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Filip Vasiljević, MD
Sam Gillespie, BSc
Pauline Rowsome, BSc (Hons)
Robyn Hughes, MScBMC
In hypothyroidism, ‘hypo’ refers to having too little, and ‘thyroid’ refers to thyroid hormones, so hypothyroidism refers to a condition where there’s not enough thyroid hormones.
Now, as treatment for hypothyroidism, we can use thyroid hormone analogues as a replacement to supply the body with normal levels of thyroid hormones.
There are 2 different thyroid hormones; triiodothyronine or T3, and thyroxine or T4.
They’re two tyrosine-based, iodine-containing hormones that are secreted by the thyroid gland, which is located anteriorly in the neck and consists of two lobes that look like two thumbs hooked together in the shape of a “V”.
Now, if we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells or thyrocytes.
Zooming in, these follicular cells have an apical side that surrounds a central lumen filled with a viscous fluid called the colloid.
The colloid contains the precursor hormone thyroglobulin.
The basolateral side of follicular cells is in contact with blood vessels that supply these cells.
Now, synthesis of thyroid hormones inside the follicles involves a few important steps.
First, the inorganic iodide ions, present in a low concentration in the blood, are actively taken up by the basolateral side of the follicular cells, along with two sodium ions, via a sodium-iodide symporter.
This step is known as ‘iodide trap’.
The iodide ion is then pumped into the colloid via the pendrin protein, where it undergoes oxidation with the enzyme “thyroid peroxidase” or TPO, which changes it into an organic iodine atom.
It’s then attached to tyrosine amino acid residues which are found throughout thyroglobulin.
This step is known as iodination.
Some tyrosine residues are bound by only one iodine, whereas others are bound by two iodine atoms, yielding monoiodotyrosine or MIT, and diiodotyrosine or DIT, respectively.
These molecules are then coupled together by the same enzyme “thyroid peroxidase” or TPO.
This process is known as coupling.
Coupling one MIT with one DIT creates T3, while linking two DIT molecules creates T4.
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