DIP Episode 602 - Endocrine Thinking (Stimulation and Suppression Tests)

All right, welcome. My name is Divine. This is episode 602 of the Divine Intervention Podcasts. In today's podcast, we're going to be addressing a super, super, super high your topic titled Endocrine Tested. And in today's podcast, we're going to be focusing on suppression and stimulation tests, suppression and stimulation tests. The thing is, this stuff tends to be very, very, very confusing for many people. But it's something where, honestly, if you understand it, it will actually explain so many things for you. It will literally explain so many things for you. So let's drop right into it. So I think a thing that's helpful to understand here is just how does the endocrine access work just in general. Right? So in general, you know, if you look at most of these endocrine axes, everything kind of starts in the hypothalamus. So you have the hypothalamus, it secrets a particular hormone, you know, usually we call those are releasing hormones. So say, for example, if we're looking at the thyroid axis, the thyroid gland release the thyroid tropin release in hormone. Right? And then that hormone that comes from the hypothalamus is going to speak to the anterior pituitary. The anterior pituitary, you know, contains like a TSH secreting cell. So those cells will secret TSH. Right? And then from the anterior pituitary, those hormones will go to a target organ, you know, in this case, it's going to be the thyroid gland. Right? There's going to be TSH receptors on the thyroid gland.

And when you make the, when you stimulate those TSH receptors, that will cause that target organ. In this case, the thyroid gland to secret T3, T4. Right? Hopefully you recognize that that TSH receptor is what you make autoantibodies against in a person that has a griff disease. Although those are stimulating antibodies, most times you know autoantibodies destroy things. But actually, in this case, they actually stimulate the thyroid gland. Right? And then generally, after you make that thyroid hormone, after that target organ has made that hormone that you want, the thing that then happens is it then goes back and suppresses. It goes back and negatively feeds back at the things that caused it to be secreted. Right? So for example, thyroid hormone will go back and feed back at the hypothalamus to suppress TRIH production. And then it's also going to feed back at the anterior pituitary to suppress TSH production. Right? Now one thing you may see, one kind of weird, unusual question you may see on your exams, is you notice a person that is very hyper thyroid. Right? And you notice that they are TRIH and they are TSH is like massively elevated. Honestly, that's a very amazing way of friends at the MBIMISCAN test. Fyroid receptor resistance, right? Thyroid receptor resistance. So like the thyroid hormone receptor doesn't work. So because remember for thyroid hormone to be able to suppress TRIH and TSH, right?

From the hypothalamus and anterior pituitary respectively, it needs to bind to a thyroid hormone receptor in those places in the hypothalamus and in the anterior pituitary to shut down the secretion of those things. But if those receptors do not work, then you will not get those responses. So you have like a resistance. So those people, they're going to keep making TRIH and TSH and keep making thyroid hormone and nothing is going to get shut down, right? Nothing is going to get shut down, right? Nothing is going to get shut down. So that's very important to know, right? So the thing is obviously there are two general classes of endocrine disorders, right? There's disorders where hormones are low, right? Hormones are low, you know, like Adesins disease, for example, Adesins disease, an example, like a very good classic case. And then there's situations where hormones are high, right? Hormones are extensive, like for patients like con syndrome, where they have like primary hyperoudnosteronism and all these things, right? But honestly, like I just want to introduce it to a general principle and then give examples. And I think it's going to make some things click in your brain. The thing is, see, if you ever have a situation in the endocrine system where hormones are low, try to stimulate the gland as a confirmatory test. I'm going to say that again, when you have a situation in endocrinology where hormones are low, as a confirmatory test, try to stimulate the gland.

But if you have a situation in endocrinology, where the gland is making too much hormone, hormone, hormone, making way too much, suppress that gland, try to suppress that gland, right? And again, you see me keep saying confirmatory test, confirmatory test, confirmatory test. These tests, these suppression and stimulation tests are typically used in situations where you want to confirm the diagnosis, right? So typically you would have done something for screening and then these suppression and stimulation tests are typically going to be for what? For confirmation, right? So like for example, when a person has a primary hyper-autosteronism, the first thing you start off with is measuring the out-dose-troned to running concentration. And then after that, you're then going to go ahead and do the some kind of suppression tests that we're going to talk about, right? Or if a person, for example, has a hyper-cordisolism, a person has like pushing syndrome, you typically start off with one of these screening tests, right? Like the 24-hour-hour-hour-cordisol or the Lodus-dexamethasone suppression tests or the late night saliva recorders on, right? Or say for example, you're dealing with a condition like a growth hormone excess, right? Like acromegaly or gigantism. Remember, typically you're going to start off by, you know, doing a checking IGF-1 levels before you then go further, right?

