8 Adrenal - Final Edit
Patrick: [00:00:00] Okay, behind the knife ab site review. Today's topic is adrenal. I'm here with Kevin Patrick. This is Jason. So let's dive right in with some high yield anatomy. So Kevin, our resident vascular surgeon, can you please describe for us the vascular supply to the adrenal gland? Yeah, for such a small organ, it has a lot of blood flow.
Patrick: So, the superior adrenal artery branches off the phrenic artery, the middle adrenal artery branches off of, directly from the aorta, and then the inferior adrenal artery branches from the renal artery. And, of course, you need your venous outflow, so you have the left adrenal vein, which drains directly into the left...
Patrick: Renal vein, and then you have your right vein that drains into the IVC. Okay, so Patrick, let's talk about the layers of the adrenal glands. So we break it up typically into the medulla and the cortex, but that break down even further, so walk us through the cortex. Yeah, so we start with the zona glomerulosa.
Patrick: That's the, the salt. Remember we have salt, sugar, sex. We're starting with salt. The zona glomerulosa [00:01:00] regulates aldosterone. Move on to zona fasciculata , this is sugar, which produces glucocorticoids. And the zona reticularis, sex. Kevin, you know anything about that? Apparently it's the androgens and estrogens.
Patrick: Yes, so GFR, salt, sugar, sex, the deeper you go, the sweeter it gets. It's a way to remember that. Back to you Patrick, so the, the down to the adrenal medulla. What's, what's significant about that? Yeah, this is where the neuroendocrine chromatin cells live. This produces epinephrine and norepinephrine.
Patrick: Okay, great. So that's a little bit of a anatomy and physiology. Like I said, with all of these endocrine organs, it's important to understand what they do, which will help you understand the pathology and help you answer these questions. One thing that we see very commonly, and I'm sure Patrick, you see this a lot in the trauma world, is what we call adrenal incidentalomas.
Patrick: So we'll stick with you, Patrick. Can you describe the epidemiology of of. Incidental adrenal masses. And what's your initial workup? Yeah. So the [00:02:00] incidence is, is one to 2 percent of, of CT scans, essentially on our patients, which is really quite common. So as you mentioned, when we're getting all these trauma scans, we do see adrenal incidental illness quite commonly.
Patrick: And when regards to the workup, you want to evaluate for concerning imaging features, right. And we'll try to determine if this tumor. is functional. So that means we're getting labs and a CT scan, specifically a CT scan adrenal protocol. Yeah, that's great. Exactly. So you want to be sure that you get that, that adrenal protocol CT.
Patrick: And what that is, is that's a three phase thin sliced scan. So the three phases you're looking for is a non contrast, a arterial and a delayed washout in 15 minutes. And that'll help you kind of classify because the two big things you're worried about with this incidental illness is, well, one, is it malignant or non malignant?
Patrick: And then we're going to talk about whether or not it's functional versus non functional because that's going to guide our management. So concerning findings on our CT adrenal would be its size. So if it's greater than four centimeters, that has a higher malignant [00:03:00] potential. Anything that's greater than 10 Hounsfield units on our non contrast scan is more concerning.
Patrick: Typically our benign lipid rich adenomas are, are less than 10 Hounsfield units or a delayed washout. So greater than less than, I'm sorry, less than 30 percent washout at 15 minutes. We'll all be concerning findings on our CT scan. So, Patrick in addition to the CT, I said, we want to worry about malignant versus non malignant, but we also want to learn to worry about functional versus non functional.
Patrick: So what kind of labs can you get to help you figure out whether this thing is functional or non functional? Yeah. So we're going to order urine metanephrines a VMA, catecholamines and also do a low dose dexamethasone suppression test. And then the classic or standard labs, I would say serum, potassium, in addition to renin and aldosterone.
Patrick: Yeah, that's going to be somewhat institution specific. Some places we'll start with a platas of a metanephrine and get the 24 hour urine as a confirmatory test. The one I would add in there as well as the DHEA sulfate. That's one that's a pretty standardly obtained to, to look for function as [00:04:00] well.
