Physicians from Penn Medicine focus on critical decision-making using clinical cases commonly seen in primary care and women’s health practices: hyperprolactinemia, adrenal incidentalomas, and chronic steroid therapy (perioperative management, discontinuation). Panelists also discuss initial evaluation and the need for subspecialty referral.
Twitter @PennMDForum Good afternoon everyone and welcome to the second endocrine spotlight series of webinars. I'm Dave Eisenberg and I'm not an entrepreneur ologists but a general internist. But I was asked to moderate what we hope will be an educational and valuable discussion about adrenal and pituitary disorders. We have three expert endocrinologist with us today, um many of whom I think we all share patients with and so it's going to be nice to hear directly from them and hope to learn a lot from them. Julia Carla is an associate professor of clinical medicine and the medical director of the Pen pituitary center, Caitlin White is an assistant professor of clinical medicine and faculty at the Pen pituitary center. She was actually a student, a resident and a fellow here and I finally remember being her chief resident when she was an intern. And Sameer, Pen Volker is a clinical instructor of medicine and sees patients at pennsylvania hospital. He graduated from the Pen endocrinology fellowship last year and we were lucky to snag him as a clinician here. A few housekeeping items. Um First is you're eligible for CMI credit for this webinar and you will be contacted via email about claiming uh this this uh CMI credit. There's also going to be an evaluation uh that you will be directed to at the end of this session. And so we really hope that your you'll be able to fill that out and we very much welcome your feedback, more housekeeping things. Um We encourage you to submit questions through the question and answer feature of blue jeans and not the comment section. And we'll have our experts periodically checking that and answering them. And if we are able to we will actually highlight some of those questions and answer them on the webinar as well. Here are financial disclosures. We actually have no relevant financial disclosures and here are objectives. So what we hope to do during this session is develop a diagnostic approach to the evaluation of hyper product anemia, recognize HP to access suppression from chronic glucocorticoids and risk of tertiary adrenal insufficiency, insufficiency, manage glucocorticoids, dozing in illness and perry procedurally. And develop a diagnostic approach to radiographic and biochemical evaluation of incidental additional modules. With that. Let's get started and we'll do a case based presentation in the first case is going to be about hyper prolactin anemia and doctor Carlo will be guiding us through that. So we have a 37 year old woman who presents for a routine physical exam and notes fatigue and new amen area of three months duration. She was previously having regular periods. She's a mother of two school aged Children and he's using barrier method of contraception. Home pregnancy test was negative. Her last gynecologic evaluation was a year ago and was normal at that time. Her exam is relevant for a slender and healthy appearing woman. Her medications include Vitamin D. S. A. Taliban, 10 mg daily, a longstanding medication and dose. And her initial laboratory evaluation includes a serum pregnancy test that is negative TSH cbc cmp. All un remarkable and a prolactin level that's elevated at 55 nanograms per mil, A leader with a normal range being from 3 to 20. So this is something that is not uncommon in primary care clinic and in G in visits a woman getting a work up for secondary and gonorrhea who has an abnormality dr carla. Can you comment on how you would interpret this prolactin level and the significance of this elevation? Of course they've elected advance the next slide, I wanted to explain that the degree of prolactin elevation makes a great different difference here and your prolactin level of 55 nanograms per mil. A liter falls into a category that's termed mild and moderate prolactin elevation and ideologies. That is that it's almost never do to a prolactin oma, but the causes for the mild to moderate product innovations that typically is a physiologic um such as a recent meal exercise, um sexual activity, breast stimulation medications are common cause hypothyroidism and exceedingly rare. There is a circumstance where a brain or paracel lesion might cause a mild productive elevation. And if you advance to the next slide, I wanted to point out that the most common cause of persistent mild prolactin elevations medications and the class that's notorious for this is antipsychotics but and the depressants can do it too. And um even anti medics medical provides the paradigm is not available in the U. S. But compose seen um would do it um And um a common antihypertensive verapamil um As well as long as long as as well as metal doper can cause mouth productive elevation. Opiates can do it briefly right after the medication administration and up to date has a pretty comprehensive tat tables so that if you're ever wondering whether the patient is on the medication that could be causing hyper collecting in May, that's a great reference. Great. That's really happened at our patient who had who has a mild proactive elevation to 54 five given what you've told us, it's unlikely