title: Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study. Double‐Blind, Placebo‐Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism Selenium and the thyroid: A close-knit connection Oxidative Stress in Graves’ Disease Effects of selenium on short-term control of hyperthyroidism due to Graves’ disease treated with methimazole: results of a randomized clinical trial Effects of Selenium Supplementation on Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice. Oxidation Products and Antioxidant Markers in Plasma of Patients with Graves' Disease and Toxic Multinodular Goiter: Effect of Methimazole Treatment A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms
abstract: 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 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 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 Increased reactive oxygen species ( ROS ) generation and the consequent oxidative damage are involved in the development of several diseases , including autoimmune diseases . Graves ’ disease is an autoimmune disorder characterized by hyperthyroidism and , less frequently , orbitopathy . Hyperthyroidism is characterized by increased oxidative stress . Untreated hyperthyroidism is associated with an increase of several parameters of oxidative stress and in most studies ( but not all ) by an increase of antioxidant defense enzymes . Restoration of euthyroidism with antithyroid drug is associated with a reversal of the biochemical abnormalities associated with oxidative stress . Animal and human studies suggest that increased ROS may directly contribute to some clinical manifestation of the disease , including orbitopathy . Antioxidants administered alone improve some clinical signs and symptoms of hyperthyroidism and , when associated with antithyroid drugs , induce a more rapid control of clinical manifestations and a faster achievement of euthyroidism . A large r and omized clinical trial has shown that antioxidant supplementation ( selenium ) may also be beneficial for mild Graves ’ orbitopathy 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 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 Oxidative stress plays an important role in hyperthyroidism-induced tissue damage , as well as in development of autoimmune disorders . To clarify influence of thyroid metabolic status and autoimmune factors on blood extracellular indices of reactive oxygen species ( ROS ) generation and free radical scavenging in hyperthyroidism , we studied patients with newly diagnosed and untreated Graves ' disease without infiltrative ophthalmopathy ( 17 female and 8 male , aged 41.8±8.9 ) and toxic multinodular goiter ( 15 female and 9 male , aged 48.4±10.1 ) under the same antithyroid treatment protocol .  Initially and after achievement of stable euthyroidism with methimazole  , plasma levels of hydrogen peroxide ( H2O2 ) , lipid hydroperoxides ( ROOH ) and ceruloplasmin ( CP ) and serum concentrations of thiobarbituric acid-reacting substances ( TBARS ) were determined . Similarly , activities of plasma superoxide dismutase ( SOD ) , catalase ( CAT ) , glutathione peroxidase ( GPx ) and glutathione reductase ( GR ) were assayed . The results were compared to those of age- and sex-matched controls . Average duration of hyperthyroidism and treatment period were similar in both patients groups . H2O2 , ROOH and TBARS concentrations were significantly higher in hyperthyroid patients compared to controls . Hyperthyroidism caused an evident increase in SOD and CAT activities and CP level , as well as a decrease in GPx and GR activities . Achievement of euthyroidism result ed in normalization of all analyzed parameters in both hyperthyroid patients groups . These findings suggest that the changes in blood extracellular indices of oxidative stress and free radical scavenging in hyperthyroid patients are influenced by thyroid metabolic status , and are not directly dependent on autoimmune factors present in Graves ' disease Background : 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 . Objective : The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms , hormone levels and /or depression and anxiety . Methods : We prospect ively 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 r and omized 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 question naires about depression , anxiety and self-rated symptoms before medication was started and after 36 weeks . Results : 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 . Conclusions : 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
target: 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 .
background: 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 .