Pituitary Disorders: Medical & Surgical Management
Neuroendocrinologist, Divya Yogi-Morren, MD, and neurosurgeon, Pablo Recinos, MD detail the diagnostic work-up, medical management and surgical approaches used in pituitary disorders.
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Pituitary Disorders: Medical & Surgical Management
Podcast Transcript
Neuro Pathways Podcast Series
Release Date: August 15, 2024
Expiration Date: August 15, 2025
Estimated Time of Completion: 36 minutes
Pituitary Disorders: Medical & Surgical Management
Divya Yogi-Morren, MD and Pablo Recinos, MD
Description
Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.
Learning Objectives
- Review up to date and clinically pertinent topics related to neurological disease
- Discuss advances in the field of neurological diseases
- Describe options for the treatment and care of various neurological disease
Target Audience
Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.
ACCREDITATION
In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
CREDIT DESIGNATION
- American Medical Association (AMA)
Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.
- American Nurses Credentialing Center (ANCC)
Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.
- Certificate of Participation
A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.
- American Board of Surgery (ABS)
Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.
Credit will be reported within 30 days of claiming credit.
Podcast Series Director
Imad Najm, MD
Epilepsy Center
Additional Planner/Reviewer
Cindy Willis, DNP
Matthew Grabowski, MD
Faculty
Divya Yogi-Morren, MD
Endocrinology
Pablo Recinos, MD
Brain Tumor and Neuro-Oncology Center
Host
Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center
Agenda
Pituitary Disorders: Medical and Surgical Management
Divya Yogi-Morren, MD and Pablo Recinos, MD
Disclosures
In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.
The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:
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Imad Najm, MD |
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Glen Stevens, DO, PhD |
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| Pablo Recinos, MD |
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Divya Yogi-Morren, MD |
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The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP, Matthew Grabowski, MD.
CME Disclaimer
The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.
HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:
Go to: Neuro Pathways Podcast August 15, 2024 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org
Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.
Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research, discoveries, and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.
Glen Stevens, DO, PhD: The pituitary gland's central role in hormone regulation can have a profound effect on multiple body systems, and as such needs multidisciplinary care when it affects neurological and endocrine health, which is estimated at impacting nearly one in a thousand people. In today's episode of Neuro Pathways we'll survey the landscape of pituitary disorders and the diagnostic, medical, radiation and surgical approaches that support them.
I'm your host Glen Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to be joined by Dr. Divya Yogi-Morren and Dr. Pablo Recinos. Dr. Yogi-Morren is an endocrinologist and medical director of Cleveland Clinic's Pituitary Center, and Dr. Recinos is a skull-based neurosurgeon and surgical director of the same center. Divya, Pablo, welcome to Neuro Pathways.
Divya Yogi-Morren, MD: Thank you so much, Glen, for having us.
Glen Stevens, DO, PhD: So, to get started and we'll start with you Divya, why don't you tell us a little bit about yourself, background, how you made your way to the Cleveland Clinic and what you do on a daily basis.
Divya Yogi-Morren, MD: So, I actually grew up in the Caribbean to Indian parents, and I spent a lot of my early life doing missionary work, and we were involved in a lot of service to community in that country. And I happened to be very good at science and math. So when I was in high school, I thought it would be a good idea to choose a profession where I could marry these two things. So that's how it seemed that the combination of service and being good at science and caring and serving people would be a good choice for me. And that's actually how I ended up going towards medicine.
Glen Stevens, DO, PhD: And the Cleveland Clinic. How'd you end up here?
Divya Yogi-Morren, MD: I actually followed my husband to Cleveland Clinic, if I'm being honest. We came to Cleveland Clinic Florida in 2008. I started there as an intern in 2009. So this is actually my 15th year anniversary at Cleveland Clinic this month.
Glen Stevens, DO, PhD: Congratulations.
Pablo Recinos, MD: Happy anniversary.
Glen Stevens, DO, PhD: Happy anniversary. Yeah. And Pablo, your background. See if you can beat that.
Pablo Recinos, MD: I can't beat that.
Glen Stevens, DO, PhD: I know you can't.
Pablo Recinos, MD: So, I'm a neurosurgeon. As a neurosurgeon, we are trained to address issues of the brain, the spinal cord, peripheral nerves. But because of my love of anatomy, my love of exploring these minimally invasive corridors, it made my way to the areas of the base of the skull and pituitary. And so nowadays I spend 95% of my time addressing tumors at the base of the skull and pituitary gland in a number of different ways. I've been at the Cleveland Clinic. I started first as a fellow within an open skull base surgery, and after finishing all of my training, came back to join the faculty to do pituitary and skull base surgery.
