Chapters Transcript Adrenal Incidentalomas: When to be Concerned and When to Let Go Course: Updates in Endocrinology 2024 Well, welcome and thank you so much. Um, I have to apologize ahead of time. I'm recovering from bronchitis and I still have the allergic cough. I may be coughing, so I have some water here. But hopefully, it will not take away from my enthusiasm, uh, that I'm trying to project about adrenal tumors. OK. So I have several objectives through, I think 7 cases that I'm going to talk about. We'll review epidemiology of adrenal incidentalomma. We'll review the recommendations from the recent 2023 ECANSAD guidelines on adrenal incidental ommas. We'll select hormonal workup targeting imaging characteristics of adrenal mass, because not everyone needs every hormone test. So just a bit of definition, the adrenal mass is, um, inside the home at least is still, um, uh, the definition is that it's serendipitously found on imaging, uh, done for reasons other than adrenal mass. However, in retrospect, these patients absolutely may have symptoms. I like to mention that at Mayo Clinic, at least 50% of people with adrenal Cushing's present incidentally. Which is interesting to me how underrecognized uh of overt Cushing's is, at least to our internal medicine colleagues. There's also this 1 centimeter uh cutoff for defining an adrenal mass. I, I think it's a reasonable cutoff, though it really depends on if you really want to find a 5 millimeter or 7 millimeter team and sometimes it is important, for example, in old astronomers, which are pretty small. So I guess what I'm saying I would not necessarily ignore a 90 millimeter adrenal mass. We also know that we are all seeing many more adrenal tumors than previously, mainly because we do many more CT scans, so we discover them. So this is a snapshot from Olmstead County, Minnesota where we have this medical linkage system where uh we could look at adrenal incident tilomas, adrenal tumors in general discovered between 1995 and 2017, and we found a tenfold increase in adrenal incidentilloma discovery. Mainly in um people above age 60 and mainly in the incident talloma uh category. Those who presented with overt features of hormone excess or symptoms of mass effect remained sort of the same percentage across the years. And in general, the um diagnostic strategy is to characterize functional status in an adrenal mass as well as malignant potential. As far as functional status, we concentrate on three pathways catecholamine excess, aldotroin excess, and cortisol excess. And for malignant potential, we'll talk about imaging phenotype and age. So commonly I see in radiology reports, uh, that, um, uh, a radiologist would say looks benign, no further workup needed, and that's sort of translated in primary care practice because I feel a lot of our primary care colleagues do not realize that just finding a benign tumor does not mean we should not test for hormones. So I've learned to put this box that 50% of benign tumors are functioning. And 50% of malignant tumors such as adrenal cortical cancers are functioning, at least overtly functioning. What about the prevalence in general? We know that 8% of all adrenal tumors are malignant. And it depends, uh, so, so what type of malignancy depends. So if you look at population, most malignant adrenal masses are metastasis, and those patients almost never get to see an endocrinologist. But if you look in our endocrine clinics, especially adrenal clinics, most malignancy we will see would be adrenocortical cancers. Actually, adrenal cortical cancers in Olmsted County represented only 0.5% of all tumors. 92% of patients have a benign adrenal mass, and depending on how you classify function, because I feel it's a continuously emerging concept, you will find non-functioning adrenal adenomas in 55 to 70% of cases, autonomous cordial secretion in up to 45% of cases, pheochromosommas in 1 to 5, and primary ostris in 2 to 10%. So let's talk about size and risk of malignancy. So clearly size does matter, but I hope to convince you in a few slides that that's not the starting point anymore. So we're not starting with a cut of 4 centimeters and everyone who has 4 centimeters and above needs surgery and everything under 4 centimeters were less forward. We actually have to start with imaging phenotype and as well as, uh, which mainly is harmful it is, but still, size does matter. And here's um what we found in Alston County. Overall risk of malignancy was 8.6%. The prevalence of malignancy was 6% if we looked at adrenal tumors under 2 centimeters. It was 9% if we looked at adrenal tumors between 2 and 4 centimeters, and it was 34% if we looked at adrenal tumors above 4 centimeters, which is pretty high percentage, but again, the majority of those tumors is not malignancies. What about, uh, that was population data. What about in endocrine clinics? Well, size test me in endocrine clinics as well. If we look at all comers. We know that 84% of all comers with adrenal tumors would be diagnosed with adrenal adenomas, another 6% with other benign masses such as myo lipomas, 4% with pheochromocytomas, and 2 sorry, 4% with adolocortical cancer, and 2% with metastasis. But if we look at patients with uh tumor size above 4 centimeters, here it's uh around uh 30% or so, we will have malignancy. And 22%, we would have few chromocytomas, with the rest being adenomas or other benign tumors. So here's a summary. Uh, what you have on the top, you'll have prevalence of a specific etiology. 