We have three great speakers with us today. And I have the honor to introduce Dr. Shivani Agarwal. She's Associate Director of the Fly Short Diabetes Institute, Director of Type 1 Diabetes Program, Director of the Supporting Emerging Adult with Diabetes Program, and an Assistant Professor of Medicine at the Albert Einstein College of Medicine. Her research concentrates on clinical and behavioral interventions in young adults with type 1 diabetes, as well as racial and socioeconomic disparities in type 1 diabetes, especially with regards to the use of diabetes technology. Thank you for that kind introduction. Thank you for having me. And thank you for coming on the last day. Sorry, it's just loading. OK. All right, so I was given the topic of diabetes, which you will see is near and dear to my heart. So these are my disclosures and my funding. So I just wanted to go through a brief outline about what health care transition is. The period of emerging adulthood to young adulthood, these terms get kind of switched on and off. Some young adult with diabetes data, both the stats on outcomes, but also transition data, opportunities, and continued challenges. So what interventions have been done so far, and what can we look forward to in the future, and then future directions. OK, so what is health care transition? So this may be review for some people, but I think definitions are good to get out of the way. So gottransition.org is a great website that is actually nationally funded. And so if you don't know about it, I would definitely recommend looking into it if you're interested in transition. But they define health care transition as getting ready for health care as an adult. White and Cooley in a position statement in pediatrics in 2018 defined health care transition as the process of moving from a child to adult model of health care with or without transfer to a new health care provider. I think pictures are worth 1,000 words. So I think conceptually, this is another way to think about health care transition, that while the patient or the person is going from a child's children's services to adult services, they're also going from being a child to a young person to an adult. And when you think about it conceptually for health care, really in childhood or in children's or pediatrics, the patient is part of the family. And so you're really treating the family as a unit. In adolescence, those circles become more like the Venn diagram, so that the family is somewhat in the patient's life and in the patient's health care, but not as much as in childhood. And then during adulthood, ideally, the patient is really the center of care and the family is just in a supportive role. And so this transition happens at the same time as this transfer of care from peds to adult, and it can be painful, it can be not so smooth. So it's just good to understand this. Okay, so I'm gonna go through the developmental period a little bit of emerging adulthood or young adulthood, because it really sets the stage for outcomes and interventions. So emerging adulthood is really a unique developmental period. These young adults, age 18 to 25, are not children, they're not adults. And so Jeffrey Arnett really kind of coined this term as a new concept of development for the period from the late teens to the 20s with a focus on ages 18 to 25, so that's kind of considered early emerging adulthood, and the ages of 25 to 30 is kind of late emerging adulthood. So you can imagine in this trajectory, they're developing cognitive skills, so executive functioning, actually, or higher executive functioning is not actually fully developed until age 26 or 27. There are educational transitions, such as going to college, there's growing independence, there's increased social ties with peers, civic engagement, and then going to the workforce is a big one, also a big transition that's happening at this time, and then eventually, hopefully, marriage and family. At the same time, however, in the orange, there are other things that are going on in emerging adulthood. So usually childhood trauma is actually emerging for the first time in this period. Impulsivity, peer pressure, risk-taking behavior, we know this, we were there, right? Reward-seeking behaviors. So all of this sets the backdrop for the healthcare transition. We also know that during the emerging adult period, there's more psychological and substance use issues. So this is SAMHSA data, looking at the millions of young adults who report having a mental illness, only under half went untreated, and a large proportion of people having a substance use disorder, and then, again, really going untreated. And lastly, historically, we know that more young adults have been living, or have not been leaving the nest, if you will, or have been living with a parent. So these are trends shown historically over time from the Peer Research Center and the Young Adult Homepage, which, again, if you're into this work, I would strongly recommend knowing that page like the back of your hand. But this is data, interestingly, that looked at how the COVID pandemic really affected independence and the share of young adults living with their parents. So if you see here, the amount of young adults living with their parents from Feb to July of 2020 went up. Doesn't look significant here, but you're thinking about a large proportion of young adults in the country. And again, when you look at the increase of share and share of those living with their parents, you can see the percent point change on the right, but that was highest among the kind of early emerging adulthood years, so the ages 18 to 24, and then notably among Hispanic and black young adults. So let's go through some diabetes statistics with emerging adulthood, and they're pretty grim. So diabetes rates are increasing among youth. This is data from the Search Consortium for Youth. We know that the trends and incidents of type 1 and type 2 diabetes among youth less than 20 years of age is going up. And to me, that means that more young adults are going through the healthcare transition, so we have a lot of work to do. We also know that for outcomes, young adults with type 1 are a high-risk group. They have higher A1Cs, so if you look at this very well-known graph from the T1D Exchange of A1C across the lifespan, you can see that those late teens, kind of early emerging adults have the highest A1Cs across the lifespan of people with type 1. We also know, again, this is search data, that A1C is rising over time. So for people with type 1 diabetes, you can see again that really high peak of A1C from the 15 to 19 in 2024 group, and that is actually going up over time. In the type 2 diabetes cohort, it's actually interesting. I think that the A1C just goes up with age, which is really scary. And there are some trends, I'm seeing that there's, you know, increases over time, but the data I think is a little more muddy, looking at trends over time. We also know that there are high rates of long-term complications in our emerging adults, so this is again from search. I'm actually not a search investigator, so I'm not trying to endorse my own data, it's just good data. Looking at young adults with diabetes developing complications from the disease, so these are young adults with type 1 and type 2 who were diagnosed in childhood. You could see microvascular complications, kidney, eye disease, nerve disease. These numbers worry me. And then risk factor for heart disease are through the roof. We know short-term complications are increased in this age group, so DKA for type 1 and type 2. This is a cohort from England. And psychiatric comorbidities, so I had said a lot of psychological issues kind of emerge in the emerging adulthood period. So this is from the Healthcare Cost Institute. Young adults with diabetes had four times more mental health and substance use admissions, and nearly three and a half times more ER visits than young adults without diabetes. Lastly, and this is some of the work that I focus on, is we can't forget that there are racial ethnic disparities in these young adults, so it's a very vulnerable high-risk group to begin with, and then for black young adults specifically, there are much higher A1Cs, and they have clearly a lot of social determinants of health that interfere with self-management. So if I haven't proven to you yet, I think young adults with diabetes are really high risk, and healthcare transition, I think, can accelerate this unfavorable trajectory, and so it's a point in time which we can try to intervene, because it's a healthcare system problem or a health problem, I guess, in our purview of healthcare. Okay, so I'm gonna go through some of the transition data now. So this is a very old study, but I love it because it's simple. It's looking at current methods of transfer of people with type 1 diabetes in Canada. This is by KIPS. So this is just showing that a lot of young adults in the transfer from peds to adult care are lost. So if you look at either quarterly visits, or you look at every six month visits, you can see the attendance rates from two years pre-transfer, one year pre-transfer to adult care, one year post, and then two years post. Now, there has been some data trying to kind of characterize the young adult who may or may not transfer to adult care kind of smoothly, and so this is a study from the Type 1 Diabetes Exchange by Kate Garvey looking at factors associated with a gap of more than six months in care between pediatric and adult providers, and that is known to be associated with higher ER visits, worse outcomes in general. And so unsurprisingly, they found that young adults