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our hypothalamus is our master endocrine regulator and what it does is, is there's nuclei in here that
release a particular type of hormone called thyrotropin releasing hormone also known as trh

trh when released by the hypothalamus moves down via the hypophyseal portal system into the
anterior pituitary.

anterior pituitary contains endocrine cells called thyrotropes.

that are stimulated by trh and once these cells are stimulated by trh it triggers them to release
another hormone called tsh also known as thyroid stimulating hormone

the thyroid stimulating hormone that's made by the anterior pituitary then goes to the thyroid
gland itself and if we look at it at the cellular level it actually binds on to receptors on follicular cells
but the overall effect is that once it stimulates the thyroid gland it tells the thyroid gland to make
two particular hormones

but the collective combination of them is thyroid hormone and that is t4 and t3

90% T4 and only 10 percent of it is t3

here we're going to have that thyroid stimulating hormone and what it does is it binds on to a tsh
receptor you see that blue little protein there it binds onto a g protein coupled receptor

we're not going to go through this path but we in engineers we know it already what would it do it
increases cyclic amp increases protein kinase a and protein kinase a phosphorylates transcription
factors that stimulate genes and these genes once activated will transcribe and translate particular
proteins

the protein that is made with response to tsh production is thyroglobulin

tsh stimulates thyroglobulin synthesis

the second effect is it increases cyclic amp, increases protein kinase a and phosphorylates another
particular protein which is a very integral enzyme here and this is called thyroid peroxidase TPO very
important one here now in order for us to understand TPO’s effect we have to talk about one quick
thing

you know these follicular cells they really depend upon iodine they need iodine in order to function
and so what happens is in our blood we have a good concentration of iodide and what happens is we
bring the iodide into the follicular cells via what's called sodium iodide symporters and once we
bring this iodide here we use this enzyme called tpo

The first thing thyroperoxidase does is it removes the electrons from iodide and converts it into
iodine

the second thing it does is it takes iodine and thyroglobulin and stimulates the fusion of these two
and by the result of that we get what's called iodinated thyroglobulin

iodinated thyroglobulin contains t4 and t3 within it’s structure

Proteolytic enzymes are in the cell take so the iodinated thyroid globulin is taken back into this
follicular cell, proteolytic enzymes cleave T3 and T4 out of the iodinated thyroid globulin and that's
where how get t3 and t4 from the thyroid gland
that follicular cell was stimulated by the tsh and it was producing thyroglobulin here in the centre so
all of this thyroid globulin iodination process is occurring inside of the central portion of the follicle

now that we've made thyroid hormone how does it exert its metabolic effect

what happens is t4 let's say we take any cell any nucleated cell okay that is capable of performing
metabolism

any kind of metabolic function what it does is it primarily takes up t4 once t4 is inside of our
metabolic cells there's an enzyme called d-iodinases which convert t4 into t3

t3 is the active form of thyroid hormone, this is the one that can exert its effect.

t3 binds onto intracellular receptors, activates genes and increases the expression of proteins.!!!!!

makes there's tons of proteins that it makes but one that i really want you to know is sodium
potassium ATPases.

every time these pumps are working they use a lot of atp if i increase the expression of these
sodium potassium atp i use more atp and that means I need to generate more atp

what are the processes that are stimulated to help generate atp:

glycogenolysis which is breaking down glycogen into glucose and then sending it through the
glycolytic pathway.

glycolysis which is breaking down glucose into pyruvate and acetyl coa and then again making atp

it also helps to stimulate lipolysis breaking down lipids into fatty acids and glycerol all of these things
generate atp but increase your metabolism within all of your cells

the next thing is talking about how thyroid hormone affects other target organs other than just
nucleated cells

THE heart:

it does a couple things to the heart one of the big things is that it helps to increase beta adrenergic
receptor sensitivity and all that means is

if the sensitivity of those beta adrenergic receptors is increased every time epinephrine
norepinephrine binds to them their effects are a little bit more amplified

the main effects this can result in is an increase in heart rate, a chronotropic action (Chronotropic
effects are those that change the heart rate) , and an increase in contractility and that is a inotropic
action (An inotrope is an agent that alters the force or energy of muscular contractions)

there's one more thing though that we really need to mention and that it also thyroid hormone its
levels maintains vasomotor tone means Constant level of nervous stimulation to the muscles in the
blood vessel walls. This gives the muscles a resting level of contraction). Basically, it helps maintain a
balance between vasoconstriction and vasodilation.

!!It maintains vaso motor tone. the next thing acts on the bones and it maintains a beautiful balance
between osteoclasts and osteoblasts
again osteoblasts deposit bone or deposit calcium into the bone osteoclasts pull calcium from the
bone

!! there's another big thing that you need to know and that is that it helps to control the
development of our skeletal system and the maturation of our skeletal system so it plays a role
within bone development as well as bone maturation

!! it also helps with our central nervous system right so it helps particularly within the nervous
system to increase your sympathetic nervous system activity

within the GI tract it helps to do what helps to increase the GI motility and it helps to increase the gi
secretions within the skin it maintains beautiful blood flow through the skin

so that's another important one is that it helps to increase blood flow to the skin if you increase
blood flow to the skin remember skin is actually your epidermis but it's also your hair your hair is
actually skin cells your nails are skin cells so it's important for the growth of hair skin and nails

good blood flow lots of oxygen lots of nutrients to those tissues so increased blood flow is
important for growth of what structures hair skin nails

it's also important because not just a lot of blood flow but also there's thyroid hormone regulates
the activity of your sebaceous glands and your sweat glands so it also helps to increase sebum and
sweat production

next thing is your reproductive system it's important not just for helping to develop the reproductive
system but also maintenance of the reproductive system

it plays a role in the development of reproduction. it also can control a particular type of
hormone/protein called sex hormone binding globulin it regulates the levels of this which is
important for when carrying particular types of steroid hormones like estrogen and progesterone

and there's one other thing trh which we'll talk about a little bit it's related to thyroid hormone also
can affect and we'll talk about this very heavily lsh and fsh that's very important okay which control
estrogen and testosterone progesterone production