80 to 85% would be adenomas, 5 to 8 other benign masses, 1 to 5 adrenal cortical cancer, 1 to 8 other malignancies, and 5 to 7 pheochromocytomas. Then you have the median tumor size. Which uh obviously is smaller in adrenal adenomas and benign adrenal masses and a bit bigger in uh metastasis, pheochromostomas, and so far, we're still diagnosing most adrenal cortical cancers a pretty big size. And here's another important point in its laterality. Why is it important? Because we can virtually exclude adrenal cortical cancer if we have bilateral masses. It's uh exceptionally bilateral. At least at Mayo Clinic, we never had a bilateral adrenal cortical cancer yet, though I, I do know that it is, um, definitely possible. While bilateral metastases are very common, up to 43% of patients would develop metastasis in both adrenal glands. Of course, in a patient with bilateral adrenal masses, we have to imaging separately for each adrenal mass, but in general theologist is the same. So, um, did I have an adrenal cortical, uh, a patient with adrenal cortical cancer on the left and adrenal adenoma on the right, yes, but it's exceptional. Usually you have the same etiology in both adrenal gland. So the rest of this, this was a bit of a theory, but the rest of this talk would be applying some of this evidence to 7 cases, 7 patients from my clinic. We'll start with the simplest and we'll go to a bit more unusual cases throughout this talk. So this is a 45-year-old woman. Um, who was found to have an adrenal mass when she was, uh, undergoing evaluation for back pain. She had a CT scan as well at that time. Adrenal mass was found, measured 2.8 centimeters, and that was in 2012. Now she's first time in the endocrine clinics. It was ignored at that time. And now she's first time in the endocrine clinic because she had another CT scan again for unrelated reason, and now adrenal mass measures 1 centimeter larger, 3.8 centimeters. Her medical history includes diabetes, um, obesity. She does have a history of acute transversomyelitis, which resolved. And this is her CT scan. And the arrow points to her adrenal mass. It measures 3.8 centimeters and um the uh Hansel unit is uh 3. Now it seems like there is an error here, it says right, so it's not on the right. So, uh, let's talk about the algorithm again. So we have in parallel to assess for adrenal hormone excess and for malignant potential. Again, cortisol, aldostri catecholaments. And if we have overt adrenal hormone excess, we would proceed usually with adrenalectomy. If we have mild adrenal hormone excess, for example, in Max, melanoma cortisol suppression, we discuss adrenalectomy versus other type of management, and we have a non-functioning adrenal mass. We don't need any further hormonal testing or monitoring. And malignant potential, we look at non-contrast CT scan at Hanslo units, or if we have MRI we'll look at chemical shift. If we have an ADT PET scan, we'll look at that. Though I'll talk about reasons to do those additional tests. And then if we have an indeterminate adrenal mass, we have some additional options. Additional imaging was an imaging test that was not yet done. Interval imaging to look for tumor growth. For example, we're not particularly worried, so let's repeat a CT scan in 6 months, or adrenalectomy right away. And rarely we could consider adrenal biopsy. So cortisol, a worker for cortisolce with 1 mg dexamethasone suppression test is needed for everyone. With or without symptoms. Remember, 50% of patients with overt Cushing's syndrome who I discovered incidentally. So I'm not sure how many people can recognize actually symptoms of overt Cushing's. Ce column in excess we need work up only if it's an indeterminate adrenal mass. Hail here is above 10. And worker for primary aldosters so far is recommended only in patients with hypertension or or and hypokalemia. So what is the most common clinical presentation of adrenal incidentalloma? Most commonly it's um uh based on CT with contrast. So contrast CT is done for whatever reason, an emergency room to evaluate some sort of acute symptom or maybe a chronic symptom, and we usually find a 1 to 4 centimeter adrenal mass. And the guidelines just point out that contra CT is not enough to assess for malignant potential and recommends non-contrast CT scan. So, Here is a recommendation. In all patients adrenallomas, non-contra CT scan should be done to understand whether the adrenal mass is homogeneous and lipid range. And why non-contra CT? Because it has most evidence and actually it can exclude with 100% certainty, um, a lot of tumors that can, are not malignant and can never become malignant. We recommend that if the non-contra CT is consistent with a benign adrenal mass, again, how unit under 10 and it's homogeneous adrenal mass, no further imaging is required, and I think it's still difficult for people to, um, accept that. So I feel like there are still a lot of patients with like 1.7 centimeters adrenal tumors and houseworthiness of zero who keep having CT scans every year for 5 years. It's not recommended. It was not recommended since 2016 because it's not needed. We better um concentrate on patients who actually do need additional worker because the biggest problem, at least in the United States, is that only 20% of all patients with adrenal incidentalloma actually get appropriate workup. So, the Hansfolk unit situation. So I'll talk a little bit more about that because that should be the starting point. Even if you start with a 7 centimeter adrenal mass, Hansfo unit can actually exclude malignancy in that patient. So the Hansfo unit is a