In this webinar, Dr. Jasim provides an overview of hyperthyroidism, including its common causes, clinical presentation, and diagnostic evaluation. She reviews key considerations for assessing patients with hyperthyroidism and discusses available treatment and intervention options, highlighting approaches to individualized patient management and care.
So, welcome back everybody. Our next speaker is Doctor is it Tina? Tina. Yeah, is it Jackson? Mhm. She received her medical degree at University of Baghdad College of Medicine in Baghdad, Iraq. Then she completed her MPH in epidemiology, and did her residency in internal medicine at WSU. She then went to MD Anderson Cancer Center in Houston, Texas, to complete her postdoctoral fellowship in cancer genetics, and then to Mayo Clinic in Rochester, Minnesota, to complete her fellowship in endocrinology, diabetes, and metabolism. She came back to Saint Louis where she is currently an associate professor of medicine with the Department of Endocrinology, Metabolism, and Lipid Research. Doctor Jassam sees patients at the Sigman Cancer Center and specializes in thyroid nodules. Thyroid cancer, adrenal tumors, endocrine tumors, and minimally invasive thyroid nodule treatment. So thank you so much for your time, and if I missed anything on your bio, feel free to fill that in as well. Thank you, Nicole. Hi, everyone. I'm Doctor Sina Jess. I'm an endocrinologist with a thyroid focus in uh WashU Department of Medicine Division of Endocrinology. So we're gonna talk today about management options in hyperthyroidism, which is something that we see, uh, commonly in clinical practice. Uh, I have no disclosures related to that talk, and these are my objective is basically to look into causes of hyperthyroidism, describe the, the evaluation of the disease and some of the treatment options that's available, and we will focus a bit on the long-term data on, uh, thyroid medications and uh review some of the recent data on some of the additional treatment options that we can provide. And so I can start with a case of 55 year old female with subclinical hyperthyroidism, and it's uh a eosinophilic esophagitis, who was actually referred to our clinic for evaluation of thyroid nodules, and she's been following with local endocrinology for about. 5 years before she came here for a second opinion and was told that she has toxic multinodular goiter and was diagnosed also with Graves' disease and so recommended therapy. So she was initially planning to pursue radioactive iodine. Uh, but she was confused about the, the nodules and the Graves' disease, and she read about radiofrequency ablation that we offer here at WSU in my clinic. So she came for a second opinion to explore all these options. And as you can see here, her thyroid nodule, this is a right-sided thyroid nodule, is benign on side. In 2019, you can see it's a pretty large nodule, about 4 centimeters and pretty vascular. Her labs were consistent with hyperthyroidism. You can appreciate why at some point it was confused with Graves' disease because her strep antibodies were not exactly within the reference range, but it was not exactly elevated. Um, overall, so the normal was 2 and hers was 2.16, and TSI negative, and she has subclinical hyperthyroidism defined as suppressed TSH, a normal free T3 and T4. So, we, uh, looked at her iodine scan here, uh, uptake and scan. And you can see there is an increased tracer uptake in the enlarged right thyroid nodule, so that same right thyroid nodule is pretty avid for the iodine, with the suppression of the entire activity in the surrounding thyroid tissue. So this is very consistent with toxic nodule. And the laboratory finding when we saw her in July suggestive of sub-clinical hyperthyroidism, and it's not Graves' disease. You can see all the antibodies, whether TPO, TSI, or TRAP were all negative. So we feel very comfortable and confident. And to call that toxic nodule. And so then we have all the options to give that patient whether surgery, iodine, maybe medical treatment, and also radiofrequency ablation. So I have to discuss all those options with her and decide what would be the next treatment. So let's talk a little bit about the epidemiology and causes of hyperthyroidism. The global prevalence of hyperthyroidism in iodine sufficient countries is anywhere between 0.2 to 2.5. If we look at the prevalence of overt hyperthyroidism, uh, clinically overt hyperthyroidism is anywhere between 0.2 and 1.4. The prevalence of subclinical hyperthyroidism, which I just defined, is approximately 0.7 to 1.4. The one I can't like highlight the definition when we talk about hyperthyroidism versus thyroid toxicosis, which we use them in clinical practice very interchangeably. But the word hyperthyroidism defines the syndrome associated with excess thyroid hormone production, so whether overt or subclinical. The thyroid toxicosis, on the other hand, refers to all conditions in which thyroid hormone levels are elevated, regardless of the underlying mechanism. So some of the causes of hyperthyroidism is