Patrick: And then we should go back to say that, of course, with all these, you know, you're, you're going to ask it. a history and physical. And so on the outside, you might see that in a form of a patient with Cushing's or a patient that's concerning for a pheochromocytoma, and that can help you guide your management.
Patrick: Additionally, you want to ask about or know about any history of prior malignancies because there can be some tumors that will metastasize to the adrenal gland, most commonly long. And that's going to that's going to affect your workup and your management as well. But getting back to some different pathologies of the adrenal gland one thing that we probably all studied in medical school and haven't thought about since then is a congenital adrenal hyperplasia.
Patrick: So, Kevin can you talk to me about the etiology of congenital adrenal hyperplasia? Yeah, unfortunately. So, there's the 21 and 11 beta hydroxylase. And what these do is they convert cholesterol to aldosterone, cortisol, and testosterone. Okay, so what, what hormonal [00:05:00] abnormalities, you know, there's three types of congenital adrenal hyperplasia.
Patrick: What are those types and what abnormalities do we see with those? I just want to know when I'm not going to be tested on these again. So, so you have the 21 hydroxylase deficiency, which is the most common, and that increases your testosterone and decreases your aldosterone. You have your 11 hydroxylase deficiency.
Patrick: This increases your testosterone and increases your aldosterone. And then finally, you have your 17 hydroxylase deficiency. This decreases your testosterone and increases the aldosterone. Okay, so I have good news from everybody. If you look at our Ab Psy Companion, there's a really easy way to remember these different congenital adrenal hyperplasias that are going to get you 99 percent of the answers correct on any test you'll ever take.
Patrick: Unless you become an endocrine surgeon it's a table and it's a little bit difficult to explain, but essentially if you take those numbers, 21, 17, and 11, and you replace the one with an up arrow, and then you create another column, one that says [00:06:00] hypertension and one that says virilization. And you plug in those numbers, it's going to tell you what's high and what's elevated in each syndrome.
Patrick: Like I said, it's difficult to explain, but just take a look at the table in the, the ab site companion, and that's all you need to know for congenital adrenal hyperplasia for the ab site. So coming back to you, Patrick. Let's talk a little bit more about some more pathologies. So, hyperaldosteronism, otherwise known as Kahn syndrome.
Patrick: So, how do these present? Yeah, these patients are often hypertensive. That's the, the, the key sign. They'll have elevated sodiums and low potassiums. Yeah. And that's exactly right. And that's, they're going to give you that in the, in the prompts to, you're going to have a patient that typically has poorly controlled hypertension, typically on three different agents and their labs show an elevated sodium and a low potassium.
Patrick: What else do you see? Yeah. So for primary hyperaldosteronism, you're going to see low renin versus secondary hyperaldosteronism in which you're going to have high renin. And typically the plasma aldosterone to renin [00:07:00] ratio is going to be greater than 25. Great. Yep. That's, and that's in all those labs that you said you're going to get, you're going to look at that aldosterone renin ratio.
Patrick: And that's gonna, that's going to clue you into that diagnosis. So what other workup does a patient with a suspected hyper aldosteronism get? Yeah. This would be the salt load suppression test. And so we're going to check urine aldosterone after the patient is salt loaded and this is going to remain elevated.
Patrick: We can also perform imaging. So we're going to want to localize the lesion with a CT scan, MRI. Or NP 59 syntagraphy. You can also, if needed to try to determine the sidedness do adrenal vein sampling. Yeah. We're going to get back to that in just a second. Cause that's an important caveat for these hyperaldosterone is that adrenal vein sampling, but let's first move into, okay, let's say we make the diagnosis.
Patrick: We have hyper hyperaldosterone patient. What's the management. Yeah. So. So bilateral idiopathic [00:08:00] adrenal hyperplasia is first and foremost, the most common reason in which these patients have hyperaldosteronism. This is a mix of about 65%. In this case, we're going to manage medically and that includes meds like spironolactone, ACE inhibitors, and calcium channel blockers like nifedipine.
