#513 Pituitary Incidentalomas

Hey, before we get to the show, I wanted to remind you to check out our Patreon at patreon.com slash curbsiders. If you haven't signed up yet, sign up now to get ad-free episodes, twice-monthly bonus episodes, and a whole bunch of other cool stuff at patreon.com slash curbsiders. Hey, Paul. A friend of mine tried to annoy me with some bird puns. I feel like I'm not going to get this one. All right, lay it on me. But I soon realized that two can play at that game. I would never have gotten there. All right. It's not bad. I don't mind it. I liked it. Yeah. You know, obviously I was thinking of cereal when I said that one. The Curbsiders Podcast is for entertainment, education, and information purposes only. And the topics discussed should not be used solely to diagnose, treat, cure, or prevent any diseases or conditions. For the more, the views and statements expressed on this podcast are solely those of the host and should not be interpreted to reflect official policy or position of any entity, aside from possibly cash-like moral hospital and affiliate outreach programs, if indeed there are any. In fact, there are none. Pretty much, we are responsible if you screw up. You should always do your own homework and let us know when we're working. Welcome back to The Curbsiders. I'm Dr. Matthew Frank-Watto, here with my great friend and America's primary care physician, Dr. Paul Nelson-Williams. Hi, Paul. Hi, Matt. How are you? Paul, I'm doing well. We had a fantastic conversation. Brain holes are going to be filled everywhere after this episode, Paul. I hate that. We talked about pituitary incidentalomas with a fantastic guest, Dr. Maria Flecheriou. And Paul, I'm really excited for people to hear this. But before they hear this, before you tell them about our wonderful co-host and producer for this episode, Paul, what is it that we do on Curbsiders? Sure, Matt. As a reminder, we are the Internal Medicine Podcast. We use expert interviews to bring you clinical pearls and practice changing knowledge. As you alluded to, we are also joined by an additional co-host and the producer of this episode, Dr. Mameen Ahmad. Dr. Ahmad, how are you? I'm doing good. How about you guys? Hey, we are happy to have you here. I would say you are a whiz kid. I had the pleasure of working with you during your residency. And I would say your future endocrine champion of the United States, maybe future chief of endocrine at Cashslack. Fantastic, fantastic guy. So thank you for putting this together. And a great guest choice as well. Yep, for sure. Just taken with modesty. I appreciate it. Why don't I tell you about our guests while we're at it? there is no response necessary for that oh and we wait before you get to the we should thank the uh your your co-fellows for helping us to write the fantastic names um on that we use for our cases here so thanks to the temple endocrinology fellows uh you all rule thank you oh yes yes i want to shout out uh dr shen fernando dr rachel ripa and victoria de millis all excellent co-fellows that help make these names. All right. So Matt, tonight we had an incredible conversation with our guest, Dr. Maria Flesheriou, as you mentioned. She taught us her approach to the work of management of pituitary incidentalomas and what makes them incidentalomas. For you to know, Dr. Flesheriou is a professor of medicine and neurologic surgery and the director of the Pituitary Center at Oregon Health and Science University in Portland, Oregon. She has been the chair of the Clinical Guidelines Committee of the Endocrine Society and has been a former president of the Pituitary Society and most recently was one of the authors of the Pituitary Society's Pituitary Incidental Loma Guidelines. She's a role model for endocrinology fellows like the great Dr. Ahmad. And so without further ado, let's get to it. Reminder that this and most episodes will be available for CME credit for all health professionals through vcuhealth at curbsiders.vcuhealth.org. Maria, we've been talking for a while, really excited for the audience to get to know you. as a way of doing that, how about you tell them a hobby or interest that you have outside of medicine? That's a good question. Do we have a life outside medicine lately? I hope so. Especially since COVID, less and less. But I really like to travel. I was born in Europe, so I'm from Transylvania, both me and my husband. I'm not saying we're vampires, but you can assume. and we like to travel and go as much as we can when we're out. We live in the, we are now West Coast converts, so we live near the mountains and the ocean. So we hike every weekend when we're not on call. And when we can, or with conferences or just for vacations, we like to travel either back to Europe where we're from or go to different continents. So I went to Australia, I went to Asia several times and trying to know each country a little bit more. So I'm not keeping track, but I hope I will hit many soon. Is Transylvania a tourist destination? Would you recommend it? Paul is a bit of a world traveler. He was just in Europe. Would you recommend Paul travel there? Right, definitely. But don't go and look for Dracula. But Transylvania is a wonderful, wonderful destination right now. And I will tell you to rush because it's getting full of tourists, both from U.S. and from Europe. And it's going to be overcrowded probably in a few years. now it's overcrowded with bears in the mountains so if you are hiking because like Pacific Trail it's also a Transylvania Trail which is nice I haven't done it yet because I need to fix my knee first but then after that we're planning of doing but I'm afraid of bears so we have make sure that you take bear spray with you but otherwise it's it's gorgeous it's a little bit of Germany with Hungary combined. As you know, that part of Europe was several hundred years was a different empire. So I think it's worse. But you go and tell me if you don't like it. All right, Paul, I challenge you. You have my email, so yes. Yeah. Okay. All right. Before we get to the cases, anything else, Paul, you want to ask? Oh, I always do like to ask the advice question. So is there any advice that you've received that has been especially meaningful or any advice that you'd like to give to your learners or trainees that you feel is especially helpful to them? Either or. Yeah. So I think the, I got many advices from many mentors over the years. One, because I worked on several continents and in different hospitals, even in US. And I think the most important, and I try to combine all of them and of course selected the one I liked as everybody, and then move from there. and what I'm teaching my mentees. So I think from a clinical perspective, because we're clinicians, physician scientists, but mostly clinicians, I tell them that they have to find something that they like, but where curiosity meets clinical relevance. Because if you focus and you have a niche on your own, and of course, for all your audience, Bitwitter is the greatest ever, maybe Adrenal too. But if you find something that you are passionate about, then all the extra work that we all have to do in our careers, it's worth it. And then you end up seeing these patients and follow them over the years and you see that your work makes a difference. And then I know it sounds cliche, but especially now in academic medicine, when we're pulled in all the directions, I think the team effort and having mentees that you sustain and not just by opening doors for them, but actually bringing their curiosity up and give them the options of asking questions and having their own career could actually make a difference for our patients for future and also for us, for our satisfaction. So I think this is a combination of the advice I got plus my career over 20 years. It's a very meta moment because you're mentoring like tens of thousands of people with by giving that advice. So that's great. I want to get to a case because we have a lot to go through. And Mobin, would you like to read our first case from Cashlack? You I believe we have some great names in store for for everyone tonight. So the first case, we have Miss Ella Tersica, a 27 year old female. She is a 27-year-old female with a past medical history of chronic migraines who presented to the clinic after being sent for an MRI of her brain with and without contrast for workup of her headaches. She was incidentally noted to have a 5-millimeter pituitary lesion described as likely indicative of a pituitary microadenoma. on physical exam her vitals are stable blood pressure 120 over 78 heart rate 75 beats per minute respiratory rate of 10 breaths per minute and afebrile she denies any changes in vision and overall states that her migraines have been stable over time so I guess you know the first question that we kind of wanted to ask you Dr. Flessario was what is usually your initial workup hormonally for these microadnomas? That's