Pediatric Thyroid Disorders with Dr. Diana Diesen

Thyroid disease in children. It's one of those topics that most of us do not see all that often. As those who specialize in this field can attest, the standards of care are constantly changing, and that's why we thought this would be a great topic for a podcast. Today we have Doctor Diana Deason from Children's Medical Center of Dallas to give us an overview of thyroid disease in children, as well as what's new, what's current, and what we need to know. We hope you enjoyed the podcast. Stay Current is a multimedia publication designed to keep healthcare professionals up to date with standards of care and new emerging ideas. Stay Current is created and edited by Todd Ponsky, Nicholas Bruns, Ian Glenn, and Avi Schlager in partnership with Global Cat MD and is recorded and produced at Akron Children's Hospital in Akron, Ohio. Welcome to Stay Current in Pediatric Surgery. This is Todd Ponsky from Akron Children's Hospital, and today we're gonna be talking about thyroid disease in children. And with us we have Dr. Diana Deason. Dr. Deason is assistant professor and pediatric surgery fellowship program director at UT Southwestern Medical Center, and, uh, Dr. Deason, thank you for joining us today. Yeah, thank you for having me. So Diana, can you tell us a little bit about yourself, where you're coming from, and, and what kind of practice you have there? Yes, well, I was born and raised in Virginia and did my schooling at the University of Virginia for both undergrad and medical school. And then I did my surgical training at Duke before coming here to UT Southwestern Medical Center to do my pediatric surgery fellowship. After I completed my fellowship, I stayed here on staff, and I'm a pediatric surgeon with a particular interest in endocrine disorders, specifically thyroid nodules and thyroid cancer. Great. And uh today that's what we're going to talk about. And you know it's interesting, Diana, so, uh, in my practice I've been at two hospitals at Rainbow Babies in Cleveland and now here at Akron Children's and I have not done uh really much of any thyroid surgery. It's all been sort of the ENT doctors. I know it's very hospital dependent. There at UT Southwestern, is it pretty much the pediatric surgeons that manage this? So yes, here at our institution, the pediatric surgeons do the pediatric thyroid surgery and parathyroid surgery. Got it. Great. Well, let's dig right into it. Let's take a patient that comes to you. Let's say it's a 10-year-old that presents with an asymptomatic thyroid lesion that was identified by the pediatrician. And that's all they tell you that that she's here in the clinic and she's here to see you about this asymptomatic thyroid nodule. How do you approach this patient? So the first thing I would do is take a detailed history and physical, focusing on risk factors for thyroid lesions and thyroid cancer. So specifically I'd want to ask the mom and the patient whether or not they've had any symptoms of hyperthyroidism or hypothyroidism. So for hyperthyroidism we're looking for symptoms like anxiety, difficulty concentrating, palpitations, um, oily skin, oily hair. Um, for hypothyroidism, we're looking for symptoms like fatigue, increased sleepiness, difficulty concentrating, dry hair, dry skin, constipation. And so I'd ask them about those symptoms first, and then I'd ask them how long the mass has been there. Had they, now that they know it's there, was it really asymptomatic? Had they had any problems swallowing, problems speaking, changes in their voice, any compressive symptoms? Have they noticed any lumps or bumps anywhere else? So any evidence of adenopathy in the neck? And then I'd move on to the patient's personal history and his family history. So questions with their personal history. I'm specifically wondering whether or not they've had any previous thyroid problems in the past, whether or not they've had any previous malignancies. So. Some risk factors for developing thyroid nodules and thyroid cancer are previous exposures to radiation or alkalating agents. So if they've been treated for Hodgkin's lymphoma or leukemia or CNS tumors, that puts them at increased risk. So I'd want to know any history of that. And then any family history. So we know that some thyroid conditions and thyroid cancers have a familial predisposition. So the most obvious ones that everybody thinks of is the MEN syndromes, but there are others, including the P10 hamartoma tumor syndromes and the APC associated polyposis syndromes that also have an increased risk of thyroid disorders. After I'd have that discussion with the family, that'd give me a general idea of whether or not this patient is in a higher risk category or not, and then I proceed with the physical exam. Things that I'm looking for is where exactly is this nodule. Uh, for one thing, is it in the thyroid? Uh, but then, assuming that it is in the thyroid, is it fixed? Is it mobile? Uh, does it move when they swallow? Or is there any other adenopathy, uh, present? Um, when I have the patients speak, do they have any voice changes or any hoarseness that I might appreciate? So those are the things that I'm looking for initially. And do you, I know this is basic, but do you stand behind them and have them drink water, or how do you examine it? And so it depends on the size of the child. I'll examine them either sitting upright, and I usually examine them in multiple different positions. Obviously from for an