Around the Practice: February 17, 2021

Jason M. Hafron, MD: Hello, everyone. I'm Dr. Jason Hafron from Michigan Institute of Urology, and welcome to Urology Times Around the Practice, a live interactive event featuring the multidisciplinary approach to challenging cases in urologic oncology. This is hosted in partnership with LUGPA. Thank you, everyone for joining me.

I'm pleased to be joined by my panel, Dr. Tyler Gunter, assistant professor and associate residency program director in the Department of Radiation Oncology at Stephenson Cancer Center in Oklahoma University. Welcome, Dr. Gunter. I'm also joined by Christopher Pieczonka who's director of clinical research and the executive vice president of the Physician Teamster Alliance of Central New York. Welcome, Chris. We're also joined with Dr. Ajeet Gajra, a clinical professor of medicine at SUNY Upstate Medical University, and also the senior medical director on the national landscape of oncology and urology. We're also joined by Dr. Byard Edwards, from Advanced Diagnostic Imaging in Nashville, Tennessee. Dr. Edwards is a diagnostic radiologist that focuses on body imaging.

We’re going to start off with our first case, which was given to us by Ben Martin from Central Ohio Urology Group. Thank you, Ben, for submitting this case. It's an incidentally discovered adrenal mass. It was a 37-year-old female, who was referred to the urology clinic for a mixed incontinence in late 2019. The HPI is significant for the patient also reported, she reported intermittent frontal headaches, occasional heart flutter, and she also lost 25 pounds while trying to change her diet, but it seemed easier than expected.

She also reported to Dr. Martin the hands and feet got cold easily. These G2P3 normal spontaneous vaginal delivery. She has no history of hypertension, diabetes, infections, she denies any pelvic pain or dysuria. Has some noted anxiety, but it was manageable. Past medical history is negative, past surgical history is negative. And her family history, she has no family history of any syndromes or malignancies.

Her blood pressure was slightly elevated. Her BMI was 31 and otherwise the rest of her exam was negative. Her laboratory evaluation, however, showed evidence of microscopic hematuria. So based on the evidence of microscopic hematuria, Dr. Martin proceeded with an office flexible cystoscopy, which reported was no tumor stones or diverticulum, essentially negative. She subsequently underwent a renal ultrasonography, which demonstrated a left upper pole 1.2 centimeter hyperechoic region with slight color flow. The radiologist felt that it might be a possible AML. The right kidney was normal.

Based on this result, Dr. Martin proceeded with a confirmatory CT abdomen of the pelvis with contrast. I selected the coordinate images, so to speak, and put an obvious red arrow so that we could focus in on the left, left adrenal gland, which you can see is enlarged. I'm going to pick on Dr. Edwards here in a second but I'll just help him a little bit because he doesn't have the complete series. But what the radiologist felt was it was a left adrenal mass that was 2.1 by 3.1 by 2.6 centimeters. It was greater than 10 Hounsfield units and there was possible areas of central necrosis. There was no lymphadenopathy, no renal masses or stones.

Dr. Edwards, before we get into this case, as urologists, we're frequently confronted with adrenal incidentalomas that occur about 3% of CT imaging and up to 10% in elderly patients. And the challenge we have is to differentiate benign adrenal tumors from malignant tumors and, and metabolic tumors. Is there an easy algorithm that urologists can use when we're forced to evaluate these quite frequent consults? Any tips or tricks you would recommend to the average urologist?

Byard Edwards, MD: So there is a white paper from the AACR, it was most recently updated in 2017, on what to do with these. And it's a flowchart that I won't go through in detail. But to s- uh, to summarize it, the first thing you look for other specific, uh, can you make a specific diagnosis. So if it is more than 50% macroscopic fat, that's a myelolipoma, you're done. If it has, measures less than 10 Hounsfield units, that's an adenoma, and you're done. If it doesn't meet those two criteria or one of those two criteria, then you go into a little more complicated flowchart that depends on several things. One is size, one is have they had a history of malignancy, and then some of the imaging characteristics.

The simplest thing is if it's less than one centimeter, no follow up is recommended. Those are so common, that's the recommendation. If there are more than four centimeters, then generally they're, the recommendation is they're highly worrisome and, you know, will probably be resected surgical consultation. It's in between one and four centimeters that's a little more complicated. But to just give a simple thing, the best next step generally in an indeterminate one to four centimeter adrenal nodule is an adrenal DT.