a very interesting case, not just and very common. And I think with so much imaging and the MRIs getting better and even the CTs, you are all going to see in your practice more pituitary incidental oma. I tell our fellows that in autopsy studies, and we mentioned this in the guidelines too, There are other studies that mention that up to 30% had something on the P2-3. Probably that's too much, but 10% for sure, even on imaging. And the problem that I see is that a lot of these small lesions are actually not read by the radiologists because it's so small that sometimes they don't think it's important, especially if the patient had an MRI for stroke. We go back for some large macroadenomas now and look and actually on an MRI 10 years ago, it was something there. So that's first information that it's more common. So a patient that's coming to an internal medicine doctor with an incidentaloma could be nothing. And I tell the patients, usually they are sent to us because an endocrinologist will do the workup. But I think soon with not enough endocrinologists, the initial hormonal workup might be done by the internal medicine clinic. Before we get too deep into the hormonal workup, so just for you to know, Maria, I'm the resident dum-dum for the group, so I will sort of ask the obvious questions. But can I ask us to define our terms? In terms of microadenoma versus macroadenoma versus functioning and non-functioning incidentaloma, I feel like those, especially the non-functioning and the incidentaloma, are kind of used interchangeably. Just so we can be explicit about what we're talking about, I feel like that'd be helpful for me. So can we define those first? That's a very good point. So between the incidentaloma, what we have defined in the guidelines, and we had discussions over discussions, because it's used interchangeable, as you are saying. And this is also the time to mention that a lot of what I'm going to say is expert opinion because there are no prospective studies. There are few retrospective studies, including ours, about natural progression. But the data that we have for pituitary incidentaloma largely comes from the non-functioning pituitary adenoma, and I'm going to talk a little bit about that. So incidentaloma, by definition, we consider it's a lesion, could be an adenoma, could be a different type of tumor, could be infectious, could be vascular, could be something that's abnormal in the cellar area. and this is the most important thing incidentally find it and the reason is that sometimes actually the patient has headaches which could be due because they have acromegaly and the gross hormone gives you headache but it doesn't matter they had it for something that who ordered it didn't think of that and i think we need to talk later about the patient perceptions because it's a paper in revision and will be published soon, that the patients, when we asked them through a survey, they said, nobody explained to me. So your point is excellent. Nobody explained to me why I had some symptoms, but then suddenly I needed to see other doctors and what's happening with that. And especially when they end up seeing something that starts with neuro, either neuroendocrinologist or neurosurgeons. So micro adenoma, what we define, and it's very artificial because it's anything that's less than 10 millimeter. Now, if you're telling me that nine millimeter or 11, it's a huge difference, and Moby knows, not really. It depends, but we had to put a cutoff somewhere, and this was done many, many years ago, that micro is considered something that's less than 10 millimeter, one centimeter, and anything larger than that, it's macro. And then, of course, because we're endocrinologists and like numbers, then we came up with even more than if it's more than four centimeters, it's called giant. Now, again, we're the four just because it's more rare. So this is the size by definition. And now with better imaging, actually, we see more details in the microadenomas, which even if it's a six or seven millimeter, might be more relevant if it's closer to the optic chiasm. And the optic chiasm is where the optic nerves are crossing. So that's very important for vision, for women that want to get pregnant. So even a small, tiny thing's close to there, it's a problem. Now, the functioning, the non-functioning, the complicated picture is, and you are correct, and not at resident level, is we change how we call them. And it's not because we like new names, which we do, but the pathology of these tumors changed Before, we call them, because we didn't have transcription factors and all that, not even staining, we call them functioning or non-functioning, meaning how the patient looked like. So if the patient had acromegaly, then it was a gross hormone secreting tumor. Then several years later came at least staining for gross hormone. And now we have transcription factors where a lot of these tumors could actually know where they are coming from. And this is probably better for determining aggressiveness and also prognosis, though we're not there yet. So still, if it's staining, if it's a null cell adenoma, it means nothing. It's on staining and transcription factors. And then we go with details what type of tumor they are. But from a clinical perspective, from a clinician point of view, what we need to do, And this is what Mubin was asking for a patient in front of you with a small lesion. We don't even know if it's a microdenoma. I usually look at the imaging because it could be a Rutgers clef cyst. That's five millimeter. Usually hypophysitis looks a little bit different. But when we decide that on imaging, it's not something that they need to see a surgeon. We need to look at the hormones. And the hormones, we need to look for two different directions. Because these, especially if it looks like an adenoma, but we don't know because it could be an adenoma that hemorrhaged and then it looks like a Rutgers clef cyst or a small craniofaryngoma. Then we have to check hormones to make sure that this is not a hypersecreting or hyperfunctioning. I told you we like multiple names for the same thing. So hypersecreting or hyperfunctioning, it's the same thing. And that's where the discussion came because it's focused in dog guidelines and it's based on data, and I'm going to tell you why we can do for all the hormones, but we check hormones to make sure that this is not a hyper-secreting tumor or hyper-functioning. And this is vital because if this is a prolactinoma, then we can treat medically and it has relevance for fertility and also other symptoms. Also, what's new compared with other previous guidance is the fact that now that we know that a lot of these tumors are actually gross hormone secreting. Because we used to think that unless you are giant when you're a child or you have the features, you open the book and this is acromegaly, that these are the gross hormone secreting tumors. And that's not the case because the delay in diagnosis is 11 years. So at the beginning, patients don't look like that. So we suggested in the guidelines, we actually recommend it even more than suggested that Everybody with a pituitary lesion should have at least a prolactin and an IGF-1, which is the marker for gross hormone, everybody. Now, what we didn't recommend, and this is because of the false positive for the test, is unless the patients have symptoms, we should not look in detail for Cushing's. And the reason is that the false positive is very high. So, of course, if you check in everybody, then you will find a lot of positive tests. If you have any clinical suspicion, that's a different story. So this is for high. Now, what happens, even with a smaller lesion, much more rare than with a larger one, just because the pituitary adenoma is creating pressure on the normal pituitary, patients could have pituitary dysfunction. So we have to check hormones, which are, of course, different because, again, we're funny. We check hormones for high, and then we have to check hormones and way more hormones for low because they are tumors that induce adrenal insufficiency. So you have a patient in front of you with maybe some fatigue or dizziness or nothing, but they can have adrenal insufficiency. So they need a morning cortisol and an ACTH. They also, if they had this tumor for a while, they can have gross hormone deficiency. Much more rare, but it could be, and usually with larger one. patients also can have thyroid dysfunction even from smaller lesions again usually with larger and what is very important from internal medicine point of view is that just the TSH is not enough because the TSH is perfect for checking for primary hypothyroidism but if it's the pituitary that's not working the TSH will be normal but the free T4 could be very low so I think that's an important point because when we're all in clinic and rushing and you're used to check a TSH and all of us, we have to put our other head for pituitary. Yeah. And most places now are defaulting TSH with reflex to T4. But if the TSH is normal because it's a central pituitary issue, then you're going to miss that the free T4 is low. That's a very good point. And that's a peep that I have with most of the labs, including ours, but I fixed it. They are still asking me, do you really want to order one? And I say, yes, yes, yes. And I think that what we should do, but again, with some electronic medical record is more complicated, would be if it's a diagnosis that you link with central hypothyroidism, and this should be a great improvement project for all the fellows. If you have a diagnosis of central hypothyroidism or pituitary adenoma, whatever diagnosis that includes pituitary automatically to link the 3D4 to TSH, not reflex. So definitely this would be important. And this could be a patient, your patient, Mabin, didn't have it, but they can be already on replacement for primary hypothyroidism or primary hypogonadism, and then they need completely different doses if they are checked properly. So that would be very important. But I think for your case for microdenoma once everybody has to have it because we do not want to miss it Every group has someone who insists on doing things the hard way. 