who had less visits in pediatric care were more likely to have a gap of more than six months between peds and adult care. But surprisingly, when we asked whether patients were prepared or not prepared to transition, those that were not prepared, or stated they were not prepared, were much more likely to have a gap of more than six months in care between peds and adult care. Again, other studies looking at kind of characteristics of patients that may or may not transfer to care smoothly and will be lost to care. So this is from Lotstein from the Surge Consortium. Again, increased age was associated with a higher likelihood of transitioning to adult care, unsurprising. But those with a lower A1C were also more likely to be able to transfer properly to adult care. In type two, this was a study that I was able to do. Looking at type two transition, it's actually the opposite. So again, higher age, more likely to transfer to adult care or no care, but basically leave peds care. But interestingly, those with higher A1C, as opposed to the type one data, those with higher A1C were more likely to leave pediatric care and then either go to adult care or no care. So that's really focusing on kind of follow-up. There's also this system piece of the providers. And so I was able to do some work looking at, I was really interested in looking at pediatric endocrinologist perceptions of transferring and what might be getting in the way of transitioning care. So we asked for, it's a national database of pediatric endocrinologists, this was a survey. And we asked, what are all the reported barriers to transition care and the primary reported barriers? And when you look, ending a long therapeutic relationship was the most rated as a barrier to transition. Then no established protocol, and then perception of adult care. So perception of resources in adult system, couldn't identify the adult provider, lack of adult endo-expertise. Some of these things I think we can work with because they're perception-based, but there may be kind of fixed issues in systems. As a kind of a partner study to what I looked at, Kate Garvey looked at the perspective of adult endocrinologists in the US. And again, looking at what might be kind of resources that had current access, that they had current access to, versus needing additional access to. And when you look, it's really the mental health kind of care coordination, exercise physiologist also, but really it's the mental health and care coordination that adult providers felt like they really needed to care for young adults, but were not available. So when we look at actually the perception of kind of patients and families, there's a really, really good body of high quality qualitative work in this field. And I just wanted to read some quotes because I think from the patient perspective, it's really important and powerful to think about how they're kind of floating through a system that is broken. So one patient says, or one young adult says, everything will be on my shoulders. There will be no her, mom, keeping records, her reminding me to check, her reminding me to take the Lantus shot. It's all up to me, which I'm trying to work on. I'm just trying to get it so I'm doing all of it so it won't be a new thing when I go off to college. It will be the same routine at a different place. Another young adult said, I was finally being treated, this is a young adult actually that had transferred to adult care, so this is a different perspective. I was finally being treated like the adult I should have been. At the age of 17, I feel I was too independent to have my diabetes center holding my hand through diabetes care. I think once a human matures, they no longer need their doctors to treat them like they're 10 years old. Another young adult, and kind of as a comparison to this prior very independent young adult, said they need to understand how you don't all of a sudden become an adult when you turn 18. You still need extra support, especially in college, learning how to take care of yourself and put yourself first. So you can really see the broad spectrum of perspectives here. Everyone is very different along the spectrum, and it's not age-based. And so really tailoring the care and understanding where that young adult is in that spectrum is extremely important to their success. Okay, so I'm going to change gears now and talk about what we can do about it. So I told you a lot of problems. So there was this position statement that has been endorsed by the ADA, by the Endocrine Society, and in many other societies, as you can see, that was written by Lori LaFell and Ann Peters back in 2011. It talked about a lot of really important, structured kind of interventions that can be done in this field. And I will say, it's been more than 10 years now, this came out when I was a fellow, I will say that I think we're still here. I think that we're still trying to build the plane as we're flying it. And there's this big divide between pediatrics and adult that I don't think we've bridged in great deal yet. Okay, so again, I really like gottransition.org, but I wanted to kind of talk about what is an approach for transitioning young adults to adult healthcare? I think they did a really good job of codifying this, and so I'm going to really center the rest of the interventions on these steps. So they talked about these six core elements, namely transition policy, transition tracking and monitoring, transition readiness, transition planning, integration into adult-centered care, and then transition completion and ongoing care. And I will say there's very little data on one and two, there's much more data on kind of three, four, five, and six, so that's what I'll talk about. So there are some readiness. Readiness has been a big focus of the PEDS community. And what does readiness actually mean? There are some validated surveys out there to kind of track and monitor readiness. This is just one of the few that have been out there, but I like this one because it's really focused on young adults with type one diabetes. Now again, if you've noticed, I've all talked about type one diabetes, there's very little about type two, so that's an opportunity. But the READY tool was developed by Sarah Carruthers and Joyce E. Frazier, and so there are several domains. So there's diabetes knowledge, health system navigation, insulin self-management, and health behaviors. And what they found when they actually tried to validate the survey in young adults was that there were actually high ratings in many of the domains, but there was low confidence in the knowledge of alcohol, tobacco, sexual health, and diabetes in pregnancy. So to me, those are opportunities for us as providers to actually counsel patients appropriately. And what I really liked was that when they looked at whether provider counseling was associated with confidence in the domain, it was associated. So we actually have power to be able to actually counsel patients, and they'll be more confident in that domain and hopefully use that going forward. So I think also this is just a very easy thing to roll out in the clinic. It doesn't cost much, and so it's just a thing to think about as you plan your transition clinic if you're in that space. So there's been a lot of data on kind of steps four and five, the transition planning and kind of transfer process. And there's three major studies, there are a few others, but the three that I highlighted. So one is the Canadian, there's the Canadian randomized controlled trial of a structured transition program in young adults. So this was actually a study of 205 young adults that were randomized to either transition coordinator versus usual care. So the transition coordinator offered care coordination from peds to adult care, diabetes education, just monitoring and just outreach, extra outreach through that transfer process. And the goal was to have three visits in pediatrics and then three visits in adults. So when you look at the results of this, in the intervention group, they had greater clinic attendance, care satisfaction, reduced diabetes distress, and a trend towards A1C improvement of almost 0.5% compared to the control group. But unfortunately, when you look at the 18 to 24 month follow up, those differences disappeared. There was still an A1C trend, but mainly disappeared at 0.3%. So to me, I think again, opportunity and challenge. I think it's an opportunity to show that transition coordinators may work, but the challenge is, what are the sustained effects? How do you pay for this? How do you systematize this? Another study looking at the LEAP program out of California, looking at another, again, kind of transition transfer process coordinator, looked at 81 young adults. The intervention was continuing education, transition coordination, and then the option to go to an adult transition clinic, which was a specialized clinic. These results were, again, very favorable. At 12 months, there was improved clinic attendance in adult care. The A1C actually came down by 0.4%, and global well-being was improved. Again, similar opportunity and challenge, because how do you actually systematize this and disseminate it? And then lastly, in Australia, Jane Holmes Walker is an adult endocrinologist, like myself, who does a lot of this work. So she has, they have a young adult clinic at their hospital, and they were really interested in looking at whether the young adult clinic versus kind of a non-intervened comparison cohort of Australian young adults in these registries improved outcomes. So they looked at 342 young adults in their young adult clinic versus 1,400 non-intervened