00:01
Alright, let’s move on to the hyperthyroidism part of our graphic here.
00:07
We have several different medications in this group.
00:10
We have the thioamides, the iodides, the beta-blockers and radioactive iodine.
00:14
I'm going to go through each of them just to give you a taste
of what we’re talking about but first let’s talk about how thyroid gets put into the cell.
00:22
You start off with an iodide ion which gets transported into the thyroid gland
where it undergoes peroxidation.
00:30
This gets incorporated into thyroglobulin, thyroglobulin then takes this mono-iodinated thyroglobulin
or di-iodinated thyroglobulin or T3 or T4 and undergoes proteolysis,
it removes the protein and you have a free T3 or free T4 released into the blood stream.
00:52
There is peripheral conversion in the peripheral tissues as well from T4 to T3.
00:59
That can be inhibited by things like radiocontrast media, beta-blockers, corticosteroids and amiodarone.
01:06
In terms of the entry into the cell that can be affected by your organic ions.
01:12
You can also have iodides and thioamides affect your peroxiadase,
you can have iodides affect the proteolysis and all of these medications
can combine to effect the way that iodide and iodine is being used to create T3 and T4.
01:29
The thioamides are probably the most commonly used drugs in the treatment hyperthyroidism.
01:35
These include two to of the major drugs that we use in clinical practice,
methimazole and propythiouracil or PTU.
01:43
These are sulfur containing thioamides so there may be an allergic concern in patients
who have allergy to sulfa.
01:50
There’s a slow onset of activity of these drugs, they may take three to four weeks for full effect
but you can see some activity in the first day. It is very, very effective in young patients.
02:00
The side effects include agranulocytosis so you have to keep an eye on the patients CBC and liver inflammation
so keep an eye, both clinically with physical exams
and with blood work looking at their liver function tests when you initiate these medications.
02:17
Let’s start with methimazole also called Tapazole in sort of the real world,
it inhibits the thyroperoxidase so this inhibits the conversation of iodide to I2.
02:32
The interactions include the anticoagulants like warfarin so if your patients are on warfarin you have to monitor the INR.
02:39
It can also interact with digoxin and it can interact with the respiratory drug theophylline.
02:45
The major side effects that we are concerned about with methimazole
as I said before is agranulocytosis and thrombocytopenia,
so again you have to monitor the complete blood counts on these patients.
02:56
It’s important that you avoid this drug in pregnant patients.
02:59
Pregnant patients can have infants who develop choanal atresia.
03:03
They can also have what’s called aplasia cutis and aplasia cutis congenita,
so you have here an image on the screen that shows a patient, a baby,
with aplasia cutis congenita where there is not development of the proper hair follicles.
03:20
Finally, you can get prenatal goiter so it’s important to watch these patients closely,
make sure that they're not on methimazole and take them off as soon as you find out.
03:29
So how does it work?
The mechanism of action is very similar to methimazole,
it inhibits the thyroid peroxidase it also does something else, it inhibits T5D
which is an enzyme that converts T4 to T3.
03:44
The pharmacokinetics are quite simple, there is oral administration that peaks in about an hour.
03:50
the euthyroid status however may take up to a month to achieve.
03:54
It has a very bitter taste so a lot of people don’t like this particular pill.
03:59
It is given every 8-12 hours. Most of my patients take this medication twice a day.
04:05
In terms of its uses it’s used in the treatment of hyperthyroidism, it’s used in toxic multinodular goiter,
it’s used in Grave’s disease and it’s also used in thyrotoxic crisis.
04:19
Now when you have a patient in thyrotoxic crisis and you're given a choice
between PTU and methimazole, I would choose the PTU.
04:27
The side effects of the medication include agranulocytosis so we should be looking out for this
and this can occur far out after initiation so you should not only check your blood work
after a month but you should be checking three and six months as well.
04:42
Liver toxicity is always a concern with this medication and this medication
has been associated with rare but potentially fatal cases of fulminant hepatic failure.
04:54
The next group of drugs I wanna talk about are the iodide salts.
04:58
This iodide salts inhibit the iodination of tyrosine.
05:03
They inhibit thyroid release as well and they cause a decrease vascularity of the thyroid itself.
05:10
It is relatively rapid onset of action and you can have an activity that is significant
between two and seven days after the initiation of therapy.