measurement of radio density of an enhanced CT scan. And to summarize the data, risk of malignancy or pheochromocytoma is 0%. If Han's filter is under 10 is 1%. If Hans is between 10 and 20, and it's 5 to 20% if Hans ulti is above 20. And um this is a graph that I like to show because it's sort of like drives this point home. We've looked at 10,000 patients uh with available hands food units and available reference standards. So we knew what those patients have. The reference standard, uh, we included was either histopathology or uh imaging follow-up for at least 2 years, or we had clinical follow-up for 5 years. So when we looked at all patients with handfuls under 10, we found that 60% of all benign tumors fell into that category. When we looked at all patients with adrenal tumors with handfuls between 10 and 20, we found that another 26% of benign tumors fall into this category, but also 4% of pheochromocytomas, 1% of adrenal cortical cancers, and 2% of other malignant masses. And finally, when we looked at adrenal tumors with houses above 20, we found that another 14% of benign tumors fell into this category. And the rest pheochromocytomas, adrenal cortical cancers, and other malignant masses. So if you see a patient with adrenal mass and house at above 20, the likelihood that it's benign, it's still pretty high because most of patients have benign adrenal tumors. Um, so, uh, the scale here is, uh, does not account for prevalence. I just wanted to point this out. So why Hansel units? So this is a most recent systematic review and meta-analysis that was included in the guidelines from July 2023. Here's a summary of. Here's a summary of this meta-analysis. If we use a handful of units of 10, the sensitivity is 100%. The specificity is low, 57.5%. So again, it's not like if you have, as I've shown you before, if you have an adrenal mass with Has unit of 12, it's still very likely to be benign. If you are brave enough to use a Hans cutoff of 20, you do get a high specificity, but you may miss uh some people with um malignant masses. So you may exclude malignancy in those exceptional cases with Hansness of 10 to 20. So I know we do not have um an audience response system here, but I thought it may help engage the audience by thinking the answer to this question. So we have this case 145 year old who is presenting with enlarging adrenal mass. Now it's 3.8 centimeters. 10 years ago it was 2.8 centimeters. Hans Vinna is 3. She has a history of obesity and type 2 diabetes. What is the next best step in management? 1 mg dexamethasone suppression test. Do you want to measure 1 mg dexamethasone suppression test and metanephrines? Do you wanna measure the same but all dust and ratio or just refer to endocrine surgery because of tumor enlargement? Maybe we can have some show of head. Who votes for one? OK, maybe like 20%. Who votes for 2? OK, another 10%, 3. Another 10 and 4. No one wants to say, so it seems like only 40% voted, so which is OK, but majority wanted to do 1 mg dexamethasone suppression test, and I, uh, would agree with that. Why don't we have to measure metanephrines and aldosterone and rein? We don't have to measure aldosterone renin because she does not have hypertension or hypokalemia. We don't have to measure um metanephrines because Hansford unit of the team is under 10, so there's 0% chance it is pheochromocytoma. Why not refer to endocrine surgeon know that any one of you wanted to do that? Because despite that this benign tumor did increase in size, the rate of growth was like 1 millimeter per 1 year, which is absolutely uh consistent with a benign adrenal adenoma. So this is uh some rationale that I've just discussed. OK. So what about um follow up? So let's say this patient had 1 mg dexamethasone suppression test and it cortisol was 1.1, which is normal. What do we do? We, we know we don't need to follow up with another CT scan, but what about with another dexamethasone suppression test? So the guidelines do not recommend monitoring for hormonal excess, any patient with initially negative hormonal workup. But if you are to measure something, the reasonable thing to do would be to repeat 1 mg dexamethasone suppression test, not every year for 4 years, but maybe once in 3 to 5 years. Why? Because if this benign adenoma continues to grow, it may be capable of more cortisol production. OK, so we'll move on to case number 2. This is a 65 year old woman with an incidental adrenal mass, history, diabetes and hypertension, BMI is 36, hypertension does not seem to be controlled on whatever she is taking, and she does have abdominal obesity. And here's her non-contrast CT scan. So the arrow points towards a right adrenal mass. It's 2.6 centimeters. Hans is 5, again, under 10. And this is her hormonal workup. So, um, by the time she came to our clinic, she already had workup for primary aldostrianism at home, which is unusual because most people don't think about screening for primary aldos, but she did, and that was negative, so we did not repeat it. Uh, so what we did do is, uh, we did work up for mild autonomous cortisol secretion, and it was positive. Cortisol, after 1 mg overnight administration was 3.4 microns per deciliter. On a separate day, we measured ACTH and DHA sulfate, and ACH was below normal ranges. Um, DHA sulfate was pretty low, low normal. So this is an algorithm from the same July 2023 guidelines. Uh, everyone with an adrenal mass needs 1 mg dexamethasone suppression test, and then if, uh, as in this lady, cortisol is above 1.8 microns per deciliter, then we ask ourselves, or