Transcript for:
Understanding Cushing Syndrome and Cushing's Disease

what's up Ninja nerds in this video today we're going to be talking about Cushing syndrome and Cushing's Disease this is a part of our clinical medicine section if you guys like these videos they help you they make sense please support us some simple ways that you can do that that goes a long way with the YouTube algorithm is just hitting the like button comment down in the comment section and please subscribe if you have the ability to I really suggest highly suggest that you guys go to our website you can do that by clicking down the description box below there's a link that'll go to our website we have a lot of a awesome tools such as things like notes illustrations we have tons of quiz questions and we're even developing exam prep courses so please go check that out I think that you'll truly benefit from it without further Ado let's talk about Cushing so there's two different types and then there's like this little extra one that we kind of Chuck in there a little bit there's Cushing syndrome and there's Cushing's Disease and we'll talk a little bit about this one last Cushing syndrome is another way of kind of calling it like a primary hypercortisolism so remember how we talked about this a lot like primary Ary and secondary hyper hypothyroidism and same thing with adrenal insufficiency you can kind of think about this the same way but pertaining to this in the sense of it's a primary hypercortisolism and a secondary hypercortisolism so that's the way we're going to look at it and it makes it easier to think about it that way so Cushing syndrome is a problem with the adrenal gland itself particularly the adrenal cortex so you have to remember there's different layers there's a Zona glosa Zona facula and the zono reticularis what happens is for some reason there's something hyperfunctioning of adrenal gland usually that ends up pumping out tons of cortisol into the bloodstream so for whatever reason there is an increase in cortisol release particularly from the zone of facula and so this thing is just pumping out cortisol whenever cortisol is released in high amounts what it does is it tells the hypothalamus that the cortisol levels are high hypothalamus has to say okay I got to shut down the cortisol pathway for a little bit so what I'm going to do is I'm going to release a molecule called CR but I'm going to release it in a very slow amount or pretty pretty much not at all all right the reason why is if there's less who he saw that that's pretty cool right if there's less CR that'll tell up anti pituitary hey less CR I need you to make less act so that's what will happen is there'll be a less production of act now Act is important because whenever the levels of this are low it's going to have less what feedback because what happens is low act means that you're going to try to tell the in this case the adrenal cortex hey stop producing as much cortisol but in this disease cycle there's no in there's no ability of the ACT to kind of say hey stop making cortisol because in this particular scenario the adrenal cortex just keeps pumping out this cortisol the question is is what's causing this increase in cortisol production it's usually two particular things one is it's from the adrenal cortex itself right there's some type of hyperfunctioning of this puppy right and we'll talk about what that reason is it's not hard to remember but there's a hyperfunctioning of the adrenal cortex the other thing is that there's no adrenal cortex problem at all what actually maybe is is that there's some type of exogenous steroid use so somebody is actually taking exogenous steroids and this is a lot of the time we'll talk about this a little bit more and and detail when we get to that point this is happening and usually patients who have underlying like autoimmune diseases of some sort but what happens is that steroid that you're giving ends up acting just like cortisol resembles cortisol even though it's not being produced from the adrenal cortex taking it via pill or injection it's getting into the bloodstream and acting like cortisol so these are the two particular components here that I want you guys to think about with respect to cushion syndrome it's a primary hypercortisolism with a reduction in act now let's talk about these two particular patho physiologies there's a hyperfunctioning adrenal gland so this thing whatever it may be is pumping out tons and tons of cortisol and that's really the trigger for all of this process but you have to start asking yourself the question what is is this thing what is this glomach that's hanging off the adrenal cortex it's an adrenal adenoma so adrenal adenomas are by far going to be the most common cause of a hyperfunctioning adrenal gland leading to its massive production of cortisol in very small populations you may have adrenal carcinomas that can cause this but it's very rare it's often times adrenal adenomas that are the trigger for this that's really all I want you guys to think about that there's no like really high y epidemiological or high yield pearls for your USM step one or step two or even your pants that really helps us any more than that other than knowing it's an adrenal adenoma it's the most common cause of a hyperfunctioning adrenal gland that leads us to the next component here which is an exogenous steroid use so we talked about this before is exogenous steroid use means that the patient's likely on some type of corticosteroids and when they're on these corticosteroids it's usually chronic use right so they're they're using chronically corticosteroids for a long long time what are the different types of cortical steroids well there's many of them right often times we can think about a couple here prazone I'd say would be the most common culprit because this is one that you usually take in