DIP Episode 191 - Updated USMLE Step 1 Endocrine Review Series 1 (Adrenals)

Okay, welcome. My name is Devine. I'm a resident. This is episode 191 of the Divine Intervention Podcast. And in this podcast I'm going to be studying a comprehensive review series of endocrinology for the USM Lista 1 exam. And one focus I'll have over the next couple of days is also to finish up the podcast I have for like the other USM Lista 1 relief ed subjects. So like finish up the one for gastroenterology, finish up the one for pulmonology, finish up the one for cardio. That will kind of be my big focus. And for those of you that are listening to my podcast remember that I have complete material for Reno, I have complete material for he monk, I have complete material for bio for metabolism, right? So I have complete material for all of the pharmacology that's present in first week, pretty much. So you know I've covered a lot of the material. I have fairly complete material for micro as well. So I mean those are things you're interested in again, please feel free to consult the website and you find a lot of useful information there. And hopefully like in the very near future, I will just make a topic list that people can just refer to like if I'm studying for this exam, for this subject, this is the podcast that applicable on dinner, I'll try to have it be something that can be updated fairly regularly. So let's just jump right into it. So today I'm just going to be focusing on adrenal glands.

Basically my goal is by the end of today's podcast, you'll feel very comfortable with anything relating in any way shape of form to the adrenal glands. So let's go ahead and chat about these adrenal glands. So we know that the adrenal glands right there are the aderite from measoderm. Right? And we know that the adrenal glands, I mean like ultimately it has two major engines, right? It has like the cortex and it has the medulla, right? The medulla, it's very high yield to remember that the medulla is derived from neurocress cells. Okay? That's something that's very high yield to remember. So it's the cortex that is derived from measoderm but the medulla is derived from neurocress cells. Right? And the thing is one thing your friends at the MDM kind of expect you to know is to know the histology of the adrenal gland. So I encourage you to look up pictures of this online, right? Basically, I feel like usually people get confused when they start from the outside in. So strongly recommend that you go from the inside out. Okay? So the thing is if you go from the inside out first you have the adrenal medulla, right? That contains chromofinselves, right? So you have the adrenal medulla contains chromofinselves because the reason I suggest people start from inside out is if you start from the outside you may confuse the capsule of the adrenal gland with the cortex of the adrenal gland. And the thing is the medulla is very distinct.

Usually on histology images is like you're seeing a bunch of circle, circle, circles, like things that look really like neurons, right? So you know that you're dealing with the medulla, right? So we have the medulla on the inside. Okay? Again, derived from neurocressels contains chromofinselves, right? And remember that those chromofinselves are basically modified post-gonglinics and pathetic neurons. So they have nicotinic acetylcholine receptors on the acel surfaces. And then if you go higher above that, if you're again proceeding towards the outside, you have the zone of reticularis that mix six steroids, right? And then if you go above that, you have the zone of acicolata that mix local coricotes like cortisol. And then if you go above that, you have the zone of lomerulosa, right? That secretes cell dosture. It's called lomerulosa because it's responsive to things that come from the kidneys, right? From the, if you want to be more specific from the juxtaglomerular cells of the kidneys, ultimately with some, give a tick a few more steps in the way. And then after that, you have the, you have the, the capsule that covers the entire adrenal gland, right? So again, very important to know that. And the thing is, if you want to remember those layers of the adrenal cortex, right? There's this numaniac, right? GFR, salt sugar, sex, the deeper you go, the sweeter it gets. I mean, everyone has read this numaniac, right? So it's like zologluberry losa, right?

Again, mix mineral coricotes like aldosterone, fascicolata mix, local coricotes like cortisol, right? And then reticularis mix androgens, right? Androgens. So you can see six steroids. Well, the most part, the adrenal, I mean, the zologluacolitis mix like D, G, S. And it also mix a androestina diondustins, ultimately converted in the, in the overuse, right? By, by an enzyme known as aromatis, right? Remember, aromatis converts androgens to estrogens. And again, the medulla, right? Like I said, it mix, got a colamine, chromafin cells derived from neurocrest. And one, I guess key anatomical piece of detail you want to keep at the back of your mind is remember that there's this weird abdominal blood vessel relationship that obtains on the left versus the right. Most things on the left end up draining into the renaul vein, okay? Before they then drain into the inferior vein, a key, but most things on the right, they drain directly into the venachiva, right? So the classic ones, they love to test on the USML exams are the adrenal veins, the gonadol veins, right? So let's say like the left testicular vein or the left, I don't know, like ovarian vein or whatever, right? So that's actually very high on to keep your mind. The adrenal vein on the left, it actually drains into the left ring of him before he goes into the IBC, but the adrenal vein on the right, it actually drains directly into the IBC, okay?

Now, what if they give you a question about a patient, you know, that came in like two days ago, this patient came in with like severe headaches, temperature of 102, this patient has no core rigidity. And then they tell you that you know, this patient was given antibiotics, but they continue to get worse, right? And let's see, maybe they tell you that, oh, they did a lumber puncture and they did like a gram stain of the CSF fluid and they saw like gram negative diplococsides. And then now this person is becoming persistently hypotensive. This person is becoming hypoglycemic. This person is, they give you like a CBC and you notice that the person you'll see no field count is going up. And the patient sodium is like 125, the potassium is like 5.8. If you see all those things, what are you thinking about? Well, I would really hope you're thinking about what a house Friedrich's in syndrome, remember, it's adrenaline, so efficiency that arises because these people have like dissimony fit meningococcal infection, right? So what are those things in syndrome? You'll torch the adrenal glands, if you torch the adrenal glands, right? You basically have loves that are consistent with adrenaline, so efficiency. So those people have hyponitrimia because our dose zone is not around. They'll have hyperchillinia because our dose zone is not around, right? They will have a metabolic acidosis because our dose zone is not around, right?

So those are all things you want to keep at the back of your mind and they will also have an eocenophilia because remember that corticosterous like cortisol, they actually cause a poptosis of eocenophiles. So whenever a person has low levels of cortisol, for example, in the setting of a Mora house Friedrich's in syndrome, then they'll be decreased the poptosis of eocenophiles. So eocenophilia will be a classic finding that you'll see on a CBC, right? So again, that's something actually very high yield to know, right? Because some people I'm sure they've always wondered like, oh, why does why is it that when a person has other sense disease, the eocenophilic count goes up? Well, that's the reason because again, corticosterous causes poptosis of eocenophiles and in other sense disease, your corticosteric pool is gone, right? Because you've had an autoimmune destruction of the adrenal cortex. So what are the things that ultimately control the release of hormone from the adrenal gland? Well, the thing is the first axis, I guess I'll talk about these things in axes, okay? The major axis I think I will talk about first is like the HPA axis, right? So like the hypothalamine, pituitary, adrenal axis, right? So that axis is the thing that ultimately controls the production of cortisol. Well, the thing is it all starts in the parventricular nucleus of the hypothalamus. Remember the parventricular nucleus of the hypothalamus?

