Does low available iron limit thyroid peroxidase activity and reduce thyroid hormone production?

The relationship between iron status and thyroid function is centered on the biochemical requirements of thyroid peroxidase (TPO), the enzyme responsible for synthesizing thyroid hormones.

Mechanistic evidence

Thyroid peroxidase is a member of the mammalian heme peroxidase family, which includes myeloperoxidase and lactoperoxidase. It relies on a covalently bound heme prosthetic group for its structural integrity and catalytic function.

• Heme Coordination: The heme group is indispensable for TPO's ability to oxidize iodide using hydrogen peroxide. This coordination, specifically involving residues like His239, enables the formation of the "Compound I" intermediate necessary for redox reactions.
• Hormone Synthesis: This heme-dependent activity facilitates two critical steps: the iodination of tyrosine residues on thyroglobulin (iodine organification) and the subsequent coupling of these iodotyrosines to form thyroxine (T4) and triiodothyronine (T3).
• Iron Dependency: Systemic iron availability directly influences intracellular heme synthesis. When iron is deficient, the availability of heme groups is restricted, limiting the catalytic capacity of TPO and mimicking the effects of iodine deficiency.

Clinical and effectiveness evidence

Iron deficiency anemia has been shown in animal models to significantly lower TPO activity in the thyroid gland. In humans, clinical studies consistently show that low ferritin levels (often <30 μg/L) correlate with reduced levels of free thyroxine (FT4) and triiodothyronine (FT3), as well as elevated TSH.

• Iodine Organification: This impairment leads to a state of hypothyroxinemia even in otherwise euthyroid populations.
• Autoimmunity: Iron deficiency is also associated with an increased prevalence of thyroid autoantibodies (anti-TPO and anti-Tg), which can further exacerbate thyroid dysfunction.

Bottom line

TPO is a heme-dependent enzyme, and low available iron limits its activity by restricting heme synthesis. This deficiency impairs iodine organification and thyroid hormone production, making adequate iron status essential for optimal thyroid health.