Glen Stevens, DO, PhD: Well good. It's great to have you both here. It's really a monumental task going through all of this, but we'll try to go into it. I'm not sure how much we'll get into the weeds, but we'll try.
So to set the stage for the conversation, I'd like you to take us through some of the different pituitary disorders that present to your center. And in full disclosure, we'll start with acromegaly. And I'll just mention that I actually was diagnosed with acromegaly and the endocrinologists are my hero. The endocrinologist actually saved my life and my hero is Dr. Kennedy. And it was really found in workup of an unrelated problem, and it was really his commitment to medicine and really doing a thorough job, which really found the problem. And Divya is actually my pituitary physician that looks after me and Pablo, I let him explore in my brain and do surgery on me. And I'm still here and I'm still doing fine. If there's a problem with the podcast, you can blame Pablo. But it's been several years now and I think the good news is my labs are all perfect and my imaging is perfect, so they won't say it, but I think I'm cured.
But let's start with acromegaly. Tell us why it was a really bad thing to have not get diagnosed.
Divya Yogi-Morren, MD: Yeah, absolutely. So I think we've jumped right into functional or secreting pituitary tumors, of which there are three main ones, and acromegaly is one of them. So acromegaly is a hormonal disorder that occurs when the pituitary gland produces excess amount of growth hormone. And even though it's a benign tumor, like most pituitary tumors are, it causes problems because the excess growth hormone can cause a bunch of problems and symptoms.
So the obvious ones that bring people running into the office is things like they've noticed that their face is different, their forehead is bigger, or there is what we call pragmatism or their chin is jotting out and also increased growth of their hands and feet. And if this occurs before puberty, you can have an increase in height. So you end up with patients that are very tall.
But more important than the physical features that acromegaly causes is the metabolic consequences. So it can lead to things like high blood sugars and high blood pressure, and those things can cause increased cardiovascular risk. And that is one of the main reasons why we want to catch this early and treat it to reduce that cardiovascular morbidity and mortality that is increased in patients with this condition. And also there are also some increased associations with different cancers.
Pablo Recinos, MD: That's a lot to wrap your head around, and when patients hear that, I think they're still processing how does that involve me? My hands are a little bit bigger, but if we think about it, there's actually some famous people who have been known to have acromegaly and patients will die frequently of heart failure, increased strain of the heart over time, and they're also at increased risks for certain cancers. So it is a serious problem even though it's originally from a benign tumor.
Glen Stevens, DO, PhD: So Cushing's.
Divya Yogi-Morren, MD: Yes. So I'll move on then to the other functioning or secreting tumors. So we have Cushing's, which is really when the pituitary gland produces an excess amount of ACTH or adrenal corticotrophic hormone. And this is a hormone that can also lead to metabolic effects such as increased blood pressure and increased blood sugars. But it also causes things such as weight gain, thinning of the skin, stretch marks and deposition of fat in areas that are not usual areas to deposit fat, such as in the supraclavicular area, also in the abdominal area. And we call this a buffalo hump, but it's that fat deposition in the dorsal cervical area that people notice I would come into the office.
And then we have prolactinomas, which is caused by, again, a benign pituitary tumor that secretes high doses of prolactin. And this overproduction of prolactin can lead to symptoms such as reproductive dysfunction, infertility, irregular menstrual cycles in women and erectile dysfunction, and changes in libido in men and milk production or breast discharge in both genders.
So those are the functional tumors or secreting tumors, tumors that are producing hormones. And then these hormones go and affect their change on some other organ.
But the vast majority of pituitary tumors are actually non-functional tumors. Their proliferation of pituitary tissue, that's usually benign. Only 0.2% of these are pituitary cancers. So that's usually not an issue in our practice, although we have come across a few cases. And these tumors, they cause problems based on how large they are and what can happen if they grow. So if they extend superiorly, you can have visual disturbances. The most characteristic of which in our practice with pituitary tumors is bitemporal hemianopsia. If they extend laterally into the cavernous sinuses, you can get cranial nerve involvement. And if they extend inferiorly, this can go into this sphenoid sinus and you can have a CSF leak. And then of course you can compress my favorite gland, the pituitary gland and cause deficiencies of these pituitary hormones, which then we will need to replace.