an outpatient basis because it's usually oral you could also consider things like pricone I would say it's less commonly utilized though another one would be methyl pricone but this is usually going to be in a patient who is more in the hospital because this is more of an IV medication so with that being said it's usually patients who are on chronic corticosteroids the reason why is these chronic cortical steroids already told you end up acting or resembling an increase in cortisol so these resemble an increase in cortisol now you have to start asking yourself the question what would be a reason that PE people would be on chronic steroids chronic cortical steroids well there could be a couple different reasons one is it maybe the patient has an underlying autoimmune disease and they need to take this suppress their immune system from attacking itself or maybe they've had a transplant of some sort they need some type of steroid use to suppress their body from rejecting that transplant either way you have to think about as a patient taking immunosuppressant medications such as corticosteroids or are they taking it for an autoimmune disease that would be something that I'd be thinking about here that's why it's really easy to elucidate this from the history as compared to this you may need Imaging all right with that being said we've talked about cushion syndrome and it takes us to the next aspect here which is now we have to talk about Cushing's disease so with Cushing's disease in ectopic act production we have to start kind of narrowing our mindset here which to talking about okay it's not no longer an adrenal gland problem my friends it's probably something to do with the pituitary or some type of ectopic source so let's talk a little bit about that so with that being said in Cushing's Disease I want you to think about it more as like a secondary hypercortisolism meaning the pituitary is the problem here and what the pituitary is doing is it's pumping out a lot of act when you pump out a lot of act you have act receptors that are present on the adrenal cortex it'll tell the adrenal cortex hey lots of AC buddy go ahead and start pumping out cortisol and as a result that's what will happen we'll end up with an increase in cortisol within the bloodstream so either way the primary end point here is that cortisol is high and just how the cortisol is elevated determines if it's Cushing syndrome or Cushing's Disease and Cushing syndrome is the adrenal cortex and Cushing's Disease it's a pituitary problem increased H production now that's one component is it's a pituitary problem right and usually the most common cause of this is hyper pituitary pituitary ISM and we'll talk about what triggers this but it's either way it's pretty straightforward the pituitary is pumping on Act the other one is you could have an ectopic site so some tissue cells are gaining the capacity to produce hormones that's interesting and so usually whenever you have an ectopic site that's producing hormones such as an increase and act same thing here here's some tumor cells they're producing act they're then triggering the adrenal cortex to make cortisol this is going to be an ectopic site act should not be being produced by any other cells except for the pituitary if it is it's an ectopic site and we call this likely a par neoplastic syndrome that means that there's likely a tumor somewhere in the body that is pumping out act and triggering an increase in cortisol so you have to think Cushing syndrome increase cortisol decrease act Cushing's disease in ectopic act production is high act and high cortisol now which with that being said let's move into the next component here which is okay it's either hyperpituitarism or a paraneoplastic syndrome what causes hyper pituitarism in otherwi in other words what's causing this pituitary gland to pump out very high levels of act and it's actually relatively straightforward if you guys remember from the pituitary disorders there is a tumor that is usually present right here in the an pituitary and it can start gaining the capacity to secrete Act this is usually what we refer to as a pituitary microadenoma so pituitary micro adenoma because you have to remember that macro adenomas these have compressive effects and whenever you compress the tissue you lose the capacity of that tissue to produce hormones this is a micro adenoma it's not going to have that Mass Effect so whenever I say microadenoma it has to be less than 10 mm in size and here's the other thing with pituitary microadenomas they don't really have impressive effects so they don't have the B temporal hopia they don't have headaches but the thing is is that they also have other hormones that are usually elevated and so you want to think about do they have an elevated prolactin which is often times the most common one do they have an elevated growth hormone that could also be possible and usually what would be kind of a giveaway from his is if they have increased act and on top of that they also have an increas in prolactin and increase in growth hormone and there is another one it's called t sh if the patient also had concominant disorders such as galaura gynecomastia acromegaly and hyperthyroidism in combination with their Cushings you should really start thinking about a pituitary microadenoma that's producing multiple hormones with that being said the last thing that I want you to think about is a paraneoplastic syndrome that's that ectopic act production there's a tumor somewhere in the body and that tumor is pumping out act and that act is the driver for cortisol salt production you have to ask yourself the question where's the tumor well it could be anywhere but by far the most common cause is going to be small cell lung cancer because this cancer will gain the capacity to produce hormones so with that being said we now know what's the