL, 4.8; P < 0.005), HT-H (%SL, 2.2; P < 0.0001), or AT (%SL, 0.9; P < 0.01). Among patients with HT, the lytic activity of IgGs from patients with subclinical and overt hypothyroidism was higher than that of IgGs from euthyroid patients (P < 0.05). The results of IgGs from euthyroid patients with HT (median % SL, -0.9) did not significantly differ from those of C-IgGs. By taking a cut-off over the upper range of % SL produced by C-IgGs (> 2), the prevalence of thyroid-cytotoxic Abs was 30% in AT, 59% in HT-SH, and 55% in HT-H. However, 37% of euthyroid patients with HT also had thyroid-cytotoxic Abs. No IgG containing TPO antibodies (TPOAb) at low titer (< 40(2)) was cytotoxic. However, the levels of thyroid-cytotoxic Abs did not correlate with TPOAb titers, and preabsorption with TPO only partially abolished the lytic effect of some HT-IgG. These findings suggest that TPO is a target of thyroid-cytotoxic Abs, but other thyroid antigens are also involved in the cytotoxic reaction.(ABSTRACT TRUNCATED AT 400 WORDS)
The total mercury (Hg) and selenium (Se) concentrations were determined in kidney cortex samples of 195 deceased, non-occupationally burdened individuals. Mercury was determined by means of Cold-vapour Atomic Absorption Spectrometry (CV-AAS) and selenium by Graphite-Furnace Atomic Absorption Spectrometry (GF-AAS). The molar Se/Hg ratio is high (up to (a) 300) in cases with relatively low mercury concentrations [Hg]. The ratio decreases with increasing [Hg]. At [Hg] of 700-1000 ng/g it reaches unity, where it remains constant even at larger [Hg]. Since in vitro mercury and selenium form relatively stable adducts, our results suggest the formation of a 1:1 Hg-Se compound that may explain mercury detoxification by selenium. This effect also results in the trapping of available selenium by mercury, too. Decreasing the reserve of free (i.e. not Hg-bound) selenium. The effect of this decrease of free selenium is under further investigation.
Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role.
It has been proposed that interaction of catecholamines and indoleamines with free radicals may result in the formation of endogenous neurotoxins. In order to better understand the mechanisms involved in neurodegenerative disorders showing evidence of oxidative stress, we have studied the basal concentrations and the turnover rates of dopamine, noradrenaline, serotonin and their metabolites in the prefrontal cortex of rats that were fed on control or low selenium diets. Nutritional deficit of selenium decreases the brain antioxidant protection in experimental conditions by the decrease in glutathione peroxidase activity. The dopamine and serotonin turnover increased and noradrenaline and 5-hydroxy-3-indoleacetic acid turnover decreased compared to experimental control animals. The increase of dopamine turnover in experimental rats was accompanied by an increase in tyrosine hydroxylase activity. These results suggest that the decrease of brain protection against oxidative damage could induce brain damage by disturbing the turnover rate of some monoamines.
The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.
To determine whether systemic oxidative stress status is associated with cognitive decline.
A longitudinal population-based study.
A cohort study of older subjects in Nantes, France.
A total of 1166 high cognitive functioning subjects aged 60 to 70 in the Etude du Vieillissement Arteriel (EVA) cohort with a 4 year follow-up.
Subjects completed a baseline interview and a global cognitive test (Mini-Mental Status Examination (MMSE)). Blood samples were obtained at baseline to determine plasma levels of selenium, carotenoids, thiobarbituric acid reactant substances (TBARS), an indicator of lipoperoxidation, and red blood cell vitamin E. Risk of cognitive decline, defined as a loss of 3 points in MMSE score between baseline and the 4 year follow-up, was assessed by oxidative stress level.
Subjects with the highest levels of TBARS show an increased risk of cognitive decline (adjusted odds ratio (OR) = 2.25; confidence interval (CI) 95% = 1.26-4.02). This result is reinforced in the lower antioxidant status subgroup. Subjects with low levels of selenium have an increased risk of cognitive decline (OR = 1.58; CI 95% = 1.08-2.31) after adjustment for various confounding factors.
These results suggest that increased levels of oxidative stress and/or antioxidant deficiencies may pose risk factors for cognitive decline. The direct implication of oxidative stress in vascular and neurodegenerative mechanisms that lead to cognitive impairment should be further explored.