comparisons. And the young adult clinic had a transition coordinator. They also had after-hour support, which was key and really was stakeholder-driven. And you can see that the median interval between visits shortened almost by half, well by half. DKA was also lowered, and there was no change in A1C, but I think these are very promising results as well. Again, opportunity and a challenge, I think. So the last piece to this is transition completion or ongoing care. So I'm selfishly going to talk about our program, because I'm here. And so I wanted to talk to you about the SEAD program, the Supporting Emerging Adults with Diabetes program that's at our Fleischer Institute at Albert Einstein College of Medicine. So I'm an adult endocrinologist. I am not a med-peds, I'm not a peds. And I think that the part that's been missing for a long time is really, how do you receive young adults into care? And how do you continue their care and make them into these adults that are very confident? So these are the components of our SEAD program model. And I'll very quickly say that we started pretty humbly. We had multi-specialty visits. We had a psychologist that would come. Sometimes we didn't have a social worker. We really kind of cobbled together what multi-specialty meant. And now with support from our institution, we've actually been able to really kind of flesh this out into not only multi-specialty visits with extra providers, but also young adult programming. We did weekly complex case reviews now, which are really amazing to be part of. And we have a patient advisory board that really helps us stay true to what their needs are. So these are preliminary SEAD outcomes from the Philadelphia program, which was kind of the first iteration of this program. And you can see that after the first six months of a convenience sample of the first 72 patients in the clinic, there's an A1C improvement of .7%. And blood glucose monitoring frequency at the time, CGM, was not as popular. Went up by one extra check per day, which to me is a measure of engagement. Our preliminary bronch seed outcomes, I was hoping that we'd have the data ready, but we didn't have the data ready in time for this talk. Our A1C, this is again, just 79 patients. We have a larger cohort of about 400 patients that we're analyzing now. A1C did not change, but the amount of A1, sorry, the proportion of patients with A1Cs over nine did go down significantly. And interestingly, visit attendance didn't change, but we were able to get more patients on diabetes technology, which I really think changed that A1C, high-risk A1C group. So for our directions, the bronch seed, we really have tailored it for equity. And we're doing this RCT right now to evaluate what the impacts of receivership. So to me, it's an opportunity. We'll see how much we can disseminate the model. But I also just wanna mention that we've added the psychologist who's not grant-funded. We've added a social needs coordinator and tech specialist who's not grant-funded. And the only grant-funded piece of this is our young adults who are our advisory board. Okay, so lastly, I just really think about future directions conceptually. So I love this figure from Terry Lippman and Colin Hawks at CHOP, where really, there needs to be a redesign of diabetes care in the way we think about this, really from the sociological model, all the way from public policy or healthcare policy down to how we deliver diabetes care. And all of these things in between really do impact outcomes. Otherwise, there's also a lot of really exciting studies coming out. So there are financial toolkits for emerging adults, virtual group appointments in young adults. There are peer support programs. There's occupational therapy. And then, of course, the big elephant in the room is what are we doing for people with type two? Okay, I think I'm running out of time. So lastly, I just wanna talk about some of the work we're doing. So we really are interested in provider factors and how they impact outcomes. We did this work, actually, in technology use and disparities in technology use. It's slightly different, but all in young adults. And we did find that a lot of provider factors, either kind of exacerbate or alleviate care outcomes and also diabetes technology use. So no shared decision making, no conversations with young adults about preferences and biases, really do potentially exacerbate disparities. So it's really something to think about. But on the other hand, optimism, tailoring of information, having the patient really understand the knowledge of benefit of these technologies really did actually improve acceptance and use. And so we're, this is unpublished data, but we're really trying to codify, again, what these provider factors are that improve young adult engagement in diabetes care. So cultural competence, communication style, expertise really do help in terms of how we manage our young adults and how they perceive their care. I'll just briefly mention here, again, this is just some work done by Molly Finnan and I, looking, again, very small cohort, but really kind of also starting to think about what are some differences and barriers to self-care based on kind of black or Latinx race, ethnicity, and how can we kind of incorporate and tailor that into our care. Okay, so I'll close out with some of our future studies. So we are currently funded by the JDRF to look at reducing diabetes distress using CBT in young adults with type 1 diabetes. This is actually actively recruiting now. It's a national study. So if anyone has young adults that might want to participate, please find me after because we are recruiting from everywhere. We also have another, I have an R01 looking at collaboration around technology using community health workers in young adults with type 1 diabetes. So again, really thinking about the sociological model and trying to kind of innovate our care and touch multiple levels. So there's many studies to come. I just briefly looked at healthcare transition in diabetes in clinicaltrials.gov, and there's actually 32 studies ongoing. So I think hopefully the next few talks we'll be able to report on that. And that is all I have. I just want to acknowledge all of the people that worked on everything with me throughout the years. So the SEED, oops, the SEED Clinical Program, Research Program, my Einstein Montefiore colleagues and mentors, my PenChop mentors, my funding. And lastly, my families. So my family, actually my biological family is on the right. But my transition family, my science family is in the pictures on the left. These are really amazing scientists who have really helped develop the field with me and kind of gave me my start. So I have them to thank for. Thank you. Thank you very much, Dr. Evermore. We'd like to entertain any questions or comments. You can come up to the microphone over here. Miller from Minnesota. Nice talk. And my main question is how you address, you'd mentioned the social and technology coordinator. How you address that emerging technology because this population is particularly savvy and approachable in that space. And what's worked and what doesn't and where do the new studies go in that respect? Yeah, thank you for your question. I know that's like a whole talk in and of itself. So we do, before COVID, when people were really coming reliably in person, we were doing social needs assessments. And so there is actually a screen in our EMR where you can ask for kind of material needs securities. And we would have kind of a conversation based on that and how that may be interfering with the person's kind of self-management. So it was really a kind of a, again, shared decision-making. And then at the same time, we'd have a conversation about technology. So I think the demos really help for patients to actually feel the things, talk it out with someone who also understands their needs a little more. So we've kind of tried to make this kind of a holistic conversation, if that helps. Yeah, I think the other question is on the provider end. How do you deal with the volume of technology and the touch points that this population needs? It's a great question. Well, so my belief is, I think providers are already so overburdened that it's really hard to ask them to do one more thing. I do think that, again, these demos really help kind of frame a conversation very quickly. Like, hey, why don't you take a look at all of these CGMs and pumps out there? We can talk more, but just know that they're out there. And we can make an appointment just to talk about that. But our R01 is really looking at other healthcare team members like community health workers who can do extra outreach, really be patient advocates in this space. So we'll see. Thank you. Thanks. All right. Okay, thank you. Thank you very much. Our next speaker is Dr. Melanie Goldfarb. Dr. Goldfarb is a professor of surgery and director of the Center for Endocrine Tumors and Disorders at the St. John's Cancer Institute and Providence St. John's Health Center. She is an associate editor of the Thyroid Journal and serves on other editorial boards. Dr. Goldfarb is a highly published health professional and Dr. Goldfarb is a highly published health services researcher with interests in health disparities, cancer survivorships, pediatric, adolescent, and young adult cancer, geriatric cancer, and secondary malignancies. Thanks so much for having me and allowing me to be part of this symposium. I have no disclosures, except as he said, I am a surgeon in the sea of endocrinologists. So I will just preface with that. Dr. Agarwal did a great job of, I actually have some of the same slides, so some things