And, and the newest recommendations that's actually preferred over an MRI, um, for the simple reason that it's more sensitive, the washout that you're looking for is very common, and adrenal advantage 98% sensitive. Whereas the effect you're looking for on MRI, which is signal drop out due to, uh, cytoplasmic fat is less common. So we still see MRIs for this and it's fine. But an adrenal protocol CT without and with contrast is the preferred method now for imaging workup of these indeterminate nodules.

Jason M. Hafron, MD: Oh, it's very helpful. Thank you. And explain to me washout a little bit more. When you say washout, are you actually calculating this or what should we be looking in the reports or on the imaging?

Byard Edwards, MD: Oh, yeah, absolutely. So there's two ways to do it. One is if you only have a normal enhanced series, so you don't have a non-contrast series. Then you do a delay at 15 minutes and there is a formula, subtract the density enhance units of the original enhance, the 70 or 90 second, minus the 15-minute delay, divided by the original one. And for that, you look for 40%. And, you know, there's the formula. If you have a pre-contrast, it's a slightly different formula. But it, that's basically it. Adenomas they enhance very rapidly, but then they, the contrast washes out more quickly than most other tumors. They have this big gap between the 70 to 90 seconds and the 15 minutes. Now, one interesting caveat in this case, which is a great case.

There are two caveats with using washouts. So if you can't make the diagnosis based on just the density or having macroscopic fat, you go to washout. And it's 98% sensitive but it's only about 92% specific of, for adenomas. And the reason for that is there are a couple of other hypervascular masses that also enhance really rapidly in washout. The, one of them is renal cell carcinoma. So renal cell carcinoma meds can mimic in adenoma and washout. And the second is a peochromocytoma. So a peochromocytoma, about one-third of them also show washout. So it's still what we use because the vast majority of these are adenomas just because there's so much more common. But those are limitations of using washout, to diagnose an adenoma.

Jason M. Hafron, MD: Now, that's very helpful. Thank you very much. So, not to spoil it but, a three-centimeter lesion that's greater than 10 Hounsfield units with not good washout or it's bright, suspicious for peochromocytoma. When you're confronted with an adrenal incidentaloma, do you routinely perform biochemical evaluation of these incidental adenomas? Dr. Edwards said the less than one centimeter. But when you have these indeterminant lesions, you have a woman with some symptoms, would you routinely, you know, do a biochemical evaluation?

Dr. Pieczonka, here are the lab results of this patient. We start with plasma free metanephrines, which was normal less than 25, normal metanephrines was elevated at 452, total is 452. Um, then got a 24-hour urine, and you can see the numbers there. We have elevated normetanephrines, aldosterone, was 31 plasma aldosterone computations. So plasma renin was also normal. I guess, Chris, my question to you is when you're confronted with these, incidentalomas, do you routinely order about chemical evaluation? And what's your typical, you know, go-to evaluation for these patients if you do that?

Christopher Pieczonka, MD: So, I think that, you didn't ask this but the question would be, "What's the role for biopsy of these patients?" Before we kind of get to the kind of the biochemical evaluation. And I think that the role for biopsy is pretty negligible on these patients. A lot of the times, a biopsy could be done. It may be non-diagnostic. In the case of peochromocytoma, you might actually irritate things. But, I think, for the viewing audience, that's important to realize that we're not talking about that specifically because that's not really recommended.

I think in this particular case, there's some suggestion that this could be a peochromocytoma. Patient has symptoms, that kind of looking back on it, could be consistent with that. I think what Dr. Martin ordered is sort of spot on, looking at the urine free and even the plasma free metanephrines are really going to kind of hone in and look in the field. I think that looking at the aldosterone level to see if this is some sort of aldosterone secreting tumor, or if it was primary aldosteronism.

It doesn't look like it has the features of adrenal cortical carcinoma, because you said that kind of the margins were negative, doesn't look like an aggressive renal cortical carcinoma. I would say in our practice, a lot of these patients, to be honest with you, are referred out to the endocrinologist, depending ... we have a very wide geographic footprint in our practice. And so some of the physicians in our practice would refer this out, some of them would do the urine free, and plasma free metanephrines.

And that kind of refer them inbound if they thought surgery is necessary to the people that do dependently invasive procedure. I think the thing that's a little intriguing here is that his free plasma metanephrine is actually not high. Or she, her, you know, her free plasma metanephrine is not high. But the normetanephrine is high, obviously, which really, I think more and more is looking like this as a potential pheochromocytoma.

