The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial Effects of Selenium Supplementation on Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice. Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population. Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. Selenium and the thyroid: A close-knit connection Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency IFNγ-Inducible Chemokines Decrease upon Selenomethionine Supplementation in Women with Euthyroid Autoimmune Thyroiditis: Comparison between Two Doses of Selenomethionine (80 or 160 μg) versus Placebo Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis. Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes Selenium in the treatment of autoimmune thyroiditis A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: Rationale, recruitment, and design issues. Randomized controlled trial of the effect of selenium supplementation on thyroid function in the elderly in the United Kingdom. [The effect of selenium therapy on autoimmune thyroiditis]. The Association between Selenium and Other Micronutrients and Thyroid Cancer Incidence in the NIH-AARP Diet and Health Study Low selenium status in the elderly influences thyroid hormones. Urine Selenium Changes During Pregnancy Do Not Correlate with Thyroid Autoantibodies in a Mildly Iodine Deficient Population Effects of selenomethionine supplementation on selenium status and thyroid hormone concentrations in healthy adults. Minimal impact of excess iodate intake on thyroid hormones and selenium status in older New Zealanders. Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma Selenium and iodine supplementation: effect on thyroid function of older New Zealanders. An estimation of selenium requirements for New Zealanders. Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes Inorganic selenium retards progression of experimental hormone refractory prostate cancer. Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study.
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 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 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 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 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 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 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 : Several studies have suggested that selenium may influence the natural history of autoimmune thyroiditis ( AIT ) . Recently , IFNγ-inducible chemokines ( CXCL-9 , -10 and -11 ) were shown to be elevated in AIT patients . Objective : This prospect i ve , r and omized , controlled study was conducted to evaluate the effect of two doses of selenomethionine ( Semet ; 80 or 160 µg/day ) versus placebo in euthyroid women with AIT , in terms of reduction of anti-thyroid antibodies , CXCL-9 , -10 and -11 and improvement of thyroid echogenicity , over 12 months . Patients and Methods : Sixty patients , aged 21 - 65 years , were equally r and omized into 3 groups : placebo , 80 µg/day of Semet ( 80-Semet ) or 160 µg/day of Semet ( 160-Semet ) . Results : Anti-thyroperoxidase antibody ( TPOAb ) levels remained unaffected by Semet supplementation  ; anti-thyroglobulin antibody levels showed a significant reduction in the 160-Semet and the placebo group at 12 months . No significant change in thyroid echogenicity , thyroid volume and quality of life was observed within and between the groups . Sub clinical hypothyroidism was diagnosed in 2 patients of the placebo group versus 1 patient in each Semet group . Serum CXCL-9 and -10 were significantly reduced in both Semet groups at 6 and 12 months , while they remained unchanged or increased in the placebo group . CXCL-11 , TNFα and IFNγ showed a transient decrease at 6 months in both Semet groups but returned nearly to the basal levels at 12 months . Conclusions : Semet supplementation had no positive effect on thyroid echogenicity or TPOAb in our patients . However , we observed a Semet-dependent downregulation of the IFNγ-inducible chemokines , especially CXCL-9 and -10 , which may serve as helpful biomarkers in future selenium supplementation trials INTRIDUCTION The thyroid is an organ with one of the highest selenium concentrations , containing many selenoproteins implicated in thyroid hormone metabolism . Treatment with levothyroxine has been recommended for all sub clinical hypothyroid patients with TSH levels > 10 mU/L , whereas for those with TSH < 10 mU/L treatment remains controversial . AIM A r and omised controlled prospect i ve study was performed to investigate the effects of Se treatment on patients with autoimmune thyroiditis and mild sub- clinical hypothyroidism ( TSH < 10 mU/L ) . MATERIAL AND METHODS A total of 196 patients with autoimmune thyroiditis were recruited in the study . Patients were assigned to receive ( case ) or not receive ( control ) an oral selenomethionine treatment . Cases received 83 mcg selenomethionine/day orally for four months . All the patient 's charts were su bmi tted to thyroid hormonal profile ( TSH , fT4 ) and TPOAb evaluation upon enrolment and at the end of the study . RESULTS In total 192 patients completed the study . Cases and controls were superimposable for age , gender , thyroid hormonal profile , and TPOAb levels . At the end of the study , 33/192 ( 17.2 % ) participants restored euthyroidism ( Responders ) . Responders were significantly more frequent among Cases than Controls ( 30/96 [ 31.3 % ] vs. 3/96 [ 3.1 % ] , p < 0.0001 ) . CONCLUSION Selenium supplementation could restore euthyroidism