we'll be able to skip over. But I think those of us that are in this field of, you wanna call it emerging adulthood, young adulthood transition, we all kind of go back to the same roots in just a little bit of a different way. So we'll skip over some stuff. So I always like to put this at the beginning of my talks. I come at this from a cancer perspective, so thyroid cancer in particular, but also I've done a lot of stuff in the general young adult oncology field. And particularly for thyroid cancer patients, pediatric, and we call them AYA, adolescent and young adult patients, become long-term survivors with many potential life years ahead of them. So in the cancer world, I try to tell people they have a chronic disease, whereas in this room, that's what you're already dealing with, so it's much easier to conceptualize. And as I'm supposed to talk a little bit about non-cancer, I'm gonna say that many of the things we talk about also apply to our juvenile, young adult, hypo and hyperthyroidism patients, and that it's really a lifelong condition. So therefore, providing young, as I call them, survivors with a planned, gradual, seamless, and proactive transition of adult thyroid care is key for optimizing their health and quality of life. Again, same concepts you just heard, though a little bit different terminology. So just to back up, to set the stage, what's epidemiology for pediatric thyroid cancer? It's one of the most common carcinomas of the pediatric population, and at least 10% of them occur in patients less than 21 years of age. We know that they have a much higher recurrence rate, and interestingly, the incidence has had one of the greatest percentage increases over the last 40 years, and they aren't just in tiny cancers, they're in real cancers. So some charts that show all this, this is for females less than 20, and you see later in the years, really the incidence is really increasing. And again, charts from the oncology world, you see that same incidence on the charts on the right really going up as time goes on, and as you'll see on the next slide, on the left really shows the percentage of thyroid cancer within those age groups. And you get to the 20, 29, you see yellow is really actually probably the highest, and it's the second highest for the 15 to 19. And so why are we really focusing on AYAs and thyroid cancer? It's exactly that. So as of about two years ago, thyroid cancer has become the number one cancer in the adolescent and young adult age group, which the National Cancer Institute defines as ages 15 to 39. So really spans that adolescent, that emerging adulthood, as we just heard, and young adulthood. And as I mentioned, especially for differentiated thyroid cancer, but this applies for medullary and anything else, they're really survivors and patients for the rest of their lives. So even after many decades of disease-free survival, issues in survivorship include lifelong use of hormone medication for many of our patients, regular blood tests, fertility management around the time of getting and being pregnant, thinking about the possibility of cancer recurrence, as well as second malignancies. Similar, if we look at the hypo or hyperthyroidism, we still have a lot of those same issues. So hopefully I'll be able to skip over some of these slides, but in the cancer space, this is what we use. We saw this before, you have the, when you talk about transition, you have the young kids, you have the let's plan it, and then let's work on the transition space. So also, as we talk about what happens in young adulthood, we saw a bunch of this. There's independence, there's self-awareness, reduced adherence to treatment, medications, and follow-up, that's with any disease, and challenges and differences in communications with physicians, families, and peers as all those relationships shift. Some of the unique needs, a little bit specific to oncology, but again, really for everybody, disruptions in education, employment, and their social life, questions about future fertility, establishing financial independence, navigating the health system, premature confrontation with mortality for our cancer patients. Some of them have changes in physical appearance from scars, from surgery, from medications, and long-term follow-up really means long-term. Similarly, as we heard, a lot of the neuropsychological research suggests that it's really not until you get much older that your brain is really developed. And my other disclosure is I have an 18-year-old at home, so I really see all of this every day. So what are some typical AYA oncology patient concerns? Physical changes we talked about, so specifically for thyroid cancer, you may or may not have a scar on your neck. Some people can have complications with voice changes. You've started hormones. You're gonna worry about your cancer recurring and other concerns, resenting that other, your peers or your family members don't have to go through what you had to go through. You may, if you get a cancer, as I'm gonna say, a young adult as opposed to an adolescent, you kind of go back to relying on your parents and your family when you were really starting to get independent. What do you tell others when you go to school, try to date somebody, start a job? And then lastly, as we move into those even 30s, marrying and having kids. So again, as you saw, young adults, they're really just a high-risk population because they are, they have a lot going on. So for many late effects, the risk may not plateau with age. There's usually, in the cancer space, a clinically silent period and the interval to when you develop some of these late effects can be two to three decades. Many young adult survivors really wanna kind of close the door and put their cancer experience behind them and so don't wanna remember what it's like being sick and coping, so they don't wanna deal with it. And also, many studies have found that young adults are often unaware and underestimate their risks of late effects. These are young adult cancer survivors, not necessarily thyroid cancer, showing that in general, they have higher rates of all these bad behaviors, smoking, obesity, poor mental health, poor physical health, unemployment, and not seeking medical care. So what about specifically, since this is a thyroid talk for pediatric and AYA thyroid cancer survivors, just like diabetes, adolescents are particularly prone to a worsening of thyroid hormone control. Clinical or subclinical hypo or hyperthyroidism can be associated with subfertility and adverse pregnancy and offspring outcomes. And then there's the question of second malignancies, which may or may not be related to any radioactive iodine they did or didn't get. There's only been a couple studies out there that have looked at pediatric and young adult thyroid cancer survivors, so I'm just gonna highlight a couple of them. One of them looked at long-term quality of life in survivors of pediatric differentiated thyroid cancer. And the great thing was is that they showed overall quality of life was pretty normal as they got older. However, they had more physical problems, more role limitations due to physical problems, and mental fatigue than their age-matched controls. Some thyroid cancer-specific complaints, which may or may not be related to their surgery, treatment, disease, were present. And unemployment and more extensive disease or treatment characteristics were more frequently associated with a worse quality of life, which is to be expected. This was a couple studies out of Utah using, they have a very good population-based database. This one looking at age-related disease risks among thyroid cancer survivors, less than 40. So they showed that these young adult survivors had higher risk of aging-related diseases, such as hypertension, cardiomyopathy, and nutritional deficiencies. They had an increased risk for gynecological and pregnancy-related complications in young female survivors. And importantly, but I didn't present the data, things such as race, ethnicity, sex, insurance, health disparities, not surprisingly, influenced the development of these comorbidities. So staying on the line of thyroid-specific, what do our American Thyroid Association guidelines talk about for, they don't really talk about transition yet. So what do they talk about in the pediatric guidelines? What you would have to follow is dynamic risk stratification so that, again, for our young adults, as they go on, we really do wanna limit unnecessarily surveillance and treatment, but we wanna make sure that there's enough there so they get all the surveillance and intervention they need. The last guidelines talked about categorizing patients and trying to change how they get stratified. This is gonna be continued in the next set of guidelines, and we'll talk a little bit about what may be coming up in a second. So I'm just gonna move over to survivorship because in the oncology space, I kind of put survivorship and transition together. Even though they're different, you saw a very similar chart in Dr. Agarwal's. What we term as a cancer survivor actually starts with diagnosis in our space, but there's different phases of that as time goes on. So in 2002, the Children's Oncology Group established the Survivorship Transition Task Force as part of its Adolescent and Young Adult Committee, which was also brand new around that time. And then International AYA Working Group was founded under the Pediatric Oncology. So I think similar to some other things, most of the young adult programming and research has been done out of the pediatric space, and so there's a lot missing once these patients get to the adult