trigger for high act and high cortisol but two microadenoma or small so lung cancer what's the trigger for high cortisol and resulting decrease in AC it's either an adrenal adenoma or chronic steroid use now let's talk about what are the long-term complications and some of the classic findings and Cushings Disease and syndrome all right my friends so now we move on to the next component of this which is talking about what are the classic findings of a patient who has Cushing syndrome or Cushings Disease and then what are the complications we really did a pretty good job I think of kind of underlying and and really explaining the pathophysiology and the causes of Cushing syndrome Cushing's Disease and ectopic act production so now what I want us to understand is okay how will these patients present well first off there's usually a very uniform presentation that's common among all of them Cushing syndrome disease and ectopic act production and that is that they usually all present with this interesting like fat redistribution type of presentation which is they can present with a buffalo hump usually on their back which looks like this they also may present with a moon face which is the swelling of their face which looks like this and then lastly they may also present with a lot of trunco abdominal obesity which usually sometimes we'll talk about in a little bit of a second here has a lot of strier stretch marks due to the skin atrophy Pro process which looks like this what I want you guys to understand here is why does the buffalo hump why does the moon face why does the trunkal Obesity actually occur when we look at the atopos tissue here what happens is cortisol plays a very prominent role in metabolism and particularly lipolysis and that's because during a stress response whenever cortisol is released it helps to trigger lipolysis which that you can utilize those fatty acids and glycerol for ATP production in the muscles but if cortisol is really elevated what it'll do is it'll trigger the lipolysis process and what you'll do is something really interesting you'll undergo lipolysis but it's more more of the appendages so in other words you'll start breaking down some of the fat tissue present in the arms and the legs and then what's weird is you'll also do something called redistribution of that fat now this is what's interesting I don't understand why this happens but you move some of the fat towards the central portion of the body so we refer to this as the kind of the more axial component of our skeleton so it moves it to the axial skeleton and then parts of that axial skeleton includes the back the abdomen and the face and so that's why you get this buffalo hump the moon face and the trunco Obesity is because of an increase in lipolysis and an increase in fat redistribution due to the high cortisol levels that's the very very common presentation you have to remember that if you see that you should have a high degree of Suspicion for Cushings the next thing is that skin atrophy and stria that we talked about this is actually due to proteolysis so whenever cortisol levels are high again your body will tap into any kind of energy source that it really can because it's using it for a stress response so whenever cortisol is high what it will do is it'll trigger what's called a proteolysis pathway and what I mean is is that she'll trigger an increase in the breakdown of proteins and there's variable amounts of of proteins and so many different types of proteins that we'll use to make amino acids and generate that for ATP in the muscles one of the big ones happens to be collagen this is a very prominent Protein that's present in the skin and if we start breaking down a lot of that protein of that collagen inside the skin the skin gets a little bit more weak and it becomes easier to stretch and that's where we get this abdominal strier and skin atrophy so it's really important to remember that here's the next thing that I really want you guys to think about we will only see this presentation so these Cushing syndrome Cushings Disease you'll see it this you will only see in Cushing's Disease what happens is in Cushing's Disease what we know is that there is likely a pituitary microadenoma that is pumping out what act that's triggering the increase in cortisol same thing triggering an increase inre in act right that tries to increase the cortisol production but you know what else is really interesting there's a molecule called called proopiomelanocortin it's a precursor molecule that when it gets broken down it makes act but it also makes Alpha melany stimulating hormone when Alpha mocy stimulating hormone is present it'll then go and act on your melanocytes and stimulate these melanocytes to incre increase the production of melanin when there is a lot of melanin that's actually produced this will particularly deposit in the skin um M the lips maybe around the face hands feet and it looks like this so we see now that hyperpigmentation is a result only of Cushings Disease not of Cushing syndrome that is super important the other concept here is that Cushings disease whenever you produce tons of act yes you will have an increase in cortisol but there's another hormone that is actually dependent on act to a small degree and it is called DHE EA dihydro epiandrosterone and andrine diione either way these are androgens now androgens and the female play a role of kind of acting like testosterone when these are produced in high levels these patients will exhibit more masculine type of masculinization type of features in other words they'll get pretty hairy they start growing like a full beard it's called heroism okay the other one is they can also get a very interesting type of libido that kind of goes crazy so this is the two particular features that you may see is heroism and increased libido and acne heroism looks