DIP Episode 357 - The Clutch Disorders of Sexual Differentiation Review (for Step 1-3)

Okay, welcome everyone. My name is Divine. This is episode 357 of the Divine Intervention Podcasts. And this podcast is going to be on a high-yield topic that many people find to be very challenging for the USML exams, you know, step one, step two, seek is step three. And I'm going to call this the Clutch Disorders of Sexual Differencesion Podcasts. The Clutch Disorders of Sexual Differencesion Podcasts. Before I roll right into things, I have a list of three courses that are coming up over the next few weeks. The first one is more immediate. It's a review for step two, seek is step three. And you know, you also, if you're taking complex level two and three, basically the course is going to start off with a test taking strategy course that will be taking place on the 27th of this month, the 27th of December. It's going to be from 12 to 230, Mountain Standard Time. Again, I got a lot of emails from people saying, oh, you know, I have my USML step two, step three exam towards the end of this month, early next month. So I decided to hold essentially an emergency test taking strategy course. So it will be on the 27th of December from noon to 2.30 pm Mountain Standard Time. And then I'm having like a compressed 10-hour review for step two, seek and step three on the 29th of this month, December from 70 M to 5 pm Mountain Time. It's a 1 D course. So you get everything in a day. That's going to be on the 29th of December.

And then next month in the month of January, I have the 24-hour course with the testing and strategy course. The 24-hour course will be on the 24th of January 2022. And then the, I mean, the MBME testing and strategy course will be on the 24th of January 2022, from you know, 2 to 4.30 pm Mountain Time. And then the 24-hour MBME review course, you know, for step two, step three will be from the 25th to the 25th from 70 M to 1 pm Mountain Time each day. Again, we'll be going over surgery, pediatrics, internal medicine, OBGYN, psychiatry, neurology, ethics, biostatistics, healthcare systems, professionalism, communications, and we'll also be discussing multi-system processes and disorders. And then finally, the next course is then what I call a foundation course is a 25-hour course. If you're a person, because the thing is many people, they struggle on the USML exams because they just have the wrong foundation. The thing is if you're building a house and you have the wrong foundation, that house will collapse when it's subjected to any sort of pressure. So if you want to build a solid foundation and just understanding things, understanding physiology and pathophysiology, the 25-hour course is precisely what you need. It's going to be taking place from the 31st of January 2022, all the way to the 4th of February 2022.

So if you're interested and it's not just for people taking step one, you know, people taking step one, yes, you know, they need that deep physiology and pathophysiology understanding, you know, integrated with multiple disciplines. But this will also be a class for people that are taking step two or step three that have a very weak foundation from step one. So if you're performing poorly on step one, you're going to find the course to be extremely helpful. So let's just go ahead and get right into it, right? So the thing is if you want to understand the disorders of sexual differentiation, the very first thing you need to get down path is just how differentiation of sexes work in the first place, right? The thing is the default program for most human beings is actually to just be female. But if you have certain activity in place, then you don't have to be female, you can be male, right? So how exactly does this work? Well, the thing is we all know that men have a white chromosome, right? That's very important, right? So as a man, that white chromosome has an SRI region, the sex determining region on the white chromosome. Okay, well, since it's original chromosome, that means it must be a gene that codes for something. So what does it code for? What protein does it code for? What gene product does it code for? Well, the thing it codes for, right, is what we call the test test determining factor. And we know that that test is determining factor.

Literally look at the name, test test, determining factor. It's a factor that makes your own differentiated gonad become a testes, right? And the thing is once you become a testes, there are many types of cells in the testes, but the two that I'm going to concern myself with today are the certainly cells and the leadic cells. So remember those certainly cells, what do they do? They make molirion inhibiting factor. So basically, the molirion inhibiting factor will inhibit everything that is derived from the molirion duct. So things like your fallopian tubes, your uterus, the upper portion of your vagina, those things come from your molirion duct. Remember, sometimes we call it the paramisonafric duct. Those things, their development is inhibited by the molirion inhibiting factor, sometimes they call it MIS or anti-molirion hormone AMH that comes from the certainy cells. Now, it is extremely high yield to remember that in men, molirion inhibiting factor kills everything that comes from the molirion duct. But the thing is the molirion duct is not completely killed off in men, right? And the molirion duct actually becomes something that we call the appendix testes, right? So our friends at the NBM exam, at the NBM, we can give you a question about like a young boy comes in, has a curon-set testicular pain, right? And then in the question, they will see something about bluish discoloration of the testicle, right? And of course, the NBM is in the agreed wisdom.