so remember development and function of repro sex hormone binding globulin control

your fibroblasts it controls your fibroblasts. fibroblasts make a particular molecule called
glycosaminoglycans and what thyroid hormone does is it controls the production of
glycosaminoglycans and the degradation of glycosaminoglycans

it plays a role within the development it plays a role within the regeneration of our skeletal muscle
cells

it also plays a role in muscle contraction and the way it does this is it controls muscle contraction by
regulating the activity of those calcium atp aces that are present on the sarcoplasmic reticulum

if we control those that controls the amount of calcium that's in the muscle that regulates our
muscle contraction

so again development regeneration and muscle contraction via the calcium atpases that covers our
physiology.
primary hypothyroidism. there's different causes let's say that we take these three causes affecting
this thyroid gland first though usually one of the most common issues is that there's antibodies that
are acting against particular proteins within the thyroid gland or that there's a virus that's actually
injuring or damaging the thyroid gland or particular drugs that are injuring or damaging the thyroid
gland.

The first main cause is called hashimoto’s thyroiditis. now hashimoto's is more common in females
and its an autoimmune disease.

autoimmune diseases are multifactorial but usually it's some type of genetic susceptibility genes that
are involved in an environmental trigger and that environmental could trigger could be a drug it
could be a pathogen it could be a pollutant it could be many different things

but when we're exposed to it our immune system will phagocytose or take in that environmental
trigger or agent when it does it expresses a piece of it on its mhc2 complex

whenever you express a particular thing let's say here i have a macrophage i express a particular
type of environmental trigger or a particular antigen if you will on my mhc2 complex what type of
cells come and react with that your t cells and when your t cells react with this the normal kind of
response is you're going to produce cytokines it'll produce cytokines that'll kind of adv you know
alert the immune system let them know hey there's some type of a trigger or pathogen or
something here that's we don't like and what that'll do is that'll tell these pathogens will tell
particular b cells called plasma cells to produce antibodies and these antibodies are supposed to be
driven against the environmental pathogen but guess what for some odd reason that environmental
pathogen or trigger

whatever it is it looks very similar to the proteins that are found inside of the thyroid gland and
because of that not only do those antibodies go and attack the environmental trigger they also
attack the thyroid tissue inadvertently and lead to destruction that is also kind of known as
molecular mimicry so that's why i wanted to take a quick second to explain that little process here
and that means that there's some type of genetic susceptibility genes that are in causing some type
of problem here with the mhc2 complex where this response is even more exaggerated

what happens is with these mhc2 complexes there's genes that regulate them and they're called hla
dr 3 hla dr5 these are the two primary ones that if there's these genes having mutations this type of
effect can be exaggerated and cause this autoimmune disease that we see

these antibodies are exerted against the thyroid peroxidase and the thyroglobulin so they're called
anti-tpo antibodies or anti-thyroglobulin antibodies

the next one similar to hashimoto's is called postpartum thyroiditis so postpartum thyroiditis now
postpartum thyroiditis again you're obviously going to see this in females usually it's within one year
of birth. what happens is usually in pregnancy your immune system is slightly weakened but after
birth the immune system kind of revs back up a little bit and this sometimes may inadvertently lead
to antibodies that are going to be produced that destroy some of the thyroid tissue similar to the
way hashimoto's

With hashimoto's this is chronic so these antibodies will continue to keep damaging this thyroid
tissue but with postpartum this is more of an acute issue and so it will lead to hypothyroidism but
usually there's resolution in time so after some time the when the immune system settles down a
little bit they'll resolve and go back into a euthyroid or normal thyroid state
okay but again what is the pathology behind this it's antibody mediated and it's the same thing tpo
antibodies and thyroglobulin antibodies okay

the next cause is usually some type of viral infection and that is whenever there's a viral infection
that's causing the thyroid to not produce enough thyroid hormone because it's being inflamed or
damaged this is called sub acute granulomatous thyroiditis.

so subacute granulomatous thyroiditis also referred to as a decoyvin's thyroiditis is usually due to a

viral infection.

whenever you have viral infections sometimes this can maybe produce a little bit of an increase in
the white blood cell count, usually this produces pain and tenderness of that thyroid gland but what
happens is whenever there's a lot of inflammation sometimes it can trigger your liver to make
particular proteins that can whenever you do this particular lab test it can be increased you know
what that is whenever there's viral infections or inflammation that inflammation may lead to an
increase in a erythrocyte sedimentation rate so an increased esr i want you guys to remember that
because that's going to come to diagnostic play later

the next one here related to this inflammation here is also going to be drug induced there's a couple
drugs three primary ones the first one that is really important is amiodarone this is an
antiarrhythmic the next one is lithium which is used to treat bipolar disorder and the next one is
iodine 131 you know what we give iodine 131 for radioiodine ablation in patients who have high per
thyroidism they're producing too much we give that and it basically inhibits thyroid gland of thyroid
hormone production by destroying the thyroid tissue but it can destroy it so much that now you
develop hypothyroidism

now we've talked about all of these causes hashimoto's postpartum subacute granulomas and drug-
induced we say that it's damaging the thyroid gland

that whenever you damage the thyroid gland what spills out of them a little bit thyroid hormone and
thyroglobulin remember we talked about that where this can spill out what kind of things it can spill
out let's say that we represent the blue here as thyroglobulin and we represent the red here as
thyroid hormone so it can spill some thyroid globulin out into the blood because of the follicular
destruction and spill some of the thyroid hormone out because of the follicular destruction what's
the problem with that if you spill some of the thyroid hormone out of these follicular cells what
could that do it could produce a transient or temporary hyperthyroidism but after time as you
continue to destroy or inflame or agitate or damage these thyroid follicles they're not going to be
able to produce enough thyroid hormone and so because of that eventually their production of t3
and t4 will plummet and drop the most common one though that you will see this with is
hashimoto's thyroiditis