infant it's a little bit different than a 10-year-old who's cooperative, but I'll examine them from the front and from either the side or posteriorly, make sure that I can actually feel their thyroid gland and feel the nodule itself, and that can sometimes Involve moving the sternocleidomastoid slightly to the right or to the left depending on the size of the nodule because you need to get right under that muscle to see whether or not you can feel that nodule. Interesting. OK, what exactly, so you said hoarseness you're looking for, is it the size of the nodule and whether it's fixed? What, what kind of findings would make you concerned that this was a malignancy? Um, the most concerning things are a large nodule that's fixed, that would be, or any associated adenopathy. Oftentimes, um, while thyroid nodules are less common in children than adults, when they're detected, they're more likely to be malignant. And so when children actually do present with a thyroid cancer, they're more likely to have an extension outside of the thyroid. They're more likely to have regional lymph node involvement. And distant metastasis. So I, I keep that in mind anytime I'm seeing a child with a thyroid nodule. That's a great summary there. You took your history. You found out if there was any factors that may have predisposed the child to a malignancy, and you've done your exam now. What? So the next thing I want to do is get some thyroid function tests, specifically TSH. Because I want to see whether or not they have they're e thyroid or they're having normal thyroid function versus uh, evidence of hyperthyroidism or hypothyroidism with a nodule specifically that becomes relevant because I'm looking for any evidence of what used to be referred to as a toxic adenoma or a hyperfunctioning nodule. Um, if I notice that the TSH is suppressed, then my, my first imaging modality is going to be a little bit different. I'm going to look for a Nuclear thyroid scan in order to see whether or not they have a hyperfunctioning nodule because that patient is handled a little bit differently than those who are not TSH suppressed. So if you, you do your exam and you send off your TSH, your thyroid stimulating hormone, and if it is low, it implies that there's a lot of functioning thyroid hormone. Uh, so it might be hyperfunctioning and so you then go ahead and get a radioactive, uh, radio, what is it, a radioactive iodine scan or what is it that you get a nuclear thyroid scentography is how that helps you identify whether or not it is a hot or cold nodule, correct? And if they have a hot nodule, a hyperfunctioning nodule, then the current recommendations are that that nodule does not need to be biopsied if it's going to be resected. And in general, a hyperfunctioning nodule that's symptomatic would, we would recommend resection. Got it. So that's it. So you do, you have a low TSH, you get a positive nuclear thyroid scan, and you get that. And if that shows it's a hot nodule, your plan is for a, is it a lobectomy? Yes, got it. OK. And you can usually pretty well tell that they don't have other hot nodules when you do that scan. That scan will tell you if there's another nodule that's hot. Now there are some instances when the in which the patient is not clinically hyperthyroid. In which you may follow those, that's allowed in the ATA recommendations, the American Thyroid Association recommendations. If the patient is asymptomatic and one chooses to not resect it, then an FNA, an ultrasound will be necessary to prove that there are no suspicious features. Got it. OK. All right, so let's say that your TSH level was normal. OK, and that's what I usually see, right? OK, so usually the TSH is normal and then we proceed to ultrasound with FNA under ultrasound guidance. So we'll get an ultrasound of the thyroid looking at the entire thyroid. So that nodule, we want to see the characteristics of that, that nodule to see if there's anything particularly suspicious or concerning. We want to see the rest of the thyroid to see if there are any other uh thyroid nodules, and then any time that we have a patient that has a thyroid nodule, we're always going to do an ultrasound of their lymph nodes as well. So we want to see whether or not there's any suspicious lymph nodes in the area and so um. Some things on ultrasound that would make us suspicious would be a hypoechoic mass, irregular margins, increased blood flow, microcalcifications, or if we have a mass that's that's associated with abnormal lymph nodes as well, that increases our suspicion for a thyroid cancer. OK. Do you ever see cystic lesions? Yes, so patients can have cystic lesions, a mix of cyst or cystic and solid lesions, or solid lesions themselves. And so thyroid cysts, if small, are observed, if large, can be either aspirated or or resected. Oftentimes you can attempt aspiration if it's completely. Completely cystic without any evidence of solid components and then follow it to see if it has any evidence of recurrence. If it has any solid component that needs to be biopsied. OK, let's say the ultrasound shows a 5 millimeter. What, what is it usually? What's the usual size? Less than a centimeter. No. So that's actually a great, great source of discussion. Usually if it's clinically apparent then it's going to be at least 123 centimeters, so the small lesions aren't usually detected on physical exam. The criteria for FNA biopsy for the adults is that you don't biopsy a lesion that's less than 1 centimeter. For