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Graves Disease - Overview (causes, pathophysiology, investigations and treatment)

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