They will put an answer that says, oh, testicular torsion, testicular torsion. And then they will put an answer choice that says torsion of the appendix testes. The thing is, whenever you see any blue anything on a man's testicle and he has a curon-set testicular pain, they've pretty much told you of something we call the blue dot sign, right? The blue dot sign is pathogenmonic for torsion of the appendix testes. For that, obviously, is supportive care. You're not going to be doing any kind of detoursing the testicle or curp exe or whatever. You're not going to be doing any of those things, right? So that's just again a nice integration there for you, for your exams. Now, right? So we've talked about the sirtoly cells mixed molirion inhibiting factor, right? Again, remember, the molirion duct does not give rise to the ovaries. That's a classic mistake that many medicals trust me, have same rates, right? I have 200,000 of people in my lifetime. I see many medicals to let's make this mistake. The ovaries do not come from the molirion duct, right? Your ovaries are not from the molirion duct. Now, so we said the testes, you know, has torsion of the cell mixed molirion inhibiting factor. Now, another thing that's made by your test, another cell type that we find in the testes are the ladyx cells, right? Now, the ladyx cells, they produce testosterone, right? The ladyx cells produce testosterone. So, what does testosterone do? Well, the testosterone makes your wolfian duct, right?

Sometimes they call it a miso-nefreak duct, but your wolfian duct, it makes it form internal male genitals structures, right? So like, for example, things like your epidemics, your vast difference, your seminal vesicles, right? All those things for them, for your wolfian ducts to differentiate down that pathway, it needs testosterone to be doing its job. That's very important to know. Now, in terms of your external genitalia, a derivative of testosterone helps with that purpose, right? So what's that derivative of testosterone? That derivative of testosterone is going to be DHT, dihydrotestosterone, right? Dihydrotestosterone is made by an enzyme called 5-alphuriductase that converts that testosterone to DHT, and in that DHT makes your external genitalia on the outside that a default female becomes default male. What do I mean by that, right? So, say, for example, in women, we know the labia, right? If you've studied any kind of female anatomy, we all know what the labia is. Well, the thing is, the labia, the labia or not, is what ultimately forms the scrotum in men. Basically, under the action of dihydrotestosterone, that labia then fuses, it fuses and becomes the scrotum, right? Or we look at the clitoris in a woman. The clitoris in a woman, believe it or not, is what forms the penis in men. Essentially, that clitoris elongates and becomes the penis in men, under the action of DHT. In fact, if you look at the fetus before DHT is made in utero, right?

That's why many times you cannot tell the sex of the fetus until a certain number of weeks or gestation. Because the thing is, prior to that, believe it or not, the fetus, the external genitalia, looks female. But after your body, after your testes, under the action of five-affered doctors, starts making DHT. Now, you notice that, hmm, this thing that was labia before looks a lot like a scrotum. This thing that was clitoris before looks a lot like a penis, right? So, the thing is, DHT is necessary for you to be very light. So, for the default external female genitalia, if you're a guy or 46x1, for that thing to look male, you need DHT to help you, at least up until a certain point, right? So, that's very important to know for purposes of of exams. And again, remember, five-affered doctors, right? Again, I said he converts testosterone to DHT. The thing is, we can use, because DHT, one of the things he does actually is to make your prostate grow. And the thing is, if you're an old guy, you don't really want your prostate growing because if it grows, it can basically cause an extrinsic or external compression of your urethra, right? Your prostate-kyrethra. If you compress the prostate-kyrethra, you're going to have a lot of problems like, I don't know, like BPH, right? It's going to be that 70-something year old or whatever old guy on the exam that is having like urinary dribbling. Sometimes he can present with like lower abdominal pain.

Well, I mean, and acutely obviously, you're going to give an alpha-1 blocker, right? So, you can do like a self catheterization. But what you can do long term for those men is to give them a five-offer adoptee's inhibitor, right? So something like finasterite or dutasterite, right? Those things will over time, over about a six-month period, cause massive shrinkage of the prostate. If the prostate shrinks, then the prostate-kyrethra will open up and that guy will not be having urinary dribbling anymore, right? So again, you see the way our friends at the MBM is, they love to integrate things on, on exams. Again, this is precisely what I love to do during my review courses. Now, so those are the big things with the way, uh, person sex develops, right? So that's one big thing I think I want to hit on today. Now, the second big thing I want to hit on today, because these disorders of sexual differentiation, many people really struggle with them, but to be honest with you, again, it's so easy if the understanding is there, simple as that. If the understanding is there, it becomes extremely easy for you, right? So let me give you a rule. I call it the breasts and pubic hair rule, okay? Now, let me tell you this, if a woman or if a person has the right kinds of breasts, that tells you that estrogen is okay. Estrogen is not a problem for them. If you have good breasts, estrogen is working just fine, right?

Now, if you have good axillary and pubic hair, then that means that your testosterone is working just fine. Again, you may see why it's dividing, introducing these rules. I promise you, you'll see as we go through the rest of this podcast, uh, guess video, since I'm putting this on You Tube, you'll see how helpful this can be for analyzing these, uh, disorders of sexual differentiation problems. I'm going to start calling them DSD problems for sure. So that's the second thing I want to establish today. Now, the third thing I want to establish today is this whole business of DSD. So many of us, we see this terms on exams because again, the MDM is right, like I've said this many times in my podcast that you love doing these things where they put a derivative answers to questions, right? Because again, what's the point of putting, because then let me put it this way. The MDM recognizes that we live in anarchy generation. So what do you do for anarchy generation? Don't put those buzzwords that they've memorized. Just put descriptors of those buzzwords, for example, right? A very easy thing to do is to call, uh, is to put an answer choice. Like you've seen me say this in many different podcasts like, oh, this person has IGNF, IGNF, right? Anyone that has looked at any archy deck for medical students probably knows what IGNF, but how can you make it harder? Well, the way you can make it harder is you can just say, oh, sinfire and jyotic, nephropathy.

