BTK Pheochromocytoma Podcast 9-15-2025
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[00:00:00] Hi everyone, and welcome back to another episode with your Behind the Knife Surgical oncology team. So this is the start of a new BTK surgical oncology season, and we're excited to have two new members to the team, and I'll let them introduce themselves. Unfortunately, Connor's unable to join us this season, but we wish him the best of luck as he starts his time as a staff.

Let's start with introductions and then we'll kick off our case for today on Pheochromocytomas. Hi everyone, I'm Joe Broderick. I am in my research here at BRI Procurement Medical Center. I'm between my second and third year of training. I'm Galy Gu. I'm also in between my second and third year of training currently in my research year as well.

Hi, I am Elizabeth Barber. You guys know me from last season. I'm a general surgeon now in the uk, but I plan on applying to surgical oncology in a couple years. I am Lexi Adams. I'm a fellow at MD Anderson. I'm Tim Brulin. I'm a staff surgical oncologist at Brook Army Medical Center. Then we have one other staff, surgical oncologist, Dr.

Daniel [00:01:00] Nelson, who unfortunately won't be able to join us today, but we look forward to hearing from him in future episodes. Okay, let's get started. Galen, you're seeing a 40-year-old man referred for an incidental left adrenal mass found on CT during a workup for kidney stones. You have in the referral that he has also been complaining of episodic headaches and diaphoresis, but no other information.

What else do you want to know from the history and physical exam? I'd start by asking about symptoms that you may have from a mass in each part of the adrenal glam. For example, I'd ask about symptoms of cortisol, excess aldosterone, excessive sex hormone selection. More specifically for him, I'd ask about catecholamine excess things like episodic headaches, palpitations, diaphoresis, flushing, anxiety, tremors, orthostasis.

I was specifically asked about any personal family history of pheochromocytomas, adrenal, ectomies, or cancers, endocrine or otherwise, or family history of endocrine [00:02:00] symptoms, specifically man, two long hip lindo or NF one. On exam, I would look for hypertension or static changes or pal powerful abdominal mass.

Okay, great. He endorses episodic diaphoresis when he is sitting and watching tv, and he feels like his heart flutters. During these episodes. He also reports a new tremor in increasing anxiety. On physical exam, his vitals are significant for a blood pressure of 180 7 over 92 with a heart rate of 1 0 2, and he's anxious appearing, but the subtle tremor.

He has no palpable abdominal masses and no signs or symptoms of the cortical adrenal hormone excess. How are you going to begin your work? I start by ordering plasma free fractionated metanephrine and norrine, as well as a confirmatory 24 hour urine for fractionated metanephrine and nor metanephrine.

If I didn't already have it, I would order an A adrenal protocol ct. And then lastly, I, symptoms of the pheochromocytoma cannot be nonspecific. I'D order [00:03:00] A-C-D-C-C-M-P-T-S-H, urinalysis and drug screen. I'd also consider sending workouts for Cushings and hyper journalism. Depending on my degree of suspicion.

Yeah, I think that's all good. I think one thing that everybody's always confused by is, which matrine to order. On the AB site, they'll ask, which is the best test, which is always a very confusing question, but in reality, you always check plasma first, and if the plasma is high and you have a high suspicion, your diagnosis is essentially sealed.

So there's no reason to get urine. If the results of the plasma test are equivocal or you're not sure, then you would get the 24 hour urine test. But it's actually pretty rarely needed in real life, and if patients hate it, they have to carry around a jug and collect all their urine for 24 hours. So that's why the plasma test really is the first test of choice is just simpler.

It's easy to get, but it can have lower sensitivity and specificity. The urine test, and when I'm talking about this in a lecture, I withdraw the area under the curve. [00:04:00] The plasma metanephrine can peak during times of stress, whereas the 24 hour urine test is gonna capture all those peaks and valleys all in one test of a 24 hours.

That's why it is, they better test in the sense that it's more sensitive and specific. And particularly specific because the plasma may peak just from a time of stress, or some people report even just from being stressed out by seeing the needle of having a blood draw that can bump your plasma metanephrine up.

