DIP Episode 440 - High Dose Dexamethasone (New USMLE Perspective)

All right, welcome. My name is divine. Welcome to today's episode of the Divine Intervention Podcasts. And this is actually going to be a really short episode. But it's something that I've seen so many people get wrong. And I just don't want many students to keep falling into this conundrum. So it's something I want to fix and fix today. So to this podcast is going to be titled the high-dose Dexamethasone Suppression Test. The high-dose Dexamethasone Suppression Test. I know some of you may be like, the divine command. I know about this. Cushing's disease and ectopic ac TH production. Boohoo. Don't talk to me. You're gonna see that there's actually a new angle that our friends at the endgame is take. Many resources either don't emphasize it or when they do, to be honest with you, many resources don't emphasize it. Or if people teach you they teach you wrong. So that's one thing I absolutely want to correct today. And again, if you're taking any of your USMEL exams, I have a step one review class that starts next week Thursday. And then I have a step two and step three review class, you know, biostatistics bootcamp, an MBA in testing and strategies class, and a social sciences quality improvement healthcare system and communications review taking place later this month. So if you're interested, shoot me an email through the website.

So, classically, people have learned the high-dose Dexamethasone Suppression Test as something that you do when a person is deemed to have an ac TH dependent cause of Cushing's syndrome, right? Because when a person has Cushing's syndrome, you can do one of three things. You can check the 24 hour urinary cortisol or you can check the lead night salivary cortisol or you can do a load those Dexamethasone Suppression Test and you'll notice that, wow, the next morning, the cortisol does not suppress. Do who? Okay. And then, so that's the usual algorithm people learn and then they go to step two, they're like, okay, let's measure ac TH to delineate between ac TH dependent Cushing's syndrome and ac TH dependent Cushing's syndrome. Obviously, if the ac TH is low, then you're like, oh, this is an ac TH independent cause of Cushing's syndrome. So it's like an adrenal adenoma that's pumping out a ton of cortisol. But if the ac TH is higher, you're like, oh, this is ac TH dependent. So the person's hypercord is all of them is being driven by increased ac TH production. And typically on exams, the thing you're trying to differentiate between in that case is a topic ac TH production from small cell lung cancer and Cushing's disease, which is a pituitary adenoma that's making a ton of ac TH.

And many people have learned that, oh, when you give high dose Dexamethasone, it will suppress the cortisol when a person has Cushing's disease, but it will not suppress the cortisol when a person has a topic ac TH production. And that is true. That makes perfect sense. Again, why does that make sense for people that are not very familiar with that? The reason that makes sense is the following. If you think about it, when a person has, when a person has like, you know, you have a normal anterior pituitary, a normal anterior pituitary should respond to low dose Dexamethasone. But when you obstig yourself to an adenoma, well, an adenoma just doesn't work as well as it should. Although an adenoma is not full blown cancer. So since it's an adenoma, you just need a little more Dexamethasone that is normal to whip it into shape. So that's why when you go with low dose Dexamethasone for Cushing's disease, it does not suppress the cortisol. When you try high dose Dexamethasone, it will suppress the cortisol. Now, another thing to also keep in mind is when you're dealing with small cell lung cancer, since it's cancer, it's not even an adenoma. It's like a full blown cancer. Full blown cancers don't really respond very well to normal signals. So even if you obstig the dose of Dexamethasone and give them a very high dose of Dexamethasone, it's not going to make any difference.

That's why in a topic, ACTH production from small cell lung cancer, you're going to notice that cortisol does not suppress. Okay, so that's the general knowledge that people have. I just thought I'll give a quick brief overview. Now, I want to establish something with Dexamethasone. Dexamethasone is not going to alter your cortisol response if your ACTH is already suppressed. I'll say that again. Dexamethasone will not alter your cortisol response if your ACTH is already suppressed. So as a corollary to that, the only time that Dexamethasone can affect your cortisol levels, especially high dose Dexamethasone, is when your ACTH is high at baseline before the study. I'll say that again, the only time high dose Dexamethasone will really affect your cortisol response is when your ACTH before the test is already high at baseline. Why am I saying this? Look at the name of the test. High dose Dexamethasone suppression. You're using high dose Dexamethasone to suppress something. So that means before you start the test, that thing is not suppressed. That thing is elevated. So with high dose Dexamethasone, you're only going to see anything if the ACTH is high at baseline. So with all this said, what is the new angle that our friends at the NBM is take? Well, the new angle is this angle of people having ACTH independent Cushing syndrome. When a person has ACTH independent Cushing syndrome, they have like an adrenaline at the normal, that is autonomously pumping out a ton of cortisol.