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And for Curbsiders listeners, there's a special offer. Use promo code CURB30 for 30% off all online courses and webcasts. That's promo code CURB30 for 30% off all online courses and webcasts. See for yourself why Continuing Education Company is considered a leading source for medical education. Visit cmemeeting.org forward slash curbsiders to learn more. That's cmemeeting.org forward slash curbsiders. recognizing that we're going to look up the guidelines and order all the correct labs regardless still the scenario i imagine this patient is seen in the primary care office they get the mri for headaches we find this incidental finding then they come back and have this conversation what are there any particular historical points like what are the really high yield symptomatic questions that you would ask i still maybe it wouldn't change testing all that much, but I mean, or I guess would it? So I guess, what do your questions look like for the patient who's physically in the office when you're kind of at this point in the workup? So I think it wouldn't change the testing for prolactin IGF-1 or for pituitary dysfunction for hypopituitarism, the initial one, but it will change when we do the follow-up testing, because if the initial labs are normal, then we suggest patients to, and we send patients back to primary care, because right now we change in an MRI, especially for a lesion so small, it's not needing for two to three years. Of course, it's individualized treatment. But for a patient that is not feeling well, and I always put in my notes, if I don't forget, call me earlier if things change. Because if a patient starts to be more fatigued, could be life in this century, but also could be development of adrenal insufficiency, especially for larger tumors. Could be severe headache if the patient has at the beginning enlarging of the, if it's a cystic lesion, most of the time it's unrelated and the MRI was done for the headaches and they found the pituitary adenoma most of the time. However, as I said earlier, if it's a gross hormone secreting tumor, the gross hormone would actually make the headaches worse by direct effects on the receptors. The one where I really look at the symptoms initially are if I think that the patient has Cushing's or not, or might have Cushing's, because this will change what we do. Because we have recommended, and I mentioned and I'm mentioning again, this is expert opinion for the large majority of the data. So what we do, and we found a consensus, This is a consensus guidelines because there are no prospective studies on that. But if I think that the patient, and it's also clinical expertise because I have over 500 patients with Cushing. So I had severe Cushings and mild Cushings and all that. And this is just in OHSU before I had even more. So the question is, from a primary care point of view, do we have any criteria or can I give you a score because you all like scoring? to say this patient has it or doesn't have it. So we don't. There's fewer done in Europe and none of them are great because this is so complex. What I recommend and I teach our students is if you think about it, just test for it. Because yes, we want to eliminate the false positives, but also, so in a patient that has obesity, hypertension, and diabetes, all of them uncontrolled. And they have some clinical features. You can have Cushing's without having purple stretch marks, but then you have to have something else, either hypokalemia or muscle weakness or something. It's extremely rare, and we're not going to talk about these cases, like glucocorticoid resistance and others that you don't see features. So you have to have some features to check for it. We might change and we'll find out that in 10 years, actually, more patients will actually have it than we missed it. But at this point, I think listening to the patient is very important. And ideally, you'll all have more time. Dr. Placerio, thank you so much for that explanation. I actually had, again, a question regarding kind of similar to this case. Obviously, every macroadenoma starts off as a microadenoma. Is there certain characteristics we can look at in the microadenoma? I know the previous Endocrine Society guidelines in 2011 referenced the 6mm cutoff of maybe they're at higher risk of progressing to a microadenoma, or what is kind of your approach? Are there certain microadenomas that you keep a closer eye on, I guess? That's a very good point, and the reason we don't have in this new consensus those guidelines are cut off is because more data show that actually that's not correct. And the six millimeter, the same thing as for Cushing's was put there just because the older MRI were able to actually see these lesions because the cuts were not even at two millimeters. There were three. So six was something that you would see. We don't really know, especially for microdenomas in men, for example, if they are not completely different than macroadenomas. So yes, everything was small at some point, but I think it's a different when we find them might have a different natural history. So not all microadenomas will grow. Very few will actually grow. Now, how many of these will grow in our large study when we looked retrospectively, almost 300 patients, about 10% grew older patients, which again, that's why all juniors and residents, that's why you have to do research to show you that you are not correct. I thought that the older you are, the slower the tumor will grow. Nope. In our study, the patients that were over 65, they had more growth in the microadenomas. So we don't really know, and I don't use a cutoff. The cutoff of 10, I use it just because it's defining micro and macro. I look where the adenoma is. And there are some studies that looked at cystic lesion, which, because both our study and also the larger retrospective data from UK, where they had the consortium all over, not all over, but larger centers in NHS in UK, that the cystic lesion will actually, some of them even shrink. So that's why it's important to do serial image. But before we definitely, and that's why we looked at our data, because we did so many MRIs. And at some point I was like, this is too much. We need to do a less frequent one because these are stable. For a while, I was not correct which one they're growing more, but at least the initial idea was good. So these microdenomas could grow. So that's what we should tell patients. and you are the first point of contact, telling patients that the large, large majority of these lesions, either small or big, are benign. This is the first thing that they want to hear. And you will be very surprised that in this patient survey, again, with a lot of biases, 14% of patients said that they didn't even know and they had visits and nobody told them that This is not cancer. So I think we have to up the communication with patients for this diagnosis. And I'm glad you chose it for your podcast because that's very important. I wanted to try to do a recap because we've gone through so much already. This has been great. So we gave you this case. It's a 27-year-old woman. She has a 5-millimeter incidental pituitary lesion. So we weren't looking for that. We were imaging for headaches. So this qualifies as a pituitary incidentaloma because we found it incidentally. And the differential for that is broad. You said it could be a cyst, infection, infiltration, inflammation, malignancy, vascular. There's just a huge list of what it could potentially be. Some of the terminology for pituitary adenoma, non-functioning pituitary adenoma refers to there's absence of clinical