a little bit like this all right so now we have an understanding here that in Cushings Disease only you will have this pathway with hyperpigmentation and this pathway with masculinization you will not see this in Cushing syndrome the big thing that you have to remember is that there are many complications that can present with chronic Cushing syndrome or Cushing disease because of that high cortisol in the body we shouldn't be having cortisol levels elevated all the time when they are you get a bunch of complications such as one which is secondary hypertension we talked about this in hypertension lectures that cortisol when released in high levels acts on these receptors called the alpha 1 receptors and what it does is is it stimulates these alpha 1 receptors by increasing the sympathetic nervous system activity of those receptors so by having lots of cortisol what you'll do is is you'll increase the alpha 1 receptor sensitivity so that when epinephrine and norepinephrine and all of those guys get around this vicinity it'll really increase the vasoconstrictive mechanisms and then what happens is your systemic vascular resistance goes up and your blood pressure will increase and so often times the reason for this elevation in blood pressure is because high levels of cortisol really squeeze the blood vessels pretty intensely it may also to some degree increase your cardiac output but it's not as profound you know what else it can do we talked about this a little bit in the adrenal insufficiency lecture more the opposite effect is that cortisol to some degree does have a mineral corticoid effect it's minimal but it is present and so it may also help to increase sodium and water retention to some degree and so if I increased my sodium and water retention all right then what I'm going to do is I'm going to have more like fluid and volume inside of my bloodstream and so what happens is the blood volume goes up and if my blood volume goes up then sub sequently so will my blood pressure so whenever these patients come in this is the mechanism of them having high blood pressure but how will it present usually secondary hypertension is classic in a patient to presents with hypertension despite 3+ anti-hypertensive agents this is the real big thing that I need you guys to remember if a patient comes in and they have high blood pressure and they're younger or they are on three plus anti-hypertensive medications with no underlying trigger you really want to think about could they have secondary hypertension due to Cushing's syndrome or Cushing disease the next concept here is diabetes and malius now it's important to remember that yes Cushing syndrome and Cushing disease can increase the risk of diabetes but it's also more common that they will worsen a patient with underlying diabetes what do I mean well cortisol you have to remember that it works on the liver and what it helps to do is it helps to be able to increase your blood glucose levels without going crazy I want you guys to remember that cortisol works on the liver and it increases your blood glucose levels via two particular Pathways one is called gluconeogenesis and the other one is called glycogenolysis either way these pathways are being stimulated and pushing more glucose into the blood causing hypoglycemia hypoglycemia as a result can lead to multiple complications long term but what it also can do is is it can stimulate the pancreas to make more insulin and as you produce more insulin your body starts to develop resistance to that insulin and that's why these patients can have insulin resistance so one of the very common manifestations of this is a patient who has very significant hyperglycemia often times maybe without a diagnosis of diabetes you really want to think about that okay my friends the next component here is osteoporosis with patients who are on chronic steroids for a long time we actually do suggest that they get like dexa scans because they're at high risk of osteopenia osteoporosis and as a result pathological fractures and so often times what happens is it's the same concept is actually right up here is that cortisol leads to proteolysis and so whenever I get a lot of proteolysis guess what one of the most common proteins are inside of the bone gives a lot of the strength and integrity to the Bone collagen and so because I get a lot of collagen that gets broken down unfortunately the bones become weaker and the patients usually progress through a couple stages where the bones become really really thin and weak called osteopenia maybe they start becoming really weak and very very poor it's called osteoporosis and and then lastly they may present with and this is usually the most scary kind of complication is they may present with pathological fractures especially have more of the weightbearing bones like the the femur and so with elevated cortisol levels you get increased proteolysis and you accelerate the bone destructive pathway that can lead to osteopenia osteoporosis and pathological fractures so in patients who are on chronic steroids you really want to be considering working them up considering these things so how do I do that usually we often do dexa scans to look at the bone mineral density to see if it gets less than -2.5 that suggests that they're going towards an osteoporosis path PA pathway and then the other concept is looking do they have any pathological fractures and seeing if they have an underlying elevated cortisol level so these are some big things that I really want you guys to think about here is underlying pathological fractures or a reduced bone mineral density due to elevated cortisol levels in the setting of Cushings last thing well almost last thing cortisol is interesting it's a again it's a stress response hormone so when it's released what it does is it tries to kind of help to amp up a lot of our systems right