we need to add iodine onto thyroglobulin so if iodine is decreased i don't make enough iodinated
thyroid globulin. because of that, if you have decreased iodinated thyroglobulin can you make
functional thyroid hormone? remember thyroid hormone in order for it to be functional it needs
iodine on it if you don't have that you can't make it

most common cause worldwide for hypothyroidism is hashimoto's is the most common within
iodine sufficient areas and iodine deficient hypothyroidism is the most common cause worldwide
there's a particular mechanism called the Wolff-Chaikoff and all this says is that if you give too much
iodine to somebody really high amounts of iodine what it'll do is the high amounts of iodine will
inhibit t3 and t4 synthesis how if you have too much iodine what it'll do is it'll inhibit a particular
enzyme called thyroid peroxidase

they'll say hey there's too much thyroid hormone that's being produced there's too much that you
guys are making here we need to slow this down i'm going to inhibit you thyroid peroxidase from
continuing to do that process there oh proteolytic enzymes you guys are cleaving too much
iodinated thyroid globulin making too much thyroid hormone i'm going to inhibit you

so it'll also inhibit the proteolysis and the overall effect of inhibiting the thyroid peroxidase inhibiting
the proteolysis due to too much iodine via negative feedback leads to decreased thyroid hormone
synthesis so that gives us the primary reasons that someone would develop hypothyroidism due to a
thyroid issue itself

central hypothyroidism causes so let's take in a scenario here let's say that it's a hypothalamus issue
you guys got to remember what does the hypothalamus make what is that hormone it is trh.

trh then tells the antipituitary to make tsh and tsh tells the thyroid gland to make thyroid hormone
okay so as a result here it's going to tell the thyroid gland hey make thyroid hormone let's say that
there's an issue where there's something wrong with the hypothalamus or there's something wrong
with the pituitary let's take the first scenario something's wrong with the hypothalamus if the
hypothalamus is not working what's going to happen to the trh production it's going to drop what
happens to the tsh production that's going to drop what happens to the thyroid hormone
production that's going to drop that's hypothyroidism

another scenario what if there's something wrong with the anterior pituitary it's not making a lot of
tsh then what's going to happen to the thyroid hormone that's going to drop now here's the
interesting effect here usually let's say that we took the scenario and avoided this issue here we
don't even know that this is going on if someone has hypothyroidism what is the normal negative
feedback type of effect i know you guys know this the normal feedback mechanism is that whenever
there's low thyroid hormone that's going to come over here and stimulate the hypothalamus and
stimulate the anterior pituitary to make more trh and more tsh but if there's something wrong with
the hypothalamus or something wrong with the pituitary is it going to be able to make trh no so it
won't respond and trh will continue to be low or if there's something wrong with the anti-pituitaries
they're going to respond and make tsh no so even though there's hypothyroidism it's still going to be
low that's very important diagnostically now the next question that you should have is what in the
heck can cause the hypothalamus or pituitary.

what if somebody experienced some type of traumatic brain injury if they had a traumatic brain
injury and that damaged the underlying brain tissue particularly the hypothalamus or what if they
have some type of tumor on near the hypothalamus that tumor is compressing on these nuclei and
affecting their ability to make trh that could be another reason but the overall effect here regardless
of what the cause is is that they have some decrease in trh production if you take the other scenario
where you take into consideration the anterior pituitary what's going on on with the anti-pituitary
that it's not making tsh a big one here is that it could also be related to some type of trauma maybe
an underlying traumatic brain injury, another one is it could be a tumor but the big one that i really
need you to remember is an underlying infarction there's a particular name that can happen in post
whenever someone gives birth and they bleed a lot and they lose too much blood they don't get
enough blood going to the pituitary gland and the actual pituitary gland can infarct and affect its
ability to not just to make tsh but a bunch of other hormones that it makes what is that condition
called very important you guys remember it it's called shihan syndrome and shihan syndrome is
associated with postpartum hemorrhage not getting enough blood flow to the pituitary infarcting
and then what's the result of that decreased tsh resulting in decreased t3 and t4 boom baby we
good all right so congenital hypothyroidism so this issue here i want you guys to remember that
there's a problem with the development the maturation of the thyroid gland or that there's one
more issue and that there's not enough iodine same thing in adults

you need to know with someone who has hypothyroidism a common manifestation can be a goiter
the whole concept behind someone developing a goiter is because they're not releasing the thyroid
hormone from the thyroid follicles and that may be because of an iodine deficient situation that may
be because of uh they're actually continuously destroying the thyroid gland and as that thyroid gland
is being destroyed it's continuing to hypertrophy

whatever it may be they can develop goiters so there's many different reasons for goiters one of the
common reasons is that if they're iodine deficient they're not releasing functional thyroid hormone
basically the thyroglobulin that you were producing and putting into that central portion it's not
being iodinated and you're not pulling it into the cells to release that hormone it's just accumulating

okay that's one thing the next thing is do you guys remember every nucleated cell that was capable
of performing metabolism we're just going to do what decrease the activity of it we're going to
decrease the activity of everything that we talked about over with physiology

so if i decrease the metabolic activity of my cells i'm going to decrease glycolysis i'm going to
decrease lipolysis and i'm going to decrease glycogenolysis that means that there's going to be less
metabolism less atp that's being produced

if that happens that means my metabolism is really shutting down it's really decreasing if i have a
decreased metabolic activity am i going to break down lipids and glycogen and stuff as well no so
because of that what happens you gain weight, one of the effects of this is weight gain

the next thing that i need you guys to remember is that whenever you guys perform cellular
respiration you break down glycogen you break down glucose you break down lipids every metabolic
activity that goes through aerobic cellular respiration you generate co2 you generate water and you
generate atp but there's one more byproduct that you generate heat that's a natural byproduct of
cellular metabolism if you're having decreased metabolism are you going to generate as much body
heat no so because of that there's going to be decreased heat production and this decreased heat
will lead to a low body temp sometimes referred to as cold intolerant so they can experience weight
gain they can experience a decrease in body temp

another thing is if you're having a decreased metabolism of these substances what happens is it also
changes your appetite and so because of that in situations of hypothyroidism where they have this
weight gain they may have a decreased appetite okay and that could also be because of the gut
brain signaling but again weight gain because of decreased metabolism and decreased body
temperature because of decreased heat from cellular respiration

