Speaker 1:

Welcome to AACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com/podcasts. And now let's meet the endocrine experts who will be talking with us today.

Dr. Lieb:

Hello and welcome to our AACE podcast. I'm Dr. David Lieb, Professor of Medicine in the division of endocrinology at Eastern Virginia Medical School at Old Dominion University in Norfolk, Virginia. I also serve as our endocrinology fellowship program director. Joining me today are Dr. Jaydira Del Rivero and Dr. Michelle Lundholm as we discuss the new 2025 AACE consensus statement on the management of multiple endocrine neoplasia type one. Thank you both for joining me today, Dr. Del Rivero, can you introduce yourself and tell us about your areas of expertise and your roles on the consensus statement?

Dr. Del Rivero:

Yes, thank you so much. And I would like to thank AACE for giving us the opportunity to discuss also this important work. My name is Jaydira Del Rivero, as Dr. Lieb introduced me, I am a medical oncologist and endocrinologist as well. I specialize in management of neuroendocrine tumors as well as familial syndromes related to neuroendocrine tumors. And I was fortunate to be co-chair for these guidelines and it was fantastic work with everyone and all the panelists. So I'm very happy that this is now available to you all.

Dr. Lieb:

Excellent. Thank you. And Dr. Lundholm.

Dr. Lundholm:

Thank you, Dr. Lieb. So I'm Michelle Lundholm. I am an endocrinologist and I work in research and providing virtual inpatient endocrine consults, and I'm developing my expertise in that area, but it's a privilege to share my insights today and I'm grateful for our listeners for taking interest in our podcast.

Dr. Lieb:

So let's start with the methodology. Dr. Lundholm, you served as a methodology fellow on this task force and this is a newer role for AACE guidance documents. Can you tell us a bit about your experience and what some of the highlights were?

Dr. Lundholm:

Absolutely. I'm happy to share what I've learned for those who might be interested. So broadly speaking, the methodology fellow's role on the task force is identifying and organizing appropriate literature references. So this process is done in collaboration with the evidence team, and I want to acknowledge Carla Steck and Kendall Alexander for guiding me through it. We began by creating some general search terms, and my job was to review the articles that we were generating and refine that search iteratively. So the goal is to narrow the evidence down to high quality literature. These are clinical studies, prioritizing randomized controlled trials where possible while excluding some of the less relevant medical materials like reviews, case reports, animal studies or publications about MEN 2, for example, and so on.

So ultimately we compiled a list of about 830 publications, which I then categorized by abstract into topic areas based on our predetermined clinical questions. And from there we generated 182 articles that were shared with taskforce subgroups to provide the literature backbone for our consensus document. So honestly, I did not expect there to be quite so much published on MEN 1, and that was really a pleasant surprise. But this was my first time conducting a systematic review and working within the GRADE framework, which stands for Grading of Recommendations, Assessment Development, and Evaluations. And it was a valuable learning experience that prepared me for further participation in future guideline development. And a highlight for me was learning from both the methodology staff and the other task force members while serving as a bridge between their areas of expertise.

Dr. Lieb:

Yeah, it's a wonderful thing that AACE has done utilizing grade and also having a methodology fellow who then can use those techniques that they learn on other work that they do, whether it's with AACE or other things that they're involved in. So it's really an awesome opportunity. And actually that brings us up, another really interesting idea. I understand that another new role on the task force is that of the patient representative, and this is the first AACE guidance document to include a patient representative as a member of the task force. Dr. Del Rivero, can you discuss the importance of including patients perspectives throughout the full guideline development process?

Dr. Del Rivero:

Yes, absolutely. This is a very important question in my opinion. I am also medical endocrinologist. I always feel like one of my other hat is patient advocacy. I really want to empower patients to have a voice, especially with these rare diseases when we don't have that many treatment options, I think is very important. And I have to say I thank AACE for also giving the opportunity to involve patients, which I feel it needs to be involved in any guidelines or any procedure that we see or work where patients are involved. And the incorporation of patients perspectives also cannot be overstated. Patients bring firsthand insight that can influence the clinical recommendations that we make.