05:20
So what are the side effects of iodide salts? Well, they include a rash, drug fever, anaphylaxis.
05:27
They can have metallic taste when you ingest them
and they also can be associated with some bleeding disorders.
05:33
Iodide salts can have something called the escape, so the thyroid can escape the block of iodide salts
after about three weeks so be very wary that just
because you started the patient on this medication
and they’ve had response in the first seven days that you don’t need to check up on them three or four weeks later.
05:52
In terms of our uses of this drug, this is why we only limit it to short term treatment of thyroid storm,
we don’t use this for long term treatment because of escape.
06:02
Now, listen, this is a great exam question, I want you to learn this slide really well.
06:08
Escape, iodide salts, short term three weeks, exam question.
06:16
Now let’s talk about radioactive iodine. So radioactive iodine is radiated and it’s 131I.
06:23
It’s avidly taken up by the thyroid and we have used it for imaging studies
like this nuclear medicine scan of the thyroid so you can see how well it’s taken up.
06:34
But here’s the other thing, that radioactive iodine gets taken up into the thyroid gland
and actually destroys the tissue because of its radioactivity and if you think about it,
if you dose 131I correctly, you can actually treat goiter and hyperthyroidism
with this imaging drug which is kind of interesting.
06:56
Never use this product in pregnant patients and never use it in nursing women
because this 131I can go into the fetal or baby circulation and kill their thyroid
so that is very important, we do not use this in pregnancy or nursing mothers.
07:14
Now, this is another questions that we see every single year on every exam
that I have ever written for and in fact for the Canadian Internal Medicine exams,
I wrote a few questions and my questions were on pregnancy
and 131I usage so I actually physically have written questions for exams on this very topic so know this quote,
“You never give 131I to pregnant patients or to breast feeding woman.”
Let’s move on to the anion inhibitors and these were kind of similar to the iodide salts.
07:49
These are drugs like thiocyanate or perchlorate, these are ions so they have a charge
and they block the uptake of iodide.
07:58
They are competitive inhibitors of the iodide transporter and they have unpredictable effectiveness.
08:04
These are one of the first agents that we had used, so some very smart chemist had figured
that this would be a good way to treat it and it was but now we have better drugs.
08:14
Side effects include aplastic anemia and for this and other reasons
it really isn’t used much anymore but it is an important set of drugs to know.
08:24
Let’s move on to a question. Let’s do a case study.
08:27
A 30-year-old woman has a history of hyperthyroidism and was placed on methimazole.
08:32
She is now pregnant. The following is the most reasonable course of action.
08:37
A, discontinue the methimazole start her on propylthiouracil and reassess at the end of the first trimester.
08:45
Continue the methimazole, PTU is contraindicated in pregnancy
and can cause aplasia cutis congenita. C, discontinue the methimazole and start her on 131I therapy;
and D, discontinue the methimazole and start her in on thiocyanate.
09:03
What's the right answer?
So the correct answer is A, discotinue the methimazole start her on propylthiouracil
and reassess her at the end of the first trimester, I think that’s an entirely reasonable answer.
09:20
You may argue that you wanna check her sooner than that but that would be splitting hairs.
09:26
The more important is -- what’s more important is that the other ones are really wrong.
09:31
B is wrong - continue the methimazole, no - PTU is contraindicated in pregnancy
and can cause aplasia cutis congenital - no.
09:40
PTU is not associated with ACC, it is methimazole that is associated with that and it can cause hair deformities
and scalp deformities in babies.
09:52
It can also be associated with choanal atresia. C, discontinue the methimazole,
treat her with 131I therapy.
10:01
Okay, if you chose that I’m going to come through the screen and kill you right now
because that is not what you should be doing. Remember, 131I therapy, pregnancy do not match,
do not come together, same goes with lactation.
10:15
D, discontinue the methimazole and treat her with another agent called thiocyanate, no.
10:22
That’s not the correct answer so definitely the correct answer is A.
10:26
Okay, hopefully that answered some of you questions on thyroid.
10:30
I know you’ve been looking forward to this lecture.
10:32
I feel very confident that you understand the material,
I feel very confident that you’re not gonna use 131I in pregnancy so go write your exams,
go make me proud and show them what you know.