that it's a prolactin oma. But many patients are going to really worry after receiving this result that they potentially have a hormone secreting tumor. Um Can you tell us anything that we can share with the patients that to help reassure them paradoxically the highly proactive elevation the more impactful will be and getting them to feel better. So um you know protecting them is usually associated with prolactin levels. About 200 micro prolactin omagh's are known to your prolactin levels in the thousands and that's the situations where you can get significant clinical relief. Um Thanks to a wonderful tool that we have the medication called Kohlberg Line which is a dopamine agonist, it's a well tolerated oral medication that's taken twice a week. It causes both reduction in tumor size and rapidly so and it normalizes prolactin so that the patients who are suffering from irregular menses or infertility or hypogonadism in the case of a man, we'll get a rapid relief. And I wanted to share this case with you um that I came across here at Penn um of a 37 year old man who came to help er because he had a sudden loss in peripheral vision. Um He could only count fingers when the hand was placed right in front of him. And so not unexpectedly on the M. R. I. Um um You could see a very large mass centered um in the in the cellar region. Um David, I'm not sure if you if you if you can point it out to the audience, yep. That's was the was the yellow arrow there. Um He you can't see the optic apparatus here because his optic nerves are stretched and draped on top of the stall mass. And that's what explained his division laws. Um He was a member of our West African community. And as I get to know him, I've learned that they left the home country because his family was extra sized for not being able to have Children. So it wasn't unexpected that the prolactin levels returned in someone thousands. He left the yard with some Coburg line a week later, his vision was almost back to normal and a month later, which is demonstrated on the MRI. On the second panel, you could see um the lesion is significantly shrunk and it's probably half of what it used to be. But what's amazing is you could see optic eye ASM and it's full glory. It's in a completely normal position. They've is pointing it at, it's that vertical bar that goes across. It was a little stock underneath it. So, and and at that time prolactin levels were in order of magnitude lower at seven hundreds by the end of the first year of treatment, which is what spectral on panel panel see, you can see that the prolactin oma is no longer visible. His optic apparatus is free and clear is prolactin is now normal and this family was able to welcome their first child was in the year of the MRI being taken. So very high prolactin levels. Dramatic and beautiful results. Thanks to treatment with cat burgling. That's a dramatic demonstration of something that's so large that did not require surgery and I think we can use some of that to reassure reassure some of our patients that may be expecting neurosurgery that they probably won't need it dr carl. You also mentioned the possibility of there being something more sinister going on and obviously patients are always scared of potential malignancy. Can you talk a little bit about that? Unfortunately, this is an exceedingly rare scenario, but persistent, mild prolactin elevation can be a sign of a paracel a lesion like the one that's pictured here. This is platinum, sooner dolly meningioma or even I cns lesion where an astro seidel. More glioma would be pressing on the hypothalamus from above, creating mild hyper prolactin anemia. And was in the past three years, I've seen a case identified by one of our wonderful family practice nurse practitioners who followed up on my leg elevated prolactin by obtaining imaging and catching a glioma. So exceedingly rare, but it does happen. And so you definitely want to get to the bottom of the cause for hyper prolactin anemia. Okay. And that's that's in a persistently mildly elevated prolactin where you would suspect that, okay, let's get back to the case. Um So just to review, we we had an initial work up for a woman who was having secondary in january and was he was found to have a mild uh proactive elevation uh dr clark. What would you suggest that we do next As as people who maybe identifying this, but don't have the expertise of of your knowledge. The first step is simply to repeat it and repeat it in the fasted state and ask the patient not to exercise and not to be sexually active, leading in the hours leading up to the test as to exclude that physiologic proactive elevation. Um And then if it continues to be abnormally it is absolutely fine too um to refer with or without an MRI to one of the uh your endocrinology colleague. And I know that sometimes holding patient's hand during during that anxious period of anticipation of an unknown until they get to the specialist system is hard. And so I came up with a couple of sort of smart phrase type of um um text that you please feel free to adapt into your smart phrase. Um Library um like maybe would be holding phrases that will help patients to get until they're until they're seen. Um And the you know the first one says that you have a mild proactive innovation um that it was often normal when repeated. Um If it's elevated it's easily treatable. We'll we'll get you in winter. Endocrinology