I also feel that by having the patient representative, it helps us understand more about what the patient's needs are. And also it also gives you guidance as well to reflect on the real world challenges and practical considerations that physicians may also encounter. I do feel this is important. I feel that by having this, it can also empower patients. I always tell my patients knowledge is power. And by having this information I think, and having somebody who can speak for patients is so important to understand where the limitations are, where we can make improvements, especially like I mentioned, a rare disease when there can be limitations in certain aspects of the management. So I'm very happy that AACE gave the opportunity to have a patient representative in this situation.

Dr. Lieb:

Me too. It's incredibly important, and I like what you said about the importance of the patient's story, especially for rare diseases. And so there's something extra special to me about our first patient representative on the guideline committee being part of this specific MEN 1 document. It makes a lot of sense to me. So moving on to the content of the document, I'd like to hear from both of you what some of the key takeaways are for clinicians that are reading the guidance document. And I'll start with you, Dr. Del Rivero.

Dr. Del Rivero:

Yes, absolutely. And one of the important takeaways of these consensus statements, this guidelines is because with these guidelines, we want to provide information to healthcare providers and practitioners that encounter a patient with MEN 1. I also feel that with this information, we can also help physicians in the community when there may be limitations and resources. Some of the takeaways of these guidelines is that we discuss about the diagnosis and importance of genetic testing and early genetic testing in patients with MEN 1. We know that this is a complex disease. It has many clinical manifestations, such as parathyroidism, pituitary tumors, pancreas, neuroendocrine tumors. In genetic counselor, you always offer to every patient that was diagnosed with MEN 1 as well as affected family.

Another important aspect of these guidelines is that it's not like one size fits all for patients with MEN 1. The management, the follow-up, the surveillance is also personalized even though we know what are the different aspects of wanting to follow, whenever there is a patient that has an active tumor related to MEN 1, the treatment is quite personalized from patient to patient. And it's important to take all of that in consideration. And I think getting the endocrinologists, the surgeons, the geneticists and different specialties can certainly help us manage patients with MEN 1, at the same time improve outcomes. But at the same time, if there is somebody in the community when they may not have access, at least they can provide some information on how to manage patients with MEN 1, how often do we need to do screening scans or imaging modalities or biochemical evaluation. I think that's also important as well.

And you asked earlier about the importance of having a patient representative. I think this can also provide support to patients as well and education about what needs to be done in patients with MEN 1. So by doing that, it can help mitigate some of the psychosocial impacts of living with this condition. We also discussed about what is the long-term follow-up, and there's the most important questions that we need in a patient with MEN 1. So these consensus statements really serve as a comprehensive guide that assist clinicians in navigating complexities with MEN 1 management and also helping patients to receive timely, informed, and individualized care and empowering patients as well.

Dr. Lieb:

Absolutely. As a clinician who has a handful of individuals that I take care of that have MEN 1 diagnoses, what you said about the screening schedule, knowing what to screen for, when to screen for those things is going to be incredibly helpful. And I love everything you've said about the patient perspective and the psychosocial aspects of the disease too. Dr. Lundholm, what are some of the key clinical takeaways that you have?

Dr. Lundholm:

Yeah, thank you Dr. Lieb. So one of the things that I truly appreciate about this guidance is like we've talked about, how it brings together a wealth of expertise from multiple perspectives. So it's not just a distillation of the literature, it integrates the insights of endocrinologists, oncologists, surgeons, geneticists, and even the patient perspective as Dr. Del Rivero just discussed with us. So I envision this document being a valuable resource for any provider who encounters a patient with MEN 1 whether it's their first patient or their 100th, because with the collective wisdom that went into crafting this paper, I'm confident that there's something here for everyone to learn from.

As someone who is personally early in my career, I wanted to highlight one particularly useful aspect of this guidance was this very practical screening recommendations that we have outlined in table one. And I would encourage all of our listeners to check that out. This table provides a reasonable approach to the method and frequency for screening each of the main MEN 1 related tumors. And it still has room and acknowledges that there's room for future study and data. And this resource can be immediately applied in clinical practice to ensure that our patients are getting appropriate care.

And another important aspect of this guidance is its discussion of the MEN 1 related tumors beyond just our classic triad of the parathyroid pituitary and the duodenopancreatic neuroendocrine tumors. It includes the growing evidence linking MEN 1 to other tumor types. And one that I would particularly want to highlight is breast cancer. This is a more recent association, and it's particularly relevant for ensuring that patients with MEN 1 receive appropriate mammography screening as part of their care. So overall, this guidance strikes a balance between being rooted in evidence and offering practical tools that providers can use in real-world settings. So this is not just theoretical, it's actionable, and that's what really makes it so valuable for clinicians.

