Hey guys. Today we're going to talk about Grave's disease.
which is a form of hyperthyroidism.
But before we get into that,
I think it's important to briefly explain
how the thyroid hormones are made
maintained and how they effect our body.
So, what happens is that
the hypothalamus releases these hormones called;
the 'thyrotropin releasing hormone'
or TRH
which act on the anterior pituitary
and causing it to release these other hormones
called the 'thyroid stimulating hormones'
or TSH
which I'm drawing here as triangles.
The TSH will then bind to its receptors on the thyroid gland
regulating thyroid hormone production
by the follicular cells of the thyroid gland.
T4 and T3 are the two forms of thyroid hormones
T3 being the more active form
and it is made in less quantity than T4
but T4 can get converted into T3
in the target tissues,
which is important to know
since there is a medication, which we will talk about
that inhibits this conversion.
Now, once we have enough thyroid hormones
meaning that there is a normal level of
thyroid hormones in our body
there will be a negative feedback on the hypothalamus.
This will lead to inhibition of the release of TRH
which then leads to inhibition of the release of TSH
and therefore, decrease production of thyroid hormones.
The thyroid hormones can pretty much affect our entire body
They can help with bone growth
neurons and CNS maturation,
they can work on the heart by stimulating the Beta-1 receptors
effecting the cardiac output,
the heart rate, stroke volume and contractility.
They can effect the respiratory rate,
body temperature,
and basal metabolic rate.
They can also lead to glycogenolysis
lipolysis and gluconeogenesis.
Now in case of Grave's disease,
which is an autoimmune, type 2 hypersensitivity reaction
The body forms these antibodies
called the 'thyroid stimulating immunoglobulins'
which mimic the 'thyroid stimulating hormones'
and bind to their receptors
and activate the secretion of T4 and T3.
Now, we're still going to have the negative feedback
on the hypothalamus.
leading to inhibition of the release of TRH and TSH.
This is very important to know because the levels of TSH
are one of the main diagnostic tests
that we measure in patients suspected of
any form of hyperthyroidism
including Grave's disease.
The reason that we don't measure the TRH levels
is due to the fact that it also causes
the anterior pituitary
to release other hormones
such as 'prolactin'.
Therefore it is not very diagnostic.
So, everything that we talked about
as far as the effects of thyroid hormone goes in our body
will increase in case of Grave's disease
leading to many different signs and symptoms
throughout the body, which includes;
bone loss,
psychosis,
mania,
agitation,
insomnia,
tremor,
excessive sweating,
heat intolerance,
weight loss despite increase in appetite,
diarrhea,
fine hair and hair loss,
palpitation,
arrhythmias such as atrial fibrillation,
and muscle weakness
due to inflammation of different muscles.
We can also see exophthalmus
or proptosis
which is the bulging out of the eyes
due to inflammation of the eye muscles
which can present either as unilateral or bilateral.
We can also see goiter
which is the enlargement of the thyroid gland
as well as 'pretibial myxedema'
which is a waxy, discolored induration of the skin
due to inflammation.
Which has an incidence rate of about,
1 to 5% in patient's with Grave's disease.
Now, what do we see in the lab findings?
Well, we're obviously going to see an increase in thyroid hormones
as well as a decrease in TSH levels.
But, what's really important
is the diffuse increase in the radioactive iodine uptake
as shown in the picture
which allows us to differentiate Grave's disease
from other forms of hyperthyroidism.
The other causes of hyperthyroidism includes;
Subacute thyroiditis, which tends to be painful
Silent thyroiditis, which tends to be painless
Thyroid adenoma also known as toxic adenoma
which is a benign tumor of the thyroid gland
Exogenous thyroid hormones,
which can be seen in some individuals, who are trying to lose weight
but end up taking too much thyroid hormones.
as well as pituitary adenoma, which is a tumor of the pituitary gland.
Now, when we compare all these together
we can see that they all present with 'low' TSH levels
except for pituitary adenoma
which actually increases the release of TSH
and therefore increases the thyroid hormone production.
But like I just mentioned the only thing that is different
is the diffuse increase in radioactive iodine uptake in Grave's disease
compared to the others.
We don't use this test in pituitary adenoma,
since the problem is not due to the thyroid gland.
Instead we can use MRI in patients who are suspected of having pituitary adenoma.
So there are different ways for treating Grave's disease.
One way is, 'propranolol',
which is a Beta-blocker
that inhibits the conversion of T4 to its more active form, which is T3.
It can also be used to treat tachycardia.
Another way to treat Grave's disease,
is by using PTU or Methimazole
which both inhibit the production of thyroid hormones.
Whats important to know, is that PTU can also be used in pregnancy.
One of the biggest side effect of these two drugs is
agranulocytosis, which causes the reduction of WBCs
and makes the patient more prone to infections as well as the opportunistic infections
So you have to make sure to check the patient's WBC count every few weeks.
and stop the medication if you see a decrease in WBC levels.
We can also use Radioiodine,
which is the most cost effective and the best longterm management
as well as the permanent cure for Grave's disease
The major side effect of radioiodine is, hypothyroidism,
since it destroys the entire thyroid gland.
Surgery is rarely done, unless the large goiter compresses the trachea
preventing the patient from breathing.
Or, if there is a suspicious nodule,
or the patient is suspected of having cancer.
Some of the side effects of the surgery includes;
damage to the recurrent laryngeal nerve
which controls the voice box, and can lead to hoarseness or voice loss.
And hypoparathyroidism
since the parathyroid glands are located
on the posterior aspect of the thyroid gland.
Therefore removing them can lead to hypocalcemia.
To treat the eye manifestation of the Grave's disease,
we can use lubricant eye drops or NSAID eye drops
in the mild form of the disease
and if the manifestations are very severe,
we can use steroids or do orbital decompression.