← The Curbsiders Internal Medicine Podcast
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A
Hey, before we get to the show, I wanted to remind you to check out our patreon@patreon.com 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@patreon.com curbsiders.
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B
Hey, Paul.
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A friend of mine tried to annoy.
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B
Me with some bird puns.
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C
I feel like I'm not gonna get this one. All right, lay it on me.
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B
But I soon realized that toucan play.
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C
At that game, I would never have gotten there. All right, it's not bad. I don't mind it.
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B
I liked it. Yeah, you know, obviously I was thinking of cereal when I said that one.
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D
The Curbsiders podcast is for entertainment, education and information purposes only and the topics discussed should not be used solely diagnosed, treat, cure or prevent any disease conditions. Furthermore, the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity aside from possibly cash. Like more 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 wrong.
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B
Welcome back to the curbsiders.
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A
I'm Dr. Matthew Frank Watto, here with my great friend and America's primary care physician, Dr. Paul Nelson Williams.
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B
Hi, Paul.
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C
Hey, Matt. How are you, Paul?
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B
I'm doing well. We had a fantastic conversation.
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A
Brain holes are gonna be filled everywhere after this episode.
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C
Paul. I hate that.
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A
We talked about pituitary.
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B
Incidentalomas with a fantastic guest, Dr. Maria Flecheriu. And Paul, I'm really excited for people to hear this.
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A
But before they hear this and before.
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B
You tell them about our wonderful co host and producer for this episode, Paul, what is it that we do on Curbsiders?
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C
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. Mabeen Ahmad. Dr. Ahmad, how are you?
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E
I'm doing good.
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C
How about you guys?
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B
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 Cashlack. Fantastic, fantastic guy. So thank you for putting this together and a great guest choice as well. Yep.
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E
For sure.
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C
Just take it with modesty. I appreciate it. All right, why don't I tell you about our guests while we're at it. Mobeen, you're doing great. There is no response necessary for that.
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B
Oh, and wait, before you get to the we should thank your CO fellows for helping helping us to write the fantastic names that we use for our cases here. So thanks to the Temple Endocrinology Fellows, you all rule. Thank you.
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F
Yes, yes. I want to shout out Dr. Ashen Fernando, Dr. Richelle Ripa, and Victoria de Milis, all excellent co fellows that helped make these names all right.
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C
So Matt, tonight we had an incredible conversation with our guest, Dr. Maria Flecheirou. As you mentioned, she taught us her approach to the workup management of pituitary incidentalomas and what makes them incidentalomas for you to know. Dr. Foscheriou 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 and Stoneloma Guidelines. She's a role model for endocrinology fellows like the great Dr. Ahmad. And so without further ado, let's get to it.
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B
Reminder that this in most episodes will.
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Be available for CME credit for all.
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B
Health professionals through VCU healtherbsiders.vcuhealth.org Maria, we've been talking for a while. Really excited for the audience to get to know you.
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A
As a way of doing that, how about you tell them a hobby or.
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B
Interest that you have outside of medicine?
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E
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're 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 tracks, but I hope we'll hit many soon.
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B
Is Transylvania a tourist destination?
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A
Would you recommend it? Paul is a bit of a world traveler.
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B
He was just in Europe. Would you recommend Paul travel there?
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E
I 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 us and from Europe and it's going to be overcrowded probably in 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. Otherwise 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.
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B
All right, Paul, I challenge you.
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E
Let's you have my email. So. Yes. Yeah.
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B
Okay. All right. Before we get to the cases, anything else, Paul, you want to ask?
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C
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.
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E
Yeah. So I think 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 mentee. So I think from a clinical perspective, because we are 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, pituitary 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, sustained 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.
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B
It's a very meta moment because you're mentoring tens of thousands of people by giving that advice. So that's great. I want to get to a case because we have a lot to go through. And Mobeen, would you like to read our first case from Cashlak? I believe we have some great names in store for everyone tonight.
