Trace Elements and Thyroid Diseases: Comprehensive Review of Endocrine and Microbiome Interactions Original paper

What was reviewed?

This comprehensive literature review examines the role 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 hormone synthesis, metabolism, and the pathogenesis of thyroid diseases. The review methodically synthesizes findings from a wide range of clinical and preclinical studies, focusing on the molecular mechanisms by which these elements modulate thyroid function and how imbalances contribute to diseases such as Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism, autoimmune thyroiditis, thyroid nodules, thyroid cancer, and postpartum thyroiditis. Special attention is given to both the detrimental effects of toxic elements (e.g., Cd, Hg, Pb) and the therapeutic or protective roles of essential micronutrients (e.g., Se, Zn), with detailed tables summarizing the mechanisms and clinical implications of each element.

Who was reviewed?

The review encompasses studies involving diverse populations, including healthy individuals, patients with various thyroid disorders (autoimmune, nodular, neoplastic, and postpartum), and special groups such as pregnant women, children, occupationally exposed workers, and experimental animal models. Clinical data from cross-sectional, case-control, and cohort studies are integrated alongside experimental findings from in vitro and in vivo models. The reviewed literature spans geographic regions with variable environmental exposures and dietary practices, reflecting a global perspective on trace element influence in thyroid health and disease.

Most important findings

The review highlights that optimal levels of trace elements are crucial for maintaining thyroid hormone synthesis and homeostasis. Key findings include:

• Iron (Fe): Essential for thyroperoxidase (TPO) activity and thyroid hormone production. Deficiency impairs hormone synthesis and increases risk for hypothyroidism and autoimmune thyroiditis.
• Copper (Cu): Modulates TPO and antioxidant enzymes; imbalance linked to thyroid nodules and cancer.
• Cobalt (Co): High exposure can inhibit iodine uptake, inducing hypothyroidism; used therapeutically in Graves’ ophthalmopathy.
• Iodine (I): Both deficiency and excess are pathogenic—deficiency leads to goiter and hypothyroidism; excess can trigger autoimmune thyroiditis, hypothyroidism (Wolff–Chaikoff effect), and modulate thyroid cancer risk.
• Manganese (Mn): Influences deiodinase activity and oxidative stress; elevated levels associated with hypothyroidism and thyroid cancer.
• Zinc (Zn): Cofactor for thyroid hormone metabolism and antioxidant defense; deficiency impairs hormone production and may increase risk for nodules and hypothyroidism.
• Silver (Ag): Accumulates in thyroid tissue; nanoparticles show anticancer activity in vitro.
• Cadmium (Cd), Mercury (Hg), Lead (Pb): Accumulate in thyroid tissue, promote oxidative stress, disrupt hormone synthesis, and are linked to cancer and autoimmunity.
• Selenium (Se): Integral to selenoproteins in thyroid hormone metabolism and antioxidant protection; deficiency exacerbates autoimmune thyroiditis and Graves’ disease, whereas supplementation shows therapeutic potential.

The review underscores distinct trace element–disease associations, including Fe deficiency in Hashimoto’s, excessive I intake in autoimmune thyroiditis, Cd and Pb accumulation in thyroid cancer, and Se supplementation reducing thyroid antibody titers.

Key implications

For clinicians, the findings reinforce the need to consider trace element status in the evaluation, prevention, and management of thyroid diseases. Deficiencies or excesses of Fe, Zn, Se, and I should be corrected to maintain thyroid health, especially in vulnerable groups (e.g., pregnant women, those with autoimmune thyroiditis). Environmental and occupational exposures to toxic metals (Cd, Hg, Pb) should be recognized as risk factors for both thyroid dysfunction and malignancy. The emerging roles of ferroptosis (Fe) and cuproptosis (Cu) in thyroid cancer open new avenues for targeted therapies. Se supplementation appears beneficial in autoimmune thyroid conditions and may mitigate some side effects of thyroid cancer treatment. Ultimately, integrating trace element assessment into clinical practice may improve disease outcomes and foster personalized management strategies.

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References

1. Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases—A Literature Review.. Bryliński Ł, Kostelecka K, Woliński F, Komar O, Miłosz A, Michalczyk J, Biłogras J, Machrowska A, Karpiński R, Maciejewski M, et al.. (Nutrients. 2025;17:398.)