You put sinfire and jyotic, personally like what? But again, if you really think about what in the world does that turn mean? It just means that you're having an nephropathy, synonymously at around the same time as when you have the firing jail infection, right? So that's what the MDM is love to do these days, right? Oh, it's not putting Kawasaki's disease, they put mucus, utenius lymph node syndrome. Again, just all, most times these derivative answers are just answers you will get right if you understand the pathophysiology behind that specific disease. So the first thing I want to establish today is let me explain to you when you use, there are some DSD terminologies they use on exams, right? So like for example, you may see this term 46xxdsd, 46xxdsd or sometimes they can say 46xxs, pseudo hemaphyrdite. Let me tell you this, whenever they give you these terms like 46xxdsd, it means that the pressing genotypically is female, the pressing is 46xx has the genotype of a female, but the pressing has the phenotype of a guy, right? So the thing is there are many types of 46xxdsd, for example, Androgen insensitivity syndrome, which I'll talk about in a bit, is an example of a 46xxdsd, right? Or if you see for example a woman that has aromatase deficiency, right? Because remember, aromatase is an enzyme that converts Androgen to estrogens, right?

So the thing is if you lack aromatase, I can convert Androgen to estrogens, you'll be a woman, you'll be 46xx, but you may look male on the outside, right? That's another example of a 46xxdsd, right? So the term 46xxdsd, one to one is the same thing as a 46xx pseudo hemaphyrdite, right? So thexxx, or xy, or whatever they give you in the actual question, right? Oh, whoops, sorry, I made a mistake there, right? Androgen is the insensitivity syndrome, it's actually a 46xxdsd, right? So the pressing is a guy genotypically, but is a woman phenotypically, right? That's a 46xxdsd, right? 46xxdsd will be something again, like I said, like aromatase deficiency. Or if a woman has like 21 hydroxylase deficiency, which is making a ton of testosterone, a ton of not testosterone, a ton of Androgen, right? Because she lacks 21 hydroxylase or she has made autoantibodies against 21 hydroxylase, right? Then the pressing may be 46xx, but you may have all these male features, why do they have these male features? Because again, they are making a ton of Androgen, right? So 21 hydroxylase deficiency, aromatase deficiency, those would be examples of 46xxdsd, those people are xx, they are females genotypically, but they are males phenotypically. But a 46xxdsd will be something like Androgen insensitivity syndrome. You literally male on the inside, you're a genotypically male, you're 46xx, but phenotypically, you look female, right? So that be a 46xxdsd or 46xxsudo hemaphodite.

Again, if you understand these naming conventions, when you start putting these different name permutations on your exam, you don't get a sport when you see something like that. So now let's go into some of these outro disorders, right? So the first one, what if they give you a question about a newborn, right? They tell you that, oh, this newborn has a big old genitalia. And you notice that, oh, this newborn has hypo-neutrhymia, has hyperkalemia, has a normal amyongapena bolyca sedosis. If you see this, what do you want to think about? Well, I would really hope you're saying, oh, the vine, this child has 21 hydroxylase deficiency, right? Remember, 21 hydroxylase deficiency is the most common cause of a big old genitalia on endemic exams, right? Because essentially, the thing that happens is, you have a deficiency of 21 hydroxylase. And when you have a deficiency of that enzyme, you're not going to be making corduzol, you're not going to be making out dust urine. The only thing you're going to be making in great quantity are Androgens, like DGS, for example, right? So for example, in a woman, right, when she's seen all that DGS, DGS, DGS, DGS, DGS, she's going to have a big old genitalia. Because the genitalia is just receiving all these mixed signals. It's like, I'm female, why am I getting all these Androgens and all these problems, right? So you're going to see I'm big old genitalia, right?

So you may be like, oh, divine, why do they have these strange electrolyte abnormalities? Well, think about it. It's because they have an outduster in deficiency. What exactly does outduster in good for human beings? When outduster in does a few things, it makes you reabsorb sodium in your nephrine, right? It makes you urinate potassium in your nephrine. And it also makes you urinate hydrogen ions in your nephrine, right? So if whatever bizarre reason you have an outduster in deficiency, well, guess what? You're going to have the reverse of all those problems. Instead of being able to retain sodium, you'll get rid of it. So you have hyponitremia. Instead of being able to urinate potassium, you'll hang on to it. You'll have hyperchylemia. Instead of urinating hydrogen ions, you'll hang on to it. You have a metabolic acidosis. More specifically, you have a type 4 RTA. Remember, the type 4 RTA is an example of a normal anion gap metabolic acidosis, right? So when you have the type 4 RTA, remember, type 4 RT As are RT As you get from a low outduster state. You get type 4 RT As because you have a low outduster in state. So if you have a low outduster in state, you're going to get a normal anion gap metabolic acidosis. So that's why they have those findings. Now, so when we be like, what do we find? Why see that some new bonds get this problem? But there's some people weeks till they are 10 years before they get this problem. Let me tell you this.