the next effect is on the heart remember we said it increases the beta adrenergic uh receptor
sensitivity well if there's decreased thyroid hormone we decrease the beta 1 adrenergic receptor
sensitivity remember what we said that would do well and before it said if we had it it would
increase heart rate a little bit and increase contractility a little bit well if we have less of that
sensitivity what is it going to do it's going to lower the heart rate so it can maybe lead to a little bit of
bradycardia and it's going to mildly decrease the contractility not as significant as the heart rate so
there'll be a significant drop in heart rate a small drop in contractility one more thing remember we
said that thyroid hormone regulates the vasomotor tone on our blood vessels in other words
constriction dilation whenever you have little thyroid hormone guess what it tips the balance
towards vasoconstriction

so if i increase the vasoconstriction that's going to leads to squeezing and clamping down on the
blood vessel

what does that do that decreases diameter it increases resistance and does what increases blood
pressure

thyroid hormone is important for osteoclast and osteoblastic activity that is very important and
maintaining the balance between it but you know what else i told you it's important for bone growth
and maturation if you don't have enough thyroid hormone it's very problematic whenever you're
developing and maturing bones very important and so decreased thyroid hormone leads to
decreased bone growth and bone maturation and you know why that's a problem whenever your
skeletal system is developing it's not going to have all the things that needs to continue to grow so
what will happen they'll develop a short stature so someone can develop a short stature as a result
of this this is one reason for delayed growth in children with hypothyroidism

boom okay what about the effect on the nervous system now we said that normally thyroid
hormone increases sympathetic nervous system activity well we have less so that's going to
decrease sympathetic nervous system activity

so that can lead to depression you know because you're having a little bit more parasympathetic
drive in this situation. when you have less sympathetic drive it can lead to fatigue and it may even
lead to a very ambiguous term referred to as lethargy

thyroid hormone is also important for your memory circuits the pay circuit that we talked about
neuro and so because of that less thyroid hormone can have less activity within your your memory
circuits and so that may lead to some memory loss or deficits or mental dulling

if you will okay the next thing is if you have less thyroid hormone it affects your reflex pathways and
what happens is very something very interesting where when there's less thyroid hormone you can
test a deep tendon reflex and that decrease what happens is with decreased thyroid hormone their
deep tendon reflex will occur but it'll occur much more delayed than usual so they can have what's
called delayed deep tendon reflexes there's a particular name for this it's called waltman sign

okay all right that covers that the next one here is the gi tract remember we said it normally
increases gi motility and increases gi secretions but we have hypothyroidism so it's going to decrease
gm motility decrease gic creations if i don't move things through the gi tract as much it's going to
absorb more water absorb more of the electrolytes and become more hard and stiff what is that
going to do it's going to form a big old poop ball and that's going to cause constipation and no
nobody wants no constipation because guess what whenever you try to poop you're gonna end up
with hemorrhoids okay so constipation could also be another issue that can be seen with this all

next issue that you can start to see is that remember we said that this helps the muscles it plays a
role within muscle contraction and it plays a role within muscle growth and regeneration.

what if i don't have enough thyroid hormone is it going to grow as well is it going to be able to
regenerate whenever it's been stimulated or injured no and because of that due to decreased
muscle growth and regeneration this can lead to what type of effect here it can lead to myopathy
where there's damage to the muscle tissue whenever there's damage to the muscle tissue
particularly damage itself it can spill out a lot of a particular enzyme called creatinine kinase so
whenever there's significant amounts of myopathy or damage to the muscle tissue due to not being
able to grow it or not being able to regenerate it when it's injured it spills a lot of these ck out the
next thing is with progressive myopathy and injury to the muscles and not being able to regenerate
and grow what happens to them they become weak and so they develop weakness and you know
where this weakness is most commonly seen within the proximal muscle groups shoulder hip areas

okay the last thing i need you guys to remember is that it also is going to decrease muscle
contraction again can playing a role with that weakness not just because of the myopathy but also
decreased muscle contractions how it decreases the expression of what remember it maintains the
activity of calcium atp aces if we have less of that do we have as many calcium atps activity no so
there's decreased calcium atpase activity think about that as less calcium within the cell when you
need it if there's less calcium in the muscle cell you'll be able to contract the muscle cell as well no.
at least to decrease muscle contractions playing a role within proximal muscle weakness.

all right let's move on to the skin the skin what do we do normally it increases blood flow to the hair
the skin the nails and helps to play a role within sebum and sweat gland production if you have
decreased blood flow because you have hypothyroidism what happens with that well now with
decreased blood flow you're not providing as much oxygen and nutrients to the hair the skin the
nails there'll be hair loss and you know there's a particular area where they lose hair which is kind of
a buzz term kind of thing where they lose it on the outer third of the eyebrows it's called queens
Anne’s signs

the other thing is that you're not providing enough blood flow to the to the nails and so the nails can
become kind of brittle and thin right the other thing is that the skin is not getting enough blood flow
so the skin is not getting enough blood flow so it's gonna appear more dry as well so they're gonna
feel more pale actually because you're not getting a lot of blood flow and a little bit dry because
you're not having as much secretions right so that goes back to this next thing so we have the hair
skin nail effect but remember we have to think about it plays a role within sebum and sweat gland
production if there's decreased sebum production what does that lead to so decreased sebum
production is going to lead to a lot of dry skin and if you're going to have decreased sweating
because you're not having as much activity of those eccrine sweat glands as well

let's move on to the liver the liver remember what did a thyroid hormone do it it maintained the uh
receptors what type of receptors on the liver it maintained the activity of the ldl receptors that are
expressed on your liver to pull ldl from the blood if you have low thyroid hormone what's gonna
happen to the ldl receptors you guys already know right you're gonna drop the ldl receptors so now
these receptors are gone if you have ldl floating here through the blood and also another one is you
pull triglycerides into there's other things for triglycerides as well but if you're trying to have ldl
primarily ldl get pulled out of the blood and into the liver you need ldl receptors if you have less of
these ldl receptors are you going to pull as much ldl into the blood into the liver no so the ldl and
triglycerides will build up and you can develop hypercholesterolemia and hypertriglyceridemia okay
so that could be problematic