and similar was was a larger prolactin elevation. Um Some of the additional helpful epic resources is that if you do feel comfortable getting the MRI while you wait, wait for them to see us. Um There is a pituitary MRI. Order an epic that's searchable, so it's easy to order that. And then if you do get an MRI and you get an abnormal response that creates another spike and anxiety until the patient is seen. Please feel free to reach out through the consult or an email and again will provide some holding information that re prioritize getting the patient in. Very helpful. Thank you. And so just to follow up on this case, the woman with the mild prolactin elevation, she had a repeat fasting prolactin level as as you suggested and it was totally normal. Her periods actually returned to normal when she scaled back her intense exercise regiment that were, that was meant to address some of her pandemic pounds, which I think we're seeing pretty frequently um in our practices. Um so overall a good result. Any last comments Julia about what we talked about? No, this is this is this was perfect. And so this is as you could see this was a physiologic proactive elevation that's cleared on its own. And she had a bit of hypothalamic amon area due to over exercising which also resolved on its own. So um I'll hand it back over to do you dave and I'll jump in at the end of the talk. Great. Um And just a reminder. If you have any questions, please feel free to use the Q. And a function here. It doesn't look like we have any at this point. And so if any come up we will do our best to answer them. But I think we're going to move on to our our second case. Um Yeah. Advance their slides. And Samir is going to be taking us through this case about chronic steroids. So we have a 55 year old woman with a past medical history including severe Crohn's disease that has progressed through multiple treatments. She was prescribed a dilemma mob and a predniSONE, 30 mg taper two months ago. Her symptoms greatly improved after one month of injections and her predniSONE dose is now down to 7.5 mg daily. She will have repeat endoscopy to assess treatment response next week On exam. She's obese with around it face but no purple Austria on proximal or proximal weakness. Her routine blood work is normal. Um And so this is another example of a case that we see in the office pretty regularly. A patient who's on uh some chronic corticosteroids a lot of times. Um It's prescribed by another specialty but comes in to us for either routine follow up or peri procedural evaluation and dr penn Volker. Can you talk us through at which dose of corticosteroids and what duration we should start worrying about HPE. A access suppression of course. Um So if we think about how the hypothalamic pituitary adrenal axis works, everybody is going to make stare H. A. C. T. H. And eventually cortisol and response to systemic stress. Cortisol then is going to negatively feedback on the hypothalamus. Exogenous glucocorticoids including hydrocortisone, predniSONE dexamethasone. We're going to have a similar effect. It can cause tertiary adrenal insufficiency by suppression of cRH. The patients who are going to be at highest risk include those who are on the equivalent apprentice on 20 mg are higher for more than three weeks. We also assume that the HP access is suppressed in anyone who looks cushion wide. Once google core courts have been lowered to physiologic levels. HBs that hB access is always going to recover but it can take months to do so we go the next slide. I want to emphasize that many of these patients are simultaneously self treating. Their tertiary adrenal insufficiency, Physiologic Cortisol production is approximately equal to about 20 mg of hydrocortisone or five mg of predniSONE. So as long as patients are at these doses are higher, they're not going to have any symptoms when these doses drop below physiologic levels or even stopped altogether that patients run into trouble. God that's so helpful because a lot of times we get patients who are lowering their dose but above physiologic levels and we always wonder could it be adrenal insufficiency from that And it's helpful to know that they won't experience that until they're actually below their physiologic replacement. Um and just to hammer the point home, can you know we get a little nervous when people are on high doses of steroids but less than less than three weeks. So even someone with 60 mg of predniSONE daily for two weeks, they're unlikely to have um tertiary adrenal insufficiency. Exactly. So they're unlikely to have persistent HP access suppression or tertiary ai they're going to have an appropriately suppressed HP access while on such a high dose of predniSONE but because it's for only a short period of time the hypothalamus is going to go right back to making cRH as soon as the course is finished. Got it. Excellent. And now that we understand the doses and the durations that put our patients at risk for adrenal insufficiency. Can you describe the signs and symptoms of adrenal insufficiency? Sure. So for all patients with all different forms of adrenal insufficiency, the low levels of glucocorticoids result in a variety of relatively non specific symptoms, fatigue is very common, but patients can also have weight loss, chronic nausea and muscle aches. Unlike in primary adrenal insufficiency where the adrenal gland is intrinsically