Graves' disease, which is not a very rare disease actually, and it's more common in women than men, and it's caused by stimulated and stimulating antibodies called TRAP. And when we do iodine scan or uptake and scan, you will see a diffused uptake in these images. Also, toxic multinodular goiter, which is more common in older population compared to younger population. It's mostly because of monoclonal expansion and and the Iodine scan, we see hot nodules, multiple heart nodules. In the case that I just showed you, it's a toxic or solitary toxic nodules. It's due to, due to activating genes and as you saw the images suggestive of hot nodule. Thyroiditis is another cause of hyperthyroidism, and you see it up to 8% in postpartum. It's typically thyroiditis is usually inflammation whether due to disease, postpartum, physiological, or medication induced. The difference here compared to Graves, the uptake and scans show. Low uptake or no uptake. There is a very common entity of amiodarone induced thyroid toxicosis which I would actually suffers from medication because it has an entity on its own. It's very common. It's 11% in patients on amio, and there are two types, type 1 and Type 2. And those typically have low or no iodine uptake. And then last but not least, which is also a common medication or exogenous, 20 to 30% prevalence, it could trigger the immune response, and we see them a lot, for example, in immune checkpoint inhibitors or other medications that include iodine or the patient take exogenous thyroid. Regardless, the uptake in the scan would be low. So we can safely divide hyperthyroidism into hyperthyroidism with normal or high uptake, the most common of which is Graves' disease, but also like toxic nodule, toxic multinodular goiter, um, TSH producing adenoma, which is pituitary adenoma, which is extremely rare, uh, and then SCG related hyperthyroidism. And the other category is hyperthyroidism with low or no iodine uptake, like thyroiditis is the most common, and all kinds of thyroiditis, whether subacute, painless thyroiditis, postpartum thyroiditis, and medication induced like amiodarone induced thyroiditis or radiation induced thyroiditis, or people who are actually taking exogenous thyroid hormone. There is a rare but very interesting entity of ectopic hyperthyroidism or stroma ovari when there is low uptake because the source is somewhere else. So what are the risk factors for Graves' disease, and Graves' disease is a pretty common disease. Um, medication induced, so sometimes people are susceptible, but they need a second hint to develop the disease. Genetics, so certain people are more produced to that. Female sex, so females are more likely to develop autoimmune thyroid disease, smoking, nobody understands why smoking induced Graves' disease or even Graves' eye disease, and then iodine exposure. In general, symptoms of hyperthyroidism can go anywhere from tremor, like central nervous system, tremor and anxiety, uh, mood changes, decreased attention, cardiac like tachyarrhythmia, hypertension, increased pulse pressure, congestive heart failure if it's severe enough. Um, and then bone and skin abnormalities such as the periosteal bone formation, uh, acropathy, and then things like sweating, heat intolerance, thinning of the hair, even itching and clubbing, uh, and Graves thermopathy. Luckily, we don't have severe cases that we see those, uh, features, but those features are rare and usually are only seen in more advanced cases if they go illness freely undiagnosed for a long time. Symptomatically, you see things, uh, clinically, you see things like lid lag, lid retraction, proctosis if there's Graves' orbitopathy, and then, um, uh, seal injection and chemosis. Of course, we see the palpable gland, and if we listen to the gland, we see, we hear a bruit because the glands tend to be extremely vascular. And people sometimes report things like weight loss and frequent bowel movement or despite eating too much, um, they're losing weight. They do have muscle weakness and then things like muscle muscle weakness and things like polyuria and polyphagia. So we could divide the symptoms of hyperthyroidism anywhere due to Graves' disease from mild to overt, um, and people can have any spectrum of the symptoms, anxiety, emotional liability, weakness, tremor, like I just mentioned, those symptoms. The one thing I wanted to highlight here, elderly patients might actually present with a new onset Afib or congestive heart failure, so they might not have any of the symptoms that we just described earlier, and we call that apathetic thyrotoxicosis, which is mainly weakness and asthenia. And then thyroid enlargement. As far as the uh signs we see is hyperactivity and rapid speech, we see stare, the lid retraction, which is the lid lag is different than lid retraction. Lid retraction is the stare, and this is usually not specific for Graves' disease. It's a sympathetic hyperactivity, so all kinds of hyperthyroidism. And then we talked about the skin, the hair, the tachycardia, the tremors. What is specific for, none