So typically there's going to be a screening test, but in my experience, these suppression and stimulation tests, they tend to be confirmatory tests, right? Okay, so let's start first by talking about the suppression tests, right? And again, the classic one, right? You're going to see a person that has moon faces, buffalo hump, skin thinning. The person may have like hypochylemia, right? You may be infertile, they may have all, you know, purple striay and all these stains, right? Obviously, I want to think about a person that has a hyper-cordisolism. I want to think about a person that has pushing syndrome, right? Although, remember, the most common cause of pushing syndrome is from exogenous terribute, right? Exogenous but if we're looking to situations endogenous to the body, the most common cause of hyper-cordisolism is going to be pushing disease, right? So what's pushing disease? Remember, pushing disease is when you have a pituitary adenoma that is making a lot of AC Ts, right? So, let's talk about these suppression tests, right? So because it's a condition of excess, right? So we're going to try to suppress the gland. Well, there are two suppression tests we're going to see with, with the HPA access and that's the low dose dexamethasone suppression test and the high dose dexamethasone suppression test. The thing is, it just so happens that the low dose dexamethasone suppression test is used as a screening test for pushing syndrome.

But before I discuss this suppression test, I think it's just very helpful to understand something. What does the dexamethasone suppression test do? Literally like what's the job of dexamethasone? Dexamethasone is a steroid. It's literally a steroid, right? And the goal of this suppression test is to see if you can suppress cortisol production. That's your goal. You want to see if you can do what? If you can suppress cortisol production, right? So what should dexamethasone do on that normal circumstances in normal people? What is it supposed to do is that it's supposed to, because it's a steroid, it's supposed to suppress ACTH production. And then if ACTH production is suppressed, then you will not stimulate the adrenal cortex. You will not stimulate the zona fascicular to make cortisol. That will internally to a suppression of cortisol. So in a normal person, normal person I give you dexamethasone suppression. It's going to suppress your ACTH. You're not going to make cortisol, because ACTH has been suppressed and you're no longer stimulating the zona fascicular. But if a person has hypercortisolism for any reason, think about it. What will the load those dexamethasone suppression tests do? You give load those dexamethasone the night before. The next morning you check the person's cortisol and you notice that the person's cortisol was not suppressed. The person's cortisol was not suppressed. The person's cortisol was not suppressed. The person's cortisol was not suppressed.

That's what we notice. So it's like, wow, okay, there must be something at play that is making our cortisol not suppressed, because the normal response is for your cortisol to suppress. But your cortisol doesn't suppress for some reason. So typically after that, you go ahead and measure like ACTH levels to see if you can differentiate an ACTH dependent cause of cushion syndrome from an ACTH independent cause of cushion syndrome. So for example, if a person has an ACTH dependent cause of cushion syndrome, like Cushing's disease, when you have a pretutor, the number that's making ACTH, the thing is if you give those people, if you give those people high dose dexamethasone, so that's the second suppression test, you give high dose dexamethasone. That high dose dexamethasone will force that pretutor at the norma to stop secreting ACTH, to stop secreting ACTH. When that pretutor at the norma stops secreting ACTH, then you'll stop secreting cortisol from the zone of a seculada of the adrenal cortex. So I know some people may be like, divine, but why is it that when a person has small cell lung cancer, the cortisol does not suppress with high dose dexamethasone. Well, the thing is, in my mind, a logical way to think about that is as follows, right? The thing is we have the HPA axis. The cells that are making this a topic ACTH in small cell lung cancer, they are not part of the HPA axis. These are like cells that are kind of like different.

So in my mind, it just makes sense that they will not respond to the normal signals you're used to seeing with most of the cells, right? So I believe that that's why, right? I believe that that's why that may be the case in that circumstance, right? Now one extra tip that I want to throw in with these are suppression tests is it's actually very important. What if a person has an adrenal adenoma that is causing them to have hypercordysolism? How would they respond with the high dose dexamethasone suppression test? How would they respond? Because this is something many resources do not cover. Many people just think of high dose dexamethasone just in the context of pushing disease where you have a pituitary denomas secreted in ACTH. But let me ask you this, what will happen? And the NBM is they know resources don't cover this so they love to test this. What do you think will happen with high dose dexamethasone? When a person has an adrenal adenoma that is making a lot of cortisol, right? That's making a lot of cortisol. Well think about this for a second. Think about this for a second. If you have this adrenal adenoma that is making a lot of cortisol. What do that adrenal adenoma do to your brain? Well it's going to cause your anterior pituitary to stop making ACTH because of negative feedback. Because your anterior pituitary is working just fine. You just have this adrenal adenoma that's just pumping out a ton of cortisol.