symptoms, basically. We're not able to detect it. That doesn't necessarily mean, I guess, on a micro level that maybe there is something happening with what we're seeing there, but we're not seeing a clinical syndrome. And then you said micro adenoma is less than a centimeter, macro is a centimeter or more, and then giant is more than four centimeters. And we said that other things we should pay attention to is how close it is to the optic chiasm because if it's closer, we're going to be more worried about that person because there's less, I guess, less space. If it grows, it could cause problems sooner. And then you said that as far as hormone testing, we want to look for, is this hyper secreting a hormone or hyper functioning, or could this be hypo functioning? So for the hyper secretion side, we always want to check prolactin and IGF-1. To Paul's question about symptoms, Cushing's, we don't want to test for that for everybody because we're going to get false positives, but we would want to test for that if we thought of it, like if someone had obesity and the moon facies, buffalo hump, high blood pressure, diabetes, et cetera. And you said that other symptoms we might see. We don't call it buffalo hump anymore. We call it dorsal cervical fat pads. See, I paid attention to you, Paul. Thank you, Marie. See, Paul, this is it. And I did not know that, so we learned on air. And also, oh, by the way, and also moon face. It's used less and less, and it's round red, cushioned face or round red face. Okay. And then we... No, TikTok is using moon face, but yeah. TikTok. for for hyposecreting we want to make sure that we check tsh but also free t4 and we don't want to order the reflex test because the the tsh may be normal but the free we're looking for low free t4 um and then you said we want to make sure there's no adrenal insufficiency so you would check acth and cortisol in the morning in the morning they are borderline then we need stimulation test. And then the IGF-1 that we use for hypersecretion, it's usually an indicator, again, with a lot of possible pitfalls that could be low on women on estrogen and all that to give us an indication of gross hormone deficiency also. But this is not the first hormone we think about for low. We care more. And then, of course, testosterone in men with an LH and FSH. And for women, if they have normal periods, sometimes I'm not checking because that's the best indicator of normal function, way better than our estrogen or LH and FSH. My follow-up question is back to the Cushing's. What are we testing for there? Because you told us if we're thinking adrenal insufficiency, we test the ACTH and cortisol in the morning. What are we doing? Are we doing a suppression test? to test for Cushing's? So that's a very good question because we are talking about pituitary adenomas. For Cushing's disease, the overnight suppression test or the overnight X suppression test is not the best one because you can have normal values. That's the perfect test for an adrenal adenoma that hypersecretes cortisol. For ACTH dependent, I usually do either a urine and if the patient has, because you want the free cortisol. So that's important. Either urinary free cortisol, which is a 24-hour test, and you can imagine the patients love it, but gives us an idea of how much of the free, and the normals are from older times and the assays are changing, but it's a good screening test. Not perfect, but good. And what I have done over the years, And if the lab has good saliva cortisol kids, it's probably the best test if we look at both sensitivity and specificity. But it has to be an accredited lab. And we tell the patients, do it before you go to bed, with the exception, of course, of doctors and everybody that works in healthcare and it's on call, that we don't really have night-day distinction. So otherwise, that's probably the best test for screening. Meaning the saliva test, cortisol should be low at night. It's usually higher in the morning. And if it's really high at night, then that's suspicious for Cushing's? Yes. That's high sensitivity and high specificity. Now, again, it can be a little bit high in patients with depression. It can be a little bit high. So the VA studies show that if you are older and have diabetes and hypertension, probably your body is a little bit more stressed. But the diurnal variation, so if you look at Cushing's in general, how it starts, First, you lose with any type of tumor. First, you lose the diurnal variation. Then you lose the suppression capability. And that's why we use overnight DEX and other suppression. And then you have so much cortisol around that you spill in the urine. The problem with the overnight DEX is for women, if the women are on estrogen, it's not good because the cortisol will look falsely high because of the CBG. You need a DEX level with most of the labs don't check. And also you need perfect instructions and also the lab to be open because the patient has to take the DEX exactly at 11 because that's how we have the cutoffs. And then go to the lab before 9 a.m. And sometimes they go at 9 or 5 and they can have the test and so on. So it's very strict to be sure that you have enough sensitivity. I'm going to send people to Mobine if they need a 24-hour urine-free cortisol. Or you have them fly to us. Yes. The important thing here is to have an endocrinologist to blame is really... Yeah. So if you read the guidelines, I know it was very self-serving, but we said, and that's one of the reasons, and this was an international guidelines, and in other countries, it's much easier than in U.S. We said that ideally, at least once, the patients should see an endocrinologist. Yeah. Now, in the U.S., it's not feasible. So that's why I'm trying to increase awareness that some of this initial workup, even if they see us, if they wait six months or nine months to see us, they can think, first of all, the labs, they have to have it. And also somebody has to explain to them that this is not cancer. This could grow, but less than 10 percent. You can get pregnant with this. You just we need to do visual fields and make sure that we check all this. But also, it's a rare chance that if this is acromegaly or Cushing's, and sometimes even with prolactinoma, you might need surgery. So it's from nothing. We don't do anything. We do an MRI in three years versus, hey, you will need to see a neurosurgeon, and that neurosurgeon needs to do brain surgery, which is very stressful for patients. And of course, they go on CHGPT and Google, and they find out that this could be brain tumor, which pituitary is not brain tumor. it's neuroendocrine tissue, but in general. So that's why I think not just the workup, but the education is as important as the workup to be done before they see an endocrinologist. I think for the first case here, I think we should move on to the next part. Maria, so our patient undergoes the hormonal workup, and this shows a normal IGF-1 level of 100 nanograms from a liter. She has a normal prolactin at 5 nanograms from a liter. We do a repeat MRI of the brain in two years, and this demonstrates that the lesion is stable. She has a stable pituitary microadenoma at five millimeters. So all seemingly very reassuring. At this point, what do we do with this patient in terms of repeat imaging or repeat hormonal evaluation, or where do we go from here after we've done this initial workup? I think that's a way more complicated question than the first one. So we know exactly what to do at the beginning. but then for follow-up we have recommended and I do this in my clinic very individualized follow-up so for imaging we can extend so this would have been a patient that probably I would have extended even two three years we said two to three years but it wasn't close to the optic asthma everything was normal and then what we could not decide in between us because again we're in different countries, different access to imaging, different thresholds for how much risk you want to take because some tumors can actually grow. The idea is that in some patients, we can probably stop it. Now, we don't know exactly which are the patients that we can stop it. So what I do, I do another one in five years. And then if it's really stable and all the hormones, again, are normal I tell the patients that I don recommend further imaging unless something is changing Either symptoms now the symptoms as you said this patient came with headaches to begin with So it going to be an enlarging gadenoma can also give you more headaches So in general, for patients with headaches, I send them to neurology or treatment if they already have seen the primary care and they are on regular treatment for migraine, for example, just in case because we need to have some markers, especially if it's a woman that wants to get pregnant soon. because then for any, if the normal pito-heter, it's enlarging with 30%. So if you have a small pito-heter adenoma that's not close to the optic as, can become close to the optic as. So this would be the time that I would do even visual fields just to have something as a marker. So I use headache for that. But in general, if it's an older patient with poor prognosis because they had the MRI done for cancer, for example, And you see this is stable. I'm not going to do repeat imaging because this is not going to change what we're doing. For the patients in between, and I'm not going to define middle age for you because I do not want to do that. These are the patients that's the hardest because we know, as I showed you, over 65, they can grow more. So I would still do one in five years and maybe another one in five, but we don't know yet. So invite me back in a few years and hopefully we'll get more data. on the side of your day job. It also gives you a chance to try out new practice settings, travel to new destinations, all while doing what you love. So if this isn't a sales pitch, why does it sound an awful lot like we're selling locums? Well, here's the catch. LocumStory.com is literally just a free, unbiased resource dedicated to educating physicians about locums. That's it. 