of that is specific for Graves' disease. What is specific for Graves' disease is exothalus, periorbital and conjunctival edema, limitation of eye movement, and infiltrative dermopathy. These are pretty specific for Graves' disease because it's immune mediated. Diagnosis involves biochemical evaluation, and this includes uh low TSH and high free T3 and free T4, assuming this is clinical and not subclinical. There's an entity called T3 toxicosis, which we see more in Graves' disease and toxic multinodular goiter. There is T4 toxicosis, we see it more in amiodarone-induced hyperthyroidism and thyroiditis. Sometimes we see them both. However, if you see a ratio of free T3 over free T4 more than 0.3, or a total T3 over T4 ratio more than 20, that makes it just Graves' disease. We also check, especially if we're suspecting Graves' disease, we check Graves' antibodies, which is TSH receptor antibodies or TSI or TBI. They have different names, but they all uh serve the same purpose. And then we could determine, um, determine the uptake uh on radioactive iodine. You don't have to do that if the biochemical testing is suggestive of Graves' disease. It can be sometimes helpful if the patient can have both pictures and multinodular goiter as well. And then ultrasound can be useful because it could tell us if there is any nodules and the thyroid and it measure the blood flow in the thyroid as well. Trap antibodies can be very useful in checking uh when we're looking at hyperthyroidism during pregnancy. If we're worried about patients with possible thyroid eye disease without the biochemical issues, uh, so biochemically they're normal, but then you suspect eye disease. Or if there's a recent iodine load where the thyroid uptake and cannot be reliable, for example, amiodarone or recent images with contrast. And to determine to, to determine the prognosis of remission uh in those treated cases. So a known case of Graves and uh Graves' disease and you have them on medication and you wanna kind of like get a sense of are they gonna get into remission or not, we usually recheck them at 6 months and 1 year on follow-up. These are examples of uh the uptake in scan that I was showing earlier in the case that I just showed, and it could be hyperthyroidism with high uh uptake or hyperthyroidism with low uptake, and we went over the causes of each. So let's move on to treatment options of hyperthyroidism. So the interesting part that uh in treating hyperthyroidism between before and now is the selection is the trend in changing um paradigm of treatment of hyperthyroidism over the years. So this actually, this paper came in 2024, late 2024, looking at the shift in paradigm in treating hyperthyroidism in the United States and how this shifted between 1999 and at least until 2023. It shifted from radioactive iodine being the most common type of initial therapy to ATD anti-thyroid uh drugs. Um, so the people nowadays are more, and this is the United States because worldwide actually the data is different, um, this is basically reflecting how people are now more utilizing anti-thyroid medication and less radioactive iodine. And the relative importance of the factors that impacted those decisions are the hope for remission. Like some people can, can have remission of their Graves' disease on medications only, and to avoid hypothyroidism, as we all know, iodine and or surgery can lead to hypothyroidism. And to avoid radiation, there's some data about the risk of radiation after for treating Graves' disease and secondary malignancy and so on and so forth. And to avoid worsening eye disease, so sometimes if you give iodine treatment for patients with eye disease, it could exacerbate Gray's eye disease, so we don't recommend iodine in these cases. Then there is a treatment for um hyperthyroidism for the symptoms itself. So, symptom control typically is done by beta-blockers. And then, we need to decrease the thyroid hormone synthesis. So these are thanamine. This has always been the medication back in the days and nowadays, methimazole or PTU. Then uh radioactive iodine ablations not recommended for patients with moderate or severe orbitopathy, I just mentioned the reason, especially if the antibodies are elevated. Surgery might be a good option, especially if the thyroid is huge or it has also like nodules, or the nodules are suspicious or the patient have hyperparathyroidism. So if there is any reason the patient will be a candidate for surgery, surgery might be the good, good plan for Graves. Then treatment of hyperthyroidism here, I divided into 4 categories and I added, if you noticed, the radiofrequency ablation, not just because I do it, but because it's an actually valid option nowadays. Not for Graves' disease, but for like thyroid nodules, and I'll get to that uh shortly. So, thyroid medication, the remission with thyroid medications such as methimazole, it can go anywhere 30 to 50%. So there is a chance that this recur. And the factors uh that can like support using the medication is patient will bee thyroid, not hypothyroid. It's