the pediatric population, we can't use size cutoffs as they do in adults. And so we use ultrasound characteristics in the clinical context to decide whether or not something should be biopsied and warrant FNA. And so if we have concerning features and the right clinical setting, then we're going to want to get a biopsy. OK. You do your ultrasound and you have a, let's say a 1.5 centimeter solid nodule in the right thyroid lobe. You're going to do an FNA. Yes, with ultrasound guidance, with ultrasound guidance, and is this usually done? I mean, do the kids usually tolerate this? Is it done just under local or? Do you do this under general anesthesia? What we do is we work with our radiology and our anesthesia colleagues to do this in as controlled a setting as possible. It depends on the child and their age. Obviously small children will not allow you to stick a needle in their neck to do FNAs without resistance, and we want to make sure that we're getting as good a sample. as possible depending on the age and the child, we use local anesthesia, mask anesthesia, or general anesthesia. All right, your FNA comes back as papillary thyroid cancer. So what I would also want to do is make sure that while we're getting that ultrasound and the FNA biopsy of that lesion, that we would have biopsied any suspicious lymph nodes as well. I mention that now because if there's no suspicious lymph nodes, that's fine you don't need to biopsy them. If there's any node that is marginal or questionable from this story, we don't have any clinical clinically positive nodes. I want to make sure that we've assessed the lymph node status. So if there are any lymph nodes, I want to make sure that we do. A FNA under ultrasound guidance then as well. And is that usually that means that they're like over 1 centimeter, is that what makes them suspicious? It's not necessarily just size. So 1 centimeter is often used with adults, but with kids we don't necessarily use 1 centimeter as a cutoff. We use the characteristics on ultrasound. So A loss of the hilums, irregularity, increased blood flow if the lymph node itself has concerning characteristics, not just size. OK, let's say the lymph node biopsy was normal and the thyroid came back as papillary, so So if it's papillary thyroid cancer, then our, our treatment for that is going to be a total or near total thyroidectomy. One thing I did want to mention, if the patients have large, large mass that's fixed with bulky metastatic lymphadenopathy to their neck, Uh, oftentimes we will then also do a CT or MRI of the neck to make sure that we can have full visualization of, um, of all the lymph nodes, including retropharyngeal or superior mediastinal to make sure that we don't miss any lymph node involvement. Um, because all of that will need to be resected in order for them to have a good response. And then if they have a large burden of cervical lymphadenopathy, we also consider whether or not to get a chest CT again to make sure that we have a full understanding of their extent of disease. Now CT is not necessary for most patients. These are patients with bulky, bulky disease at presentation. OK, Mom says, wait a second, Dr. Deason, you can't you just take out that lobe? Yes, and so in years past there had been more of a debate on lobectomy versus or partial thyroidectomy versus total or near total thyroidectomy, total or near total thyroidectomy, so near total being that you leave only 1 to 2% of the tissue just near critical structures like the recurrent nerve or the parathyroid. the current recommendations for patients with papillary thyroid cancer because of the risk of bilateral disease, which is seen in up to 30% of patients, multifocal disease, which is seen in up to 65% of pediatric patients. There's also an increased risk with just doing a lobectomy, knowing that you have a papillary thyroid cancer. There's an increased risk of recurrence or risk for secondary surgery. And once you have the entire thyroid out, you are able to optimize the patient for radioactive iodine if they were to need it. Now, based on the description that you gave me 1.5 centimeters, nothing else suspicious, that patient probably wouldn't need radioactive iodine. And but it also allows you to use thyroglobulin as a marker of persistent or recurrent disease, so you don't have to make sure that you destroy all of the little bit of thyroid that you left after the operation. Well, so it depends on what stage they are, on whether or not they need radioactive iodine based on their TMN staging and their ATA pediatric risk level. There are recommendations for radioactive iodine in select patients, so intermediate and high risk. OK, talk me through how do you do your thyroidectomy. So it's a papillary, so you're going to do a total thyroidectomy. Give us some tips and tricks on how you do it. So some tips and tricks. So in pediatric patients, you have to adjust your operation to their size. So the general recommendations for adults is that you use 1 to 2 finger breadths above the sternal notch. Now that may not be applicable if you're operating on a 4 year old. You make an incision above the sternal notch below the thyroid cartilage, and you make the incision. It's usually somewhere between 3 and 4 centimeters on the inferior aspect of the neck through the skin and the platysma, splitting the strap muscles, and then I turn my attention first to the affected side. I will elevate the strap muscles, ligate the middle thyroid vein, rotate