Cognitive impairment is a major component of age-related dementing diseases and it has been suggested that it could share the same pathological pathways with neurodegenerative processes and cerebrovascular lesions. The free radical theory of ageing could be one of these pathways. Implication of free radical damage in processes related to cerebral ageing is a good argument in favour of the hypothesis that antioxidants may protect against cognitive impairment.
Observational studies (mostly cross-sectional) of relationships between cognitive impairment and antioxidant status are based on the evaluation of dietary intake or on the levels of carotenoids, selenium and vitamins A, C and E in plasma or red blood cells. More convincing results were obtained on vitamin C and carotenoids. Despite some limitations, the comparison between results obtained in various populations is becoming increasingly informative and these studies argue for a protective effect of antioxidants on cognitive performance.
Selenium supplements contain selenium in different chemical forms. In the majority of supplements, the selenium is present as selenomethionine. However, in multivitamin preparations, infant formulas, protein mixes, weight-loss products and animal feed, sodium selenite and sodium selenate are predominantly used. In some products, selenium is present in protein- or amino acid chelated forms; in still others, the form of selenium is not disclosed. Current evidence favors selenomethionine over the other forms of selenium. Extradietary supplementation of selenium at the dosage of 200 micrograms per day is generally considered safe and adequate for an adult of average weight subsisting on the typical American diet.
The aim of the present work was to clarify whether the activities of selenoenzymes can serve as markers for different tumors or goiters, as classified by histological criteria. The following parameters were determined: 1) selenium content of plasma (Se), 2) activities of the selenoenzymes: plasma glutathione peroxidase (plGSHPx), cytosolic glutathione peroxidase (cGSHPx), type I and type II iodothyronine deiodinases (ID-I, ID-II), thioredoxin reductase (THRR) in human thyroid tissues. The material came from follicular neoplasm, papillary carcinoma, struma nodosa, struma lymphomatosis Hashimoto, other thyroid surgery specimens, and normal tissues. There was no difference in Se nor in plGSHPx between patients and healthy volunteers. No significant differences were found for any parameter in thyroid carcinoma versus normal or goitrous thyroid tissue. In the whole group of thyroid surgery specimens the statistically significant correlations were found between ID-I and ID-II and between THRR and selenoperoxidases. Principal components analysis confirmed the above correlation and moreover revealed correlation between Se and plGSHPx, but did not detect any clear distinction between patients with the different diagnoses.
We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves' disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves' disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves' disease. The low selenium levels in the thyroid tissue may increase thyroid cancer risk.
We investigated the possible differences among the concentrations of copper, zinc, and selenium, and their mutual relations in the whole blood and thyroid tissue of patients with various thyroid disorders. Trace elements were determined by total-reflection X-ray fluorescence. The mean levels of these metals in blood as well as the mean Cu/Zn, Cu/Se, and Zn/Se ratios in the patients with thyroid cancer were significantly higher that in other patients and the control groups. However, the mean Zn and Se concentrations in the thyroid cancer tissue were significantly lower than in the thyroid tissue of other patients. In addition, the mean Cu/Zn and Cu/Se ratios in the thyroid cancer tissue were significantly higher than in the patients with other thyroid diseases. We confirm that the highest levels of copper and zinc as well as the Cu/Zn, Cu/Se, and Zn/Se ratios in the whole blood of the patients with thyroid cancer may suggest the progression of the proliferation process in the thyroid gland. We suggest that the low concentrations of zinc and selenium in the thyroid tissue confirm their participation in the carcinogenic process.
We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.
The effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the speed of attaining euthyroidism in a group of patients with Graves' disease, treated with methimazole.
The activity of glutathione peroxidase in whole blood and the concentrations of selenium, pituitary and thyroid hormones in serum were measured, prior to commencement of therapy and after 30 and 60 days. RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole (Group A, n=29) attained euthyroidism faster than the patients treated with only methimazole (Group B, n=28). The concentration of selenium in the serum of patients in Group A increased significantly during treatment (p<0.001), while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01) after the commencement of therapy. Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients. However, a statistically more significant increase occurred in Group A compared to Group B, 30 days after the commencement of therapy (p<0.01).
The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves' disease is justified, particularly those containing selenium.