So it's going to suppress your adrenal it's going to suppress your your anterior pituitary to stop making ACTH. So guess what? Before you even do any kind of dexamethasone suppression testing, your ACTH has already been suppressed. Your ACTH has already been what? It has already been suppressed. So let me ask you this. If your ACTH has already been suppressed, is there any substrate for dexamethasone to act on anymore? No. Dexamethasone the only gig it has is to suppress ACTH. But if the ACTH has already been suppressed because of the condition you have, then you will notice no nothing. Whether you do low dose dexamethasone or you do high dose dexamethasone nothing happens. Literally nothing happens. Why? Because the ACTH has already been suppressed by the cortisol coming from the adrenal adenoma that are suppressed at ACTH. That is a very important thing to understand, right? So cortisol will not suppress with low or high dose dexamethasone. When a person has an adrenal adenoma that is the cause of the accushing syndrome. Make sure you understand that. Make sure you understand that, right? But remember high dose dexamethasone will suppress cortisol production in a person with cushing disease. But remember that low dose dexamethasone will not suppress cortisol production in a person with cushing disease. Remember cushing disease is when you have a pediatric adenoma that's making easy to teach. Now let's go to the next suppression test.

The next suppression test is going to be the glucose suppression test. Many times we're going to use this to confirm the diagnosis of acromegaly or gigantism when you have growth hormone excess. Because we know that growth hormone is a diabetes genic hormone. Its job is to raise blood glucose levels. But after your blood glucose rises, that high blood glucose in turn suppresses growth hormone production. So the thing is if a person has growth hormone excess, they have a pediatric adenoma making growth hormone. One of the ways you can confirm the diagnosis is by doing the glucose suppression test. Again, obviously you should have measured IGF1 levels first. But then you give the person an oral glucose load. You measure their growth hormone before and after you give the glucose. In a normal person, you give that glucose load that should suppress growth hormone production. But in a person that has a pediatric adenoma for example making a lot of growth hormone, the growth hormone will not suppress in response to that glucose load. That's the basis of the glucose suppression test for growth hormone excess. What's another excess disorder that's usually tested on the exams? Think of con syndrome, think of primary hyper-adosteroneism. Think of primary hyper-adosteroneism. Con syndrome. You usually have a problem with your adrenal glands. Either an adrenal adenoma or adrenal hyperplasia. We are making a ton of audosterone.

Typically you're going to start off working on that disorder by measuring the audosterone to renein concentration. Because you have this adrenal adenoma pumping out a lot of audosterone. That's going to cause you to reabsorb a lot of fluid and salt in your kidneys. That's going to raise your blood volume. It's going to raise your blood pressure. Your body is going to be like, my blood pressure is high. My blood pressure is high. What is your body going to do? Your body is literally going to turn down. It's literally going to turn down. It's literally going to do a turn down renein production. It's going to turn down the renein and your tensile audosterone system. These people are making tons of audosterone, but their renein is low. The audosterone to renear ratio should be high. Typically it's going to be more than 20 or 30 on your exams. That's how you scream. How do you confirm? You confirm by doing something called the salt suppression test. In a normal person like me and you, if you notice many times to understand things in this world, understand the normal situation. When you understand the normal situation, the abnormal situation is going to make a lot of sense to you. The normal situation is, hey, if I give you salt, if I give you a bunch of salt, I can tell you, hey, good, good, McDonald's or whatever, right? Just take any processed fast food on healthy food, stomach, McDonald's, right? But take a lot of unhealthy food, right? A lot of salt containing food.

In a normal person like me and you, if you take that salt containing food, your body is going to be like, whoa, I'm taking all this salt in because salt is very smolically active. It's going to hold onto water. Your body is going to be like, I don't want to have this going on with me, right? So your body is going to say, okay, my blood volume and blood pressure is too high, right? So you're going to suppress our dust room production because of that, right? But in a person that has con syndrome, in a person that has primary hyper-industrial disease, if you give them a salt load, you give them a salt load, measure the out dust room before and after the test, you'll notice that the out dust room will not suppress. That failure of suppression is diagnostic of con syndrome, right? And another way you can actually do a similar test for con syndrome is to do something called a saline-infusion test. Believe it or not, there are many different versions they can test with confirming the diagnosis of con syndrome on your exam, right? Like the saline-infusion test, I literally give you a bunch of normal saline. Again, by giving a person a bunch of normal saline, you're increasing the blood volume, you're increasing the blood pressure. That's to suppress our dust room production. But you're going to notice that these people, the out dust room, fails to suppress, even with that saline load, right?