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So, for example, I do a visual field this year and I do the MRI next year and I do the labs the other year just to have something in between to make sure we have a red, if we have a red flag, we can. But for microdenomas, usually no. We do one more time and then we can stop it. For microdenoma, it's different. but what i wanted to point out because this patient had a normal prolactin but i think what's important and this is what paul was asking what do you do next next time the prolactin could be a little bit high but that doesn't mean it's coming from the denoma the differential diagnosis as you all know for hyperprolactinemia is huge and the medications any antidepressant can increase the prolactin up to 60 that's the level that you see with a microdenoma that's secreting prolactin And antidepressants are used in a large proportion of population. A lot of the supplements that the patients are taking can increase prolactin. So this is a real problem. So I usually tell patients to stop all the supplements, including biotin, but also all the other supplements. I can stop the antidepressants, of course. But if it's a big change, then even oral estrogen can increase prolactin. So a patient that wasn't on birth control before and suddenly it's on oral birth control can have a high prolactin. So you should think through, and sometimes I have to think, is this now a prolactinoma? And they change or it's related to medication. So this is a real conundrum. But for that, you will send it to an endocrinologist. Yeah, that's what I'm phoning you. Oh, that's your one sealed. You have my email now, so you can definitely do it. Okay. Paul, let's go to the second case here. Sure. Yeah, I'm going to take this one because I'm just excited to say the name. So, Maria, we're going to be talking about Mr. Adam Noma, 10 out of 10 name. Also a good one. This is a 27-year-old gentleman with a past medical history of presumed sinus headaches who presents after a fall to the ER after a bike accident. During his trauma workup, the patient undergoes a CT scan to the head, and this incidentally demonstrates a 2.6 by 2.5 by 2.2 centimeter cellar mass. For work of this mass, the patient undergoes an MRI to further classify this lesion, which confirms the mass is extending into the right cavernous sinus. On exam, his vital signs are normal, his blood pressure is 119 over 75, heart rate 75, respiratory rate, let's call it 12, and he's afebrile. His visual examination is grossly intact. To our exam, maybe a medical student walks by with a Snellen card, but we're not doing really super-duper in-depth testing at this point in time. So this case different in a couple of ways, but probably most noteworthy, in fact, based on the size of lesion that we found. So how does your approach differ for this patient compared to our first patient who had a relatively small finding found incidentally? So I think that's a case that's actually even more frequent, and we had several similar cases just this week. with the population getting older, and now everybody getting an imaging after every fall and more sports, and also patients have headaches during knee surgery, for example, and they have imaging because of hemorrhage. And the proportion of patients that are found with larger adenoma, it's increasing significantly, and it's probably also more awareness. So this would be a patient that I would get the surgeon involved much, much faster, even if the prolactin would be high, which will make it a prolactinoma. And that depends how high it could be because everything that's for a tumor so large, if it's less than 200, that doesn't mean that the tumor is secreting prolactin. It could be more like a stock effect. And what we call a stock effect is the prolactin depends on dopamine. That's why the antidepressants are messing up the prolactin. So the dopamine cannot come to the pituitary from the hypothalamus because if the stock is this normally and the tumor is pushing it like this, it cannot come down. So because of that, the prolactin could be elevated in almost every large tumor. If patient will have vision changes, which sometimes is described, and if we don't do a full formal evaluation, as you said, It's just the student asking the patient now it's seeing, and I'm not saying anything bad about students, but they are also in a rush like all of us. I will also order a visual field, and sometimes we're asking them to have it in the hospital if the patient is in ER, just because it can change what we do. Rapid enlargement could mean that when the patient fell, it's actually pituitary hemorrhage. So we need to make sure this is not apoplexy. And CT is very helpful for that, sometimes even more than the MRI. I think we didn't cover in the first case, and I think for a smaller lesion, I think it's important for everybody. Because I've seen patients with brain MRI, which was done by the primary care for a different reason, and immediately order a pituitary MRI without sending the patient to us, which it's not. It's correct. That's what it says in most of the guidelines. But the idea is that if I see very well on an MRI of the brain, and I know this is a microadenoma, sometimes I don't do a more dedicated one and I do the dedicated one next time when it's due. So I'm just saving the patient an MRI. So we put in the guideline some criteria, which is hard to look through for every case. And we don't have definite strict, like you have to do it or you don't have to do it, a dedicated one. most of the patients will need it, but not everybody. So I think from your audience point of view, if you are thinking of sending the patient to an endocrinologist, especially an endocrinologist in a pituitary center, that it's reading their own MRI and working with a surgeon, sometimes send it with a brain MRI and all the labs, because that might save an MRI to the patient. And then of course we need a dedicated one next time. So definitely when we do the repeat one. This patient, the CT is helpful, especially this could be a craniofaryngoma. This could be where you see calcification on the CT. The MRI is helpful. If it's no vision changes, usually the patients get discharged from the hospital. We check all the labs. I'm expecting in a patient like this significant pituitary dysfunction. So definitely the hormones here are always important, but the other one I'm checking to make sure the patient doesn't have it. In a patient like this, I will do it to see what they have. So the chance of having central hypogonadism, it's almost 100%. The chance of gross hormone deficiency, which wouldn't treat, but we know it is, it's again, very high. Then would be the thyroid. And then the last one for larger tumors, the last one would be adrenal insufficiency. Now, this is very, very important to check all hormones at once, because then if one of them, it's abnormal. And everybody knows not to start thyroid before starting steroids, but also they change the values. So all these hormones will interact in between them. And if you start treatment for one, yes, you can put a patient in adrenal crisis if you start thyroid. But even if you start testosterone replacement before actually replacing the steroids or the thyroid, the values can change. So it's important to have all of them at once when it's possible. And I told you I'm a vampire, so I tell patients that's what you have to do. All of them will be more vials, but we'll get enough information for you. And then get a surgeon involved. If it's a macro prolactinoma, and for something like this, I need a, and I tell patients, I want them to see the surgeon anyway. Because if it's a larger tumor, it's a risk of CSF leak, even if it's a prolactinoma. But otherwise, they will need surgery. If