Thyroid Flashcards
The thyroid has three major hormones. What are they and what is this organ in charge of?
It regulates growth and metabolic rate through the actions of T3 (Triiodothyronine) and T4 (Thyroxine). Also, the parafollicular cells of the thyroid produce calcitonin, a hormone that lowers serum calcium levels, hwever, in humans, it is not usually significant in maintaining calcium homeostasis.
There is rich blood supply tot he thyroid. What two major vessels feed it? Where do they come from?
The superior thyroid artery is the first branch off of the external carotid artery and supplies the superior half of the thyroid.
The inferior thyroid artery stems from the thyrocervical trunk, which is a branch of the subclavian artery.
What veins drain the thyroid?
Three sets of veins drain the thyroid. The superior and middle veins, which drain into the internal jugular veins, and the inferior thyroid vein which empties into the brachiocephalic vein.
Discuss the story of the embryology of the thyroid
The thyroid is formed from an epithelial outpouching called the thyroid diverticulum which develops from the floor of the foregut at 3-4 weeks gestation. The progenitor of the thyroglossal duct migrates caudally and the thyroid gland eventually assumes its normal position under the larynx. his duct remains patent as a pathway between the thyroid and foregut until it closes forming the foramen cecum. At 18 weeks, the thyroid starts making hormones
Discuss the histology/microanatomy of the thyroid gland (3 major parts and what their roles are. This will seem like a longer card, but memorizing these few major functions based on the location/what it looks like will help to cement why the thyroid is organized the way it is)
At the microscopic level the thyroid is made up of sspherical, closed follicles that are lined with cuboidal epithelial cells. The basal surfaces of the follicular cells are in contact with a rich blood supply that allows for the absorption of iodide to be used in hormone production.
The apical membranes of follicular cells face a lumen filled with a secretory substance refered to as colloid, made mostly of a glycoprotein called thyroglobulin, which stores the iodine and is a precursor of the thyroid hormones.
Interspersed within the walls of thyroid follicles are small collections of parafollicular C cells that synthesize and secrete calcitonin.
How does the thyroid extract iodide from circulation?
Follicular cells possess a sodium iodide symporter on their basal surfaces that actively transports iodide out of the blood and into the cytosol of follicular cells. This process of intracellular accumulation is known as ioide trapping.
Intracellular iodide rapidly diffuses across the apical membranes of follicular cells into the colloidal lumen. Here it binds to tyrosine residues on thyroglobulin.
What stimulates/inhibits the iodide extraction process?
TSH facilitates iodide transport. Bromide thiocyanate and perchlorate inhibit this process.
Before we start doing stuff with this iodide we just got into the thyroid, we need to make thyroglobulin. Discuss the importance of thyroglobulin and how we make it
Thyroglobulin is a large glycoprotein produced by the thyroid that plays an important role in thyroid hormone synthesis. Thyroid hormones are synthesized from tyrosine residues in the protein structure of thyroglobulin. It serves as both a precursor and a storage of thyroid hormone.
Thyroid globulin is synthesized by thyroid follicular cells and is secreted across the apical membrane. It is the principal component of colloid.
Following iodide uptake and thyroglobulin synthesis, the next step of thyroid hormone synthesis is iodination of thyroglobulin (big jump right) which reguires oxidation and organification steps. Discuss these two steps.
Thyroid peroxidase, an apical membrane enzyme, binds an iodide atom and a tyrosine moiety, brings them in close, and promotes their oxidation, generating short lived free radicals that enable the reaction between iodide and tyrosine residuesof thyroglobulin.
In organification, these free radicals (i.e., iodide and tyrosine moieties) undergo an additional reaction to form monoiodotyrosine (MIT). A second organification can take place, turning MIT to DIT with the addition of iodine to MIT.
The final step in thyroid hormone synthesis is the coupling of two iodotyrosine residues (MIT or DIT) to form iodothyronine. Discuss this process
With MIT and DIT still bound to thyroglobulin, they undergo coupling reactions to form T4 and T3, which remain attached to thyroglobulin as stored hormone until TSH stimulation. Coupling, like the earlier oxidation step, is performed by thyroid peroxidase.
T3 = MIT + DIT T4 = DIT + DIT (most common)
How do we release thyroid hormone?
TSH binds to surface receptors on thyroid epithelial cells and serves as the chief stimulus for hormone release, resulting in pinocytosis of luminal colloid.
Within the follicular cells, lysosomes fuse with pinocytic vesicles, and thyroglobulin is proteolytically digested. Products of protein breakdown include T3 and T4, both of which are transported across the basal membrane and into circulation.
What is Deiodinase?
Continued cleavage of thyroglobulin produces a large proportion of MIT and DIT molecules within follicular cells. Deiodinase mediates iodine moiety cleavage from MIT/DIT and recycling for future thyroid hormone synthesis.
T4 and T3 are principially bound to TBG once in circulation. What is TBG?
Thyroxine-binding globulin. A protein made by the liver.
TBG slows inactivation and urinary excretion of thyroid hormones, therby extending their half-lives. T4 is the major hormone secreted by the thyroid and carried in circulation; however, T3 is the physiologically active form of the hormone.
How do we activate Thyroid hormones?
5’deiodinase (Deiodinase 1 or 2) catalyzes the conversion of T4 to T3 by the removal of an iodine atom. It is present in the liver, kidneys, thyroid and target organs.
How do we deactivate thyroid hormones?
A separate deiodinase enzyme, 5-deiodinase or deiodinase 3 (sometimes 2), targets another site on the T4, forming biologically inactive reverse T3 (rT3). This occurs primarily in the liver and kidneys
