Thyroid Gland Flashcards
What part of the thyroid produces the hormones?
what is colloid composed of?
thyroid hormones are synthesized by the follicular epithelial cells
colloid is composed of newly synthesized thyroid hormones attached to thyroglobulin
what are the secretory products of the thyroid gland called?
iodothyronines
how is T4 converted to T3 (its more potent, active, and less produced form)
what clinical states are associated with a reduction in the conversion of T4 to T3
fasting, medical/surgical stress, catabolic diseases

Synthesis of thyroid hormones, and treatment locations

How can activity of the thyroid gland be assessed?

Transport of thyroid hormones
-

how can you assess thyroxine binding protein levels?

How does hepatic failure affect the following:
TBG levels, T3/T4

how does pregnancy affect the following?
tbg levels, bound t3/t4, free t3/t4, synthesis and secretion of T3/T4
what is clinically euthyroid?

what is the major control of synthesis and secretion of the thyroid hormones?

what are the actions of TSH on the thyroid gland?
what is its secondary messenger

Stimulatory factors of thyroid hormone secretion (x3)
Inhibitory factors of thyroid hormone secretion (x6)

What proteins are synthesized under direction of thyroid hormones?
In cardiac muscle cells?

Thyroid hormone affect on BMR
-what accounts for the change?
how long does dose of T4 last?

How do thyroid hormones affect lipid metabolism?
How do Thyroid hormones affect carbohydrate metabolism?

what are the indirect and direct effects of thyroid hormones on the CV system?

What type of adrenergic receptors are increased by thyroid hormones? what does this cause?

Hyperthyroidism
primary
secondary
TSH levels

Major clinical signs of grave’s disease?
- eyes?
- serum levels of T4/T3
- TSI?
distinguishes graves from what ?

Hypothyroidism:
primary due to what?
other potential causes?

Treatment of hypothyroidism
- T4 in younger vs older patients
- risks?

Pathophysiology of Hashiomoto’s
- thyroid hormone synthesis impaired by what?
- TSH levels?
- Trophic effect?

What is cretinism?
Cretinism is a condition of severely stunted physical and mental growth owing to untreated congenital deficiency of thyroid hormone (congenital hypothyroidism) usually owing to maternal hypothyroidism.
causes of cretinism?
symptoms?

hypothyroidism due to iodine deficiency?
leads to what effect on thyroid hormones
TSH levels?
what is main characteristic

Goiter
Hyperthyroidism causes?
Hypothyroidism causes?

TSH testing

How are thyroid hormones absorbed into the follicular cells when thyroid gland is stimulated?
endocytosis
First step in Thyroid hormone synthesis:
Where is TG synthesized?
Thyroglobulin (TG), a glycoprotein containing large quantities oftyrosine, is synthesized on the rough endoplasmic reticulum and the Golgi apparatus of the thyroid follicular cells. TG is then incorporated into secretory vesicles and extruded across the apical membrane into the follicular lumen. Later, the tyrosine residues of TG will be iodinated to form the precursors of thyroid hormones.
What is the second step in Thyroid hormone synthesis?
- what is costransported?, via what protein/pump?
- regulation of the pump?
- competitive inhibitors of the pump?

Na + -I − cotransport, or “I-trap.” I − is actively transported from blood into the follicular epithelial cells against both chemical and electrical gradients. The activity of this pump is regulated by I − levels in the body. For example, low levels of I − stimulate the pump. When there is a dietary deficiency of I − , the Na + -I − cotransport increases its activity, attempting to compensate for the deficiency. If the dietary deficiency is severe, however, even Na + -I − cotransport cannot compensate and the synthesis of thyroid hormones will be decreased.
There are several competitive inhibitors of Na +-I − cotransport including the anions thiocyanate and perchlorate,which block I − uptake into follicular cells and interfere with the synthesis of thyroid hormones.
Third step of Thyroid hormone synthesis:
What is oxidized?
Via what enzyme?
What is an inhibitor of this enzyme?
What is this inhibitor a good treatment for?

Oxidation of I − to I 2 . Once I − is pumped into the cell, it traverses the cell to the apical membrane, where it is oxidized to I 2 by the enzymethyroid peroxidase. Thyroid peroxidase catalyzes this oxidation step andthe next two steps (i.e., organification of I 2 into TG and the coupling reactions).
Thyroid peroxidase is inhibited by propylthiouracil (PTU),which blocks the synthesis of thyroid hormones by blocking all of the steps catalyzed by thyroid peroxidase. Thus administration of PTU is an effective treatment for hyperthyroidism.
Peripheral conversion of T4 to T3
- what enzyme converts to T3
- what enzyme converts to reverse T3

fourth step of thyroid hormone synthesis?
- what is happening at the apical membrane?
- what two products are formed?
- high levels of I lead to what effect?
Organification of I 2 . At the apical membrane, just inside the lumen of the follicle, I 2 combines with the tyrosine moieties of TG, catalyzed by thyroid peroxidase, to form monoiodotyrosine (MIT) anddiiodotyrosine (DIT). MIT and DIT remain attached to TG in the follicular lumen until the thyroid gland is stimulated to secrete its hormones. High levels of I − inhibit organification and synthesis of thyroid hormones, which is known as the Wolff-Chaikoff effect.