Patrick: We're also going to make sure, as we mentioned earlier, that these patients have low K. We want to make sure their potassium is replaced and if we can localize it, we're going to perform an adrenalectomy. If the patient has bilateral lesions, then they're going to need flusher cortisone supplementation postoperatively because we're going to be messing with both the glands.
Patrick: That's great. That's a great overview. You know, I will say that there are some places that are doing subtotal adrenalectomies for bilateral adrenal hyperplasia. But that's a little in the weeds for the ab site, but what I think is pertinent is Kevin. Let's say that you have a two centimeter adrenal mass and the patient has hyper aldosterone.
Patrick: Let's say it's left sided. So what are you going to do? So you have a left sided adenoma [00:09:00] and they're, they are it's functional with hyper aldosterone. I'm going to remove it. Okay. You do that and they still have clinical hyperaldosteronism. What happens? You screwed up, man. So, oh, so you still do the adrenal vein sampling even after, so e Exactly.
Patrick: So, so aldosterone is tend to be very, very small and it's getting less and less common with CT scans get, as CT scans get more and more sensitive. But the, the functional. Aldosterone adenoma tends to be very small. So what most likely happened was that two centimeter incidentaloma was a benign adenoma and your functional tumor was actually on the contralateral side.
Patrick: So hyperaldosteronoma is one thing where most people or most places are still doing a selective or doing venous sampling to localize prior to surgery. You don't have to remember that for the other ones, but for aldosteronomas you need to be sure to remember that. Okay. So Kevin, we're going to stay with, stick with you.
Patrick: And we're going to talk about Addison's disease or [00:10:00] hypo cortisol ism. Can you describe the presentation workup and management of hypo cortisol cortisol ism? Yeah. So it can present in a couple of different ways. Kind of the more chronic presentation is when they have weakness, fatigue, hyperkalemia. They can also present in an acute adrenal crisis due to sudden or complete loss of adrenal function.
Patrick: And this would be with refractory hypotension, fevers, lethargy, pain, nausea, vomiting. All right, Jason, you seem to be our relative endocrine expert here. So I'm going to bump it back to you for the workup. Sure. So with a workup of, of Addison's disease, what you're trying to distinguish is between primary and secondary Addison's disease.
Patrick: So you're trying to figure out whether the problem is the pituitary gland or whether the problem is the adrenal gland. So you'll start by measuring your EM cortisol. Okay. So if that's low, okay, you know that there's a problem. You still don't know where it is yet. So what you do is you give cosentropin and if the adrenal gland is functioning, you should see a rise in cortisol after that.
Patrick: Okay. But let's say you [00:11:00] don't, well, you still need to kind of confirm that the pituitary is functioning okay. And the way you do that is measuring the ACTH. So you stop and think about it. Think about your feedback mechanisms. If your cortisol is low, your ACTH should be high. So if you have low cortisol, that doesn't respond to a cocentripin stimulation test.
Patrick: Okay, you know there's a problem with the adrenal gland. Now, is it pituitary functioning? Well, if your ACTH is not elevated, in other words, if it's normal or low, then you have to consider there's a component of secondary hypocortisolism. Does that make sense? I think I got it. Okay, well, I'll kick it back to you then.
Patrick: Let's say we made the diagnosis. How about management? So chronically you give them corticosteroid replacement in the acute setting, you're going to use high dose drugs like IV fluids. Of course. And then we're always going to worry about this if we're stress dosing patients for elective surgery and those types of things as well.
Patrick: Okay. [00:12:00] So, okay. Moving on to hypercortisolism. So Cushing syndrome, Patrick. Can you describe the pathophysiology workup and management for a patient with suspected hypercortisolism? Yeah. Most, like, so, what's the most common cause, just first off? Yeah, so these are exogenous steroids. So Kevin, I'm sorry, you don't have Cushing's syndrome, right?