Congenital adrenal hyperplasia does not only arise because you just have like a genetic deficiency of 21 hydroxylis. Believe it or not, so people get congenital adrenal hyperplasia because they make on-wanty buddies against 21 hydroxylis, right? It's essentially almost like a type 2 hypersensitivity reaction. You make on-wanty buddies against 21 hydroxylis. You knock it out of circulation. You're not going to be making quarters all. I'm not going to be making out of us from anymore, right? So I've talked about the female presentation. Can this presenting males? Absolutely. Men can absolutely positively get 21 hydroxylis, their vigency on Mbim exams. It's just in the case of a guy, it would not be called a 46xxdsd. In the case of a guy, it will actually be a cause of precocious puberty. Because if you're a man and you're seeing all these androgens, you're going to be like quote, quote unquote, like a supercharged male. And if you're a supercharged male, right? You're going to have precocious puberty. So if you see a child that, you know, has especially a male child, that's when one hydroxylis deficiency, right? He will have precocious puberty. He will actually have a kind of precocious puberty. We call peripheral precocious puberty, right? Because again, it's not a problem in the brain. It's a problem outside the brain. This would be a peripheral cause of precocious puberty. Okay, let me go to my next thing. So what if they give you a question, right?

About a 21 year old female, they tell you that she has never had lenses before. She's never had a period. And then they tell you that have vagina into the blind pouch and they tell you that she has Tanner Stage 1, pubic and axillary hair. Okay, look at what I just said. Tanner Stage 1, pubic and axillary hair. Just knowing that alone tells you, oh, there's something wrong with the androgens of this patient, right? If you're 21, you should not be at Tanner Stage 1 in terms of pubic and axillary hair. So that tells you androgens don't work. So what does that mean? It means this patient has androgens sensitivity syndrome, right? Again, remember these people have male genetic genetically, right? They have 46 X Y. But on the outside, they are females. So this is an example of a 46 X Y DSD, 46 X Y DSD. So what's the pathophysiology behind this? Well, the thing is these people are genetically guys. We have testes. They make testosterone. But the problem is that the testosterone receptor just does not work. So you can have all the testosterone you want, but testosterone receptor doesn't work. If it doesn't work, then you're gonna have a lot of problems. Again, all these problems are very predictable. If you're going by principle, if you're going by understanding instead of just brute force memorization. Because think about it. If your testosterone doesn't work, then what do you think is going to happen to the Wolfian dot? The Wolfian dot is not going to develop, right?

So all those things like semifrostubules, epidemics, vast difference, blah, blah, blah, blah. Those things are not going to develop well, right? So the Wolfian dot derivatives are going to be gone. Okay. Well, these people have certainly cells that make malaria and inhibiting factor. And the malerining inhibiting factor works just fine. So guess what? Everything from the malaria and dot, everything from that thing we call primers, the lefric dot doesn't develop like what? The fallopian tubes, the uterus, the upper vagina does not develop. So internal male reproductive structures, these people don't have. Internal female reproductive structures, these people don't have. And again, if your testosterone is not working well, guess what? You're not going to be making DHT. If you do not make DHT, then your external genitalia will stay by the default female mood. It won't virilize and become like a scrotum or become like a penis. No, it will stay, right? It will be like a labia, you'll see labia, you'll see clitoris, right? And you'll, because remember the the lower vagina, the lower two thirds of the vagina. On any, because it kind of ver, you see people see some of these two thirds one thirds. Let me just say this, the lower vagina calms from the urigenital science. It doesn't come from the malaria and dot, right? So that's that blind vaginal pouch that you're seeing in these people, right? So again, because the adjaging doesn't work, the pubic and axillary hair will not be good.

Again, this is an example of a 46 XY disorder of sexual differentiation. And one thing you want to keep at the back of your mind for purposes of USML exams is that these men, you actually need to resect their testes. If not, you have a very high risk of developing a testicular mask called a gonado blastoma, right? They can develop gonado blastomas on MBME exams. Okay. Now, when they give you a question about, you know, like a 12 year old boy, a 12 year old female, you know, they tell you that she has like fused labia. She has a non-descript clitoris. It tells you that, you know, she had very girl-like features for the first few years of life. But that over the last like 12 months, it's almost like she's been undergoing like a metamorphosis of a sword. It's almost like she's transforming from being female to male. And they tell you that, oh, they perform an ultrasound and they see normal male internal genital structures. If you see this, then I want you to think of a person having five alpha reductes, deficiency. I want you to think of five alpha reductes, deficiency. So this is one of those DS Ds that is very hard for people to pick up on exams. Now, let me tell you what the hallmark will be. The hallmark will be a person because you may say, oh, wouldn't they have like a straight-up, you know, completely clean fine, okay, labia and clitoris? No, they won't. They won't. Let me tell you what will happen. The labia and clitoris in these women will be abnormal.