The rest of that workup all sounded very reasonable. On an AB site, you get this history of episodic sledding and palpitations. You know what it is. Just make sure you get the plasma metanephrine before you do anything funny, like trying to biopsy or doing surgery. Thanks Dr. Er. Yeah, that'll make sense in.

In this case, we did end up getting plasma free rine and nor Metanephrine as well. It's a 24 hour urine for fraction metanephrine norrine, which were all found to be significantly elevated. And then our CT demonstrated a highly [00:05:00] attenuated four centimeter left adrenal mass. So now that we're underway, let's review some background information on Pheochromocytomas Galin.

You can take it from here. So pheochromocytoma is our a rare neuroendocrine tumor arising from the chromin cells of the adrenal medulla. So normally these Crohn's in cells contain storage vesicles of norepinephrine and epinephrine. That's no surprise that these tumors are all in the classic presentation that we think of for pheochromocytoma.

They compromise about 0.05 to 0.1 of all hypertensive patients with the annual incidence in the United States with about 500 to 1500 cases. The peak incidents around 30 to 50 years old. Joe, do you remember the rules of 10? Yes, though it's not entirely accurate. 10% are bilateral, 10% are extra adrenal, 10% are malignant.

10% occurred children and 10% are familial. As a pediatric [00:06:00] surgery tie in, up to 30% of tumors in children can be extra adrenal. That's compared to 10% in adults. One real quick thing on the rule of tens, that only applies to sporadic fis. So familial fis are ones that are genetically driven. Those rules go outta the window.

They're much more commonly bilateral. The rule of 10 is only for sporadic fis. Awesome. Thank you Dr. Reland. Informed update to this WellTalk rule is that over 40% are associated with germline mutations such as men, two Von Hippo Linde, and F1 sub eight Dease deficiency, or a number of other susceptibility genes not related to the syndrome.

So genetic testing is crucial, especially in younger patients that Can you tell us more about the workup for these patients? Yeah, definitely. So we talked about this a second ago, but just to drive the point home, a key part of the discussion is that plasma free fractionated metanephrines are a screening tool.

They have a 99% sensitivity, but their [00:07:00] specificity is lower, about 80. 85% and it can also be affected by a number of medications. So medications like Tylenol, even the blood pressure medications, TCAs to name a few. So the confirmatory 24 hour urine testing has a 99% specificity, just like Dr. Rein said.

Elevations that are three times above the upper limit of normal are diagnostic. Also, we mentioned this a second ago as well, but if there's any uncertainty about the diagnosis of a pheo, you definitely should get lab testing before you biopsy, because manipulation of the tumor increases the risk of a catecholamine surge.

Lexi, can you talk to us about the imaging findings typical for pH. Yes, fast. So when you know you have an adrenal mass, you ideally get an adrenal protocol ct, which is a multi-phase CT with very thin cuts through the adrenal gland. And for those you'll typically see a mass that's greater than three centimeters, greater than 10 hound yield units.

You could also consider getting an adrenal protocol, MRI. These masses will be [00:08:00] characteristically bright on TTU phase. So just to give a little more practical and clinical perspective. So when I think about imaging an adrenal gland, I'm thinking about is this a benign adenoma or is it everything else, right?

So there are these characteristic imaging characteristics of a C, CA, Theo and a met, but really they're not very good, and they're not gonna actually help you differentiate those. So really what you're trying to figure out is, does this have characteristics of a benign adenoma or is it one of everything else?

Right? And then once you get your. Elevated plasma metanephrine, who cares what it looks like? It's a the right. So if it doesn't look like a fatty adenoma, and it's again, you talked about the higher hounds field units, the brighter on T two on MRI, those are the things that tell you it's not a benign adenoma.

