3 - thyroid Flashcards
what the role of thyroid hormones
growth, development and maintenance of tissues, metabolic and respiratory rate
what is the structure of thyroid hromones
conjugated iodinated tyrosines
what are the major forms of thyroid hormones
T3 and T4
what is the ratio of T4 to T3 release
14:1
is T3 or T4 the active form
where is it converted
T3 is active, converted in periphery
where does T3 bind
to nuclear receptors to activate certain genes
where are the T3 and T4 receptors located
in nearly all human tissue
why cant you measure T3 and T4 for disorders
they are regulated by negative feedback, its easier to measure TSH
which disorder is high TSH
hypothyroidism (no negative feegback)
which disorder is low TSH
hyperthyroidism (strong negative feegback)
what is TSH
thyroid stimulating hormone
how does TSH change with a two fold change in free T4 and T3
100 fold change
what is hypotheyroidism
clinically significant reduction in thyroid hormone production
what is the most common cause of hypotheyroidism
auto-immune
is hypotheyroidism or hypertheyroidism more common
hypotheyroidism (5-6X)
are women or men more affected by hypotheyroidism
women (7 - 10X)
what are some symptoms of hypotheyroidism
fatigue, cold dry skin, hair loss, brittle laids, hypotension, bradycardia
what is the treatment of hypotheyroidism
supplement T4 via levothyroxine
what was the historical treatment of hypotheyroidism
chew cow and pig thyroid glands
why is chewing a thyroid gland not very safe
there can be a variability in amounts of T3 and also other harmful substances
what is levothyroxin
T4 to treat hypotheyroidism
why give the body T4 and not T4
so the body can convert it to T3 as needed
if it was just T3 then peripheral tissues lose the ability to control local metabolic rates
what is the half life of T4
7-10 days
smooth
what is the half life of T3
24h
peaks bad
what is thyrotoxicosis
too much T3 (not necessarily from the gland)
what is hyperthyroidism
increased thyroid hormone synthesis and secretion from the thyroid gland
what is the most common cause of hyperthyroidism
Graves disease
what is Graves disease
autoimmune disease where antibodies bind to the TSH receptor on thyroid gland follicles resulting in unregulated stimulation of thyroid hormone synthesis
what are the symptoms of hyperthyroidism
high metabolitic rate, cardiovascular disease, osteoperosis, agitation, insomnia, muscle wasting
what is opthalmopathy
when the eyes pop out due to the antibodies from graves disease triggering TSH receptor in eyes
what happens to beta adrenergic receptor expression in hyperthyroidism
increased beta adrenergic expression, increased cAMP, reduce Gi
what is a way to treat hyperthyroidism using radioactivity
radioactive iodine
how does radioactive iodine work (131I)
partially destroy the thyroid gland (very selective, accumulation)
how does the radioation kill the thyroid
energy kills follicular less, gamma rays pass through tissue with no damage, beta particles damage surrounding tissue
what do beta particles do with radioactive iodine
damage surrounding tissue
what do gamma rays do with radioactive iodine
pass through tissue with no damage
how long does radioactive iodine take to work and why
6-18 weeks because there is already lots of stored hormone
how can radioactive iodine be used for diagnosis
detect for abnormalities in the thyroid gland
what is toxic adenoma
benign tumor
what is the most common cause of hyperthyroidism
Graves disease
what is Graves disease
autoimmune disease where antibodies bind to the TSH receptor on thyroid gland follicles resulting in unregulated stimulation of thyroid hormone synthesis
what are the symptoms of hyperthyroidism
high metabolitic rate, cardiovascular disease, osteoperosis, agitation, insomnia, muscle wasting
what is opthalmopathy
when the eyes pop out due to the antibodies from graves disease triggering TSH receptor in eyes
what happens to beta adrenergic receptor expression in hyperthyroidism
increased beta adrenergic expression, increased cAMP, reduce Gi
what is a way to treat hyperthyroidism using radioactivity
radioactive iodine
how does radioactive iodine work (131I)
partially destroy the thyroid gland (very selective, accumulation)
how does the radioation kill the thyroid
energy kills follicular less, gamma rays pass through tissue with no damage, beta particles damage surrounding tissue
what do beta particles do with radioactive iodine
damage surrounding tissue
what do gamma rays do with radioactive iodine
pass through tissue with no damage
how long does radioactive iodine take to work and why
6-18 weeks because there is already lots of stored hormone
how can radioactive iodine be used for diagnosis
detect for abnormalities in the thyroid gland
what happens differently in toxic adenoma and nodeular goiter
they produce hormones regardless of TSH signal
why are the thyroid abnormaties detectable
because they synthesize excess hormones so they use a lot of the radioactive iodine
how can iodine be used to track metastasis
because iodine if it spreads, they still use it to make the hormones so iodine will show up in a scan
what are antithyroid drugs used for
reducing thyroid hormone levels
what group of drugs are antithyroid drugs
thiourelyene
what is an important part of antithyroid drugs’ structure
thiocarbamide (S-C-N)
how do antithyroid drugs work
they inhibit the enzyme peroxidase, which results in less hormone synthesis
what is the halflife of propylthiouracil
1.5hours
what is the halflife of methimazole
6 hours
why is the duration of antithyroid drugs longer than their halflives
because the thyroid gland accumulates the drugs
why is the onset of antithyroid drugs effect often delayed
due to large store of hormone in follicles
what are the two antithyroid drugs
propylthiouracil and methimazole
which antithyroid drugs has to be dosed more than once a day
propylthiouracil
which antithyroid drugs can be dosed once a day
methimazole
which antithyroid drug inhibits conversion of T4 to T3
how
propylthiouracil
inhibits the activity of T4 deiodinase
which antithyroid drug is preferred due to less hepatotoxicity
methimazole
what do the antithyroid drugs do to the immune system
why may this be helpful
overall supression
good if autoimmunity is the caus
how does Iodine transport into the follicle
Na+/I- symporter proteins
what is pendrin
a transport protein that pumps accumulated iodine into the follicle
what does thyroid peroxidase do (2 things)
oxidize iodide(-1) to form iodine (0) AND conjugates MIT and DIT within thyroglobulin to form T3 and T4
what is iodide organification
iodine added to tyrosine (in thyroglobulin)
what happens once iodinated thyroglobulin is formed
taken up by cells via endocytosis
what happens once thyroglobulin is degraded
T4 and T3 are released and secreted
what is the structure of thyroid peroxidase (TPO)
where is it found
heme group with bound iron, a membrane-bound protein
how does thyroid peroxidase (TPO) make TPO-O ox
uses H2O2
how does thyroid peroxidase (TPO) make TPO-I ox
add iodide (I-)
what happens to TPO-I ox
the iodine is donated to tyrosine in the thyroglobulin protein to form either DIT or MIT
what is the mechanism of action of antithyroid drugs
the sulfylhydryl groups of these drugs is iodinated instead of the thyroglobulin (competitively)
what causes methylimidazole to form
iodinated drugs can bind to one another with disulfide link
what is the most serious side effect of antithyroid drug use
agranulocytosis (autoimmune)
when do most cases of agranulocytosis occur and which %
0,37 and 0,35
within 90 days, but sometimes after a year
what are other risks other than agranulocytosis for antithyroid drugs
hepatotoxicity, vasculitis, arthritis
