Effects of selenium on short-term control of hyperthyroidism due to Graves’ disease treated with methimazole: results of a randomized clinical trial Double‐Blind, Placebo‐Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study. The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial Randomized controlled trial of the effect of selenium supplementation on thyroid function in the elderly in the United Kingdom. Selenium and iodine supplementation: effect on thyroid function of older New Zealanders. Minimal impact of excess iodate intake on thyroid hormones and selenium status in older New Zealanders. Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population. Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency Supplementation with antioxidants in the treatment of Graves' disease; the effect on glutathione peroxidase activity and concentration of selenium. Effects of Selenium Supplementation on Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice. Effects of selenomethionine supplementation on selenium status and thyroid hormone concentrations in healthy adults. The Association between Selenium and Other Micronutrients and Thyroid Cancer Incidence in the NIH-AARP Diet and Health Study Selenium and the thyroid: A close-knit connection Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial An estimation of selenium requirements for New Zealanders. Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Selenium supplementation does not improve vascular responsiveness in healthy North American men. Low selenium status in the elderly influences thyroid hormones. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.
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 r and omized clinical trial was carried out aim ed 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 r and omly 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 . Results Baseline 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 Context : Supplemental selenium ( Se ) may affect the clinical course of Graves disease ( GD ) . Objective : Evaluate efficacy of add‐on Se on medical treatment in GD . Design : Double‐blind , placebo‐controlled , r and omized supplementation trial . Setting : Academic endocrine outpatient clinic . Patients : Seventy untreated hyperthyroid patients with GD . Intervention : Additionally to methimazole ( MMI ) , patients received for 24 weeks either sodium selenite 300 & mgr;g/d po 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 ( OR ) 0.93 ; 95 % confidence interval ( CI ) , 0.26 to 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 ; 95 % CI , 0.29 to 2.66 ; P = 0.81 ) in the Se and placebo groups , respectively . Serum concentrations of Se and selenoprotein P were unrelated to response 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 ; 95 % CI , 0.31 to 2.32 ; P = 0.80 ) . Serum levels of free triiodothyronine/free tetraiodothyronine , thyroid‐stimulating hormone receptor antibody , prevalence of moderate to severe Graves orbitopathy , thyroid volume , and MMI starting dose were significantly lower in responders than in nonresponders . A total of 56 and 63 adverse events occurred in the Se and placebo groups , respectively ( P = 0.164 ) , whereas only one drug‐related side effect ( 2.9 % ) was noted in 35 patients on placebo + MMI . Conclusions : Supplemental Se did not affect response or recurrence rates in GD The effect of selenium supplementation on recurrent hyperthyroidism caused by Graves ' disease is unclear . Our study aim ed 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 . R and omized trials with large number of participants are needed to vali date the finding above Background Patients with chronic autoimmune thyroiditis have impaired health-related quality of life . The thyroid gl and 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 r and omized 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 r and omized , 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 underst and 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 ) question naire . 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 design ed . 12 months intervention duration was selected in consideration of the primary outcome , thyroid-related quality of life . Trial registration Clinical Trials.gov ID : NCT02013479 Background Graves ’ hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gl and . The concentration of selenium is high in the thyroid gl and 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 st and ard treatment with anti-thyroid drugs versus st and ard 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 , r and omised , 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 , r and omised ( 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 r and omisation ; level of thyroid stimulating hormone-receptor antibodies at 18 months after r and omisation and at the end of the