useful in pregnancy. You can't give iodine in pregnancy. It's good for cases with mild Graves' disease. It's cheap and it's good for thyroid iodine. Disease because you don't want to give iodine. The issues there, there's a high chance that they will relapse, and the old education, if they relapse in 2 days, you give them more permanent treatment like surgery or iodine. This is no longer the case, and that's part of the presentation today. I'll give you some of the data on why not. Radioactive iodine, more than 90% success rate, but uh it might be not a good thing to offer for. People with eye disease or pregnancy or worries about radiation risk. Technically, the only treatment that gives you almost 100% cure is thyroidectomy because you're technically removing the whole gland, and it's good if the eyes, as I mentioned, if there's a concern for thyroid nodule with malignancy or compressive symptoms. Of course, the disadvantage is the surgical risk, the cost, the neck scar and hypothyroidism. Hypothyroidism is not a side effect, it's an expected outcome after removing the thyroid, but the side effect is related to surgery like recurrent laryngeal nerve, hypoparathyroidism. Hypoparathyroidism, believe it or not, is pretty common if the patient, if the patient has a Graves' disease because it's, it's risky, especially if the surgical skills are not very experienced with, with doing that. So sometimes we prepare the patient prior to surgery. And so it's reasonable to send patients with Graves' disease if you're sent to surgery is for skilled surgeons. Radiofrequency ablation, even though it has been emerged as one of the treatment options for toxic nodules, not for Graves' disease, the success rate is 60%. There are more data that might be better, we'll get to that later, but it's still 60%. It is useful for patients who don't want to do surgery, who don't want to do radiation. It's not ideal for Graves' disease, like I mentioned, it's not ideal for toxic multinodular goiter because you're basically ablating one nodule at a time, so it's not cost effective. So this is a very nice review that published in JAMA to look into like all uh treatment options uh for hyperthyroidism, which I just mentioned uh earlier. So if you go by uh uh anti-thyroid drugs. We usually use methimazole. Sometimes we use PTU. Methimamazole generally is the preferred first choice treatment over over PTU, except, except for pregnancy, the first trimester of pregnancy. The first trimester of pregnancy, we prefer PTU over methimazole, and you like to get like baseline CBC because of the risk of a granulocytosis and A baseline liver function test. It doesn't have to be monitored frequently, but a baseline. The dose can go anywhere between 5 to 14 mg per day for methimazole and 50 to 150 q3 um daily for PTU. And with these cases we monitor uh thyroid function test every 8 to 12 weeks and then we continue. The therapy. If the patient responded well and went into remission, we can discontinue thyroid medication 12 to 18 months, and if they have a remission, that's great, but if they have a persistence of recurrent disease, you can either have to use medication longer duration of medical therapy or offer more permanent therapy, which is iodine or thyroidectomy. Uh, radioactive iodine is contraindicated if the disease is active, like active grades ophthalmopathy or patient is pregnant or lactating. So in these cases, we don't give radioactive iodine. Other cases, it's an option, and uh we usually give anti-thyroid medication anyway as pre-treatment, and we stop it a few days, anywhere between 2 to 7 days prior to iodine treatment, then give the iodine. Some people put them back on methimazole, so it doesn't release all the thyroid, and people can get into thyroid toxicosis. If it's mild, you don't have to, and then you monitor thyroid function tests every 4 to 6. Weeks patient might be in your thyroid state or they start developing hypothyroidism. If they develop hypothyroidism, you start levothyroxine. If they did not have a good response and they continue to have hyperthyroidism at 6 months, usually we repeat the radioactive iodine. It's pretty rare, but sometimes if they were underdose to begin with or the goiter is huge. Especially in multi multinodular toxic goiter. Surgery, we all know the, the surgery and risk with thyroidectomy, but it's a preferred option if there's compressive symptoms, large goiter, suspicious for malignancy, and severe Graves' eye disease. We still treat it with medical therapy prior to surgery, and then we only stop it. Postoperatively, sometimes we use glugol solution or SSKI or iodine, basically saturated iodine to lower the vascularity of thyroid gland in cases of Graves' disease because vascular adhesive, it could create issues like I mentioned like hypoparathyroidism. And then after surgery we monitor thyroid function test. If it's total thyroidectomy, you start thyroid hormone right after surgery. If it's partial for like nodular goiter. Then we assess thyroid function test. The idea is they should not develop