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F
So the first case we have Ms. Ella Turcica, a 27 year old.
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E
That's a good one.
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F
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 pressure120 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 the first question that we kind of wanted to ask you, Dr. Flisserio, was what is usually your initial workup hormonally for these microadenomas?
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E
That's a very interesting case, not just an very common. And I think with so much imaging and the MRIs getting better and even the CTs, you are all going to senior practice. More pituitary incidentaloma. I tell our fellows that in autopsy studies, and we mentioned this in the guidelines too, there are autopsy studies that mention that up to 30% had something on the pituitary. Probably that's too much, but 10% for sure, even on imaging. The problem that I see is that a lot of these small lesions are actually not read by the radiologist 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 endocrinologist, the initial hormonal workup might be done by the internal medicine clinic.
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C
Before we get too deep into the hormonal workup. Just for you to know, Maria, I'm the resident dum dum for the group, so I will 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 incidental 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?
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E
That's a very good point. So pituitary 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. And the reason is that sometimes actually the patient has headaches which could be due because they have acromegaly and the growth hormone gives you a headache. But it doesn't matter. They had it for something that who order 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 what 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, neuroendocrinologists or neurosurgeons. So microadenoma, 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 9 millimeter or 11 is a huge difference. And Mobi 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 or 1 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 4 centimeter, it's called giant. Now, again, where the four, just because it's more red, this is the size by definition. Now, with better imaging, actually we see more details in the microadenomas, which even if it's a 6 or 7 millimeter, might be more relevant if it's closer to the optic ASM and the optic ASP means where the optic nerves are crossing. That's very important for vision for women that want to get pregnant. So even a small tiny thing, scratch close 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 growth hormone secreting tumor. Then several years later came at least staining for growth 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, means nothing. It's on staining and transcription factors. And then we go with details, what type of tumor they are. But from clinical perspective, from a clinician point of view, what we need to do, and this is what Mobine was asking for. A patient in front of you with a small lesion, we don't even know if it's a microadenoma. I usually look at the imaging because could be a Rutger's cleft cyst, could be that's 5 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 Rhatke's cleft cyst or a small craniopharyngioma, then we have to check hormones to make sure that this is not a hyper secreting or hyper functioning. I told you, we like multiple names for the same thing. So hyper secreting or hyper functioning, it's the same thing. And that's where the discussion came because every and it's focused in the 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 hyperfunctioning. 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 growth 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, 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 recommended even more than suggested that everybody with a pituitary lesion should have at least a prolactin and IGF1, 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 positives is very high. So of course if you check in everybody, then you'll 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 acth. If they had this tumor for a while, they can have growth hormone deficiency. Much more rare. But it could be. And usually with larger one. Patients also can have thyroid dysfunction even from smaller lesion, again, usually with larger. And what it's 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 that's. We have to put our other head for pituitary.
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B
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.
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E
That's a very good point. And that's a beep 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 free T4 to TSH, not reflex. So definitely this would be important. And this could be a patient, your patient Mobine 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 for, they are checked properly. So that would be very important. But I think for your case for microadenoma, once everybody has to have it because we do not want to miss it.
- [21:03]
A
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- [24:38]
C
Recognizing that we're going to look up the guidelines and order all the correct labs regardless. Still this scenario, I imagine this patient is seen in the primary care office, they get the MRI for headaches. We find this incidental finding and they come back and have this conversation. Are there any particular historical points like what are the really high yield symptomatic questions that you would ask 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?
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E
I think it wouldn't change the testing for prolactin IGF1 or for pituitary dysfunction, for hypopituityism, 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 who 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 growth 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 had severe Cushing's and mild Cushing 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 are 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, you know, 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.
- [28:29]
F
Dr. Pluserio, thank you so much for that explanation. I actually had again a question regarding 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 reference a 6 millimeter 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?