increase our sugar increase our blood pressure and do a lot of these things to help to initiate the stress response however one of the unfortunate things that can happen is that cortisol can actually cause an immunosuppressive effect what do I mean by that so in other words we have different types of cells called neutrophils we can inhibit these nutrifil and we do it via an interesting way neutrophils are supposed to move from the bloodstream and squeeze through the blood vessels and go out and fight off this bacteria that's called diapedesis it'll actually inhibit that process and so lots of neutrophils actually stay up in the bloodstream and sometimes it actually can create a false interesting like lab value called a very prominent lucyisanerd the other thing is it can also suppress lymphocytes te- cells and B cells and so now you inhibit these lymphocytes which produce antibodies and help to play a role within our immune system function now you lose the ability of these immune system cells to come out here and fight off these pathogens as a result these pathogens can stay inside of the interstitial fluid or wherever the tissue space is and colonize and build up and as a result this can lead to infections and there's so many different types of infections and that's what you have to watch out for often times it's usually fungal infection that is the most common because it's kind of like an opportunistic infection if you want to think about it you're immunosuppressed you allow for fungi to grow so fungal infections tend to be the most common I'd say one of the biggest ones is going to be candidasis so candidasis would be a really big one that you want to think about think about the oral thrush sometimes it can even get down into the esophagus as well the other one is like skin infections so watch out for cellulitis and I think one of the big ones that it really is an opportunistic bacteria is MCA so you really want to watch out for Mera which is a methylin resistant stafas arus the last one is another opportunistic infection but particularly to the lungs and this is called pneumonia now pneumonia is usually something that we see in infections that are again opportunistic which is called pneumocystic gerovich pneumonia and this is someone who is usually having HIV with a CD4 count that's relatively low like less than 200 or they're significantly immunosuppressed so watch out for infections but i' the most common one is going to be usually your fungal infections the other thing that's actually really helpful to remember is that sometimes cortisol whenever it's really really elevated it will inhibit this diapedesis pathway where nutrifil are supposed to come out here so nutrifil stay in the bloodstream and so watch out because sometimes these patients can have very very high white blood cell counts and it'll make you think that they have like some type of infection they have a ation pathway and so instead they stay in the bloodstream so watch out for a increase in the white blood cell count with a prominent nutrifil amount but it's not due to an underlying infection it's just due to this inhibition of margination lastly when cortisol levels are elevated again it plays a role with our stress response so when cortisol levels are low we're kind of lethargic you're more fatigued everything's kind of shut down in the brain but whenever the cortisol levels are high you're amped up your stress response your sympathetic nervous system is on and on on edge and so often times these patients develop severe agitation severe agitation and sometimes I'm not even kidding these patients can develop psychosis I've seen it in the ICU a lot where patients can develop like agitated delirium and it progresses to fullon psychosis this is usually whenever you're giving them large amounts of steroids for whatever reason but you want to watch out for this because over time patients can develop agitation they can develop insomnia and and they can even develop psychosis so these are really really prominent things that I have to have you guys remember respectively with Cushing syndrome and Cushing's disease so with all of this being said we see a lot of things going on here with Cushing syndrome and Cushing's Disease the biggest ones that you have to remember for classic findings is the skin atrophy stria and the fat redistribution signs that is the most important thing to think about oh this pushing could have Cushings then think about do they have other complications going along with it most commonly secondary hypertension is a big one osteoporosis and very high risk of fungal infections May Q you to start thinking about does this patient have Cushings and now let's move into the diagnostic workup so the first question is is the cortisol High that's all I got to know problem is we got to do at least two to three tests to see if it's positive so one is the 24-hour urinary cortisol if that cortisol is elevated throughout the entire 24-hour period that suggests the hyper cortisol State the other one is I want to do something called a lowd do dexamethasone test maybe like one milligram of dexamethasone it's basically a steroid it's a little bit of cortisol what it'll do is in normal individuals normal patients patients who don't have Cushing syndrome or disease it'll suppress the antipituitary tell it to stop making act tell the adrenal cortex to stop making cortisol and their cortisol levels should be low but if their cortisol levels are high that tells me that there's a Cushing's Disease or syndrome present it means that the anti pituitary is not responding to this the low dose of dexamethasone and it's still producing act or it tells me that it doesn't really matter because the adrenal cortex is still producing um cortisol regardless of what you give them so if they have high cortisol despite getting a little bit of steroid it tells me