Thyroid

1393

Develops embryologically from the endoderm of the primitive foregut.

It arises in the embryological ventral pharynx in the region of the base of the tongue and descends into the neck.

Weighs 10-20 g in the average adult which is approximately 1-2/10,000 of the average human.

Cells derived from 2 embryonic lineages: endodermal follicular cells arise from the thyroid diverticulum in the midline pharyngeal floor between the first and second pharyngeal pouches, and the ectodermal neural crest C-cells arising from the ultimobranchial body.

The embryological descent of the thyroid results in the pyramidal lobe and thyroglossal duct cysts and undecided thyroid at the base of the tongue.

C-cells comprise less than 0.1% of epithelial mass of the thyroid.

Consists of two lateral lobes connected by a thin isthmus located below and anterior to the larynx.

Weighs about 15 gms, shaped like a butterfly with wings flanking the trachea and connected in front of the trachea.

Structural variations of the gland include the presence of a pyramidal lobe, a remnant of the thyroglossal duct above the isthmus.

Well vascularized gland with one of the highest rates of blood flow per gram of tissue in the body.

Made up of multiple acini, follicles, surrounded by a single layer of cells and filled with pinkish proteinaceous material, colloid.

When inactive the thyroid gland colloid is abundant, with large follicles and flat lining cells.

When the thyroid gland is active the follicles are small, lining cells are columnar or cuboids and the edge of the colloid is scalloped, forming lacunae.

Microvilli project into the colloid from the apex of thyroid cells.

Thyroid gland cells have prominent endoplasmic reticulum, and secretory droplets of thyroglobulin.

Thyroxine (T4) and triiodothyronine (T3) do not display pulsalitity or have a circadian rhythm.

T3 mediates thyroid hormone action by binding to nuclear thyroid hormone receptors in almost all tissues.

Thyrotropin controls all aspects of thyroid hormone synthesis and release.

Secretion of thyrotropin is stimulated by thyrotropin releasing hormone and inhibited by negative feedback through thyroid hormone.

20% of T3 made up from daily secretion which comes directly from the thyroid and the other 80% is derived from the monodeiodination of T4 to activate T3 in peripheral tissues.

T4 serves as a prohormone for T3, having almost no intrinsic biological activity of its own.

Normal serum T3 levels can be achieved with T4 therapy, although some studies suggest that some individuals have impaired physical and psychological well being and cognitive function and mood compared to a control population (Jonklaas).

T4, also known as thyroxine and levothyroxine, has 4 atoms of iodine in each molecule.

T4 is the main hormone secreted by the thyroid and more than 99% circulates in the blood stream attached to proteins, particularly thyroid binding globulin.

T4 that is unattached and free (FT4, free thyroxine) can leave the circulation and enter cells.

Levothyroxine sodium is absorbed at 70-80% and occurs in the small bowel.

Levothyroxine traditionally has been given in the morning before breakfast to prevent interference of absorption by food and medications.

Levothyroxine given at bedtime significantly imroves thyroid hormone levels, and should be considered to be administered at that time (Bolk N et al).

T3 (triiodothyronine and levothyroxine) has three atoms of iodine in each molecule, is secreted by the thyroid gland and also made from T4 in cells outside the thyroid gland capable of converting T4 to T3.

Over 99% of T3 circulates in the blood stream attached to proteins, particularly TBG.

Unattached T3, known as free T3 and only that small portion of T3 can leave the circulation to enter cells.

Free T3 is active thyroid hormone and work’s by entering cell’s nucleus and by binding to receptors to regulate gene activity affecting the metabolic rate.

T3 receptors are found in most cells of the body indicating the widespread effect on the body.

T3 is also formed in peripheral tissues by deiodination of T4.

T3 and T4 are iodine containing amino acids.

The thyroid secretes 80 microgm as iodine in T3 and T4.

Forty microgm of iodide diffuses daily into the extracellular fluid.

Iodide derived from diet is transported into the thyroid against a concentration gradient by means of the sodium-Iodide symporter and diffuses through follicular cells for transport into the follicular lumen by means of the anion exchange protein pendrin.

Within the follicular lumen iodide is oxidized and bound to tyrosine residues in thyroglobulin molecules through the activity of thyroid peroxidase.

Iodinated tyrosine groups in thyroglobulin are coupled together to form either thyroxine T4 or triiodo thyroxine T3.

Through pinocytosis, follicular cells respond to increased thyrotropin level by ingesting luminal colloid within vesicles, which then infuse with lysosomes, leading to proteolytic release of T4 and T3 from thyroglobulin.

T3 and T4 are metabolized in the liver and other tissues with release of 60 microgm of iodide per day into the extracellular fluid.

Naturally occurring T4 and its cogeners with an asymmetric carbon atom are the L isomers, while D thyroxine has only a small fraction of the activity of the L form.

Thyroid cell membranes contain a symporter, an iodide pump, that transports, sodium and iodide into cells against an electrochemical gradient for iodide.

The symporter can produce intracellular iodide concentrations 20 to 40 times as great as the concentration in plasma.