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E
I guess so. That's a very good point. And the reason we don't have in this new consensus guidelines a cutoff 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 2 millimeters, they were a 3. So 6 was something that you would See, we don't really know, especially for microadenomas in men, for example, if they are not completely different than macroadenoma. 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 microaders 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. 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 start 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 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 microadeanomas 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.
- [31:57]
B
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're calling. 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 microadenoma is less than a centimeter, macro is a centimeter or more, and then giant is more than 4 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 hypersecretion side, we always want to check prolactin and IGF1. 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 someone had, 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.
- [33:57]
E
Would say we don't call it buffalo hump anymore. Yeah, we call it dorsal cervical fat pads. See, I paid attention to you, Paul.
- [34:05]
C
Thank you, Mar.
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B
This is.
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A
See, Paul, this is it.
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B
So. And I did not know that. So we learned on air. And we.
- [34:11]
E
And also. Oh, by the way, and also Moonphase, it's used less and less and it's more. It's round red Cushingoid face or round red face.
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B
Okay. And then we though TikTok is using.
- [34:26]
E
Moonphase, but yeah.
- [34:29]
B
For hypo secreting, 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 TSH may be normal, but we're looking for low free T4. And then you said we want to make sure there's no adrenal insufficiency. So you would check ACTH and cortisol in the morning?
- [34:53]
E
In the morning if they are borderline then we did stimulation test and then the IGF one that we use for hyper secretion. And 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 growth 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 NH 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 Ellagn fsh.
- [35:33]
B
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?
- [35:51]
E
So that's a very good question for Cushing because we are talking about pituitary adenomas for Cushing's disease. The overnight suppression test or the overnight dex 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, 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 kits, it's probably the best test. If we look at both sensitivity and specificity. But it has to be an accredited labs 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 so on call that we don't really have night day distinction. So otherwise that's probably the best test for screening.
- [37:13]
B
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.
- [37:22]
E
Yes. And 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 X and other suppression. And then you have so much cortisol around that you spill in the urine. The problem with the overnight DAX 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 done, check. And also you need perfect instructions. And also the lab to be open because the patient has to take the decks exactly at 11 because that's how we have the cutoffs. And then go to the lab before 9:00am and sometimes they go at 9:05 and they can have the test and so on. So it's very strict to be sure that you have enough sensitivity.
- [38:39]
B
I'm going to send people to Mobeen if they need a 24 hour urine.
- [38:42]
E
Free cortisol or you have them fly to us.
- [38:46]
C
The important thing here is to have an endocrinologist to blame is really.
- [38:50]
E
Yeah. So if you read the guidelines, I know it was very self serving but we said, and that's one of the reason, and this was an international guidelines and in other countries it's much easier than in US we said that ideally at least once the patients should see an endocrinologist. Now in US 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% 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 saccharomegaly 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 ChatGPT and Google and they find out that this could be brain tumor, which is 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.
- [40:17]
B
I think for the first case here, I think we should move on to the next part.
- [40:22]
C
Maria. So our patient undergoes the hormonal workup and this shows a normal IGF1 level of 100 nanograms per milliliter. She has a normal prolactin at 5 nanograms per milliliter. 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 5 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?
- [40:51]
E
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 that 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 to 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, 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't 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's going to be an enlarging gaudenoma can also give you more headaches. So in general, for patients with headaches, I send them to a neurology for 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 the normal P2 either it's enlarging with 30%. So if you have a small P2 either adenoma that that's not close to the optic as can become close to the opticas. 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 as the hardest because we know as I showed you over 65 they can grow more but 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 few years and hopefully we'll get more data.
- [43:25]
A
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- [43:39]
B
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A
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- [44:18]
B
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- [44:20]
A
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- [45:54]
B
How about the hormone evaluation? I guess that part of that will depend on if there's symptoms. But let's say if there's no symptoms, do you have to redo the hormones? The evaluation again, for hyper functioning, no.