Glen Stevens, DO, PhD: So I guess that takes us to hypopituitarism. How common is that?
Divya Yogi-Morren, MD: It's very uncommon and it's really characterized by a deficiency of one or more pituitary hormones. And it can be caused by many different things. I, of course, mentioned the pituitary tumors, but autoimmune conditions, trauma, infection, inflammation, bleeds, those things can definitely cause hypopituitarism. And then the clinical features of this varies depending on which hormone is deficient. So if it's ACTH, you can have adrenal insufficiency and present with symptoms such as fatigue, weakness, weight loss, and hypotension. If you have a TSH deficiency, the patients may present with symptoms of hypothyroidism such as fatigue, weight gain, cold intolerance, and dry skin. And if there's a growth hormone deficiency, you can have decreased muscle mass, increased fat mass, reduced energy levels, and in children even short stature, and they stop growing. And then you have the luteinizing hormone and follicle stimulating hormone deficiencies, which can lead to infertility, menstrual irregularities, decreased libido and erectile dysfunction in men. Prolactin deficiency can lead to inability to lactate after delivery. So those are the features of hypopituitarism.
Glen Stevens, DO, PhD: So I'll move over to Pablo now, pituitary apoplexy, something that you deal with, medical emergency or surgical emergency potentially. Tell us about what that is.
Pablo Recinos, MD: Pituitary apoplexy shares a lot of features with stroke. So when we think about a stroke, it can mean an ischemic stroke or that area of tissue is just dying, or a hemorrhagic stroke where somebody had a bleed in their brain and it's impacting the function of that area of the brain. In the pituitary, it functions the same way. And we actually see those two type of variants. The more common variant, unlike in the brain, is when there's a bleed. This typically tends to happen when there's a tumor of a reasonable size that can spontaneously bleed, that blood can rapidly expand, and if that expansion causes pressure on adjacent tissues such as the optic nerves, you can start having symptoms, visual symptoms if it's the optic nerves. If it extends laterally, it can impact the nerves that move the eyes. And so they won't move in sync and the patient will have diplopia or blurriness of vision.
Glen Stevens, DO, PhD: Is there a size cutoff that if it's below a certain level it is very uncommon to see or that not necessarily?
Pablo Recinos, MD: Well, I do think it tends to happen more in larger tumors than smaller tumors, but we do see that phenomenon in tumors of all sizes. Sometimes it's as simple as seeing it on a follow-up scan as Divya will see when she's following up somebody. The central strategy historically for pituitary apoplexy, particularly if there's any symptoms, has been surgery, almost in an emergency way. We were fortunate to participate in a registry study with numerous other institutions across the United States, in your home country of Canada and made us realize that perhaps emergent surgery was not necessary in absolutely everybody.
So while we do operate in a more pressing way on patients in particular when they're having visual disturbances, specifically by pressure on the optic nerves. If it's double vision for example, or if the event happened a while ago and the tumor is now showing signs of shrinking, we sometimes don't operate on them at all and they'll shrink up to a smaller size where it will even look like they had surgery when they didn't. So that the management now of that, of pituitary apoplexy is becoming tailored based on the patient's clinical presentation, the history as well as the imaging findings.
Glen Stevens, DO, PhD: So Divya then you may just see a patient in follow up that's not reporting anything, and you'll look at the MRI and you'll see there's some blood or something in the pituitary and realize they've had an issue. But I guess at that point you just check the hormones, see how they're doing, and-
Divya Yogi-Morren, MD: Yeah, absolutely.
Glen Stevens, DO, PhD: ... keep closer eye on them, right?
Divya Yogi-Morren, MD: Yes, absolutely. So sometimes it's very clear from the imaging or the imaging reports that were done somewhere else, that there was a bleed or an accident, either an infarction or hemorrhage into the pituitary gland. Sometimes it's not that clear. We just see some maybe heterogeneous enhancement or something in the pituitary gland. But if you ask questions, the patient may tell you something like they had a sudden severe headache and they lost consciousness or something like that. And the history really corroborates what is seen on the imaging. And then my job here is really to check the pituitary hormone function and see if there's anything that needs to be replaced because of any damage that may have been done to the pituitary gland during that event or accident.
