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Selenium and Thyroid Function
Abstract
Selenium is an essential trace element embedded in several proteins. Most of the known selenoproteins are found in the thyroid gland and this is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet, geographic area, and soil composition. In the thyroid, selenium is required for protection from oxidative damage and for the metabolism of thyroid hormones. The literature suggests that selenium intake is associated with autoimmune thyroid disorders and selenium supplementation in those patients is associated with a reduction in antithyroid antibody levels, improved thyroid ultrasound features, and improved quality of life. Selenium supplementation in Graves’ ophthalmopathy is associated with an improved quality of life, less eye involvement, and delayed orbitopathy progression. Supplementation with the organic form is more effective, and benefits in immunological mechanisms have been observed in patients with autoimmune thyroiditis.
... AITDs encompass a wide spectrum of disorders. Amidst them, Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the most common ones [225][226][227][228][229]. ...
... It is a well-known fact that the thyroid organ is particularly rich in Se, which is incorporated into selenoproteins, such as glutathione peroxidase (GPx), thioredoxin reductase (TrxR), iodothyronine deiodinases (DIO), and selenoprotein P (SELENOP). Some of them are involved in hormone metabolism and have a crucial antioxidant activity directed against the oxygen free radicals generated in the production of the thyroid hormones (THs) [225,226,228,[230][231][232]. Furthermore, there is mounting evidence that patients with thyroid pathologies (i.e., hypothyroidism, AITDs, and enlarged thyroid) present reduced levels of this micronutrient [225,233]. ...
... Over the last years, several literature reports have indicated that this element, in combination with myo-inositol, has a beneficial effect as it can reduce the thyroid-stimulating hormone (TSH) and the antithyroid autoantibodies levels, thus decreasing the risk of progression to hypothyroidism in AITDs patients [225,237,[241][242][243][244][245]. Moreover, the protective effect of Se supplementation on thyroid autoimmunity during and after pregnancy has been studied [5,228,238,239]. In this regard, the SERENA study has evaluated the effect of SeMet on AITDs in euthyroid pregnant women with positive antithyroid antibodies. ...
Selenium (Se) is an essential element for human health as it is involved in different physiological functions. Moreover, a great number of Se compounds can be considered potential agents in the prevention and treatment of some diseases. It is widely recognized that Se activity is related to multiple factors, such as its chemical form, dose, and its metabolism. The understanding of its complex biochemistry is necessary as it has been demonstrated that the metabolites of the Se molecules used to be the ones that exert the biological activity. Therefore, the aim of this review is to summarize the recent information about its most remarkable metabolites of acknowledged biological effects: hydrogen selenide (HSe−/H2Se) and methylselenol (CH3SeH). In addition, special attention is paid to the main seleno-containing precursors of these derivatives and their role in different pathologies.
... Elemental Se is not biologically active per se. However, this trace element exerts its biological function(s) through its incorporation as selenocysteine and selenomethionine with subsequent integration into 25 selenoproteins encoded by the human genome [10,11] and 24 known proteins in rodents [12]. Thus, selenoproteins are Se-dependent proteins Citation: Mojadadi, A.; Au, A.; Salah, W.; Witting, P.; Ahmad, G. ...
... The thyroid has the highest Se concentration among all other endocrine organs, indicating the significance of the functions of thyroid [46,54]. In humans, optimal Se status is essential for the maintenance of thyroid health, metabolism of thyroid hormones (TH), and protection from thyroid disorders [10]. Though debated, numerous clinical studies have illustrated that Se supplementation had anti-inflammatory effects in patients with autoimmune thyroiditis, characterised by reduced anti-thyroid peroxidase complement-fixing autoantibody (TPOAb) levels and restored thyroid features [55,56]. ...
... Selenium exerts its biological functions through its incorporation as selenocysteine into selenoproteins in humans [10,11] and rodents [12]. Selenoproteins have various biological roles in the thyroid, ranging from catalyzing enzymatic redox reactions, regulating thyroid hormone metabolism, and protecting against oxidative DNA damage induced by hydrogen peroxide (H2O2) and lipid hydroperoxide, and inflammation (Table 1) [57]. ...
Selenium (Se) is a micronutrient essential for life. Dietary intake of Se within the physiological range is critical for human health and reproductive functions. Selenium levels outside the recommended range have been implicated in infertility and variety of other human diseases. However, presently it is not clear how different dietary Se sources are processed in our bodies, and in which form or how much dietary Se is optimum to maintain metabolic homeostasis and boost reproductive health. This uncertainty leads to imprecision in published dietary guidelines and advice for human daily intake of Se and in some cases generating controversies and even adverse outcomes including mortality. The chief aim for this review is to describe the sources of organic and inorganic Se, the metabolic pathways of selenoproteins synthesis, and the critical role of selenprotenis in the thyroid gland homeostasis and reproductive/fertility functions. Controversies on the use of Se in clinical practice and future directions to address these challenges are also described and discussed herein.
... Biological methods will be a research hotspot for a long time to solve the problems of the preparation mechanism and instability during production. (2) The appropriate concentration of nanoselenium used in food is still a problem that needs further study, and no unified standard and corresponding laws/regulations are established. ...
Nanoselenium is a promising selenium supplement as a result of its low toxicity and high bioavailability. However, the understanding on the preparation, stability, bioavailability, possible risks, and related underlying mechanisms of nanoselenium is not in-depth. Thus, the above aspects were reviewed on the basis of the latest literature. The reducing capacity and stability of the reducing agent and binding force between nanoselenium and the template decide the nanoselenium stability. Although research on nanoselenium application in food, agriculture, livestock, and aquaculture has been widely carried out, it is not widely applied in the fields. Se-containing amino acids are synthesized using nanoselenium adsorbed by organisms, and they constitute Se-containing proteins with other amino acids, which improves the health of organisms via scavenging excessive radicals. Notably, excessive nanoselenium intake generates redundant Se-containing amino acids, leading to dysfunction of key proteins in organisms, and its toxic doses vary with organisms. Furthermore, some issues related to nanoselenium still need to be solved urgently.