hypothyroidism, but if they do, then we start them on thyroid hormone. And then medical management of Graves' disease. So when you think of medical management of Graves' disease outside the the anti-thyroid drug, like I mentioned for symptomatic treatment, we use beta blockers. Now you could say which, which part of beta blockers, I would say. Beta blockers we prefer propranolol because it's not selective beta blockers, preferred in pregnancy and block the conversion of T4 to T3, so it could be useful in certain cases. It's also given 3 to 4 times daily. Metoprolol is equally effective. And atenolol is once daily, so if you worry about, worried about compliance, atenolol would be great, but you don't want to give it in pregnancy. Esmolol is IV, so that's only given in the ICU setting if there is a severe thyroid toxicosis or thyroid dyston, and we'll get to that later. Anti-thyroid medication, I mentioned that PTU and methimazole. These are the doses, and then some of the side effects that could be related to uh those medications. Mainly a granulocytosis is a very alarming side effect, but it's extremely rare. So you watch mainly for gastrointestinal distress, itching, hepatotoxicity. The metabolism of thyroid hormone, and this is a a uh a paper that we published last year about management aspect of medical therapy. Both, uh, so if you look at the, um, if you look at like methimazole here. Look at methimazole here. It inhibits the coupling of iodine iodothyrosine residues forming T3 and T4 and lower thyroid autoimmunity, and nobody knows exactly how medical therapy can lower the immunity, but believe it or not, a few months later, you see the antibodies could could disappear. That's the whole idea of engaging. Remission and inhibit TPO mediated iodination of thyrosine, so inhibit inhibit the synthesis steps of thyroid hormone. PTU also prevents the conversion of T4 to T3 within the thyroid and peripheral tissue by inhibiting type 1 diiodin A. So sometimes we use it more frequently in. Thyroid stones, they're both orally absorbed and they peak within 1 to 2 hours. Methimazole takes longer duration of action than PTU, so you can give it once daily if you want. They both transfer across the placenta and breast milk, but methimazole more. They both excreted urinary excretion metabolite, and there is no dose adjustment necessary in renal failure, which is good. Liver metabolism PTU is mostly bound to albumine. Methimazole is free in the serum, so sometimes there are more issues with hepatitis with with PTU than than um. The methimazole, that's why we don't like to give it in the second trimester of pregnancy if you heard of fulminant hepatitis and pregnancy. The American Thyroid Association provides some rough estimate to guide us on the initial diag initial dosing of methimazole. So for example, I said you can start anywhere between 5 mg and 40. Then how do you decide? Should I start 5 mg? Should I start 40 mg? So the free T4 is 1 1.5 times upper limit of normal. You start anywhere between 5 to 10 mg. If the free T4 1.5 to 2 times the upper normal limit of the normal, you start 10 to 20 mg. If the free T4 2 to 3 times, which is really high, the upper normal limit, you start 30 to 40 mg. Giving more doses does not add much. So let's talk about remission of Graves' disease. What is remission of Graves' disease? Remission from Graves' disease is defined as the maintenance of biochemical eut-thyroidism for at least one year after stopping ADDs. So that's the definition of remission. Surgery and iodine therapy are considered more permanent treatment options for Graves' disease, but they do cause lifelong hypothyroidism. Withdrawal of ATDS after the conventional 12 to 18 months of treatment may result in recurrence, like I said, anywhere between 20 to 70. The old teaching, like you give it for 12 to 18 months and nobody knows where did that come from. It's not based on data, it's just the way that we learn how to do it, and then if they didn't go into remission, then they, you offer surgery or or iodine. Realistically speaking, you can give methimazole for longer duration, and we'll get to that data shortly. So what leads to remission of Graves' disease on anti-thyroid? Like what are some of the Factors that make you predict like this patient will respond to anti-ATDs or not, so biochemically responsive patient is higher frequency of hypothyroidism during treatment, like you start small dose and they become hypothyroid, that means they probably respond pretty quickly. Lower degree of thyroid toxicosis, not severe, smaller goiter and TRAP antibodies are on the lower side, they're positive but not too high. Biochemically persistent or recurrent disease are more likely if the trap antibody is pretty high and it's not disappearing after 6 months, 1 year, every time you check traps still positive. So that might give you an idea that patient's not going to go into remission if you stop ATD. And in my opinion, in these cases, you continue on ATD or you offer other treatment, you don't stop. The goiter size, of course, the bigger