reproductive system. hypothyroidism can affect sex hormone-binding globulins okay so i want you to
remember reproductive effects from hypothyroidism is due to hyperprolactinemia, reproductive
effects from hyperthyroidism is due to the increased sex hormone binding globulins so with
hypothyroidism. here's what i want you to remember in hypothyroidism, thyroid gland say a primary
issue they are making less thyroid hormone the natural effect that we talked about before is that
this will go back to the hypothalamus, the hypothalamus will respond to this low thyroid hormone
and make a hormone called thyrotropin releasing hormone it'll make more of it that thyrotropin-
releasing hormone when you increase the production of it, it stimulates two cells in the anterior
pituitary one of them releases an increase in tsh because you need more tsh to try to drive this
thyroid hormone level up that's one effect all right so not only is there an increase in this tsh but
there's also an increase in prolactin whenever there's these higher than usual levels of that trh so
remember that elevated levels of tsh as well as elevated levels of prolactin what's the problem with
that whenever you have high levels of prolactin that loves to inhibit fsh and lh production when you
inhibit fsh in lh production you inhibit the production of testosterone and you inhibit the production
of estrogen that's very important why because in males what happens if you have very low
testosterone we're gonna put test there what would happen remember we need it for sperm
production if you don't have enough testosterone that leads to a decreased sperm production what
happens to the sex drive because it plays a role in sex drive there's a decreased sex drive also known
as a decrease in libido what else it's also important for masculinization of the male so because of
that decreased testosterone leads to decreased masculinization particularly within the breast tissue
and they develop little you know little moves called gynecomastia now these are the primary effects
right so you can see a decreased burn production you can see decreased sex drive you can see
gynecomastia if you want to remember one more it also plays a role within the activity of the so it
can lead to erectile dysfunction as well the next thing is what can this do within the females so
remember there's decreased estrogen production if there's decreased estrogen we need this in
order for ovulation to occur so if there's not enough there's decreased ovulation what happens if
there's decreased ovulation infertility because if you don't pop a little oocyte out there to be
fertilized by the sperm then you can't actually develop a a potential pregnancy so they can lead to
infertility it also is important for regulating your menstrual cycles maintaining the normalcy of
menstrual cycles if there's less of it that can lead to oligomenorrhea and if there is not enough at all
and it affects it to the point where you don't have any menstrual cycles this can lead to amenorrhea
one more thing whenever there's high prolactin levels not only can it cause exacerbate the
gynecomastia within males but it can also do something within females very interesting where it's
important for milk production we know that prolactin is important for milk production but
sometimes it can lead to inappropriate milk production within females and it can lead to milk actual
like being let out from the nipple and that's called galactoria galactoria so remember that issue as
well okay i think we really drilled home the reproductive effects let's take it home with the last one
which is this fibroblast activity now remember what i told you the thyroid hormone regulates the
activity of the fibroblast glycosaminoglycan production and degradation whenever there is low t3
and t4 there's still going to be some gag production but here's the problem so the gags will still be
produced but you know what happens the degradation of the gags are that's not going to happen so
what happens is this results in decreased degradation so the decreased degradation of gags and that
leads to what an increase in the amount of glycosaminoglycans why is that a problem whenever
there's a lot of glycosaminoglycans that pulls a lot of water to where the glycosaminoglycans are and
so if you pull a lot of water where there's a lot of glycosaminoglycans it can lead to that space being
a little bit more edematous where do we see these gags really accumulating particularly within the
body the first one is we see these gags accumulating in the dermis within the actual tibial region and
it pulls a lot of water into that area leading to a lot of edema where the tibia is and this is called pre-
tibial a mixed edema that's the first thing i want you guys to remember so pre-tibial max edema is
due to a lot of gags within the dermis because of less degradation of the gags because of
hypothyroidism and that causes edema there the next thing is it can also accumulate in the tissue
and the dermis around the eyes and as it does that that leads to a lot of water being pulled into
those tissues if you pull a lot of water into those tissues what's going to happen it's going to lead to
edema and this edema that's occurring around the eye is called periorbital edema all right beautiful
so we have pre-tibial mixed edema periorbital edema there's one last one this is actually probably
the coolest one the gags can also accumulate near the carpal tunnel and the tissues the connective
tissue and muscles around the carpal tunnel if that happens a lot of water gets pulled into the tissue
around the carpal tunnel if you pull a lot of water into there what's that going to do it's going to
cause edema and that edema around the muscles and fibrous tissue and tendons in that area is
going to become a little bit more edematous and put pressure on that little orange nerve that's
running through there you know what that is the median nerve and whenever you compress that
sucker it's called carpal tunnel syndrome and that could be due due to what an increase in gags
because they're not being degraded because of the hypothyroidism so again increasing gags because
of decreased degradation leads to pre-tibial maxidemia periorbital edema or carpal tunnel syndrome
we hit all of the clinical features let's go into the diagnostics all right beautiful now let's start talking
about the diagnosis of hypothyroidism the first thing that we need to talk about is is it primary
versus central that's the first question that we need to ask and this should be very easy we've
already kind of gone through this a little bit so the first thing is is it primary how do we determine if
it's primary or central the first thing that you need to remember is that you have to order what's
called thyroid function tests and with the thyroid function test comes two things free t4 is going to
be one of the things that you obtain and the second thing is going to be a tsh one other thing that
we may add on here for the simplicity of this diagnosis part is a trh we might add that one on okay
so let's talk about what would we get what would it look like with these three parameters versus
primary and central so if someone had primary so let's say that we have primary hypothyroidism low
t3 and low t4 in this situation here in this scenario we know that hypothyroidism all of these primary
versus central all of them are going to have low t4 right we know that so in this scenario here this
first scenario is we're going to see a low free t4 now if someone has a primary hypothyroidism
meaning it's a thyroid issue there's nothing wrong with the pituitary gland what should happen
negative feedback mechanism wise low free t4 should tell the anterior pituitary to do what it should