care that I can tell you in our surgeon space, most of them have never heard of AYA Oncology, at least in the medical oncology field they have, but it's really, there's a void in knowledge. So in general, for young adult survivors, many childhood cancer survivors really decrease their amount of appropriate followship after they complete treatment, and a Childhood Cancer Survivor Survey, that's CCSS, showed that only 18% of young adult survivors report receiving adequate follow-up care related to their childhood cancer, and less than 50% reported having any cancer-related outpatient follow-ups during the previous two years. So what are some components of survivorship care? Many of this is gonna look similar, some will look different. Prevention and detection or surveillance of new cancers in recurrent care, intervention for long-term and late effects, both medical and psychosocial, coordination between specialists and primary care providers to ensure that all survivors' needs are met, and health promotion and healthy lifestyle. Other things we think about are health education, about their cancer and long-term effects, referral to specialists and resources and indicated, maybe some genetic cancer risk assessment, financial and insurance issues, and really empowering survivors to advocate for their own healthcare needs. Long-term survivorship care aims to reduce survivor and family anxiety and burden, decreased emergency room visits, healthcare costs, improved knowledge, and surveillance. So in the cancer space, we talk about survivorship care planning, which the ideal thing includes not only written treatment summaries and follow-up care plan instructions, but also an actual visit that talks about this. And many, but not all studies have shown this may reduce unmet information and service needs of survivors. It has been shown to increase both the primary care providers, the patients and the families knowledge. And like I said, the visit, in addition to the written care plan, is important. But implementing this in thyroid cancer has really lagged behind all the other cancers. Because many of you guys know thyroid cancer is usually treated in the endocrinology space, which is separate from the oncology space. Whether you have a cancer center, are you treated or not, you're just not plugged into those oncology resources. So for thyroid cancer patients, we are really behind in a lot of these things. And even more so for pediatric thyroid cancer. It is very rare, except in a few institutions, for them to be plugged into the pediatric oncology resources, of which that there kind of is a lot. But many pediatric thyroid places are not able to take advantage. So what should a transitional care visit look like? I like this quote that I found. Inadequate transition support and service providers for survival of childhood cancer has led to what some describe as a transition chasm. So key concerns and services, late effects, psychosocial functioning, health-related education, and financial challenges. We want to optimize, we talked about all this, care continuity, clinical and biological outcomes, quality of life with self-management, and improve understanding and disease. Family structure and prevental involvement are one of the key features that can both prevent as well as help combat this problem. I wanted to highlight this is a process rather than an event. As we heard earlier, we need to start early. And I don't really think this is being done. It's never too early to begin mentioning transition, depending on how old you are when you're diagnosed with cancer. And when you start 18, sometimes it's almost a little late. You should always talk about the future, so life looking beyond cancer treatment, which really should be maintained the whole time you're in therapy. And really try to cultivate some sort of medical independence appropriately through childhood and adolescent development so that they have greater participation in taking on their medical decision making. Specific transition should really start about a year to two before you plan to actually transition. And as I talk about AYA, so up till age 40, really talking about insurance coverage can be an important part of these conversation. One study I wanted to bring up, these are parents' perspectives, so not the child's, of what needs to happen. Transition needs to include seamless communication, and the survivor's medical history must be effectively communicated to the accepting provider in the adult community. So I think many people feel like that their child gets to this adult provider, and they know nothing about what happened in their whole time in PEDS. Survivors needed to demonstrate sufficient health care self-efficacy in order to have a successful transition. So the patients or the survivors need to feel a sense of responsibility, and they should have achieved some independence from their parents. So again, perspective of the parent. Survivor-focused care should include support for their overall well-being, which is psychosocial, financial, and health insurance literacy. You saw this slide already, so I'm going to jump over it. But again, it has most of the pieces that I can tell you we don't see, especially in the thyroid cancer oncology world. This is a more developed way of that. So what is transitional care from the oncology perspective? Even though I put it as part of survivorship, I do think this has broken out into its own individual thing, but it's still generally part of survivorship. So transition practices need to be flexible and individually tailored. What the optimal age is is variable. Communication is really critical. Continuity of providers is needed during transition. So many people talk about, as you heard, maybe having some overlap, like you're still seeing your pediatric when you start your first one or two visits into adulthood. And comprehensive care really includes psychosocial as well as financial insurance and education. So when I was trying, I decided I should Google what's on the internet for thyroid cancer and transition. I came up with almost nothing. I'll show you what I found. What is there? There is transition. So the endosociety has stuff, as you see, for we heard about diabetes and for a couple other endocrinology conditions. These are the assessments and skills that they put on the website for what we should talk about. So provider assessment of patient skill set, transition readiness, clinical summary and transfer records. So in the cancer space, there would be a survivorship care plan, adult care recommendations, and patient self-assessment. So I think we can probably use this template for thyroid cancer. And as I'm part of the group that's going to be writing the pediatric thyroid guidelines, so hopefully it's kosher that I'm going to put some of this stuff in here. But what's a preview of what the new guidelines may say? So transitional care should take place when the survivor is between 18 and 24, should be with either an endocrinologist or a primary care physician that will take over cancer surveillance and late effects. So I think here's where something's a little bit different. For some of these low-risk cancers, a primary care physician is probably sufficient to be following you long term. But that can be challenging if you're going from a peds endo to an adult primary care physician. So that's a lot of work needs to be done there. The pediatric team should prepare a detailed treatment summary and survivorship history, along with existing potential medical and psychosocial late effects. Again, super important if this is going to a primary care physician instead of an adult thyroid cancer endocrinologist, because they may not know all this stuff. The survivor and their new care team can then create their own new care management plan going forward and address any current supportive needs. And I think this is important. So it may be helpful if your first or second visit with a new adult endocrinologist or primary care really rework your care plan going forward so that it makes sense to you as now in the adult space. And if you are with a peds endo thyroid cancer, you should really also share this with your new primary care physician. For the younger one of those patients, consider asking the patient to sign a form so the health care team can communicate with the parent, at least for a while, when the parent is still involved. Really pay special attention to a lot of these psychosocial things, so body image, fears, coping, stressors, reproductive issues. Always ask about any concerns or questions. And encourage support in some sort of thyroid cancer support or other cancer support network. Oh, here was my Google. Sorry. I didn't find very much. So there were a couple institutions that had a paragraph on their website about, hey, maybe at some point you're gonna transition to care, but that's really it in the thyroid space. And then I found one poster that was done at the European Pediatric Endo meeting a couple years ago, but I haven't seen this in publication yet. There was also, I haven't found this in the U.S., but there was a British Thyroid Foundation that actually had a page on transition. So more than the one or two paragraphs that I found in the U.S. So in summary, and my pictures, I think, are worth a thousand words, is that pediatric and young adult thyroid patients are lifelong survivors. And patients, that's what we're really dealing with is all this whatever goes on in our young adult's brains. Transitional care should be planned, but gradual and flexible. Communication is key. A smooth transition for cancer patients includes both survivorship planning as