deiodinase

Deiodinases are selenocysteine-containing enzymes critical for peripheral thyroid hormone metabolism. Type 1 deiodinase (D1) is found mainly in liver, kidney, and thyroid; it converts T4 to T3 (activation) and also degrades rT3, contributing significantly to circulating T3 levels. Type 2 deiodinase (D2) is located in the brain, pituitary, brown adipose tissue, and skeletal muscle; it converts T4 to T3 locally, providing tissue-specific control of thyroid hormone action, importantly regulating pituitary feedback (TSH suppression) and thermogenesis. Type 3 deiodinase (D3) inactivates thyroid hormone by converting T4 to rT3 and T3 to T2, and is highly expressed in placenta, fetal tissues, brain, and skin—protecting the fetus from excess maternal thyroid hormone and modulating hormone action during development. Clinically, deiodinase activity is altered in nonthyroidal illness ("sick euthyroid syndrome"), where D1 activity decreases and D3 activity increases, leading to low T3, elevated rT3, and normal/low TSH without primary thyroid pathology. Drugs like propylthiouracil inhibit D1, and amiodarone can affect deiodinase function, contributing to thyroid dysfunction. Understanding deiodinases helps explain discrepancies between TSH, T4, and T3 levels seen in various clinical scenarios, and is tested in questions about thyroid hormone physiology and abnormal thyroid function tests unrelated to primary gland pathology.