physiology of thyroid hormone Flashcards
what is goiter?
enlarged thyroid gland
why does goiter happen?
due to overstimulation of thyroid gland
what are the scenarios where you could have goiter?
Hypothyroidism
hyperthyroidism
euthyroid
how does hypothyroidism cause goiter?
in hypothyroidism we have low amount of T3 , T4 –> this low amount will cause the release of excessive TSH —–>
TSH will overstimulate leading to the division and enlargement of thyroid gland
how will hyperthyroidism cause goiter?
in case of hyperthyroidism , we have a HUGE amount of T3, T4 –> this most commonly due to antibody that bind to TSH receptors on the thyroid gland leading to the overstimulation ——-> this over stimulation will cause goiter
usually the level of TSH is low in this scenario
how does euthyroid cause goiter?
in euthyroid goiter is mostly physiological like in cases of pregnancy, there js overproduction of T3,T4 and stimulus
what is the location of thyroid gland?
located below the larynx on each side of the trachea anteriorly
15 to 20 grams in weight
what are the major hormones released by thyroid gland ?
Thyroxine ( T4 )
triiodothyronine ( T3 )
what is the main regulator of T3 and T4 ?
regulated by TSH from pituitary
TSH is regulated by TRH from hypothalamus
what is the main component of the anatomy of the thyroid gland?
follicles
what is the component of the follicle?
colloid
what is the major protein found in the colloid ?
thyroglobulin which is used to store the hormone
which cells in the thyroid gland produce the thyroid hormone?
follicular cells
what do the parafollicular cells produce?
calcitonin
calcitonin –> decrease plasma level of calcium
what is the main form that thyroid hormone is produced as?
Thyroxine (T4 ) –> 93%
When is T3 produced?
T4 are going to be converted to T3 in tissues
so inside the gland in the blood –> T4 is more in quantity
in tissues T3 is more abundant
what converts T4 to T3?
5- iodinase
which one has longer half T4 or T3?
T4 has longer half life because it has higher affinity to binding proteins than T3
So in the blood it is more bound to binding proteins therefore it is less prone to degradation
which one is more potent T3 or T4 ?
T3 is more potent–> 4x more active and stronger
so T3 has shorter half life but stronger effect
what is Revere rT3 ?
a version of T3 that is not biologically active
what happens to T4 when it reaches the tissue?
it gets converted from T4 to T3 by 5 IODINASE enzyme –> which then will result in the function
which plasma proteins does T3 and T4 bind to?
thyroxine binding globulin
thyroxine binding prealbumin
albumin
how are T3 and T4 released to the tissue ?
slowly due to high affinity of plasma proteins for the thyroid hormones
they bind to the plasma proteins so their half life long
what can happen to T4 if it is not converted to T3?
T4 can be stored in target tissues and can used later
T4 will bind to intracellular proteins for storage
describe the onset and duration of action of thyroid hormones? T4
slowly released and slowly starts to take action as it is strongly bound to plasma proteins then as it it gets released its activity will increase progressively —> reach maximum in 10-12 days –> decreases afterwards –> stops but some activity remains for 6 weeks or 2 months
describe the action of T3 ?
similar to T4 but it starts faster and ends fast
T4 –> starts slowly –> ends slowly and has long latent period before action
T3 —> start faster –> ends fast
what is the mechanism of action of thyroid hormone?
it is lipid soluble so it enters the cell goes to the nucleus and then binds to it and increase gene expression and transcription
what are the effects of thyroid hormone on cellular activity?
increased metabolic activity of all tissues from 60% to 100%
increase rate of protein synthesis first then afterward it increases degradation
increase growth rate ( physically and mentally )
Increased mental processes
increase activities of other endocrine gland
increase the number of mitochondria and mitochondria enzymes and ATP synthesis rate
increase the activity of NA/K ATPASE —-> increased Transport of ions through cell membrane
what is effect of thyroid hormone on CVS?
increase cardiac output –> due to increased metabolism in tissue and vasodilation and increased blood flow to tissue
Increase heart rate —> ( thyroid hormone increases excitability of heart )
increase heart strength at first with the increases enzymic activity and protein synthesis
decrease heart strength afterwards due to the protein catabolism and degradation
what could severe thyrotoxicity do to the heart?