And then you gotta elevated plasma metanephrine. So now really you're just thinking, is it on the left or on the right? And if you have a mass on one side and a high plasma epinephrine. [00:09:00] Go after that one is the bottom line. Don't get too excited about the imaging characteristics. The one weird thing about Theos is that because they're biochemically active, they will show up on an MIDG scan and the newest thing is on dotatate.

So if you can't see it on a regular ct, but you still have a very high suspicion suspicion of Theo and you're trying to find it, the old answer was MIBG. The newer is a Dotatate PET Scan. Which is typically done for neuroendocrin tumors, but these will also light up on that. Okay. Thanks Dr. Rein. All right, let's get back to our case.

So to summarize, we have a 40-year-old gentleman who presented with signs and symptoms concerning for pheochromocytoma. He has elevated plasma and urine fractionated metanephrine, and he has a four centimeter left adrenal mass. So we perform genetic counseling, recommend multi-gene testing for hereditary endocrine neoplasia syndromes, which are otherwise unremarkable.

Just a quick comment on that. What does anybody, why do you have to get genetic testing before you go to the operating room? What are you gonna do differently if they have [00:10:00] a mutation versus if they don't? Let's say they turns out they have a men syndrome and a pheo, what are you gonna do different?

You might be concerned about our bilateral cytomas. Or extra adrenal, the depending on the mutation. Yeah. So mostly bilateral. It's not that you're concerned that they necessarily have bilateral right now, but particularly in a young patient at a 16-year-old with a pheo who has a men's syndrome, you're very concerned that they're gonna develop a contralateral theo at some point in their life.

That would be the role for what's called a cortical sparing adrenalectomy, right? Where you intentionally take the tumor and the adrenal medulla, but you try to leave some cortex behind in case you then have to go and attack the other side later in life. So that's why it's important, especially in young patients, as you guys mentioned.

But the indication is now for every patient with a fi, you should get genetic testing, but it's particularly important in the young patient 'cause it may actually change the surgery that you do. Thanks again, Dr. Rein. Beth, so what are some of the other things you'd consider when planning an [00:11:00] operative intervention on this patient?

Yeah, so I think it's very important to discuss preoperative management for these patients because surgical resection of AEO can result in labile blood pressure, arrhythmias, and tachycardia in the perioperative period. Intraoperatively patients undergoing surgical resection can have arrhythmias, volatile blood pressure, and postoperative complications like MI, stroke or pulmonary edema.

So hopefully I've painted a good picture that multidisciplinary preparation for surgery to optimize the patient is crucial. So Lexie, can you tell us about the preoperative pharmacologic blockade? Yes. And just a quick plug, there's a great behind the knife surgical oncology board review episode on adrenal masses that discusses all of this as well.

But for most sources recommend alpha receptor blockade such as doxy CIN two milligrams daily. You can titrate that up for a period of two weeks. Preoperatively, your goal is to get their systolic blood pressure below 120, and ideally even some mild [00:12:00] orthostasis or people describe slightly runny nose, they should also be counseled to hydrate sufficiently preoperatively because they potentially might bottom out a bit when the mass comes out.

If the patient remains tachycardic after a period of three to four days, you can add a beta blocker like metoprolol and titrate that up. Phenoxybenzamine is the one we all remember from medical school and the traditional test answer that's typically no longer used, it's pretty costly and it has some bad side effects and honestly, hard to find.

I think it's always preferable to understand rather than memorize. So why do we use this new alpha blockade agent? Cardura is the one that everybody uses pre-op, and the reason is because it's a selective alpha blocker. So going back to like medical school and understanding all the alpha one, alpha two, if you block alpha one is a, is negative feedback on your sympathetic drive.

So if you block alpha two, you earn up the sympathetic drive, which is exactly what you don't [00:13:00] want to do in these patients Now. If you're using a non-selective alpha blocker and blocking alpha one and alpha two, you will lower their blood pressure with the alpha one, but then turn up their sympathetic drive with the alpha two blockade and you end up causing worsening tachycardia.