tell the anterior pituitary to make tsh and so response to that is it would stimulate the anterior
pituitary and the anterior pituitary would increase its production of tsh so if someone had primary
hypothyroidism they would have low free t4 and high tsh now let's take for example the central
causes the central causes you have to remember there was two types there was hypothalamus that
was one of the issues there was a hypothalamus lesion or there was a hypothalamus trauma or
something of that nature and then the other one was there a a pituitary issue so there was
something wrong with the pituitary how do we know which one it is again same concept here
they're both going to have a low free t4 so both of them will have a low free t4 because it's
hypothyroidism right generally if someone has a normal hypothalamus or a normal anterior pituitary
let's say hypothalamus first what would happen if they have low free t4 the hypothalamus it would
tell the hypothalamus hey you need to make trh so that you can tell the anterior pituitary to make
more tsh but the hypothalamus is not responding because there's something wrong with it so the
trh production is going to decrease it's not going to respond to the low free t4 and as a response to
that that's going to lead to decreased tsh and that decreased tsh is going to lead to a continuous low
free t4 okay so that's how we would determine hypothalamus low trh low tsh and low free t4 if
there's a pituitary problem that means that there's low free t4 again it would tell your hypothalamus
and your pituitary but generally you can also tell the pituitary and what happens is if there's low free
t4 the pituitary the anterior pituitary should respond and say okay hey you're telling me there's low-
free t4 i got you baby i'm going to go ahead and produce your tsh for you but there's a problem with
the pituitary if there's a problem with the pituitary it's not going to make the tsh it's going to cause a
decreased tsh production a decreased tsh production will continue to lead to low free t4 and again
the pituitary will still not respond and the tsh production will continue to drop so if you had to
differentiate primary they have high as they have low free t4 high tsh central if it's hypothalamic
they both have low free t4 but hypothalamus has low trh low tsh and pituitary would have low free
t4 and just low tsh what's another way that we could differentiate if it's hypothalamic or pituitary
once we've kind of gotten these lab values back and we find ah there's something wrong with either
the hypothalamus or the pituitary get an mri so obtain an mri and mri may be the thing that you
need to determine oh i see there's a tumor in the hypothalamus oh there's some hemorrhage near
the hypothalamus oh there's some infarction in the pituitary or there's some injuries to the pituitary
that may give us and clue us into really what's the problem okay all right now that we've gone
through this and we've determined oh all right we've figured out that it's actually central boom we
know how to go about that way but now we have primary and there was a ton of different types of
primary causes how do i know what the cause of the primary hypothyroidism hypothyroidism is the
way that we go about this is a couple different ways let's actually go through a couple of those and
write them down the first one is we said hashimoto's what is one way that we can determine
hashimoto's thyroiditis well one way is we could say all right more common to females that could
help epidemiologically but the next thing we should say is okay we remembered that they have
positive tpo and positive antithyroid globulin antibodies so i would have antibodies against tpo
antibodies and i would have thyroglobulin antibodies that would be one thing that would come back
positive the next thing is remember i told you that whenever there's injury to the thyroid gland what
leaks out from the fat between the follicles thyroglobulin so another thing is they could have
elevated serum thyroglobulin but there's one more thing if we wanted to take it to the next level
and really come up with a definitive diagnosis of hashimoto's the only particular definitive way is to
do a biopsy and to actually look at the tissue for the particular types of infiltration so biopsy would
be the definitive diagnosis okay all right so that's one way we could go about this another thing is
you could do the radioactive iodine uptake there's no need to but it would show low uptake or no
uptake okay the next thing that we set is postpartum thyroiditis so if someone has postpartum
thyroiditis what's going to be the issue with this one postpartum thyroiditis again we can take into
consideration their history right it's within uh less than one year since birth that could be one
particular thing again you can check the tpo antibodies and you can check the thyroglobulin
antibodies they'll be positive but what's the big thing i told you that you guys need to remember
with this condition usually they may have hypothyroidism but over time they may return to
euthyroid states it's acute not chronic in comparison to hashimoto's so it's acute and that means
that they may return to you thyroid all right beautiful the next one we said was drug induced this
again is another easy thing to figure how you want to know why hey buddy or hey ma'am what uh
you taking any medications like amiodarone or lithium or have you had any radioiodine ablation
therapies recently oh you have okay well this could be the reason why and so that's something that
we'd have to look at is look at their history so do they have a history of you know a use of
amiodarone lithium or have they had iodine 131 recently for radio iodine ablation that could be
reasons and again these are also injuring the thyroid gland so they may also have an elevated serum
thyroglobulin so we'll postpartum thyroiditis but again it's as simple as saying oh you're taking any of
these medications oh i see you are okay beautiful the next thing we said is renal thyroiditis renal
thyroiditis is actually a little bit more difficult to identify and there's something important that we
could actually use as key indicators that it could be renal thyroiditis so one thing that you'd have to
do is obviously this would produce a very that from that fibrous tissue that they have it can produce
a very hard hard and painless thyroid that's a very important thing i want you guys to remember
they're a very hard and painless thyroid but because they develop all this fibrous tissue around them
it can compress it can really compress some of the nearby structures and just be a big fibrous tissue
mess in that area what are some of the structures that are near the thyroid gland take it take it as
simple as possible compress what what if it compresses the esophagus because of that fibrous tissue
what can that lead to dysphagia so if they present with maybe a hard nodule with dysphagia or it
compresses onto the trachea what can that lead to maybe that leads to dyspnea difficulty breathing
maybe it compresses the recurrent laryngeal nerve that may lead to hoarseness so you see how they
may have compressive symptoms that are similar to actually like a tumor and so if they have a hard
kind of a painless nodule they have these compressive symptoms maybe thinking oh man i think
these guys have thyroid cancer and a plastic carcinoma made because that presents similarly the
only way that you can really determine that is that you'd actually have to go and you can check their
igg4 antibodies not that great of a test they may come back positive but the best way is to go in and
take a biopsy and once you biopsy you'll be able to determine is this cancer or is this just a lot of