cardiac decompensation and secondary myocardial failure
what happens to the mean arterial pressure?
it stays normal
what happens to pulse pressure?
it increases :
systole increases
diastole decreases
what is the effect of thyroid hormone on respiration ?
since it increases CO and heart rate it has to increase respiration as well
increases respiration and metabolism and oxygen utilization
what is the effect of thyroid hormone on GIT?
it increases the rate of secretion of digestive juices and motility
Hyperthyroidism —> diarrhea
hypothyroidism –> constipation
what is the effect of thyroid hormone on CNS?
speed up the process of thinking and reflex
hyperthyroidism —> nervousness , anxiety , extreme worry
lack of thyroid hormone decreases thinking process
what happens to the reaction time in both hyper and hypothyroidism?
it is shortened in hyperthyroidism
it is prolonged in hypothyroidism
what is the effect of Thyroid hormone on muscles ?
increase muscle contraction
hyperthyroidism leads to tumors –> afterwards thyrotoxic myopathy due to decreased protein and protein degradation
hypothyroidism —> causes sluggishness in muscles -> also associated with muscle weakness and cramps and stiffness
what is the effect of thyroid on sleep?
hyperthyroidism leads to –> tiredness and decrease in sleep because of the increased brain activity
hypothyroidism –> increased periods of sleeps 12-14 hours
what is the effect of thyroid on weight?
hyper —> decrease body weight
hypo —> increases body weight
what is the effect of thyroid on glucose?
increases glucose absorption
increase glucose synthesis
increase glycogenolysis
increases glucose lvl in blood
what is the effect of thyroid on fat?
lipolysis
what is the effect of thyroid on insulin level?
it increases glucose level therefore increases insulin
what is the effect of thyroid on parathyroid hormone level?
increases many metabolic activities related to the bone formation so it it causes hypocalcemia and then so it increases its level
what is effect thyroid on adrenal glucocorticoids?
it increases the glucose level so it inhibits the secretion of glucocorticoids BUT this inhibition and decrease in the level glucocorticoids will lead to stimulation of ACTH from pituitary and increase its secretion back up
what is the effect of thyroid on men sexual function?
hyperthyroidism —> impotence
hypothyroidism —> loss of libido
what is the effect if thyroid on women sexual functions?
hyperthyroidism –> commonly oligomennorhea
occasional amennorhea
hypothyroidism –> menorrhagia, polymenorrhea , loss of libido, irregular periods ,amenorrhea
what is the effect of thyroid on growth?
essential for normal growth and skeletal maturation
hypothyroidism –> bone growth slow down and epiphyseal closure is delayed
inhibit GH secretion as well
mental retardation
why is thyroid hormone critical for fetal development?
it is important for normal brain development and regulates especially during fetal and first few years of postnatal life
synaptogenesis
neuronal intergration
myelination and cell migration
what happens if thyroid hormone is not produced in sufficient quantities by fetus?
brain maturation is impaired –> small brain
child without thyroid gland –> mentally deficient throughout life
how is thyroid hormone regulated?
it is mainly stimulated by TSH –> which is stimulated by TRH
T3, T4 negatively inhibit TSH ( negative feedback )
it also inhibit TRH but to lesser extent
what is the effect of TSH on thyroid gland ?
growing of the gland in size and proliferation
stimulating thyroid to produce T3, T4
Proteolysis of thyroglobulin –> release of T3, T4 in 30 minutes
increased Activity of iodine pump –> make more T3, T4
increase Iodination of tyrosine
what is the signaling mechanism of TSH?
it is G protein coupled
second messenger –> adenylate cyclase
how is TRH produced to stimulate TSH?
Produced by periventricular nucleus –> the axons empty in the median eminence –> hypothalamo hypophyseal portal blood to anterior pituitary gland
what is the mechanism of signaling of TRH?
