DIP Episode 466 - USMLE Step 2/3 Rapid Review Series 97

Okay, welcome. My name is Divine. This is episode 466 of the Divine Intervention podcast. Into these podcasts I'm going to be continuing the Rapid Review series for the US Emily step two, CK step three exam. This is going to be series 97. So what if they give you a question about a 35 year old female? They tell you that she has a history of diabetes and her A1 C has been poorly controlled despite the use of metformin and gliburite therapy. And then they mention that her current BMI is 30, right? Currently, MMI is 30 and the patient has been trying to lose weight and blah, blah, blah, blah, blah. And then they ask which of the following pharmacotherapeutic agents represents the most appropriate next step in management. I'll really hope you're saying, huh, Divine, you know what? Let's pick some kind of GLP1 agonist like Exenatide or Lyra Glutide. So I know so maybe like Exenatide Lyra Glutide, Divine, like what's the deal? So the thing is this is a GLP1 analogues. These drugs, if you've been around in medicine for any period of time, you can see why they matter these days. They're pretty, pretty important drugs. You know, if you've heard of the drug, you know what I'm going to reserve that comment. But there's a very popular drug. I'm sure you'll see everywhere online that there's marketers and drug to help you lose weight. Since GLP1 analog, many pharmaceutical companies are kind of pumping out these drugs because one, it's making a ton of profit.

And two, a lot of people are seeking after them. So, you know, people will always go after what makes the most money. So the thing is, this GLP1 adenis, why would they be a good idea for this person? Well, they're going to be a good idea for this person because one the person needs to lose weight and two the person has diabetes. But GLP1 analogues they are associated with weight loss, okay? They are associated with weight loss. That's actually pretty, pretty, pretty high-autonomous. So the representative drugs here are going to be drugs like exenatide or lyraglutide. The GLP1 agonis, basically how does GLP1 typically work? GLP1 typically works in the setting that you see a person. They are when you eat, even before the food hits your bloodstream, literally just as you're eating that food, it's almost like insulin is secreted in preparation for that. One of the major agents that controls that pre-insulin, like that early insulin secretion is GLP1. So it makes sense that if you give a drug that's an agonist of those GLP1 receptors, you can achieve that same effect. You can release insulin and that can help with the person's blood glucose levels. So that's how GLP1 agonists work. Now, honestly, if I almost had to postulate, this is me like completely thinking wildly here. So don't think this is some exam factor.

But I just kind of imagine that if these drugs can make you secret insulin, because normally the thing that makes you secret insulin with this GLP1 system is if you eat, but assuming you're taking these drugs, so it's making you secret insulin, getting all those insulin benefits, by using a drug instead of using food, that may actually be a linking to why some of these drugs we actually help with weak loss. Again, I'm completely postulate in here. Anyway, but the big thing I just want to say is that these drugs, they help you increase insulin production, they decrease the secretion of GLP1 agon, and they help with weak loss. That's kind of like the big, big, big thing. Now, what are some problems with these drugs that you kind of need to be aware of? You need to be aware that these drugs can absolutely cause acute pancreatitis. They can absolutely cause acute pancreatitis. And these drugs as well, they are contraindicated in people that have ME2. Well, why is that? The thing is these drugs are associated with the development of medallary thyroid cancer. So for president, it has like a family who's from medallary thyroid cancer, or they have some kind of genetic disease that might predispose them to medallary thyroid cancer. A GLP1 agonist is not a good idea. Honestly, the same rule applies to the DPP4 inhibitors. The dipeptidial peptidase 4 inhibitors. How in the world do these drugs work?

