Where is T4 (thyroxine) converted to T3 (triiodothyronine)?

T4 to T3 Conversion Sites in the Body

T4 (thyroxine) is primarily converted to T3 (triiodothyronine) in the liver through type 1 deiodinase (DIO1), with additional conversion occurring in other peripheral tissues. 1, 2

Primary Sites of T4 to T3 Conversion

• The liver is the major site of T4 to T3 conversion, accounting for the majority of peripheral T3 production 2
• Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination, with the remaining 20-30% coming from direct thyroidal secretion 2, 3
• The conversion is catalyzed primarily by type 1 5'-deiodinase (DIO1), a selenoenzyme 1

Other Tissues Involved in T4 to T3 Conversion

• The kidney is another significant site of T4 deiodination 2
• The thyroid gland itself contains deiodinase enzymes that can convert T4 to T3 4, 5
• Various other peripheral tissues throughout the body contribute to the overall T4 to T3 conversion 2

Mechanism of Conversion

• The conversion process involves monodeiodination - the removal of one iodine atom from the outer ring of T4 2
• This enzymatic process is primarily catalyzed by type 1 deiodinase (DIO1) in the liver 1
• The process is ATP-dependent and requires selenium as a cofactor for the deiodinase enzymes 1

Clinical Significance

• Since T3 is the major active form of thyroid hormone, the peripheral conversion of T4 to T3 is essential for normal thyroid hormone action 1
• In healthy individuals, approximately 72% of circulating T3 is produced by peripheral conversion of T4, with only 28% coming from direct thyroidal secretion 3
• Conditions that affect liver function can impair T4 to T3 conversion, potentially leading to relative T3 deficiency despite normal T4 levels 6
• Iron deficiency can impair thyroid metabolism and affect the conversion process 1

Factors Affecting T4 to T3 Conversion

• Certain medications can inhibit T4 to T3 conversion, including propylthiouracil (PTU) 4
• Systemic illness can reduce the peripheral conversion of T4 to T3 (sick euthyroid syndrome), with conversion rates significantly reduced in sick patients 3
• Nutritional factors, particularly selenium status, can affect deiodinase activity since these are selenoenzymes 1
• Transport of T4 into T3-producing tissues (particularly the liver) can be impaired in certain conditions, resulting in decreased T3 production 6

Quantitative Aspects

• In normal subjects, the conversion rate of T4 to T3 is approximately 25% 3
• In sick euthyroid patients, this conversion rate can drop to about 13% 3
• The half-life of T4 is 6-7 days, while T3 has a much shorter half-life of less than 2 days 2