Thyroid Research Thyroid Research Archive Thyroid Hormone Production

Conversion of thyroxine to triiodothyronine outside the thyroid is mediated primarily by type 2 deiodinase

(November 2005)

The background of the study. Approximately 80 percent of the triiodothyronine (T3) in plasma is produced by deiodination of thyroxine (T4) outside the thyroid gland. This conversion is mediated by two deiodinase enzymes. Type 1 deiodinase (D1) is found mostly in the liver and kidneys and type 2 deiodinase (D2) mostly in muscle. The extent to which each deiodinase contributes to plasma T3 was estimated in this study.

How the study was done. Human embryonic kidney epithelial cells were treated to express D1 or D2. The cells were incubated with T4 labeled with radioactive iodine (I-125) for varying times and under different conditions, and the I-125 iodide released was measured.

The results of the study. The rates of deiodination by D1 and D2 increased with time for up to 24 hours. Deiodination of T4 catalyzed by D2, but not D1, decreased when high concentrations of T4 were added to the cells. At a medium T4 concentration of 2 pmol/L (severe hypothyroidism), the conversion mediated by D1 was approximately 0.1 percent and that by D2 0.2 percent. At a medium T4 concentration of 20 pmol/L (normal), the respective rates for D1- and D2-mediated deiodination were each approximately 0.1 percent, and at a medium T4 concentration of 200 pmol/L (severe hyperthyroidism) the respective rates were 0.1 and 0.05 percent.

Based on the efficiency of D1 and D2, estimates of liver and muscle weight, the contributions of liver and muscle D1 and D2 activity, respectively, to daily extrathyroidal T3 production in a normal adult were estimated. At low and normal free T4 concentrations, D2-mediated deiodination accounts for most extrathyroidal T3 production, whereas D1-mediated deiodination predominates at a high free T4 concentration.

The conclusions of the study. Both type 1 and type 2 deiodinase contribute to the extrathyroidal production of T3. With rising plasma T4 concentrations the D2 contribution decreases and the D1 contribution increases.

The original article. Maia AL, Kim BW, Huang SA, Harney JW, Larsen PR. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 2005;115:2524-33.