the thyroid medially. And then take the superior pole vessels. I'll then identify the recurrent laryngeal nerve and the parathyroid glands on that side. I do routinely use a nerve monitor in my practice, knowing that it will not decrease my risk of nerve injury, but I do find it helpful in identifying the nerve, especially in patients with bulky cervical disease. And then after I've identified the parathyroids and the recurrent laryngeal nerve, then I will take the inferior pole vessels, rotate the thyroid medially off of the trachea, taking the ligament of Barry. I'll then proceed to the unaffected side and do the same thing, removing the thyroid in total and marking the specimen. Great. And while you're in there, do you go looking for nodes? I usually find that the ultrasounds are very sensitive. I have not come across a patient yet where I came across nodes that I was not previously expecting. Now, if a patient has clinically apparent nodes on exam or and or they have pathology that Confirmed that they have disease to their nodes, then we proceed with a nodal dissection, so we don't individually pick nodes or berry pick the nodes. We'll do a compartment dissection that either involves the central neck and or the lateral neck if the lateral neck is involved. Got it. So if they found what looked like a concerning node on ultrasound, they did an FNA and it came back as positive for papillary carcinoma, let's say that was a central node. Then you would do just a central node dissection. Correct. There's no evidence to do a prophylactic lateral neck dissection, so I would proceed with a central node dissection, but I will have made sure that on ultrasound that I've evaluated the lateral node sufficiently. And if it was, there's nothing suspicious, OK. And let's say it was a lateral node on the side of the affected lobe. So if it's a lateral node, then I will do a central neck dissection as well as a lateral on the affected side. Got it. OK. Before we move on to the next diagnosis, tell me how you manage them postoperatively. So postoperatively, if I'm just removing half of the thyroid, then those patients can go home the same day. Follow up in clinic, we'll review their pathology. Obviously those are patients that I don't think have papillary thyroid cancer. For the total thyroidectomies, I tend to keep them in the hospital overnight to monitor, monitor for any complications nausea, vomiting, pain. Or any evidence of bleeding, I will also in recovery get a PTH in order to check their PTH level and their calcium level. If their PTH level is low post-op, then that, especially if it's less than 10 to 15, then I already know that they're going to be at higher risk for hypocalcemia. And so I will go ahead and start calcium replacement or calcitriol depending on the levels. Do you check ionized calciums or just calcium levels throughout the night? It depends on their levels. So if I do a total thyroidectomy and I identify the parathyroid glands and I'm able to preserve them and they have a mild hypocalcemia and recovery, then I won't necessarily check frequent calciums. If, on the other hand, I was removing a thyroid. I did an extensive neck dissection and I knew I had to auto transplant the parathyroids into the sternocleidomastoid. Those aren't going to work right away, so I will start those patients on calcium supplement as well as calcitriol, and then I'll measure their calcium level postoperatively, and then depending on how low it is, I may check it once again in the morning or I may check it every 6 hours if it's particularly low. Got it. All right, so the PTH was normal. They did great. They went home. What now? I see them in my clinic and follow up, and then I figure out what stage they are. So the patient that you had described previously, 1.5 centimeter mass. The question on pathology, is it limited to the thyroid? Is there any evidence of extrathyroidal extension? It doesn't sound like it by description. So a 1.5 centimeter mass would put me at a T1B. And if there's no evidence of regional nodes, that would give me an N zero status, so that would put me at a low risk. So disease confined to the thyroid. With no metastatic lymph nodes, that patient just needs to be postoperatively staged with just thyroglobulin levels with the goal of keeping the TSH at 0.5 to 1 and then doing surveillance initially every six months or an ultrasound at six months postoperatively and then annually for five years and then measuring thyroglobulin levels. So that's the lowest risk thyroid cancer patients. So you use for staging the. TNM staging, correct? OK. Who would qualify then for radioactive iodine postoperatively? So the patients that often will get the radioactive iodine are either the ATA pediatric risk level intermediate or high, and so that means they had extensive nodal disease, either extensive central neck disease or any sort of lateral neck disease, and that puts them at the intermediate risk. A high risk patient would be, uh, extensive regional disease, so, um, the lateral neck or local invasion of the tumor itself, uh, with or without distant metastatic disease. And so those patients postoperatively will have thyroglobulin levels monitored, and then they'll get a diagnostic I-131 or I-123 to see whether or not they have evidence of disease or uptake. Anywhere else in their body or in their thyroid bed. OK. The patient who has, let's say the one that we talked about that was low risk, you start Synthroid the day of