T4 (Thyroxine) is Secreted by the Thyroid Gland
T4 (thyroxine) is exclusively secreted by the thyroid gland, not the pancreas or posterior pituitary. 1, 2
Thyroid Hormone Production and Secretion
The thyroid gland plays a central role in thyroid hormone physiology, being responsible for the production and secretion of thyroid hormones. The process occurs through several key steps:
Iodine uptake: The thyroid gland concentrates iodide (I-) against an electrochemical gradient through a carrier-mediated mechanism driven by ATP 1
Hormone synthesis: Within the thyroid gland:
- Iodide is oxidized and incorporated into tyrosyl residues of thyroglobulin (Tg)
- This forms monoiodotyrosine (MIT) and diiodotyrosine (DIT)
- These iodinated tyrosines couple to form T4 and T3 3
Hormone secretion: The thyroid gland primarily secretes T4 (thyroxine) as the main product, with a smaller amount of T3 4, 3
Role of Thyroid Stimulating Hormone (TSH)
Thyroid hormone production is regulated by TSH from the anterior pituitary:
- TSH stimulates all steps in thyroid hormone biosynthesis, from iodide oxidation to the secretion of T4 and T3 into circulation 1
- Only in the thyroid does TSH regulate this process, distinguishing it from similar iodide uptake mechanisms found in other organs 1
T4 as a Prohormone
While the thyroid gland is the sole source of T4, it's important to understand that:
- T4 functions primarily as a prohormone 4
- Most of the bioactive T3 is produced by outer ring deiodination of T4 in peripheral tissues 5
- This conversion is performed by iodothyronine deiodinases types I and II in target tissues 6
Clinical Significance
Understanding the source of T4 is critical for diagnosing and treating thyroid disorders:
- Central hypothyroidism presents with low free T4 with low/normal TSH 2
- Untreated hypothyroidism has significant cardiovascular consequences 2
- When monitoring thyroid function in patients with central hypothyroidism, free T4 levels (not TSH) should be targeted to the upper half of the reference range 2
Unique Biosynthesis Pathway
The biosynthesis of thyroid hormones is remarkable in that they are constructed from ribosomally synthesized precursors:
- T4 and T3 are assembled from tyrosine residues embedded in thyroglobulin, a large glycoprotein 1
- Thyroid peroxidase diiodates the aromatic rings of proximal tyrosine residues and catalyzes their oxidative coupling 1
- Hydrolysis then releases T4 and a smaller amount of T3 1
This unique biosynthetic pathway distinguishes thyroid hormones from many other hormones in the body and confirms their exclusive production in the thyroid gland.