that they're not normal and they likely have Cushings if I also test a late night salivary cortisol and that ends up being elevated again tells me the cortisol levels are high so if two out of these three tests are positive now I can go ahead and move on and say this patient probably has some degree of Cushings I just got to figure out which one is it coming from the pituitary and ectopic tumor or is it coming from the adrenal gland if I get an ACT test that should tell me if the ACT is high it's then coming again from some type of pituitary tumor or a lung tumor so it's probably Cushing's Disease the next thing I got to figure out is is it the tumor from the pituitary or is it a tumor from the lung now you can do two tests or you can do one of the two tests you can do a CR stimulation test or you can do a high do dexamethasone test the concept behind this is that the pituitary if you give it if you have pituitary microadenoma and you give it CR it will stimulate that anti pituitary to make more act it it won't really do that for the ectopic site if you give them high dose dexamethasone that'll actually suppress if you give them like 8 to 10 milligrams of dexamethasone it is strong enough to suppress the anti pituitary tumor and tell it to stop making as much act and therefore cortisol so if I do this and I suspect that it's pituitary I will have an increased response to CR and I will have a decrease response to dexamethazone this right here tells me that it's coming from the pituitary but if I think that it's ectopic I'll give them CR and it won't make any difference it won't really change their act it'll still remain elevated if I give them highd do dexamethasone it won't really matter the AC and the cortisol will remain the same because it's not going to be suppressed or it's not going to be stimulated now before we show you that here again if I think it's pituitary Source what's the best thing to do once I have this kind of degree of confirmation I can get a pituitary MRI oh there she blow there's our pituitary microadenoma that's the cause of this but again if I do this test and I say no change no change it's likely that's some type of ectopic site so what's the most common area the lungs so I can probably do a pan C scan or a pet scan usually just make sure the most common one is lung cancer but make sure it's not a tumor somewhere else in the body that's the cause of this all right now the other scenario is what if the ACT is low that's definitely primary so that tells me the cortisol is high it's suppressing the anti pituitary it's telling it to shut down the act so it's Cushing syndrome so then I got to remember the most common causes here is usually adrenal adenoma or chronic corticosteroid use so what should I do get a CT if I get a CT of the abdomen adrenal CT adrenal Amara and I see that they got a big old adrenal adenoma I'm done I got the diagnosis and if it's not there and I look in their history and it suggests oh it's probably the you know chronic steroids that they've been on forever then I know the cause and this is how we we go about diagnosing this now for treating Cushing syndrome and disease it's important to again remember which one it is so if a patient has Cushing syndrome it's usually due to steroids that they're taking chronically or it's due to them having an adrenal adenoma so you have to ask yourself the question is it steroid related if it is start tapering down the steroids so reduce their dose so that they're not having that high jump of cortisol and then suppression of act production all right so start tapering them down if it's not steroid related then it's probably adenoma related so in that particular situation you have to reduce the endogenous production of the steroid I have to suppress the adrenal adenoma and how do I do that often times you give them a drug called ketoconazol so you're like wait a second I'm going to give him an antifungal yes but ketoconazol has been shown to be able to suppress steroid hormone synthesis especially cortisol so if I give them ketoconazol I'm only really doing it because I'm trying to suppress the cortisol production and it's usually going to temporize them long enough to be able to get them to a surgical procedure like cutting out that tumor if they're not a surgical candidate though I'm just going to unfortunately have to continue the ketoconazol and monitor their lfts pretty consistently if they are a surgical candidate cool I've tampered down the cortisol pretty well I've suppressed it now we can go ahead and we can cut out that adrenal tumor by doing an adrenalectomy Cushing's disease is a little bit different right so so it's a pituitary problem or it's a Squam cell a small cell carcinoma problem with the lung you have to again for these patients regardless reduce their endogenous production of cortisol so they're going to continue to keep pumping out act that's going to tell the adrenal cortex to continue to make cortisol at least suppress the pathological effects of the high cortisol by giving them ketoconazol and again for these patients you're not going to be doing an adrenalectomy because their adrenalectomy is not the particular issue it's the adrenal gland is the problem it's the pituitary gland that could be the problem so what would you do to remove a pituitary tumor if they have one you do a transphenoidal rection of the pituitary microadenoma and then you lose the source of high act the other scenario if a patient has small cell lung cancer that's a little bit more intense we'll talk about that in the actual lung cancer section uh but that may involve more chemotherapy and radiation you might have to continue those patients on ketoconazol for a long time all right my friends that covers Cushing syndrome and Cushing's Disease I hope it made sense I hope that you guys did enjoy it and as always until next [Music] time