Background
Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells. Methods
Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique. ResultsOur results show a decrease in the expression of GPx1 and TrxR1 (− 45.7 and − 43.2% respectively, p < 0.01) in the thyroid cancer cells compared to the healthy cells. In addition, the EPR technique shows an increase of free radicals in tumor tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%, p < 0.01). Conclusions
Our findings underscore the relationship between thyroid cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant system in thyroid cancer tissue. These results suggest that either the inability to produce adequate antioxidant defense or an increased consumption of antioxidants, due to the hyper-production of free radicals, may play a crucial role in thyroid cancer.
Introduction. Selenium is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet, geographic area, and soil composition. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. Methods. We performed a review of the literature on selenium’s role in thyroid function using PubMed/MEDLINE. Results. Regarding thyroid pathology, selenium intake has been particularly associated with autoimmune disorders. The literature suggests that selenium supplementation of patients with autoimmune thyroiditis is associated with a reduction in antithyroperoxidase antibody levels, improved thyroid ultrasound features, and improved quality of life. Selenium supplementation in Graves’ orbitopathy is associated with an improvement of quality of life and eye involvement, as well as delayed progression of ocular disorders. The organic form of selenium seems to be the preferable formulation for supplementation or treatment. Conclusion. Maintaining a physiological concentration of selenium is a prerequisite to prevent thyroid disease and preserve overall health. Supplementation with the organic form is more effective, and patients with autoimmune thyroiditis seem to have benefits in immunological mechanisms. Selenium supplementation proved to be clinically beneficial in patients with mild to moderate Graves’ orbitopathy.
Background
The real efficacy of selenium supplementation in Hashimoto’s thyroiditis (HT) is still an unresolved issue. Objectives
We studied the short-term effect of l-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of l-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. Methods
In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive l-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. ResultsTSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. Conclusion
The short-term l-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term l-selenomethionine supplementation in HT.
The present study aims to examine the changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. The study registered 50 individuals, of whom 25 were female and 25 were male. The patients were allocated to four groups: group 1: male thyroid cancer patients group (n = 15), group 2: female thyroid cancer patients group (n = 15), group 3: male control group (n = 10), group 4: female control group (n = 10). The subjects in groups 1 and 2 were the patients who were post-operatively diagnosed with a pathological malignancy in the thyroid tissue samples. Blood samples were collected from all subjects before the operation, immediately after the operation, and on the post-operative day 15. Additionally, thyroid tissue samples were taken from all subjects post-operatively. Some elements in the blood and tissue samples were determined using the atomic emission method. Zinc and selenium levels of groups 1 and 2 in the pre- and post-operative measurements were significantly lower than those in the control groups (p < 0.05), but were higher in the thyroid tissue (p < 0.05). Serum zinc and selenium levels measured in the subjects on the post-operative day 15 were similar to those measured in the controls. Our study show that changes in the serum and thyroid tissue levels of trace elements like zinc and selenium, which play a critical role in thyroid function, might be associated with the pathogenesis of thyroid cancer.
Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients. In mild GO, a watchful strategy is usually sufficient, but a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms. High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO. The optimal cumulative dose appears to be 4.5-5 g of methylprednisolone, but higher doses (up to 8 g) can be used for more severe forms. Shared decision-making is recommended for selecting second-line treatments, including a second course of intravenous GCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab or watchful waiting. Rehabilitative treatment (orbital decompression surgery, squint surgery or eyelid surgery) is needed in the majority of patients when GO has been conservatively managed and inactivated by immunosuppressive treatment.
Epidemiological studies have supported the premise that an adequate selenium intake is essential for thyroid-gland function Objective: To investigate whether the prevalence of thyroid disease differed in two areas, similar except for very different soil/crop selenium concentrations.
Cross-sectional observational study.
Two counties of Shaanxi Province, China, here defined as adequate- and low-selenium.
6152 participants selected by stratified cluster-sampling.
Participants completed demographic and dietary questionnaires and underwent physical and thyroid-ultrasound examinations. Serum samples were analysed for thyroid-function parameters and selenium concentration. Serum selenium was compared between different demographic, dietary and lifestyle categories in the two counties. The relationship between selenium status, dietary factors and pathological thyroid conditions was explored by logistic regression.
Complete data sets were available from 3,038 adequate-selenium and 3,114 low-selenium participants in whom median (IQR) selenium concentrations differed almost two-fold [103.6 (79.7, 135.9) vs. 57.4 (39.4, 82.1) μg/L; P=0.001]. The prevalence of pathological thyroid conditions (hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, enlarged thyroid) was significantly lower in the adequate-selenium than in the low-selenium county (18.0% vs. 30.5%; P<0.001). Higher serum selenium was associated with lower odds (OR; 95% CI) of autoimmune thyroiditis (0.47; 0.35, 0.65), subclinical hypothyroidism (0.68; 0.58, 0.93), hypothyroidism (0.75; 0.63, 0.90) and an enlarged thyroid (0.75; 0.59, 0.97).
Low selenium status is associated with increased risk of thyroid disease. Increased selenium intake may reduce the risk in areas of low selenium intake which exist not only in China but in many other parts of the world.
In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added.
The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety.
We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se/day or placebo. The selenoprotein P concentration was determined in plasma at inclusion and after 36 weeks. The patients were also assessed with questionnaires about depression, anxiety and self-rated symptoms before medication was started and after 36 weeks.