Many times they're going to be fused or they're going to be ambiguous on MDMA exams. And then many times in the question, they'll be kind enough to say, oh, they perform an ultrasound and they see normal internal males general structures, right? And you'll also notice this person when he hit puberty, they almost undergo this thing I call like metamorphosis. This is something probably learned, you know, maybe back in the day and I don't know, I learned this back in the day like in Nigeria as a very little kid, you know, how certain animals just change from one thing to the other over a few hours or a few days, right? This is almost like a human metamorphosis. You're like, this person was like a woman like, look very female like a year ago, but now this person's voice is now deep and all those states. If you see that think of five alpha reductes, deficiency. So what's the pathophysiology? Well, the name of the disease tells exactly what happens. You have a deficiency of five alpha reductes. If you have a deficiency of five alpha reductes, the thing that's going to happen is you're not going to convert testosterone to DHT. Well, you have testosterone. So you're going to your internal male genital structures are going to be A, okay, because those depend on testosterone to work right. Again, things like your semifers, tubules, epidermis, vast difference and things of that nature. But your external genitalia is going to stay female or stay close to female, right?

That's why these people tend to have a big genitalia. But the thing is when you hit puberty, right? P puberty is like the time of raging hormones. Those men are going to start making tons and tons and tons of testosterone. That testosterone that is produced in high quantity is going to force realization. And then those people over time will stand looking like males, right? In fact, they are starting cultures. I think they call it like wevedocis that have this problem, right? But again, if you understand all these things, I just mentioned, I don't see why you should not be able to get a five alpha reductes deficiency question right when you're exact. Okay. Now, wouldn't they give you a question about a 21-year-old female, they tell you that oh, she has never had men sees and they tell you that her vagina into the blind pouch. She's like, huh? But she's not into the blind pouch. But then they tell you that the axidory and pubic here are like tenor-stiche, four-tenor-stiche, five. If you see this, I would really hope you're not seeing androgenian sensitivity syndrome, right? Because they will give you that blind again, the endgame is they're not stupid. They will give you the blind vaginal pouch. So they will know some people will be like, oh, this must be AIS. And of course, they will put AIS as an answer, right? But they will also put molarian egenesis as an answer. Which answer should you pick? I hope you're picking the answer that says molarian egenesis.

Remember, molarian egenesis is also called MRKH syndrome. I believe it's called like Meyer Rockitansky Custer-Hauser syndrome. I think that spelled as Meyer, M-A-Y-E-R, and then hyphen, then Rockitansky, R-O-K-I, Rocky Tansky, T-A-N-S-K-Y, Custer is K-U-S-T-E-R, H-A-U-S-E-R. So Meyer, Rocky Tansky, Custer-Hauser syndrome. So essentially, the thing that happens with that is, these people, they are molarian.foreverbizarre is in just as not form. Well, if he doesn't form, then all the derivatives of the molarian.re not going to form. Like what? Well, like euphanopian tubes, which we call the oviducts on some exams, right? Euphanopian tubes, your uterus, your upper vagina, does not form properly. But your lower vagina is just fine. So maybe like, what do you divine? Why do these people have like normal pubic and axillary here? Well, I'll think about it. They have ovaries. Remember that ovaries are not derived from the molarian duct. I'll say that again, your ovaries are not derived from the molarian duct. So those ovaries will make androgens. It will make your DHES and everything. But then under the action of aromatis, you're going to make estrogens from those androgens, right? So they have a source of androgens. They have a source of estrogens. So their breasts are going to be great. Their axillary and pubic here is going to be fine as well. Why? Because again, those things are coming from ovaries that are there. Those things are coming from ovaries that are there, right?

So that's the long and short of molarian agenesis, right? That's pretty much that's pretty much it. Again, many of these things you notice that they are just extremely easy. If the pathophysiology, if the right foundation is there. Okay, and we'll be wrapping this up soon because I don't want this to go on for too long, right? Now, again, one thing that is pretty close that, you know, I talked about at the beginning as an example of a 46xx DSD is aromatis deficiency, right? Again, remember aromatis, what does it do? Aromatis is job is to convert androgens to estrogen. So if a woman has an aromatis deficiency, she doesn't have an enzyme that will help her make estrogens. So she will be a woman, right? But you have a lot of androgens, right? So the thing unfortunately in these women is that you notice that they have male features. They have like a deepening of their voice. They have like male partner hair growth. They have a lot of acne, things like that. And here's one very good thing that may tell you that you're dealing with aromatis deficiency on your mbim exams. Here's what they will tell you, right? They will tell you that, oh, the pressing gets pregnant. And during the pressing's pregnancy, the pressing's symptoms or signs of hyperandrogenism seem to get worse. Well, why did that happen? The thing is the fetus is making a ton of androgens crossing the placenta and then causing problems for mom, that's many times a pretty classic homework for aromatis deficiency.

