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Challenges and perspectives of selenium supplementation in Graves' disease and orbitopathy.

ABSTRACT: PURPOSE:This review focuses on the results of prospective randomized clinical trials and the conclusions from respective meta-analyses in order to summarize experiences with adjuvant selenium (Se) supplementation in Graves' hyperthyroidism and orbitopathy, while identifying ambiguous findings and highlighting important open research issues. METHODS:We searched the PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through May 31, 2019, for relevant studies. RESULTS:The available evidence concerning routine use of Se in the treatment of Graves' hyperthyroidism remains ambiguous. Results of meta-analyses, including ten RCTs, suggest that adjuvant Se supplementation can enhance the restoration of biochemical euthyroidism. Unfortunately, these results must be judged cautiously owing to several important limitations. Moreover, an in-depth analysis of relevant long-term clinical measures of therapeutic success (such as remission rate after antithyroid drug treatment), besides surrogate markers (for example, hormone or autoantibody concentrations), is generally missing. Based on a single study, Se supplementation is recommended in patients with mild orbitopathy of short duration because it may decrease inflammation and eye-specific symptoms while also achieving a marked improvement in disease-specific quality of life. The effects of Se supplementation on moderate-to-severe orbitopathy remain as yet unknown. CONCLUSIONS:Additional randomized clinical trials with clinically relevant endpoints are urgently needed to further aid in clinical decision-making, including better stratification of Graves' disease patients, who are most likely to benefit from Se supplementation.

SUBMITTER: Bednarczuk T

PROVIDER: S-EPMC7033064 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Challenges and perspectives of selenium supplementation in Graves' disease and orbitopathy.

Bednarczuk Tomasz T Schomburg Lutz L

Hormones (Athens, Greece) 20191113 1

<h4>Purpose</h4>This review focuses on the results of prospective randomized clinical trials and the conclusions from respective meta-analyses in order to summarize experiences with adjuvant selenium (Se) supplementation in Graves' hyperthyroidism and orbitopathy, while identifying ambiguous findings and highlighting important open research issues.<h4>Methods</h4>We searched the PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through May 31, 2019, for relevant studies.<h4 ...[more]

PMID: 31721133

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Project description:IntroductionMethimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.MethodsIn the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.ResultsAt baseline, circulating total CD3-CD56+NK cells and CD56bright NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56bright NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56dim NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56bright NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69+ NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%).DiscussionThis pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.

Project description:Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

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Challenges and perspectives of selenium supplementation in Graves' disease and orbitopathy.

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Challenges and perspectives of selenium supplementation in Graves' disease and orbitopathy.

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