surgery, and that's pretty much all they do. Synthroid the next day, and then we have to monitor their TSH levels to keep them in goal, goal range. OK, got it. Let's go backwards now. So now when you saw the child in your office, you did the FNA for this. 1.5 centimeter nodule and it came back follicular. That's a common pathologic diagnosis that we see probably in about a third of our patients. And so follicular is really an indeterminate specimen. Our options on the thyroid pathology that we can get from FNA are either that it's a non-diagnostic, it's benign, it's indeterminate, or it's malignant. And so in the indeterminate group is this follicular group. And within follicular there are 3 subtypes, and there's a follicular lesion of undetermined significance. There's the follicular lesion concerning for neoplasm, and then there's the suspicious or suggestive of a malignancy with a follicular component. And so previously in pediatric patients, the thought had been that some of these you could watch and others that you needed to take out. The most recent recommendations from the ATA are that all of these indeterminate lesions be resected. And the reason that they have recommended that, which is different than the recommendations for adults, so the reason that children are recommended to have resection for their indeterminate lesions is their risk of malignancy is higher than adults. So for follicular lesions of undetermined significance, the risk of malignancy is somewhere between 5 and 15%. In the pediatric literature, literature, it seems to be about 28%. And for follicular lesions that are follicular neoplasms. The reported malignancy rate was 15 to 30%, but more recent data suggests that it's somewhere between 50% and 60%. So considering the risk of malignancy in the pediatric population, the most recent recommendations are that these lesions be resected. Now some of these patients are going to have cancer, but some of them are not. So the recommendation currently is to take them to the operating room, obviously do the preoperative staging that we talked about before, ultrasound, looking at their lymph nodes, but if there's no suspicious lymph nodes, to do a lobectomy and removal of the isthmus and then send it for final pathology. Can you determine on frozen section if something is malignant or not? So on frozen section, we can't determine whether or not a follicular cancer exists. We can see perhaps on frozen section whether or not there's a papillary component. So if there's a papillary component, they can see that on Frozen, and so that can be helpful partly because papillary tends to spread to the lymph nodes while follicular does not. So for example, if you have a patient in which you have an FNA that's diagnostic of follicular, but you have suspicious looking lymph nodes, you may be thinking that it's a papillary variant. And so a frozen section may be helpful for you in that situation, but a frozen section will not be able to tell you a follicular adenoma from a follicular carcinoma. OK, so if the frozen section does show that it's a papillary variant, Do you then go ahead and do a total thyroidectomy? You treat it like a papillary thyroid cancer. Great. Let's say you take out the lobe and the final pathology comes back as a follicular malignancy. So then I have more questions for the pathologist. So I, I want to know whether or not, um, how much vascular invasion there is. And then it'll also depend on how big the tumor is. So if there is evidence of significant vascular invasion or the tumor is greater than 4 centimeters, then the current recommendations are for completion thyroidectomy. If there is minimal vascular invasion and a smaller tumor, then that patient can be monitored. Interesting, even if it's a follicular carcinoma, correct? OK. Now if it came back as follicular adenoma, then what? Then surgically we're done, so we don't need to do any further treatment for that patient. They don't need any more surveillance. They will need to be followed though. To monitor their thyroid function. So even though you take out half of the thyroid, the remaining thyroid should be sufficient to produce enough thyroid hormone. About 30% of patients at some point may develop hypothyroidism. So it's important for patients that even if they've undergone just a lobectomy, that their thyroid function is monitored. A postoperatively, do you ever put them on Synthroid for thyroid suppression? So we do the thyroid suppression in the patients that have papillary thyroid cancer. So we adjust their TSH levels depending on their ATA pediatric risk level. So, um, the goals are different if they're, um, higher risk versus lower risk. For example, the, uh, low risk patients, our TSH goal is 0.5 to 1, and for our high risk patients, our TSH goal is less than 0.1. Um, but we don't do that for patients who have follicular adenomas, for example, OK. And just to clarify, you keep mentioning ATA. Is that the American Thyroid Association, correct? And they put out guidelines every 5 years or so. For adults with differentiated thyroid cancer, medullary thyroid cancer, and just recently have put out recommendations last year on pediatric thyroid cancer. OK. Let's go back to that child again who presented to you and their FNA says benign. Oh good. And so for benign lesions, it's important to take into consideration other clinical characteristics. For example, size, compressive symptoms, cosmesis, family choice. Those may all be reasons to still