hello in this video we're going to talk
about Graves disease this is an overview
and introduction Graves disease is the
most common cause of hyperthyroidism
which is essentially the thyroid gland
working on overdrive producing a lot of
thyroid hormones and Graves disease is a
syndrome that may consist of
hyperthyroidism gorta optimal path II
and occasionally droppeth II which is a
skin disease associated with the
overactive thyroid gland in order to
understand Graves disease it is
important to learn or recap the anatomy
and physiology of the thyroid gland and
it's hormones as well as the
hypothalamic pituitary thyroid axis so
here is the brain important structures
to note in the brain is the hypothalamus
and below the hypothalamus is the
pituitary gland which actually consists
of two lobes the anterior and posterior
lobes but here we will mainly focus on
the anterior lobe here I'm drawing the
circulation which is the blood and the
most important organ in the story is a
thyroid gland the thyroid gland sits on
the trachea the tracheal rings right
below the larynx and here again is a
circulation the blood so the
hypothalamus in the brain secretes
thyroid releasing hormone or T or H
which will stimulate the anterior
pituitary to secrete thyroid stimulating
hormone or TSH for short
TSH will travel in circulation and
target the thyroid gland the thyroid
gland has receptors for TSH the binding
of TSH to the TSH receptor on the
thyroid gland will stimulate the thyroid
gland to produce and secrete thyroid
hormones and it will secrete thyroid
hormones into circulation
hormones are t3 and t4 t3 and t4 are
carried in circulation in the blood via
proteins thyroid binding protein an
increase in t3 and t4 in circulation
will have a negative feedback on the
hypothalamus on the brain and the
negative feedback will tell the
hypothalamus to stop producing T RH and
thus TSH to reduce the thyroid hormone
production when we already have enough
in circulation so what does t3 and t4 do
well t3 and t4 are lipid soluble and so
when they're at the target cell or
target organ they simply detach from the
thyroid binding protein and move inside
the cell t4 will get converted to t3
because t3 is the more potent one you
can say it's the more effective one and
so t3 is actually also known as triad
o'the irony but let's just call it t3 t3
will bind onto thyroid hormone receptors
within the nucleus where it will
stimulate transcription or it will tell
the DNA to make things that will result
in production of proteins enzymes all
these things that will cause an increase
in metabolic rate metabolic activity as
well as increase sympathetic activity
and growth and development Graves
disease is where there is elevation of
the thyroid hormones t3 and t4 an
increase in t3 and t4 in circulation and
the effects of these is called
hyperthyroidism a Graves disease is not
the only cause of hyperthyroidism there
are other causes of hyperthyroidism
which include pituitary adenomas which
can cause more thyroid stimulating
hormone TSH being produced by the
anterior pituitary gland more TSH means
more stimulation to the thyroid gland to
secrete t3 and t4
thurid medication is also another cause
meaning fired hormone analogues can of
course cause hyperthyroidism iodine and
amiodarone can cause or induce
hyperthyroidism thyroid adenoma
specifically toxic thyroid adenoma can
cause more thyroid hormones being
produced which then will cause
hyperthyroidism
similarly toxic multinodular goiter can
cause hyperthyroidism it's really
important to understand that the use of
the word toxic really means that it's
cause more things are being produced
it's and thus it's more toxic so toxic
in this case means more overproduction
of thyroid hormones have the physiology
of Graves disease again here is the
brain here we have the hypothalamus and
the anterior pituitary gland here is a
thyroid gland and the circulation on the
thyroid gland we have the receptor the
TSH receptor in Graves disease there are
auto antibodies being produced what I
mean by OTO antibody are antibodies
against our self the main auto
antibodies are the antibodies which
basically mimic thyroid stimulating
hormone so these antibodies will target
thyroid stimulating hormone receptors
the binding of the thyroid stimulating
hormone receptors by these Auto
antibodies will actually stimulate the
thyroid gland to produce more thyroid
hormones t3 and t4 the increase in t3
and t4 of course will cause a negative
feedback to the hypothalamus to tell it
to stop making trh and TSH because we
already have enough t3 and t4
but regardless of the decrease in TSH
the thyroid stimulating hormone receptor
Oh two antibodies will still exist and
so we'll keep telling the thyroid gland
to produce more thyroid hormones this
means that there are a lot of thyroid
hormones in circulation and so there's
over activity of the thyroid hormones
causing hyperthyroidism
in Graves disease the main antibodies
are the thyroid stimulating hormone
receptor or two antibodies
however there are other antibodies such
as thyroglobulin or Auto antibodies and
thyroid peroxidase antibodies or TPO
antibodies but these are less common in
Graves disease
on a sidenote thyroid peroxidase
antibodies are more often seen in
hypothyroidism particularly Hashimoto's
disease the next question to ask is
where do these antibodies come from well
like most autoimmune diseases there is
no exact pinpoint cause rather it is
postulated that many factors cause
inappropriate or abnormal activation of
immune cells against the thyroid gland
within the lymph nodes cells called
antigen presenting cells normally
activate naive t-cells in situations
where there is an infection or when the
body is in trouble the antigen
presenting cell in this scenario may
present thyroid stimulating hormone
receptor like antigen and this will
activate the naive T cell within the