So that's why we don't use that non-selective alpha blockade anymore. We use selective alpha blockade where we're blocking alpha. But we're intentionally not blocking Alpha two. So that's why now we don't use Phenoxybenzamine because now there are selective alpha blockers. Because of that, the traditional teaching about like alpha blocker, then beta blocker.

You often don't need a beta blocker anymore because we're not causing this reflex tachycardia. So you alpha block to orthostasis, which you guys mentioned, and then a lot of people use rhinorrhea as a marker of effective alpha one blockade as well. And then you see whether or not they need a beta blocker, which most patients will not if they don't have that reflux tachycardia.

Okay, thanks everybody. So let's talk about our operative approach. Now, there's [00:14:00] multiple considerations to talk about when we talk about the surgical approach to Pheochromocytomas, MIS versus open, transabdominal versus retroperitoneal scopic, as well as cortico sparing, which we brought up earlier or total adrenalectomy.

So let's start with our plans for this patient. Again, we have a patient with a four centimeter left adrenal mass and no evidence of other lesions. Lexie, what are your thoughts? So there are several approaches you can take to perform an adrenalectomy, but in this case, I would perform a laparoscopic posterior retroperitoneal adrenalectomy.

Okay, great. So while ultimately the surgeon should do the procedure, they're most comfortable with NCCN guidelines do recommend usually a minimally invasive approach when feasible. The whole concern with an MIS approach for a patient with a malignancy is concern for capsule rupture and malignant dissemination, or a non R zero resection Times that you may consider an open approach are when the tumor is large, so potentially greater than six centimeters or some surgeons cut off, and therefore higher risk for [00:15:00] rupture or difficult removal when there are invasive features or if you're considering potentially a lymphadenectomy at the time of surgery.

Also, if the patient has high risk mutations such as SDHB, which is known to have a higher likelihood of extra adrenal involvement, you may consider an open approach. Instead, there's no official recommendations for retroperitoneal or a transabdominal approach. There's some retrospective data, but ultimately familiarity with the approach is key for performing this operation safely.

So you should do it how you feel that you can most comfortably resect the lesion. Lexie, how would you go about performing this operation? If I would place the patient in a prone jackknife position, I would palpate at the tip of the 12th rib, make a transverse incision below that, pop through the fascia, develop the retroperitoneal space, and place my additional trocars.

I would dissect through the aerial retroperitoneal tissue and draw fascia to identify in the superior border the kidney. Then ultimately I would mobilize that medial and inferior border to [00:16:00] identify the adrenal vein control that prior to doing any significant tissue manipulation to prevent significant hormone release, finish mobilizing it with my energy device of whatever choosing, and then extract the specimen.

But there are many other ways to also do an adrenalectomy. Beth, how would you do an transabdominal approach? So after port placement, I'd mobilized the splenic flexor of the colon from the lateral inflection down to the inferior pole of the spleen. I'd divide the ple renal ligament. I'd develop a plane between the tail of the pancreas and the kidney.

We know that the adrenal gland is located in the perinephric fat at the superior pole of the kidney. I'd dissect along the inferior medial border, exposed the adrenal vein, which I'd clip and divide. I take the smaller arterial vessels with a Carie device and clear any remaining attachments to free up the specimen again throughout the dissection.

It's super important. We're taking care to avoid manipulation of the adrenal gland. Not only is it fryable in general, but any excessive traction, [00:17:00] pressure manipulation can lead to that catecholamine surge we're trying to avoid. Yeah you're talking about the left there, because you're talking about splenic flexture, obviously there's a right as well.

The right's pretty easy. You just kinda lift the liver up and there's the adrenal gland. On the last. The other thing that's described is sometimes people do not split the splinter rail ligament. They just roll the spleen, pancreas, and colon together all over together. And that is a little bit simpler in some ways.

You have to mobilize things quite a bit and slip the pancreas over on itself to get all that stuff outta the left of the quadrant. But it does simplify a bit 'cause you're not wasting, particularly on the robot, you're not wasting an arm to hold the pancreas up out of the way. You just roll everything over.