Well, these drugs, they kind of work like GLP1 agonists, but it basically prevents the breakdown of GLP1 because GLP1 itself is broken down by an enzyme known as dipeptidyl peptidase 4, DPP4, dipeptidyl peptidase 4. So if you inhibited dipeptidyl peptidase 4 with drugs like aloe-gliptine, lena-gliptine, saksag-leptine, seda-gleptine, or ending-gleptine, then you can potentially help with boosting the GLP1 levels, and that can be very, very helpful in these folks. So the only thing that I will say is that DPP4 inhibitors, right, so they can certainly cause pancreatitis. They are also contraindicated if you have like a history of MEN2 or medallary thyroid cancer. But these drugs are classically not associated with weight loss, okay? These drugs are classically not associated with weight loss. So your N-S-W-FU, this is actually something that, you know, you keep getting one information or the other from different resources. But I'm just going to tell you this right now, the diabetes drugs that are generally associated with weight loss are your GLP1 agonists and your S-G-L-T-2 inhibitors. Just remember you're one and you're two. Your GLP1 agonists or your GLP1 analogs are your S-G-L-T-2 inhibitors. Those are generally the diabetes drugs that are associated with weight loss. The ones that tend to be associated with weight gain, it's going to be your softener, your areas, your GLP2 side, your GLP2 right, your glimmer pride. And also your P-PAR, your, what are these drugs?

Your thyroid is only the endions, very good, your thyroid is only the endions, your thyroid is only the endions. These are P-PAR agonists, P-PAR agonists, right? Remember those drugs cause fluid retention because they are P-PAR agonists, they are receptors in the kidneys as well. And if you stimulate those receptors, it's going to cause you to literally retain fluid. Well, if you're retaining fluid, I would hope you kind of imagine that you're going to be beginning weight. I mean, think about it if you're fast. Within the first 20-fours, you see these dramatic first 24-48 hours, you see these dramatic weight loss. Well, what do you think that dramatic weight loss is? Is water weight that's gone, right? So if a drug is literally causing you to kind of pick up water weight, well, you're probably going to be heavy as a result of that kind of makes sense, right? And also insulin causes weight gain as well. Insulin literally causes weight gain. Insulin literally causes weight gain. Because if you think about it, insulin is a growth factor. Many people don't give you that benefit. But insulin is a growth factor. One is the almost thing of insulin as almost like pro-cort, like, you know, like how people that take steroids gain weight, insulin kind of does the same thing. Insulin is a growth factor. So because it's a growth factor, it can certainly cause a person to gain gain weight. Okay. So again, you see a person that's a diabetic and they need to lose weight.

A GLP1 analog is not a bad idea for those people. And SGLT2 inhibitor is also not a bad idea for those people. But if you have to pick between those two for a person that has diabetes and is trying to lose weight, go with a GLP1 analog. The reason why you go with an SGLT2 inhibitor is see, for example, a person has diabetes and they have heart failure. Heart failure, diabetes, SGLT2 inhibitors, good idea. Because SGLT2 inhibitors, they're actually one of the drugs that actually improves survival in heart failure. Right? Those drugs actually pretty, pretty, pretty beneficial. Okay. Now, what if they give you a question about a patient? They tell you that it's a, he's a 55 year old male and he has a history of polycontrol grades disease. And he comes to the emergency room. Actually, he's brought to the emergency room because he collapsed, you know, during like a soccer game. And they tell you, they give you a bunch of labs and you notice that, you know, his vital signs, his blood pressure is like 225 over like 150, some crazy high number. You see his heart rate is like 200 beats per minute. We see that this person is, they tell you they show you TSH, they tell you that it's completely undetectable and blah, blah, blah, blah. Well, what's going on there? It looks like same blah, it doesn't really matter whether we need details here or here or here. But what is going on here? Again, if the USM is wanted to be wise, what kinds of answers should they put?

Well, one answer that would be great to put is a few chromosituma. People fall for that long and hard, right? A feel, like, oh gee, blood pressure is really, really high. Well, a fear is not going to cause your TSH to be undetectable. It's kind of ridiculous. So going to scrub that out. Another bizarre idea, they mean kind of throwing theirs an answer choice. I'm just trying to play the USML game here with you. And that bizarre answer, they can throw it as an answer choices. It makes sense to put HOKEM as an answer, right? But HOKEM doesn't cause people to have these insane blood pressures. It doesn't cause people to have this insane heart rate, right? Doesn't really make sense. And it's kind of weird that we kind of wait till your age 55, first of all, to figure out that you have HOKEM. Come on, like that's a young person's problem, right? It just doesn't really make sense for HOKEM to be an answer in this circumstance. Another answer they can throw in here is going to be like a panic attack, right? You can see, let's just put panic attack as an answer, right? And when they put panic attack as an answer, some people will literally fall for that because they're like, wow, look at the suddenness of this person's symptoms. It is certainly not a panic attack, right? Because a panic attack is not going to cause TSH abnormalities, right? And again, it's really, really hard for you to have a panic attack and your systemable pressure is in the 200s. It's kind of ridiculous, right?