FT4 decreased more in the Se group at 18 weeks (14 vs. 17 pmol/l compared to the placebo group, p = 0.01) and also at 36 weeks (15 vs. 18 pmol/l, p = 0.01). The TSH increased more in the Se group at 18 weeks (0.05 vs. 0.02 mIU/l, p = 0.04). The depression and anxiety scores were similar in both groups. In the Se group, the depression rates correlated negatively with FT3 and positively with TSH. This was not seen in the placebo group.
Se supplementation can enhance biochemical restoration of hyperthyroidism, but whether this could shorten clinical symptoms of thyrotoxicosis and reduce mental symptoms must be investigated further.
This review aims to illustrate the importance of selenium (Se) for maintenance of overall health, especially for the thyroid, immunity, and homeostasis. Furthermore, it outlines the role of Se in reproduction and in virology and discusses the effects of Se supplementation in critical illness. The multifaceted aspects of this essential nutrient have attracted worldwide clinical and research interest in the last few decades. Se exerts its activity in the form of the aminoacid selenocysteine incorporated in selenoproteins. The impact of Se administration should be considered in relation to its apparent U shaped effects, i.e., exhibiting major advantages in Se-deficient individuals but specific health risks in those with Se excess. Addition of selenium to the administration of levothyroxine may be useful in patients with low Se intake and with mild-form or early-stage Hashimoto’s thyroiditis (HT). Serum Se concentration (possibly also at tissue level) decreases in inflammatory conditions and may vary with the severity and duration of the inflammatory process. In such cases, the effect of Se supplementation seems to be useful and rational. Meanwhile, Se’s ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral disease. However, the evidence, and this should be stressed, is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves’ Orbitopathy. The role of Se in type 2 diabetes mellitus (T2DM) is ambiguous, driven by both Se intake and serum levels. The evidence that insulin and glycaemia influence the transport and activity of Se, via regulatory activity on selenoproteins, and that high serum Se may have a diabetogenic effect suggests a ‘Janus-effect’ of Se in T2DM. Though the evidence is not as yet clear-cut, the organic form (selenomethionine), due to its pharmacokinetics, is likely to be more advantageous in long-term prevention, and supplementation efforts, while the inorganic form (sodium selenite) has proven effective in an acute, e.g., sepsis, clinical setting. Recent data indicate that functional selenoprotein single-nucleotide polymorphisms (SNPs) may interfere with Se utilization and effectiveness.
Purpose
Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response. We aimed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody (TPO-Ab) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population.
Methods
Samples and data were from a secondary analysis of Selenium in PRegnancy INTervention (SPRINT), a double-blind, randomized, placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation. Women were randomized to receive 60 µg/day selenium or placebo until delivery. Serum thyroid peroxidase antibodies (TPO-Ab), thyrotropin (TSH) and free thyroxine (FT4) were measured at 12, 20 and 35 weeks and thyroglobulin antibodies (Tg-Ab) at 12 weeks.
Results
93.5 % of participants completed the study. Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy. In women who were either TPO-Ab or Tg-Ab negative at baseline (Thy-Ab−ve), TSH increased and FT4 decreased significantly throughout gestation (P
The therapeutic effect of selenium (Se) has already been proven in thyroid disease and thyroid associated ophthalmopathy (TAO). In spite of clear scientific proof of its benefits in TAO, there appears to be no clear agreement among the clinicians regarding its optimum dose, duration of the treatment, efficacy and safety to date. In this review, the author summarises the findings of 135 English language articles published on this subject over the past four decades from 1973 to 2013. The regulation and metabolism of thyroid hormones require a steady supply of Se and recent studies have revealed several possible mechanisms by which Se improves the severity of thyroid disease and TAO. These mechanisms include 1) inhibitory effect of HLA-DR molecule expression on thyrocytes; 2) profound reductions of thyroid stimulating hormone (TSH) receptor antibodies (TSHR-Ab) and TPO antibodies (TPO-Ab); 3) prevention of dysregulation of cell-mediated immunity and B cell function; 4) neutralising reactive oxygen species (ROS) and inhibition of redox control processes required for the activation, differentiation and action of lymphocytes, macrophages, neutrophils, natural killer cells involved in both acute and chronic orbital inflammation in TAO; 5) inhibition of expression of pro-inflammatory cytokines and 6) inhibition of prostaglandin and leukotriene synthesis. An increased oxidative stress has been observed in both acute and chronic phases of thyroid disease with raised tissue concentrations of ROS. The benefits of Se supplementation in individuals with TAO appear to be proportionate to the degree of systemic activity of the thyroid disease. The maximal benefit of Se supplementation is therefore seen in the subjects who are hyperthyroid. Restoration of euthyroidism is one of the main goals in the management of TAO and when anti-thyroid drugs are combined with Se, the patients with Graves' disease (GD) and autoimmune thyroiditis (AIT) achieved euthyroidism faster than those treated with anti-thyroid drugs alone. Se status of normal adult humans can vary widely and Se supplementation may confer benefit only if serum Se levels are insufficient. The author recommends that serum Se levels of patients with TAO to be assessed prior to and during Se supplementation at regular intervals to avoid potential iatrogenic chronic Se overdose.
Background:
Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis.
Methods/design:
The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis.
Inclusion criteria:
age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent.
Exclusion criteria:
previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 μg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 μg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events.
Discussion:
In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life.
Trial registration:
ClinicalTrials.gov ID: NCT02013479.
Context:
The association between selenium and inflammation and the relevance of selenoproteins in follicular thyroid cell physiology have pointed to a putative role of selenoproteins in the pathogenesis of autoimmune thyroid diseases.
Objective:
The aim of this study was to evaluate the role of a promoter variation in SEPS1, the selenoprotein S gene, in the risk for developing Hashimoto's thyroiditis (HT).
Design:
A case-control study was performed to assess the association of genetic variation in the SEPS1 gene (SEPS1 -105G/A single-nucleotide polymorphism, rs28665122) and HT.
