Adrenal cortical tumors: Workup, surgical approach, and post operative care

Hi, I'm Rod Gerardo, research resident at Cincinnati Children's Hospital, and to continue our series of the Cincinnati Children's Surgery Department grant rounds, today, we're gonna talk about adrenal cortical tumors. With an expert. We're talking about adrenal tumors. That's Doctor Dan von Almen. He's the surgeon in chief at Cincinnati Children's Hospital Medical Center, and I brought the whole team. Hi, I'm Ellen Ancisco, another research resident at Cincinnati Children's. Hi, I'm Todd Ponsky, pediatric surgeon at Cincinnati Children's Hospital. Let's start off with a case. Uh, this is an 11 month old female who presents with obesity, acne, and pubic hair. What kind of workup do you want to do for this child? What's the labs and what's the imaging? Ellen, what do you think? Hey, he called on me. Well, we should check a cortisol level. OK, so what do we just get a cortisol level right then and there? Not quite, Rod. For these patients, we need a 24 hour cortisol. OK, right, so, uh, just getting a spot cortisol doesn't really help you necessarily. Uh, you want to get, the ideal is 24 hour, so that's correct. And since this is a talk about adrenal tumors, a cortisol is a good test to get. So how about imaging? A safe bet to start with is usually an ultrasound. So the ultrasound of the abdomen suggests a right suprarenal mass. Ultrasound, of course, but what are we looking for on that ultrasound imaging? Great question. Make note of the size of the mass, the density, the vascularity, and the borders. You'd be surprised how much information you can get from an ultrasound. Yes, uh, so it's 4 centimeters in diameter, solid mass, homogeneous. OK, great. So are we done with imaging now? Uh, no, uh, not quite yet. You get the ultrasound, I should have pushed you further on what you would get next, but you're smart and you decided you would get an MRI. You could get a CT scan as well. Check out the right adrenal mass. It looks pretty well circums. s cri b ed and with some vascularity. It looks like it has about a 4 centimeter diameter like the ultrasound showed us. Kind of a spoiler alert with the title of the podcast, but I think this is an adrenal cortical tumor. And this is, it appears that the mass extends up the vena cava. So how might that alter your management? You have very super high cortisol levels in a child who has, um, Some You know, acne and obesity, has clitoromegaly, has pubic hair. Hmm. I don't know. Can we give like chemotherapy to try and shrink this? So I won't beat this to death anymore, but the bottom line is if you think this is an adrenal cortical tumor, uh, you have to take it out because there is not effective chemotherapy that's going to shrink it. So the treatment for this is There, there really isn't effective medical therapy. How about surgical therapy? How are you gonna approach this? For this patient, the surgical approach would be an open adrenalectomy. Considering the extension up the vena cava from the MRI, she might also necessitate a venotomy as well. What we were actually able to do was to open the adrenal vein, which was huge because it had this big hunk of tumor going through it, and just do a venotomy there and pull this out of the cava and then ligate the vein. Awesome job. OK, let's take a step back and talk about some basics. I mean, how common are adrenal cortical tumors anyway? So, adrenal cortical carcinomas or tumors, very uncommon, 0.2% of all pediatric tumors, 6% of all adrenal tumors, um, 75% are adrenal cortical carcinoma, and that's really in the older kids, um, and there's a slight female predominance in the older kids. Most of them, as opposed to adults where like 50% of them are hormonally active, uh, the majority are hormonally active in kids. Quick anatomy refresher, the adrenal gland has a few layers. The cortex, which has these three different zones. First, glomerulosa, which is where aldosterone and the mineral of corticoids come from. The next layer is the fasciulata, which is cortisol. And lastly, and reticularis, which is the sex hormone. And then there's the medulla, which derives from the ectoderm, and that's where you get uh epi and or epi. So that's where you're gonna pheochromocytomas will come from the medulla. This part is kind of rare and maybe more of the pimp question material, but remember that patients can also have ectopic adrenal tissue. It could be in a hernia sac up the aorta, or even at the root of the SMA. That's called the organ of Zuckerkundal is sort of pimp question on if you find a neuroblastoma that's at the bifurcation of the aorta down in the pelvis, that theoretically originated from the organ of Zuckerkcundal. There are gene mutations associated with adrenal cortical tumor as well, but which one is the most common? P53 mutations are. Very common. 50 to 80% of individuals with adrenal cortical carcinoma have germline mutations, and there's a population in Brazil that has a very high prevalence of this mutation. And so they have a very high incidence of adrenal cortical tumors. And that's why you see a lot of the studies that are published on adrenal cortical carcinoma come from populations in Brazil. And coming back to haunt you from medical school, remember that adrenal cortical tumors are also associated with some well-known syndromes hemi hypertrophy, Beckwith Wiedemann. Uh, Lei for mommy, Lynch, Carney complex, uh, neuroblastomatosis type 1 and MEN type 1, not type 2. MEN type 1 is adrenal cortical tumors. Um, extra credit, who knows what Carne complex is. Good. I really don't know that much about it either. So Cushing's syndrome is different than Cushing's disease. Who knows the difference between those? Oh jeez, I always get these mixed up. All right, let me see if I can get this straight. So Cushing's syndrome is hypercortisolism from something like an adrenal cortical tumor. Whereas Cushing's disease, that is specifically a pituitary tumor. I think I got that right. 