One very high yield thing you should know for exams that it produces is oxytocin, but another thing that actually produces is corticotropin releasing hormone, CRH, okay? And then that CRH travels to the anterior pituitary and acts on CRH receptors, okay? CRH receptors, it is very high yield to know that they are G-protein coupled receptors, they are G-stimulatory coupled receptors. So when you activate them, you actually have an increase in cyclic AMP, okay? So cyclic AMP is basically the second messenger for the CRH receptor, but remember the CRH receptor will be found on the surfaces of corticotropes that are in the anterior pituitary gland, okay? And then when CRH acts on those corticotropes in the anterior pituitary, they begin to release ACTH, okay? And look at the name adrenal corticotropic hormone, right? So that means it's a hormone that is tropic, that means it goes to the adrenal cortex, okay? So the thing is, ACTH is released and then it goes on acts on ACTH receptors that you find on the cells that constitute the adrenal cortex. And those ACTH receptors, they also G-protein coupled receptors, they are responsive to, they are responsive to a, basically, right? Like they are G-stimulatory G-protein coupled receptors. So your levels of cyclic AMP actually go up when you attack those, right? And the thing is, ACTH, right? It literally causes a hyperpleasure of the adrenal glands, right?

That's why if a person has very high levels of ACTH for whatever reason, they will have hyperpleasure of the adrenals, they will typically have bilateral adrenal hyperpleasure. And the thing is, right, when ACTH acts on its receptors, the zone of fascicule, for example, right, begins to make cortisol. And that cortisol will then exert negative feedback, right? It will shut down the release of C-R-E from that part of the trigolonyl nucleus of the hypothalamus. And then it will also shut down the release of ACTH from the anterior pituitary gland. Now, one quick thing I want to say because it will be useful for some conditions we'll talk about later is this fact that a levels of cortisol actually highest just before you wake up in the morning. The way I just kind of remember that is when you wake up in the morning, you need to attack the day like a lion, right? So because you need to attack the day, you need energy, you need glucose and everything. And cortisol is a bit of a genic hormone, right? So your levels of cortisol are very, very high just before you get up in the morning, right? But at the end of the day, you know you are going to sleep, you don't need as much energy, your metabolic needs go down, right? So levels of cortisol actually very low just before you go to bed, right? All right? Right around midnight, your levels of cortisol are very low.

And the thing is one of the, I mean, there are many reactions in the adrenal glands to be honest with you, you probably don't need to memorize most of them. But there are some key ones that I would strongly recommend making sure that you understand. And I will begin to mention them as we go along in this podcast. One key one you want to keep at the back of your mind is that ACTH, the way it actually increases the synthesis of most of the hormones, right? The steroid hormones, remember the adrenal cortical hormones are all steroid hormones. One way ACTH increases the synthesis of adrenal cortical hormones is to actually activate an enzyme known as cholesterol desmoleys, okay? Cholesterol desmoleys is a very, very high-yield enzyme you want to know for the USNL Esteban exam, it converts cholesterol to pregnant lume, okay? Pregnano lume, okay? So again, ACTH activates cholesterol desmoleys, converts cholesterol to pregnant lume. And then one of the thing I also want to talk about is, I mean, if you're looking at the outdoosterone, right? The thing is outdoosterone is actually not under the control of the ACTH system, it's actually under the control of the ring and juntencin outdoosterone system, right? So for example, if you have a release of ring from the juxtaglomerulus cells of the adrenal glands, right? That ring in all convert and juntencinogen, which I believe comes from the liver into and juntencinone.

And then and juntencinone, then travels to the lungs and then it's converted by the endothelial cells that we find in pulmonary capillaries to undertencin two. And then that undertencin two has a lot of functions, right? One function of undertencin two is that it goes to the zona glomerulosa of the adrenal cortex and causes the release of outdoosterone, okay? It goes to the zona glomerulosa of the adrenal cortex and causes the release of outdoosterone. And the thing is obviously, right? Whenever a person has high levels of, high levels of outdoosterone, they will have a hypochylineia, right? And they will have a mild high-prinid trinia. The reason they will have a mild-hyperinid trinia is if you remember from my renal video, right? Or my renal podcast. When a person has high levels of outdoosterone, one of the things outdoosterone does is that it increases the activity of the enect channel, that you find that the level of the principle of the collecting duct, right? So if you increase the activity of that enect channel, you will draw sodiums into the principle cell, right? So you get hypochyline trinia. But at the same time as you're drawing those sodiums into the principle cell, you're creating negative charges on the urine site. And that will drop potassium ions out of the principle cell, right? So you essentially waste potassium in the urine, so you get a hypochylineia.

So when a person has outdoosterone excess for whatever reason, they will have hypochylineia and they will have a mild-hyperinid trinia. Another thing those people will have is they will have a metabolic alkalosis, okay? And the reason behind that is, if you remember in the nephronin, the distal nephronin, we also have something known as the alpha-intercalidate cell. The thing is the alpha-intercalidate cell has a proton pump on its epico-surface, its urine surface, right? That is responsive to our doster. So the thing is when you have high levels of our dosterone, you will increase the activity of that proton pump that you find on the epico, or you can see the urine surface of the alpha-intercalidate cell in the distal nephron. And that will lead to the secretion of protons, right? So you waste protons in the urine, so you develop a metabolic alkalosis. Now, one thing I think I also want to mention, because I guess I don't necessarily want to mention it later, also that it can be more efficient is that, is this whole thing about like the Dixamethasone suppression test, right? So the Dixamethasone suppression test is a test that will come up in like, in a later part of this presentation, where I will talk about like certain causes of like hyper cortisolism. The thing is basically right, Dixamethasone is a synthetic glucocorticoid. The thing it does is that if you give a normal person Dixamethasone, right?

The thing that will happen is you will suppress the levels of cortisol, because the Dixamethasone will shut down the production of ACTH. And if the ACTH is shut down, then you'll stop making endogenous cortisol, right? So cortisol normally suppresses in response to to low dose Dixamethasone, okay? Now, let's assume a person has something known as Cushing's disease. Remember Cushing's disease is a cause of Cushing's syndrome, right? The thing is this is one terminology that seems to, you know, kind of mess with people's heads a lot. So let me try to break this down for you. Cushing's syndrome is a syndrome that is highlighted by any person having signs and symptoms of hyper cortisolism. If you have very high levels of cortisol, for any reason, you are set to have Cushing's syndrome. But Cushing's disease is a cause of Cushing's syndrome that arises from an adenoma in the pituitary gland that secreting ACTH. So Cushing's disease is a specific cause of Cushing's syndrome, okay? Cushing's disease is a specific cause of Cushing's syndrome. Cushing's disease is just an adenoma that is a cause of hyper cortisolism. The thing is when people have this ACTH like secreting a pituitary adenoma, when you give those people low dose Dixamethasone, their cortisol levels will actually not suppress, okay? So on an administration of low dose Dixamethasone, levels of cortisol actually does not go down when a person has Cushing's disease.