Patrick: It's all the steroids you've been doing and all those wrong websites, right? Yeah, so I'm gonna try okay, and this is something that everyone needs to take some time to wrap their head around for the test You will have a question on this on the exam And so initially we're going to perform a 24 hour urine cortisol and or a late night kind of evening serum cortisol check.
Patrick: Now, if this is high and it matches up with our clinical presentation and we have concern for Cushing syndrome. So next we're gonna check the ACTH. Okay. So this is low. Then I'm concerned for an adrenal source. So primary hypercortisolism. [00:13:00] If ACTH is high, then I'm concerned for a secondary source like Pituitary, which would be Cushing's disease or an ectopic source.
Patrick: Now to further determine the difference between, you know, the secondary source like pituitary or ectopic, we're going to perform a high dose dexamethasone suppression test. This will inhibit the pituitary gland. It will not inhibit our ectopic source. So I gotta go searching now for where these things are.
Patrick: So if I'm worried about a primary primary hypercortisolism, I'm gonna perform an adrenal CT scan. Try to find the sidedness here and identify which gland is involved. If I'm worried about a pituitary source, we're going to do a brain MRI. And if I'm worried about an ectopic source, we're going to do a CT scan of the chest, the abdomen, and the pelvis.
Patrick: Great. I think it's a great overview. You know, I feel like we maybe skipped ahead a little bit. We didn't talk about how these patients presents. So let's backtrack just a second. And Kevin, What do we see in what's your standard, you know, Cushing's patient that walks in? [00:14:00] Yeah, they're generally overweight and have a abdominal stria.
Patrick: And. And a buffalo hump. Yeah. So these are your patients that you, that have, you know, or are diabetic, they have poorly controlled insulin. They typically have hypertension. So don't confuse them with, you know, they can present similar to, you know, patients with hyperaldosteronism as far as hypertension goes that buffalo hump, abdominal strea, obesity.
Patrick: You know, all the peripheral wasting, all of those things that we see with Cushion Syndrome. And, and like Patrick said, you, you, you, you gotta just figure out if their cortisol is high, if their cortisol is high, you gotta figure out what the cause of it is. Is it adrenal gland? If it's too much ACTH from the pituitary and you use your various cortisol tests and your low and high dose dexamethadone suppression test to parse that out, and then you move to localization with imaging.
Patrick: So perfect. How about management, Patrick? Yeah. So if it's a cortisol producing adrenal tumor, we're going to perform an adrenal leptomy. If we have Cushing's disease, again, a pituitary mass that's producing [00:15:00] ACTH, then we're going to move forward with trans sphenoidal resection. And if we have an ectopic ACTH producing tumor, most commonly metastasis or small cell lung cancer, then we're going to try to identify where that's at and perform resection.
Patrick: Okay, moving on, working through our functional adrenal tumors, let's go with the ever popular pheochromocytoma. So, Kevin, when we talk about pheos we frequently hear about the rule of 10 for pheochromocytoma. What was the rule of 10? Yeah. So that's the 10 percent are malignant, 10 percent are bilateral, 10 percent are in children, 10 percent are familial, and 10 percent are extra adrenal.
Patrick: Great. Okay. So, our, our Pheo patients, these are the ones that show up with impending sense of doom. You know, they have palpitations, they have very poorly controlled hypertension. So these are the ones that we're suspecting is having a Pheo. Now we, we talked a little bit about it before, but what's the, what's the workup for a patient with a suspected pheochromocytoma?
Patrick: So [00:16:00] you're going to start with a plasma free metanephrines. is the initial test. And then you'll get your urine metanephrines. These are more specific, but less sensitive and good for confirming the diagnosis. I'll pause you right there. So that is, I will say that's a little bit controversial and this, this, I remember this question showing up on the outside and it always made me angry.
Patrick: So the way it will be worded. So I'll ask, what's the best test for a pheochromocytoma? And there's multiple right answers. Yeah. I think that's not fair. Cause it best are you looking for more sensitive or more specific? And I still don't know exactly what they're going for. If it was me answering that question.