the volume, the bigger the size, then higher risk of recurrence. Smoking, again, nobody knows, but smoking is a high risk of recurrence and postpartum period. Other factors possible, uncertain, meaning the data is not strong but suggestive. If you require a higher dose of methimazole, if there is Graves of ophthalmopathy at presentation or beatopathy, higher free T4 level, patients with insomnia, male gender. Younger age, family history, and grade score. Grade score is definitely useful to use, and I will get to that next. So grade score is basically the graves recurrent event after therapy, and so it's basically summarized some of the features that predict recurrence, which is trap antibody, volume, severity, smoking, age, and gender. So the factors that I just went through and you cal. Calculate the factors. So what's the trap? Is it high or low? What's the volume and what's the severity, which is basically free T4, um, thyroid size, and you calculate the score. And the higher the score, the more likely the disease is not going to go into remission. So I think this is a very good tool. There are also calculators to do it and that give you some idea, and these are the references about the grave score. It's been, it's been validated by multiple studies and modified as well. So let's talk about long-term uh ATDs. Um, the meta-analysis of patients with the Graves' disease treated with ATDs showed 16% increase in sustained remission rate for every additional year of treatment beyond the 24 months. So since I mentioned the 24 months because the historically the guidelines says 18 to 20 months. So beyond 24 months, after 2 years, every year you keep ATD, there's a higher chance they will go into remission, up to 85% remission rate if it's more than 5 years. So decent data that says if you long, the patient did not respond well to um respond well, but they keep getting remission, um, relapses, just keep the methimazole longer. recurrence of hyperthyroidism was reported in 40 to 50% in short-term group and then 8 to 15% in the long-term group. Here, long term group is 5, anytime between 24 to 48 months, so almost 5 years. And the dose is actually pretty small. So the red line here is the dose of methimazole, the blue line here is the The mean serum TSH. So you see, as the TSH improved, you start lowering the methimazole and eventually at 24 months, TSH maintained to be in the normal range with the lowest possible uh methimazole dose. So in some cases, anywhere between 2.5 to 5 mg. So in that study, which was actually published last the past two years, uh, they basically proposed that historically, like I said, they're teaching 12 to 18 months. If the trap is normal, great, you're in remission. If it's still high, then maybe give iodine or surgery. Then we said we don't like iodine with high antibodies because we worry about eye disease. So then uh they suggested, well, why don't we give the option of longer duration of uh methimazole, and they revised the proposal into, if the antibodies are not too high, and the patient is likely to have remission, just continue with anti-thyroid medication, especially if they didn't have side effects and they're on a very small dose. If they continue to require high dose of methimazole, antibodies continue to be really high, every time you try to lower the dose, they continue to have high thyroid hormone, then it's definitely reasonable to consider more permanent options. So we came up with this algorithm with the overall treatment or therapeutic options, surgery, ATD versus iodine, and I focused here on ATD is basically you start with methimazole, check CBC and LFTs, start with anywhere 5 to 40, then measure thyroid function tests 2 to 6 weeks, and then once the thyroid levels start normalizing, not the TSH, the T3 and T4, then we start tapering the dose to half. Then once TSH normalize, we go down to the lowest possible dose, which is typically 5 to 10 mg. Then we check levels every 8 to 12 months, then every 6 months to 1 year. At 1 year, we recheck 1, 1.5 year, we check the antibodies. If they're undetectable, great, that means. They're in remission, we can trial to discontinue methimazole. If they develop relapse, then we give the same options, whether permanent iodine thyroidectomy or go back to giving methimazole. If they are not in remission, just continue methimazole and give that option to the patient and reevaluate every 6 to 12 months. So let's address some uh special clinical scenarios that's related to uh thyroid disorders, so preoperative preparation. So if we decided that this patient is going to go for surgery, like I said, this is typically almost always elective surgery. So, there is a room and time to prepare the patient. Going to urgent surgery for hyperthyroidism, it will not have good outcome and patient can have a nerve injury and could have hypoparathyroidism, and then there's just a lot of bleeding. And so ideally we try uh preparing patients prior to surgery with thionamine, typically methimazole, but you could do PTU as well, uh, 3 to 8 weeks, uh, to