But if you give those people high dose Dixamethasone, and you check their AM cortisol, remember I said your morning cortisol is highest in the morning, you know you check the AM cortisol, right? So I mean, obviously if you're suppressing something, that means you're looking for that suppression at a time when nothing is supposed to be high, it can end the morning, right? So when you give a person high dose Dixamethasone, you will actually go ahead and suppress, you actually go ahead and suppress the AM cortisol, right? So that's like a kind of like a big thing you want to keep at the back of your mind with Cushing's disease. And remember, Cushing's disease, right? Obviously this is a cause of hyper cortisol is now be associated with an with elevated levels of ACTH, right? And then if a person has like a topic ACTH secretion, right? That's the one that does not suppress, that's the cortisol that would not suppress like again, the AM cortisol would not suppress whether you give low or high dose Dixamethasone, it does not matter, okay? But one sneaky thing your friends at the MVME can actually do to you is that they can actually give you a question about a person that has like AM cortisol that does not suppress with low and high dose Dixamethasone and the person actually does not have any a topic ACTH secretion. What kind of condition can you think about?

That will be associated with suppressed, I mean with with non-suppressed cortisol production like AM cortisol production without the presence of a topic ACTH production, what condition can you think about? Well, I would really hope you're thinking about like a person that just has a tumor in the adrenal cortex that's making cortisol, right? If you have a tumor in the adrenal cortex that's autonomously secreting cortisol, then it's not going to respond to low high dose Dixamethasone supplementation, right? So, but you may say, okay, so define how do I differentiate between an adrenal adenoma that secreting a ton of cortisol from Cushing's disease or a topic ACTH production when a person has, when a person has this, okay, let me put it this way. Your question may be, oh, divine, how can I separate a cortisol secretion adrenal adenoma from like a topic ACTH production that also does not suppress with high and low dose Dixamethasone. Well, the thing is look at the levels of ACTH, if the levels of ACTH are low, then that means you have cortisol secretion from the adrenal cortex, okay? And that would happen because that would happen because the individual is suppressing the ACTH normally through negative feedback, right? But if a person has a topic ACTH production, the ACTH levels will be high, so that's how you tell those two things apart.

Now, one weird thing, this is probably less likely to shop on step two, but this is very likely to shop on step one, is see, for example, a person does like a low dose Dixamethasone suppression test, or you know, you do one of these Dixamethasone suppression tests, and you're like, hey, these results are not very interpretable. If you want to really figure out, if a person has, if a person has like, cushions disease as the cause of the hypercord is also, one nifty thing you can actually do on an NV Me exam is actually to do something called inferior petrol cell sinus sampling, okay? Inferior petrol cell sinus sampling. The thing is the inferior petrol cell sinus is a vein, right? I mean, all those venous, all those sinuses in the vein, I mean, sorry, all those sinuses in the brain, not vein in the brain, okay? They are known as venous sinuses, they're just modified veins for all intents and purposes. So the thing is, if you check the levels of, in general, in a person that is normal, right? In a person that is normal, if you check the levels of ACTH in the inferior petrol cell sinus, it should be roughly similar to the ACTH that you find in most other veins of the body, right?

But if a person for whatever reason has a local increase in ACTH secretion, for example, in the setting of like, cushions disease, where they have a pituitary, the number that's making a ton of ACTH, when you measure the levels of ACTH in those people's inferior petrol cell sinus, it'll be a lot higher than the ACTH that you would find in like some other vein in the body, right? So if you notice, you're like, man, this person's ACTH in the inferior petrol cell sinus is way, way, way higher than what I would, what I see in like, I don't know, like the left vein, for example, then you should also expect that the person very likely has cushions disease. And again, remember all of this, a topic ACTH that puts the child of that on an embankment exam, is small cell lung cancer. Remember, small cell lung cancer has all these panoplasmic fins, like a topic ACTH production, that again, does not suppress with low high dose dexamethasone, right? And then they will also have SIDH, right? Because the tumor can produce a ton of ADH. And then in addition, these people can also have lumbar etian myesthenic syndrome, where the tumor makes all antibodies against the presynaptic voltage-gated calcium channel, right? So that's the muscle weakness that improves with use.

Again, these are all, I know you may say, or the vineyard, you're going too much on the dipend with these, I promise you, I am not going on the dipend with these, these are things that are pretty very high yield and very important to know. So the next thing I think I want to go ahead and talk about, let's see, how do I, how do I drive this? I think, yeah, I think the next thing I'll go ahead and talk about is, let's actually talk about the things that are done by these different hormones that come from the adrenal glands, right? So again, we know that the adrenal glands, again, we have the cortex, that's probably the biggest one we care about, right? We have the quadricoids coming from the glomerulosa, the glucocococococococlein from the fasciculata, and the Androgen, so the sex steroids coming from the reticularis, right? And then we know that the adrenal medulla produces like epinephrine for the most part, although it also, to eliminate the extent, produces like more epinephrine and like dopamine, right? And that should make sense if you listen to my biochem, my biochemavidio, right? So the thing is, quadrizol, I mean probably the one of the more important, although all of them are important, don't get me wrong, but probably one of the more important adrenal quadricoal hormones, right? And the, it's quadrizol, the glucocococococleicoids, so let me go ahead and talk about those first, right? So the thing is, glucocococococleicoclein, they do many things, right?

Like they help you adapt to stress, they help you adapt to fasting, they help you deal with metabolic injury, they help you deal with like surgery, right? They raise your blood pressure, right? Because they actually put, they actually, because remember, quadrizol is a steroid hormone, right? So it works at the nuclear level, right? So one thing it does is it actually increases the production of out like the insertion of more alpha-1 on the surfaces of arterial, right? So obviously if you put more alpha-1 receptors, then you, then be more responsive to cardiac colomins, like in our opinion, for example, so you have an increase in systemic vascular resistance, and that can cause hypertension. Well another thing that quadrizol also does is it also kind of like re- causes insulin resistance, right? That's why most people that are long-term quadricostero-therapy, they tend to have diabetes, right? And then some other things that steroids do, right? Again, they actually raise your blood glucose level, it's right, the stimulant gluconeogenesis, and they actually also stimulate like the breakdown of fat, like like polices, they stimulate the breakdown of protein, and one other thing quadrizol does is it actually shuts down the activity of fibroblasts. So think about it, if you shut down the activity of fibroblasts, then you will not be able to synthesize collagen appropriately, right?