hopefully we already know that because we did a physical exam, but as this patient has overt features of Cushing's and, and if so, we followed that pathway and in that case, the pathway would be adrenalectomy. If the patient does not have uh features of overt hormone excess, what we do, we look for comorbidities potentially attributable to cortisol excess, and if there are none, not this patient, this patient has diabetes and hypertension, but if there are none, then we monitor for those because we know that these patients are at risk for developing of new cardiovascular comorbidities. But if the patient does have comorbidity is potentially attributable to Max, then we want to make sure that this cortisol excess is ACTH independent because many patients with Cushing disease or with mild Cushing disease in this case, uh, would have adrenal nodules, so we don't want um to miss potential pituitary origin. And if ACTH is low normal or low, in that case we consider specific treatment. Now, what is that specific treatment? Well, right now it's individualized discussion with a patient on adrenalectomy versus conservative management of comorbidities. For example, if a patient has diabetes, hypertension, obesity, and so on, we can treat each of those individually. In unilateral disease, unilateral adrenalectomy can be done, and I would say if you have a good surgical access, I frankly don't know I I'm, I don't see much risk of doing that, but of course after unilateral adrenalectomy, adrenaline insufficiency may develop and global cortico withdrawal may develop, so these patients need to be counseled about temporary adrenaline insufficiency and um get the full education on that. If it is bilateral adrenal mass, which thankfully our patient does not have, that becomes a bit more challenging because then we need to distinguish between bilateral adenomas and macro nodular adrenal hyperplasia. So I'm not sure how much is visible, um, from where you sit, but this is a phenotype of multiple nodules, uh, in a person actually with positive RMC5 mutation. Um, this is, um, a clear cut imaging phenotype of macro nodular adrenal hyperplasia. But in practice, not everyone presents with clear cut imaging phenotypes. So if we are not sure, and it may actually be bilateral adenomas, at our institution, we would do adrenal vein sampling if the patient still wants, uh, to undergo surgical solution. So we do, um, adrenal vein sampling under dexamethasone suppression, and we measure catecholamines to make sure that, uh, to, to, to make sure that we can determine whether cannulation was optimal. Now, um, the field is moving forward and there are several clinical trials now looking at medical management with, uh, um, cortisol affecting drugs or whether it's cortisol sensitivity or it's cortisol metabolism or it's actually cortisol synthesis. So maybe several years from now we'll be talking about the third management path for Max, which would be medical management, but as of now there are no approved therapies for Max as far as medical therapy and no studies published on it. Please no, no large status. So, um, follow up for overt hormone excess. So again, this is a synthesis of what the guidelines summarized. We know that if you initially find negative workup for primary aldostrous, negative workup for catecholamine excess, and negative workup for. Cuz says the chance that this patient will develop any of these is anywhere between 0 and 2.1% for pheochromocytoma. So because it's such a low percentage, we don't monitor this patient so we, we shouldn't. Um, however, uh, we should advise our patient that should they develop symptoms of this type of, uh, hormone excess, they should let us know, or their primary care physician know to reassess. So I keep telling that to all my patients since 2009, and as of now, no one called back and say, I think I have overt features of hormone excess now, so I, I suppose at least my experience is similar to what the systematic review showed. So what if patient decided on conservative follow up of uh MAC? So our patient had unilateral adrenal adenoma, but she says, you know, I don't want to have surgery. What guidelines recommend that yearly reassessment and uh monitoring for comorbidities associated with MAC. And if this com comorbidities develop or worsen, re-referral to endocrinologist to reconsider um other therapist is recommended. So actually, The guidelines suggest that all of this annual follow-up is done not by endocrinologist, but by primary care physician because 1% of population has max, and there are just not enough endocrinologists to do all of this. Let's talk about follow-up for malignancy. So this patient has a, I believe, 2.6 centimeter adrenal mass and household unit was under 10, I believe it was 5. So the pathway for these patients, no further imaging is required. So we just tell this patient, this is it. We are done, you don't need any CT scan for this purpose. We'll talk about other pathways as we go through different patients. And this is the next patient. Case number 3. We have another 45-year-old woman with incidental adrenal mass. She was found with this adrenal mass while workup for cholecystitis. Adrenal mass in this case measured 1.9 centimeters and unenhanced CT attenuation, the non-contrast CT scan. Showed Hansfeld unit of 38. So in this case it's an indeterminate but smaller adrenal mass, 1.9 centimeters. Medical history is consistent with hypertension. She started amlodipine three months ago for that. And let's have some show of hands again. So 1.9 