What is the cause of low Triiodothyronine (T3) with normal Thyroid-Stimulating Hormone (TSH), Free Thyroxine (FT4), and other thyroid function tests?

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From the Research

Low T3 levels with normal other thyroid labs is a condition called "low T3 syndrome" or "euthyroid sick syndrome," which typically occurs during acute or chronic illness, malnutrition, or severe stress, and is not recommended to be treated with T3 supplementation, as addressing the underlying condition usually resolves the thyroid abnormality. This condition is characterized by a decrease in serum triiodothyronine (T3) concentrations, which is correlated with morbidity and mortality 1. The pathogenesis of low T3 syndrome involves altered hepatic T3 production from T4, T4 serum protein binding, and hepatic transport, as well as TSH secretion, with many mediators and drugs involved 2.

The enzyme that converts T4 to T3, deiodinase, becomes less active during illness, while another enzyme that converts T4 to reverse T3 (an inactive form) increases, resulting in lower T3 levels despite normal TSH and T4 2, 1. This is a protective physiological response rather than true thyroid dysfunction. Common causes of low T3 syndrome include severe infections, heart failure, liver disease, kidney disease, major surgery, trauma, cancer, or significant caloric restriction.

Some studies have suggested that non-thyroidal illness syndrome (NTIS) may be a manifestation of hypothalamic-pituitary dysfunction, and that replacement therapies may be beneficial 3. However, the most recent and highest quality study found that there is insufficient evidence to support the use of thyroid hormone supplementation in patients with NTIS, and that adequately powered randomized clinical trials are needed to fill this knowledge gap 1.

Therefore, the focus should be on treating the primary illness or nutritional deficiency, rather than the low T3 levels themselves. Treating the underlying condition usually resolves the thyroid abnormality, and T3 supplementation is generally not beneficial and might even be harmful. The role of inflammatory pathways and tissue TH concentrations during NTIS is complex and not fully understood, and further research is needed to clarify the mechanisms involved 1.

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