4_Thyroid Flashcards
Describe the location of the thyroid gland.
below larynx of either side, anterior to trachea in an H-shape
What percentage of thyroid hormone does T3 make up?
7%
t1/2 of T3
1 day
t12 of T4
6 days
Describe the relative potencies of T3 & T4.
T3 4x more potent
Describe the cell structure of the thyroid gland.
follicles of cuboidal epithelium surrounded by colloid
How is iodine trapped?
Na/K ATPase & TSH-linked NIS (Na/I symporter)
Where is TRH synthesized?
PVN of hypothalamus (affected by emotion, temp, etc)
Where is TSH secreted?
anterior pituitary
Other name for TSH?
thyrotropin
Describe the receptor pathway for TSH.
G-alpha-S
What is the effect of TSH binding its receptor in the thyroid?
increased activity of NIS, iodination of Tyr, Tg proteolysis; thyroid hyperplasia
What is the feedback circuit for TSH?
T3 & T4 only
Describe the steps in the formation of thyroid hormones.
1) TSH-dependent I trapping, 2) peroxidase oxidation, 3) Tg precursor secretion, 4) peroxidase iodization, 5) Tg auto-coupling, 5) pinocytosis, 6) proteolysis and secretion
Where is peroxidase located in the thyroid cuboidal cell?
at the apical membrane (colloid side)
Describe the action of peroxidase in the thyroid?
1) oxidizes iodide to yield I2 or I3-, 2) iodizes Tyr
What are the products of Tg auto-coupling?
1) MIT + DIT = T3; 2) DIT + MIT = RT3; 3) DIT + DIT = T4
What is the chemical numbering name for T3?
3,5,3’-T3
What is the chemical numbering name for RT3?
3,3’,5-T3
What is the physiologic function of RT3?
none known
Describe the structure of Tg precursor.
chain of Tyr
How is Tg proteolyzed after reuptake via pinocytosis?
fusion with a lysosome
Describe the relative concentrations of T3 and T4 in the plasma.
T4 much greater than T3
How are T3 & T4 transported in the plasma?
thyroxine-binding globulin
How are T3 & T4 imported?
via AA transporters
Describe the storage of T3 & T4.
stored for days-week intracellularly
Why is T3 more potent?
T4 binds stronger intracellularly
What are the adverse effects brought about by the T3/T4 receptor?
CV: increased HR, contractility, tissue flow, CO
What is the function of T3/T4 via its receptor?
increase BMR (via increased Na/K-ATPase, increased plasma glucose, increased protein turnover, increased mitochondria)
Describe the receptor action of T3/T4.
nuclear hormone receptor forms a homodimer or heterodimer with RXR at specific thryoid HREs
What is graves disease?
a toxic goiter
What is TSI?
thyroid-stimulating immunoglobulin, an antibody that mimics TSH
How is hyperthyroidism caused?
by a toxic goiter (Graves Disease)
How is hyperthyroidism diagnosed?
1) increased T3 or T4, 2) TSI, 3) BMR +30 to +60
How is hyperthyroidism treated?
surgery or propylthiouracil
How does propylthiouracil work?
blocks MIT/DIT coupling and iodination via inhibiting peroxidase
What is a side effect of propylthiouracil?
can increase TSH and cause a goiter
What are non-obvious symptoms of hyperthyroidism?
sweating, fatigue, fine hand tremor, diarrhea, exophthalmos
What is exophthalmos?
protrusion of eyeball caused by swelling of retro-orbital tissues and degeneration of extra-ocular muscles
How is an endemic nontoxic colloid goiter caused?
iodine deficiency
How is an endemic nontoxic colloid goiter treated?
iodine
What causes an idiopathic nontoxic colloid goiter?
thyroiditis: inflammation causes hypothyroidism, which increases TSH; or T3/T4 synthetic enzyme defects
What is myxedema?
facial swelling due to increased proteoglycans and hyaluronic acid
What are the effects of hypothyroidism?
failure of trophic functions (less hair, scaly skin, husky voice), myxedema, arteriosclerosis, altered lipid metabolism, less bile/cholesterol secretion
What is cretinism?
extreme hypothyroidism in infance or early childhood leading to growth failure
What are the various forms of cretinism?
1) congenital, 2) genetic, 3) endemic
What causes congenital cretinism?
no thyroid
What causes genetic cretinism?
no T3/T4 production
What causes endemic cretinism?
inadequate dietary iodine