intervention period ( 24 to 30 months ) ; hyperthyroid symptoms during the first year after r and omisation ; eye symptoms during the first year after r and omisation , 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 design ed 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 design ed 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 data bases 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 Clinical Trials.gov : NCT01611896 BACKGROUND Thyroid function depends on the essential trace mineral selenium , which is at the active center of the iodothyronine deiodinase enzymes that catalyze the conversion of the prohormone thyroxine ( T(4 ) ) to the active form of thyroid hormone , triiodothyronine ( T(3 ) ) . OBJECTIVE Because selenium intake in the United Kingdom has fallen during the past 25 y , we wanted to determine whether current selenium status might be limiting conversion of T(4 ) to T(3 ) in the elderly , in whom marginal hypothyroidism is relatively common . DESIGN We investigated the effect of selenium supplementation in a double-blind , placebo-controlled trial in 501 elderly UK volunteers . Similar numbers of men and women from each of 3 age groups , 60 - 64 y , 65 - 69 y , and 70 - 74 y , were r and omly allocated to receive 100 , 200 , or 300 microg Se/d as high-selenium yeast or placebo yeast for 6 mo . As part of the study , plasma selenium , thyroid-stimulating hormone , and total and free T(3 ) and T(4 ) were measured . Data from 368 euthyroid volunteers who provided blood sample s at baseline and 6 mo were analyzed . RESULTS Although selenium status at baseline correlated weakly with free T(4 ) ( r = -0.19 , P < 0.001 ) and with the ratio of free T(3 ) to free T(4 ) ( r = 0.12 , P = 0.02 ) , we found no evidence of any effect of selenium supplementation on thyroid function , despite significant increases in plasma selenium . However , baseline plasma selenium in our study ( x : 91 microg/L ) was somewhat higher than in previous supplementation studies in which apparently beneficial effects were seen . CONCLUSION We found no indication for increasing selenium intake to benefit T(4 ) to T(3 ) conversion in the elderly UK population BACKGROUND The New Zeal and population has both marginal selenium status and mild iodine deficiency . Adequate intakes of iodine and selenium are required for optimal thyroid function . OBJECTIVE The aim of the study was to determine whether low selenium and iodine status compromises thyroid function in an older New Zeal and population . DESIGN We investigated the effects of selenium and iodine supplementation in a double-blind , r and omized , placebo-controlled trial in 100 Dunedin volunteers aged 60 - 80 y. Participants received 100 microg Se/d as l-selenomethionine , 80 microg I , 100 microg Se + 80 microg I , or placebo for 3 mo . Thyroid-stimulating hormone ( TSH ) , free triiodothyronine ( T(3 ) ) , free thyroxine ( T(4 ) ) , thyroglobulin , plasma selenium , whole-blood glutathione peroxidase ( GPx ) activity , and urinary iodine concentrations ( UICs ) were measured . RESULTS Plasma selenium ( P < 0.0001 ) and whole-blood GPx activity ( P<0.0001 ) increased from baseline to week 12 in the selenium and selenium plus iodine groups in comparison with the placebo group . Median UIC at baseline was 48 microg/L ( interquartile range : 31 - 79 microg/L ) , which is indicative of moderate iodine deficiency . UIC increased in the iodine and selenium plus iodine groups and was significant only for the iodine group ( P = 0.0014 ) . Thyroglobulin concentration decreased by 24 % and 13 % of baseline in the iodine and selenium plus iodine groups in comparison with the placebo group ( P = 0.009 and P = 0.108 , respectively ) . No significant treatment effects were found for TSH , free T(3 ) , free T(4 ) , or ratio of T(3 ) to T(4 ) . CONCLUSIONS Additional selenium improved GPx activity but not the thyroid hormone status of older New Zeal and ers . Iodine supplementation alleviated the moderate iodine deficiency and reduced elevated thyroglobulin concentrations . No synergistic action of selenium and iodine was observed . The trial was registered at www.anzctr.org.au/registry/ as ACTRN012605000368639 OBJECTIVE Iodine deficiency has re-emerged in New Zeal and , while selenium status has improved . The aim of this study was to investigate the effects of excess iodine intake as io date on thyroid and selenium status . METHODS In a r and omized controlled trial on older people ( mean±s.d . 