What is the Origin of Deiodinase Dysfunction?

The concept is rooted in the discovery and characterization of the three deiodinase enzymes in the late 20th century, revealing that T3, the most potent thyroid hormone, is primarily generated in peripheral tissues rather than solely by the thyroid gland. Dysfunction gained clinical relevance as a mechanism explaining why some patients experience symptoms of hypothyroidism even when receiving T4-only replacement therapy.

What is the Mechanism of Deiodinase Dysfunction?

The core mechanism involves a disruption in the selenium-dependent removal of iodine atoms from the thyroid hormone molecule. Type 1 and Type 2 deiodinases (D1, D2) are responsible for converting T4 to T3 by outer ring deiodination, while Type 3 deiodinase (D3) inactivates T4 and T3 into reverse T3 (rT3) and T2 by inner ring deiodination. Dysfunction is often triggered by factors like nutrient deficiencies (selenium, zinc), chronic inflammation, or high cortisol, which suppress the activating D1/D2 enzymes or upregulate the inactivating D3 enzyme.

Deiodinase Dysfunction ∞ Area

Deiodinase Dysfunction

Meaning

Deiodinase Dysfunction refers to an impaired enzymatic activity of the iodothyronine deiodinase family (D1, D2, and D3), leading to an imbalance in the peripheral and tissue-specific conversion of thyroid hormones. This condition results in an inappropriate ratio of the inactive prohormone thyroxine (T4) to the biologically active triiodothyronine (T3) within various cells and organs. It represents a post-thyroidal defect in hormone metabolism, often manifesting with hypothyroid symptoms despite normal circulating TSH levels.