centimeter, houses of 38, hypertension, what would you measure? It's really the same answers as in the 1st 1 mg dexamethasone suppression test, that plus metanephrines, that plus metanephrines and aldosin, or just sort of refer to endocrine surgeon because it's indeterminate. Any show of hands? For the 1st 1 1 mg dexamethasone suppression test. OK, the second option. The 3rd OK, Maity want to do the 3rd and the referral to endocrine surgeon. I guess not yet. Well, so, so I agree. I hope the next slide will, will say that too. So we should measure dexatin suppression test in everyone. She does have hypertension, so we should do work for primary aldotroin though if, if that 1.9 centimeter is an 11.9 centimeter tumor is an aldostronoma, I would have expected much more severe hypertension, but I guess it is possible. And because her tumor is indeterminate with Hansen is above 10, we do need to test for catecholamine excess. So I would agree with what everyone said, um, that we have to test for everything. And this is the rationale that I've already discussed. So we did do everything and here's the results. 1 mg dexamethasone suppression test was normal. Her plasma free metanephrines and plasma free normetanephrines were both slightly abnormal, and her aldosterone renin was negative for, um, primary aldosters. So in this case, she ended up having pheochromocytoma that was confirmed by pathology. Why not referral to endocrine surgeon right away? Well, because we need to alpha block these patients before surgery. Moving on to case number 4. This is a 68 year old man with an enlarging adrenal mass, and here's a history. So, uh, he had a CT scan for known renal cyst. And we had quite a few CT scans to follow adrenal mass that actually no one told him about until recently, but that's nothing unusual. So over the last two years we knew based on those CT images that his adrenal mass enlarged from 2.1 centimeters to 3.4 centimeters. So it's what a 13 millimeter, 1.3 centimeter difference in two years, and that's a bit more than what's expected in an adenoma, I would say. So medical history, benign prosthetic hypertrophy, he has his complex left renal cyst on physical exam, normal blood pressure, he's obese, no cushion good features. And So here's um uh what, OK, so this is from two years ago, so you see a 1.7 centimeter adrenal mass, and enhanced CT at that time was 33, and this is 2 years later, 3.4 centimeter adrenal mass. Um, and as you see, this is a contrast enhanced CT scan, so we were not able to measure how on this one, but obviously if it was 333, it would not become 5. So then we've done hormonal workup for him. 1 mg dexamethasone suppression test was abnormal, cortisol was 3.4 microns per deciliter, and workup for catecholamine excess was normal. So let's talk about the guidelines again. So what do the guidelines recommend for uh tumors with Hass between 11 and 20 and smaller tumors? In this case, if you recall, the chance for malignancy or pheochromosotomas in this category is around 1%. So in this case, additional imaging, such as interval imaging in 12 months was recommended. What if we have, like, like let's look at this category, which is the um the most uh worrisome. We have a tumor with housefulness above 20 or the tumor is heterogeneous, and we should not measure house units, and the tumor is large, above 4 centimeters. On this case, discussion on multidisci tumor uh meeting and also considering surgery right away or further imaging if it's helpful, was recommended by the guidelines, and our patient is in this category. So currently he has a 3.6 centimeter adrenal mass that's under 4 centimeters with Hans above 20. The als here did not also include tumor growths, but again, that's another thing that is important in this case. So again, we should not ignore this patient. What other imaging uh could be done in this case, because guidelines strongly suggest like uh considering additional imaging, so let's talk about what's possible here. CT with contrast. But in general, more and more publications appear showing that contrast CT scan is not very accurate, especially using the cutoffs that are sort of like we're used to, which would be 60% for absolute contrast washout and 40% for uh relative washout. At least in our adrenal tumor board meeting we had at least 10 patients with proven adrenal cortical cancer who had excellent contrast washout, and all of them had baseline enhanced units above 30. So if uh you have an indetermined adrenal mass, in my mind, contrast washout does not particularly help you. And if not, why do this test that I cannot trust? Guidelines do not recommend uh proceeding with contrast washo. What about chemical shift analysis on MRI? Well, um, MRI and chemical shift analysis specifically looks at lipid content just as household units on CT scan. So, in general, if you have non-contra CT scan, obtaining additional MRI is not helpful. Now, if I already have MRI I will probably not do CT scan because it can be used interchangeably. But it really does not help, uh, classify the tumors as far as like, definitely not malignant or definitely benign, if you already have an enhanced CT and it says howsin is above 10. So, um, it has weaker data and the chemical shift analysis is not completely uniform. So it seems like different radiologists calculated differently, and this is why it's a bit difficult to generalize the results from systematic review and meta-analysis to clinical practice. What about FDG PET scan? This is actually the additional test guidelines do you recommend. If you do