Patrick: I'm going to put plasma free metanephrines because it's more sensitive. Most places are using that as their initial screening test and then when the 24 hour urine is their confirmatory test. But I guess it's how you interpret the question. If, if in your mind you think best means more specific, then the question is probably the 24 hour.
Patrick: Good luck. Yeah, so that's the best advice I have. I, I remember seeing that question four or five times throughout my time taking the abcide and every time I felt like I was [00:17:00] gambling. Okay. So how about some imaging? Yeah. So this is where you get your dedicated CT adrenal scan and an MRI. Okay, great.
Patrick: And what about you don't see anything on CT adrenal or MRI. This is where you get your MIBG scan. Yeah. So your MIBG scan again, going back to your rule of tens, you know, 10 percent are extra adrenal and the most common site for an extra adrenal, anybody, anybody. ? No, I don't know. Your organ of Zucker candle.
Patrick: Oh, you remember this? Yeah. Oh, the aortic bifurcation. Yeah, the aortic bifurcation. You work around that area? Yeah. Yeah. So, well, again, really deep into the weeds, but it's a, it's described as either the aortic bifurcation or the the takeoff of the IMA. Mm-Hmm. . But I think most people consider it the aortic bifurcation.
Patrick: Okay. So, this, the lot, there's a lot to talk about here, so. Are you going to rush these patients off to the O. R. for their adrenalectomy? No. Why not? You, you need to get them optimized before you take them to the O. R. Yeah, these can be very [00:18:00] human dynamically labile interoperatively. So, how do you get these patients ready for the O.
Patrick: R.? So you start with volume replacement as they've chronically become, you know, more or less dehydrated. And then you start an alpha blockade on them with phenoxybenzamine or prozacin. Yeah, phenoxybenzamine is probably the main answer on the test. In reality, it's, it's cost prohibitive for phenoxybenzamine, so you typically Parazicin.
Patrick: So how do you know when you've had them adequately blockaded? I think you look at their blood pressure and their heart rate. Yeah. So while you go for a, you want it to be orthostatic and also dry mucous membranes are your indicators that you have them appropriately alpha blockade. And then you can add a beta blocker too.
Patrick: If you, if you need to but you want to make sure they're alpha blockaded before you beta block them. Okay. Is beta blockade universal after the. Adequate alpha blockade. Not everybody will need that, but if you, if you, if you do need it you can add it. You just want to make sure that you add the alpha blockade so you don't get unopposed alpha agonism.
Patrick: Sure. Okay. So, Kevin, what's the management? [00:19:00] So the management is an adrenalectomy. Okay. And how do you want to you're in the OR, you're staring at the adrenal. You got the artery, you got the vein isolated. What do you want to make sure that you're, one, communicating to your anesthesia provider, and two, what order are you going to take those in?
Patrick: Yeah, so we're going to let them know that, hey, we're about to ligate some vessels, and you might see a drop here in their catecholamines, so you might need to give them some volume ASAP. So I ligate the adrenal veins first to avoid a catecholamine crisis with tumor manipulation. Perfect. Okay. So let's let's wrap that up with with for feel and move on to now adrenocortical carcinoma.
Patrick: Okay, Patrick. So what can you tell me about adrenocortical carcinoma? Yeah, it's a rare malignancy. Unfortunately it often presents in advanced stages and most typically presents in the fourth and fifth decade of life. These patients will often have Cushing's syndrome, signs of utilization and hypertension.[00:20:00]
Patrick: Okay. Can you describe the management to me? Yeah. So you want to take out as much as you can. So radical adrenalectomy with debulking as needed for patients who require adjuvant treatment. This is somewhat unique in that we get mitotane and you can consider external beam radiotherapy as well. And this would be indicated for patients who are at high risk for local recurrence and some of those factors.