damaged. Patients with tertiary general efficiency. Um From exogenous glucocorticoids use aren't going to have any of these signs of mineral core decoy deficiency because they're running angiotensin. Ambassador system is still working perfectly fine, ideally. We we cast these patients before they present in general crisis which can be life threatening. And if we go to the next side, I just want to emphasis that, you know, we may all have this classic presentation in mind for adrenal insufficiency. But the reality is that these diagnoses are often delayed because the symptoms are relatively vague and non specific. Only about half of patients are diagnosed within six months and some have symptoms for years before they're diagnosed. It's something really important to keep in mind that it could be a really prolonged kind of delay in diagnosis. And so that's something great to learn. A lot of times. We're tapering steroids and patients who have been on corticosteroids for quite some time. And although their primary reason for being on steroids is much improved, like this patient here and her Crohn's disease, we worry about taking them completely off of the steroids because we worry about the Treasury adrenal insufficiency. Can you give us some guidance on how to brood approach that question of when is it safe to take someone off? Definitely. So when exploring the risk of tertiary I values, cortisol values are really going to be most interpret all when patients are on lower doses of glucocorticoids. The patients can be decreased to physiologic dose. That's ideal. There was like decks and methadone or very long lasting. So you're going to get a more valid and accurate results if they're on something with a shorter half life like hydrocortisone. Corporatism course All levels peak in the early morning. So it's easiest to identify deficiencies at approximately eight. a.m. or really within a couple hours of awakening. So if we check that cortisol, anything less than five is consistent with the adrenal insufficiency. Anything above 10 is likely to represent normal physiology and certainly above 15 it's a century ruled out The question really comes. If it's in that gray area of 5-10, it's probably safest to just continue the medication and repeat testing in like three months. Um mainly because the risk of under treating these patients is really just too high to prematurely discontinue until we're sure that the blood work ensures that they don't need it anymore. Got it. And if we eventually make the diagnosis of tertiary or retro Jinich adrenal insufficiency, can you walk us through the management of this? Yeah. So hydrocortisone best matches physiologic production of cortisol and has the lowest side effects of the different glucocorticoids formulations. So that's a preferred patients would benefit from a medical alert in case they're not coherent enough in an emergency situation. Like E. M. S. Can administer hydrocortisone if they see that. Um And then what I like to tell our patients is that our cortisol levels rise in terms of stress. So if we're not capable of making more quarters old and we have to increase our doses of hydrocortisone. So someone is dealing with an illness they should triple their dose for three days until they're feeling better. It's the three by three role. Um If they can't keep down their steroid pill that becomes a medical emergency and then for outpatient procedures they should double their doses before the day before the day of and the day after. Um During major surgeries Requirements can be quite high as high as 200 mg in 24 hours. And so will communicate with the surgery and anesthesia teams to give inter operative recommendations. Um And the basics of all these points are really nicely summarized. Then smart phrases. So if you guys want to copy this endo ai precaution smart phrase in an epic. It can be a helpful thing to give patients in like a letter or like after visit instruction form if you go the next side. Um revisiting kind of that physiologic dose that I talked about it earlier. Um I just want to reiterate that patients who are on super physiologic doses may not need to increase their doses based on the clinical scenario. So for example, someone who's already on predniSONE 15 mg of predniSONE five is an average physiologic dose. They probably have enough of a glucocorticoids level in their system that they're not really going to have to increase further in times of illness or outpatient procedures. But that same dose is not going to be adequate for something like major surgery so they wouldn't need something higher than got it. And just to clarify when when you say sick days, how do you define that? Do they need to have a fever? Or is it really subjective when they're not feeling well, they'll do their sick dozing? Yeah, I would say any any sort of illness federal or not that something that they would call out of work for skip school for. Um But yeah, they don't they don't need to do uh they don't need to have a fever necessarily. Okay. And the question in the chat while we're on this topic, if you determine that a patient has recovered from tertiary ai and you take them off of glucocorticoids, how for how long if at all, might you recommend stress dozing for the symptoms or for symptoms? That's a that's a really great question. So, um you know, there may be some level, depending on the clinical circumstance, on what you get