want an additional test, you should do PET scan. And this is why um the systematic review and meta-analysis was included in the guidelines showed that Depending on what SUV max cut off you use and depending on what type of adrenal liver uh adrenal to liver ratio you use, the sensitivity varies between 85 to 100% and specificity varies between 85 and 100%. So you still have a chance for 15% false negatives, false positives. So when would you have false positives? It's usually. Hormonally active adrenal adenomas like cortisol producing adenomas, those with mass or vertical sings may really light up on the PET scan. One could you have false negatives in some uh metastases, especially smaller metastasis. So let's go back to our patient, 64 year old man with an enlarging adrenal mass. We actually decided an adrenalectomy for him, and interestingly enough, he did not have malignancy. He had an adenoma with hemorrhage, so it was really good diagnosis for him. So let's sort of like see if that's consistent with what we found here. He has a known adrenal mass for 2 years. His dexamatine suppression test is abnormal, and the enlargement rate is at least 1.3 centimeters in 2 years, larger, but more than what would be expected in an adenoma. So, um, obviously it cannot be anything but adrenal cortical lesion because only adrenal adenommas, adrenal cortical cancers produce cortisol. So it's between the two. And actually he had adrenalectomy with the thought that it could be a small adrenal cortical cancer. However, when a hematoma was found in his, uh, adrenal adenoma that explained the enlargement. So he probably developed a hemorrhage sometimes for here and we've documented it on pathology. So occasionally you have nice surprises. OK, case number 5, we have a 67 year old woman with an incidental adrenal mass. This was found while undergoing workup for recurrent urinary tract infections. She actually feels well, has no complaints. Adrenal mass was present in 2006, so we obtained the outside images, and it measured 3.6 centimeters at that time. Of course, it was ignored, like the whole, you know, like it's, it's usually happening, but Now it measures 10 centimeters. So it has been a while. I think I've seen her actually a couple of years ago, so it was, let's say 15 years, um, and in 15 years, adrenal mass enlarged from 3.6 to 10 centimeters. She has type 2 diabetes, hypertension, and stage 3B chronic kidney disease. Her blood pressure is well controlled, and her BBMI is 26. She has no overt features of Cushing's syndrome. And this is um a CT scan right now. We were not able to obtain the actual images from 2006. So now we have, um, in this particular case we decided to do a uh a CT scan with and without contrast because we strongly suspected adrenal cyst. And the reason we've done, um, also contrast enhancement, because we know that adrenal cysts don't enhance. And this is what this is illustrating. So we have a sort of a rounded, very homogeneous lesion. Hans was 18. So if you just look at houses and size, it's a bit worrisome. But um, when you look at enhancement and you find that Hans is still around what is like 17, we already know that this is not the actual tumor tissue, that it's fluid. So that was very reassuring. She did do um hormonal workup and it was negative. So what do we do in this case? We have a 67 year old woman with a non-functioning adrenal mass likely an adrenal cyst. Um, again, negative hormonal workup. Referral to endocrine surgeon for adrenalectomy, repeat CT scan in 6 to 12 months. Repeat hormonal testing in 12 months, or no follow-up is needed. Who would like to vote for one? I'll just vote for all four, not to confuse people. No one wants to remove it. It's 10 centimeters. OK. What about repeating CT scan? OK, we have a we have a few people. What about hormonal testing repeat in 12 months? OK. No follow up. OK, I feel like the majority of you are abstaining, but it's OK. So thank you for everyone who committed. OK, well, she, um. Depending on what symptoms she has, I would say either 1 or number 4 would have been equally reasonable. If she said, look, I really have the symptoms of mass effect. Uh, I have discomfort, I have abdominal pain. What I would have said that we're not sure whether this discomfort is because of this 10 centimeter cyst, but it's reasonable to consider some sort of surgery, maybe not necessarily adrenalectomy, maybe cystectomy. Or something else. But because she was absolutely asymptomatic, it, you know, nothing is mentioned in the question as well as far as far as symptoms of mass effect. We know that it's benign adrenal cyst. No follow up is needed, um, from my point of view. So why not repeat CT scan in 6 to 12 months? Well, because it would not change, let's say in 6 to 12 months, adrenal cyst now is not 10 centimeters but 11 centimeters. She's still asymptomatic. The option is still the same. You have a cyst and you don't have any symptoms, it's OK. What if it's 20 centimeters, still the same? Because as long as patients don't have symptoms of abdominal mass impact, we don't really the the benefit of intervention is lower than the risk of intervention. What about repeating hormonal testing in 12 months? Well, I, I think those who chose it are probably aware of the fact that sometimes we have cystic chromocytomas or cystic malignancies. But in those cases we clearly see also the meat part of it, the tumor part of it. It's uh pretty easy to distinguish based on the thin wall of the cyst. So if you already have non-functioning cyst right now, it's unlikely