60 to 80% of pediatric Cushing's syndrome is due to adrenal cortical carcinoma. So when you see a baby like this, like you guys said, the first test you get is some sort of imaging of the abdomen looking for an adrenal mass. Um, the presentation, obesity, hypertension, weakness, stria, acne, and glucose intolerance, and this child had all of those things. So what happens when these tumors produce sex hormones? With virulization, you get precocious puberty with penile enlargement, acne, pubic hair. Um, girls, you got clitoromegaly, uh, hirsutism, and acne. The feminizing, which are much less common, you can get gynecomastia in the boys and in girls you can get precocious puberty and breast development. That's much less common than the virulizing tumors. Let's change gears and do another case. All right, for a total zebra case two, this is an 8-year-old boy who presents with weakness and fatigue, hyperdipsia, and urinary incontinence. On exam, he's hypertensive. And his laboratory studies show significant hypokalemia. Hypertension with hypokalemia. My money is on hyper aldosterone. Very good. My first call would be to endocrine to tell me what to do, but you're right. You would get an aldosterone level and then imaging looking for an adrenal cortical mass producing hyper uh aldosterone, and that's Khan's syndrome, which is there is a tumor or hyperplasia. There's secondary um or primary aldosteronoma is very rare in kids. I've actually seen. One in my career, um, but it does happen. OK, great. So we got lab work, but what imaging should we do on this patient? Ultrasound, as, as you all suggested, is a good first test just to look for an adrenal mass, and as noted by Mira, the most common thing you're going to find for an adrenal mass is going to be neuroblastoma, not, not an adrenal cortical tumor, unless you have those other physical findings. Um, CT or MRI, um, PET CT is also very helpful. It looks at obviously the, um, metabolic function of the tumor. You want to evaluate the chest to rule out lung mets. All right, so this is the other thing that I always mess up. I'm not even gonna try it this time. So how do you diagnose hypercortisolism? As we talked about initially, um, uh, random cortisol is not particularly useful. You want to get a 24 hour urinary free cortisol level which is 98% uh sensitive. You can do a low dose dexamethasone suppression test, uh, looking for overnight suppression. The, you can get an ACTH level which will help you to determine the source of the cortisol. And then you've got to put together a broad differential. If it's bilateral, it is likely to be hyperplasia, um, neonatal adrenal hemorrhage, and we talk about that a lot when you get scans on fetuses and you think they may have a neuroblastoma, 3 to 4 times more common on the right bilateral in 10%, um, and it usually just involutes and leaves some calcifications. Obviously we keep mentioning neuroblastoma. You would find elevated urine catecholamines with that. And a neonatal adrenal abscess, which I have to admit I have never seen. Once you take the adrenal mass out, we send it to pathology for staging and grading, and there are a number of different staging systems that have been used to characterize this. OK, what's the WIS system? The WIS system, there are 9 items that you score 3 concerning architecture, 3 about the nucleus, and 3 about the presence of invasion. Um, the presence of one item equals the score of 1. The sum of the positive items defines the score, and if it's more than 3, that's an adrenal cortical carcinoma. Uh, whereas if it's 0 to 2, that's an adenoma. But more commonly used is the Wernicke system. It's really based on size. If the tumor weighs more than 400 g, it's more than 10.5 centimeters in diameter or extension, then those are important things that suggest there's invasion and that this is a malignant tumor as opposed to a benign tumor. Here's a table showing the TNM staging criteria for malignant tumors. Don't worry, we're going to give you this image in the stay current in pediatric surgery app. Scroll down under the media player and click the image to open it. All right, let's move on to the treatment. Do we have any medical options? Mitotane, the medical treatment mitotane is an adrenolytic agent. There was a trial done, which I'll get to in a second, looking at systemic therapy using cisplatin, etoposide, and doxorubicin for tumors that are over stage 1, and then you can give other things to ameliorate the metabolic effects of aldosterone if there is hyperaldosteronism. For surgery, the key is to get complete resection, and that means. If it's stuck to stomach, take that out. If it's stuck to the colon, take that out, stuck to diaphragm, take that out. So, so you really want to be very aggressive with your surgical resection. But the surgical anatomy can make things difficult, specifically the venous drainage. And the venous drainage on the left is the adrenal vein, drains into the left renal vein, whereas opposed to on the right, the adrenal vein is this very short thing that drains into the retropatic vena cava. When you're like when we're doing living donor from that angle, that's Doctor Alex Bonddock. He's a pediatric transplant surgeon at Cincinnati Children's Hospital Medical Center. So safe to say he had some thoughts about the retrohepatic