proceed with surgery. Um, so for example, I have a patient who presented with a 7 centimeter thyroid mass. Even though it's benign on FNA, it's obviously causing some cosmetic issues and it's causing significant discomfort. So that one I will resect. Also, you need to be cautious that in masses that are greater than 4 centimeters, the sensitivity and specificity of FNA is somewhat decreased, and so it's still important to follow lesions if they are benign. The recommendations are now that you get a repeat ultrasound in 6 to 12 months with repeat biopsy if the mass is enlarging or if it's developed suspicious features. OK. 01 more thing on that patient. If even if a lesion comes back benign, the other thing that's important to consider is the patient's characteristics. So high risk patients, so patients that have had exposure to radioactive iodine or who Uh, I'm sorry, who have had exposure to radiation or alkylaating agents or have a family history of thyroid cancer, you may choose to be more aggressive in those patients. OK, that's a good point. I mean, the FNA is good, but it's not 100%, so, OK. What if they told you you had an inadequate specimen? Uh, so, an inadequate specimen occurs in roughly 1 to 3% of the time. And so, um, uh, again, you have to take into consideration the, the clinical scenario in which the patient presents. Um, but usually what you'll do is a repeat ultrasound with FNA in 3 to 6 months. You don't want to do it right away because you may pick up some atypia on a subsequent FNA specimen that may just be the result of the trauma from your initial FNA. So usually you'll wait about 3 to 6 months to do a repeat ultrasound with the FNA. If the nodule is stable and or benign, um, then you'd repeat an ultrasound 6 to 12 months from there. OK, let's say you did the FNA and it came back as medullary. Yes, so if it comes back as medullary, we have to go back again and make sure that we didn't miss anything on our initial history and physical. The question is whether or not there is any family history, and it's important when you're taking a family history on a patient with a thyroid disease, they may or may not know terms like MEN. And so I'll often ask, does anybody in the family have calcium problems? Does anybody in the family ever have belly tumors? Trying to get at, has anybody in the family had PO's or has anybody in the family had hyperparathyroidism. If there's no evidence of that, then the concern is that the patient likely has a new RT mutation. And so, If it comes back medullary, we need to make sure that we have a full ultrasound of the neck. Those patients are much more likely to present with a more extensive disease at the time of diagnosis, and we're going to want to measure the calcitonin levels and CEA levels. The recommendations for adults is that you may or may not routinely measure calcitonin levels in every patient. Has a thyroid nodule. Sporadic medullary thyroid cancer is unusual in children, so the current recommendations are not to do routine calcitonin monitoring in every patient that presents with a thyroid nodule. But when the FNA comes back as medullary, it's very important to give you an idea of the extent of disease, and it'll be important for tracking the patient's response to surgery. We also will then send off a RET germline mutation study to see what kind of mutation they have. At the same time, if they're RET positive, then our concerns are looking for other associated conditions such as a PO or hyperparathyroidism, and it depends on what kind of mutation they have. So, if they have IN2B, that would be a 918 mutation, they're at higher risk for, uh, PEIOS, up to 50% of those patients. And they're at risk of developing PHIOS in their teenage years. And so, uh, screening would usually begin at age. 11 or at the time of initial diagnosis for MN2A patients, POs don't tend to present until later, but usually we'll screen initially when they present for POS as well as hyperparathyroidism. The other thing that's important for a patient that has a medullary thyroid cancer. So before proceeding to the OR, in addition to the ultrasound of the neck, the calcitonin, and the CEA levels, they may need further imaging, depending on what their calcitonin level is at their initial presentation. So if their calcitonin level initially is greater than 500, then we proceed with imaging to exclude metastatic disease. And so that includes CT of the neck, CT of the chest, MRI or CT of the abdomen, looking at the liver. And then plus or minus a bone scan to look for any evidence of regional regional metastatic disease. OK, can you give us a brief review course here on the multiple endocrineoplasia types and how they usually present? A brief review. You have MEN 2A and 2B. And so for MEN 2A, those patients often will have, um, if left untreated, medullary thyroid cancer, POs, and hyperparathyroidism. And then you have MEN2B patients that can develop medullary thyroid cancer, POs as well, mucosal neuromas, and then a Marfan's type habitus where where they'll have this elongated features and laxity of their joints. So MEN2B, those patients often will have the, um, the 918 mutation, the RET 918 mutation. And they tend to present with thyroid cancer very early on. So this is an infancy. So the recommendations are if you have a family in which you know you have MEN 2B, then it's important that they get genetically screened right after birth to see if their children have MEN 2B. If they do and they have