Setting:
The study was conducted in north Portugal, Porto, in the period of 2007-2013.
Patients or other participants:
A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study.
Main outcome measures:
Genetic variants were discriminated by real-time PCR using TaqMan single-nucleotide polymorphism genotyping assays.
Results:
There is a significant association between the SEPS1 -105 GA and AA genotypes and HT [odds ratio (OR) 2.24, confidence interval (CI) 1.67-3.02, P < 5.0 × 10(-7), and OR 2.08, CI 1.09-3.97, P = .0268, respectively]. The A allele carriers are in higher proportion in the patient group than in the control population (46.2% vs 28.1%, P < 5.0 × 10(-7)) with an OR (CI) of 2.22 (1.67-2.97). The proportion of patients carrying the A allele is significantly higher in male patients with HT, representing a 3.94 times increased risk (P = 7.9 × 10(-3)).
Conclusion:
Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.
Background:
Graves' hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects on autoimmune hypothyroidism and on Graves' orbitopathy, but the effects of selenium on Graves' hyperthyroidism is unknown.We hypothesize that adjuvant selenium may be beneficial in the treatment of Graves' hyperthyroidism. The objective is to investigate if selenium supplementation plus standard treatment with anti-thyroid drugs versus standard treatment with anti-thyroid drugs will lead to a decrease in anti-thyroid drug treatment failure (that is, failure to remain euthyroid, without further treatment, one year after cessation of anti-thyroid drug treatment), faster and longer lasting remission (that is, anti-thyroid drug treatment success), and improved quality of life in patients with Graves' hyperthyroidism.
Methods and design:
The trial is an investigator-initiated, randomised, blinded, multicentre clinical trial. Inclusion criteria are: age 18 years or older; diagnosis of active Graves' hyperthyroidism within the last two months; and informed consent. Exclusion criteria are major co-morbidity; previous radioactive iodine treatment; ongoing anti-thyroid drug treatment for more than two months; treatment with immunomodulatory drugs; known allergy towards the components in the selenium and placebo pills; pregnancy or breast-feeding; and intake of selenium supplementation above 70 μg per day. We plan to include 492 participants, randomised (1:1) to two tablets of 100 μg selenium once daily for the 24 to 30 months intervention period versus two identical placebo tablets once daily.The primary outcome is the proportion of participants with anti-thyroid drug treatment failure (see above) at the end of the intervention period (24 to 30 months). Secondary outcomes are: thyroid-specific quality of life during the first year after randomisation; level of thyroid stimulating hormone-receptor antibodies at 18 months after randomisation and at the end of the intervention period (24 to 30 months); hyperthyroid symptoms during the first year after randomisation; eye symptoms during the first year after randomisation, and at the end of the intervention period (24 to 30 months); adverse reactions during the intervention period; and serious adverse events during the intervention period.
Discussion:
It was of great importance to the initiators of this trial, that the results would be directly applicable to daily clinical practice. Therefore, it was designed as a pragmatic trial: the patients follow their usual treatment at their usual hospitals. In order to still collect high quality data on the clinical course and quality of life, an elaborate trial management system was designed to keep track of patient input, need for trial personnel input and action, and to collect data from medical chart systems. Meticulous follow-up on missing responses to the QoL measurements has been incorporated into the system, to minimise missing quality of life data. Monitoring of adverse reactions and events is achieved by thorough instruction of the participants, surveillance of patient-reported outcomes, and integration with national databases regarding hospitalizations. A very long intervention period was necessary, since patients are not considered in remission until one year after stopping anti-thyroid drugs. Usually, patients are treated for 12 to 18 months with anti-thyroid drugs, yielding a total intervention period of 24 to 30 months.
Trial registration:
ClinicalTrials.gov: NCT01611896.
Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.
Background:
Low serum selenium concentrations have been associated with a diagnosis of differentiated thyroid cancer in small studies in selenium deficient areas. We conducted a pilot study to explore associations between selenium concentrations and the diagnosis of thyroid cancer in an area of selenium sufficiency in the United States. As low 25-hydroxyvitamin D concentrations have been associated with several malignancies, we also examined 25-hydroxyvitamin D levels.
Methods:
This study was designed as a pilot study of prediagnostic selenium and 25-hydroxyvitamin D concentrations. We identified 65 euthyroid patients at an academic medical center who were scheduled for thyroidectomy for thyroid cancer, suspicion of thyroid cancer, or nodular disease. Blood samples were obtained two to four weeks prior to thyroidectomy. Samples were analyzed for thyrotropin (TSH), free thyroxine, total triiodothyronine, selenium, and 25 hydroxyvitamin D levels. Concentrations of these analytes were correlated with whether the patient was diagnosed with benign or malignant disease following their thyroidectomy. In patients with thyroid cancer, the concentrations of selenium and 25-hydroxyvitamin D were correlated with various prognostic features.
Results:
Although selenium concentrations were not significantly lower in patients with thyroid cancer, serum selenium concentrations were inversely correlated with disease stage (p = 0.011). There were no associations between vitamin D concentration and a diagnosis of thyroid cancer. Within the thyroid cancer patients, vitamin D concentrations were not associated with disease stage or any other prognostic features. In contrast, TSH concentrations were significantly higher in patients with thyroid cancer, and were positively correlated with the number of involved lymph nodes (p = 0.011) and disease stage (p = 0.022).
Conclusion:
These data confirm the association between serum TSH and advanced thyroid cancer. In addition, they also suggest a potential association between selenium concentrations and higher thyroid cancer stage. No such association was seen for 25-hydroxyvitamin D concentrations. Larger prospective studies will be required to confirm this association. If confirmed, future studies would need to determine if the association is causative in nature. If causation exists, it seems likely that selenium concentrations would influence thyroid cancer development via an independent mechanism from that of TSH.