- [46:08]
E
For hypofunctioning, yes, because you can have subtle changes. And I do it again at least once. And how I do it, especially for lesions that are close to the optica, for example, even imaging, I change them and do so. For example, I do a visual field this year and I do a DMRI 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 microadenomas, usually, no, we do one more time and then we can stop it. For macroadenoma 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 microadenoma 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 an 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 it change or it's related to medication. So this is a real conundrum. But for that you will send it to endocrinologist?
- [48:01]
B
Yeah, that's what I'm phoning.
- [48:05]
E
You have my email now, so you can definitely do it.
- [48:09]
B
Okay, Paul, let's go to the second case here.
- [48:14]
C
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.
- [48:22]
E
10 out of 10 name, also a good one.
- [48:24]
C
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 the 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.
- [49:23]
E
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 large 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 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 they describe, and if we don't do a full formal evaluation, as you said, it's just a 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. Mr. Just because it can change what we do. Rapid enlargement could mean that when the patient fell, it's actually a 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 smaller lesion, I think it's important for everybody because I've seen patients with 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 guidelines, 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 is 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 craniopharyngioma. 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, 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 growth 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 adrenaline 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, yes, you can put a patient in adrenal crisis if you start thyroid. But even if you start testosterone replacement before actually replacement, 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 the surgery. If it's a macroprolactinoma. And for something like this, I need 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 microadenoma. But then it's becoming. It's going to be a little bit supracellar. 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 US a lot of patients prefer to have surgery, not to have serial follow up. In UK they are following sometimes patients even in their registry, which we had none of them, when the tumor was actually touching the opticasm, 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. 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 contraindication. 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 it's do you want 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.
- [56:42]
C
Can I ask a very practical question about the visual field testing? And I apologize for this being so basic, but 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. When you're talking visual field testing for someone who has this finding, are we talking referral to ophthalmology? For how good does the testing have to be? I guess is the question that I'm asking.
- [57:03]
E
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 opticasm 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 microadeanomas, because if it's close to the opticasm, you need a baseline, you need to know where you are and when you need to intervene.
- [58:17]
B
So it sounds like it's a pretty individualized decision whether or not someone's gonna 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, of compressing the tissues and so they're hypo secreting 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?
- [58:49]
E
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 that he wasn't invited. So would be very important to mention to the audience that if it's a larger tumor, latinoma, the one you described, now we need a prolactin with dilution. Just a regular prolactin could be significantly misleading because it could. Look, we seen pituitary, 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, 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, that 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 that'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 of course for that one we have a score, it's called KNOSP from 0 to 4. How advance 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.
- [61:30]
B
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 vision testing?
- [61:40]
E
Not the right order, the other order.
- [61:43]
B
First endocrinologist, visual field testing and then a surgeon.
- [61:47]
E
Because most of the surgeons will not even see the venom unless they have all the data. But neuroendocrinologies, 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, lost 50 pounds. And they have dizziness and nausea, which I have seen several patients with this presentation because remember when you are pan hypopit you can walk with a cortisol of 2. It's amazing because the metabolism is so low because they don't have any thyroid. They have, I had many patients and I'm not going to give you more details but that the cortisol was one or two, the free T4 was barely detectable, the growth hormone was undetectable and the, 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 bi temporal 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. So I want you to have it and I will tell you to take it. And sometimes I give some steroids in cleaning because 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 6 or 7 morning cortisol. But for pan hypopiate it's amazing how the body's 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 insufficiency. Very important because with all the new cancers 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 act agent and the cortisol. So that's completely different.
- [64:41]
B
These are with the checkpoint inhibitors with all the immunotherapies.
- [64:44]
E
Yes. Okay. Yeah.
- [64:47]
C
All right, Maria, we'll move on to our next case. So another A plus name. So great work, Mobeen. 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's 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 Sella consistent with about 60% of the Sella 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, 95, a BMI of 35, a heart rate of 98, and she is afebroil. So we are now in, I guess, potentially empty Sella territory. Though 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.