Glen Stevens, DO, PhD: So I guess while anybody could present with the first diagnosis of pituitary tumor with apoplexy, I guess the important point is that if you have a known pituitary tumor and you develop very bad headache or some focal neurologic problem, you need to be seen immediately.
Divya Yogi-Morren, MD: Absolutely, I think with most of my patients that have pituitary tumors and especially large tumors, I do talk to them about just the blood supply of the pituitary gland. This is a very vascular gland, blood flows, and some of that communication between the hypothalamus and the pituitary gland is just because of a very rich network of blood vessels and that portal system that carries those factors from the hypothalamus to the anterior pituitary and tells it what hormones to secrete. So that very rich blood supply really predisposes this gland in particular to spontaneous hemorrhage. And that risk is increased when there's already a pituitary tumor there.
Pablo Recinos, MD: The other piece of advice that you give them in particular if you find that they have a deficiency of a hormone such as the ability to make cortisol, is for them to have a medical bracelet in case they're in a car accident or have any event because that becomes a really important part of their care, right?
Divya Yogi-Morren, MD: Yes, absolutely. The most life-threatening hormone deficiency is really having a secondary adrenal insufficiency, ACTH deficiency or cortisol deficiency that arises from pituitary tumors that have had apoplexy. If you have that, you have to be wearing a medical bracelet or some of my patients have even gotten tattoos. Some of them have specific watches with a USB port in them so that their information is available, but it is critical that they understand that they need to have that on their bodies at all time because if they're found down, the first place an EMT is going to look is for either a bracelet or a dog tag that tells what medical condition you have and what is the most important thing to do. And in this situation, the most important thing is to administer parenteral steroids via injection, and that in itself might save someone's life. So that's very important.
Glen Stevens, DO, PhD: Well, excellent information, that's for sure. So moving along pituitary cyst, I guess we're really maybe looking at Rathke's cleft cysts here, Pablo. Do we see hormonal dysregulation with cyst in the pituitary or is it more a surgical question or could be either, I guess.
Pablo Recinos, MD: Yeah, cyst, that's an umbrella term because we definitely see cysts of different kinds, such as a Rathke's cleft cyst, which is a cyst that's a developmental cyst. Another one is an arachnoid cyst in that area. Both can need surgical treatment but don't often do. It's something that we have to counsel patients and evaluate them individually, but we also see a different spectrum of cysts, which are all associated with inflammatory changes, and they can be much harder to treat. They can impact the pituitary function from a medical standpoint. They can also grow and require drainage, but that drainage in those inflammatory cysts can at times put them at risk for recurrence. More recently, there's been more literature and also some experience that we've had in treating them medically with some medications that suppress the immune system a little bit, such as steroids or other immune modulating drugs in order to suppress that inflammatory response, which is causing that cyst to form in the first place. So to circle back, pituitary cyst can mean a lot of different things, and it can also mean a tumor, a tumor that made a cyst.
Glen Stevens, DO, PhD: So Divya, I'll go back to you from something that Pablo just mentioned. We're using a lot of immune modulating therapy in cancers now with the checkpoint inhibitors and you can get a lot of itises-
Divya Yogi-Morren, MD: That's right.
Glen Stevens, DO, PhD: ... associated with it. So how much are you seeing, how many itises are you seeing affect the pituitary from these drugs?
Divya Yogi-Morren, MD: Yeah, I think definitely over the past decade with the increase in the use of immune checkpoint inhibitors, which have been really revolutionary in the prognosis of different cancers, we have seen a lot of endocrinopathies. So we have a lot of endocrine deficiencies, notably ACTH deficiency and thyroid deficiency that might arise from these. There's also pituitary enlargement that can occur in the initial stages, so sometimes that is detected on MRI as part of whatever surveillance the patient is undergoing for their cancer, and they're referred to us. But my job here really is to treat any hormone deficiencies that might come from the use of these medications. The pituitary abnormality and enlargement usually resolves, the hormone deficiencies rarely do.
Glen Stevens, DO, PhD: All right, Pablo, one last one before we move on. Craniopharyngiomas.