That's why people tend to have like proposed try, or sometimes you may see pinks try on an mbim example in people that have, you know, pretty high levels of quadrizol. Now, probably one of the bigger, I guess maybe more from a pharmacological perspective, uses of quadricosteroids, right? Is that they actually have the ability to suppress the immune system, and they actually do it in a multitude of ways, right? So one thing they can do is they can kind of like, shut down your T cells from producing and to looking to, because again, remember they function at the genetic level, right? So they actually shut down your T cells, your T cells, are not able to make an interlooking tool, and if you remember interlooking tool is a T cells stimulating factor, right? So if you have low levels of interlooking tool, your T cells will not be stimulated, that's why in general steroids can be useful like induction therapy, or they can be useful like crises when you are beginning to have like organa rejection. And then if you remember, there's this enzyme known as phospholipase A2 that converts membrane phospholipids to a rachidonic acid. Remember a rachidonic acid can ultimately go towards the production of personal glands and local trines. So one thing that happens is that that phospholipase A2 is actually inhibited by corticostero. So you may see, oh, divine. How do corticosteroids inhibit phospholipase A2 well?

The thing is, again, corticosteroids remember they are steroid hormones, so they work at the level of the, like at the genome level. The thing is they actually increase the expression of a genome as like bocortine. The thing is like bocortine is a direct inhibitor of phospholipase A2, okay? So ultimately, if you inhibit phospholipase A2, you will not convert membrane phospholipids to rachidonic acid. So you ultimately not make the inflammatory monoclesin as a local trines and prostaglandids, okay? Now, if you also think about it, if a person has like really severe allergies, they are told, you know, you can take corticosteroids and that will help. One of the thing is histamine and serotonin, right? Remember the, maybe it may not be these allergies, talc symptoms. So it actually does not come as any surprise that the production of actually histamine and serotonin is actually inhibited by corticosteroids. And then one final thing I guess I'll go ahead and say here this is just something you do need actually two things I'll go ahead and say here, these are things that are really very high up for you to know. Is that corticosteroids, I remember they actually go at, they shot, they cause de-margination of your white blood cells, right? So when a person is placed on steroids, it actually raises their white blood cell count. It shots down that de-margination, right? Basically, essentially makes your white blood cells less sticky to the surfaces of endophilia cells, right?

So when a person gets corticosteroids, their white can classically goes up. That's a very high-yield thing to know. And then one other thing I also said is that if a person has high levels of cort, low level, I mean I said this earlier, I said if a person has like other scents disease that is accompanied by low levels of corticosteroids, well, you will notice that those people will in turn have very high levels of your xenophiles because I said that corticosteroids cause a profound hipoptosis of your xenophiles. Well, the reverse is the case. If a person has like, pushing syndrome for any reason, then those people have very low levels of your xenophiles because again, those people's immune systems, I mean, those are people's, your xenophiles begin to undergo pretty rapid hipoptosis. And that actually kind of explains again, one of the mechanisms behind corticosteroids being good for allergy-style symptoms because if you are causing hipoptosis of your xenophiles, remember your xenophiles meet eat a lot of hypersensitivity reactions. But if you want to be a little more specific, maybe like the type one hypersensitivity reaction. So that's again, just all high-yield things you want to keep at the back of your mind, for example.

And then our doctrine already talked about the effects of our doctrine that again, it causes hyperneutrimea because it increases the activity of that inek channel at the principal cell of the collecting duct because it's hypokillemia because it causes the dumping of potassium in the urine at the level of the principal cell of the collecting duct. And then it also causes the metabolic alkalosis because it increases the activity of that proton pump that you find on the epi-col of the urine surface of the alpha-intercalated cells of the distal nephra of the collecting duct. And then some, I guess some things, other things I think I want to mention, just to again kind of like try to integrate a lot of concepts here. If you remember from my biochem review, if you remember, I talked about this in this one carbon carry in the body known as SAM, like S-adenosil methyonine. Well, the thing is SAM actually plays a pretty big role in the adrenomidala. So it's a co-factor of an enzyme known as PNMT. PNMT, phenol ethenolamine and methyl transferase, PNMT for short. Basically, it's the enzyme that converts noripinephrine to epinephrine. It converts noripinephrine to epinephrine. And it's actually very high yield to know that co-dicoesterroids increase the activity of PNMT.

So that's actually one of the ways that co-dicoesterroids have a primitive effect on the sympathetic nervous system in addition to also putting more alpha-1 receptors on the surfaces of materials so that they are more responsive to those categorical means you're making from the adrenomidala. And then one other again, Keynes, I want to talk about is again, I've kind of talked about aromatics. Remember, it's expressed pretty heavily by cells in the ovaries, right? That's what helps us convert things like DHES and Androsthin dion to estrogens, right? And that should also help you understand why drugs like anastrosol or letrosol or exymesine can be used to treat breast cancer, right? Because those drugs, they are aromatis inhibitors, right? Typically those drugs are given to mean that you know, need breast cancer, chemotherapy, like an ER, PR, positive breast cancer, where you need, where you need, like in a postmenoposal female, right? So like postmenoposal females, they get these aromatis inhibitors for breast cancer, chemotherapy, and again, it's important to remember, testosterone is not the primary androgen that comes from the adrenocortex, from your zeneretic laryz, your zeneretic laryz for the most parts, I mean, for the most part gives you DHES and Androsthin dion. So again, I think these are all important things, again, you want to make sure you know and understand.

Now, I think the next thing I want to talk about is, let's talk about let's talk about adesins disease, right? Let's talk about adesins disease, you know, it's a pretty, it's a pretty high-yield topic to know for the USML standpoint, for sure. Basically, adesins disease is the most common cause of primary adrenonins efficiency in the US, right? So primary adrenonins efficiency, right? Basically, let me maybe go through some terminology here. Whenever they tell you that a problem in endocrine is a primary problem, it means it's associated with an organ, right? The primary organ that secrets the hormone, right? So like primary adrenonins efficiency means that your adrenal organ, your adrenal gland, most specifically your adrenal cortex is shot, right? But if a person has secondary adrenonins, like a secondary endocrine problem, it means the problem is at the level of the anterior pituitary, most of the time, right? And then if a person has like a tertiary, like problem, it means that the problem typically is at the level of the hypothalamus, okay? Those are all important things to keep in mind. Now, one common misconception amongst people that oh, like divine primary adrenonins efficiency means the entire adrenal gland is destroyed. That is not true, okay? That is actually very far from the truth. When a person has primary adrenonins efficiency, the only thing that is destroyed is the adrenon cortex, okay?

It's the adrenon cortex that does not function, not the adrenon medulla. I'll say that again, it is the adrenon cortex that does not function, not the adrenon medulla, okay? Because your friends at the MBM know that it's a common misconception amongst people taking these USML exams. So let me try to rub that into try to get you thinking in the wrong direction. So do not make that mistake in the exam. Let me see divine. Why would I just destroy the adrenon cortex and not the adrenon medulla? Well, think about it. Those two things have very different embryologies. It's almost like two different organs that are slapped together in two one. It's almost like the anterior pituitary and the posterior pituitary. We have somewhat different embryology. They're almost like two different organs slapped in two one. So really, the soldiers that affect the adrenon cortex may not necessarily affect the adrenon medulla, okay? So again, that's why, like, I mean, in fact, the instead of seeing the word adrenon in sufficiency, to be honest with you, I very much prefer the term adrenon cortical in sufficiency because it's the adrenon cortex that is screwed over. Now, what are some things that can cause adrenon in sufficiency? Obviously, the most common cause in the US is it's an autoimmune disease, right? Adescent disease, right?