lymph node the activated t cell can then
activate B cells the T cells will tell
the B cells to become another cell
called a plasma cell and it becomes a
plasma cell so that it can produce
antibodies against the antigen plasma
cells are the cells that secrete and
produce antibodies and so in this
scenario thyroid stimulating hormone
receptor Auto antibodies are produced
but instead of damaging the thyroid
stimulating hormone receptor it actually
stimulates it and acts similar to a
thyroid stimulating hormone the thyroid
stimulating hormone receptor Auto
antibody produced are not very specific
meaning that they most often bind to
thyroid stimulating hormone
but there are third stimulating hormone
like receptors all around our body
particularly the eyes and the legs and
so the thyroid stimulating hormone
receptor OTO antibodies can cross react
with other parts of the body such as it
can cross react with things in the eyes
leading to up the mapa the-- or
cross-react with skin causing demography
pathology of Graves disease after some
time there are some notable changes seen
in the thyroid gland of patients with
Graves disease so normally the thyroid
gland are made up of follicular cells
which form the inner colloid where
thyroid hormones are produced in Graves
disease the follicular cells become
packed and squeezed together becoming
tall cells this then subsequently causes
a scant colloid further in Graves
disease there are presence of
lymphocytes so there's a lymphocytic
infiltration the risk factors for Graves
disease include female gender family
history infection leading to thyroiditis
which is inflammation of the thyroid
gland stress is also risk factor as well
as smoking and amiodarone now remember
that Graves disease is hyperthyroidism
and is characterized by increase in
metabolic rate and increase in
sympathetic activity and so now let us
look at the signs and symptoms of Graves
disease the clinical presentation can
include hyperactivity irritability
insomnia sweating heat intolerance
fatigue weakness graves ophthalmopathy
feeling thirsty dis near palpitation
weightloss Allah Gherman area
amenorrhea decreased libido and symptoms
of Graves
de mapa thei clinical examination or
clinical findings can include patient
being anxious and irritable presence of
goiter abdullah petha hair loss presence
of congestive heart failure tachycardia
or atrial fibrillation patient might
have a fine tremor that can be increased
in bowel sounds that can be uncle Isis
essentially clubbing hyperreflexia and
also presence of Graves droppeth II the
investigations with someone with
suspected Graves disease again just
recapping here's the brain the
hypothalamus and the anterior pituitary
gland which produces thyroid stimulating
hormone or TSH the thyroid gland has the
thyroid stimulating hormone receptor in
Graves disease there are presence of
antibodies Auto antibodies so an
investigation is to check serum thyroid
stimulating hormone which will show a
decrease Bloods may also show presence
of thyroid stimulating hormone receptor
Auto antibodies another investigation is
a thyroid ultrasound which can look at
the thyroid architecture and structure
to see any signs of other causes of
hyperthyroidism such as toxic thyroid
adenoma or toxic multinodular goiter the
most important investigation is to check
Thurid function which will show an
increase in t3 and t4 levels
a fire it's can such as sinter scanning
is an investigation where iodine dye is
injected into the bloodstream in a
normal thyroid iodine is taken up by the
thyroid gland and so we can see
distribution of iodine uptake in the
thyroid because the iodine is tagged
however in Graves disease there is a big
increase in iodine uptake by the thyroid
gland because the thyroid gland is
working on overdrive it is producing a
lot of hormones management the
management of Graves disease can be
divided into pharmacological radio
iodine therapy and surgery
pharmacological or pharmaceutical
therapy include the use of anti-thyroid
drugs such as Co mind the mechanism of
action of theö MI it basically inhibits
the enzyme thyroid peroxidase which
normally helps in the synthesis of t3
and t4 and so inhibiting thyroid
peroxidase or TPO will decrease t3 and
t4 fired hormone levels ena blockers is
also another form of pharmacological
management and the mechanism of action
is to decrease the sympathetic activity
by blocking the beta adrenergic
receptors beta blockers are given
because we see signs of heightened
sympathetic activity in Graves disease
just tachycardia radioiodine therapy is
the second management for Graves disease
and it is used for people who don't want
to take medication or want something
alternative then surgery or medication
essentially in radioiodine therapy a
radioactive iodine is taken either via
liquid or pill the iodine taken is
radioactive and so naturally decays to
xenon when it decays it emits energy
which theoretically destroys the
surrounding thyroid tissue
thus the destroyed thyroid tissue will
decrease thyroid hormone production
surgery is a third type of management
for Graves disease and for people who do
not want radioiodine therapy and where
medication is not useful or is
ineffective
the surgery is thyroidectomy which is
removal of the thyroid gland and this
can be partial or total thyroidectomy
complications of Graves disease include
congestive heart failure atrial
fibrillation decrease in bone density
leading to osteoporosis graves
ophthalmopathy complications include
blurry vision and Graves droppeth II the
complication of this in severe cases is
elephantitis ramappa thee finally it is
important to know the complications
associated with thyroidectomy such as a
laceration to the laryngeal nerves
internal bleeding infection post-surgery
and accidentally removing the
parathyroid gland which actually sits on
the thyroid gland
you