that morning cortisol, there may be some level that you feel comfortable. Maybe they don't need a daily replacement. Um but you might increase in times of illness. I would say that situation is pretty, pretty rare and pretty, pretty nuanced and those patients should almost always see us in general, if the court is always going to be like adequate, most of those patients are not going to need increase those thing in times of stress. And as um Derek Carr Lopez has pointed out in the chat Penn Actually, a few years ago, switch to Cortisol essay where 13.5 in our system is really equivalent to 18 on the older essays, which would be a level that we look for for like cost and open stimulation testing. And so that's something that If they're clearing 13.5 on our essay, that's very, very encouraging that they have a very robust HB access. Okay, that's helpful. And you know, you mentioned patients seeing you, you know, in this specific situation, what when would you recommend that we refer patients to you if we're suspecting diagnosed uh androgenic adrenal insufficiency? Yeah. So um definitely send over any patients who you feel like you no longer need to manage their steroids for their original indication, but their access is either clearly suppressed or not clearly normal. Um dozing for major surgeries is also relatively complex and should just be handled by us and really if at any point in their management, you're ever hesitant about anything. Just reach out to us via console her email. We'd love to help out in any way. Big plug for the E consult. It's really been a remarkable edition and I've used it many times and have received really timely advice. So thank you for doing that. Um Let's just take a look if there are any additional questions. It doesn't look like there are. Um So Samir thank you very much for for taking us through that that case. Um And if any other questions come up we'll be sure to answer them in the Q. And a. Uh I I forgot to go back to the case. Uh And everyone is on the edge of their seat to find out what happened to this patient. Uh So let's let's go back before we finish up this case. And uh she has apparent disease control and she's about to get a colonoscopy to evaluate how her Crohn's disease is going. And she's on 7.5 mg daily. So sameer what dose should she received for her colonoscopy? If any dose adjustment. Yeah. So 7.5 is going to be super physiologic for an expected average predniSONE dose of five mg being physiologic. So she is above physiology but it's insufficient for an outpatient procedure. So I would recommend increasing her to 10 or double the five mg for the days surrounding her colonoscopy. And then in terms of the future if predniSONE is no longer going to be indicated from and you know suppressive standpoint we can taper that five mg that we talked about checking am cortisol and hopefully um check it before she takes her dose for the day and hopefully it's above 10 ideally above 13.5 we can stop the predniSONE if it's indeterminant or clearly low we'll just continue it and re check in in three months. Excellent. Thank you very much. Thanks again. Samir. Let's move on to our third case and dr white will be guiding us through this one and it's a case of an incidental adrenal nodule, something that's the bane of many discharge summaries that I've read with patients coming out of the hospital or getting imaging for other reasons. And so let me just read you the case. We have a 39 year old woman who presents for an evaluation of an incidentally founded renal nodule. She was seen in the emergency department with acute flank pain two weeks ago and was diagnosed with a kidney stone that has since passed spontaneously C. T. Of the abdomen performed in the er showed a 12 millimeter right adrenal nodule. Her past medical history significant for hypertension diagnosed at age 27 that is now controlled on a load up in Los are tan and hydrochlorothiazide. Just type two diabetes diagnosed at age 37 for which she takes metformin and do a good tight. Her exam is notable for well appearing. A woman with the blood pressure of 1 28/78 heart rate 72 BMI 31. Her face is not round or red, there are no violation Austria or archnemesis and she has no lower extremity edema. So dr white adrenal articles are just so common to find on cT scans. Seems like we're identifying them all the time. Can you walk us through your general approach when one of these is identified? Yes, absolutely. And you're right. Dave these are incredibly common, occurring in 3-4% of adults and with increasing prevalence with rising age. And so it can be really helpful to have a standard approach here. And so what's depicted here is the framework proposed by the European Society of endocrinology and their 2016 clinical practice guidelines. And I think it provides a good framework for approaching these incidental findings. So essentially when an adrenal incident Aloma is identified, there are two important considerations. Is it potentially malignant and is it functionally active? And then that drives your further investigations? And undoubtedly our patients worry about underlying malignancy when they have any nodule identified on a CT scan. Can you tell us about the risk of malignancy for an incidental adrenal nodule and what features we should be considering? Yeah, so that's really important. So fortunately incidental adrenal masses are rarely malignant and