Aromatis deficiency, again, is an example of a 46xx dsd. This pressing literally looks is female genetically, but on the outside may look male many times because that because something maybe like, I'm divine, how do I know this aromatis deficiency? The thing is, if people will not look fully male, but they will have signs of hyperandrogenism. In fact, the mdm is they will try to write it as being almost like a PCOS question, right? They're going to have signs and symptoms of hyperandrogenism, but on the outside they will not look fully, fully male. Again, that's something high you to know, for example. Remember, aromatis is a pretty high-densum to know for many reasons, right? Like, for example, if a woman needs breast cancer chemotherapy, and she's already aged 50, are you going to be using tamoxifen on exams? I hope you answer to that is, no, right? Don't use tamoxifen because again, the risk of endometrial cancer, remember tamoxifen is an estrogen receptor agonist in the uterus. So it increases the woman's risk of endometrial hyperplasia and endometrial cancer. So when a woman goes past the age of 50 on mdm exams, as she needs breast cancer, chemotherapy, relaxes, you're going to be using an aromatis inhibitor, something like anastrozo, or electrozo, or exemesting on exams, right? Now remember, we also use aromatis inhibitors in women that have PCOS that are trying to get pregnant, right?

The classic poster child for this on mdm exams is electrozo, well, why does electrozo help? Well, think about it, even if you get aromatis, you're going to be making an estrogen anymore. If you don't make estrogen, well, guess what? There's not going to be any negative feedback at the level of the hypothalamus. So you're going to be making more gn R-H, you're going to make more FSC and L-H, you're going to stimulate those follicles and you're going to get pregnant, right? Although remember, for that purpose, you can also use clumifin. Clumifin is actually a sir, right? Clumifin, believe it or not, it kind of works like tamoxifen. Essentially, what clumifin does is it's a partial estrogen receptor agonist in the central nervous system, right? Remember, whenever something is a partial agonist, it's essentially an antagonist. So it's essentially antagonizing estrogen activity at the level of the hypothalamus and anterior pituitary. So that's going to make you make more gn R-H, and you're going to get pregnant, right? So again, those are all uses of aromatis inhibitors. You can also use them for malignancy, but if it or not, on NV Me exams, especially malignancies that are driven by estrogen, right? Again, certain breast malignancies are treated with aromatis inhibitors, again, like anastrosol, letrosol, you know, and extremesting things like that. Okay, now let's go to another question. What did they give you a question?

About 25-year-old female, they tell you that, oh, she comes to the emergency room with, you know, a very bad chest pain going over the last 30 minutes, and they tell you that, you know, she has sharpness of breath, she has the left side of plural of fusion, right? If you see something like that, and they tell you that this female is like 4 foot 5 inches tall, that tells you all you need to know. This lady has a tuner syndrome, right? This lady literally has a tuner syndrome, right? So remember, a tuner syndrome, again, this is not necessarily a disorder of sexual differentiation, but I just figured out, throw these, some of these reproductive disorders in for you as a bonus at the end of this podcast, right? So remember, a tuner syndrome, they are many high-ealt classic findings, you need to know for your test. I mean, you'd be like, wow, defiant, why does this person have chest pain? Well, let me tell you this, people that have tuner syndrome, they actually predisposed to having aortic dissection on NV Me exams, right? Because again, these people tend to have manyortic abnormalities. Yes, you know, they can have by cosperiodic valve, but they also predisposed to having aortic dissection, which this female has, right? So remember, these people, they can get the murmur of aortic stenosis very early in life, right? Usually around like their 40s or like 50s. Most times when people have aortic stenosis, aortic stenosis is supposed to be a senior citizen's disease.

So this will be a problem you'll find in people that over the age of 60, over the age of 70, right? When you see in the present that is in their early 50s, in their 40s, those people have by cosperiodic valve on an exam. So why do they get aortic stenosis early? Or think about it. Your urethic valve is supposed to have three cossps, right? In a by-cospid valve, your urethic valve has two cossps. Well, do you see a problem with that? If two people, handling the job of three, something is going to have to give, right? So those things wear out on an accelerated basis compared to a normal three-cosped aortic valve, right? So that's why by-cospiodic valve can cause aortic stenosis. Now, what are some other problems we find in turners? We remember these people, they can give you that these people have like recurrent UT Is or they have hydrogen and process or they have renal fear. Well, why is that? Again, that's going to be from Hoshu kidney, right? Again, the inferior pores of the kidneys are fused and they are stuck on the one of the mesenteric arteries, right? And then remember, people that have turner syndrome, right? They have this web neck, right? You see many times they call it the cystic hygroma. Again, our friends at the MBM is they're not stupid, they're not.

They know that any person that has the job description, medical students has memorized that, oh, you know, people that have turner syndrome, they have the cystic hygroma on the neck, they know, they know, they know, right? So instead of putting cystic hygroma as an answer, what is the smart thing that friends at the MBM is you? They put the term congenital lymphedema, congenital lymphedema. So what will help you get that question kind of question, right? Is having the understanding? Because those cystic hygromas arise because you have abnormal development of your lymphatic channels. Simple as that. If you understand the path of physiology, if you don't see the classic thing you're used to, cystic hygroma, you will still get the question right on your test. Simple as that, right? And then they can even give you a question about a patient, the hasty-order syndrome, and they tell you that, oh, this person has low extremity clodication, you know, they walk for like a few blocks and they have to stop because their legs are hurting. And they tell you that, oh, the person has like a radio femoral pulse delay, right? The thing is the, the artery doesn't matter. It's just going to be a prepetition of an upper extremity artery and a lower extremity artery where you feel the pulse in the upper extremities and it takes a long time before you feel the pulse in the lower extremities. That person has a quotation of the order. The person literally has a quotation, right?