That's not something you usually see all the time, right? So again, just be wise with the USME Lies, right? Don't fall for these little things because you see people, I'm sure, you know, they, if they're right or right out of full vignettes, they'll probably see like one small thing that kind of agrees with some of these different answers that I've mentioned. And then they're like, oh, because I saw this one small thing, I'm going to pick that answer. No, that's an awful, awful way to take exams, right? So this person clearly has thyroid stored, right? We see the person has a serious disease, not well controlled, not a good idea. Now they're in thyroid storm. And whenever a person has like symptomatic thyroid toxicosis, like a thyroid storm, the first thing you always want to give those people is a beta blocker. That's the first thing you always want to give those people. You want to give a beta blocker. You want to give a beta blocker. Beta blockers, they pretty much serve two roles when you're dealing with a thyroid storm. The first is that the inhibitor ends, I'm known as a 5 prime diodeinis, a 5 prime diodeinis, a 5 prime diodeinis. By inhibiting that 5 prime diodeinis, you're preventing the peripheral conversion of T4, do T3. Remember, T3 is the very potent form of thyroid hormone. T4 is kind of like a wimpy form of thyroid hormone. So if you inhibite that conversion, you'll have more wimpy thyroid hormone, unless super potent thyroid hormone.

And that would probably be helpful for for the patient. That's the first thing. Now the second thing is that we know the thyroid hormone, one of the things it does is that it increases the number of beta one receptors that we find on the surfaces of myocardial cells. So if you give a beta blocker, you would pretty much block many of those beta one receptors. And that can help with bringing down some of those hyperagenergic symptoms that these people that have a thyroid storm have. Because again, I'm telling you that thyroid storm is not a good situation to be in. That thing actually has a pretty, pretty, pretty high mortality and morbidity. So this is one of those things you kind of want to be careful about. Actually, I think I've actually seen this once in clinical practice. This person was super, super, super unstable. So just be careful with stuff like that. Be careful with stuff like that. Be very, very careful with stuff like that. You're going to give a beta blocker. You can give per per on a low. But again, keep your ice peeled for all other kinds of beta blockers that you may put on the exam. They can put something like like Esmolol. For example, for thyroid storm, they can put something like Labidolol, for example, a thyroid storm. Just FYI, I want to keep those things at the back of your mind. So if a person is in thyroid storm, first give them a beta blocker.

And honestly, even if a person is not in thyroid storm, if a person has symptomatic thyroid toxicosis and it's acute, it's acute, look at that. It's acute. The first thing I want to give them is a beta blocker, to be honest with you. After giving them a beta blocker, so let's continue on treatment for thyroid storm, I've been giving a beta blocker. A second thing to give is P.T.U. Propyl-File Uralsil. Propyl-File Uralsil. Propyl-File Uralsil. This is actually a pretty good drug. It's an anti thyroid drug. How does it work? Well, it inhibits the enzyme known as thyroid peroxidys. Thyroid peroxidys is an extremely pretty much does almost every step of thyroid hormone synthesis. So P.T.U. won't help with inhibiting thyroid peroxidys. And remember, you make auto antibodies against thyroid peroxidys. In people that have Hashimoto's thyroid dietis, people that have Hashimoto's thyroid dietis. But we know that P.T.U. in Hittis-Tyropyroxidys, but it also has that extra job of inhibiting the 5 prime guiaidinis. That 5 prime guiaidinis I talked about that covers T4 to T3. Now remember, P.T.U. has a bunch of problems that he can cause. He can certainly cause agronolosaytosis. That's kind of a shared problem with a methemazole. That's the other anti thyroid drug that may be going to help you compare and contrast P.T.A. and methemazole. And he can also, you know, by causing that agronolosaytosis, he can pretty much give you an A-plastic anemia. And this drug is also very hepato-toxic.