Dr. Del Rivero:

And Dr. Lieb, can I make a comment? And Dr. Lundholm, you say very beautiful and summarize the guidelines and thank you so much. But another aspect that I want to mention here is that in the United States, this is actually the first guidelines from MEN 1. So we sometimes use information from the European guidelines, but this is the first guidelines in the United States, and I have to say, thanks AACE for doing that. This is a very important work for our patients living with MEN 1, because sometimes some patients really suffer not only to find different specialists and in continuum of care and having communication with the different specialists, but at the same time because of the complexity of the disease and the different tests that needs to be done, sometimes it's difficult that insurance can cover some of that. And they always ask, where's the guidelines? So I think this is a very important information for physicians and patients that can help in those situations and they can have better follow-ups and better outcomes.

Dr. Lieb:

Absolutely. And I know Dr. Lundholm, you mentioned that you had what, 900, 1000 articles almost at the beginning that you went through. It's clearly a lot, but there's also still much that we need to learn about MEN 1. And so I wanted to start by asking Dr. Del Rivero, where do you see gaps in research? What's the next guideline going to look like with the research that you hope is done or that you've done by that time?

Dr. Del Rivero:

That's an excellent question. And I do research, that's what I do, and I'm always asking questions about how we can improve the outcomes of endocrine tumors, of the adrenal tumors, and that's my area of expertise. But I feel that there's opportunities to improve the management of patients with MEN 1, and I do think there's a few gaps. What are those gaps? I do feel that we need more longitudinal studies so that way they can help us understand more about the biology of the disease, understand disease progression, who is a risk to develop endocrine tumors that may have a worse outcome, and that will be something that it can help us also have better surveillance protocols.

Right now, even with most of the papers that we review is based on retrospective data, and I think prospective study, longitudinal studies will be also important to then establish more surveillance protocol and help us understand how often these patients, even though we have this information of surveillance and follow-up, but I think it will be important to understand who are at risk sometimes to develop thymic neuroendocrine tumors and other clinical manifestations. I think that is important. Another aspect about patients with MEN 1 is to also understand the psychological impact which is not addressed in the current literature. And I think future research should focus on that because patients, when they have MEN 1 and they have to follow these different aspects of the, and complexity related to the disease, it can be quite overwhelmed and patients can feel isolated. And not just that. It's the financial impact. Sometimes they have to travel long distance to see a specialty. So I think that that can also burden the patients that have hereditary cancer syndrome. And I think addressing that, how we can help these patients, what could be the resources, I think that will be important.

Also, one thing is about treatment modalities. I mean, patients with MEN 1 can also, they have a risk to develop neuroendocrine tumors and these neuroendocrine tumors can metastasize. So what are the treatment options? One aspect as a person who runs clinical trials is to understand what other options may offer to different cancer types. One of the eligibility criteria is they cannot have any other active cancers. And sometimes for MEN 1, that can be a little difficult because they may have two or three different tumors at the same time. So I think that that's something that we need to understand, that these patients, they have the condition, but also not exclude them to the treatment studies that we have. I think that will be very important as well.

Also explore the benefits of different surgical interventions as well, and understand as well, as I say earlier, management of these neuroendocrine tumors is personalized from patient to patient, but also understand what are the treatment options too and the treatment options, how that can affect other aspects of MEN 1. I also feel that other gaps is that we need to have more focus in developing what we call patient-centered care models so that way we can understand the patient's preference, the follow-up, and also effectively engage with patients and share decision-making. One other aspect I think is biomarkers, predictive prognostic biomarkers. We don't have that information for MEN 1.

So I think that would be important. If there is a patient that we may recommend certain therapy, what would be the predictive biomarkers for that? Is there is any prognostic biomarkers? I think that will be something that can help us so that way we can have more personalized approaches for these patients even with MEN 1. Yes, I do think there is a gap for improvements in every aspect. And I'm very proud that this is a start with having this knowledge and guidelines for everyone in the community for every other healthcare providers. And I'm very grateful for this opportunity.

