Endocrinology: Thyroid Flashcards
2 major hormones of the thyroid gland
Thyroxine (T4)
Triiodothyronine (T3)
function of thyroid hormones
increase metabolic rate of cells in the body
hormone that controls secretion of thyroid gland
TSH from anterior pituitary gland
93% of metabolically active hormone secreted by thyroid is
Thyroxine
How do thyroxine and triiodothyronine differ if they have the same function?
Intensity and speed of effect
Compare and contrast thyroxine and triiodothyronine
Both have same function of increasing metabolic rate
Triiodothyronine is in less concentration, but is 4 times more potent than thyronine and persists for a much short time. the opposite is true for thyronine
Type of epithelium lining follicles of thyroid gland
single Cuboidal epithelial
Substance in follicles and its composition
colloid
mostly made of the glycoprotein thyroglobulin
Why does thyroid have almost greater blood supply than any other area of the body?
Its blood flow is almost five times its weight each minute
Iodine is required to form
thyroxine
Mechanism of iodide trapping
ATPase on basal membrane creates sodium potassium gradient. Sodium flows back down its concentration gradient into the cell together with Iodine with the help of the symport sodium-iodie symporter.
Process of concentrating iodine in the cell is called iodide trapping
Function of pendrin
A counter-transporter on apical membrane of cuboidal cells that transports iodine into the follicular space in exchange for chlorine
Effect of increasing TSH concentration on iodide trapping
increases rate of iodide trapping
Thyroglobulin is synthesized by
the cuboidal cells
Importance of thyroglobulin
To which iodine binds and within which iodine used to make T3 and T4
Define organification
binding of iodine to thyroglobulin
Importance of peroxidase system at the apical cell membrane
It oxidizes iodine so that it binds to thyroglobulin. Without this system, production of thyroid hormone falls to 0
To which molecule does iodine bind to in the thyroglubulin to form thyroid hormones?
Tyrosine amino acids
Number of tyrosine amino acids in a thyroglobulin molecule
70
Why is peroxidase action on iodide important?
Oxidizes the iodide to iodine, the only form of iodide which can bind to tyrosine amino acids
Shortly list steps of T3 and T4 formation from iodide
Tyrosine –> Monoiodotyrosine –> Diiodotyrosine
Monoiodotyrosine + Diiodotyrosine = T3
Diiodotyrosine + Diiodotyrosine = T4
Location of the peroxidase enzyme and its strategic importance
Located in apical membrane or attached to it. Importance is that when iodide is being pumped into the follicles, it is oxidized almost immediately into iodine so that by the time it enters the follicles it is ready to bind to thyroglobulin
Why it’s difficult to detect hypothyroidism immediately at its onset.
Because it has enough thyroid hormone in store for 2 to 3 months so no physiological symptoms are produced
2 Mechanisms of release of thyroid hormones.
1.Pinocytosis of colloid together with its thyroglobulin found to thyroid hormones
Pinocytotic vesicles fuse wit lysosome vesicles containing proteases that cleave thyroglobulin
Thyroid hormones released
Cross basal membrane into adjacent capillaries
- Binds to megalin on the apical membrane
Taken in by endocytosis
Edocytotic vesicles move via transcytosis to basal membrane
Thyroid hormones released via exocytosis into adjacent capillaries
How is majority of iodine recycled in the body?
about 3/4 of iodinated tyrosine does not form T3 and T4, remaining as monoiodotyrosine and diiodotyrosine
deiodinase enzyme cleaves the iodine from these thyroglobulin molecules to make it available again for making more thyroid hormones
True or false: The thyroid hormone that reaches cells is thyroxine since it’s secreted in greater amount than triiodothyronine.
False: Although thyroxine is secreted in greater amounts, it is converted to triiodothyronine so most tissues get T3 instead of T4.
Which thyroid hormone binds more strongly to intracellular proteins? plasma proteins? intracellular thyroid receptors?
Thyroxine binds more strongly to intracelullar proteins.
Triiodothyronine binds more strongly to intracellular thyroid receptors.
Thyroxine binds more strongly to plasma proteins.
Name the receptor thyroid hormone receptor complex binds to at the thyroid hormone response element.
retinoid X receptor
State non-genomic effects of thyroid hormone
activation of cAMP system
regulation of ion channels
regulation of oxidative phosphorylation (of iodide)
cAMP mechanism of TSH
binds to TSH receptors on basal membrane of thyroid cells activation of adenylyl cyclase formation of cAMP phosphorylation of protein kinases effects of TSH observed
What class of hormones based on chemical structure does TSH fall into? and TRH?
TSH –> a glycoprotein
TRH –> amide
Structure of TRH
made of 3 amino acids
glutamate
histidine
proline
True or false: When hypophyseal blood portal system is blocked, TSH secretion falls to zero because no more TRH is reaching it
False: It falls close to zero, but not completely
Molecular mechanism for how TRH exerts its effects on anterior pituitary cells
Binds to TRH receptors
Activation of phospholipase C
Cleavage of phosphatidyl inositol to form IP3 and DAG
= TSH release
Difference in mechanisms of TRH and TSH
TRH uses phospholipase second messenger system while TSH uses cAMP system
Factors affecting amount of TSH and TRH secreted
Cold - exposure of animal to cold increases TRH and TSH secretion = high metabolism due to high heat produced
Emotions that cause excess stimulation of sympathetic nervous system (fear, anxiety, stress) = increase in TSH and TRH, but the thyroid hormone released in turn goes to inhibit TSH resulting ultimately in low levels of TSH secretion
Effect of cold and emotions on the thyroid secreting activity of thyroid gland after hypothalmic stalk is cut
No effect since TRH can’t reach anterior pituitary = reduced TSH = reduced thyroid
General differences in the clinical presentations, diagnosis, and treatment of hypothyroidism versus hyperthyroidism
Hyperthyroidism
- weight loss (due to increased BMR), sweating, muscle weakness, anxiety, diarrhea, intolerance to heat
- usually presents with high levels of Thyroid hormone and low levels of TSH in blood but depends on the cause of hyperthyroidism
- treatment is by partial removal thyroid gland, radioactive iodine to destroy thyroid tissue
Hypothyroidism
- weight gain, muscle sluggishness, reduced cardiac output, atherosclerosis (due to buildup of cholesterol in blood), constipation, sleepiness and slow thinking
- usually presents with high TSH levels, but low thyroid hormone levels *varies
- treatment is by administration of T3 tablets
How is a patient with hyperthyroidism prepared for surgery?
several weeks before operation, antithyroid drug like propylthiouracil is administered to return BMR to normal
Then 1-2 weeks, inorganic iodides are given to reduce the size of gland + its blood supply to reduce amount of bleeding