Remember, on MBME exams, when they give you a question about a person that has an autoimmune disease, they will typically give you elsewhere in the question that, oh, they have some autoimmune disease. So if they're giving you an adrenon disease question, they can tell you that, oh, this person is taking levothyroxin for ashtamodos or the person has like takes B12 supplementation because they have a preneasio-sanemia or the person has vidiligo or you know, something to that effect, right? So the most common cause is very high to know. The most common cause of adrenon primary adrenon in sufficiency in the US is autoimmune destruction, aka adescent disease. And then, actually, the most common cause of primary adrenon in sufficiency in the world is actually just from granulomas that take over the adrenon cortex. In this case, TB for the most part, TB is actually the most common cause, very high yield is the most common cause of primary adrenon in sufficiency in the world. In fact, I will say maybe, well, let me be a little more specific. Let's just say more like in like developing countries, TB will be the most common cause of primary adrenon in sufficiency in those folks, right? And I mean, obviously, for a person has like waterhouse-frigicin syndrome in the setting of like disseminated meningocoxemia that can also cause primary adrenon in sufficiency, right?

If a person takes this anesthetic agent, it omnidate, it omnidate can also cause an adrenon in sufficiency can actually suppress the production of adrenon cortical hormones. That's actually one of those weird things that you don't find in many resources that is typically very high yield to know for the US Emily exams. And then I mean like HIV, right? If a person has like metz, right? Like long cancer loves to go to the adrenon, breast cancer loves to go to the adrenon, those things can all cause a primary adrenon in sufficiency. And the thing is again, I've explained what can happen if a person has primary adrenon in sufficiency. Those people will be hypotensile, right? Because again, if you have low levels of outdoor steering, right? Then you are not able to reabsorb sodium in the principle cell of the collecting duct. So you're not able to retain volume, right? So you become volume duct. So you become hypotensile. Also, if your adrenon cortex does not work, right? You are not making cortisol. So you are not operating alpha-1 receptors on your arterios, right? So you're not able to increase systemic vasilar resistance. So you become hypotensile. You also get like mild hypermetrymia, right? Because again, I mean, sorry, hyponitrhymia because our doctrine is not around. So you're not able to reabsorb sodium. You get a hyperkidemia because again, our doctrine is not around. So you're not able to waste potassium at the level of the principles and of the collecting duct.

And then you also get a metabolic acidosis because those alpha-entricular cells, the upper tons do not work. So you do not waste protons in the urine anymore. So if anything, you retain protons. So actually, I'll go ahead and integrate this with reno. When a person has adecine disease, aka a low outdoor steered state, because the adrenal cortex and by default, the zonal glomerulosa is destroyed. Those people actually have a type 4 RT. Remember a type 4 RT is an RT that arises when a person has a high pool outdoors. So that's a very nice high-yield intuition when you keep at the back of your mind for mbiming exams. Now, one classic thing that your friends at the mbiming love to test with regards to primary genolins of fission C is that these people have skin hyperpigmentation. So you may say, oh, why do they have skin hyperpigmentation? Well, think about it. If you are a general cortex, those not work. And you're not able to make cortisol. Well, you will release that negative feedback that typically happens at the level of the anterior pituitary and at the level of the hypothalamus. So you'll be being to make a ton of ACTH. Well, the thing is, ACTH is not made alone. ACTH actually comes from a precursor known as pomc, okay? P-o-m-c. P-o-m-c literally stands for pro-opio melanocortin. And one thing you've probably learned about me from listening to all these podcasts is that I love to break down terms, okay? I love to break down terms.

Because if you think about it, pomc stands for pro-opio. So pro-precocer. So pro means, right? If you are pro-something, right? That means you are in favor of something. So pro-opio opioid, right? So the opioid beta endorphine actually comes from pomc. So pro-opio melanoc, right? So pomc also gives rise to MSH. MSH is known as melanocytes stimulating hormone, right? So if you stimulate your melanocytes, you have hyperpigmentation. That is why skin hyperpigmentation is a classic finding in people that have primary adjournalins of efficiency, right? So pro-opio melanocortin, quartin, something that goes through the adjournal cortex, okay? So that's why ACTH also comes from pomc. It is very high yield for the purposes of the USM list, the point example, to know the different derivatives of pomc. Okay? You definitely need to make sure you know the different derivatives of pomc. And then, so I've talked about primary adjournalins of efficiency. Secondary adjournalins of efficiency will be more along the lines of your pituitary gland doesn't work, right? Your pituitary doesn't work, so you don't make ACTH. And then on the flip side, you can also think of tachery adjournalins of efficiency where your parvin-triculonucleus of the hypothalamus has probably been destroyed or whatever, and you're not able to make a CRH, you're not able to make corticotropin releasing hormone, right?

So you should definitely keep on the back of your mind that different presence has like secondary adjournalins of efficiency. They are not going to have, so these again, some very key subtle differences you will not make sure you understand. These people actually do not have skin hyperpigmentation because think about it. If a parvin-triculonucleus has secondary adjournalins of efficiency, well, they're not going to be making ACTH. If a parvin-triculonucleus has tertiary adjournalins of efficiency, well, they're not going to be making CRH. So because they're not making CRH, they're not going to be making ACTH either. So those are two low ACTH disorders. So because they are low ACTH disorders, that means you will not have a formulation of pomc production. So that means you will not have a formulation of MSH production. So you are not going to have skin hyperpigmentation. If you have secondary or tertiary adjournalins of efficiency. Now, one other thing you want to keep at the back of your mind is these people also, people that have secondary adjournalins of efficiency, they actually do not have electrolyte abnormalities like they don't have like, you classically will not see these people having, they will not have the hyperneutrimea, I mean, they will not have like the hyponitrimea or the hypercalemia or the metabolic acidosis that you come to expect with like primary adjournalins of efficiency.

Because remember, if a person does not have primary adjournalins of efficiency, aka if you have secondary or tertiary adjournalins of efficiency, that means that your adjournal cortex is still intact. Because your adjournal cortex is still intact, guess what? Your zona glomerulosa will be functioning just fine. And remember that the zona glomerulosa is not under the control of ACT. Your zona glomerulosa is under the control of guess what? Your ringing and your tensing out those current system. So our those current levels typically are relatively okay in people that have secondary and tertiary adjournalins of efficiency. So again, that's very, very high yield to keep at the back of your mind. Now, one thing you want to ask you may ask yourself okay, so divine, how can a person get like secondary or tertiary adjournalins of efficiency? Well, here is how. The way that happens is typically what I write in the setting of a person potentially having like you know, like they've been on like long-term blocochoricoid use right for like some autoimmune disease or whatever right. And because they are long-term blocochoricoids, they've just suppressed their endogenous HPE access okay. That is actually let me go ahead and tell you this. Let me cite some epidemiological things that are high yield to know for the USML exams one. The most common cause of hypercordisolism is just the endogenous use of I mean the exogenous, not endogenous, endogenous means it's coming from within you.

