The Evolving Role of Selenium in the Treatment of Graves' Disease and Ophthalmopathy

Graves' disease (GD) and ophthalmopathy (GO) are organ-specific autoimmune-inflammatory disorders characterized by a complex pathogenesis. The inflammatory process is dominated by an imbalance of the antioxidant-oxidant mechanism, increased production of radical oxygen species (ROS), and cytokines which sustain the autoimmune process and perpetuate the disease. Recently, selenium, which is a powerful antioxidant, has been successfully applied in patients with mild GO, slowing the progression of disease, decreasing the clinical activity score, and appreciably improving the quality of life. The mechanisms of selenium action are variable. The aim of this review is to summarize the actions of selenium in GD and GO. Selenium as selenocysteine is incorporated in selenoproteins, such as glutathione peroxidase which catalyzes the degradation of hydrogen peroxide and lipid hydroperoxide that are increasingly produced in hyperthyroidism. Moreover, selenium decreases the formation of proinflammatory cytokines, while it contributes, in synergy with antithyroid drugs, to stabilization of the autoimmune process in GD and alleviation of GO. It is now to be clarified whether enforced nutritional supplementation has the same results and whether prolonging selenium administration may have an impact on the prevention of disease

Selenium and inflammation : potential use and future perspectives

The essential trace element selenium (Se) is constitutively incorporated as selenocysteine, in proteins, among others in antioxidative selenoproteins, such as glutathione peroxidase(s) and thioredoxin reductase. Since chronic inflammation is thought to deplete Se stores in the body, Se supplementation should be considered in prolonged inflammatory states, Se being the trace element the most affected in chronic or low-grade inflammation. Se administration might also be beneficial in bacterial and viral diseases as well as metabolic and autoimmune diseases. In order to maintain a Se steady state, or "selenostasis", Se supplementation, via either diet or compounds, is required to preserve the activity of selenoproteins in antioxidative and redox processes. Importantly, Se could play a pivotal role in the maintenance of homeostasis in infected tissues by inhibiting the proinflammatory toll-like receptor nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and counteracting proinflammatory cytokine action. Finally, while Se status shows considerable promise as a valid marker of inflammatory and autoimmune disease, new functional Se nanoparticles and highly bioavailable selenomethionine compounds will in all probability provide a more efficacious and reliable intervention tool in both preventive and therapeutic disease management

THE THYROID UNDER THREAT IN A WORLD OF PLASTICS

Among the various categories of thyroid disruptors, plasticizers, particularly phthalates and bisphenol A and substitutes, are most frequently examined due to their very extensive use and extreme durability. Both experimental and clinical studies have shown the deleterious effects of plasticizers on, among other major organ systems, thyroid physiology and thyroid hormone metabolism. Though the mechanism(s) are not as yet well clarified, it is hypothesized that plasticizers exert a suppressive effect on thyroid function and disrupt thyroid signaling. Similar effects have been reported in wildlife, which is also increasingly exposed to the plastic contamination of both solid and aqueous environments. By presenting the results of several recently published large studies linking plastics to thyroid dysfunction, this review aims to sound the alarm and thus call to action all academic organizations in order to counteract a threat which imperils not only the thyroid and the reproductive system but also the entirety of life on our planet

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism

A systematic review and meta-analysis investigating the relationship between metabolic syndrome and the incidence of thyroid diseases.

PURPOSE To assess the prospective association between metabolic syndrome (MetS), its components, and incidence of thyroid disorders by conducting a systematic review and meta-analysis. METHODS A systematic search was performed in Ovid Medline, Embase.com, and Cochrane CENTRAL from inception to February 22, 2023. Publications from prospective studies were included if they provided data on baseline MetS status or one of its components and assessed the incidence of thyroid disorders over time. A random effects meta-analysis was conducted to calculate the odds ratio (OR) for developing thyroid disorders. RESULTS After full-text screening of 2927 articles, seven studies met our inclusion criteria. Two of these studies assessed MetS as an exposure (N = 71,727) and were included in our meta-analysis. The association between MetS at baseline and incidence of overt hypothyroidism at follow-up yielded an OR of 0.78 (95% confidence interval [CI]: 0.52-1.16 for two studies, I2 = 0%). Pooled analysis was not possible for subclinical hypothyroidism, due to large heterogeneity (I2 = 92.3%), nor for hyperthyroidism, as only one study assessed this association. We found evidence of an increased risk of overt (RR: 3.10 (1.56-4.64, I2 = 0%) and subclinical hypothyroidism (RR 1.50 (1.05-1.94), I2 = 0%) in individuals with obesity at baseline. There was a lower odds of developing overt hyperthyroidism in individuals with prediabetes at baseline (OR: 0.68 (0.47-0.98), I2 = 0%). CONCLUSIONS We were unable to draw firm conclusions regarding the association between MetS and the incidence of thyroid disorders due to the limited number of available studies and the presence of important heterogeneity in reporting results. However, we did find an association between obesity at baseline and incidence of overt and subclinical hypothyroidism

Potential Risks of Excess Iodine Ingestion and Exposure: Statement by the American Thyroid Association Public Health Committee

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140261/1/thy.2014.0331.pd

New aspects of an old dilemma: treatment of hypothyroidism with L-thyroxine combined with L-triiodothyronine

The current review summarizes the most recent developments in the field of combined treatment with LT4+LT3 in hypothyroidism. Though it was well established for the past 20 years that T3 combined with T4 was best able to achieve euthyroidism in hypothyroidectomized rats, several recent studies and meta-analyses did not demonstrate any increased benefit of combined treatment as compared with T4 monotherapy. Moreover, patients under combination treatment are more prone to experience adverse effects, such as tachycardia, nervousness and fatigue. Conversely, T4 monotherapy usually leads to lower FT3 and higher serum FT4 levels as compared to the LT4+LT3 regimen thus resulting in a FT3:FT4 ratio closer to that of healthy subjects. Today, T4 monotherapy constitutes first-line treatment of hypothyroidism according to both the ETA and ATA Guidelines. However, in many cases the guidelines are not followed, with patients often taking compounded desiccated thyroid hormones or various T3 preparations available on the web. Recently, single nucleotide polymorphisms (SNPs) in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes and in the phosphodiesterase 8B gene have been associated with T3 decrease and thyroid dysfunction. The above observations point to the necessity for more research into the application of customized treatment as well as to the need for the long-awaited LT3-retard formulations or low-dose (about 5g/tablet/capsule) LT3 preparations to be appropriately dosed with LT4 in the context of a personalized treatment strategy. The recent finding that SNPs in DIOs or in thyroid hormone transporter genes may affect serum T3 in tissues opens up the way to the genotyping of those thyroidectomized patients who complain of symptoms and have a lower FT3:FT4 ratio