well as transitional planning. And thyroid transitional care should be easy, but we are way behind other cancers and other diseases. So thank you very much. Thank you very much. I wonder if we have some questions. Maybe Dr. Miller has a question about this too. I do, sorry. I'm involved in our cancer survivor population and my question for you, actually twofold. One is the transition of pediatric thyroid cancer patients to primary care providers and the challenges that that might have in terms of making sure that the appropriate follow-up is obtained. And so why them versus the adult endocrine or the cancer center? What's the rationale? So maybe I should clarify. In my personal opinion, though there's zero data or anything on this, I would advocate for you should have at least one visit with an adult thyroid cancer endocrinologist. And if you are in that low risk category, then go to a primary care. With that said, as you know, many peds endos will follow their patients till they're in their early 20s. And if they really are that low risk that doesn't need much of anything, it may be more appropriate to just go to primary care because of the health system. In California, it can take six months to get an appointment with an adult endocrinologist. So I think that there's not a one size fits all, but I think it's something to think about. And then your guidelines are pretty much US focused in terms of your perspective. Yes. Because I know that transitions are a very different process in other parts of the world. And so will the ATA guidelines reflect that or are you focusing on the US perspective in that realm? That is a great point, which I'm gonna bring back to our little group. I think that, I think it's hard to really take every international thing into account. Completely agree. And so I think it's a great point and I highly doubt we're gonna be able to really talk from a lot of perspectives and maybe just mentioning that this may look different. Yeah. I mean, the nuances that I've heard as many times in other countries, you can transition kids to the adult provider at 14 or 16. And as you said, any adult provider that I know doesn't wanna see anyone under the age of 18.1. Yeah. Yeah. So yeah, I think, but I think the concepts are the same. So, and that's why I said the age is variable when the appropriate time is variable, but I think the concepts remain the same no matter at what age and how you do it. Thank you very much. My pleasure. Okay. Thanks. Thank you very much. Our next speaker is Dr. Andrew Hoffman. Dr. Hoffman is Professor and Senior Vice Chair for Academic Affairs in the Department of Medicine at Stanford University School of Medicine and Chief of Endocrinology at the VA Palo Alto Healthcare System. Thank you very much. I think you've had a terrific introduction to what the transition is and how it's being handled in different places. What I'm gonna emphasize today is growth hormone deficiency because we have some data on that, and I'll throw in some other examples of patients with other pituitary diseases which are extremely rare in children. So what is the clinical dilemma that we face? I think most pediatric endocrinologists believe that short stature caused by growth hormone deficiency and often short stature not caused by growth hormone deficiency should be treated with growth hormone. Perhaps a smaller fraction of the adult endocrine world believes that adults with severe growth hormone deficiency should also receive growth hormone treatment. So the question is what do adolescents and young adults with a history of childhood onset growth hormone deficiency, do they need growth hormone therapy as they transition to adult care or do they not need the transition at all? Are they all done? Growth hormone producing cells constitute half of all the cells in the anterior pituitary. Growth hormone goes to all the cells in the body, it causes the production of IGF-1 in most of these cells, and the two anabolic hormones have an effect on essentially every tissue in the body, including fat cells, the brain, the kidneys, and the bone. As we've heard, the adolescent brain is still developing and these are some data from some PET scans that were done about 20 years ago, and as you can see, even by the age of 20, there are still some very light-shaded areas here indicating the brain development is continuing. I should put in a plug for my colleagues at Stanford who've shown that adolescents simply can't hear their parents' voices. There's... And that is, I found that to be true in my own case. Another very important factor is that bone development continues well into our 20s, and often up until about the age of 30, and it's very important for us to do everything we can for our transitioning patients to maintain bone health and to encourage the continual accrual of bone, because after age 30, we all begin to lose calcium from our bones, and there's really nothing we can do at that point. Well, what are the clinical features of adult growth hormone deficiency? There are a variety of adverse cardiovascular risk factors. These individuals have decreased muscle strength and aerobic capacity and abnormal body composition with increased abdominal and visceral adiposity, decreased lean body mass, and decreased bone mineral density. And finally, many patients with adult GHD also have a very poor quality of life that's associated with low energy, reduced functional capacity, and social isolation. Patients who are panhypopituitary and have been replaced with gonadal, thyroid, and adrenal hormone replacement therapy have a greatly increased mortality. This is data from actually before 2000. All of them showed about a twofold increase in mortality. In those individuals who had growth hormone replacement, however, you can see the data from a number of studies show that the mortality has now gone back to one. Now, we can't prove that giving growth hormone to panhypopituitary individuals will actually improve mortality. We'll never be able to do a controlled study, but I think these data are very compelling. The goals and the management of the transition for patients with growth hormone deficiency is really to reassess whether there is a presence of growth hormone deficiency in these younger adults. If there is, we will have to modify the dose of growth hormone. We'll wanna make sure that we're giving enough hormonal therapy to achieve mature body composition, including bone and muscle mass. We have to begin to address sexual and reproductive maturation and psychosocial development. And again, as the other speakers have really emphasized, education regarding lifelong health benefits are really very important for us. Now, it turns out that about three quarters of children who have growth hormone deficiency diagnosed have idiopathic growth hormone deficiency. There's no organic cause that can be found in abnormal pituitary MRIs and no genetic cause is seen. The other quarter have a variety of causes, including craniopharyngiomas, some genetic diseases, CNS radiation, or other brain tumors. I'd like to illustrate some of the issues we have by sprinkling three case reports in the rest of the talk. So the first one is a typical 18-year-old male who's referred for short stature at age three. At birth, he was normal, had a normal full-term pregnancy, was a healthy child, but growth began to slow at about 18 months. A metabolic screen, thyroid function, cardiac and celiac testing were all normal. By age three, his growth velocity had further decreased and he was described as being pudgy and dowel-like in appearance. The IGF-1 level was very low, as was the IGF-BB3 level. And when he was given growth hormone provocative testing, the growth hormone level only increased to about 2.7, with a normal in that assay being 10. Thyroid and adrenal function were normal, a head MRI was normal, and he was diagnosed with isolated idiopathic growth hormone deficiency, a very typical child who gets treated with growth hormone. He was put on replacement therapy and grew normally, and then achieved his expected mid-parental height. Well, in general, pediatric endocrinologists will stop growth hormone therapy in such a patient once they've achieved final height, but it's important to then reconsider after you've stopped therapy for at least a month or three months, to see whether the individual still is growth hormone deficient. And patients with panhypertuitism or with genetic causes of growth hormone deficiency and a low IGF-1 level really don't need any further therapy, they should stay on growth hormone, they aren't going to become growth hormone sufficient at all. But a certain fraction of those who have idiopathic growth hormone deficiency will continue to be growth hormone deficient as an adult. And then we need to do growth hormone stimulation tests, and we'll talk about which tests should be done, and whether we should do one test or two tests, that's an insurance policy question. So about half to two, maybe 80% of patients with isolated growth hormone deficiency as children will not be growth hormone deficient on retesting. If they have an organic cause of growth hormone deficiency, again, that's a different story, they will be growth hormone deficient. Those who have an early age of growth hormone deficiency will tend to remain growth hormone. If the IGF-1 levels are very low, or if there are MRI abnormalities, even subtle ones, and certainly if they have additional pituitary hormone defects, that group will probably remain growth hormone deficient. And in fact, if you look at how many other pituitary deficiencies they have, and then look at their growth hormone responses later at the