A range of Se species has been shown to occur in a variety of different foodstuffs. Depending on its speciation, Se is more or less bioavailable to human subjects. In the present study, the role of speciation as a determinant of Se bioavailability was addressed with an investigation of species-specific mechanisms of transport at the intestinal level. The present work focused on four distinct Se compounds (selenate (Se(VI)), selenite (Se(IV)), selenomethionine (SeMet) and methylselenocysteine (MeSeCys)), whose intestinal transport was mimicked through an in vitro bicameral model of enterocyte-like differentiated Caco-2 cells. Efficiency of Se absorption was shown to be species dependent (SeMet>MeSeCys>Se(VI)>Se(IV)). In the case of SeMet, MeSeCys and Se(VI), the highly polarised passage from the apical to basolateral pole indicated that a substantial fraction of transport was transcellular, whilst results for Se(IV) indicated paracellular diffusion. Passage of the organic Se species (SeMet and MeSeCys) became saturated after 3 h, but no such effect was observed for the inorganic species. In addition, SeMet and MeSeCys transport was significantly inhibited by their respective S analogues methionine and methylcysteine, which suggests a common transport system for both kinds of compounds.
Sepp1 is a widely expressed extracellular protein that in humans and mice contains 10 selenocysteine residues in its primary structure. Extra-hepatic tissues take up plasma Sepp1 for its selenium via apolipoprotein E receptor-2 (apoER2)-mediated endocytosis. The role of Sepp1 in the transport of selenium from liver, a rich source of the element, to peripheral tissues was studied using mice with selective deletion of Sepp1 in hepatocytes (Sepp1c/c/alb-cre+/− mice). Deletion of Sepp1 in hepatocytes lowered plasma Sepp1 concentration to 10% of that in Sepp1c/c mice (controls) and increased urinary selenium excretion, decreasing whole-body and tissue selenium concentrations. Under selenium-deficient conditions, Sepp1c/c/alb-cre+/− mice accumulated selenium in the liver at the expense of extra-hepatic tissues, severely worsening clinical manifestations of dietary selenium deficiency. These findings are consistent with there being competition for metabolically available hepatocyte selenium between the synthesis of selenoproteins and the synthesis of selenium excretory metabolites. In addition, selenium deficiency down-regulated the mRNA of the most abundant hepatic selenoprotein, glutathione peroxidase-1 (Gpx1), to 15% of the selenium-replete value, while reducing Sepp1 mRNA, the most abundant hepatic selenoprotein mRNA, only to 61%. This strongly suggests that Sepp1 synthesis is favored in the liver over Gpx1 synthesis when selenium supply is limited, directing hepatocyte selenium to peripheral tissues in selenium deficiency. We conclude that production of Sepp1 by hepatocytes is central to selenium homeostasis in the organism because it promotes retention of selenium in the body and effects selenium distribution from the liver to extra-hepatic tissues, especially under selenium-deficient conditions.
Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy.
We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score.
At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems.
Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).
The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients.
In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n=18), levothyroxine plus 100 microg sodium-selenite (group B, n=13), or levothyroxine plus 200 microg sodium-selenite (group C, n=18). Mean age at diagnosis was 12.2+/-2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6+/-0.5 microg/kg body weight to lower TSH to the treatment goal of 1-2 microU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p=0.03 and p=0.01), but not in group B (p=0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 microg daily nor given in the "adult" supplementation dose of 200 microg daily.
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.
Myxoedematous endemic cretinism is prevalent in African goitre endemies. It has been related to a thyroid 'exhaustion' atrophy occurring near birth. It is proposed that this might result from the low resistance of a fragile tissue to enhanced H2O2 generation under intense thyroid stimulation by thyrotropin. In support of this hypothesis, low selenium and glutathione peroxidase serum levels have been found in the African endemic area of the Idjwi Island (Kivu, Zaire). Serum selenium and plasma glutathione peroxidase were lower in the area of high endemicity of goitre and cretinism (Northern part of the Island). However, only the former difference is statistically significant. These data thus suggest a role of oligoelements and oxygen toxicity in the pathogenesis of endemic cretinism.
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.
In recent years, the role of selenium in the prevention of a number of degenerative conditions including cancer, inflammatory diseases, thyroid function, cardiovascular disease, neurological diseases, aging, infertility, and infections, has been established by laboratory experiments, clinical trials, and epidemiological data. Most of the effects in these conditions are related to the function of selenium in antioxidant enzyme systems. Replenishing selenium in deficiency conditions appears to have immune-stimulating effects, particularly in patients undergoing chemotherapy. However, increasing the levels of selenoprotein antioxidant enzymes (glutathione peroxidase, thioredoxin reductase, etc.) appears to be only one of many ways in which selenium-based metabolites contribute to normal cellular growth and function. Animal data, epidemiological data, and intervention trials have shown a clear role for selenium compounds in both prevention of specific cancers and antitumorigenic effects in post-initiation phases of cancer.
Liver-specific inactivation of Trsp, the gene for selenocysteine tRNA, removes SePP (selenoprotein P) from plasma, causing serum selenium levels to fall from 298 microg/l to 50 microg/l and kidney selenium to decrease to 36% of wild-type levels. Likewise, glutathione peroxidase activities decreased in plasma and kidney to 43% and 18% respectively of wild-type levels. This agrees nicely with data from SePP knockout mice, supporting a selenium transport role for hepatically expressed SePP. However, brain selenium levels remain unaffected and neurological defects do not occur in the liver-specific Trsp knockout mice, while SePP knockout mice suffer from neurological defects. This indicates that a transport function in plasma is exerted by hepatically derived SePP, while in brain SePP fulfils a second, hitherto unexpected, essential role.
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.