Another way you may will see this on the exam, the thing is, see, there's a test I'm about to mention that probably nobody does anymore. But the fact that they don't do it anymore clinically does not mean it doesn't show up on the USME Ls. In fact, the USME Ls, they have this habit of things that are no longer done anymore. The major is bringing it in a question stem just as a way to assess a person's understanding of basic physiology. Like a very good example of that is that shielding test for B12 deficiency, right? It's kind of a long complicated test. Almost very few people do that anymore, but it's a very, very good way to see if a person has a good understanding of B12 physiology, right? So the test I'm going to talk about here is the captopryl suppression test for con syndrome, right? So what is captopryl? Captopryl is an is inhibitor. It literally inhibits the conversion of angiotensin 1 to angiotensin 2. And we know what angiotensin 2 does. Angiotensin 2 goes to the zonal glomerulosa, at least one of its jobs, is to go to the zonal glomerulosa of the adrenal cortex to cause you to make out a doster. Right? So think about it in a normal person if I give you a captopryl, you suppress ACE, you suppress angiotensin 2 production. You will not stimulate the zonal glomerulosa to make out a doster. So your outdoster level should fall.

But in a person that has con syndrome, it doesn't matter what you do, give them captopryl, you will notice that their outdoster production will fail to fall. The outdoster production will fail to fall, even with you giving them a captopryl, which is an is inhibitor. So those are the suppression tests. Now let's talk about the stimulation tests. The classic ones they love to test, they love to test like other sins disease, primary adrenaline, sufficiency. So what is one classic test they love to go after? They love to go after the ECT stimulation test, the co-synthropin stimulation test. In other sins disease, you've made all the antibodies, you've destroyed the adrenal cortex. So it's like, oh no, I'm not making cortisol, I'm not making out doster, I'm not making a DHS. Well, you can actually like that, no side sins disease. If I do the co-synthropin stimulation test, co-synthropin is an ECTH analogue. In a normal person like me and you, if I give you a bunch of ECTH, it's going to stimulate your adrenal cortex to make a ton of cortisol. But if I give you a bunch of ECTH, in this case co-synthropin, COSYNTROPIN, I give you a bunch of co-synthropin, and your cortisol fails to rise in response. That is confirmatory. That's diagnostic of Adescent's disease. Now, the thing is our friends at the MDM is they know that all of you know, Adescent's disease, co-synthropin stimulation test. So what do they do sometimes these days?

Sometimes they actually use the co-synthropin stimulation test to test for the the introducing in a question. It may not be something that's done clinically, but it may introduce it in a question as a way to see if you understand the physiology of congenital adrenal hyperplasia. If you really think about it, if a person has congenital adrenal hyperplasia, they will have the same results with co-synthropin stimulation. Because think about it, if you give a person co-synthropin and they have, for example, 21 hydroxylides deficiency, they have that enzyme defect. It doesn't matter how much ECTH you give the person. They still will not be able to make cortisol because they literally lack the enzyme for making cortisol. So when people have congenital adrenal hyperplasia, they will also have a failure of their cortisol to rise with co-synthropin stimulation. That's a very good classic example of a derivative that our friends at the NBM Es can test. Right? Our friends at the NBM Es can test. And one other thing I think I want you to keep in mind with primary adrenal insufficiency is that if you give a person insulin, what would you expect to happen in a person with primary adrenal insufficiency? See, if I give you insulin, what would that do to your blood glucose levels? It's going to literally tank your blood glucose levels. If your blood glucose levels tank, your body is going to get stressed. When your body gets stressed, it's going to make cortisol in response.

It's going to operate your axis. You're going to make a lot of, you know, CRH, a lot of ACTH, a lot of cortisol in response to that. That's what it's supposed to happen. But if a person has an abnormal HPA axis, an abnormal HPA axis, right? Let's say, for example, they have other scents disease. In response to the hypoglycemia, they may make a ton of CRH. They may make a ton of ACTH because those glands are working. But they will not make cortisol in response. That's a way to provoke. That's a way to provoke to see that. Hmm. Does this person have adrenal insufficiency or not? But let's say, for example, the HPA axis problem, let's say it's in your, uh, it's in your antirapitritory and you provoke hypoglycemia by giving insulin. Then you notice that the person may be making a lot of CRH, but because the antirapitritory doesn't work, they won't make ACTH. And because they're not making ACTH, they will not stimulate the adrenal cortex to make cortisol, right? So sometimes this is called like the insulin tolerance test. It's a very good way to see if a person's HPA axis works. But honestly, it's also a very good way to see if a person's growth hormone axis works because we know that hypoglycemia should stimulate growth hormone production. But if you notice that you give up, you, you induce hypoglycemia by giving insulin and a person's growth hormone feels to rise.