what is the fifth step in thyroid hormone synthesis?
-what are the coupling reactions occuring?
what combines to form T4? T3?
- which reaction is faster?
- what happens to portion of MIT/DIT that is not coupled?
Coupling reaction. While still part of TG, two separate coupling reactions occur between MIT and DIT, again catalyzed by thyroid peroxidase. In one reaction, two molecules of DIT combine to form T 4 . In the other reaction, one molecule of DIT combines with one molecule of MIT to form T 3 . The first reaction is faster, and as a result, approximately 10 times more T 4 is produced than T 3 . A portion of MIT and DIT does not couple (is “left over”) and simply remains attached to TG. After the coupling reactions occur, TG contains T 4 , T 3 , and leftover MIT and DIT. This iodinated TG is stored in the follicular lumen as colloid until the thyroid gland is stimulated to secrete its hormones (e.g., by TSH).

what is the sixth step in thyroid hormone synthesis?
- what is being endocytosed?
- where/how is TG transported?

Endocytosis (pinocytosis?) of thyroglobulin. When the thyroid gland is stimulated, iodinated TG (with its attached T 4 , T 3 , MIT, and DIT) is endocytosed into the follicular epithelial cells. Pseudopods are pinched off the apical cell membrane, engulf a portion of colloid, and absorb it into the cell. Once inside the cell, TG is transported in the direction of the basal membrane by microtubular action.
What is the 7th step in Thyroid hormone synthesis?
- what is occuring to T4/T3
- via what type of enzymes, where?
Hydrolysis of T 4 and T 3 from TG by lysosomal enzymes. TG droplets fuse with lysosomal membranes. Lysosomal proteases then hydrolyze peptide bonds to release T 4 , T 3 , MIT, and DIT from TG. T 4 and T 3 are transported across the basal membrane into nearby capillaries to be delivered to the systemic circulation; the gland secretes 90% of its thyroid hormone as T 4 and 10% as T 3 . MIT and DIT remain in the follicular cell and are recycled into the synthesis of new TG.

what is the final (8th) step in thyroid hormone synthesis?
-What event is occuring?
Where?
which enzyme?
Deiodination of MIT and DIT. MIT and DIT are deiodinated inside the follicular cell by the enzyme thyroid deiodinase. The I − generated by this step is recycled into the intracellular pool and added to the I − transported by the pump. The tyrosine molecules are incorporated into the synthesis of new TG to begin another cycle. Thus both I − and tyrosine are “salvaged” by the deiodinase enzyme. A deficiency of thyroid deiodinase therefore mimics dietary I − deficiency.

A deficiency of deiodinase mimics what?
mimics dietary Iodine deficiency
What are the main binding proteins of thyroid hormones in the blood stream
Thyroxine-binding protein TBG, synthesized in the liver, binds 70% of Thyroid hormones. Binds 1 molecule of either T3 or T4, and has a higher affinity for T4
Transthyretin (TTR) does 10-15% of TH binding
Albumin does (15-20%)
Which Thyroid hormone has a longer half life?
T4 half life is 6 days whereas T3 is 1 day
T3 resin test in:
Hyperthyroidism, Hypothyroidism, High TBG, Low TBG, Hepatic Failure, Pregnancy

Thyroid hormone affect on the following:
Growth (x2)
CNS (x1)
BMR (x4)
Metabolism (x5)
CV (x1)

Thyroid hormone affect on metabolism
Lipid
-Stimulates what?
Enhances what chemical process of FA?
Plasma concentration of Cholesterol and triglycerides are correlated how with thyroid hormones?
- what happens to blood cholesterol in hypothyroidism?
- what is required for conversion of carotene to Vitamin A, and what happens in hypothyroid patients?

How does Thyroid hormone influence carb metabolism?
increases gluconeogenesis/glycogenolysis to generate free glucose, enhances insulin-dependent entry of glucose
what do thyroid hormones act synergistically with? and to do what?
GH and somatomedins to promote bone formation
Thyroid pathophysiology costanzo

What are the major clincial signs of exopththalmos
Diagnosed by what?
what is present in the circulation?
what does that help distinguish graves disease from?
exophthalmos (protrusion of eyeballs)
periorbital edema (caused by recognition by the anti-TSH receptor antibodies of a similar epitope within the orbital cells)
Diagnosed by: elevated serum free and total T4 or T3 level and clinical signs of goiter and opthalmophaty
- presence of circulating TSI (thyroid-stimulating immunoglobulins)
- helps distinguish graves disease from adenoma of pituitary thyrotrophs
what are the primary causes of hypothyroidism?
Other causes:
hypothalamic disease
pituitary disease (e.g. sheehan’s syndrome)
Resistance to thyroid hormones