Exogenous means it's coming from outside of you. So the most common cause, very high yield, the most common cause of hypercordisolism is the exogenous use of blocochoricoids. So basically, blocochoricoids you buy at a pharmacy, now if a person has endogenous hypercordisolism, the most common cause is actually pushing disease. Cushing disease causes like 70% of cases of hypercordisolism from endogenous like causes of hypercordisolism. Probably the second most common cause I will say is probably like an adrenal adenoma or whatever like yeah either like an adrenal adenoma or something that's over-secreted in a cortisol okay. Those are just weird high yield things that again you may not see mentioned in many resources, but it's very high yield to know for purposes of the USML exams. So the thing is one thing that again the reason the USML is step one and also the USML is step two and step three, the reason they love endocrinology is that it's one of those things where if you don't have deep understanding you can go of the reservation pretty easily. So they love to like you know describe all these experiments or give you all these scenario-based questions and then give you all these powers and then you need to understand oh this arrow goes up this arrow goes down this arrow goes this arrow goes down.

So one thing I guess I will go ahead and talk about is say for example if a person has primary adrenal insufficiency right the levels of cortisol will be low right the levels of cortisol will be low so and again typically if you want to say oh a person's levels of cortisol are low you it doesn't make sense to measure those people's cortisol when you expect it to be low aka night so it doesn't make sense to do that right so for a person has primary adrenal insufficiency you measure their cortisol in the morning because cortisol is typically very high in the mornings right so if you're like oh this person just before they wake up you measure their cortisol levels it's low well that's that that's not okay right those people very likely have very likely have a primary adrenal insufficiency so the screening test for primary adrenal insufficiency is to just go ahead and measure their morning cortisol if their morning cortisol is low that's not normal okay that's not what remember for every screening test you need a confirmatory test so one way that you confirm the diagnosis of hyper cortisol is in I mean sorry of primary adrenal insufficiency is you then do something called a co-centroping test okay you do a co-centroping test co-centroping is an analog of ACTH if you give a person ACTH you would expect their levels of cortisol to rise failure of a person's cortisol to rise with co-centroping augmentation is diagnostic okay is diagnostic of primary adrenal insufficiency okay and again in primary adrenal insufficiency your cortisol will be low for your ACTH will be high but in secondary and tertiary adrenal insufficiency your levels of ACTH will be low in secondary adrenal insufficiency you literally don't just make an ACTH in tertiary adrenal insufficiency you're not making CRH so your levels of ACTH will be low as well now there's this thing I believe I've explained it in

a prior podcast but I'm just gonna explain again because this is just something that people still seem to confuse on MBM exams right and it's this test known as the metiropon test okay it's a test known as the metiropon test the metiropon test the thing is the metiropon test can help you distinguish between a person that is normal or let me put it this way can help you distinguish between a person that has primary adrenal insufficiency or a person that has secondary slash tertiary adrenal insufficiency so let's explain what will happen with metiropon but I think before I explain what happens with metiropon well let's actually understand what in the world metiropon dose dose so the thing with metiropon is that metiropon is actually an inhibitor of an enzyme known as 11 beta hydroxylase I'll talk about 11 beta hydroxylase are later right but 11 beta hydroxylase it's an enzyme that converts 11 deoxy cortisol to cortisol okay I'll say that again metiropon is an inhibitor of 11 beta hydroxylase the job of 11 beta hydroxylase is to convert 11 deoxy cortisol to cortisol so think about it if a person is completely normal right and you give them metiropon well what should you expect because the thing is typically when they give you these metiropon questions they give you all these arrows that you need to fill in on your exam right so the thing is if you give a normal person because I feel like to be honest with you if you really want to understand the analogy always ask yourself what happens in a normal person and then ask yourself okay what part is broken in this person that has pathology and typically you're able to fill your things out from there right so if you think about it right if you give a normal person metiropon you'll inhibit 11 beta hydroxylase well guess what if inhibited 11 beta hydroxylase your levels of cortisol will go down right and if your levels of cortiso

l go down what will happen to negative feedback at the level of the anterior pituitary it will be gone and if it's gone your easy-to-each levels will go up and if your easy-to-each levels go up it will basically stimulate everything until you get to that metiropon inhibited step aka 11 beta hydroxylase so your levels of 11 the oxy cortisol will go up in a normal person so I'll widen say this if a person that is normal gets exposed to metiropon their cortisol levels go down their easy-to-each levels go up because there's no more negative feedback and then their 11 the oxy cortisol levels go up okay now let's assume a person has primary adrenal insufficiency well for presence primary adrenaline insufficiency well the adrenal glands essentially not let me again let me know say adrenal glands the adrenal cortices do not exist okay the adrenal cortex does not exist if your adrenal cortex does not exist well there is nothing there's no 11 beta hydroxylase to inhibit right so if your 11 beta hydroxylase is not in here I mean it's basically non-functional right then your levels of cortisol right will still stay low as this right your levels of acth will show will still be like it will still be increased and you will not have any changes in your levels of 11 the oxy cortisol right so basically like because whenever you do a lab right you know you measure some baselines and then give them a tyropon and then you measure afterwards your cortisol levels won't change your 11 the oxy cortisol levels won't change your acth won't change because my tire basically if a person has primary adrenaline insufficiency and you're giving them a tyropon is like you're just like throwing the tyropon into the into the sea you're not gonna get anything from it because there's just no place for me to work right but if a person has like secondary adrenaline insufficiency or tertiary adrenaline insuff

iciency well they have intact adrenal glands right so guess what will happen for those people you know you measure if a person has like secondary adrenaline insufficiency you check their labs beforehand right obviously their acth levels will be low right the acth levels will be low and because the acth levels are low the 11 the oxy cortisol levels will be low their cortisol levels will be low right but if you then give me tyropon well if you give me tyropon that me tyropon you'll say okay that will suppress the person's levels of cortisol right but the thing is these people even if you suppress their levels of cortisol then they will not be able to respond appropriately because they're and triopitritory or they're hypothalamine don't work right so because those things don't work you will actually not see any changes in the levels of like acth or 11 the oxy cortisol okay because again remember acth drives this whole axis so if you don't have acth then you pretty much not have any changes in anything okay so those are it's just the important that you understand the concept of how the body responds right on that different pathological scenarios to the administration of me tyropon now how do you treat primary adrenaline efficiency well obviously you know you give those people what they what they need right so you give them the cortisol that they are missing you can give them like glucocorticoids back you can give them like hydrochlorizone you can give them prednisone remember prednisone for the most part just has glucocorticoid activity what hydrochlorizone actually has glucocorticoid and mild mineral aquaticoid activity you know again you can replace them in our aquaticoids by giving a drug man as flu drug cortisol okay flu drug cortisol is a synthetic mineral aquaticoids like an aldustra and amok in a sense and then I mean I don't know if most times people don't bother