73±4.8 years ; n=143 ) , two groups received > 50 mg iodine as io date /day for 8 weeks because of supplement formulation error , either with 100 μg selenium ( Se+highI ) or without selenium ( highI ) . Four other groups received 80 μg iodine as io date /day with selenium ( Se+lowI ) or without selenium ( lowI ) , selenium alone ( Se+ ) , or placebo . Thyroid hormones , selenium status , and median urinary iodine concentration ( MUIC ) were compared at weeks 0 , 8 , and 4 weeks post-supplementation . RESULTS MUIC increased nine- and six-fold in Se+highI and highI groups , decreasing to baseline by week 12 . Plasma selenium increased in selenium-supplemented groups ( P<0.001 ) . The level of increase in whole blood glutathione peroxidase ( WBGPx ) in the Se+highI group was smaller than Se+ ( P=0.020 ) and Se+lowI ( P=0.007 ) groups . The decrease in WBGPX in the highI group was greater than other non-selenium-supplemented groups , but differences were not significant . Ten of 43 participants exposed to excess io date showed elevated TSH ( hypothyroidism ) at week 8 . In all but two , TSH had returned to normal by week 12 . In three participants , TSH decreased to < 0.10 mIU/l ( hyperthyroidism ) at week 8 , remaining low at week 12 . CONCLUSIONS Excess io date induced hypothyroidism in some participants and hyperthyroidism in others . Most abnormalities disappeared after 4 weeks . Excess io date reduced WBGPx activity and result ed in smaller increases in WBGPx after selenium supplementation OBJECTIVE Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism . The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function , under conditions of suboptimal dietary selenium intake . DESIGN The Danish PREvention of Cancer by Intervention with SElenium pilot study ( DK-PRECISE ) is a r and omized , double-blinded , placebo-controlled trial . A total of 491 males and females aged 60 - 74 years were r and omized to 100 μg ( n=124 ) , 200 μg ( n=122 ) , or 300 μg ( n=119 ) selenium-enriched yeast or matching yeast-based placebo tablets ( n=126 ) . A total of 361 participants , equally distributed across treatment groups , completed the 5-year intervention period . METHODS Plasma sample s were analyzed for selenium and serum sample s for TSH , free triiodothyronine ( FT3 ) , and free thyroxine ( FT4 ) at baseline , and after 6 months , and 5 years of supplementation . RESULTS Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium ( P<0.001 ) . Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l ( P=0.010 ) and 0.11 pmol/l ( P=0.015 ) , respectively , per 100 μg/day increase , with insignificant differences between 6 months and 5 years . No significant effects were found for FT3 and FT3:FT4 ratio . CONCLUSIONS In euthyroid subjects , selenium supplementation minutely and dose-dependently affects thyroid function , when compared with placebo , by decreasing serum TSH and FT4 concentrations . Based on these findings , selenium supplementation is not warranted under conditions of marginal selenium deficiency . However , a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved 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 aim ed 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 Sample s and data were from a secondary analysis of Selenium in PRegnancy INTervention ( SPRINT ) , a double-blind , r and omized , placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation . Women were r and omized 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 < 0.001 ) , with no difference between treatment groups . In women who were Thy-Ab+ve at baseline , TSH tended to decrease and was lower than placebo at 35 weeks ( P = 0.050 ) . FT4 fell more on Se than placebo supplementation and was significantly lower at 35 weeks ( P = 0.029 ) . Conclusions Low-dose selenium supplementation in pregnant women with mild-to-moderate deficiency had no effect on TPO-Ab concentration , but tended to change thyroid function in Thy-Ab+ve women BACKGROUND 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 .  METHODS 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 ) . CONCLUSION The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves ' disease is justified , particularly those containing selenium BACKGROUND Recent clinical studies have demonstrated the suppressive effect of selenium ( Se ) treatment on serum thyroid-specific antibody titers in patients with autoimmune thyroiditis ( AIT ) , but the mechanism underlying this process is not clear . The aim of the present study was to investigate the effects of selenium on the incidence and severity of AIT , titers of thyroid autoantibodies , and selenoprotein expression in thyroid in a spontaneous autoimmune thyroiditis ( SAT ) model . METHODS NOD.H-2(h4 ) mice at four weeks of age were r and omly divided into control , iodine supplement ( SAT ) , and selenium supplement groups ( SAT+Se ) . Mice were given 0.005 % sodium iodide water for eight weeks to induce SAT and then 0.3 mg/L sodium selenite in drinking water for 8 weeks and 16 weeks . The severity of lymphocytic infiltration in the thyroid , serum thyroglobulin antibody ( TgAb ) titers , serum selenium concentration , expression of glutathione peroxidase-1 ( GPx1 ) , thioredoxin reductase-1 ( Txnrd1 ) , and peroxiredoxin 5 were measured . RESULTS Serum selenium concentration significantly increased after selenium supplementation . Serum TgAb levels were significantly lower in the selenium group compared with the SAT group ( p<0.05 ) . The prevalence of thyroiditis and the degree of infiltration of lymphocytes decreased gradually over time in the group provided with selenium supplementation . The expression of GPx1 and Txnrd1 by Western blotting were found to be significantly higher in the SAT+Se group than in other groups ( p<0.05 ) . CONCLUSIONS These results indicate that selenium treatment can increase the function of antioxidation by upregulating the expression of selenoproteins in the thyroid and have an inhibitory effect on TgAb titers , which may have an impact on AIT BACKGROUND 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 . OBJECTIVE The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations . DESIGN 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 mid study ; 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 . RESULTS 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 . CONCLUSIONS Selenium supplementation produced no clinical ly 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 Background Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gl and from oxidative stress . The association of selenium , as well as intake of other micronutrients , with thyroid cancer is unclear . Methods We evaluated associations of dietary selenium , beta-carotene , calcium , vitamin D , vitamin C , vitamin E , folate , magnesium , and zinc intake with  thyroid cancer  risk in the National Institutes of Health – American Association of Retired Persons Diet and Health Study , a large prospect i ve cohort of 566,398 men and women aged 50–71 years in 1995–1996 . Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients , assessed using a food frequency question naire , and thyroid cancer cases , ascertained by linkage to state cancer registries and the National Death Index . Results With the exception of vitamin C , which was associated with an increased risk of thyroid cancer ( HRQ5 vs Q1 , 1.34 ; 95 % CI , 1.02–1.76 ; Ptrend , < 0.01 ) , we observed no evidence of an association between quintile of selenium ( HRQ5 vs Q1 , 1.23 ; 95 % CI , 0.92–1.65 ; Ptrend , 0.26 ) or other micronutrient intake and thyroid cancer . Conclusion Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients  and thyroid cancer risk . More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis Introduction : In areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells . Aims and Objective : To study the effect of selenium supplementation in patients with autoimmune thyroid disease . Material s and Methods : This is a blinded placebo-controlled prospect i ve study done in 60 patients with autoimmune thyroid disease ( as defined by an anti-thyroid peroxidase antibody ( TPOAb ) level more than 150 IU/ml ) irrespective of the baseline thyroid status . Patients with overt hyperthyroidism who are on antithyroid drugs , patients on any other medication , which may alter the immunity status of the patients , and pregnant patients were excluded from the study . Patients were r and omized into two age and TPOAb-matched groups ; 30 patients  received 200 μg of sodium selenite/day , orally , for 3 months , and 30 patients  received placebo . All hypothyroid patients were given l-thyroxine replacement . Results : Of 30 patients in the selenium treated group , 6 patients were overtly hypothyroid , 15 were sub clinical hypothyroid , 6 were euthyroid , and 3 were sub clinical hyperthyroid . The mean TPOAb concentration decreased significantly by 49.5 % ( P < 0.013 ) in the selenium treated group versus 10.1 % ( P < 0.95 ) in the placebo-treated group . Conclusion : Selenium substitution has a significant impact on inflammatory activity in thyroid-specific autoimmune disease . It would be of interest to determine whether early treatment with selenium in patients with newly developed autoimmune thyroiditis may delay or even prevent the natural course of these diseases OBJECTIVE To investigate the relationship between selenium status , thyroid Volume and gl and echostructure . DESIGN Cross-sectional . METHODS In 792 men ( 45 - 60 Years ) and 1108 women ( 35 - 60 Years ) from the SU.VI.MAX study , thyroid Volume and gl and 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 question naire . A stepwise linear and a logistic regression model were used , adjusting for antioxidant vitamins , trace elements status and age . RESULTS 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 . CONCLUSION Our findings suggest that selenium may protect against goiter . Selenium was related to thyroid echostructure , suggesting it may also protect against autoimmune thyroid disease Abstract Objective : To investigate whether early selenium ( Se ) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism , since the first week after trauma is characterised by low plasma Se and negative Se balances . Design : Prospect i ve , placebo-controlled r and omised supplementation trial . Setting : Surgical ICU in a tertiary university hospital . Patients : Thirty-one critically ill trauma patients aged 42±16 years ( mean±SD ) , with severe multiple injury ( Injury Severity Score 30±7 ) . Intervention : Supplementation during the first 5 days after injury with either Se or placebo . The selenium group was further r and omised to receive daily 500 µg Se , with or without 150 mg α-tocopherol ( AT ) and 13 mg zinc supplements . The placebo group received the vehicle . Circulating Se , AT , zinc , and thyroid hormones were determined on D0 (= day 0 , admission ) , D1 , D2 , D5 , D10 , and D20 . Results : Plasma Se , low on D0 , normalised from D1 in the  selenium group ; total T4 and T3 increased more and faster after D2 ( P=0.04 and 0.08 ) , reverse T3 rising less between D0 and D2 ( P=0.05 ) . Conclusions : Selenium supplements increased the circulating Se levels . Supplementation was associated with modest changes in thyroid hormones , with an earlier normalisation of T4 and reverse T3 plasma levels . The addition of AT and zinc did not produce any additional change BACKGROUND Current US dietary recommendations for selenium are based on maximization of plasma glutathione peroxidase ( GSHPx ) activity according to data from one study of Chinese men . OBJECTIVE The effect of various amounts of supplemental selenium on GSHPx activities in blood of New Zeal and adults was investigated to calculate a selenium requirement for New Zeal and ers . The effect on plasma selenoprotein P and thyroid hormones was also investigated . DESIGN Fifty-two adults with low blood selenium concentrations ingested a placebo or 10 , 20 , 30 , or 40 microgram Se as L-selenomethionine daily for 20 wk . RESULTS Plasma and whole-blood GSHPx activities increased in all supplemented groups but reached a plateau only in the group receiving 40 microgram Se , as determined by statistical analysis . Increases in selenoprotein P were greater than those for selenium and GSHPx at all supplement intakes . Thyroxine concentrations decreased in supplemented groups but the decrease was significantly different from that in the control group only for the 10-microgram group and for all supplemented groups combined . CONCLUSIONS An upper estimated requirement of 90 microgram Se/d was calculated as the intake necessary for maximization of plasma GSHPx activity , as used in the derivation of the US recommended daily allowance . Our lower estimated requirement of 39 microgram Se/d was the intake necessary to reach two-thirds of maximal GSHPx activity , as was used in calculating the World Health Organization normative requirement . The lower estimate is a realistic goal for New Zeal and but the upper estimate could be achieved only with regular inclusion of high-selenium foods BACKGROUND The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer ( PCa ) risk but a 17 % increased risk from vitamin E supplementation . This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status . METHODS There were 1739 total and 489 high- grade ( Gleason 7 - 10 ) PCa cases and 3117 men in the r and omly selected cohort . Proportional hazards models estimated hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for effects of supplementation within quintiles of baseline toenail selenium . Cox proportional hazards models were used to estimate hazard ratios , and all statistical tests are two-sided . RESULTS Toenail selenium , in the absence of supplementation , was not associated with PCa risk . Selenium supplementation ( combined selenium only and selenium + vitamin E arms ) had no effect among men with low selenium status ( < 60th percentile of toenail selenium ) but increased the risk of high- grade PCa among men with higher selenium status by 91 % ( P = .007 ) . Vitamin E supplementation ( alone ) had no effect among men with high selenium status ( ≥40th percentile of toenail selenium ) but increased the risks of total , low- grade , and high- grade PCa among men with lower selenium status ( 63 % , P = .02 ; 46 % , P = .09 ; 111 % , P = .008 , respectively ) . CONCLUSIONS Selenium supplementation did not benefit men with low selenium status but increased the risk of high- grade PCa  among men with high selenium status . Vitamin E increased the risk of PCa among men with low selenium status . Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes BACKGROUND Dietary selenium intakes in many countries , including the United Kingdom , are lower than international recommendations . No functional consequences of these lower intakes have been recognized , although experimental studies suggest that they might contribute to reduced immune function , increased cancer incidence , and increased susceptibility to viral disease . OBJECTIVE The objective was to assess whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus : live attenuated polio vaccine . DESIGN Twenty-two adult UK subjects with relatively low plasma selenium concentrations ( < 1.2 micromol/L , approximately 60 % of those screened ) received 50 or 100 microg Se ( as sodium selenite ) or placebo daily for 15 wk in a double-blind study . All subjects received an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable (74)Se intravenously 3 wk later . RESULTS Selenium supplementation increased plasma selenium concentrations , the body exchangeable selenium pool ( measured by using (74)Se ) , and lymphocyte phospholipid and cytosolic glutathione peroxidase activities . Selenium supplements augmented the cellular immune response through an increased production of interferon gamma and other cytokines , an earlier peak T cell proliferation , and an increase in T helper cells . Humoral immune responses were unaffected . Selenium-supplemented subjects also showed more rapid clearance of the poliovirus , and the poliovirus reverse transcriptase-polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations . CONCLUSIONS The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral h and ling . They also suggest that the additional 100 microg Se/d may be insufficient to support optimal function Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase , the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease . Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals , and a low selenium status is associated with cardiovascular disease in humans . Endothelial dysfunction , measured as the impaired flow-mediated vasorelaxation of the brachial artery , is a reliable indicator of future cardiovascular disease risk in healthy individuals . To test whether selenium supplementation affects endothelial function , we conducted a r and omized , placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk .  Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation . The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes . However , there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin . This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets 1 . Iodothyronine 5'-deiodinase , which is mainly responsible for peripheral triiodothyronine ( T3 ) production , has recently been demonstrated to be a selenium-containing enzyme . In the elderly , reduced peripheral conversion of thyroxine ( T4 ) to T3 and overt hypothyroidism are frequently observed . 2 . We measured  serum selenium and erythrocyte glutathione peroxidase ( as indices of selenium status ) , thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects ( 52 women , 57 men ) , carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction . The subjects were subdivided into three age groups . To avoid conditions of under-nutrition or malnutrition , dietary records were obtained for a sample of 24 subjects , r and omly selected and representative of the whole population for age and sex . 3 . In order to properly assess the influence of selenium status on iodothyronine 5'-deiodinase type I activity , a double-blind placebo-controlled trial was also carried out on 36 elderly subjects , resident at a privately owned nursing home . 4 . In the free-living population , a progressive reduction of the T3/T4 ratio ( due to increased T4 levels ) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age . A highly significant linear correlation between T4 , T3/T4 and selenium was observed in the population as a whole ( for T4 , R = -0.312 , P < 0.002 ; for T3/T4 ratio , R = 0.32 , P < 0.01 ) and in older subjects ( for T4 , R = -0.40 , P < 0.05 ; for T3/T4 ratio , R = 0.54 , P < 0.002 ) . 5 . The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects ; serum selenium , erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects . 6 . We concluded that selenium status influences thyroid hormones in the elderly , mainly modulating T4 levels 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 , prospect i ve 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 r and omized 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
TRAb levels decreased at 6 but not 9 months .
At 6 months , patients on selenium supplementation were more likely than controls to show improved thyroid function ; however , the effect disappeared at 9 months .
Low selenium status is associated with increased risk of Graves ' disease ( GD ) .
While several trials have discussed the efficacy of selenium supplementation for thyroid function , in GD patients , the effectiveness of selenium intake as adjuvant therapy remains unclear .
In this systematic review and meta- analysis , we aim ed to determine the efficacy of selenium supplementation on thyroid function in GD patients .