- [65:49]
E
So the empty Sella, by definition, it's not actually empty. That's another misnomer that we're using in medicine because it's replacing instead of having pituitary tissue 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 empty Sella. What I want you to point, or at least 60% is partial empty sella. 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 patient per se, but we see it as incidentalomas because this was a patient that was obese, had hypertension with intracranial hypertension. So we see more cases of empty Sella 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 Sella, that I will check and make sure that the patient doesn't have cushion shanks, the other hormones that we need to check. It's exactly what we do for any type of pituitary lesion. Incidentaloma or not incidentaloma, we check prolactin and IGF1. I've seen few cases with acromegaly. Prolactin would be high in many patients because the same thing as for large tumors, large adenoma 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 the exception of the prolactin which is under the tonic inhibition of the dopamine. So prolactin is special in our hearts in general but and seems like it has way more effects now that 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 doesn't mean that I'm not going to treat with dopamine agonist because this patient had irregular period. So I might treat but doesn't mean I would treat the value of prolactin and not for a a tumor at the normal 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 that brain injury or the empty cell on itself. Some patients are actually even born with partial empty sella. So how do you know that the pituitary is not 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 Mt Sella, especially if I think they had it for a long time. If they have no symptoms, this patient has irregular periods, hyperlactin and so on, it's different. But if they have no symptoms besides headache and the first evaluation is normal, I do it one more time and sometimes I don't even see them back to I tell them that they should see their internist primary care have another recheck 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% 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 I. Sometimes for partial empty cell, I don't do repeat imaging per se.
- [69:59]
B
But the repeat. It would make sense to repeat the labs because you're really. That's what you really care about is are they. Are they going to become hypo or. Yeah, hypo secretors. If that's a word that I just made up.
- [70:10]
A
Maybe.
- [70:10]
E
Yeah, you made it up. It's hypo pituitary, but hyposecretors, I guess, under secretor. So worthy has three names for this. Why not the fourth one? So good. Good job.
- [70:22]
B
So the hormones that were in this case. You said you would check for Cushing's in someone with empty Sella. Did I hear you right there?
- [70:32]
E
Yeah. So not in everybody but these patients. So I would check the same thing as we said before, for prolactin and IGF1 for hypersecretion in case they have a tumor, which most of the empty cells. Not most, but many of the empty cell I have. And the hemorrhage. And that's why they have empty cells. So you have to check that and then you have to check for insufficiency. Exactly. ACTH, cortisol, thyroid 3, T4TSH, gonadotrophs in men or women. This patient has irregular periods, so definitely we have to check estrogen and agent FSH and INGF1. 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 sella 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.
- [71:31]
B
Okay, let's give you some more information about this patient then. Paul, do you want to?
- [71:37]
C
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, 25 picograms per deciliter. I just love all these different units. I'm feeling good.
- [71:57]
E
Yeah.
- [71:57]
C
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?
- [72:10]
E
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 an 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 of impulse control disorder is something that we didn't think too much about it. But now there are more and more reports. I always ask patients about gambling and I asked about depression, and we did in our patient survey 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.
- [73:29]
C
You're not sad, are you? Like, that's the best way to scream for depression.
- [73:32]
E
That's exactly. Yeah. I should do that next time.
- [73:35]
B
Yeah, we're gonna give. So we're gonna 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. If they have Cushings. 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.
- [74:07]
E
So the dopamine, it almost cut off, cannot come in properly.
- [74:11]
B
Right.
- [74:12]
E
And then of course, if sometimes. But this was partial empty cell in large empty cells. You can also think that this was a hemorrhage. So then you don't have enough vasculature for the dopamine to come down. So then this would be more of a Permanent hem hyperprolactinemia versus the stock effect, which sometimes it's changing and then.
- [74:33]
B
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. Bromocriptine 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 times. I just don't remember.