Jason M. Hafron, MD: Now, those are great points, Chris. Yeah, and it's kind of interesting that the plasma free, which is the most sensitive, is actually normal. But, you know, this patient obviously has a peochromocytoma, based on the radiologic imaging, as well based on the biochemical evaluation. You know, peochromocytomas are the 10% tumor, because it's considered 10% are malignant, 10% are bilateral, 10% are familial and 10% are, uh, extra adrenal and 10% occur in children. So that's, you know, something we, are pounded into our brains as medical students.

What's also interesting, as urologists evolve into genetics and next gen sequencing, I think we have to get back to evaluating these patients for familial associations with these patients. 30% are associated with familial syndromes. This patient had no family history. But, men have multiple endocrine neoplasia is common, Von Hippel-Lindau or neurofibromatosis or these obscure familial paraganglioma.

So, I think it's, it's important to keep that in the back of your mind. And if necessary, a reference for genetic evaluation, if there's any family history of any syndromes. That's something that we as urologist or as we frequently forget. So with this in mind, the patient was taken for a robotic assisted left adrenalectomy. Chris, what about surgical approach, preoperative evaluation? Any comments here you would make when, when managing these patients?

Christopher Pieczonka, MD: This has changed in the last decade or so, going from a large open incision to a robotic type of approach and minimally invasive approach. The adrenal gland is obviously very well-positioned to be done robotically. We would probably then maybe send it to nephrology because this patient, you know, looking like they have a pheochromocytoma was going to need to be pre-treated with either alpha and potentially beta blocking agents to minimize a cytokine, a hormonal storm interoperatively.

Now, I'm old enough that when we used to do these procedures, we would do these open, and you put your hand and you kind of mess around with the adrenal tumor. And I think that, you know, we can be much more delicate and much more finesse using the robotic approach that having been said, you need to make sure that you don't have the anesthesiologist get caught behind the eight ball with this. The other thing is that you're going to end up talking to your anesthesia team. We all have, you know, kind of the anesthesia providers that we think are the best ones.

And this is one of the cases that you don't want to have, the resident in the case or the brand new CRNA. You know, this needs to be kind of the attending level anesthesiologist to understanding what we're dealing with so that they don't have any, uh, issues, sort of, of, you know, kind of, of above the, uh, e- ether drapes, you know, at the patient's head so that they know what we're getting into. Um, so, you, you know, so I think that there's a step in here that requires making sure that you get this patient block down appropriately for a couple weeks before the procedure.

Jason M. Hafron, MD: Yeah. I kind of agree with you Chris. It's very important to communicate with the anesthesiologist. This patient needs to be seen and pre-screened, the anesthesiologist needs to be prepared for this case, they need to have the appropriate lines, uh, the appropriate drips available, nitroprusside, if it's a really hot pheo. We typically also work with them within, they'll do a lot of the medical management up to the surgery, the alpha blocker, the beta blocker, and whatever else is needed. I can't stress that enough. I agree with you, Chris. That it's critical.

Most of these in our practice would be treated robotically. Me, personally, I see a handful of these a year. I think the key was with the robotic approach or even the open approaches, early control of that adrenal vein, you want to get that hypertensive crisis that's coming. And what's interesting about these, there's a lot of variability. There's a spectrum of how active the fields are. Some of them you can barely even touch. And you'll trigger hypertension or severe blood pressure changes.

So what I'd like to do is essentially a touchless approach that basically will score out the outline of the adrenal after the colons were reflected, and use ... Well, in this case, you know, use the spleen, get the spleen way away from the adrenal. Mobilize the kidney away from the adrenal gland. And once I have that, I can minimize my manipulation of it after I've taken the vein and can typically avoid that hypertensive crisis from manipulation. So, this can be tricky, to Chris's point, you need to have very careful coordination with your anesthesiologist. These people need the A lines, they need central lines, they need their nitroprusside drips, uh, and nitrile drips if necessary.

So, um, you know, when I asked Ben for a case that Raoul Concepcion has been for a case, he actually had a run of like five of these, which is unheard of. So, Ben, great work and thank you for submitting this case. So, basically, follow up, she saw the endocrinologist, all of her labs returned to normal, she feels better, less fatigue, more energy and, and the BP, uh, remain normal, and she did great. So, you know, not a common case that we see but obviously, an interesting case, from a radiological perspective, as well as biochemical medical perspective.