Pablo Recinos, MD: Craniopharyngioma are one of the most challenging to treat tumors. They're considered or formally considered benign, but locally aggressive tumors, they can arise both in young adults, even children as well as older adults. So they have a bimodal distribution of appearance. The reason why craniopharyngiomas can be so challenging to deal with is they can involve the pituitary stock or infundibulum, the floor, the third ventricle, and even more critically, the hypothalamus. In adults that may be less of an issue. So when we go in and we do a surgery, for example, and we're removing tumor from the area close to the hypothalamus, as long as we don't damage the hypothalamus, then I rely on Divya to replace the hormones that were impacted based on a treatment for that. But in children, it can become a major problem with them developing problems with their development and specifically hypothalamic obesity, a sort of uncontrolled predisposition to become obese despite behavioral modification.
Glen Stevens, DO, PhD: Very good. So you are both part of the Pituitary Center. Anybody else involved with the Pituitary Center? Who's it made up of?
Divya Yogi-Morren, MD: Yeah, so of course Dr. Recinos and I, we form the primary team, so I'm the neuroendocrinologist, so my job is to diagnose these pituitary tumors and any hormone deficiencies or overproduction that might be there. And then we have neurosurgeons and we have ENT surgeons and we have radiologists and radiation oncologists and even neuro-oncologists such as yourself, Glenn, as well as neuro-ophthalmologists who help us addressing a lot of these vision related problems that these patients may present with before and they also need to be monitored after. And then we also have pathologists that are really vital for accurate tumor classification and sometimes we need to also utilize our geneticists here at the clinic and also in follow-up and monitoring of these patients, we sometimes need to have psychiatrists and psychologists involved. I think most importantly, and I am sure Pablo will agree with me, is that we have our care coordinators, our nurse specialists, that are really essential in coordinating care amongst all of these medical subspecialists and making sure that we're all working together, getting the information that we need in real-time so that we can be effective in managing these patients.
Pablo Recinos, MD: The one other group that I would mention, the advanced practice providers, the physician assistants and nurse practitioners, while more widely trained, they also develop a specialty focus in this area and are a vital part of our team.
Glen Stevens, DO, PhD: And do you do pituitary specific tumor boards?
Pablo Recinos, MD: We do. And during the pituitary specific tumor boards, we really discuss a lot of the topics that have been structured here, functional tumors, non-functional tumors, cysts, and related tumors such as craniopharyngiomas.
Glen Stevens, DO, PhD: So Divya, I know you've discussed some of this a little bit in terms of the diagnostic workup for patients. National guidelines, are they available, are they helpful? Who puts out standards of what we should do or is it up to you?
Divya Yogi-Morren, MD: So we do use guidelines, national guidelines from the major endocrine society such as the Endocrine Society and the American Association of Clinical Endocrinologists. So we have evidence-based guidelines just to standardize our diagnostic approaches and inform our treatment decisions. So we have the hormone evaluation, which I've already spoken about, but we also have to do dynamic testing in pituitary tumors sometimes to evaluate pituitary reserve, but also to evaluate the behavior of the tumor and how these tumors are producing their hormones. That's critical from the endocrine standpoint. We also have MRIs, that's the gold standard for visualizing pituitary tumors. And sometimes we also have to do something called inferior petrosal sinus sampling, where we sample blood from the inferior petrosal sinuses that drain the pituitary, and we measure hormone levels there. So we also have to access another subspecialist, our neuro-interventional radiologists to do that procedure. And then when it comes to monitoring, we also have to do visual field-testing with our neuro-ophthalmologist. So we definitely need a variety of different tools and specialists so that we can diagnose these conditions correctly prior to patients having surgery or radiation or any other intervention.
Glen Stevens, DO, PhD: And I'm sure a lot of people just order an MRI. You have very specific protocol where you do a pituitary specific MRI that will blow up and get the important sequences in that area?
Pablo Recinos, MD: Absolutely. And it depends actually if we're looking from a diagnostic perspective or from a surgical perspective if we're using it for image guidance or like a GPS type system for surgery.
Glen Stevens, DO, PhD: So Divya, let's go to non-surgically based treatment at this point. And again, I know it depends on the type of tumor that you have, but go through some of the medical managements.
Divya Yogi-Morren, MD: Yeah, so now we've come to my favorite part of today where I get to talk about my tools, which are not scalpels, but just medications. And it's a very exciting time to be practicing in pituitary medicine. I think I was telling the group on Tuesday in clinic that when I graduated from my fellowship more than 10 years ago, we really had very few options for acromegaly and for Cushing's disease. And now we have many more options that are FDA approved and have gone through that rigorous regulation process that are available to us. So I'll start with prolactinoma because the first line treatment for prolactinomas is medication. It's not surgery.