- [74:59]
E
So the other. So if you want. And that's a very good one. And it's. I. 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 if in a patient like this, the problem is not the high prolactin, the problem is irregular periods because if you have hyperactin, the hyprolactin, it's inhibiting the LH and fsh. And then you have low estrogen, 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 women have milk coming out without being pregnant. So that's something that you have to fix with dopamine agonist. Then the main issue with hyperlactin 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 galacteria. Now if they don't have galactoria, the options are oral contraceptive, they have their periods back, back. And then, you know, prolactin stays there, but it's not doing anything. Now we know that actually might have some metabolic effects, but that's different. And. 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 NHL FSH and will return periods. I had patients having periods within a month with dopamine agonist. So you can do either way if you have a tumor. 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 laboratory 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 adrenaline insufficiency, because then you have symptoms, but when you test for Cushing's because the cutoffs are so strict, for the overnight decks, the cutoff is 1.2. So if you can have, if you have a patient on oral estrogen, then almost everybody's going to be higher than that because you measure the cortisol binding globally. 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 eggs, which is the best test, for example, for adrenal adenomas, to rule out Cushing's. And 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 that was 2.4 because they were on oral estrogen. So this is a relatively big deal.
- [78:50]
B
I have like three full pages of notes which only I can read, but.
- [78:54]
E
Yeah, but if you find a Cushing's case with saliva cortisol, email me, please.
- [78:59]
B
Yeah, I will. And the audience, that goes for the audience too. Where's the audience hanging out? Paul? Blue sky, I guess. Or message us on one of the social media.
- [79:10]
E
I am on blue sky.
- [79:11]
C
Oh, I shut you down.
- [79:13]
E
I am on this guy.
- [79:14]
B
Okay, I think. Paul, are we ready for take home points? You think this has been great, but I think we are.
- [79:19]
C
I'm not sure my brain can hold anymore. So yeah, now's the time.
- [79:23]
B
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.
- [79:30]
A
What do you want the audience to Remember?
- [79:32]
B
Just maybe 2 or 3 favorite take home points for them.
- [79:37]
E
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 pituitary 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 size, it's low but not non existent. Then we have to do serial imaging that we have extended the intervals 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 for larger adenomas, this is a multidisciplinary process that they need to see the neurophthalmology, 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, 1 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.
- [81:35]
B
Fantastic. Anything that you would like to plug, any websites, organizations, et cetera that you want the audience to check out?
- [81:44]
E
Of course I'm biased because I'm part of several great organizations for pituitary in particular, because we discuss 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 institution, international organization that I'm part of it.
- [82:17]
B
All right, well check those out and we will head into our outro. Thank you.
- [82:21]
E
Thank you. It was a pleasure.
- [82:27]
C
This has been another episode of the Curbsiders bringing you a little knowledge food for your brain hole.
- [82:32]
F
Yummy, yummy.
- [82:37]
C
That was authentic. I loved it. Still, still hungry for more. Join our Patreon and get all of our episodes ad free plus twice monthly bonus episodes at patreon.com curbsiders you can find our shownotes thecurbsiders.com and sign up for our email 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 and internal medicine.
- [82:56]
B
And we're committed to high value practice.
- [82:58]
A
Changing knowledge and to do that we want your feedback.
- [83:00]
B
So please email us@askcurbsidersmail.com a reminder that this and most episodes episodes are available for CME credit for all health professionals through VCU healtherbsiders.vcuhealth.org A special thanks to our writer and producer for this episode, Dr. Mobine Ahmad, and to our whole Curbsiders team. Our technical production is done by Pod Paste. Elizabeth Proto does our social media. Jen Watto runs our Patreon, Krista Chumencu moderates our discord. Stuart Brigham composed our theme music and with all that, until next time, I've been Dr. Matthew Frank, Watto.
- [83:33]
C
Ahmed and as always, Irene, Dr. Pell Nelson Williams. Thank you and goodbye.