So these are just all things you want to make sure that you know with P.T.U. Right? And also P.T.U. just like methemazole can also cause A-plasia cuties. It's a terrarogen. It can cause A-plasia cuties. It can cause A-plasia cuties. It can cause A-plasia cuties. Although to be honest with you, that A-plasia cuties problem. It's kind of something we want to worry about a little bit more with methemazole than P.T.U. Something we'll worry about a little more with methemazole than P.T.U. If you're kind of looking for like some very salient differences. I'm not saying P.T.U. is not a terrarogen, but methemazole is kind of a problem. In fact, if you're trying to look for a very good differentiating factor between P.T. and methemazole, in general, we like to use P.T.U. in the first trimester of pregnancy. For breast and really needs anti thyroid medication, the first trimester of pregnancy, P.T.U. is actually pretty good in that sense. But in the second and third trimester, we're going to pull out methemazole. The thing is, by the time you hit second trimester, you know, most of like the basic features, like the very very core embryology, don't get me wrong. The ton of stuff happens in the second and the third trimester, right? But the thing is that very early embryologic period is maybe not a good idea to expose a child to methemazole. So we'll use P.T.U. in the first trimester. Methemazole is something we go after more in the second and in the third trimester of pregnancy. Okay?

In the second and third trimester of pregnancy. So you're just going to keep those things at the back of your mind. But remember, unlike P.T.U. that can inhibit that 5-prime deiodinase. Methhemazole does not have that ability. Methhemazole does not inhibit the 5-prime deiodinase. It is only P.T.U. that does that. Okay? It is literally only P.T.U. that inhibits said 5-prime deiodinase. That's something you want to release for quality in your mind. So you don't get sold down the river on your exams. Okay? P.T.U. and give it 5-prime deiodinase. That's not using a thyroid storm. Methhemazole does not really do that. So we can use it in thyroid storm. But if you were to pick between P.T.U. or Methhemazole for thyroid storm on your exams, you absolutely should pick P.T.U. for thyroid storm. Do you remember what said P.T.U. is something you're going to give second? Now, what's the third thing you can give in a person that has thyroid storm? Well, one thing you can give these people is a super saturated solution of potassium iodide. You can give them SSKI, SSKI, a super saturated solution of potassium iodide. Oh, why in the world would that be a good idea? Well, the thing is, when you give that super saturated solution of potassium iodide, one of the things he can do is that he can pretty much inhibit the entry. He can pretty much inhibit thyroid hormone synthesis. He can pretty much inhibit thyroid hormone synthesis.

So you give this super saturated solution and that really, really helps. So you may wonder like, divine, but I thought we make thyroid hormone with iodine. For giving a bunch of iodine, is that not going to make us make a ton of a thyroid hormone? Not really. So let's kind of break it down. Well, there's this fancy thing in the thyroid gland known as the wolf chikof effect. In fact, the wolf chikof effect is almost like a kind of thyroid gland auto regulation. The thyroid gland actually has the ability to auto-regulate itself. It tries to keep thyroid hormone production almost like in some kind of informal hormone use thesis if you may. Basically, if you bring in a ton of, like just a large amount of thyroid of iodine all at once into the thyroid gland, that actually is going to inhibit the organification step of thyroid hormone synthesis. It pretty much inhibits and it's a transient effect inhibits the organification step of thyroid hormone synthesis. Okay? Of thyroid hormone synthesis. Of thyroid hormone synthesis. It inhibits that organification step and when you inhibit the organification step, that's going to cut down on the synthesis of thyroid hormone. Okay? Although you may be like, wow, divine, can I just keep spamming this thing? No, you cannot keep spamming it. Okay? It's a very short-term effect. But the thing is when the person has thyroid storm, they're going to be dying pretty soon if you do nothing.