And that the stuff about manipulation is obviously important until you take the vein. Once you take the vein, then you can manipulate the adrenal gland, which you don't wanna do is rupture the tumor. And particularly with the robot, I think that's important. 'cause the robot, you don't have tactile sense and the robot is very strong.

So you want to try not to touch the tumor with a bipolar or something that could potentially dig into the capsule of the [00:18:00] tumor. So you wanna try to grab the gland or grab the sat around the gland that even the gland can rip. When you are manipulating the adrenal gland, just so that you don't accidentally poke into the tumor with your robotic instrument.

All right, Beth, what about open? Why would you do open and how would you do it? Like we said earlier, you might consider that in patients with large tumors potentially above six centimeters, though again, different societies and institutions have their own cutoffs. You may consider it with signs of invasion or tumor mutations resulting in a higher risk of malignancy, and so that's when an open approach is traditionally recommended.

This can be approached through a subcostal, midline, or machy incision. I'd also like to highlight some differences with the right adrenalectomy here as well. So in an open approach, this requires mobilization of the right lobe of the liver and exposure of the retro hepatic IBC to identify the adrenal vein and gland.

Remember the right adrenal vein is shorter and it drains directly into the IBC. This makes it easier to tear, and so you really wanna be careful and not [00:19:00] manipulating and pulsing that as then this may potentially retract and cause bleeding that's difficult to control. Dr. Lin, do you have a size cutoff for when you might pursue an open approach or any other thoughts on right versus left?

I don't think there's a specific size cutoff, but it's probably more like 10 centimeters than six. I think six. You can handle MIS pretty easily, but part of the reason that these really big tumors are a problem is exactly what I was talking about earlier. Trying to manipulate a 10 centimeter giant tumor with a robotic arm without poking into it, can become difficult.

And the other thing is that particularly on the right. That adrenal vein usually comes off of the back of the IDC and the tumor, when they're that big, it'll push the IDC and liver anterior. So you're almost having to kind of reach around the back of the vena cava to get control of that vein. MIS can be really difficult and you're really pushing on the tumor, whereas granted, it's an incision and everybody wants to do any everything MIS, but [00:20:00] you're just gonna be better at manipulating the tumor safely with your hand than you are with an instrument.

So when you have a really big tumor that you gotta pull out of the retroperitoneum to be able to get stretch on that vein to control it, sometimes having your hands in there is just safer. And when it's really big, I don't know what that cutoff is, somewhere around nine or 10 centimeters, then I'll probably convert to an open.

And unfortunately, I do think that having inverted l or modified kuchi on the right or a L-shaped incision on the left does help in some ways to get that exposure. It just depends. If they're thin and you think you can stretch 'em to get over there with a midline, that's totally fine. But if it's really big, 15, 20 centimeters, then having that transverse portion of the incision allows you to safely get around it, and that's okay to do.

Great. And then we also should mention the cortical sparing approach. Dr. Breland brought it up earlier, but this is a good approach to consider when you have patients with bilateral pheochromocytomas or if they've had a previous [00:21:00] adrenalectomy. Also if they are an me N two patient. There's an interesting retrospective study of 563 patients with me, N two and Pheochromocytomas.

This was multicenter across 30 centers on three continents, and they found that adrenal sparing resections led to similar rates of recurrence with lower rates of adrenal insufficiency and steroid dependency. This was a pretty impressive reduction of only 43% of patients versus 86%. There was no difference in pheochromocytoma related overall survival.

And of course more studies are needed. This was just a big retrospective study, but, but ultimately, it's good to consider a cortical sparing approach. So once you've exposed the adrenal gland like we've previously described, you can do an interoperative ultrasound to identify the tumor. You wanna look at its relationship to the adrenal vein and make sure there aren't any other nodules.

If it's a single mass, you can nucleate it with a energy device, and then ideally you [00:22:00] preserve the adrenal vein when you're doing a cortico sparing adrenalectomy so that you preserve the function of the root of the remnant. If you suspect there's gonna be less than 30% of the gland left, then you probably should just perform a total because the remnant is likely to be non-functional at that point.

