Extra-Thyroidal Factors Impacting Thyroid Hormone Homeostasis
Brock McGregor, BSc, ND


Peripheral thyroid metabolism


Peripheral metabolism plays a significant role in maintaining thyroid hormone expression in local tissues. The thyroid secretes thyroxine (T4) at substantially greater levels than triiodothyronine (T3), relying on peripheral mechanisms to convert T4 to T3. Peripheral control is exerted through a number of pathways. These pathways include deiodination, facilitated by deiodinase enzymes, as well as conjugation and lipid peroxidation. Factors influencing any or all of the peripherally active pathways continue to be explored and may help explain why many patients continue to experience symptoms consistent with hypothyroidism, including low body temperature, even when their thyroid blood tests are normal. These factors include liver and kidney function as well as seasonal changes. Although non-thyroidal illness syndrome was originally defined as a condition occurring without direct thyroid function impact, there is evidence that the thyroid itself may alter T3 and T4 during illness via modified gene regulation in the presence of pro-inflammatory cytokines. There are also a number of lifestyle behaviors, including fasting, alcohol dependence, and smoking that have been shown to affect peripheral metabolism of thyroid hormones. Zinc affects both the synthesis and mode of action of action of thyroid hormones. For example, thyroid transcription factors, which are essential for modulation of gene expression, contain zinc at cysteine residues. Selenium is required for the selenocysteine moieties that confer the function of the deiodinase enzymes. Selenium supplementation has been shown to reduce anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies in patients with autoimmune thyroiditis. Selenium has been shown to increase the level of glutathione peroxidase, which contains selenocysteine. Both Withania somnifera and Commiphora mukul have been shown to improve hypothyroidism by elevating T3 levels and increasing T3:T4 ratios through peripheral metabolic pathways.



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