transition, you can see that those who have isolated growth hormone deficiency, and those are the ones who look at GHD zero, have a very high response to growth hormone on average, whereas those who have three deficiencies generally have a very poor response and usually remain growth hormone deficient. Now, how do we make the diagnosis? This is somewhat cumbersome. Growth hormone is secreted, as you know, in pulses. It has a very short half-life, about 10 minutes, and so you just can't do an isolated growth hormone level. Serum IGF-1, on the other hand, is a pretty good biomarker of growth hormone activity. The levels are pretty much constant throughout the day, but about a third of growth hormone deficient patients will have a normal, usually a low normal, IGF-1, because IGF-1 is also controlled by a variety of other factors. And so numerous growth hormone stimulation tests have been devised to try to make the diagnosis. And over the years, many tests have been devised and used by pediatric and adult endocrinologists. These are just a sampling of them. We now know that L-DOPA, clonidine, arginine by itself, and ferroperidostigmine are not good tests in an adult and should not be used as stimulation tests for adult growth hormone deficiency. We used to use growth hormone releasing hormone in arginine. It was an excellent stimulation test involving an infusion of arginine and then a stimulation with a subcutaneous GHRH, but GHRH is not currently available in the United States, so we can't do that anymore. And we're now left with three kinds of stimulation tests. The insulin tolerance test, which we've always considered to be the gold standard, the glucagon stimulation test, and a molecule called mesomorrelin, which is a ghrelin analog, which will powerfully stimulate growth hormone release. And each test agent has its own unique set of cutoff labels. So, again, those individuals who have three or more other pituitary hormone deficiencies do not need a stimulation test. If their IGF-1 level is low, you can go ahead and treat them with growth hormone. And in my practice, I've not had any trouble with the insurance companies without doing the stim test. But if they don't have three hormone levels, you have to do a stim test. And we'll get into those in just a minute. In the patient I just described to you, the growth hormone therapy was stopped for several months. The IGF-1 level was completely normal. The glucagon stimulation test, with the normal value of being three, was more than sufficient. And so this patient does not have adult growth hormone deficiency. We can tell him he no longer has to worry about growth hormone, and there's no reason to think that he has to worry about any other pituitary deficiency. And he can be sent on his way. And hopefully this is being done by the pediatric endocrinologist, but usually is not. So, again, those with multiple pituitary deficiencies or genetic syndromes or organic causes are more likely to remain growth hormone deficient. So this is a case of a 17-year-old man referred for transitional care. Craniofringioma was diagnosed at age five, when he was short. The tumor was completely removed by transplantable resection. Has never recurred, no radiation therapy was given. At age six, the growth hormone level was undetectable on an insulin tolerance test. He also had secondary hypothyroidism and hypoadrenalism. At age 15, testosterone was started. And growth hormone therapy was initiated at age six. He achieved a height of 168 centimeters at age 16. It is not necessary to stop growth hormone therapy in patients like this. They're panhypopituitary. They're not going to regrow their pituitary, although many patients ask if there's some organic thing you could take that will do that. And they will remain growth hormone deficient throughout life, and there's no reason to stop the therapy or to retest them. But many patients do have therapy stopped, and they stop when they've achieved the dull height, because they don't want to take daily injections of growth hormone. We will change the dose of growth hormone during the transition. And that's because our biomarkers is the IGF-1 level. And as you can see in the slide here, our IGF-1 levels peak in mid-teenage years, and then they decline quite rapidly, and they continue to decline throughout life. And we try to keep the IGF-1 level roughly in the mid-normal range with a standard deviation score of between zero and plus two. And then we monitor for clinical signs. Overdosing is very, very rare now that we start out at low, we've lowered the dose. We watch out for things like carpal tunnel syndrome and fetal edema. We expect that we will see increased lean mass and decreased fat mass. The bone density may improve. There will be an improvement in muscle strength, lower HDL, the HDL cholesterol, which had been low, will increase. And we expect improved cardiac function. I just wanted to show one example of an interesting study that showed what happened in some individuals who were growth hormone deficient and had growth hormone withdrawal. And as you can see, their left ventricular ejection fraction six months after withdrawal decreased substantially. And when growth hormone was restarted, it normalized again. Quality of life in general in these patients isn't overall diminished, but there are several parameters that are very abnormal. So self-confidence, which I think is a problem of all kids who've had childhood medical issues, is low. Physical endurance, issues concerning body shape and their body dysmorphia, and issues regarding sexual arousal were all somewhat abnormal in these kids. Anxiety also tends to increase when the growth hormone deficiency occurs, and it responds fairly well to growth hormone therapy. We expect that the signs and symptoms for starting somebody or restarting them on growth hormone may require six to nine months of therapy. The time to reach maintenance dose depends pretty much on how often you see the patient, but if you see the patient frequently enough, you can usually get a maintenance dose by three months, but it may take up to a year. You have to tell patients with adult growth hormone deficiency that their body composition will improve a bit, but their total weight may not change unless they exercise and diet. And the side effects may ultimately dictate the final dose. In addition to following IGF-1 levels, I follow hemoglobin A1c and lipid levels. One can also look at BMI and waist circumference, and bone mineral density and quality of life indices are measured as appropriate. One of the most important things, I think, for all physicians seeing patients is to continually emphasize the importance of exercise, and patients will often not be completely honest as to how much they exercise, and I think with the availability of an Apple Watch and Fitbits and other things, we can now demand proof from our patients and actually see how much exercise they're doing and can encourage them to get more steps in. When we have somebody on growth hormone therapy, there are important hormone-hormone interactions. So growth hormone increases the tissue conversion of cortisol to inactive cortisone and can unmask secondary adrenal insufficiency even later in life, and in fact, deaths from adrenal insufficiency have been seen in some of the growth hormone trials. So you have to evaluate the HPA axis, and sometimes change or start hydrocortisone therapy. Similarly, growth hormone will enhance the metabolic conversion of T4 to T3 and can unmask secondary hypothyroidism, so you have to evaluate the thyroid axis. Another important factor is that oral, but not transdermal, estrogen therapy will blunt the ability of growth hormone to increase IGF-1 levels, and often you have to give extremely high levels of growth hormone to get the IGF-1 in the normal range, and we often have to recommend that they switch to a transdermal estrogen preparation if they want to actually achieve the adequate IGF-1 levels. Other things that come up is testosterone replacement. Many of my pediatric colleagues do not give enough testosterone to some of these teenagers, and we have to give full adult doses, and we have to begin talking about gonadotropin therapy for fertility and for cosmetic effects in boys for achieving a normal testicular size. Many of these kids who are panhypopituitary don't realize that they're infertile unless they do get this therapy. Similarly for young women, gonadotropin therapy for ovulation induction. This is something that should be discussed, I think, very early on. It takes multiple discussions for people often to understand what's going on, and you want to be able to have women in their early 20s understand what their options are, and then we can talk about the issues of growth hormone therapy during pregnancy, which is not FDA-approved, and nursing, which is safe. Let me give you a last case of a patient with an intracranial irradiation. This is a 18-year-old woman who developed ALL at age seven, was treated with chemotherapy, and cranial and spinal irradiation, and was cured of her leukemia. At age nine, her IGF-1 level was low. A growth hormone level was low after stimulation testing. The TSH was undetectable, and the free T4 was borderline low, and a cortisol response during an insulin tolerance test was inadequate at 12. We made a diagnosis of growth hormone deficiency due to cranial irradiation, and she was treated with growth hormone for a number of years. Central hypothyroidism was treated with thyroid hormone, and while I thought she had evidence of ACTH deficiency, the endocrinologist did not wanna give cortisol at that point. Part of the worry was that it