typically adrenal cancers have um classic radiographic features that are easily recognizable. And our radiologists are really good at pointing these out to us. So some reassuring imaging features for benign adrenal adenomas Our diameter less than four cm low density lesions. So these benign adrenal adenomas are lipid, rich and low density homogeneous appearance and rapid contrast washout on C. T. And so the figure on the right depicts a comparison of the mass size and centimeters of histological proven cortical adenomas in the triangles and carcinomas in the solid circles. And so this is a surgical cohort. So you can see that the adenoma sizes for you to be a little bit bigger because these are um us that ultimately underwent surgical resection. But still that four centimeter threshold identified most of the carcinomas and those few carcinomas that were under that four centimeter threshold would have been identified by some of these other features. Yeah. And this could be really reassuring to our patients especially since most of the incidental modules that we find are significantly smaller than four cm and so by far most of them are going to be benign. Um One of the things that you briefly touched on earlier was hormonal secretion. Um can you refresh your memory about what hormone excess syndromes can occur from these modules and um what we should do to evaluate for these? Yes. So when thinking about the hormone excess syndromes and biochemical evaluation of incidental adrenal masses, I find it really helpful to think about what are the hormones normally produced by the adrenal gland. And so in the adrenal cortex zone of Mariel osa produces elderhostel own Zona physical. Lotta produces cortisol, zona ridiculous, produces adrenal androgens D H. E A. S. And then the adrenal medulla is responsible for cata column in production, epinephrine and norepinephrine. And so these are the hormones that we think about being produced in excess with these incidental masses. So then thinking about each of these in a little bit more detail for primary hyper elderhostel own is um The main clinical feature here is hypertension and notably hypo colonia is not always present. And it's really important to recognize this clinically because these patients have an increased cardiovascular risk that's above that than expected um for the degree of hypertension that they have. And so if you can advance the slide, there's a figure here that depicts the accumulative incidents of composite cardiovascular events over time. And patients who have primary Aldo Stallone is um that's sub optimally treated with mineral, a quarter queen antagonists. Those who have primary old austin is um that's adequately treated with mineral according to antagonists such that their plasma rent an activity is no longer suppressed. Those patients who have essential hypertension without primary old austin is. Um And then lastly, those patients with primary old Austin is um that are treated with surgical adrenal ectomy. And so I think this figure nicely illustrates that it's really helpful to think about and to diagnose Primary old austin is um because this is readily treatable and can improve clinical outcomes. So then the other hormone to consider being produced in excess here is autonomous cortisol production. And so the clinical features here are hypertension, glucose intolerance, obesity, osteoporosis and display academia. And notably it's been recognized that especially adrenal modules can have mild autonomous cortisol production where there's subtle cortisol excess, even if the patient doesn't have overt physical stigmata of cushing's. But yet they can still have deleterious metabolic impact. And so it's important to consider this. And then lastly, fia chromosome Natomas are something that needs to be considered anytime there's an incidental adrenal mass. The main clinical feature of ferrochrome acetone is hypertension, which can be either sustained or paroxysmal, and the classic features of fetal chromosome toma that we think about paroxysmal palpitations, sweating, headaches, and shortness of breath are not always present. And so it's important to consider this test for this and patients who have adrenal um nah jewels, especially because these are arising from the adrenal medulla. These often don't fit those reassuring adenoma characteristics that I described previously and are more likely to be higher density lesions. And so this should certainly be considered in those circumstances. The other important consideration for fetal chromosome toma when thinking about diagnostic evaluation is that there's several commonly used medications that can give us falsely abnormal results. And so it's worth considering tapering and holding these interfering medications for about two weeks prior to biochemical testing. And just to clarify this says withdrawal from cloNIDine. And so I'm assuming that if someone is on cloNIDine but has an incidental adrenal nodule, you're suspecting theo cuomo said toma that you would continue the quantity and that would be okay. Exactly. You really want to avoid the circumstance for like they take cloNIDine on a regular basis and then held their medication in the morning that they were getting blood work. So if they're stable e on that medicine then you should check it while they're taking it. Got it. So then putting this all together and thinking about the biochemical and radiographic