Patrick: Are certainly a positive margin vascular or capsular invasion intraoperative tumor spillage and a K I 67 of greater than 10%. Great. So, Kevin, I'm going to throw a little bit of a curve ball at you, but let's say you're, you're laparoscopically taken out of the adrenal gland for a presumed functional aldosteronoma.
Patrick: You get in there and you see that the adrenal mass is invading into the abdominal sidewall. What's your first step? I think at that point I would just biopsy it and stop. Wrong. So what you would do is you would convert to an open procedure because adrenocortical [00:21:00] cancer is one of the few that has a theoretical risk of spread through aerosolization.
Patrick: So, it's doubtful. Although it's pretty theoretical there, well, there are some advanced centers that are doing laparoscopic resection of adrenocortical cancers, but the, the board answer is still convert to an open procedure. I'm likely to show up on the app side, but you can. file that one away for your oral boards potentially.
Patrick: I like picking on Kevin cause he's a very smart vascular surgeon. So whenever we talk about topics that I mean that I know more about than him, I like to, I like to Tease him a little bit. Okay. So back to you, Patrick. So, so your patient has completed his treatment for his adrenal cortical carcinoma.
Patrick: What's the appropriate surveillance? Yeah. So for this one, remember it's pretty aggressive, right? So it's quite frequent. You're gonna get CT scans of the chest, the abdomen and the pelvis every three months for two years. Okay, so just one last thing to mention before we get into our quick hits, and that's the adrenal myelopoma.
Patrick: So this is a benign tumor of fat and bone marrow. It can be small, but they can also be very [00:22:00] large, sometimes greater than 10 centimeters. The important thing to remember is that they have a very characteristic finding on CT scan, and they can also be diagnosed on CT. So, when we talk about those size cutoffs, like greater than four centimeters, a higher risk for malignancy, that does not apply to these.
Patrick: So you can typically observe these. So if you get a question that very clearly describes an adrenal myelolipoma it's okay to watch those unless they're symptomatic or, you know, very large say over, you know, seven to 10 centimeters in size. Okay, so I think that wraps up a good discussion of our, our, our adrenal tumors.
Patrick: Again, Incidental Lomas, your two main questions are. Benign versus malignant. And we talked about ways of distinguishing these two and then parsing out functional versus non-Functional. Mm-Hmm. . You always want to do a resection for anything that's concerning for malignancy or that's functional. And there's various things to consider depending on the particular patho or physiology and pathophysiology of that tumor, getting that patient ready for the or.[00:23:00]
Patrick: So you guys ready for quick hits? Ready? All right, let's do it. So Kevin, most common etiology of Cushing syndrome, exogenous steroids. Okay, great. Patrick. Most common etiology of adrenal insufficiency. Globally, it's tuberculosis. In developed countries, it's autoimmune. Perfect. Okay. Kevin. Screening test for adrenal insufficiency.
Patrick: AM serum cortisol. Great. Patrick, a patient's undergoing a resection of a pheochromocytoma and becomes hypertensive. What would you want your anesthesiologist to give? So, first line would be nitroprusside, among other antihypertensive agents. Yeah, it's very important to be communicating with your anesthesiologist throughout a resection for a FEVO, because those patients are incredibly labile and you need to be prepared for everything.
Patrick: Okay, Kevin the most common primary cancer site for an adrenal metastasis? Yeah, so if you're concerned about metastasis we didn't really talk about it, but if you're, you know, concerned about metastasis, that's one of the few indications for a biopsy of an adrenal mass. You do not want to biopsy most of [00:24:00] these, and certainly if you're thinking about biopsying something, you want to rule out a Pheo before you stick a needle in it.
Patrick: But lung is the most common and so if you're concerned you should include a CT chest in part of your workup. So last one, Patrick. A patient with suspected pheochorobocytoma has normal plasma and urine metanephrines. What additional tests can be performed? This is of course the clonidine suppression test.
Patrick: Exactly. Clonidine suppression test for confirmation of a questionable phea. Okay, that does it for adrenal. Hopefully you guys found that helpful and thanks for listening.