fibrous tissue related to the retail thyroiditis okay all right the next thing that we need to do is we
need to test for that we need to think about sub-acute what if they have sub-acute granulomatous
thyroiditis so what else could they have sub-acute granulomatous thyroiditis how do i determine this
well they may present with a elevated esr remember i told you that that's one of the things that we
may see the other one is they may present with flu-like symptoms so they may present with muscle
aches joint eggs maybe a low-grade fever what else a painful and tender thyroid upon palpation
that's very very important okay so that's one of the ways that we can help to differentiate subacute
granulomatous thyroiditis from some of these other ones the next thing that you want to be thinking
about is what if this is an iodine issue it's simple check their iodine so is this an iodine deficiency okay
is this an iodine deficiency check the serum iodide okay or again take into consideration their area is
this an area that particularly iodine deficiency may be more endemic okay that may also be another
thing and again remember i told you that sometimes if you have too much iodine it can exert that
wolf chakov effect which can also cause a negative feedback inhibiting thyroid hormone synthesis
that's very short-lived it doesn't last very long so it's not something that you're going to see with a
chronic hypothyroidism so don't worry too much about that diagnosis but again low iodine simple
check the iodine okay after we've gone through this this has helped us to rule out particularly any of
the primary hypothyroidism one of the big things i really want you guys to talk about because you
see it a lot in medicine is that they can have associated conditions which may key you into the
hypothyroidism as well i really want to take a quick second to talk about that alright so what are
some of these associated conditions i want you guys to be thinking about we kind of talked about a
little bit of these later but some of the things that i want you to also be considering to order are
things that you may get tested on your boards it may not be just this picture-perfect diagnosis kind
of step-by-step process they may give you very little ambiguous symptoms clinical features and then
a couple kind of like abnormal labs and i really want you guys to interpret these labs and understand
what they're telling you with respect to hypothyroidism so remember one of the things that we said
is that whenever you have hypothyroidism and inhibits the ldl receptor uptake okay and so what
could that result in high ldls so be on the lookout when someone has high ldls within the blood or
high triglycerides in the blood and presenting with the clinical features of hypothyroidism again
something to think about not always truly diagnostic but something to think about the next thing is
remember we also said that whenever someone has significant hypothyroidism it damages the
muscle cells they don't regenerate they cause less muscle contraction and so because of that they
may have elevated creatinine kinase levels so that may also be something to think about okay when
you're having a person present with these clinical features the next one that i want you guys to
remember is that remember it decreases glycolysis glycogenolysis and lipolysis but there's one more
pathway that we didn't mention and this is another one it decreases [Music] gluconeogenesis this is
a big one and because of that if there's really low thyroid hormone levels this can result in decreased
glucose levels within the blood hypoglycemia so if someone also presents with hypoglycemia beyond
the alert for that the last thing i want you guys to remember here is that uh whenever there's
hypothyroidism right hypothyroidism there's a mechanism that we're look that's being looked into
that what happens is this may actually stimulate adh production and adh may increase water
reabsorption now if you increase water reabsorption what's the problem with that if it happens a lot
it may dilute the sodium that's actually in the blood if you dilute your sodium enough it can cause
what's called a hypotonic hyponatremia okay so sometimes you may also see a patient with a
hypotonic hyponatremia be on the alert for again someone with hypothyroidism okay so these are
some a couple of these associated things that i want you guys to be looking at that can add an aid in
the diagnosis of hypothyroidism but again not diagnostic like definitive diagnostics the next thing is
congenital hypothyroidism this will finish up for the diagnoses within 24 to 48 hours after a child is
born it's actually mandated by law that they test for congenital hypothyroidism and so one of the
things that they do is they check tsh so again within 24 to 48 hours post birth by law they have to
check a tsh okay now think about this without us even knowing if someone has congenital
hypothyroidism we said it was primarily an issue where the thyroid gland wasn't developing it was
being destroyed he didn't have enough iodine or the enzymes were all jacked up we're not making
thyroid hormone if there's low thyroid hormone but the pituitary is intact what would happen to the
tsh it would come back high so if you checked the tsh on a little baby and it came back high that's
making you think oh hypothyroidism how do i confirm what do i do order a free t4 and that free t4
would come back what low and that may key you into saying that this patient has hypo congenital
hypothyroidism along with the clinical features that we talked about as well with the seven ps okay
that keys up our entire diagnosis let's finish up with treatment and then a quick complication all right
so the next thing is hypothyroidism how do we treat it it's actually probably the easiest thing
possible give them thyroid hormone right so how do we do that there's a particular drug a synthetic
thyroid hormone which is called levo thyroxine and this is literally t4 it's literally synthetic t4 so
whenever you give someone levothyroxine what happens is that t4 that synthetic thyroid hormone
gets taken up into your target cells and then you remember what the mechanism is t4 has to get i uh
deionize remove an iodine and convert it into t3 and then t3 binds to an intracellular receptor
activates genes and increases the expressions of particular proteins that increase metabolic activity
exert all the physiological effects that we saw over there basically trying to reverse the
hypothyroidism that is the easiest concept you can also there is another drug and and you basically
can give t3 the uh leothyronine but it's not as effective as t4 levothyroxine so again this will be your
first line treatment what i really wanted to take a quick second to talk about because this is actually
more important than just knowing the drug is knowing how is this is this drug even effective you
might have am i giving them the right dosage am i giving them too much how do i know think about
this let's say that you have a patient here who you give t4 to right and let's take the two scenarios
here let's say that you actually have the first one which is you don't give enough of that thyroid
hormone if you don't give enough of the thyroid hormone what does that do to the pituitary gland
what was the response from that the pituitary gland should respond by doing what increasing the
tsh production telling the thyroid gland hey make more thyroid hormone if you can if you're giving
too much t4 too much levothyroxine then what would the problem be then this would tell the
anterior pituitary hey antipituitary too much of me you got to chill out bro decrease the tsh
production so let's say that you give someone levothyroxine but you give them too little they're
going to have a high tsh when you monitor to see hey is it this drug if i'm giving him too much is it
