Which enzyme is responsible for the conversion of T4 (thyroxine) to T3 (triiodothyronine) in peripheral tissues and is inhibited by beta-blockers and glucocorticoids?

Explanation

## Peripheral Conversion of T4 to T3 **Key Point:** Deiodinase type 1 (D1) is the primary enzyme responsible for converting T4 to T3 in peripheral tissues, particularly the liver and kidneys. This conversion is essential because **T3 is 3–5 times more biologically active than T4**. ### Types of Deiodinases | Deiodinase | Location | Function | Regulation | |---|---|---|---| | **Type 1 (D1)** | Liver, kidney, thyroid | Converts T4 → T3 (main source of circulating T3) | Inhibited by β-blockers, glucocorticoids, PTU, propranolol | | **Type 2 (D2)** | Brain, pituitary, brown adipose tissue | Converts T4 → T3 locally; maintains intracellular T3 | Stimulated by low T3 states | | **Type 3 (D3)** | Brain, placenta, skin | Converts T4 → rT3 (reverse T3, inactive) | Increases in illness, fasting | **High-Yield:** - **Beta-blockers** (propranolol) inhibit D1 → reduced T3 formation → useful in thyroid storm management - **Glucocorticoids** inhibit D1 → reduced T3 in critical illness - **PTU** (propylthiouracil) inhibits both TPO AND D1 (dual action) - **Methimazole** only inhibits TPO, not D1 **Clinical Pearl:** In severe illness (sepsis, trauma, fasting), D3 activity increases and D1 decreases → low T3 syndrome (euthyroid sick syndrome). This is why T3 levels drop in ICU patients despite normal TSH. **Mnemonic:** **"D1 = Delivery of active T3"** — Type 1 deiodinase delivers the active hormone to the circulation.