keep the, to maintain the normal labs, so it doesn't have to be exactly normal, but close to normal is ideal. There is no rush. Then we give beta blockers. Single daily dose to keep the heart rate less than 100. Once they have normal thyroid function tests, there's no need to continue on beta blockers. And then I mentioned iodine, iodine like SSKI, which is basically comes as a drops, or uh potassium iodine, whichever is available in your pharmacy. It's called glugol solution. And it's only given after you already started PTO or methimazole, it has to be on board before you give it, because if you give iodine for a person who's already making, uh, having hyperthyroidism, they will go into a thyroid stone. Uh, steroid is optional, plus minus, we can give steroid prior to surgery or we don't have to, depends on the severity. Thyroid storm, on the other hand, is acute life threatening complication of hyperthyroidism, and the patient could have it if they went to surgery unprepared, but they could have it for other reasons too, and it could affect multiple systems in the body, and the mortality rate can go anywhere between 8 to 25%. So the treatment of thyroid storm is more or less the same medication we use for surgical preparation, except it's more scheduled and different dosing. So for example, we still use beta blocker for rate control. You can see higher doses for propranol. 40 to 80 mg 4 to 6 hours or if they're in the ICU we're talking about esmol trip, then we want to lower the synthesis of thyroid hormone, so that's by thanamine. We want to block the thyroid hormone from being released, so that's SSKI and lugol solution. These are the doses. We want to inhibit the conversion of T3 to T4, and that's achieved by propranolol as the favored beta blocker, PTU or glucocorticoid. So steroid hydrocortisone does that more than others, but also dexamethasone, but PTU more than methimazole does that for the conversion. And then we want to also reduce the enteropathic recycling of thyroid hormone by using cholestyramine. We don't have to use that in every patient, but it could actually expedite uh resolution. The second situation or scenario is pregnancy and lactation. Hyperthyroidism complicates 0.1 to 0.4 of pregnancies, and Graves' disease accounts for 85 to 89% of the cases, so it's pretty common because they usually it's the most common in young, uh, young age and more female, so that's what the pregnancy, uh, age group. Maternal hyperthyroidism associated with increased incidence of gestational hypertension, preeclampsia, gestational diabetes, spontaneous miscarriages, premature delivery, and intrauterine growth restrictions. So, um, generally speaking, Graves' disease in pregnancy treated with anti-thyroid drugs. Both PTU and methimazole can cross the placenta and may cause birth defects, but in the first trimester, we use PTU more than methimazole because the birth defects are more common and with methimazole or worse with methimazole. Beta blockers for symptomatic control. And then we check thyroid function every 2 to 6 weeks to aim for serum free T4 level in the upper limit of normal for non-pregnant women. Trap levels can fall in pregnancy, actually, and so much so for uh they can normalize, and ATD can be discontinued in about 1/3 of cases after the 30th week of gestation. So beyond a late, late pregnancy, if they're not requiring a lot of methimazole and the antibodies are negative, I think it's fair to stop it. ATD is also secreted in breast milk, but at very low levels like methimazole do up to 20 and PTU levels at 450 at the highest dose, it can be considered and it's still safe, but for higher doses, they can actually go into breast milk. Next, thyroid eye disease, which is an interesting entity we call it, uh, they keep changing the terminology, Graves' ophthalmopathy, Grave's orbitopathy, but the most current name is stent, thyroid eye disease. It's an autoimmune disease driven by trap activating activation of orbital fibroblasts. Um, the incidence is 16 in 1,100,000 in women and 3 per 100,000 in men. What are the risk factors for thyroid eye disease? Like I said, smoking, smoking, smoking, advanced age, high trap level, high pre-treatment level of T3 and T4, and radioactive iodine therapy. Mild cases, we give topical cyclosporine, glucocorticoid, and selenium actually proved to be useful. In moderate to severe cases, we give high dose glucocorticoid and tiprotumumab or Tipaza, which is a monoclonal antibody block, the IGF receptor. It's an infusion that we use for these cases and proven to be very useful. Obviously, in certain cases, surgery is recommended. Next is subclinical hyperthyroidism. Like I said, the prevalence globally is 0.7 to 1.4. It can progress to avert hyperthyroidism in 8% by 1 year and 26% by five years. So it's definitely worth watching. Graves' disease, uh, constitutes 40% of all subclinical hyperthyroidism cases. Treatment only indicated if the TSH is suppressed like 0.1 and less. If it's 0.3, 0.4, like just a little bit below normal, you don't have to. Age is 65 and above, if