in one third of sub clinical hypothyroidism patients with autoimmune thyroiditis . ( Endokrynol Pol 2016 ; 67 ( 6 ) : 567 - 571 ) 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 CONTEXT 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 . OBJECTIVE We examined whether Se supplementation , during and after pregnancy , influences the thyroidal autoimmune pattern and function . DESIGN This was a prospect i ve , r and omized , placebo-controlled study . SETTING The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology . PATIENTS A total of 2143 euthyroid pregnant women participated in the study ; 7.9 % were TPOAb(+ ) . INTERVENTIONS 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 ) . MAIN OUTCOME MEASURES We measured the prevalence of PPTD and hypothyroidism . RESULTS 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 ) . CONCLUSION Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism Purpose To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT , evaluating the response in subgroups with different GPx1 genotypes . Methods CAT patients ( n = 55 ) with positive antiTPO were r and omized to selenomethionine ( SeMet ) 200 μg daily ( n = 28 ) or placebo ( n = 27 ) for 3 months . Assessment s included GPx1 genotyping at baseline and serum levels of plasma selenium , erythrocyte GPx1 activity , antiTPO and thyroid echogenicity at baseline , and 3 and 6 months . Results In the SeMet group , the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes . In the overall cohort , patients r and omized to SeMet showed a 5 % decrease in antiTPO levels at 3 months ( p = non-significant ) and 20 % at 6 months ( p < 0.001 versus 3 months ) . In contrast , patients in the placebo group did not show significant changes in antiTPO levels at any time point . Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet . Conclusions Selenium supplementation decreased serum antiTPO levels in CAT patients , with similar response among patients with different GPx1 genotypes We recently conducted a prospect i ve , placebo‐controlled clinical study , where we could demonstrate , that a substitution of 200 μg 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 μg sodium selenite ( Se‐Se ) , one group stopped taking selenium ( Se‐0 ) ( n = 9 ) , another group which received placebo started to take 200 μg 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 μg sodium selenite after  placebo , the TPO‐Ab concentrations decreased significantly ( p = 0.029 ) from 1182 ± 723 to 643 ± 477 U/ml Deficiencies of selenium have been associated with an increased cancer risk , and several clinical and animal trials have suggested that improved selenium nutrition may reduce the incidence of several kinds of cancer , including lung , colorectal , and breast . Results from recent trials also show an anticarcinogenic effect of selenium in the prostate . There is converging evidence from epidemiologic , experimental animal , and molecular biology studies for an antitumor effect of selenium . Evidence suggests there are two modes of action of selenium affecting cancer risk : first , by functioning as an essential nutrient that provides the catalytic centers of a number of selenoenzymes , including some with antioxidant and redox functions ; second , by serving as a source of selenium metabolytes that affect carcinogenesis in other ways . The first mechanism appears most relevant to protection against cancer initiation , the second against cancer progression . There is conclusive evidence of the increased risk of prostate cancer for a male with a family history of the disease . As a result of this evidence , and the evidence supporting the chemopreventive properties of selenium , this study proposed that a trial to test the effect of selenium on men at high risk for development of prostate cancer is appropriate . This article describes the Australian Prostate Cancer Prevention Trial Using Selenium ( APPOSE ) trial to test the hypothesis that daily dietary supplementation with selenium will reduce prostate cancer incidence in a population of men who are at increased risk because of a first-degree relative with prostate cancer 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 UNLABELLED Selenium as an essential trace element is capable of exerting complex effects on the endocrine and immune system by its antioxidant capacity . The role of selenium is important because the level of free oxygen radicals is elevated in the physiological thyroid hormone synthesis . THE AIM OF STUDY was to determine whether selenium therapy can influence the level of antithyroid peroxidase and antithyroglobulin antibodies or whether there is a correlation between antioxidant capacity and the titer of autoantibodies . METHOD 132 patient with autoimmune thyroiditis were investigated in a prospect i ve , blind and placebo-controlled study . L-thyroxine substitution therapy was made in both groups and the level of TSH remained in the normal range . The selenium-treated group ( n = 70 patients , 68 female , mean age 41,4 + /- 9,5 year ) was compared with the placebo-treated group ( n = 62 patients , 61 female , mean age 42,7 + /- 8,3 year ) . Selenium therapy was continued by L-seleno-methionine ( per os 2 x 100 microg/day ) for one year . Determination of TSH , fT4 , fT3 and autoantibodies was carried out by chemiluminescence method . Total antioxidant capacity was determined by R and ox kit , the level of selenium in the sera by atomic absorption technique was measured . In the follow-up study , patients were controlled every third