Glen Stevens, DO, PhD: Sorry, Pablo.
Pablo Recinos, MD: I don't know what she's talking about.
Divya Yogi-Morren, MD: That's unlike Cushing's and acromegaly where first line treatment remains surgery. So dopamine agonists are the medications that are used to treat prolactinomas. These dopamine agonists are bromocriptine and cabergoline, and they act on the lactotroph cells in the pituitary gland and inhibit prolactin secretion. And that reduces tumor size in prolactinomas, and it also hopefully can normalize prolactin levels. And then we can move on to acromegaly. Sometimes we can also use dopamine agonists in acromegaly and Cushing's, but they're used mostly as adjunctive treatment for milder cases. So the mainstay of acromegaly treatment is really somatostatin analogs. These are medications such as octreotide, lanreotide, and pasireotide that mimic the action of somatostatin and inhibit secretion of growth hormone and helps to control the symptoms of acromegaly.
And then we have the growth hormone receptor antagonists such as pegvisomant, which binds to growth hormone on receptor tissue and actually blocks the action of growth hormone and then reduces the level of insulin growth factor one, and that controls acromegaly. And then when we get to Cushing's disease, we have adrenal enzyme inhibitors such as osilodrostat, ketoconazole, metyrapone. And these drugs inhibit enzymes that are involved in the cortisol synthesis pathways. So it basically shuts down the cortisol factory and that's how they reduce secretion of cortisol. We also have another class of medication that's called glucocorticoid receptor antagonist, and that's mifepristone, which blocks the receptor and prevents cortisol from exerting its effect on target tissue. So those are the main medications that are used. Yes, we put them in a class for prolactinomas, Cushing's or acromegaly, but sometimes there is a little bit of overlap.
Glen Stevens, DO, PhD: Well, I'm very glad Pablo did such a good surgical resection on me. I didn't have to use any of these medications, so thank you, Pablo.
Pablo Recinos, MD: Happy to help.
Glen Stevens, DO, PhD: So, anything else you want to mention medically, or no?
Divya Yogi-Morren, MD: Just that sometimes these tumors are very large and extensive. They have sometimes repeat pituitary surgery or radiation, and patients may have hormone deficiencies, which I'm also responsible for replacing. And really it's sort of like a recipe. You have to put the right levels of hormone so that someone can feel good and we can optimize their health.
Glen Stevens, DO, PhD: Yeah. Not to be understated, right?
Divya Yogi-Morren, MD: Absolutely.
Glen Stevens, DO, PhD: Pablo, let's go to surgery.
Pablo Recinos, MD: It's so exciting seeing Divya is so excited about the medical management. It's cool.
Glen Stevens, DO, PhD: It is cool.
Pablo Recinos, MD: It is cool because the number of drugs and options available has increased so much, especially since any of us were in medical school, which is exciting. The same actually applies to surgery. Probably one of the bigger areas of development more recently or innovation is entry into an area called the cavernous sinus. Those areas sit just to the side or lateral to where the pituitary gland sits and tumors can frequently invade that area. It wasn't that long ago where that was considered an absolute no-go area. People have been trying to enter the cavernous sinus for a long time, but through a better understanding of anatomy in the era of endoscopic endonasal techniques, we're entering more aggressively yet safely into that area using adjunct tools such as intraoperative neuromonitoring to monitor the nerves that move the eyes. And we're entering these areas, peeling tumors off of the carotid artery, hopefully to get patients in remission like yourself, Glen. But if we can't, at least to reduce the tumor so much that they can be more easily and safely targeted with radiation or more easily treated with medicine.
Glen Stevens, DO, PhD: And just the role of ENT, I know you work very closely with your ENT colleagues.
Pablo Recinos, MD: I can't overstate the role that they play. For uncomplicated tumors they play a central role, particularly in the approach and the reconstruction. But for the complicated tumors, we really work synergistically. Our team has been together for 10 years now. And really it's another set of eyes too. So even when I'm doing my part partners such as Raj Sindwani or Troy Woodard, they're another set of eyes that are looking as we're doing the operations. They've also advanced and the boundaries of what can be done from a reconstructive standpoint so we can make bigger openings and close them in a safe way and do the surgery safely.
Glen Stevens, DO, PhD: And what percentage of your cases are an open craniotomy now versus an endonasal approach?