that if we're missing cysticheochromocytoma or cystic adrenal cortical cancer in this case. So probably unnecessary to then repeat hormonal testing again. And this is borrowed from a review that, um, I had a chance to collaborate with um uh a team from Karolinska and basically what, uh, uh, this algorithm states is that after doing hormonal workup and discussion of multidisciplinary adrenal team meeting, if you have the non-contrast enhancing cyst with thin walls, which is our patient, conservative management, uh, should be strongly considered, especially if there are no symptoms. OK, so we move on to the next case. So we have now a 51 year old man again with incidental adrenal mass, and that was found during worker for abdominal pain. Abdominal pain is intermittent but severe. He also has back pain for the last 6 months, has type 2 diabetes, uncontrolled hypertension, and, uh, no Cushing good features on exam. And this is what his uh CT scan shows. He has a 7.4 centimeter adrenal mass with unenhanced CT attenuation between -20 and -97. And the hormonal workup was negative for cortisol, catecholamine, or um aldotin excess. It's debatable whether some of those hormonal, uh hormone workups should have been done, but we had it. So, so this was a patient with pathognomonic features of myelolipoma, who has some symptoms of mass effect, back pain, intermittent severe pain. So, um, these are heterogeneous tumors, but with very low Hansford units because really there are two components, fat and my component, and both of them have low Hansford units. I just wanted to point out, uh, this table because I think we should consider undiagnosed congenital adrenal hyperplasia in patients with large myelippomas or bilateral myellipomas, especially in men. Why? Because while myelipomas are the most common benign adrenal mass in all comers, like if you look at the column one here, you see that up to 6.5% of patients we will see in our clinic will have a mild lipoma. Usually these are small, uh, the median tumor size is like 2 to 4 centimeters. Usually they're unilateral though this patient also had unilateral uh myelipoma. But if we have a person with congenital adrenal hyperplasia. The proportion of my lipomas in that population is 36.6% based on a systematic review and those patients present younger. And the median tumor size is much larger, 10.2 centimeters, and also look at the proportion of bilaterality. Almost 60% of patients with CH would have, if they have mylippoma, it would be bilateral myelipoma versus only 5% of people without CH. So, I think measuring 17H progesterone in patients with larger or bilateral myelippoma is not unreasonable. So that's another review that I, I collaborated with Karolinska Group, um, and, uh, basically it's the pathway here is to consider hormonal workup, mainly because, uh, rarely there are tumors that look like my lipomas, but they are not. In my experience, I had adenomas with lipomatous metaplasia that looked identical to my lipoma, but. Uh, we knew that it was not because it was cortisol producing and then we documented it based on, uh, surgery. So I think it's important to consider hormonal workup in these patients despite pathognomonic features of my lipoma and obviously 17H progesterone if you suspect CH. And um uh the on the right here you'll see imaging characteristics that are usually hard to miss. As far as management in general, these like adrenal cysts, the patient before, these should be or could be managed conservatively. I know my colleague and friend from Germany, Martin Fassen, has this horror case of a patient who was a 4.2 centimeter mile lipoma, where because it was above 4 centimeters she had surgery and she died. Um, died because she had a rare complication from adrenalectomy. So I personally never had um a horror story like this, but this is one of the things we're trying to avoid, to, to do surgery for unclear reasons. So most of these, uh, my lipomas can really be. Followed conservatively. I personally have a bunch of people with mylippoma 1012 centimeters who never grow and don't cause any, uh, symptoms in my patients. But if we do have a patient with, um, a mass effect symptom, adrenalectomy should be considered. So, uh, in, in this particular case, This patient does have symptoms of mass effect, so that's why um we uh thought that considering adrenalectomy is a good idea. Um, I think it's important to, uh, counsel our patients that really uh the the symptoms may may be completely unrelated. In this particular person they were thankfully, because they did resolve with surgery. And this is my last case, a 66-year-old woman with uh early satiety. She presents with 4 weeks of weight loss, nausea, weakness, and fatigue. Uh, her past medical history is consistent with hypertension, well controlled on two medications, and breast cancer treated with bilateral mastectomy six years ago. She also had the chemotherapy at that time. Now she comes with hypertension, heart rate is elevated, and she's ill appearing. And this is a CT scan. She has a 12 centimeter right adrenal mass, and that measured on non-contra CT scan 45 Hansford unit. She also has a 9 centimeter left adrenal mass. Heterogeneous Hansfo unit was around 39 in some areas. Otherwise, she has no other um abnormalities on CT chest, abdomen and pelvis. And this is a hormonal workup that again she actually had done before uh coming to our clinic and everything was negative. But I do want to point out that aldosterone was undetectable and rein was quite high. That may become important. Just wanted