month and at the end of a one-year observation period . RESULTS The level of selenium in the untreated patients was significantly lower than in treated patients and controls . The fT3/fT4 ration proved to be higher in patients after selenium therapy . The titer of antithyroid antibodies ( mostly the antithyroid peroxidase ) significantly decreased at the end of the study . An inverse correlation was found between antioxidant capacity and the level of antithyroid peroxidase antibodies . The volume of thyroid gl and slightly diminished in treated patients . Side effects were not observed . CONCLUSIONS Selenium completed with L-thyroxine is a suitable therapy for patients with autoimmune thyroiditis 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 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 Selenium ( Se ) is a key component of iodinases ; higher Se levels are associated with lower titers of antithyroid peroxidase antibodies ( anti-TPO ) . Pregnancy exerts profound effects on thyroid function and autoimmunity . To assess the relationship of urine Se levels with thyroid function and autoimmunity in pregnant women residing in Athens , Greece , we studied prospect ively 47 euthyroid women in uncomplicated singleton pregnancies ( mean age + SD : 30 + 5 years ) in each trimester , measuring urine Se levels , urine iodine , plasma thyrotropin ( TSH ) , free thyroxine and triiodothyronine ( FT4 and FT3 ) , as well as levels of anti-TPO antibodies . Changes of the measured parameters were assessed over each trimester ; thyroid parameters were assessed with relation to Se levels . Urine Se dropped by the third trimester , whereas urine iodine did not change appreciably during pregnancy . TSH and anti-TPO did not show appreciable changes ; FT4 and FT3 gradually decreased as the pregnancy advanced . No relationship between urine Se levels and anti-TPO was found . During pregnancy , changes in urine Se levels accompany mild changes in thyroid function . However , we did not find some association between these changes and thyroid autoimmune activity over this period , probably because the effect of Se on thyroid autoimmunity may only become apparent in case of excess Se fortification 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 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 Background : Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls . The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants . Methods : A r and omised , double blind , placebo-controlled trial of selenium supplementation was performed in adults with asthma in London , UK , the majority of whom ( 75 % ) reported inhaled steroid use at baseline . 197 participants were r and omised to receive either a high-selenium yeast preparation ( 100 µg daily , n = 99 ) or placebo ( yeast only , n = 98 ) for 24 weeks . The primary outcome was asthma-related quality of life ( QoL ) score . Secondary outcomes included lung function , asthma symptom scores , peak flow and bronchodilator usage . Linear regression was used to analyse the change in outcome between the two treatment arms by “ intention to treat ” . Results : There was a 48 % increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group . While the QoL score improved more in the active treatment group than in the placebo group , the difference in change in score between the two groups was not significant ( −0.05 ( 95 % CI −0.19 to 0.09 ) ; p = 0.47 ) . Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo . Conclusions : Selenium supplementation had no clinical benefit in adults with asthma , the majority of whom were taking inhaled steroids 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 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 Context Research suggests that selenium supplements may improve glucose metabolism . Contribution The investigators examined the incidence of type 2 diabetes among participants in a clinical trial design ed to assess the effects of selenium supplementation on skin cancer . Participants r and omly assigned to receive selenium  were more likely to develop type 2 diabetes than were those assigned to placebo . Caution s Diabetes was a secondary outcome of the original trial . The diagnosis was self-reported , and most participants were older and white . Implication Long-term selenium supplementation appears to increase the risk for type 2 diabetes .  The Editors Insulin resistance , impaired glucose tolerance , and type 2 diabetes are all linked to oxidative stress , which may be the pathogenic mechanism that links these conditions to cardiovascular disease ( 1 ) . Observational epidemiologic studies show a protective association of dietary or plasma antioxidants against the development of type 2 diabetes ( 2 , 3 ) . However , the few clinical trials that have examined the efficacy of antioxidant supplementation in the prevention of type 2 diabetes or its complications have had negative results ( 46 ) . Experimental evidence from animal models suggests that supplementation with low doses of the antioxidant selenium may exert beneficial effects on glucose metabolism , possibly through many insulin-like actions , and may delay complications of diabetes . The effects of high-dose selenium supplements , however , are less clear ( 710 ) . Some studies in patients with diabetes suggest that selenium supplementation may help to prevent vascular complications ( 11 ) and that diabetic patients may be deficient in selenium relative to healthy persons ( 12 ) . Conversely , recent findings from the SU.VI.MAX ( Supplementation