doing this but you know if a person is having like very low libido because they're not making androgen because they are primary and genus of agents you can give them you know you can try to give them like some supplementation of androgens but that's not something you would like this on an example what again remember for president has like secondary atrocher and genus of efficiency the aldustra levels are just fine so you do not need to give those people flu drug cortisol okay all you need to give those people is the glucocorticoids that they are that they are that they are missing okay all you need to do is to give them the glucocorticoids that they are missing okay so I think with that said since we've talked about you know adrenaline's of agency it probably I guess makes sense to talk about another disorder that may look somewhat like adrenaline in sufficiency and this disorder I think I'll go ahead and talk about is congenital adrenaline hyperplegia congenital adrenaline hyperplegia is unfortunately one of those disorders that you want to make sure that you understand for the purposes of the USMA Ds basically congenital adrenaline hyperplegia arises when you have some mutation or some deficiency of a key enzyme that is needed to synthesize like one of those terrible ones that you find in the adrenal cortex right and there's three big ones you want to keep in mind for the USMAD exams the first one is 21 hydroxylase deficiency does actually the most common right and then other ones we have like 11 beta hydroxylase deficiency and then we have 17 alpha hydroxylase deficiency and the thing is you may see why are these disorders important there is an important and maybe this will be a nice way for me to set this so you can understand them as we go along is that whenever you have a deficiency of one of these enzymes typically you have decreased production of some hormone t

hat's supposed to come from the adrenal cortex but because you have decreased production of one hormone then the rest of the feedstock to that pathway will then go towards other pathways so you have hyperproduction of other hormones right and one thing I'll go ahead and tell you right now is in every cause of congenital adrenal hyperplasia the levels of cortisol are low that's one thing you can pretty much take to the back okay in every cause of congenital hyperplasia that you will see on your USMAD exams the presence levels of cortisol will be low okay and basically the thing that marks you as having oh 17 alpha hydroxylase deficiency or 11 beta hydroxylase deficiency or 21 hydroxylase deficiency is just basically building from there like okay in addition to having low cortisol what else do I have that's the thing that will tell you what enzyme disorder you have and before again I teach you what is deficient with these enzymes I will go ahead and teach you one principle I guess one rule okay basically the rule is these enzyme deficiencies because people are like oh divine going into memory these entire pathways probably not right so there's a rule you can come into memory that can help you here the thing is if there is a one in the first letter I mean in the first because again you see these numbers 21 11 17 if there is a one as the first number of these enzyme deficiencies those people will have hypertension okay if there is a one as the first and I will explain why these rules actually work right but let me just give you these rules to kind of set the stage so that you you can you know feel a little motivated to learn this and learn this stuff and pretty well so again if there is a one in the first letter of the in the first number of the enzyme deficiency those people will have hypertension they will have hypochylinea they will have metabolic alkalosis okay and th

ey will have a mild hyperneutrilo but if there is a one in the second number of the enzyme deficiency those people will have virulization okay so just remember those two rules and for the most part you can recreate pretty much every finding in these different congenital adrenal hyperplasia and the thing is it's actually very high to know that when a person has congenital adrenal hyperplasia they will actually have hyperplasia of both adrenal glands it's not just one that will have hyperplasia to be both because again if even if it's one adrenal gland that is all screwed up let's say oh you know it's just the left adrenal gland that has like a 17 hydroxyline deficiency well here's what will happen you won't be able to make cortis or although typically it's it's usually in both right so if you have like decreased production of cortisol right from those adrenovates right you will not have negative feedback so your levels of actage will go up and actage again remember I said very early in this podcast that actage is a stimulating factor for the adrenal glands right so actage will stimulate for the adrenal cortex so actage will stimulate both adrenal cortices because it's just high so those people will have bilateral hyperplasia of the adrenal glands so let's start with the most common one and the one you likely see on your exam 21 hydroxyline deficiency right the thing is when one hydroxyline is right it's actually an enzyme that you needs to make cortisol again remember I said all these enzyme deficiencies will cause cortisol problems right so 21 hydroxyline is required for a person to make cortisol but it's also required for a person to make our doster right so the thing is people that have to know and drop these deficiencies deficiency the outdoor levels will be low the cortisol levels will be low and one thing that's actually very high to remember is that they'll have

increased levels of something known as 17 OHP well what a 17 OHP Stanford 17 OHP 17 hydroxy progesterone okay measurement of levels of 17 OHP is very instrumental anybody that way on USMELY exams if you want to diagnose an individual with having a congenital adrenal hyperplasia okay it is very instrumental on USMELY exams if you want to diagnose a person with congenital adrenal hyperplasia so you need I promise you you need to make sure you commit that agent to memory it's one of those things in the bathroom you do actually want to you do actually want to know right so the thing is there are actually many types of 21 hydroxyline deficiency there is one called like the salt wasting form this is the one that will present in infancy as a like as a child is born you're like man this child is like super hypotensive right because again they are not making a cortisol right so again that permissive effect on the sympathetic nervous system is not there right so they're like super hypotensive and because they don't make an out of stone right they have hyperchill I mean they have hyperchillemia they have hyponitrogen they have a metabolic acidosis if you see that in a newborn in an infant that will be the salt waste in form on an MDM exam and then there is one that is like laid on set you know it can shop like in a person's teenage years again for the most part the one that presents in people's teenage years like the laid on set forms on people calling like the non-classic form of 21 hydroxyline deficiency but the most part the only thing you'll see in those folks is just the androgen excess right so you know they may be her suits or they may have like acne they may have like problems with like demonstration and all that stuff so that will be the thing you'll see in that non-classic form and then there is one form known as the simple virilizing form is just basically people tha

t have the simple virilizing form for the most part they just have signs of virilization you know so if it's a woman she can have like she can have a you know she may have like her suitisim she may have like really bad acne she may have like masculinization if it's a guy he may have like precocious puberty kind of deal but these people usually don't have the electrolyte abnormalities that you would expect from having low levels of our dosture right so the only one I will say on the US Emily exam they should peg as having like all these bad electrolyte abnormalities is the salt we send from the infantile the newborn form of 21 hydroxyline deficiency and again if we're going off of those roads right I said 21 it doesn't have a one as the first number but it has a one as the second number right so people that have 21 hydroxyline deficiency they will have virilization okay they will have virilization but they will not have hypertension they will not have hypochylemia they will not have metabolic alkalosis okay now 11 beta hydroxyline deficiency right basically it essentially works like 21 hydroxyline but it just sort of shows up above it just shows up above it's the enzyme that's like needed like right above 21 hydroxyline so the thing is people that have 11 beta hydroxyline deficiency they will actually not have increased levels of 17 hydroxyline progesterone so their 17 OHP levels will be just fine okay but sorry sorry sorry make it a mistake here because I was like wait these things don't make any sense to me so sorry let me backtrack a little when a person has 11 beta hydroxyline deficiency the thing that happens is that they will actually have decreased so 11 beta hydroxyline is right earlier I erroneously said that it comes before 21 hydroxyline that's not true 11 beta hydroxyline comes after one step after 21 hydroxyline it's okay it comes one step after 21 hydroxy