it would be, you gave me 2.2 centimeter. If it's 1.5, it's still macrodynamic, but then it's becoming, it's going to be a little bit supra-cellar, but then depends on the patient age. That depends. And we put, and we had neurosurgeons also in the guidelines discussing all this because that would be very interesting to just hear the differences between countries, but also patient preference. So in the U.S., a lot of patients prefer to have surgery, not to have serial follow-up. In the U.K., they are following sometimes patients, even in their registry, which we had none. When the tumor was actually touching the optic asm, they wouldn't get surgery, and the patients decided to observe, even with the risk of vision loss. So they were able to calculate, I had zero patients like this. As you can imagine, we offer surgery to everybody that can lose vision. So, they are different perspectives, but we got the data that even with minimal growth, these patients can have vision loss. Now, do we know if they will lose more hormones with growth? That's not clear. And also, if you have a smaller tumor, let's say 1.5, if they lose more with growing, more hormones with growing tumors, they're going to lose with surgery also. So, that's not an indication per se. What I tell the patients when I repeat the hormones, if they decide if it's a smaller one, this one most likely will need to go to surgery unless the patient has contraindications. But I look at the age of the patient. If the patient doesn't have vision loss and doesn't want surgery and have a lot of complication and the patient is 85, for example, the chances of growing the need in surgery, it's still there. And we had patients having surgery at 90. But the chance of growing, it's 10%, maybe 20. But also the risk of having a stroke during surgery, you know more because you do all the perioperative workup. It's actually probably higher. Can I ask a very practical question about the visual field testing? I apologize for this being so basic. But, you know, I made the joke about the medical student with the Snellen card. They may also be the only ones who remember how to do visual fields by confrontation, too. So when you're talking visual field testing for someone who has this finding, are we talking like referral to ophthalmology? How good does the testing have to be, I guess, is the question that I'm asking. That's very good. And I do it in clinic and I still tell the patient that if I find it, then it's a big problem. So confrontation is and we do it for students, residents and fellows to show because it's cool. And I take the red pen and show them how to do it. But you need a formal one. Of course, for a very large tumor that's pushing the optic asm significantly, the bitemporal hemianopsia is so bad that you are able to actually find it on confrontation. And it's amazing how these patients are able to drive. So they move their neck and still can see. Almost every patient that I found on confrontation, forget about the formal one. I use neuro-ophthalmology, not even local visual fields, just because then we want to look at the optic nerves. And there are countries where they do automatically for these patients, CTs and looking specifically at the optic nerve and all that. But at least formal visual field, we recommend it for everybody, even for micro-adenomas, because if it's close to the optic chasm, you need a baseline. And you need to know where you are and when you need to intervene. So it sounds like it's a pretty individualized decision whether or not someone's going to get surgery. And there's a lot of factors because you said that whether if the hormones are, they have hormone loss because of the size where it's kind of compressing the tissues. And so they're hyposecreting certain hormones. but if you take the whole pituitary out and the mass out, you're probably going to lose all the hormones there too. So either way, so that's not the only reason to do surgery. How do you make the decision? Yeah. So I don't make the decision by myself. We are in a pituitary center of excellence. So we are working and once the patients are coming and I review all the referrals. So when I see the referral, of course, from ER, it's easy to the call that, yeah, we need to see both of us, we make the appointments that they are seeing in the same time, both me and the neurosurgeon. So then the patient, and that's why it's helpful if we already have some lab results. Yes, I will do in a case like this with a 2.2 centimeter tumor, we need a prolactin with dilution. So I think that's very important. Oh, look who's there. Now my dog would be jealous us that he wasn't invited. So it would be very important to mention to the audience that if it's a larger tumor, the one you described now, we need a prolactin with dilution. Just the regular prolactin could be significantly misleading because it could look, we've seen, for example, for giant tumors, the prolactin is 14,000 and looks like it's 300 if it's not done with dilution. If it's smaller tumors, it's less important, though we recommend dilution in every larger tumor. But for giant tumor, this is important. And it's important for the patients to know what type of tumor they have. So if it's a prolactinoma, it's medical therapy with some risks and the patients can have CSF leak and other problems, but still main one is medical treatment. And sometimes, and I love it, the tumor can disappear and they don't need surgery versus if it's prolactin is 300 and it's real 300 or 200, that means they will need surgery sooner than later because maybe their vision will improve. Now, the cavernous sinus, it's a little bit different than the problem. The patients get really worried because they read cavernous sinus and then it's where carotids are and all that. But it's not proven. Of course, they can go now with the endoscope, even the surgeons and clean that area, which is very cool for us, but still tricky to do unless you're an expert. But it's not as severe as it sounds. The tumor can expand. And we, of course, for that one, we have a score. It's called CNOSP from zero to four, how advanced is in the cavernous sinus, but that's not so much of a major issue that you would think that it is in compression. So we see this all the time. We're more worried about the vision. Yeah. Paul, are we ready to put this case to rest and say, this person needs to see a surgeon and an endocrinologist and get formal visual field testing? No, that's not the right order. The other order first. Endocrinologist, visual field testing, and then probably surgery. Because most of the surgeons will not even see the face, no, unless they have all the data. But neuroendocrinology is visual field in the same time. All the labs, including prolactin dilution. If somebody sees this patient in ER and they should get a cortisol and then start steroids, don't wait for all the results if the patient has any symptoms because the likelihood of adrenal insufficiency is pretty high. But if the patient presents with acute presentation that you don't know if this was hemorrhage or not, and they have any symptoms, the likelihood of adrenal insufficiency is very high because that means all of them are destroyed. So you check a cortisol, you can treat and then find out if they need it after that. So just in this particular case. Otherwise, if somebody shows up to my clinic and they don't look like they lost 50 pounds and they have dizziness and nausea, which I have seen several patients with this presentation, because remember when you are penhypopid you can walk with a cortisol of two It amazing because the metabolism is so low because they don have any thyroid I had many patients and I not going to give you more details but the cortisol was one or two, the free T4 was barely detectable, the gross hormone was undetectable, and the testosterone was very, very low. So especially in men, because women find out easier because periods and all that. but they can walk to clinic. They cannot see very well because they have a large tumor, but they drove there because you can move your neck and the bitemporal hemianopsia, you adapt for it. And then when we see those labs, usually by symptoms and by now, I give them a prescription when they leave and I say, I want you to have it because I don't want to send the prescription Friday. So I want you to have it and I want to tell you to take it. And sometimes I give some steroids in cleaning after I draw the labs because I know what's going to happen. But it's amazing the difference between when you have primary and just one hormone. The patient will have symptoms of a cortisol already at six or seven, morning cortisol. But for pan-hypopiate, it's amazing how the body is adapted to even much lower values. and it's much slower, not with hemorrhage, but in general, it's slower, slower, slower, and it's different functioning. So these are the patients that you want to think about this