Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases—A Literature Review Original paper
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Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
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Graves Disease
Graves Disease
OverviewGraves’ Disease (GD) affects approximately 0.5% of the population, predominantly women. First-line treatment options—antithyroid medications, radioactive iodine, and surgery— often result in significant side effects, incomplete remissions, and frequent relapses. Further, current first-line treatment options focus on symptoms management, and reflect an inadequate understanding of the etiology of the condition. However, recent research reveals a […]
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was reviewed?
This narrative literature review comprehensively examines the roles of trace elements—including iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se)—in thyroid physiology, hormone synthesis, and the pathogenesis of thyroid diseases. The review details the molecular mechanisms by which these elements affect thyroid hormone biosynthesis, metabolism, immune function, and oxidative stress within the thyroid gland. It further explores how imbalances in these elements contribute to the development and progression of various thyroid disorders, including Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism, autoimmune thyroiditis, thyroid nodules, thyroid cancer, and postpartum thyroiditis. Special attention is given to the dual role of certain elements as both essential micronutrients and potential endocrine disruptors, and to their emerging roles as therapeutic targets or biomarkers.
Who was reviewed?
This review synthesizes findings from a wide range of studies involving diverse populations—adults and children, both healthy and with thyroid disease, from various geographic regions (including iodine-deficient and iodine-sufficient areas). It includes research on different subgroups such as pregnant women, patients with autoimmune thyroid diseases, those exposed to occupational or environmental heavy metals, and individuals undergoing specific thyroid treatments. Evidence is drawn from human epidemiological studies, clinical trials, animal experiments, and cellular/molecular investigations.
Most important findings
The review highlights that optimal concentrations of Fe, I, Cu, Zn, and Se are critical for healthy thyroid hormone synthesis and metabolism. Deficiencies in Fe, Zn, Se, or I, or toxic exposures to Cd, Hg, and Pb, disrupt thyroid hormone production, immune tolerance, and redox balance, predisposing individuals to hypothyroidism, autoimmune thyroiditis, and thyroid cancer. For example, Fe is essential for thyroperoxidase activity; Cu and Zn are components of antioxidant enzymes; Se is vital for deiodinase function; while both deficiency and excess I impact hormone synthesis through mechanisms such as the Wolff–Chaikoff effect. Heavy metals (Cd, Hg, Pb) promote oxidative stress, immune dysregulation, and oncogenic transformation. The review also notes gender-specific and age-dependent differences in trace element effects, and complex interactions between environmental exposure, genetic susceptibility, and thyroid disease risk. Recent research into ferroptosis and cuproptosis (forms of metal-dependent cell death) suggests potential for novel biomarkers and therapeutic strategies in thyroid cancers.
Key microbial and microbiome associations:
While the review centers on trace elements, it references the gut microbiome’s role in thyroid autoimmunity, especially its impact on trace element absorption (notably Fe and Se) and immune modulation. Dysbiosis may impair micronutrient status, influencing the risk and severity of autoimmune thyroid diseases. This emerging connection between trace element metabolism, the gut microbiome, and thyroid autoimmunity is a promising area for further investigation and may be relevant for microbiome signature databases.
Key implications
Clinical management of thyroid disorders should consider patients’ trace element status, exposure to environmental toxins, and dietary habits. Screening and correcting micronutrient deficiencies (Fe, Zn, Se, I) can help prevent or ameliorate thyroid dysfunction, while minimizing exposure to toxic metals (Cd, Hg, Pb) is crucial for thyroid health. Personalized approaches, considering genetic and microbiome influences, may optimize prevention and treatment. Some trace elements (Se, Fe, Cu) and related molecular pathways (ferroptosis, cuproptosis) hold promise as therapeutic targets or diagnostic/prognostic biomarkers in thyroid cancer and autoimmunity. Integration of trace element assessment into clinical and public health practice, alongside continued research into their interplay with the microbiome, could significantly improve thyroid disease outcomes.