with Antioxidant Vitamins and Minerals ) study ( 13 ) showed no effect of supplementation with a combination of antioxidants , including selenium ( 100 g/d ) , on fasting plasma glucose levels after 7.5 years of follow-up . Because no r and omized , placebo-controlled clinical trials to date have tested the effect of long-term supplementation with selenium alone ( 200 g/d ) on the risk for type 2 diabetes , we examined the efficacy of selenium supplementation in preventing new-onset type 2 diabetes in the NPC ( Nutritional Prevention of Cancer ) trial , a r and omized , double-blind clinical trial design ed primarily to evaluate the efficacy of selenium supplementation for prevention of cancer ( 14 , 15 ) . Specifically , we assessed the incidence of type 2 diabetes as a secondary end point throughout the blinded phase of the trial ( 19831996 ) among participants who did not have type 2 diabetes at baseline ( n= 1202 ) . Methods Design and Participants The rationale , design , and methods of the NPC trial are described in detail elsewhere ( 14 ) . In brief , the NPC trial was a r and omized , double-blind , placebo-controlled study of 1312 participants who were recruited in 1983 to 1991 from 7 dermatology clinics in areas of low selenium consumption of the eastern United States . R and omization was blocked by time and stratified by clinic . Persons were eligible if they had a confirmed history of nonmelanoma skin cancer in the year before r and omization , had an estimated life expectancy of 5 years , and had no reported internal cancer in the previous 5 years . Participants with a history of clinical ly important liver or kidney disorders were excluded . Because the primary aim of the trial was to determine the effects of selenium supplementation on nonmelanoma skin cancer , we excluded nonwhite persons . This restriction served to control the effects of skin pigmentation on the risk for skin cancer recurrence . As a result , almost all participants in the NPC trial were non-Hispanic white persons ; about 1.4 % ( n= 18 ) of persons who were r and omly allocated were identified as Hispanic , and some persons were from other ethnic groups . Although recruitment was sex-neutral , about three quarters of the participants were male . Of the 1316 persons recruited , r and om assignment was successful for 1312 . At the end of the blinded treatment period on 1 February 1996 , no participant was lost to vital follow-up , generating a total of 9301 person-years of follow-up . Self-reported adherence indicated that 79.3 % of participants ( 80.3 % in the placebo group and 78.4 % in the selenium group ) adhered to the intervention ( 16 ) . This was corroborated by the fact that plasma selenium levels remained constant throughout the trial in the placebo group but were substantially higher in the selenium group ( Figure 1 ) . Figure 1 . Mean plasma selenium levels . We analyzed only participants with a valid baseline selenium value obtained within 4 days from the date of r and omization ( 1250 of 1312 participants ) , a decision that is consistent with previously published studies from the NPC trial ( 1517 ) . Baseline characteristics of the total NPC cohort of 1312 participants and the sub sample of 1250 participants with valid baseline selenium levels did not statistically significantly differ ( 17 ) , and our findings did not change substantially when analyses were exp and ed to include all 1312 participants ( data not reported ) . We focus on the 1202 participants who did not have type 2 diabetes at baseline ( 600 selenium recipients and 602 placebo recipients ) . Ascertainment of prevalent type 2 diabetes at baseline was based on a self-reported diagnosis of type 2 diabetes before r and omization , with subsequent evaluation of medical records ( 48 cases [ 21 in the selenium group and 27 in the placebo group ] ) . Figure 2 shows the flow diagram of the NPC participants included in our analysis . Figure 2 . Flow diagram of the Nutritional Prevention of Cancer Trial , 19831996 . Clinical Examination and Laboratory Methods The intervention agent was 200 g of selenium daily , supplied in a 0.5-g , high-selenium baker 's yeast tablet provided by Nutrition 21 ( La Jolla , California ) through 1995 and by Cypress Systems ( Fresno , California ) thereafter . The placebo group received a tablet containing yeast only . Selenium and placebo pills were coated with titanium oxide to ensure identical appearance and smell . Each patient was assigned a unique sequential treatment number . Treatment group assignment was made central ly by using sealed identical pill bottles that were distributed at the clinic . The coordinating center held all treatment information in blinded form ( 14 ) . The selenium content of each batch of pills was determined in the laboratories of Dr. Combs and of I.S. Palmer , MD ( South Dakota State University , Brookings , South Dakota ) , by the diaminonapthalene fluorometric procedure after nitricperchloric acid digestion ( 18 ) . Plasma selenium level was determined in the laboratory of Dr. Combs by using an automated electrothermal atomic absorption spectrophotometer ( Perkin Elmer 3030 , Perkin-Elmer , Norwalk , Connecticut ) equipped with an electrodeless discharge lamp and automatic Zeeman-effect background correction . Quality control included multiple aliquots of human plasma as external control sample s. A coefficient of variation less than 7 % ( for duplicate analyses ) was the criterion for acceptance ( 19 ) . Participants visited their respective clinics biannually to