the 918 mutation, then their recommendation is for a thyroidectomy before one year of age. There are reported cases of having medullary thyroid cancer as young as 3 months in the MEN2B group. Is it fair to say, Diana, that most of the MEN2B patients that you see, you see, because they have the family history and they were screened and they were found to have a mutation, so that is some, but then you also have some patients who have spontaneous, they are the de novo mutation. And so for example I have a patient who's 12 years old who presented with a large thyroid mass and extensive cervical adenopathy, and she came back as MEN2B. So if you have the de novo mutation, it's more likely to be MEN2B than A. Got it. Well, tell me how the MEN2A patients usually present. Is it with a PO? The MEN2A patients that I see in the pediatric population have usually been referred to me because their family knows they have MEN and they were detected early. And so when it comes to MEN2A patients, it's important to look at which mutation they have specifically because there are quite a few. And their risk of developing thyroid cancer at certain ages has been studied and looked at based on the individual codons, and so they are broken up into high risk and moderate risk depending on which re mutation they have. And then the recommendations for treating those patients are based on their mutation. So, for example, an MEN2A patient that's at high risk, the most common being the 634 mutation, they should have a total thyroidectomy before the age of 5, but their surveillance should start at age 3 and include calcitonin, CEA, and ultrasounds. And if there's any elevation in their calcitonin levels or any abnormalities on their ultrasound, they should proceed with thyroidectomy at that point. If their calcitonin levels get above 40, when you're first starting to surveil them, then they, uh, it's also recommended that they have a central neck dissection at the time. Now this is particularly challenging, as you can imagine, a 345 year old is smaller, as, and their parathyroid glands are smaller, and so their risk of, uh, complications from surgery, including hypoparathyroidism or nerve injury, are increased. Children under the age of 10, that is why we don't prophylactically do thyroidectomies on all children at the youngest age. So for patients with MEN2A that are at moderate risk, the recommendation is that a total thyroidectomy be performed when the serum calcitonin level becomes elevated or if the parents don't want to proceed with the frequent surveillance that is necessary, so ultrasounds and calcitonin monitoring. And so depending on their particular mutation, they may have their prophylactic thyroidectomy performed sometime in childhood or early adulthood. Now wait a second, so these MEN2A patients also have pheochromocytoma and they also will have parathyroid hyperplasia. Well they can, yes, right? So what, what about that? What do you do with those problems? It depends on their mutation. There are certain mutations that are known to be more associated with POS or hyperparathyroidism. So for the MEN 2A and the moderate risk, those patients don't tend to develop POs until they're in their twenties or above. And so the recommendation is to begin screening those patients at age 16. And the MEN2A high risk patients, PO screening begins at 11 years of age. OK. And for the, the parathyroid hyperplasia, when does that usually present? That also begins in their, uh, that also begins in their teen years. I don't remember the exact number. That's OK. So usually when these patients present to you, that's not a concern at the time we're really focusing on the thyroid. Correct. Got it. When you do your thyroidectomy for medullary carcinoma or prophylactically. I guess it depends if it's prophylactic or not whether or not you do a central node dissection. Um, so, so central node dissections for medullary thyroid cancer depend on a few things. One, if they have known medullary thyroid cancer to begin with, and two, what their calcitonin levels are. So when you do a prophylactic thyroidectomy for a patient with known MEN syndrome, your plan is to do the thyroidectomy before they have any abnormalities on ultrasound or elevated calcitonin levels. If you are able, for example, in MEN2A patients to perform the thyroidectomy before their calcitonin levels are above 40, then a central lymph node dissection is not necessary. There is debate in the literature on whether or not MEN 2B patients need to have a central lymph node dissection. And it's dependent on your ability to appropriately identify and preserve and or transplant the parathyroid glands. The parathyroid glands in an infant can be quite small. They're small in adults and they're quite small in infants and relatively translucent. You're increasing your risk of hypoparathyroidism by adding the central neck dissection to the total thyroidectomy. OK, now with medullary carcinoma. Is the postoperative management different? Do you do radioactive iodine? Do you get chemotherapy or radiation? Chemotherapy? No, not usually. And radiation, there's some debate in the literature. So after you've done a thyroidectomy plus or minus lymph node dissection that comes back with medullary thyroid cancer, it's important to see them in clinic. And measure their calcitonin levels. So if their calcitonin levels are undetectable or within the normal range, then you're going to proceed with a physical exam, routine ultrasounds of