line but again levels of 17 OHP are fine in a person that has 11 beta hydroxyline deficiency okay now one key thing I'll see this is probably the most critical thing you want to keep in mind with 11 beta hydroxyline deficiency is that these people they have or maybe let me put it this way what is one thing 11 beta hydroxyline does 11 beta hydroxyline converts 11 deoxycoticosterone to corticosterone okay it converts 11 deoxycoticosterone to corticosterone so you may see well divine why you're making a big fuss about 11 deoxycoticosterone well here's the deal 11 deoxycoticosterone actually has um partial activity admiral corticoid receptors so if it has partial activity admiral corticoid receptors it means you can get an out dostero-like effect from 11 deoxycoticosterone that is why if a person has 11 beta hydroxyline deficiency and the levels of 11 deoxycoticosterone goes up right they will have hypertension because basically anything you expect without dostero-nexes they will have they will have hypertension they will have hypochylemia they will have metabolic alkalosis okay but again because you're shunting so much stuff towards the energy pathway these people will also have individualization okay they will also have your realization if it's a guy though you'll see more things more along the lines of precocious puberty right because you already a guy so if you have more testosterone you will almost be like a super guy right so you can have like precocious puberty basically you become like a guy before you're supposed to become a guy at puberty um you kind of understand what I'm saying um I'm gonna move on from that so um um and one thing that your friends at the MVM me do to you on an exam is to try to get you to see if you can piece apart differences between 21 hydroxyline deficiency in terms of like reading levels and in 11 beta hydroxyline deficiency in terms of r

eading levels as well if a person has 21 hydroxyline deficiency they're not making out dostero they're not making cortisol they're not making 11 the oxycolicosterium so they are hypotensive right so because they are hypotensive they are written and they will be hypoprofusion of the afferent material so those people actually have increased levels of reading right contrast this with a person that has 11 beta hydroxyline deficiency because they have an outdostero-ne-like effect from 11 the oxycolicosterium right um actually you know retain sodium retain fluid so they are hypotensive so there is hyper-perfusion of the afferent material so those people actually have decreased levels of reading okay now um last one I guess I'll talk about is 17 alpha hydroxyline deficiency basically this one um if you're going with our rules there's a one in the first number so these people will have hypertension um but there's no one in the second number so these people actually do not have realization okay so basically the thing that happens is that if a person has 17 hydroxyline deficiency they actually make a crap ton of outdostero but they actually are not able to make they're not able to make uh androgens and they're not able to make cortisol okay they're not able to make androgens they're not able to make cortisol and these people I would hope that you understand that these people will have um low levels of reading as well because again they have high levels of outdostero so they will be they'll be hypertensive okay now one I guess subtle thing I should go ahead and mention is that people that have um 17 alpha hydroxyline deficiency if if they're female right the thing is these females will actually look completely fine at birth because remember you do not need androgens for a woman's uh external genitalia to look normal right everything will be completely fine at birth at birth okay

but the thing is when a guy is born because you need like again androgens to for a guy's external genitalia to look normal at birth those people have like ambigious genitalia right they even have like undecended testis but the thing is for puberty in both males and females you do need uh androgens that are alive and well okay you do need androgens uh that are alive and well right so those people will have like as they get to puberty they'll begin to have problems with a secondary sexual development okay again these are all how you things to learn understand for purposes of the US Emily exams the thing is I think I want to keep this on there an hour I would make an adonadrenal podcast you'll be much shorter than this one to just go over a few more topics that I have at the back of my mind as I do at the end of every podcast I do offer one or one tutoring for many exams step one step two ck step two cs step three pre-clean cool med school exams third year shelf exams if you're medicine resident you need tutoring for the intranin exam or the the abi and board exam feel free to reach out to me um if you're if you need like one or one tutoring or you know like large group tutoring for any of these exams I've mentioned just reach out to me through the website so you can send me an email at divineinterventionpodcasts with an sadeand at gmail.com and then if you know you're a medicine and applying to residency so like an iris app or college student applying to med school so like an amcas app I do offer like one on one coaching for these things so like rec letters personal statements editing applications mock interviews again I've worked with tons of people and most of the people I've worked with have actually matched at their first choices and again I actually have admissions committee experience I've been on the admissions committee of a top two med school for a year right

so again I have a lot of experience reviewing very high quality applications and then if for example you have like a college buddy that needs tutoring for like general chemistry organic chemistry physics biochem histology physiology I offer tutoring for tutoring for all those things so have a wonderful rest of your day I'll see you in the next podcast episode 1292 thank you and God bless you

The cortex (from mesoderm) and the medulla (from neurocrest cells).

The zona glomerulosa.

Melanocyte-Stimulating Hormone (MSH), which is a derivative of ACTH/POMC.

The Hypothalamic-Pituitary-Adrenal (HPA) axis.

Hyponatremia, hyperkalemia, and metabolic acidosis.

Because low cortisol levels lead to high ACTH release, which stimulates both adrenal cortices.

Increases $\text{Na}^+$ reabsorption (via E NaC) and increases $\text{K}^+$ secretion/$\text{H}^+$ excretion.

Cholesterol desmolase.

Primary AI has severe electrolyte abnormalities ($\text{Na}^+$ low, $\text{K}^+$ high); Secondary/Tertiary AI does not because aldosterone production remains intact.

US: Autoimmune destruction (Addison's disease). Global: Granulomas (e.g., Tuberculosis).

21-hydroxylase deficiency.

Cosyntropin stimulation test (failure of cortisol to rise after ACTH analog administration).

MSH (Melanocyte-Stimulating Hormone).

Increases $\text{Na}^+$ reabsorption (via E NaC) and increases $\text{K}^+$ secretion/$\text{H}^+$ excretion.

Cholesterol desmolase.

Primary AI has severe electrolyte abnormalities ($\text{Na}^+$ low, $\text{K}^+$ high); Secondary/Tertiary AI does not because aldosterone production remains intact.

US: Autoimmune destruction (Addison's disease). Global: Granulomas (e.g., Tuberculosis).

21-hydroxylase deficiency.

Cosyntropin stimulation test (failure of cortisol to rise after ACTH analog administration).

MSH (Melanocyte-Stimulating Hormone).