Dr. Lieb:

Awesome. And Dr. Lundholm, what sorts of gaps did you see emerge as you were going through the studies?

Dr. Lundholm:

Absolutely. There are many aspects of MEN 1 care that we do not have strong medical evidence for, and I appreciate all the things that Dr. Del Rivero just pointed out for us about all these areas that are still lacking. But the main thing is the rarity of MEN 1 disease. So in the absence of large multi-institutional collaboration, it is difficult to determine, for example, MEN 1 specific efficacy of the surveillance and treatment strategies that we provide. And not to mention, I really like the point that Dr. Del Rivero made about the psychological impact of the surveillance and the treatment strategies. We do not even begin to discuss any of the investigational treatment in this guidance.

So clinical trials will go a long way to clarify how best to care for our patients with MEN 1. And while we've come a long way in our genetic discoveries, there is yet still so much to understand about why there is significant variability of the disease even amongst family members and our lack of clarity on the genotype phenotype association and what is driving, for example, genotype-negative disease. This just highlights how much we have yet to determine in the pathogenicity of MEN 1. So yeah, there's still a lot that we do not have strong medical evidence for. And I want to echo what Dr. Del Rivero said, which is that I'm glad that this is a start that we can make here.

Dr. Lieb:

Thank you both so much for joining me today for this discussion about this fantastic guidance document. Before we wrap up, I want to give you each an opportunity to make some closing comments and additional thoughts. And Dr. Lundholm, any recommendations for people that are interested in the methodology fellow position?

Dr. Lundholm:

Yeah, so first I want to say it was such an honor to be part of this task force, and I want to say thank you to Dr. Del Rivero for leading this consensus statement and to all of our co-authors for their hard work on this paper. And thank you to Dr. Lieb and the podcast team today for hosting us. And thank you to our listeners for their attention and their interest. It's through these discussions that we can continue to advance our understanding and improve care for patients with MEN 1. But in speaking about the methodology fellow, for anyone who's considered applying for this role, who's interested in this role, I would like to clarify that the term fellow is a little bit of a misnomer. So this role is absolutely not limited to trainees. In fact, early career members should consider it as well. Timing is important. So I found it worked perfectly well for me because most of the literature review process occurred during the few-month transition period between when I finished my fellowship and when I started my new job.

So the writing and the editing that came later were spread out a little bit more gradually over the following year. So the methodology role has a large upfront time commitment, so planning ahead for that is key. But you do not need significant experience in literature searches to succeed in this role. Though some familiarity with advanced PubMed searches and writing journal articles can certainly be helpful. But overall, it's a fantastic opportunity to develop skills and evidence synthesis and guideline development while working with an excellent team.

Dr. Lieb:

Dr. Del Rivero, any final thoughts?

Dr. Del Rivero:

Yes, certainly. First, I would like to thank each one of the panelists, and I hope I have the opportunity to mention all of them. So I would like to thank my co-chair, which is Dr. Alejandra Gangi. She's a surgeon at Cedar-Sinai. I was very fortunate to work with her too. Justin Anz who was the geneticist with wealth of knowledge and Jason Keller, who is our patient representative. And we are so grateful to him for all of his feedback and making this paper possible. Of course, Michelle Lundholm, Julie Silberstein, Tinash Bastiwala, Dr. Werner. I think it's important to acknowledge all of these wonderful physicians that have dedicated their time to go all over the evidence-based documentation that we have for MEN 1, making this possible. And I'm grateful for them, of course, AACE and everybody who supported us through this process too.

And just as a closure, whenever I feel something like this, and that's one of the things I always feel, I feel hopeful. I feel hopeful that there will be something that can help patients with MEN 1, that can help us understand more about the disease biology, more about how we can follow this patient, how we can treat these patients. I think this is so important for patients, and I hope they can help improve the outcomes in the long term. And this is just a start, so and hopefully with more collaborative efforts, different organizations with different patient advocacy, we can certainly make a greater impact overall.

Dr. Lieb:

Thank you both so much. To read the full consensus statement as well as the commentary drafted by the patient representative, visit pro.aace.com/clinical-guidance

Speaker 1:

Thanks for listening to another great AACE podcast. Join us for another episode at aace.com/podcasts and help us in our mission to elevate clinical endocrinology. Together we are AACE.