evaluation for incidental adrenal modules first you should measure morning fasting blood work. And so for patients who have hypertension or hypoglycemia they should have paired measurement of Valdosta rhone and plasma Renan activity. If elderhostel own is greater than 10 and Renan is suppressed less than one. Then this suggests high progesterone is um and these patients should either be referred to us or to nephrology for further evaluation. At the same time you could measure a C. Th cortisol and D. H. E. A. S. And if A C. T. H. And D. H. A. S. Are overtly suppressed then this is suggestive of autonomous cortisol production and then finally consider sending measurement of plasma metal reference or urinary meta reference for investigation of fio chroma saitama. And one no notable point here is that meta reference are better diagnostic test for fia chroma saitama as compared to cata cola means. And so plasma or urinary meta reference should be sent then second. These patients should all have a test to investigate for cortisol excess. And among the tests that we do to look for cortisol excess. The one mg dexamethasone suppression test is the most sensitive for adrenal modules and cortisol excess associated with adrenal modules. So for that dexamethasone suppression test, what you would ask the patient to do is to take one mg of dexamethasone at 11 o'clock at night and then the following morning measuring eight a.m. Serum cortisol and serum dexamethasone level. And I want to emphasize that the serum dexamethasone level is really valuable to measure because this a confirms the patient had taken dexamethasone and be confirms that they had appropriate absorption and metabolism of dexamethasone such that the cortisol result is interpret herbal. And so then if you have a therapeutic vaccine episode level a cortisol level less than 1.8 micrograms per deciliter is a normal response and of cortisol level above this would warrant further investigation and referral to us. I think you had a question maybe on the first. I I do actually, especially with the neurologic work up of hyper holocaust alone is um or potential hyper holocaust alone is um we're taught that there are many medications that could potentially um alter the levels of Aldo and read in. Um But that really the only important one to hold the spironolactone is that true? Should we be holding spironolactone? And if so for how long or is that something that we could still you know get the level while they're on it? Yeah that's a really good question. I mean I think when thinking about Aldo Stallone and Renan testing there's sort of a pragmatic approach and a conservative approach and I think it's a field we've in our underground society guidelines have sort of been moving more in the direction of a pragmatic approach to Valdosta. Run and run and testing, recognizing that people need their antihypertensive. Um There on the for a reason and that if you can measure paired eldest alone and Renan regardless of their antihypertensive regimen, then you're going to be screening more people and hopefully capturing more people with high progesterone is. Um And if they have suggestive results then these patients could be referred to nephrology or under chronology for further investigation of all of the medications mineral according receptor antagonist as you mentioned, Dave are the most interfering with interpretation. And so that's one medication to consider tapering and withholding for diagnostic testing. The caveat is if somebody is overtly hypothalamic or the Renan is still suppressed even on mineral according receptor antagonists then you know that they're not fully blocked. And you're testing could still be valuable. That's very helpful. Great. And did you want to make a comment about the imaging? Yeah. So then, you know, as what happened in this patient that you have presented. Oftentimes these adrenal incidental lomas are picked up on imaging done for another purpose. And so many times it can be helpful to get dedicated adrenal imaging to better characterize these lesions. Um with an adrenal protocol cT or an adrenaline MRI And reassuring imaging features. For adrenal adrenal adenomas again would be size less than four cm, low density homogeneous appearance and rapid contrast wash up great. And I think a lot of us would feel comfortable especially doing the initial hormonal evaluation and maybe ordering some follow up imaging. But I see a lot of variation on when people are sent to endocrinology for consultation. What would be your recommendations on when to pull the trigger and get get a patient like this to you. So truly we're happy to see these patients with or without further diagnostic evaluation. But going back to the framework that I had presented earlier once you've assessed adrenal incidental lomas for the potential of malignancy and for functionally active lesions. If you've identified clinically relevant hormonal excess syndrome or have radiographic features that are suspicious from malignant tumor, then these patients should absolutely be referred and will likely require surgery If in this evaluation there indeterminant radiographic features or there's possible autonomous hormone production. Then these patients also should be referred to us for further biochemical evaluation and diagnostic imaging. And then in the instance where you have a nonfunctioning tumor with clearly benign imaging