cava. Your first move is to obviously occlude the cava, and you can do that when it's that lateral, potentially with just manually or with a side bitter. And then the first move, in my opinion, is always to get to incise the um The retroperitoneal attachment of the liver right above where the right adrenal is because without that, you're gonna tear into the liver, you'll tear the adrenal, and then you'll be in a lot of trouble. OK, so hypothetically, we did all that, we get through the adrenalectomy. What sort of stuff do we need to keep in mind in the post-operative period? Obviously you want to get your endocrinologist involved if they have bilateral adrenalectomies because they're gonna need replacements of both leucocorticoid and mineral minerallocorticoid, that's hard to say. And then post-op, you also have to be careful because these kids have had huge um cortisol levels from their tumor and you will, they've been suppressed, um. Uh, with that, and once you take that out, even if, if it's a unilateral tumor, you need to make sure that you give them replacements until you can wean them back and their, uh, their contralateral adrenal gland has the ability to take over their cortisol production. OK, so let me get this straight. You have all this hormone therapy, you have really major abdominal surgery, and then you have these postoperative complexities to consider. I, I, I gotta ask, I mean, how are the outcomes for these patients? So the outcomes favorable indicators as an age less than 3.5 and symptoms for less than 6 months unfavorable are the usual things you would expect in older age, a higher mitotic rate, lower percent of necrosis, larger tumor size, extension locally, and obviously metastatic disease and positive margins. A study that was done through the Children's Oncology Group, the survival rate, event-free survival was 91.3% for stage one, and then it went from 80% down to basically 14%. Here's a graph depicting what Dr. von Almen mentioned. You can see really good survival for stage one tumors, but look at how survival drops off as stage increases. All right, let's move on. Let's do one more case. An 11 year old girl who presents for a routine checkup. She is found to be very hypertensive with a blood pressure of 190/95, and she complains of headaches and palpitations. How would you work up that child? That's a high blood pressure. OK, first things first, we've got to do a history and a physical exam. With that hypertension, I'm worried about pheochromocytoma, so I would also want to get some lab work like urine metanephrines. But what about imaging? If you get an imaging study like this CT scan and it shows this left solid left adrenal mass. For this patient, they got an abdominal CT scan, but you could also get an MIBG scan. I know we get tested on pheochromocytoma a lot, but how common is it actually, like IRL? So PO's even more uncommon, 0.3 cases per million, 50 to 80% of them have this P53 mutation. It's 0.2% of all pediatric tumors. Again, this has familial syndromes associated with it, and again, this is the MEN type 2, not the MEN type 1. The cortical tumors are type 1, the medullary tumors are type 2. And here's Carney's triad has these paragangliomas. What's the difference between a p pheochromocytoma and a paraganglioma? Uh, let's see, Alan. The difference between a paraganglioma and a pheochromocytoma, hm, it's a difference in tissue origin, right? Exactly. So you're right, basically, Ellen, the PO is an adrenal mass. A paraganglioma is essentially the same thing but not in the adrenal. So and it's typically along the sympathetic chain. We should talk about the preoperative management. So it's alpha blockade, beta blockade, and hydration. You have to start with alpha blockade first. Never give them beta blockade first. Here's why. So if you start with beta blockade, you'll kill the patient because they're super tight peripherally. They have this very, very high peripheral vascular resistance, and if you block their heart, then they will not profuse. So you always start with alpha blockade. This is one of these cases where communication between the surgeon and the anesthesia team is really critical, um, and it has to go in both directions. Because if they're up there turning the dials on their drips and they have, you know, are struggling and you're manipulating the tumor, all you have to do is stop manipulating the tumor and that will help them to stabilize the vital signs. Obviously, you have to manipulate the tumor at some point to get it out, but you have to have really good communication. Conversely, when you ligate the vein, you have to tell the anesthesiologist that you're about to. Do that because they're going to go from having dealing with significant hypertension to dealing with significant hypotension, and they have to be ready for that. I won't torture you with reading through this whole thing, but this is just a slide that has the various drugs and the side effects and the approach to how you treat patients pre-op in preparation for resecting a field. Don't worry, we'll give you the whole table. Scroll under the media player below and open up the image there. Well, that's a wrap on adrenal cortical tumors. If you like this episode, go ahead and follow us on social media, subscribe to our YouTube channel, like, comment, all of that, but maybe most importantly, download the Stay Current Pediatric Surgery app. It's in the Apple App Store, it's in the Google Play Store. We've got content like this and so much more for you, but until then, I'm Ellen Ancisco. I'm Todd Ponsky. I'm Rod Gerarder from Cincinnati Children's. And remember, knowledge should be free.