So you can take advantage of that wolf chikof effect, the wolf chikof effect. It usually lasts right around 10 days. But the thing is, after a while, that spam is not going to work anymore. You're going to have to kind of break away. Your thyroid gland has to figure something else out. Okay? So after about 10 days, believe it or not, there's actually an escape phenomenon that happens from the wolf chikof effect. Okay? It's going to happen from the wolf chikof effect. So the thing is, if you keep inhibiting that organification step, after about 10 days, the thyroid gland will literally escape from that effect and you're going to resume the production of thyroid hormone. But obviously 10 days is a good enough time for a person to recover from this issue. And maybe if I want to throw in an extra tip bit of information for you here. And I promise maybe at the end, I'm going to go ahead and summarize this, this thyroid storm business because I've kind of taken different roads here. But again, taking those different roads is adding to your understanding. But the thing, I guess, to maybe keep in mind here is, if you think of a motor run because maybe a few kind of wonder, man, how can a motor run cause hypothyroidism, but also cause hyperthyroidism? Well, I'm going to explain the way a motor run causes hypothyroidism. It causes it by this wolf chikof phenomenon. Because a motor run literally has iodine.

I mean, literally look at the name, amyoderoan, amyoderoan, where do you think that iodine part of amyoderoan comes from? Well, it comes from iodine, it contains iodine. So again, transiently, transiently as a transient effect, you can have that inhibition of that organification step of thyroid hormone synthesis. And that can certainly suppress thyroid hormone production. So amyoderoan can cause hypothyroidism. The reverse effect is the Yodbizdal phenomenon. The Yodbizdal phenomenon is a phenomenon where you make a ton of thyroid hormone when you're exposed to iodine. Usually that happens in people that have like an iodine deficiency at baseline, right? So see, for example, a person has like an iodine deficiency and give them thyroid, you give them a bunch of iodine. The thyroid is like, ah, I've almost seen iodine for a long time. Oh, you better believe I'm going to be making a ton of thyroid hormone. So usually it's going to be in people that have like poor baseline thyroid function, right? You have like an iodine deficiency at baseline and then give them iodine and then the thyroid just goes absolutely berserk and makes a ton of thyroid hormone. Okay, that's the Yodbizdal phenomenon. So that's how iodine can cause both, I mean, amyoderoan can cause both hypothyroidism. It can cause hypothyroidism by the wolf chikof effect. It can cause hyperthyroidism by the Yodbizdal phenomenon. Right? So those are kind of big things to do.

And then the fourth thing you can give in thyroid storm. So remember, I said I'm going to summarize, I said that for precius thyroid storm, the first thing I'm going to give is some kind of beta blocker, especially something that has beta one blockade activity. You want to give those things. The second thing you want to give is PTU, propylthyl, uracil, propylthyl, uracil. The third thing you want to give is you want to give a super saturated solution of potassium iodide, a super saturated solution of potassium iodide. Super saturated solution of potassium iodide. Now, a fourth thing you can give is you can actually give steroids. The thing is believe it or not, people that have thyroid storm think about this logically. Fyroid storm, your body goes into like a hyper metabolic state, like a crazy, crazy, crazy, crazy, crazy state. Right? Your body is like firing on all cylinders. Well, the thing is when your body fires on that many cylinders, you can already begin to imagine that, maybe this can induce like a relative adrenaline sufficiency. Because think about it, right? You probably have a family out of this whole phenomenon of getting a stress dose of steroids. You see a person, they've been on steroids for like a long time, right? So, you know, their HP axis is kind of suppressed. But then they get like a bigger than normal metabolic stress. Let's see, they are on the going surgery or they get a very serious medical illness or they get in an accident for whatever reason.