features. So for example, size less than four cm, homogeneous appearance, low density and rapid contrast washout. Then these patients may not need to see us and may not need further investigation. Great, thank you. I think that's a really good framework on how to approach this. So let's get back to the case. Um and just to review, we have a 39 year old woman with hypertension on read drugs and diabetes who was found to have a right adrenal nodule on imaging performed for the evaluation of a kidney stone. We initiated getting some of the hormonal studies that you talked about with the th being normal cortisol. Being in the normal range for plasma. Met and friends and norman and friends were normal. And after one mg dexamethasone suppression, her 88 AM cortisol was suppressed appropriately. And the dexamethasone level, as you pointed out that we should get was also in the range where we know she took it appropriately. But her elderhostel own level was high 41.7 and Arena was low at less than 2.5. And she was hypovolemic with the potassium of 3.1. So with that those findings, her care was handed off to endocrinology. Um And Caitlin. Can you tell us what happened to her? Yes. So she came to me with a diagnosis of primary hyper old Austin is um but still required adrenal vein sampling and this was to confirm first that this was unilateral, not bilateral, high progesterone is um and then second to confirm that the source of high progesterone is um lateral eyes to the side of her visible tumor. And so on her adrenal vein sampling, it did confirm lateralization to the right adrenal gland and she underwent two right adrenal ectomy and actually three months post op terribly. She's doing really well. Her blood pressure is most recently won 11/76. She's normal Kalinic and she's now only on and load up in 10 mg daily. So a really a really good outcome in her circumstance. And I think her case sort of illustrates that although it can be scary for patients to hear that they have an incidental adrenal mass, we can reassure them that adrenal cancers are very rare, that typically they're large and easily recognizable by our radiologist on initial radiographic imaging and that adrenal masses are almost never the first manifestation of a cancer elsewhere. Um and that 80-85% of the time, this is just an inactive lump that's not causing them any problem. And the remaining 15-20% of the time could be a really incredible find. If we identify a hormonal excess syndrome that then we can act on and improve some of their active clinical issues like hypertension, obesity and develop anemia. That's great. There's one question in the question and answer that I think we have time for and then we'll wrap up if initial testing is within normal limits. What is your recommendation for repeat testing? Both imaging? When do you stop imaging the adrenal nodule and for biochemical evaluation If the initial testing was normal? Yeah, that's a really important question. And so what we recognize now is that for a small adrenal tumor that clearly looks like an adenoma. If your initial biochemical testing is normal then it's very unlikely that patients are going to develop an over syndrome of hormonal excess. The situation in that in that case that you should repeat biochemical testing is if their clinical situation changes. So if they have worsening hypertension, worsening diabetes, new osteoporosis then they should be reevaluated for this. Now the other thing is if patients have mild abnormalities on their dexamethasone suppression test like close to abnormal or mildly abnormal cortisol results then there may be a syndrome of autonomous cortisol production. And these patients should be sent to us to sort of think through further evaluation and potential intervention. Excellent. Thank you for answering that. Um And with that I think we're nearing the end of this webinar. I wanted to thank Dr Scarlett Pen Volker and White for sharing really valuable clinical Proles. I know I learned a lot prepping for this and also just listening to your expertise on some common adrenal and pituitary issues that we see in our offices all the time. Thanks to the audience who logged in and listened and and ask questions during this webinar. Um I wanted to remind you that right after this presentation uh you are going to be directed to an evaluation so please fill that out and then you'll get an email on how to claim cmI credit. Um And for the final word, I'm going to turn the virtual mike over to Dr Carlin who wanted to just say a few words in closing. Um Thanks Dave. I am um as you can probably tell Samir Caitlin and I a love what we do and be we really enjoy this role of being a consultant to our colleagues and we're so grateful to serena Cardella and to Dave Eisenberg for giving us this this opportunity to be consultant to a large group of you. Um We we really enjoyed working, working, putting this together. And then lastly I wanted to say that it was really thrilled to be able to talk to primary care community and and because we really love what you do, we really um um we see we see you we see that you're Iraq for our patients in common. And we I just wanted to say thank you for being our doctors, Hopefully everybody is doing well and and hopefully something useful comes out of this. Thanks for for all that you do. Thank you very much with that, we're going to sign off. Thanks for joining Take care. Bye bye.