The only other thing I'll talk about for surgical management is really not in your hands, but. Just make sure anesthesia team that day have pressors I beta blockers and fluid all ready to go, and they have to be able to deal with the ups and downs because inevitably you may manipulate the tumor a little bit at the beginning, and then once you clip the vein, they can have a profound kind of drop off in their catecholamine then.

Require pressure support. I think it's just important that you have a good anesthesia team. And one of my attendings in fellowship said, you know, if you come in and they're inducing and it's already looking like a rocky road, you should probably cancel the case for that day and get a better anesthesia team the next time.

So if they can't handle induction, they're probably not gonna do well throughout the operation. Perfect. Joe, can you touch on the [00:23:00] postoperative management for these ectomy patients? Yeah, definitely. For patients with an uneventful intra course and minimal hemodynamic instability, the mission of the floor is acceptable for patients with ongoing hemodynamic instability.

Monitored bed with telemetry or ICU may be required. These patients are at risk for hypotension and hypoglycemia in the immediate postoperative period. Hypotension, likely due to residual, preoperative alpha blockage, hypovolemia, or intraoperative blood loss. And hypoglycemia, although relatively rare can occur due to preoperative insulin resistance from the elevated calcho levels suppressing alpha and beta cell function.

Most patients who have had an MIS Adrenalectomy are often able to go home within 24 hours unless they need ongoing blood pressure or hormonal management. Awesome. That's. Okay. Let's talk a little bit about surveillance. So currently the NCCN guidelines recommend history and physical and then plasma free or 24 hour urine metanephrines or meta difference between [00:24:00] three and 12 months, followed by every six, 12 months for the first three years, and then annually for up to 10 years.

Aging a chest CT or MRI abdomen pelvis is only recommended as clinically indicated. So if you're concerned for occurrence or ssis, then you would order those in. After 10 years, surveillance is recommended just as clinically indicated. Thanks cn. Lastly, let's briefly discuss Thermo Cytomas presenting with concerns for metastasis.

Yeah, so for patients they have a concern for metastasis. Those would be patients with large tumors, signs of invasion or high risk mutations. And for those patients you wanna do a complete workup. So that's gonna include chest ct. Donate PET CT or an FG G PET ct and all this. In order to identify and quantify the extent of their disease.

Patients should be discussing multidisciplinary tumor more in order to identify targeted therapies and treatment options. So these may include chemotherapy, radiation, cyto, reductive resection when [00:25:00] possible smat STEM analogs for those with tumors expressing soan receptors and even peptide receptor radionucleotide therapy such as lucid.

There. The only other thing to mention there is medical therapy for pheos that are unresectable. So you can give a false tyrosine analog MET tyrosine and that will basically biochemically decrease catecholamine production across the body to include in aio. And so that can reduce symptoms, but it won't prevent the tumor from progressing.

Thanks, Dr. Reland. Let's do a quick summary of our episode before we sign off. OC Carbo Cytomas are rare neuroendocrine catecholamine secreting tumors arising from caric cells of the adrenal medulla. Patients present with symptoms of catecholamine, excess, and workups should include plasma free fractionated metanephrines with confirmatory 24 hour urine metanephrines as indicated, as well as cross-sectional abdominal imaging to include an adrenal protocol CT prior to operative intervention, patients require pharmacological blockade with alpha [00:26:00] receptor blockers like doxys.

And beta blockers like metoprolol as indicated, starting two weeks preoperatively. Minimally invasive approaches for resection are preferred. However, open approaches should be considering the setting of large tumors in those with invasive features. Additional considerations for cortical sparing procedures is warranted in the setting of bilateral disease or hereditary syndromes.

Postoperatively patients require serial histories and physical exams, as well as plasma free or 24 hour urine in fractionated metanephrines and nor metanephrines. That's it for this episode. Thank you so much for joining us on Behind the Ninth Surgical Oncology dominate the day.