Pablo Recinos, MD: For pituitary, if we're just talking about pituitary surgery or pituitary and craniopharyngioma surgery, I would have to say 95% of the cases are for my own practice, about 60% of all the surgery that I do is endoscopic and 40% open.
Glen Stevens, DO, PhD: And I know none of us are radiation oncologist, but any comments about radiation for pituitary tumors?
Pablo Recinos, MD: Yeah, I think that's also where we've seen a lot of additional development. We're not in the days of wide beam radiation anymore. We're in the days of very precisely delivered radiation at higher doses that can still be delivered safely. Here we use a lot of, as you know Glen, we use a lot of Gamma Knife radiosurgery, whether it's in single session or multi-session. And again, combined with some of the techniques, either the ability to shrink the tumor with medicine or the ability to reduce the tumor bulk size in difficult locations can allow us to pull the target of tumor away from critical structures to be able to treat it more safely with radiation if it's needed.
Glen Stevens, DO, PhD: Let's just discuss research for a minute. Any active trials going on that you're participating in? Anything exciting in the area?
Divya Yogi-Morren, MD: So at any point in time, we usually have either one acromegaly or one Cushing's study going on at our site. So we recruit eligible patients from our pituitary practice. And over the past two decades, we have been involved in almost every major acromegaly and Cushing's medical trial. And that not only puts us at the forefront of innovation, novel treatments, pharmaceutical treatment for these conditions, but it also gives us a level of comfort and expertise in prescribing these treatments. So when patients need that and they come to our center, we have that expertise and experience among our group to deliver that type of treatment to them.
Pablo Recinos, MD: From a surgical standpoint, we've been involved in a lot of imaging studies, but even quality of life studies. So for example, what we prescribe for patients afterwards, if it's particular rinses or in the use of antibiotics, it may not seem like a big deal, but for patients when they're dealing with their sense of smell, with their quality of life and smell affects taste, those are things that people care about once the tumor has been addressed. A few years ago, we were involved in a multicenter trial regarding the use of antibiotics that actually won the paper of the year at the Congress of Neurological Surgeons, which was a big honor, but for a relatively straightforward problem that really impacted patient's quality of life. So on one hand, we're dealing with the tumor side, and on the other hand, we're still looking at refining the techniques to make them as least disruptive on patient's quality of life.
Glen Stevens, DO, PhD: Yeah, I can certainly say on a personal level, because I really was not symptomatic. Quality of life was my biggest issue with having surgery. Will I get a CSF leak? Will my smell be affected? Will my hormones, will I have hypopituitary related problems? These are really the things that if you're in a life-defining moment, you're just concerned about that. But if you're not, it's really quality of life.
Pablo Recinos, MD: Absolutely.
Glen Stevens, DO, PhD: So, Divya, we're pretty much here. Closing comments.
Divya Yogi-Morren, MD: So, Dr. Recinos and I, we do very different things. You have here a neurosurgeon and you have an endocrinologist, which is a medical subspecialty. These pituitary tumors are just very complex, very multifaceted. Their effects can affect many organs in the body. And it's very important that you assemble your A team when you have a tumor such as this. And I think that is the one thing I would like to leave with our audience, is that if you want your patient to have the best care and for you to have more favorable outcomes in someone with a pituitary tumor and pituitary disease, it's very important that you send your patient to a tertiary center with a dedicated pituitary center where you have these specialists that really just specialize in this very rare condition that have the expertise to deal with it.
Glen Stevens, DO, PhD: Pablo.
Pablo Recinos, MD: Well, as you've heard, this is what keeps us motivated and going throughout the day. This is what makes us excited to come to work, to help patients with these type of problems. I think it's one of the most exciting times in caring for patients with pituitary tumors because we have more to offer them that's not only focused on simple survival, but also their quality of life to get them past this.
Glen Stevens, DO, PhD: So Divya, Pablo, I'd like to thank you both for joining me in Neuro Pathways today. I put my life in your hands. I love you. It's fantastic what you do and couldn't be happier to work with you guys. So appreciate it and wish you both well.
Divya Yogi-Morren, MD: Thank you so much. It's an honor to take care of you and to take care of all of our pituitary patients.
Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.
Neuro Pathways
A Cleveland Clinic podcast for medical professionals exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab and psychiatry. Learn how the landscape for treating conditions of the brain, spine and nervous system is changing from experts in Cleveland Clinic's Neurological Institute.
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