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.
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
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 .