Thyroid Gland Flashcards
What is colloid made of?
newly synthesized thyroid hormones attached to thyroglobulin
What is the general reaction to make T4 or T3?
tyrosine + I2 –> MIT (one I) or DIT
DIT + DIT –> T4
DIT + MIT –> T3 (outer ring w/ 1 I)
What is the difference btw T3 and reverse T3?
reverse T3 = inactive, minor product of rxn
2 I atoms on outer ring of rT3
1 I atom on outer ring of T3
What is the major secretory product of the thyroid?
T4
converted to T3 in periphery
What occurs in TH synthesis when the availability of iodide is restricted?
formation of T3 is favored
What is the I trap?
I- is brought into follicle cells from blood w/ 2 Na
I- moves against its electrochemical gradient - powered by Na/K ATPase pump on basolateral membrane
What does pendrin do?
on lumen side of follicle cell
pumps out I- into lumen and Cl into follicle cell
peroxidase simultaneously turns I- to I2 –> Iodide pumped out to lumen to be added to TH
What does TSH stimulate specifically in a follicle cell?
Stimulates it to pinocytose TG bound to T4 and T3
(then is secreted to blood)
What occurs when there are high levels of I-?
inhibits organification and addition of I2 to MIT and DIT
*Wolff-Chaikoff effect
What do perchlorate and thiocynate do?
inhibit the NIS pump –> I- cannot be pumped into follicle cells to synthesize T3 and T4
What does PTU do?
inhibits the peroxidases that turn I- to I2 on the lumenal membrane of follicle cells –> can’t add I to thyroxine
Where is most of iodine in the thyroid gland located?
most stored iodinated as tyrosines of thyroglobulin
8000 ug total
600 ug is T4 and T3
How much new thyroid hormone is secreted a day?
60 ug
enough stored as iodinated TG in colloid to last the body 2-3 months
What does radioactive I123 allow you to see?
activity of thyroid gland
highest in hyperthyroidism
slightly lower in graves (idk why though)
normal = 25%
depressed in hypothyroidism
How is Thyroid hormone found in the blood?
equilibrium btw bound and free T3 and T4
TBG = main binding protein, higher affinity for T4
TTR and albumin minor binding protein
How does the affinity of TBG for T4 and T3 relate to their half-lives?
higher affinity for T4 –> contributes to its longer half life
T4 = 6 days
T3 = 1 day
What does the T3 resin uptake test do?
measures circulating levels of TBG
unbound and labeled T3 added –> binds to unbound TBG spots –> anti T3 Ab/resin absorbs leftover labeled T3
higher the T3 uptake –> lower the TBG
What occurs to TBG and and T3 uptake levels during pregnancy?
increased TBG = increased total T4, FT4 usually normal
decreased T3 uptake
What occurs to T3 uptake levels in hypothyroidism?
decreased T4
decreased T3 uptake
What occurs to TGB during hepatic failure?
decreased blood levels of TBG
transient increase in FT3 and FT4 –> followed by negative feedback and inhibition of sythesis –> levels normalize
How does TSH regulate the thyroid gland?
TSH regulates growth and secretion of thyroid hormones
regulated by TRH form hypothalamus and - feedback of FT3
TSH secretion occurs at steady rate
What type of receptor does TSH bind on follicle cells?
Gs GPCR –> increases adenylyl cyclase –> cAMP –> increases synthesis, secretion, and growth of cells
What occurs to Na/K ATPase in response to T3?
synthesis of Na/K ATPase increased in most tissues
How does T3 affect cells?
binds to thyroid hormone receptor-retinoid X receptor complex in the nucleus –> stimulates synthesis of new proteins
What is the affinity for thyroid hormone receptor for T3 and T4?
higher affinity for T3
How does T3 affect cardiac tissue?
increases synthesis of:
myosin
B1 adrenergic receptors
Ca+ ATPase
How is T3 deiodinated in peripheral tissue?
by 5’ iodinase
How does T3 affect metabolism?
increases glucose absorption
increases gluconeogenesis and glycogenolysis
increases lypolysis
increases protein synthesis and degradation (net catabolic)
How does T3 affect basal metabolic rate?
increased synthesis of Na/K ATPase –> more O2 consumption and heat production –> increased BMR
How does a dose of T4 affect BMR?
increases BMR after several hours
long lasting
How does T3 affect lipid metabolism?
stimulates fat mobilization –> increased FAs in plasma
enhanced oxidation of FAs
the more T3 –> the less cholesterol and triglycerides in blood
converts carotene to vitamin A
Why can hypothyroid pts have blidness and yellowing of the skin?
T3 required to convert carotene to vit A
Why is blood volume increased in response to T3?
stimulates RAS system
How does T3/T4 indirectly affect the cardiovascular system?
increased heat production and CO2 in tissues –> decreased peripheral vascular resistance –> decreased diastolic BP –>
reflexive indreased adrenergic stim
How does T3 affect bones?
work w/ GH and somatomedins –> promote bone formation
How does T3 affect the CNS?
important for maturation
deficiency during perinatal development –> abnormal synapses and decreased dendritic branching and myelination
What occurs in Graves’ disease?
TSI –> binds TSH receptor –> unregulated overproduction of thyroid hormones
What is exophthalmos?
abdormal protrusion of the eyeball
seen w/ periorbital edema in graves disease
due to recognition by anti-TSH receptor Abs of similar epitope w/in orbital cells
What are the primary causes of hypothyroidism?
agenesis
gland destruction
inhibition of hormone synthesis and releae (iodine deficiency, inherited enzyme defects, drugs)
transient (afer surgery or therapeutic radioiodine, postpartum, thyroiditis)
What causes hashimoto’s thyroiditis?
autoimmune
thyroglobulin or TPO Abs –> decreased T3 and T4 secretion
What is Cretinism?
untreated postnatal hypothyroidism; caused by:
iodide def, maternal intake of anti-thyroid meds, impaired dev of thyroid, inherent def in synthesis of thyroid hormones
What can cause a goiter?
hyperthyroidism
primary hypo - lack of iodine, idiopathic, chronic thyroiditis (hashimotos)
What do you see in pituitary abnormality causing hypothyroidism?
low TSH
Low T3/T4
negative antithyroid antibody