Right? And then you see them, you see this, will you keep giving them pressures and they're not responding to said pressures? Well, guess what? There isn't another responding. It's because they've suppressed their HP axis. And yes, they've been taking their regular dose of steroids. But their body needs a little extra because a little extra metabolic stress has come to the body. That's why we give that stress dose of steroids. Well, the thing is when a person is a thyroid storm, the body goes under goals like just some very, very, very, very, just significant metabolic stress. And the body is like, man, I need more cortisol. Well, you can give that cortisol, you can give steroids in the setting of a thyroid storm, right? To help with that relative adrenal insufficiency. Adrenaline insufficiency has an association with thyroid storm. So again, just something to keep on the back of your mind as you study for these, for these exams. Okay, I think I'm going to go ahead and stop here. Again, it's a rapid review series. I don't want it going too long. Again, if you're interested, I go over review classes for step one, step two and step three. I have an, I have a 25-hour step one class, I have a 20-hour step two, step three class. I actually have that coming up from the 10th to the 14th of July. I have an MBME testicking strategies class on the 6th of July. That's for step one to step three. It's two and a half hour class. I have a bias that's class on the 7th of July.

It's from four to 8pm, Pacific Standard Time on the 7th. It's also over step one to step three. And then I have a five-hour social sciences, quality improvement, healthcare systems, ethics and communications course. It actually takes place on the 8th of July. It's a five-hour class, also, for step one to step three. Again, there's tons of people that have taken these classes. I found it to be just remarkably helpful. And then also a four-one-one tutoring for all the USMVL exams, for med school exams, for shelf exams. And then I have these podcasts on Apple, on Google, and on Spotify. And I have a You Tube channel, Divine Intervention, USMVL. Podcasts and videos. That's why I post the videos that I make. And then I also have another website called Divine Intervention Lifelessens.com. Many of you have probably heard me say a life lesson or two here and there during my podcast. So I'm probably like, man, the vineery love these your life lessons. So I said, literally, from a separate website, Divine Intervention Lifelessens.com. There's actually an Apple podcast, so shite with that. It's got the Divine Intervention Life Lessons podcast. From a biblical perspective, I address a life lesson. It posts like two podcasts every week. And I think I have almost 200 podcasts right now. So just head over there. I think it's something you can find to be very oblift in for your soul, think something you can find to be really, really helpful.

Now, the quick life lesson, do I want to plop on you guys today. It's just the importance of being a change agent. The importance of being a change agent. Wherever you go, just try to live it better than you met that place. You see some people when they're living in a place, people are like, I'm so glad this person is gone. You don't want that to be the kind of testimony that people have about you. When you leave, what are people still saying about you? Are they saying positives about you? Or are they saying negatives about you? What kind of testimony do you live in a place? Are you a change agent or you're an agent for evil? You don't want to be an agent for evil. You don't be an agent for good. You want people to still be saying, man, this person when they were here, they really turn things around. So wherever you are in your community, in your medical school, at your place of work, in your home, even in your home, in your home, don't be a toxic person, be a positive person. Be a person that brings good, not evil to a place. So I'll see you in episode 467. Have a wonderful rest of your day. Bye for now. God bless you. Thank you.

They help with weight loss AND they improve blood glucose control (diabetes management).

DPP-4 inhibitors.

Beta-blocker, Propylthiouracil (PTU), and Super Saturated Solution of Potassium Iodide (SSKI).

PTU inhibits 5'-deiodinase, preventing peripheral conversion of T4 to T3.

The Wolff-Chaikoff effect.

To counteract relative adrenal insufficiency caused by the massive metabolic stress of the hypermetabolic state.

SGLT2 inhibitors, because they are proven to improve survival in heart failure.

5'-deiodinase (which prevents T4 $\rightarrow$ T3 conversion).

GLP-1 receptor agonists or SGLT2 inhibitors.

Acute pancreatitis (and MEN2/medullary thyroid cancer risk for GLP-1 agonists).

First trimester; because it inhibits 5'-deiodinase.

The Jod-Basedow phenomenon.

SGLT2 inhibitors, because they are proven to improve survival in heart failure.

5'-deiodinase (which prevents T4 $\rightarrow$ T3 conversion).

GLP-1 receptor agonists or SGLT2 inhibitors.

Acute pancreatitis (and MEN2/medullary thyroid cancer risk for GLP-1 agonists).

First trimester; because it inhibits 5'-deiodinase.

The Jod-Basedow phenomenon.