might blunt the effective growth hormone, but birth control pills were added at age 13. Growth was completed at age 17. We waited three months, and her IGF-1 level at that point was low. Her free T4 was normal, and we did growth hormone provocative testing just to be sure, and she had essentially zero growth hormone, and the cortisol response was even worse. So we restarted growth hormone, and we do not use weight-based dosing. We started on a dose of about 0.4 milligrams per day, and we followed the IGF-1 levels. We continued to monitor her oncologic status as we would in any such patient, and we do other things like DEXA testing. One of the questions here is whether she should have undergone provocative testing, or whether having low IGF-1 after radiation therapy was sufficient, and I think my own feeling is that we don't need to do it, but the insurance companies often disagree about that. I think she should have gotten her glucocorticoids early, and again, we usually will start dosing these young adults at about half of the childhood dosage that they were used to. Kids who have gotten cranial irradiation will have a very high incidence of growth hormone deficiency. In this, the risk of growth hormone deficiency does not end at the transition. It continues essentially for the rest of their lives, and they may also lose other pituitary hormones. So these kids, even if they, who have received cranial irradiation, need to be seen by an adult endocrinologist, I think, at least once a year for the rest of their lives. And again, we've talked about cancer survivors, and there are really an increased risk for many late effects, not only hypothalamic pituitary deficiencies, but as we've heard, diabetes, thyroid deficiencies, gonadal deficiencies, and osteoporosis. So there's still some unresolved issues. Should growth hormone therapy be interrupted in some of these kids? Most of the kids wanna stop growth hormone. It's quite understandable. Nobody wants to take a daily injection. And even if they have organic disease, and I know they're gonna require growth hormone therapy, many of them will have a break of a few years. And it's not clear whether that break really will affect the development later on, but I try to avoid that. And part of the issue is that the pediatric endocrinologist needs to tell those kids who clearly will need growth hormone therapy that they shouldn't stop. The question of who should be doing the retesting is a ball that we've been tossing back and forth between the pediatric and adult endocrinologist. We've not been successful in having a transition clinic. Even though we've not hired a MedPeds endocrinologist, it usually falls to the adult endocrinologist. But what happens when the patient declines follow-up? And this is a major issue. A lot of these kids don't want to be seen again. They are leaving home. They are tired of being sick. And just as the other issues we talked about before, their control of their endocrine disease tends to really deteriorate at this age. And now we have a new hormone therapy that has been approved for adults. We have a lung acting growth hormone. It's only taken once a week. I hope that this will improve adherence throughout the lifespan. And it may be easier to convince a young adult that taking a weekly shot isn't so bad and we can avoid that problem. So in conclusion, childhood onset GHD patients should be reassessed during the transition. About 70% of them aren't gonna need a transition. They'll be finished and you can tell them that they don't have anything more really to worry about. But persistent deficiency is associated with a whole host of other metabolic problems and these individuals need lifelong adult endocrine care. And ideally, a coordinated team approach should be used in the transition. And we've heard in the earlier two talks about some of the very creative ideas trying to do that. So I'd like to thank you all for your attention. Thank you. Do we have any questions? Fred, you've gotta ask me a question. Yeah. We'll spare you from Dr. Miller for a second here. So I'm actually a bone adult endocrinologist but I'm interested in how often do you monitor bone densities in these individuals? You mentioned lifelong kind of monitoring of some things, I believe. Well, the issue, when these kids have been treated during childhood, especially if they've been treated early on, their bone density will be fine. But if they have been off growth hormone, if they've reached their adult height at age 14 or 15 and they come to see me when they're 20 and they've been off for five years, I like to get at least a baseline at that point. And then if we put them on growth hormone, I treat them just like anybody I have on a laundromat and I get bone densities every few years as appropriate. So I wanted to follow up on his comment and ask about how easy it is to get body composition measurements in young adults from an insurance perspective by DEXA since we're able to do it at our institute till about 20 and then they disappear. Now, as an adult endocrinologist, I can send them to our research lab and get it. It's one of these things when I was in training, I was told if I only want a sodium, I shouldn't order a whole chemistry panel, I should order the sodium and the lab will run the whole chemistry panel and just report the sodium. I always thought that was kind of stupid because I'd like to see the other results and we can get that from a DEXA, they could report it to us but they don't because they don't get it in person. So I've never been able to get it. If I need it, I send them to our research lab. I wanted to make one comment. Recent literature from Wasim Shamatili and the St. Jude cohort talked about intrathecal chemotherapy as being an increased risk of growth hormone deficiency on top of radiation therapy. So there's some additional risk factors for this population. And then my last question was we still struggled to find adult endocrinologists who are interested in providing growth hormone therapy for our transition patients. And I wondered what kinds of things are being done to help with that. I've been part of some of those efforts and just wanted to get your comments. Yeah, getting adult endocrinologists to prescribe growth hormone has been difficult. In our academic center, there are only three of us who prescribe it, I think. And we have a dedicated pituitary clinic. It's very cumbersome to do the stimulation tests. So most endocrinologists don't want to do that. We have to bring them into our infusion center. And that's costly. And then having to deal with insurance companies on an annual basis is a pain in the neck. And what happens to the vast majority of my patients is that the insurance every year changes the growth hormone product that they will pay for. They don't tell anybody that. And they get a denial, and so usually there's a month or two interruption. This is something the insurance companies do on purpose, by the way, to decrease what they have to pay out. So it is a problem. I'm hoping that with the long-acting growth hormone preparations, they're not approved for adults yet, but I'm hoping by another year or so, we'll have that, that we'll have better adherence, that we try to educate the next generation of general endocrinologists to treat these patients. I'd also like to bring to your attention the Growth Hormone Research Society has just published a very, I think, important workshop on the question of growth hormone and the development of cancer later on, either primary tumors or secondary tumors, and generally showing its safety, but it's currently in press in the European Journal of Endocrinology. I have a virtual question for you. The question says, is there a role for IGF-1 in patients with childhood onset growth hormone deficiency, like idiopathic, or just go straight to growth hormone stimulation test? Well, again, the IGF-1, if the IGF-1 level is low, you're still gonna need to do, if you have just isolated growth hormone deficiency, I think you still need to do the stimulation test. Because there are other factors in nutrition, variety of other things that can affect the IGF-1 level. So I think in isolated growth hormone deficiency, I always do a stimulation test. We run into the problem of people who have been given the diagnosis of growth hormone deficiency as adults, who have just had an IGF-1 level that was slightly low when somebody put them on growth hormone, and the insurance wouldn't pay, and most of those patients are not growth hormone deficient if you test them. And I think the question is, because third of the patients who have normal IGF, can have growth hormone deficiency on normal IGF-1 level, is if you have a normal IGF-1, do you go ahead and do a growth hormone stimulation test anyways, if you're worried still about growth hormone deficiency? That data comes from all of the early studies that were done looking at growth hormone deficiency. And those studies showed that those people who had growth hormone deficiency, even with a normal IGF-1, had the same clinical response as those people who had low IGF-1s. But in almost all of the cases, the IGF-1 level is below one SDS, minus one SDS. So if the IGF-1 level's above zero SDS, I do not do any testing. Those people are not generally growth hormone deficient. Thank you. Looks like we have no more questions. So thank you very much. That was very informative. Thank you.

healthcare transition

young adults

type 1 diabetes

cancer

proactive care

seamless transition

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racial disparities

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growth hormone therapy