And again, what is the quotation? Well, quotation is where you have an instruction, right? It's almost like a compression in the walls of the order, right? So you're profusing your upper extremity as well, but you're not profusing your lower extremity as well, right? And many times if you get a chest text here for these people, you're going to see that affectionately described as three sign, right? You're going to see the three sign because again, you're forming all these intercostal vessels that are almost forming like a, you know, like another for blood across the, across the obstructed order, right? But again, remember the arteries are very pulsatile, right? So for each position of the artery, you're literally wearing away your ribs. As you wear away your ribs, you're going to run into troubles, right? That's where you're going to find that rib notch in on a chest text tree. Remember a quotation of the order, you need surgery to treat. There's no drug that can save you from quotation of the order. Okay, now what if they give you a question about a lady that has never had a period, right? Or, you know, the tale that you have this man and he has like tenor stage one pubic an axillary hair and the tale that he has a problem should smell. Well, if you see this, I hope you're saying, oh, divine, this is common syndrome, right? Common syndrome. Remember in common syndrome, you have problems with cells migrating, right?

And the two cells you need to care about are one, your neurons that make going to the tropine releasing for more and then your neurons that, uh, create on earth one, your factory, your factory nerve. So you can't smell, but you also, I mean, literally common syndrome if you think about it, these people have something that again, our friends at the NBA means, is that putting common syndrome as an answer. What is one smart thing they do? They call it hypogonadotropic hypogonadism on exels. Okay, so you feel like, divine. Common syndrome? Hypogonadotropic hypogonadism. What's up with that? Well, let me explain. Let me explain. Hypogonadotropic hypogonadism means that the gonadotropines are low, right? Because think about it. If your generic producing neurons don't work, then your generic is going to be low. If your generic is low, your FSH and LH will be low. If your FSH and LH are low, then your sex steroids like estrogen and testosterone will be low as well, right? That's an example of a hypogonadotropic hypogonadism. But on the flip side, if you think about the pressing the Hustonus syndrome, remember, Turner's is 45xO. And so since they have only one excrema's on the have no bar body, right? Turner's syndrome, these people have street ovaries. Their ovaries don't work. They are pretty much nonexistent. Well, if you don't have functioning ovaries, you're not going to be making estrogen. So you're going to be hypogonadotropic. But guess what?

Your, so your gonads are not working, but because you're not making estrogen, there is no negative feedback at the level of the brain, right? So you're going to be making a ton of generic, a ton of FSH, a ton of LH, but you're not making estrogen. So you're going to drop in the high, but your hypogonadot, right? That's an example of emenoria secondary to a hyper gonadotropic hypogonadism, right? Hypergonadotropic hypogonadism. Or you see a pressing that has athletic emenoria, right? Where they are not eating enough so their HBGX is shut down. There will be an example of an aphahypogonadotropic hypogonadism, right? And then to wrap up here today, remember they can give you a question about a man, you know, has low libido, right? Has poorly developed pubic and axillary hair. But they will tell you his tall. That's going to be the keyword. The pressing is tall. Pressing is tall is like six foot tall, right? And they tell you he has a family history of breast cancer, right? Or they can tell you that he has gynecomasia, has a micro penis. If you see this, right? This is easier, right? This is client filters. Remember what a client filter is, is 47 XXY, right? Again, remember as a guy, he's supposed to be 46 XY, not 47 XXY. So that means this guy has an extra extremism. So guess what? He actually does have a bar body, right? He has a bar body, right? So bar body spelled B-E-W-R, a bar body, right? Bar body, bar, body, right?

So you're going to see a tall guy, poorly developed pubic and axillary hair, micro penis, gynecomasia. The thing is client filter is actually a risk factor for male breast cancer, right? Remember, also having a brach amniutation is one of those risk factors for male breast cancers, when it may be exempt. So I think I'm going to go ahead and stop here. I think this podcast is going for long. Again, as I go at the end of every podcast, I go for one or one two or three for many exams. Step one, step two, three, preclinical medical exams, 30-ish of exams. I have another website. It's called Divine Intervention Life Lessons.com. I try to post like one to two podcasts on that website every week because many people have emailed me, oh, Divine, I love your life lessons. So it's actually an Apple podcast as well. I have about maybe like 43 episodes or so right now. And basically just Bible-based teaching, very short podcasts that just address like common problems that are faced by humanity. And then again, I offer a view courses for the USML exams. Again, I've had people like my MBA test against strategy scores, I've had people that literally take the course today. And by tomorrow, they take a practice exam and they bump up like 30-40 points from their previous practice exams, right? Well, I've seen people, again, West days are probably one of my happiest days during the week. I get emails from people that have attended my review courses and they've done extremely well on the exams.