Context
Supplemental Selenium (Se) may impact the clinical course of Graves’ disease (GD)
Objective
Evaluate efficacy of add-on Se on medical treatment in GD
Design
Double-blind, placebo-controlled, randomized, supplementation trial
Setting
Academic endocrine outpatient clinic
Patients
Seventy untreated hyperthyroid patients with GD
Intervention
Additionally to methimazole (MMI), patients received during 24 weeks either sodium selenite 300 µg/day p.o. or placebo. MMI was discontinued at 24 weeks in euthyroid patients.
Main Outcome Measures
Response rate (week 24), recurrence rate (week 36), and safety.
Results
A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24, odds ratio 0.93 (95% CI 0.26–3.25, p=0.904) in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13, 0.29–2.66, p=0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response and/or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85, 0.31-2.32, p=0.80). Serum levels of fT3/fT4, TSH-R-Ab, prevalence of moderate-to-severe Graves’ orbitopathy, thyroid volume and MMI starting dose were significantly lower in responders versus non-responders. 56 and 63 adverse events occurred in the Se and placebo groups, respectively (p=0.164), while only one drug related side-effect (2.9%) was noted in 35 patients on placebo +MMI.
Conclusions
Supplemental Se did not impact response or recurrence rate in GD
Background:
A recent clinical trial has shown a beneficial effect of the antioxidant agent selenium in Graves' orbitopathy (GO). In order to shed light on the cellular mechanisms on which selenium may act, this study investigated its effects in cultured orbital fibroblasts.
Methods:
Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H2O2to induce oxidative stress, after pre-incubation with selenium-(methyl)selenocysteine (SeMCys). The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, glutathione peroxidase (GPX) activity, cell proliferation, hyaluronic acid (HA), and pro-inflammatory cytokines.
Results:
H2O2induced an increase in cell GSSG and fibroblast proliferation, which were reduced by SeMCys. Incubation of H2O2-treated cells with SeMCys was followed by an increase in glutathione peroxidase activity, one of the antioxidant enzymes into which selenium is incorporated. At the concentrations used (5 μM), H2O2did not significantly affect HA release, but it was reduced by SeMCys. H2O2determined an increase in endogenous cytokines involved in the response to oxidative stress and GO pathogenesis, namely tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. The increases in tumor necrosis factor alpha and interferon gamma were blocked by SeMCys. While the effects of SeMCys on oxidative stress and cytokines were similar in GO and control fibroblasts, they were exclusive to GO fibroblasts in terms of inhibiting proliferation and HA secretion.
Conclusions:
Selenium, in the form of SeMCys, abolishes some of the effects of oxidative stress in orbital fibroblasts, namely increased proliferation and secretion of pro-inflammatory cytokines. SeMCys reduces HA release in GO fibroblasts in a manner that seems at least in part independent from H2O2-induced oxidative stress. Some effects of SeMCys are specific for GO fibroblasts. These findings reveal some cellular mechanisms by which selenium may act in patients with GO.
Objective
In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves’ disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). Methods
Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days. ResultsBaseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT3 and FT4, with no difference between groups. Heart rate, SHBG and symptoms of hyperthyroidism decreased, whereas total cholesterol increased in both groups with no difference between groups. Conclusions
Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.
The effect of selenium supplementation on recurrent hyperthyroidism caused by Graves' disease is unclear. Our study aimed to assess the efficacy of selenium supplementation therapy on recurrent Graves' disease. Forty-one patients with recurrent Graves' disease were enrolled in this study. All patients received the routine treatment using methimazole (MMI), while patients allocated to the selenium group received additional selenium therapy for 6 months. The influence of selenium supplementation on the concentrations of thyroid stimulating hormone (TSH), anti-TSH-receptor antibodies (TRAb), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed. The remission rate was also compared between 2 groups. There was no obvious difference in the demographic data and the levels of serum FT4, FT3, TSH, and TRAb between the 2 groups at baseline. Both FT4 and FT3 decreased more at 2 months in the selenium group than the controls, while the TSH level increased more in patients receiving selenium supplementation (p<0.05). The TRAb level was significantly lower in patients receiving selenium supplementation (2.4 IU/l vs. 5.6 IU/l, p=0.04). The percentages of patients with normal TRAb level at 6 months was also significantly higher in the selenium group (19.0 vs. 0%, p=0.016). Kaplan-Meier survival curve showed patients receiving selenium supplementation had a significantly higher rate of remission than controls (Log-rank test p=0.008). In conclusion, selenium supplementation can enhance the effect of antithyroid drugs in patients with recurrent Graves' disease. Randomized trials with large number of participants are needed to validate the finding above.
© Georg Thieme Verlag KG Stuttgart · New York.
There are conflicting reports on the correlation between serum levels of selenium (Se), copper (Cu), and magnesium (Mg) with thyroid cancer. The purpose of the present study is to clarify the association between Se, Cu, and Mg levels with thyroid cancer using a meta-analysis approach. We searched articles indexed in PubMed published as of January 2015 that met our predefined criteria. Eight eligible articles involving 1291 subjects were identified. Overall, pooled analysis indicated that subjects with thyroid cancer had lower serum levels of Se and Mg, but higher levels of Cu than the healthy controls [Se: standardized mean difference (SMD) = -0.485, 95% confidence interval (95%CI) = (-0.878, -0.092), p = 0.016; Cu: SMD = 2.372, 95%CI = (0.945, 3.799), p = 0.001; Mg: SMD = -0.795, 95%CI = (-1.092, -0.498), p < 0.001]. Further subgroup analysis found lower serum levels of Se in thyroid cancer in Norway [SMD = -0.410, 95%CI = (-0.758, -0.062), p = 0.021] and Austria [SMD = -0.549, 95%CI = (-0.743, -0.355), p < 0.001], but not in Poland (SMD = -0.417, 95%CI = (-1.724, 0.891), p = 0.532]. Further subgroup analysis also found that patients with thyroid cancer had higher serum levels of Cu in China [SMD = 1.571, 95%CI = (1.121, 2.020), p < 0.001] and Turkey [SMD = 0.977, 95%CI = (0.521, 1.432), p < 0.001], but not in Poland [SMD = 3.471, 95%CI = (-0.056, 6.997], p = 0.054]. In conclusion, this meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer. However, the subgroup analysis found that there was significant effect modification of Se, Cu levels by ethnic, like China and Poland. Thus, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between Se, Cu, and Mg with thyroid cancer of different human races or regions.