G protein second messenger
Phospholipase C second messenger
what is primary hypothyroidism ?
hypothyroidism due to thyroid gland problem itself for example :
Destruction of gland , chronic autoimmune thyroitis
idiopathic atrophy of gland
surgical removal of thyroid
irradiation of gland
endemic colloid goitre
idiopathic colloid goitre
what is secondary hypothyroidism ?
the problem is outside the thyroid gland –> hypothalamus, pituitary destruction
what is cretinism?
hypothyroidism in CHILDREN
what is myxoedema / thyroiditis ?
hypothyroidism in ADULTS
what are the causes of cretinism ?
extreme hypothyroidism in fetal life, childhood, infancy
untreated congenital deficiency of thyroid hormone
congenital lack of thyroid gland
lack of iodine diet
anything that leads to lack of thyroid in childhood
what are the signs and symptoms of cretinism?
enlarged protruded tongue , obstructs swallowing and breathing
cold intolerance ( cuz no thyroid to heat )
decreased metabolic rate
accumulation of myxedamtous tissue under the skin and mucous membranes
swollen eyes lids
mental retardation
growing of soft tissue but impaired bone development –> short and fat
are the crestina symptoms reversible ?
they are reversible with replacement therapy except mental retardation UNLESS STARTED EARLY
what is myxedema?
total lack of thyroid hormone function in adults
due to :
Thyroiditis , endemic colloid goiter
idiopathic colloid goiter
destruction of the thyroid gland by surgery or irradiation
what are the signs and symptoms of myxedema ?
metabolic rate bewlow 40%
weight gain
cold intolerance
bagginess under eyes
Thickened skin and fascial features –> enalrged tongue , periorbital edema
impaired memory
mental sluggishness and confusion
muscle aches and weakness
Dry skin, hair thin and brittle
Slow heart rate and cardiac output
what is grave diseases ?
autoimmune disease
where immunoglobulin are similar to TSH —–> bind to the receptor and activate thyroid hormone release
what is the name of the immunoglobulins that stimulates thyroid release in Graves disease?
Thyroid stimulating immunoglobulins ( TSI )
what is the difference between it and TSH in regard of duration of effect?
TSI —> longer duration of actions 12 hours
TSH –> shorter duration of action ( 1 hour )
what happens to the level of TSH in grave disease?
it is gonna get suppressed by negative feedback inhibition cuz soo much Thyroid hormone is being secreted due to the effect of TSI
what are the signs and symptoms of graves disease?
muscle weakness and muscle wasting
polyphagia
extreme fatigue
exophthalamas ( eye protruding outward )
Localized MYXEDEMA IN THE TIBIAL
increased calorigenic effect of thyroid hormone
high excitability
heat intolerance
increased sweating
weight loss
diarrhea ( in hypo it is constipation )
tachycardia
nervousness
Hypocholestrolemia ( low cholesterol )
tremors
outstreched fingers
what causes protrusion of eye ball in grave disease?y
deposition of mucus behind the eye
degeneration of muscles behind the eye
what is simple nontoxic goiter?
aka euthyroid goiter?
could be diffused or nodular
it is noncancerous hypertrophy of the thyroid without hyperthyroidism or hypothyroidism inflammation
does thyroiditis cause goiter?
No in thyroiditis theres inflammation and death of thyroid gland so no hypertrophy or hyperplasia
at first will release all the already produced thyroid then afterwards khalas no more thyroid and the gland dies
what is the scenario where you have normal physiological goiter?
in pregnancy we have pregnancy goiter due to increased secretion of hormones
do we have goiter in hypothyroidism secondary to hypothalamic or anterior pituitary failure?
No because in this cause we have deficiency in TSH and TRH so no stimulation no GOITER
do we have goiter in hypothyroidism caused by gland failure itself or lack iodine?
Yes because when we have low amount of thyroid regardless of the cause this will increase TSH lvl –> overstimulation –> goiter
do we have goiter in excess TSH secretion resulting from hypothalamus or anterior pituitary defect?
yes because in this case we will overstimulation of the gland
do we have goiter in Graves disease?
yes becaues TSI antibody will cause overstimulation and increased size and number of the cells —> GOITER
do we have goiter in theres overactivity of the gland without overstimulation from TSH? such as in the cause of thyroid tumor?
No because the only way to cause goiter is overstimulation via TSH or stimulus from anywhere