provide blood sample s and report new illnesses and medications . Patient medical records from both study and non study visits were periodically review ed to ensure completeness and accuracy . At the baseline interview , data were collected on sociodemographic , anthropometric , and behavioral characteristics , including education ( 0 to 18 years ) , body mass index ( BMI ) , use of vitamin supplements , alcohol consumption ( drinks consumed per day ) , smoking status ( never , former , or current ) , and pack-years of smoking . For participants who became inactive , annual monitoring was attempted by using the National Death Index and ChoicePoint Services ( formerly Equifax , Atlanta , Georgia ) to determine vital status and identify diagnoses of new illnesses . Ascertainment of Type 2 Diabetes and Follow-up Participants who had a new diagnosis of type 2 diabetes during the blinded phase of the trial ( 15 September 1983 to 1 February 1996 ) were noted . The initial report of diabetes came from 3 sources : self-report during the clinical interview , reported use of drugs for diabetes , and reports in medical record documents . Medical record requests were then sent to the primary physicians for every patient with a report . This process of requesting and review ing documentation was done in a blinded manner . About 92 % of these reports , regardless of source , were corroborated with medical record documentation , as determined by registered nurse review ers . Person-years of follow-up were accrued from the date of r and omization as the start date to the date of an incident case of type 2 diabetes , the date of death , or the end of the blinded period of the trial . Statistical Analysis For continuous and categorical variables , we used t tests and chi-square tests , respectively , to determine the statistical significance of any difference in the distribution of baseline variables between treatment groups . Cumulative incidence curves of type 2 diabetes by treatment group were constructed by comparing NelsonAalen cumulative hazard function estimates that were calculated at different time points of the trial and by using the 2-sided log-rank test ( 20 ) . In unadjusted analyses , incidence data were statistically analyzed by calculating relative risks as the ratios of the incidence density for the treatment groups , with corresponding 95 % CIs . P values were derived from log-rank tests . In adjusted analyses , hazard ratios and 95 % CIs were calculated by using the Cox proportional hazard model , which allowed adjustment for age , BMI ( continuous variable ) , sex , and smoking status at baseline as covariates . We decided a priori to adjust for these diabetes risk factors regardless of whether they differed between treatment groups . Tests of proportional hazards assumptions were based on PURPOSE The development of hormone refractory prostate cancer marks the onset of the terminal phase of the disease . Despite the use of traditional chemotherapeutic drugs as well as many novel agents life expectancy is not significantly increased beyond palliative care alone . Selenium is a micronutrient that is incorporated into a number of essential enzymes and a minimum intake is necessary for the maintenance of health . In the last few years evidence has accumulated from case-control and limited r and omized control data that supranutritional doses of selenium could inhibit the progression of prostate cancer . While much attention has focused on its use as a chemopreventive agent , its use as specific therapy has been limited . We hypothesized that dietary supplementation of selenium would inhibit the progression of hormone refractory prostate cancer in an experimental model . MATERIAL S AND METHODS We established orthotopic PC3 tumors in the prostates of 6-week-old male nude mice and fed them a baseline selenium replete diet ( 0.07 ppm ) , supplementing intake with different forms of selenium ( sodium selenate , selenomethionine , methylselenocysteine and selenized yeast ) at 2 different concentrations ( 0.3 and 3 ppm ) in drinking water . RESULTS Inorganic selenium ( sodium selenate ) significantly retarded the growth of primary prostatic tumors and the development of retroperitoneal lymph node metastases , which was associated with a decrease in angiogenesis . CONCLUSIONS High dose dietary supplementation of inorganic selenium inhibits the progression of hormone refractory prostate cancer , which is due at least in part to a decrease in angiogenesis 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 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
Two systematic review s have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies .
The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release .
In Graves ’ disease , some , but not all , trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism , and might benefit patients with mild Graves ’ orbitopathy .
The available evidence from trials does not support routine selenium supplementation in the st and ard treatment of patients with autoimmune thyroiditis or Graves ’ disease .
However , correction of moderate to severe selenium deficiency may offer benefits in preventing , as well as treating , these disorders .
Purpose of review This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases , and discusses possible effect mechanisms .
Recent findings Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake .
However , clinical ly relevant effects of selenium supplementation , including improvement in quality of life , are more elusive .