Euthyroid TPO-Ab positive subjects are at risk for progression to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease of TPO-Ab and improvement of quality-of-life (QoL) in L-T4 treated hypothyroid patients upon selenium supplementation.
To evaluate in euthyroid TPO-Ab positive women without thyroid medication whether selenite decreases TPO-Ab and improves QoL.
Randomized, placebo-controlled, double-blind study.
Euthyroid (TSH 0.5-5.0 mU/L, FT4 10-23 pmol/L) women with TPO-Ab ≥100 kU/L were randomized to receive 200 mcg sodium selenite daily (n=30) or placebo (n=31) for 6 months. TSH, FT4, TPO-Ab, selenium (Se), selenoprotein P (SePP) and QoL were measured at baseline, 3, 6 and 9 months.
There were no differences in baseline characteristics between the Se group and the placebo group. During selenite supplementation, serum Se and SePP did not change in the placebo group, but increased in the Se group. TPO-Ab and TSH did not change significantly in any group. TPO-Ab in the Se group were 895 (130-6800) at baseline, 1360 (60-7050) kU/l at 6 months, in the placebo group 1090 (120-9200) and 1130 (80-9900) kU/l respectively (median values with range). TSH in the Se group was 2.1 (0.5-4.3) at baseline, 1.7 (0.0-5.3) mU/L at 6 months, in the placebo group 2.4 (0.7-4.4) and 2.5 (0.2-4.3) mU/L respectively. QoL was not different between the groups.
Six months selenite supplementation increased markers of selenium status but had no effect on serum TPO-Ab, TSH or quality-of-life in euthyroid TPO-Ab positive women. This article is protected by copyright. All rights reserved.
Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease-associated polymorphisms in selenoprotein genes has drawn attention to the relevance of selenoproteins to health. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type-2 diabetes. The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional selenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenium supplements.
The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine-immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.
The objective was to study the associations between serum selenium concentration and thyroid volume, as well as the association between serum selenium concentration and risk for an enlarged thyroid gland in an area with mild iodine deficiency before and after iodine fortification was introduced. Another objective was to examine the association between serum selenium concentration and prevalence of thyroid nodules.
Cross-sectional study.
We studied participants of two similar cross-sectional studies carried out before (1997-1998, n=405) and after (2004-2005, n=400) introduction of iodine fortification. Serum selenium concentration and urinary iodine were measured, and the thyroid gland was examined by ultrasonography in the same subjects. Associations between serum selenium concentration and thyroid parameters were examined in multiple linear regression models or logistic regression models.
Serum selenium concentration was found to be significantly, negatively associated with thyroid volume (P=0.006), and a low selenium status significantly increased the risk for thyroid enlargement (P=0.007). Furthermore, low serum selenium status had a tendency to increase the risk for development of multiple nodules (P=0.087).
Low serum selenium concentration was associated with a larger thyroid volume and a higher prevalence of thyroid enlargement.
G raves' ophthalmopathy, also called Graves' orbitopathy, is a potentially sight-threatening ocular disease that has puzzled physicians and scientists for nearly two centuries. 1-3 Generally occurring in patients with hyperthyroidism or a history of hyperthyroidism due to Graves' disease, Graves' ophthalmopathy is also known as thyroid-associated ophthalmopathy or thyroid eye disease, because it sometimes occurs in patients with euthyroid or hypo-thyroid chronic autoimmune thyroiditis. The condition has an annual adjusted in-cidence rate of 16 women and 3 men per 100,000 population. 4 This review explores the perplexing relationship between Graves' ophthalmopa-thy, hyperthyroidism, and thyroid dermopathy, the associated skin condition. I ex-amine clinical features, histologic findings, and laboratory studies, with an empha-sis on mechanisms that could be targeted in the development of new treatments for this debilitating disease.
Our study aimed to investigate whether physiological doses of selenium (Se) influence the natural course of autoimmune thyroiditis (AIT).
A total of 76 consecutive patients (65 F, 11 M, median 43, range 15-75 years) with AIT, normal or slightly elevated TSH and fT4 within the normal range were divided into two groups: Group 0 (30 cases) was given no treatment while Group 1 (46 cases) was treated with sodium selenite 80 μg/day as a single oral dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; Tg-Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and after 6 and 12 months of follow-up. Thyroid ultrasonography (US) was performed at each follow-up point. Echogenicity was measured by histographic analysis of gray-scale pixels (gsp) ranging from 0 = black to 255 = white.
Thyroid echogenicity decreased significantly in both groups after 6 months, but after 12 months, it had changed no more in Group 1, whereas it had dropped further in Group 0. No significant variation in TPO-Ab or Tg-Ab levels was observed between the two groups after 6 months, but both values decreased significantly after 12 months in Group 1, and five patients in this group became negative for TPO-Ab. TSH and FT4 showed no significant variations in either group.
Dietary supplementation with physiological doses of Se seems to be effective in preventing a reduction in thyroid echogenicity after 6 months of treatment and in reducing TPO-Ab and Tg-Ab after 12 months, but does not modify TSH or FT4.
This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia.
Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue.
Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status.
High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.