That's actually pretty confirmatory of a person also having a, like, you know, like a growth hormone, a deficiency or something along those lines, right? And then I think the last stimulation test I'm going to discuss is the GNRH stimulation test, right? The GNRH stimulation test. I'll use this to diagnose a precocious puberty, right? Precocious puberty, right? So the thing is you give a person a bunch of GNRH, right? Again, at a certain age, your HPG axis should not be working like crazy, right? But if you give a person GNRH, and you notice that they are going to do tropines, they are LHFSE trice significantly crazy, crazy, crazy amounts of both certain thresholds. That tells you that, mmm, this person probably has central precocious puberty, you know, their, their, their, their anterior pituitary is working a little too well in making gonadotropines, which are stimulating their gonads to make a lot of sex hormones, just to make a lot of sex hormones, right? So I think I'm going to go ahead and stop here. I think I'm going to go ahead and stop here, right? Although if you notice that, hey, I give a person a bunch of GNRH and their LHFSE does not rise, their estrogen testosterone does not rise, then that pretty much tells you that, oh, this person may have like a hypo gonadotropic hypo gonadism, right? They must have some kind of problem at the anterior pituitary, right?

Where they are not making FSH or LH and then those things because they are not being made, you're not stimulating the gonads to make sex hormones, right? Or you can even be a condition like common syndrome, right? In common syndrome, your GNRH producing neurons are not working, right? Your GNRH producing neurons are not working, right? But if you were to give that person GNRH, remember in those people, the anterior pituitary is intact, their gonads are intact. So when you give those people, when you give those people GNRH, then you're going to notice that, oh, wow, this person's access works. This person's access works because by giving that GNRH, you're going to stimulate the anterior pituitary. The anterior pituitary is intact. So it's going to start making FSH LH. And then when you start making FSH LH because your gonads are intact, they're going to start making estrogenant testosterone, right? So do you see why the USML is they love this because they are just so many different permutations they can go after, right? So I hope you find this podcast to be helpful. If you're interested in any of my classes, have a bunch of classes starting next week for all the USML young complex exams, shoot me an email and I can give you some more information, right? And I also offer one on one tutoring and I have this podcast on the major podcast apps and I also have another website called divineinterventionlifelessons.com.

You know, every week I post like two or three podcasts from a biblical perspective address a life lesson. There's actually an Apple podcast for that called the divine intervention life lessons podcast. So thank you for listening to me today. I will see you in episode 6133. Have a wonderful day. God bless you and bye for now. Thank you.

Suppression tests are typically used when you suspect a patient has excess hormone production, and the goal is to confirm the diagnosis by showing that the gland cannot be suppressed artificially.

It helps distinguish between pituitary-dependent causes (like Cushing's disease) and adrenal/ectopic sources of ACTH. High dose suppresses cortisol in Cushing's disease but not in an adrenal adenoma.

Failure of plasma aldosterone concentration to suppress, despite increased blood volume and pressure from the salt load.

High (>20 or 30). This indicates high aldosterone production with inappropriately low renin levels.

Failure of cortisol to rise significantly above baseline, confirming primary adrenal insufficiency.

The Hypothalamic-Pituitary-Gonadal (HPG) axis.

Salt loading test; failure of aldosterone suppression confirms primary hyperaldosteronism.

Cortisol levels significantly decrease/suppress, indicating pituitary responsiveness to negative feedback.

Cortisol will not suppress, because the adenoma secretes cortisol autonomously and independently of HPA axis regulation.

Failure of cortisol to rise significantly above baseline.

Primary hyperaldosteronism; high aldosterone from the adrenal gland coupled with low renin (due to volume expansion).

The HPG axis. A positive test shows elevated LH/FSH response.

Acromegaly or gigantism (GH excess), indicating autonomous GH secretion from a pituitary adenoma.

Salt loading test; failure of aldosterone suppression confirms primary hyperaldosteronism.

Cortisol levels significantly decrease/suppress, indicating pituitary responsiveness to negative feedback.

Cortisol will not suppress, because the adenoma secretes cortisol autonomously and independently of HPA axis regulation.

Failure of cortisol to rise significantly above baseline.

Primary hyperaldosteronism; high aldosterone from the adrenal gland coupled with low renin (due to volume expansion).

The HPG axis. A positive test shows elevated LH/FSH response.

Acromegaly or gigantism (GH excess), indicating autonomous GH secretion from a pituitary adenoma.