efficiency. Very important because with all the new cancer therapy that now they're approved for more than 50 cancers and are seen in primary care, the difference is that there, the first hormone that goes down, it's actually the cortisol, the ACTH and then the cortisol. So that's completely different. These are with the checkpoint inhibitors? With all the immunotherapies, yes. Yeah, okay. All right, Maria, we're going to move on to our next case. So another A-plus name. So great work, Mobin. This is Ms. Mary Todd Seller. And the reason this is especially special is that her friends call her MT. So this is MT Seller. She is a 35-year-old female with a past medical history of obesity and idiopathic intracranial hypertension. She's presenting to our office for evaluation of a pituitary lesion noted on an MRI of her brain that was done for workup of headaches. On reviewing the MRI, the imaging shows CSF protrusion into the cella consistent with about 60% of the cella being replaced, which sounds alarming on its face, but we'll talk more about that. The patient's only complaints are irregular menstrual cycles, which have developed over the past year. Physical examination is noteworthy for a blood pressure of 140 over 95, a BMI of 35, a heart rate of 98, and she is afebrile. So we are now in, I guess, potentially empty cella territory, though it's just even the wording itself. I find kind of nerve-wracking and alarming. So I guess for this case, I'd love to hear your initial approach and how we should think about it as we kind of move forward in her workup. So the empty cell, by definition, it's not actually empty. That's another misnomer that we're using in medicine because it's replacing, instead of having pitochary tissue, it's replaced with CSF fluid. So it's not really empty. It's fluid. And that's why in T2, it looks different. So we know it's fluid. It's hard to differentiate between this and an arachnoid cyst, but let's say for the purpose of this talk, most likely it's M.T. cella. What I want you to point, or at least 60% is partial M.T. cella. What I want you to point out, though, that in a patient, we see this very frequently, and I'm not sure this is an incidentaloma per se, but we see it as incidentalomas, because this was a patient that was obese, had hypertension, with intracranial hypertension. And so we see more cases of empty cellar in this particular type of patients. What I want to make sure in these patients is that they did not have cushings. So these would be a patient that with everything you told me, even with partial empty cellar, that I will check and make sure that the patient doesn't have cushings. The other hormones that we need to check, it's exactly what we do for any type of between the lesion, incidentaloma or not incidentaloma. We take prolactin and IGF-1. I've seen a few cases with acromegaly. Prolactin would be high in many patients because the same thing as for large tumors, larger than a mother that I described earlier, it's the stock effect. So the dopamine cannot come to tell the prolactin to be lower. Remember that for the purpose of your audience, all the pituitary hormones are under stimulation from the hypothalamus with exception of the prolactin, which is under the tonic inhibition of the dopamine. So prolactin is special in our hearts in general, but it seems like it has way more effects now than we even know. and it's not good even to have low prolactin. So that's the topic of another podcast, which is super cool now what we found about prolactin in general. But for this purpose, high prolactin doesn't mean is, of course, if it's 2000, then we have to look for a prolactinoma somewhere and it wasn't described. But if it's up to 100, I would consider stock effect. Now, it doesn't mean that I'm not going to treat with dopamine agonist because this patient had irregular period. So I might treat, but it doesn't mean I would treat the value of proractin and not for a tumor adenoma purpose. Now, the pituitary deficiencies are very hard. And if you're asking me what's the rate of insufficiency, it's very hard to say because a lot of these patients have been found after they had traumatic brain injury and then they have imaging. So you don't know which one gave insufficiency, the brain injury or the empty cell on itself. Some patients are actually even born with partial empty cell. So how do you know that the pituitary is not smaller to begin with? So I give the patients, based on my experience, about the 10% chance, but I do a full evaluation once in everybody. Now for empty cell, especially if I think they had it for a long time, if they have no symptoms, this patient has irregular periods, type prolactin and so on, it's different. But if they have no symptoms and the first, besides headache, and the first evaluation is normal, I do it one more time. And sometimes I don't even see them back. I tell them that they should see their internist, primary care, have another check. And then if it's normal, the repeat imaging, it's not clearly recommended because you don't know if it's going to progress or not. And also what we don't know, it's even if it's progressing and you read the report at 60 percent, Somebody can read the 65. That's a variation. But if it's 70 next time in two years, what does it mean? We don't know. So that's why sometimes for partial empty cell, I don't do repeat imaging per se. But it would make sense to repeat the labs because that's what you really care about is are they going to become hyposecretors, if that's a word that I just made up maybe. Yeah, you made it up. It's hypopituitarism. But hyposecretors, I guess, undersecretors. So Wordy has three names for this. Why not the first one? So good job, Matt. So the hormones that were, in this case, you said you would check for Cushing's in someone with empty cella. Did I hear you right there? Yeah. So not in everybody, but these patients. So I would check the same thing as we said before for prolactin and IGF-1 for hyposecretion in case they have a tumor, which most of the empty, not most, but many of the empty cell are had, and they hemorrhage, and that's why they have empty cell. So you have to check that. And then you have to check for insufficiency. Exactly. ACTH, cortisol, thyroid, 3D4, TSH, gonadotrophs in men or women. This patient has irregular periods. So definitely we have to check estrogen and LHFSH and IGF-1. Gross hormone deficiency, it's about 10%. So that's the highest that it is in this and irregular periods. For Cushing's, it's just in this particular patient. Because if you have partial empty cellar with obesity, with intracranial hypertension, with hypertension, if the patient has any other features, but you already have three, I would check to make sure that the patient doesn't have Cushing's. Okay. Let's give you some more information about this patient then. Paul, do you want to? Sure. So we do some hormonal testing, as is our want now, because we feel so much expertise. And this patient has a morning cortisol of 19 micrograms per deciliter, normal free T4 level of 1.2 nanograms per deciliter, a normal TSH of 2.3 international units per milliliter, low estradiol of 25 picograms per deciliter. I just love all these different units. I'm feeling good. And a normal FSH. Let's just say normal. And a prolactin that is 150 nanograms per milliliter, which is actually elevated. So does this change anything else that you would do, or does this change your approach in terms of management or further evaluation? I would probably, if the patient has irregular period with a cortisol of 19, I would do the testing for Cushing's, as I said earlier, just to make sure, assuming she's not on estrogen, and clearly she's not because the estrogen was low when you checked it. And then if the patient doesn't have Cushing's, I will treat the hyperprolactinemia with dopamine agonist, assuming you didn't tell me that the patient, if the patient has a history of depression or not. With intracranial hypertension, with a lot of symptoms long-term, the risk of depression is sometimes higher. And we know now that the dopamine agonists are actually increasing the risk of depression. And also the impulse control disorder is something that we didn't think too much about it. But now there are more and more reports. So I always ask patients about gambling And I asked about depression and we did in our patient surveys when we had time in COVID. And the risk of depression was higher after they started in patients, which I knew for a long time. So it's different when you give them the survey versus just asking, hey, this is the only medication I can give you. Is it true that you're doing great? So then the answer is yes. Versus and, you know, how you put a question, it's changing. You're not sad, are you? Like the best way to scream for depression. That's exactly, yeah. I should do that next time, yeah. We're going to give, so we're going to either send a 24-hour urine