So again, if you want to register for the review courses, shoot me an email through the website Divine Intervention Portcasts.com, right? Just hit the contact button, shoot me an email or you can email me directly at Divine Intervention Portcasts with an Savn at gno.com. And then I also have this podcast on Apple Podcasts, on Google Podcasts and on Spotify, right? So at least the most recent 150, if you want everything from episode one, all the way to this current episode, they need to go to the website. Actually, if you subscribe to the website with your Word Press account, whenever I make a new podcast, you'll get an email notification. And then I also help with like, Eras applications and mock interviews and recommendation letters and personal statements. So if that's something you're interested in, just again, shoot me an email and I'll be more than happy to point you in the right direction. And then I actually have a very quick life lesson I want to share today. And that life lesson is how do you handle power? How do you handle power? The thing is, one of the best ways to know the true content of a person's character is what they're like when they're in a powerful situation of life. The thing is for some people power doesn't destroy them. But for some other people power is what ends up destroying them. So just ask yourself, if you have everything you need, if you have everything at your fingertips, I used to going to be a person of good moral virtue, right?

When you achieve it all, when you get to that pinnacle because you see many people, they get to the pinnacle of life, you know, they get to the very top of their fields and then they commit suicide or whatever. Or this that means behaving. Well, the thing is, those people did not have the character to sustain that success. So one thing I'm going to try to encourage you today, as I wrap up this podcast is, make sure you're a person of moral virtue. Again, you can be very talented, you can have all the gifts, you can have everything in the world. But power can be very destructive in the hands of a person that does not have the right character. So I'm really encouraging you today. Watch how you handle power, develop your moral compass, have that moral compass, be a principled person because that's the thing that will keep you going when you get to the top. The thing is, when you're on a low level in life, people don't really care. When you get to a high level in life, you're going to be targeted. And when you're targeted, is those principles that will keep you going well. So I'm really encouraging you today, be a person of principle. Have a good moral standing. For me personally, again, I'm not saying I'm perfect in this way, but I'm doing my very best every day to live by the Bible. The Bible really guides people in the right direction. So again, just don't don't you're talented or whatever can get you to the top.

But the thing that will keep you at the top is having just a good moral compass. Don't lose your way. You see some people, they become very wealthy and once they become wealthy, their lives completely fall apart. They start using drugs, doing all these things, right? Just be careful, right? Be careful to be honest with you. When you are the low situation of my dish up in Nigeria, just to say this, now when you are the very low situation of life, and basically paraphrasing pray. But when you when your prayers are answered, when you get to a very, very high situation in life, you should pray even more. You should be even more careful because those are like the time of greatest prosperity is one of the time is many times the time where the greatest level of caution is thrown to the wind, right? Like for example, if you think about it, like when the stock market is doing really well, and every company is doubling every year, right? People just throw all caution to the wind. They start borrowing money to invest in stocks, right? When the economy crashes, then you know what means when the type goes out, right? As Warren Buffett will say, when the type goes out, you know the person that has been swimming naked, right? So I'm encouraging you at every level of life, be a person that follows good moral principles. If you follow those good moral principles, they will keep you regardless of where you are in life.

Be at a low level, be at a high level, they will literally preserve your soul. So I really hope you found this podcast to be helpful. Thank you for listening to me today, and I really hope that after this, you will understand the shoulders of sexual differentiation really well. Have a wonderful rest of your day. God bless you, Americanism is in advance. So though, I will be making other podcasts before that. God bless you.

Female (XX). Male development requires specific genetic and hormonal signals.

Sertoli cells within the testes. AMH inhibits structures derived from the Müllerian duct (uterus, fallopian tubes, upper vagina).

It is pathognomonic for torsion of the appendix testis.

Testosterone.

5-alpha reductase. It is necessary for the development of external genitalia (e.g., clitoris $\rightarrow$ penis; labia $\rightarrow$ scrotum) and prostate growth.

The individual has the genotype of a female (46,XX), but presents with the phenotype of a male (e.g., due to androgen excess).

Hypergonadotropic hypogonadism (High FSH/LH because low estrogen levels fail to provide negative feedback).

Müllerian duct derivatives (uterus, fallopian tubes, upper vagina).

Sertoli cells.

Hyponatremia, hyperkalemia, and normal anion gap metabolic acidosis (Type 4 RTA).

Androgen Insensitivity Syndrome (AIS).

Müllerian Inhibiting Factor (AMH) deficiency/failure of Müllerian duct development.

High risk of developing a testicular malignancy, specifically a gonadoblastoma.

Aromatase deficiency (failure to convert androgens to estrogens).

Müllerian duct derivatives (uterus, fallopian tubes, upper vagina).

Sertoli cells.

Hyponatremia, hyperkalemia, and normal anion gap metabolic acidosis (Type 4 RTA).

Androgen Insensitivity Syndrome (AIS).

Müllerian Inhibiting Factor (AMH) deficiency/failure of Müllerian duct development.

High risk of developing a testicular malignancy, specifically a gonadoblastoma.

Aromatase deficiency (failure to convert androgens to estrogens).