to remind you that with a bilateral adrenal mass, it's extremely unlikely to be adrenal cortical cancer and being so large, I guess the differential would be between bilateral malignancy and bilateral pheochromocytoma. Work of catechoma excess was negative, so it's very unlikely to be bilateral pheochromocytoma. So what do we do in this case? Here I would like to consider biopsy. But not right away. Potentially not right away. So, so at least I give you the answer I would not do right away. But, uh, this patient presents with fatigue, nausea, weight loss, bilateral heterogeneous adrenal masses. What is the best next step in management? Measure cortisol ACTH, do FDG PET scan, biopsy, or bilateral adrenalectomy? Who votes for one? OK. What about PET scan? Another maybe 15% biopsy? OK. And bilateral adrenalectomy? OK. Well, that's good. We've looked at prevalence of primary adrenal insufficiency in patients with bilateral metastasis, and we found that 12.4% of patients had primary adrenal insufficiency, 20% if adrenal mass was above 4 centimeters. So, and this is an underestimate because unfortunately even at Mayo Clinic, not everyone had testing for primal insufficiency or at least a cortisol. So mortality was very high in this group, not surprising, but I wonder how many died of malignancy versus undiagnosed adrenal crisis. So I would say before we do any procedures such as biopsy, we do need to diagnose adrenaline insufficiency because otherwise, any procedure can really um uh cause an adrenal crisis precipitate, I guess would be a better word, adrenal crisis, so. Um, she did have primal insufficiency. We started her on hydrocortisone, we biopsied her, and that was bilateral breast cancer metastasis. So this is my summary slide. Um, Hansel unit is key. Don't start with tumor sizes, Start with Hansel units, because right away, 70% of patients, you can tell them you have a benign adrenal mass. Uh, if you are to do an additional test, MRI and CT with contrast, uh, not particularly helpful, uh, but PET scan could be. Then we did not talk about steroid profiling during this talk, um, but it's another, um, non-invasive diagnostic test that could be considered. I know Mayo Clinic offers it from, uh, United States, um, um, um, institutions. Adrenalectomy and follow up can be considered. Biopsy almost never should be done except in the cases like I've said I've shown before. We also, we also talked a bit about hormone excess, we talked mainly about Max. Um, 30 to 40% prevalence, so we should always consider 1 mg dexamethasone suppression test. But if you have a non-functioning adrenal mass, the risk of future hormone excess is low, though it's 7% for max and under 0.5% for overt features. Thank you so much. Uh, that was great talk. I have a quick question about um case three. So, um, Bill Young used to say that theos are usually, I can't remember, 3 centimeters or 4 centimeters. So that patient had a baby Theo. If the patient did not have hypertension. Do you know what the natural history of that, you know, baby is? Well, I think the natural history would be continuous very slow growth, uh, though we don't really have much data to know that because we, we usually remove them. Um, now more and more we discover pheochromosommas at a smaller size, um, mainly because of genetic screening. So we actually published, um, a study a couple of years ago in JCM, uh, with Bill Young as well, uh, looking at the tumor size based on discovery, uh, mode of discovery, and if it's genetic screening, it's like 2.5 to 3 centimeters medium size. If it's incidental, it's more like 4 to 5 centimeters, and if if symptoms of hormone excess, it's even larger. There is no doubt that size is uh increasing size is proportional to catecholamine production in most people. Yeah. Please go ahead. Quick question, um, with your incidental illness in your yearly workup, you didn't mention looking for subclinical Cushing's. Can you comment on that? Yeah, so, uh, so Max is really mild autonomous cortisol secretion or Max is, um, what was previously called subclinical Cushing's. In 2016, this term was replaced with autonomous cortisol secretion because it was a bit inaccurate. It's not really subclinical. Those patients have a lot of clinical features. So they may not look like they have a word Cushing's, but it's definitely not subclinical. So it was replaced with autonomous cordial secretion and as of 2023, it's termed max, mild autonomous cortisol secretion, and that's, um, um, 30 to 40% prevalence of all patients with adrenal adenomas and cut off of 1.8 microns per deciliter. Do we have more time or? Last question. Thank you. That's, that's another topic that I can talk forever. I'll take only 30 seconds to reply. So assuming this patient with primary does not have max and xhasone suppression test is normal, what I do is I check potassium once a week for 4 weeks after surgery to detect maillocortica deficiency. I do calculate contralateral suppression index to identify people at risk for that. And if hyperkalemia develops, um, my first step is low potassium diet. My second step is hydrochlorothiazide. My third step start fludrocortisone. As you, I've had a couple of patients I had to keep on flurocortisone, but thankfully it's rare. So, um, 3 months after surgery, I do all doranin and complete metabolic panel, and this concludes my postoperative approach to primary aldostris. I can talk about more about it later. Published March 22, 2024 Created by Related Presenters Irina Bancos, MD
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