effective you get the person's lab back after they've been on the level their oxygen for a little bit the
tsh comes back high what does that mean i'm not giving them enough increase the dosage so that's
very important i want you guys to know that increase the dose of the free t4 or the thyroxine and
then recheck if they come back after they've been on the level thyroxine for a little bit and their tsh
is low that means that you're giving them too much what do you do drop the dose of the free t4 or
in this case the levothyroxine pretty straightforward pretty simple right not too bad the last thing i
need you guys to to know because it's very important for real life scenarios because a lot of people
could be on other medications that alter the t4 levels as well and so that's very important things that
are the most significant here is that let's say that somebody is on an oral contraceptive and that
contains a lot of estrogen in it if that's the case what this does is is it actually increases the
concentration of what's called thyroxine binding globulins what does that do that binds the t4 in this
case it binds more of the levothyroxine so let's say that you give them a dose of levothyroxine but
they're on this estrogen pill it's going to increase the amount of tbg which is going to decrease the
amount of circulating free t4 that means that even though you're giving them thyroid hormone this
estrogen may effectively lower the amount of circulating t4 so what we have to do sometimes in
someone who's on estrogen you may have to increase the dose so you may have to increase the
dose in these scenarios the last situation is another commonly given drug that's you know used a lot
is going to be corticosteroids corticosteroids these ones are very interesting you give these for tons
of reasons but one of the things that you need to think about is that it decreases the thyroxine
binding globulin and so what that will do is it will actually increase the amount of circulating free t4
or levothyroxine that's being delivered to the tissues if that's the case and i have too much free t4
what would i want to do i'd want to reduce the dose so in these situations i'd want to reduce the
dose these are just important little kilo things that you guys should know when you're talking about
treating someone and managing someone with hypothyroidism with levothyroxine let's finish up the
last conversation here with mixodemocoma all right so myxedemocoma is a very serious
complication from hypothyroidism and what i want you guys to take away from this is what are the
triggers what are the primary clinical features diagnosis we already talked about it and what's the
emergent treatment that you guys should know so what happens is the most common triggers for
someone with myxidemacoma is it is the same as actually for the most part the thyrotoxicosis and
that is infection so some type of underlying infection maybe it be sepsis or they've had some type of
surgery whether that be a thyroidal surgery or non-thyroidal surgery but that's a big trigger as well
as some type of trauma and there can be other reasons another common reason could be extreme
cold temperatures so extreme cold so here we'll throw that one out there extreme cold
temperatures okay you're out there shoveling snow for i don't know too long either way any of
these triggers what they do is they increase your sympathetic nervous system drive that's what they
want to do but remember what happens when you have low thyroid hormone what does it do to
your sympathetic system it decreases the sympathetic system activity so what happens is these
things want to increase your sympathetic drive but your thyroid hormone is saying uh-uh i'm going
to decrease the sympathetic drive so now what happens the sympathetic drive that you would
usually have to deal with these significant stressors is diminished it's gone and because of that the
hypothyroid effects are even more pronounced than usual what do i mean i remember the heart this
is the big one what did it do what would that that sympathetic effect on the uh the the heart
particularly what was it doing it was we were generally increasing beta 1 at genetic receptor
sensitivity if i super shut down the sympathetic drive what's going to happen i'm going to shut down
my heart rate really really bad right and this is going to lead to severe bradycardia i also can really
affect the pumping function of the heart and what happens is this remember we said that there was
a mild decrease in contractility due to a decreased beta adrenergic sensitivity if we have really really
high low levels of thyroid hormone that contractility drops a lot and that contractility can eventually
lead to a decreased cardiac output what happens with the decreased cardiac output decrease blood
pressure and so these patients may also go into shock so remember bradycardia shock or
hypotension the other thing is it decreases the sympathetic activity within the central nervous
system and that's a problematic issue as well because that can lead to altered mental status that can
lead to confusion that can lead to significant lethargy and eventually worst case scenario a coma
okay the last thing i need you to remember is remember say remember how it really our normal
thyroid hormone jacks up our metabolic activity well if we really shut down that sympathetic drive
and we really shut down the hypothyroidism issues we really have a really really low thyroid
hormone and a really low sympathetic drive that's going to significantly drop the metabolic activity
more than usual so the problem where cellular respiration is occurring so little that so little heat is
being produced and if so little heat is being produced by our cells what does that lead to with our
body temperature that's going to lead to severe hypothermia and that can be super problematic
right so what are the cardinal features of scene with this bradycardia hypotension or shock
confusion progressing to coma a significant hypothermia and with these underlying triggers okay
once you've gone through the same diagnostic steps as you would with someone who has
hypothyroidism in general without this complication and you come to the diagnosis you're going to
start treating them empirically and you're going to do this with iv substances the first one that you're
going to give is you want to give a bunch of t4 so the levothyroxine and you also give another drug
called the t3 leothyrone just so that you have an amplified effect of both of them in this severe
hypothyroid state the other thing that you're going to want to do is put a lot of fluids in them
because they could be hypotensive and their heart rate may be low and we just need to make sure
that we maintain a good blood volume in them as well and also fluids are also important when it
comes to people with hyponatremia we may want to give a little bit more salt in the fluids again not
getting too crazy here though the next thing that we want to give is sometimes severe
hypothyroidism like myxodemocoma can mimic someone with a concomitant adrenal insufficiency
and sometimes it's really hard to rule that out and so what we do is is we treat them initially the
same way as we would treat adrenal insufficiency until we've completely concluded that it's not
there so what do we give for adrenaline sufficiency we give iv hydrocortisone hydrocortisone until
we rule out adrenal failure and then after we've adrenal fail failure you can decrease the iv
hydrocortisone or discontinue it but again most important thing is ivt4t3 fluids iv hydrocortisone
until you rule out adrenal crisis or insufficiency that is the treatment of mexidemocoma and that
finishes our discussion on hypothyroidism