The trace elements iodine and selenium (Se) are essential for thyroid gland functioning and thyroid hormone biosynthesis and metabolism. While iodine is needed as the eponymous constituent of the two major thyroid hormones triiodo-L-thyronine (T3), and tetraiodo-L-thyronine (T4), Se is essential for the biosynthesis and function of a small number of selenocysteine (Sec)-containing selenoproteins implicated in thyroid hormone metabolism and gland function. The Se-dependent iodothyronine deiodinases control thyroid hormone turnover, while both intracellular and secreted Se-dependent glutathione peroxidases are implicated in gland protection. Recently, a number of clinical supplementation trials have indicated positive effects of increasing the Se status of the participants in a variety of pathologies. These findings enforce the notion that many people might profit from improving their Se status, both as a means to reduce the individual health risk as well as to balance a Se deficiency which often develops during the course of illness. Even though the underlying mechanisms are still largely uncharacterised, the effects of Se appear to be exerted via multiple different mechanisms that impact most pronounced on the endocrine and the immune systems.
TSH, the major signalling factor for the thyroid follicles, controls thyrocyte function in concert with other modulators of cell growth, differentiation and structural organization of the follicular-endothelial network. Most of the TSH effects are mediated by TSH binding to the TSH receptor which stimulates adenylate cyclase catalyzed cAMP production. TSH is involved in the regulation of thyroidal uptake of small molecules and nutrients, intracellular transport of thyrocyte specific proteins, and in most of the steps of thyroid hormone synthesis, storage and release. These cellular events require the fine tuned regulation of metabolic reactions, morphological differentiation and cell proliferation. Thyrocytes also express a highly active Type I iodothyronine 5' deiodinase which is controlled by TSH stimulated cAMP production. The thyrocyte specific 5' deiodinase isozyme has marked influence on the amount of T3 secreted by the thyroid. This 5' deiodinase isozyme shows most of the characteristics of the type I 5' deiodinase found in liver and kidney and is also blocked by PTU, other 5' deiodinase inhibitors, and iodinated X-ray contrast agents such as iopanoic acid, which are occasionally used in thyrotoxicosis to inhibit thyroidal T3-production by this enzyme. In contrast to the liver and kidney type I 5' deiodinase T4 and T3 are not able to induce this enzyme in thyrocytes. However, TSH stimulated cAMP production increases the thyroidal isozyme activity in contrast to the liver and kidney enzyme. This review summarizes the data on the various experimental models used up to date to characterize the thyroidal type I 5' deiodinase in various species including man.
Instrumental radioactivation analysis was used to determine amounts of selenium bound to the plasma and cell fractions of the blood of 254 normal individuals. Variations with time, age, sex and hematocrit were investigated. Analysis of sub-fractions of plasma and cells indicated the highest selenium concentration in the plasma α- and β-globulins. The selenium content of human tissues was determined for two individuals. Attempts were made to correlate blood selenium levels with a few cases of selected diseases and traumatic states.
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.
Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.
The thyroid gland is rich in selenium (Se) and expresses a variety of selenoproteins that are involved in antioxidative defense and metabolism of thyroid hormones (TH). Se deficiency impairs regular synthesis of selenoproteins and adequate TH metabolism. We recently generated mice that lack the plasma Se carrier, selenoprotein P (SePP). SePP-knockout mice display decreased serum Se levels and manifest growth defects and neurological abnormalities partly reminiscent of thyroid gland dysfunction or profound hypothyroidism. Thus, we probed the TH axis in developing and adult SePP-knockout mice. Surprisingly, expression of Se-dependent 5'-deiodinase type 1 was only slightly altered in liver, kidney, or thyroid at postnatal d 60, and 5'-deiodinase type 2 activity in brain was normal in SePP-knockout mice. Thyroid gland morphology, thyroid glutathione peroxidase activity, thyroid Se concentration, and serum levels of TSH, T4, or T3 were within normal range. Pituitary TSHbeta transcripts and hepatic 5'-deiodinase type 1 mRNA levels were unchanged, indicating regular T3 bioactivity in thyrotropes and hepatocytes. Cerebellar granule cell migration as a sensitive indicator of local T3 action during development was undisturbed. Collectively, these findings demonstrate that low levels of serum Se or SePP in the absence of other challenges do not necessarily interfere with regular functioning of the TH axis. 5'-deiodinase isozymes are preferentially supplied, and Se-dependent enzymes in the thyroid are even less-dependent on serum levels of Se or SePP than in brain. This indicates a top priority of the thyroid gland and its selenoenzymes with respect to the hierarchical Se supply within the organism.
Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis.
We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function.
This was a prospective, randomized, placebo-controlled study.
The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology.
A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+).
During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C).
We measured the prevalence of PPTD and hypothyroidism.
PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01).
Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.
We studied the effects of selenium (Se) treatment on serum anti-thyroid peroxidase (TPO) levels in Greek patients with Hashimoto's thyroiditis (HT).
We prospectively studied 80 women with HT, median age 37 (range 24-52) years, for 1 year. All patients received 200 microg Se in the form of l-selenomethionine orally for 6 months. At the end of the 6-month period, 40 patients continued taking 200 microg Se (Group A) and 40 patients stopped (Group B). Serum thyrotropin (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4)), anti-TPO, and anti-thyroglobulin (Tg) levels were measured at baseline and at the end of each 3-month period.
There was a significant reduction of serum anti-TPO levels during the first 6 months (by 5.6% and 9.9% at 3 and 6 months, respectively). An overall reduction of 21% (p < 0.0001) compared with the basal values was noted in Group A. In Group B, serum anti-TPO levels were increased by 4.8% (p < 0.0001) during the second 6-month period.
Our study showed that in HT patients 6 months of Se treatment caused a significant decrease in serum anti-TPO levels, which was more profound in the second trimester. The extension of Se supplementation for 6 more months resulted in an additional 8% decrease, while the cessation caused a 4.8% increase, in the anti-TPO concentrations.
Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients.
Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration.
No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p > 0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration.
We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.