their neck every 6 months for a year, and then annually, and then monitor them closely. If their calcitonin levels are greater than 150, then you do some imaging procedures to detect metastasis. So, the things that you're going to need to do in order to detect for metastatic disease is, um, a CT scan of the neck, CT scan of the chest, Either an MRI or a CT of the abdomen looking for liver metastasis, and then a bone scan looking for any evidence of disease in the bone, and that includes a bone scan itself and an MRI of the pelvis and axial skeleton. And so you're looking for regional disease and you're looking for local disease. If your imaging is negative, then you're just going to follow their calcitonin levels with physical exam and repeat ultrasounds. And then you're going to look for a trend. If your imaging is positive, then it depends where it's positive on what you need to do next. If it's, say, positive in the neck, you did a total thyroidectomy, um, but you didn't do a lateral neck and it lights up in the neck, then that patient would benefit from a repeated surgery. If they have disease elsewhere. Um, then you need to discuss with your oncologist and endocrinologist and the patients whether or not they may benefit from systemic therapy. And so systemic therapy can include a tyrosine kinase inhibitor and then sometimes external beam radiation, but both of those have significant side effects. And so those. Always done for patients just because they have elevated calcitonin levels. Those are usually reserved for patients with progressive disease that is not treatable with surgery. It's interesting. I mean, medullary is pretty complicated. It's a lot of factors that go into the treatment. Let's just quickly touch on patients with Graves' disease, surgery versus medical treatment. Yeah, so Graves' disease, I usually get those referrals from the endocrinologist, so they have seen a patient with Graves' disease. They've been managing them. And they've tried them on methimazole, and they're still having persistent symptoms of hyperparathyroidism in children. We have the discussion of radioactive iodine versus surgery. So for younger children in particular, the concern is the risks of radioactive iodine, risks of secondary malignancies, for example. And so often in young children we will perform a thyroidectomy for Graves' disease that is not controlled with medical therapy. In school-age children, we have a discussion with the family and the endocrinologist on the risk of radioactive. Iodine versus surgery as patients approach adulthood, often radioactive iodine therapy is the treatment of choice. And what about patients that present to you with a painful thyroid? So I must say again, I don't see very many of those patients. Those tend to present more commonly to our endocrinologists. And when I'm, when I hear painful thyroid, the first thing that I'm thinking of As thyroiditis. The ones that are painful tend to be the subacute thyroiditis, and it's thought that those are often from a viral cause. They will have a painful swollen thyroid and initially have a thyrotoxicosis or elevation in their thyroid function, initially followed by some hypoparathyroidism or hypothyroidism. Um, but those are, those usually resolve, um, and, um, patients recover well. Uh, normal thyroid function usually at 1 to 2 years. Now the one patient though that, that we haven't talked about that I think is important. That's pediatric specific. So there are some patients with papillary thyroid cancer that have instead of a discrete nodule, a diffuse infiltration of their thyroid, and that is a characteristic of papillary thyroid cancer that's more common in children. And so if you have a patient and they demonstrate an infiltrative process in their thyroid, In children, you have to think in the back of your head papillary thyroid cancer, especially if they have clinically suspicious nodes as well. And so consider a biopsy to make sure that you don't miss a papillary thyroid cancer, OK? And in that case there's really no particular place to biopsy since it's diffuse. You just get an FNA of the thyroid, where, OK, yeah, and any nodes as well. OK, Diana, I want to tell you I know very little about this since I don't do much of it, and you have given me a very clear, concise. Summary of thyroid disease. I'm, I'm impressed. This is, uh, in a short period of time, you, you've, you've given us a lot of information. I, I really appreciate you taking the time to go over this with us. I do want to tell the listeners that on the app, you will be able to listen to the podcast and choose whichever part you want to listen to. And also be able to read and just fast forward just to the parts you're looking for. Diana, I don't know if you have any videos, but we'll look online and see if we can find some videos to associate with this as well. I really appreciate you uh taking the time to do this. This was fantastic. My pleasure. I appreciate it. Also, we want to invite people to have questions and we'll ask Dr. Deason to check out on the app if anyone has any comments or questions so we can get those answered as well. So thank you very much and uh we'll be talking to you soon. Thank you very much. Thank you. We hope you enjoyed this episode of Stay Current in Pediatric Surgery. You can listen, watch, or read all content by downloading the Stay Current and Surgery app. Please send questions or comments to us attacurrent podcast@gmail.com. We'll see you next time.