That cortisol is going to exert negative feedback on the hypothalamus and on the anterior pituitary. Your corticotropic relicin hormone is going to go down. Your ACTH is also going to go down as well. So your ACTH just by virtue of the pathology you have is going to be suppressed. I'll say that again. Your ACTH just by virtue of the pathology you have is going to be suppressed. So think about it. If your ACTH is already suppressed, is any change going to happen when you give high dose Dexamethasone? No. Because your ACTH, like the thing that Dexamethasone is supposed to suppress, is already suppressed. So there is not much that Dexamethasone can do in those circumstances. It's a subtle point, but it's a very important point to know for exams. It's a very important point that pops up a lot these days on exams. Many people screw this up. You don't have to be one of those people. You literally do not have to be one of those people. So again, please I'm begging, begging, begging you from the bottom of my heart. When a person has an adrenalinoma that is overproducing cortisol, aka they have an ACTH independent cause of their pushing syndrome. You need to know that those people, their cortisol will also not suppress with high dose Dexamethasone. So it doesn't matter what the dose of Dexamethasone is. Low dose Dexamethasone, high dose Dexamethasone, it literally does not matter. It literally does not matter. Those people's cortisol will not suppress. Why?

Because their ACTH at baseline is already suppressed. So there is literally nothing for high dose Dexamethasone or low dose Dexamethasone to suppress in the first place. That's very important. Like I'm telling you our friends at the USMEL is these days. They've been kind of throwing out questions where they'll say oh the person's cortisol does not suppress with low and high dose Dexamethasone. And one of the answers they'll throw in there in the question is they'll put small cell lung cancer. And then another answer they'll slot in in the question is adrenalinoma. And then the answer ends up being adrenalinoma. People are like how can be answered by adrenalinoma. No that's not possible. Yes it is possible. It is absolutely possible. So so people may be like okay divine. So if they give me a question where they say low and high dose Dexamethasone does not suppress the cortisol. What am I supposed to do? What am I supposed to do? The thing you're supposed to do is to either find the ACTH level in the question because obviously the ACTH will be low in in ACTH independent Cushing syndrome. And the ACTH is going to be high in an ACTH dependent Cushing syndrome. Alternatively the skin findings can be your clue. If the person has skin hyperpigmentation then that tells you that it's ACTH dependent Cushing syndrome. But if the person does not have skin hyperpigmentation that tells you that it's ACTH independent Cushing syndrome. Again why does that make any sense?

There isn't that makes any sense is that when you have ACTH dependent Cushing syndrome your ACTH is high. Well the thing is ACTH does not just fall out of the sky. No. ACTH is made from an ancestral molecule known as POMC. What is POMC stands for POMC stands for pro opiol melanocortin. Pro opiol melanocortin. So pro pro means is a precursor to something. Opio opio means opioid. In this case is betaendorphine which is a muagulis. Betaendorphine is one of the endogenous opioids we make in the brain. Remember the other endogenous opioids are like things like encephaline that work on delta receptors and the endorphine that works on copper receptors. But that's a step one concept also you know you see it on step two step three but anyhow but that's not the main focus so pro opiol melanocortin. Pro opiol opiol opioid that's betaendorphine melanoc that's MSH. Melanocystimulating hormone. Quartin that's ACTH. So whenever a person has high ACTH they're going to have skin hyperpigmentation. So if they give you a Cushing syndrome question and the person has skin hyperpigmentation that tells you right off the bat that this is an ACTH dependent cause of Cushing syndrome. It's an ACTH dependent cause of Cushing syndrome. ACT dependent so the ACTH is high so the MSH was behind so that's the same little melanocytes to give you that skin hyperpigmentation.

So again I'm going to go ahead and stop here please I am really really begging you this sounds like a benign podcast but I promise you it is not. I absolutely promise you this is not a benign podcast. So thank you for listening to me I'll see you in episode 441. Bye for now God bless you. Thank you. And by the way you know I also again offered to you during fall the US ML exams step one to three and I help with personal statements here as applications and whatnot and then I have these podcasts apps on my web I have this podcast on the podcast apps Spotify Google Apple and also have a You Tube channel. Dividing intervention US ML podcasts and videos and then also have a website divided intervention life lessons.com where post life lessons I post about two every week based on the Bible to help you address some life problems. So thank you. I'll see you next time. Bye for now again.

Skin hyperpigmentation, because high ACTH levels are derived from POMC, which also yields MSH (melanocyte-stimulating hormone).

Low/Suppressed, due to negative feedback exerted by the autonomously overproducing cortisol.

It only works if the ACTH is elevated at baseline; it cannot suppress cortisol if ACTH is already suppressed.

Ectopic ACTH production (e.g., SCLC) or Adreninoma (ACTH-independent).

POMC (Proopiomelanocortin), which yields both ACTH and MSH.

An ACTH-independent source, such as an adreninoma.

ACTH-dependent etiology (e.g., pituitary adenoma or ectopic source).

Because the high cortisol from the adenoma causes negative feedback, suppressing baseline ACTH levels, leaving nothing for dexamethasone to suppress.

Cushing's disease typically shows suppression with high dose dexamethasone; SCLC usually does not suppress at all.

POMC (Proopiomelanocortin).

Adreninoma (ACTH-independent cause).

ACTH-dependent etiology (e.g., pituitary adenoma or ectopic source).

Because the high cortisol from the adenoma causes negative feedback, suppressing baseline ACTH levels, leaving nothing for dexamethasone to suppress.

Cushing's disease typically shows suppression with high dose dexamethasone; SCLC usually does not suppress at all.

POMC (Proopiomelanocortin).

Adreninoma (ACTH-independent cause).