cortisol or a saliva test for this person to see if, which has good sensitivity and specificity. You said the saliva test to see if they have Cushing's. And we think the prolactin is high because of the stalk effect where the connection between the dopamine suppressing prolactin is kind of cut off by the, I guess, there's pressure on the stalk, right? And that's so the dopamine can't get down. It almost cut off, cannot come in properly. Right. And then, of course, if sometimes, but this was partial empty cell, I enlarge empty cell, you can also think that this was a hemorrhage. So then you don't have enough vasculature for the dopamine to calm down. So then this would be more of a permanent hyperplatinemia versus the stock effect, which sometimes it's changing. And then I'm a little confused or I just don't remember. How might oral contraceptive pills be beneficial here? I know there's cabergoline is one of the ones, bromocryptine are some of the medications you might use for prolactin. But what about these oral contraceptive pills? How do those work? And the connection between estrogen, you mentioned it a couple of times. I just don't remember. So if you want, and that's a very good one, and we're hoping that there will be some essays that this is not going to be an issue, but it's not coming closer. So in a patient like this, the problem is not the high prolactin. The problem is your regular periods. Because if you have high prolactin, the high prolactin, it's inhibiting the LH and FSH. And then you have low estrogen. So then you can treat with two things. For tumors, no, you have to get rid of the tumor. But if you don't have a tumor, and especially if you don't have, and I didn't hear from this patient that had galactoria. Sometimes you can have even with antipsychotics that the woman have milk coming out without being pregnant. And so that's something that you have to fix with dopamine agonist. Then the main issue with hyprolactin in women is not having periods. And of course, because they don't have periods, also low bone density and osteoporosis and other issues longer term. But short term is they have irregular periods. And some of them, especially initially, they could have galacturia. Now, if they don't have galactoria, the options are oral contraceptive. They have their periods back and then prolactin stays there, but it's not doing anything. Now, we know that actually might have some metabolic effects, but that's different. Or you decrease the prolactin with dopamine agonist. And then if you decrease the prolactin, that prolactin will stop having so much inhibitory effects on an agent FSA general return periods. I had patients having periods within a month with dopamine agonist. So you can do either way. So that's why the discussion is here for this, because you don't have a tumor. If you have a tumor that's larger, then you have to shrink the tumor. So of course, then you use dopamine agonist. What you heard me earlier, especially in this patient with a cortisol of 19 is that if you are already on oral estrogen, the cortisol that we measure in most of our labs is total cortisol. So that cortisol is a cortisol bound. So it's the cortisol binding protein that's increased by the oral estrogen. And we don't know how much it is. So this is the major issue, not so much for adrenal insufficiency because then you have symptoms, But when you test for Cushing's, because the cutoffs are so strict for the overnight DEX, the cutoff is 1.8. So if you have a patient on oral estrogen, then almost everybody is going to be higher than that because you measure the cortisol binding globulin. So that's where it's essential. Otherwise, yes, it's potentially increasing. And the free cortisol assays we have are expensive and are not good and takes a week to come back. So it's not feasible. Sometimes we use it in the unit, but we're not there yet. So that's why I wanted to raise awareness about the oral estrogen. But that's where we have to think. Because I have seen patients that they have overnight X, which is the best test, for example, for adrenal adenomas, to rule out Cushing's. because I want your audience to know that when I said the overnight X is not great, it's because for Cushing's disease, we have other tests. But for adrenal, this is it. And if the patient is on oral estrogen, the patient will have an adrenal adenoma, and then they will think they have Cushing's, and it takes six months until they see us. And then we tell them that they don't have Cushing's because that actually was 2.4 because they were on oral estrogen. So this is a relatively big deal. I have like three full pages of notes, which only I can read. But yeah, but if you find a Cushing's case with saliva cortisol, email me, please. Yeah, I will. And the audience that goes for the audience, too. You know, you know, where we where where's the audience hanging out? Paul, blue sky, I guess. Or, you know, message us on one of the social media. I am on the sky. Yeah, I am on the sky. OK, I think, Paul, are we ready for take home points? you think? This has been great, but I think we have to... I think so. I'm not sure my brain can hold me more. So yeah, now's the time. Maria, thank you so much. Really, this has been fantastic. I told you I have so many pages of notes here. I learned so much. What do you want the audience to remember? Just maybe two or three favorite take-home points for them. I would like the audience to first think about the pituitary as a conductor of all the hormones, or not all, all, but many, many glands. And also that for a patient with bituidary disorders, they should think a little bit differently because some of the labs that we're used to are not the same. And we need, as I gave the example with a thyroid, so I think that would be very important. That's one. Two, that most of the time the patients need to be listened to. We need to hear all their symptoms and then check the biochemical workup both for high and for low if the patient has a pituitary adenoma, that we need to do significant better work in explaining to the patient what we're looking for and also what's the prognosis. To tell the patients that the rates of increasing in size, it's low, but not non-existent, then we have to do serial imaging that we have extended the interval, but we still don't know when to stop for most of the patients. But sometimes we know and we offer the patients to stop that this is a month for larger adenomas. This is a multidisciplinary process that they need to see the neuro ophthalmology. They need to see the neurosurgeon. They need to have surgery sometimes, and then they have to come back to us and check all their hormones. And also that it's largely benign, and it's very, very common. I start with telling the patients that if we look on imaging, one in 10 patients can have it, and then suddenly some of them relax. And then I tell them in the next sentence, but you might be that one that needs to have surgery, but let's see where we are with that. Fantastic. Anything that you would like to plug, any websites, organizations, et cetera, that you want the audience to check out? Of course, I'm biased because I'm part of several great organizations. For pituitary in particular, because we discussed about the consensus guidelines from the Pituitary Society. Pituitary Society is an organization of all the pituitary specialists around the world. It's truly international. And then for endocrinology in general, the Endocrine Society is the umbrella organization, also a very large international organization that I'm part of it. All right. Well, check those out and we will head into our outro. Thank you. Thank you. It was a pleasure. This has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole. Yummy. That was upsetting. I loved it. Still hungry for more? Join our Patreon and get all of our episodes ad-free, plus twice monthly bonus episodes at patreon.com slash curbsiders. You can find our show notes at thecurbsiders.com and sign up for our mailing list to get our weekly show notes in your inbox. This includes our Curbsiders Digest, which recaps the latest practice changing articles, guidelines, and news in interval medicine. And we're committed to high-value practice changing knowledge. And to do that, we want your feedback, so please email us at askcurbsiders at gmail.com. A reminder that this and most episodes are available for CME credit for all health professionals through vcuhealth at curbsiders.vcuhealth.org. A special thanks to our writer and producer for this episode, Dr. Mobin Ahmad. And to our whole Curbsiders team, our technical production is done by Podpaste. Elizabeth Proto does our social media. Jen Waddle runs our Patreon. Krista Chumenchu moderates our Discord. Stuart Brigham composed our theme music. And with all that, until next time, I've been Dr. Matthew Frank Waddle. Dr. Mobin Ahmad. And as always, I mean, Dr. Paul Nelson-Williams. Thank you and goodbye.