it's less than 65 of age, um, usually if they have symptoms, if they have osteoporosis, if they have heart disease. But if the age is more than 65 or the TSH is less than 0.1 indicated treatment. So I promised to touch base a little bit on novel treatment with radiofrequency ablation, which is a minimally invasive alternative to surgery or to radioactive iodine for treating toxic nodule. The volume reduction rate of a nodule, toxic nodule, can go anywhere between 52 to 86%. What we look at here, normalization of thyroid function as well, so that can be achieved to 61%, not great, because sometimes if the nodule is big, it can be tricky. It is a preferable option in younger patients with the smaller nodules. So, we call them pre-toxic nodules. So if the nodule is small, Um, and the, the pre-toxic meaning subclinical hyperthyroid, RFA would be actually ideal choice. So it might be considered in larger toxic multinodular goiter who are not a candidate, so it's not contraindicated in toxic multinodular goiter, but it's not preferred. But if the patient is not a good candidate for surgical procedure or iodine, we may consider radiofrequency ablation. Safety and efficacy of radiofrequency ablation and toxic nodule. It is currently recommended for Afton. Autonomous autonomously functioning thyroid nodule and small nodules by European and Korean practice guidelines. For the American thyroid guidelines, I think the newer guidelines will be released later this year. It is also suggested, it's not the first line treatment, but definitely one of the treatment options. Success is defined by 3 parameters. The nodule gets smaller, so nodule shrinkage, and typically shrinkage success is defined as more than 50% shrinkage at 1 year. The normalization of thyroid function test, and then if you do iodine uptake and scan, you want to repeat it and make sure it's actually changed. So, you don't have to do the last, the third one, if the nodules shrink and the thyroid function test is smaller, great, and normal is great, but I think it would be just good to confirm that. So this is a perfect example here, we published that in our guidelines on minimally invasive thyroid nodules, and it shows a 30-year-old woman with Afton and had a radiofrequency ablation. She has subclinical hyperthyroidism, and at 3 months, she had a 3 month shrinkage of the nodule to 52%, and her thyroid function test has normalized. I'll show you a case of mine, a 50 year old female with a toxic nodule, thyroid nodule initially found a few years ago, and she has subclinical hyperthyroidism, no TSI, no trap, so not Graves' disease. Her neck ultrasound showed some growth of that nodule. It's benign, right thyroid nodule and benign. But it's becoming larger and larger. It was 3 centimeters and became 4.6. She did have a prior FNA that says it's benign, and when it gets larger, also biopsied again, it was still benign. But she was bothered by the fact it's um it's growing and the TSH kept going down. Still subclinical hyperthyroidism, but it's, you're worried about progression. So she was interested in uh discussing radiofrequency ablation. So this is uh her nodule on ultrasound, and you see the nodule is not small, 4.6 centimeter. Like I said, it's benign, but it was growing. So we end up, uh, and she didn't want surgery, and it's a single nodule, not multiple nodule, so it's fair. The only disadvantage we told her, it's a pretty large nodule, so potentially she might need more than one session for radiofrequency ablation. She agreed and she really was determined to get non-surgical treatment. So, she got her um treatment and at 6 months, uh, so her ultrasound in September 2025 showed some post ablation changes. So you can see how the nodule changed. Now it's smaller, but it also looks uglier. Something to keep in mind when we do this procedures because the nodule will be hypoechoic, irregular border, but we know it's benign. It's just these are the ablative changes. And the nodule got smaller, uh, volume reduction rate was 40% at 6 months, so it's still not one year, uh, supposed to be following, uh, actually this month or next month since it was done in March, and the hope is to achieve 50% or more. Obviously, the more shrinkage, the better, but you can already see her thyroid function has been improving, so TSH was suppressed. And then after ablation was March 2025, uh, 2 months after the ablation, TSH became normal, lower normal, and then again in July, and then we continue to monitor. So it's definitely a good option for toxic solitary thyroid nodules, especially if smaller. There are other uh therapeutic options uh for Graves' disease that's currently under investigation. I will not dwell on that because a lot of these are small open label studies um with these agents. The initial presentation or results are promising, but there is no randomized multi-center trials. They're still to come. So, but to hear more about it in the future. Um, they're all under 4 categories, the B lymphocyte immune modulators, the TSH receptor antagonists, the immune modulator TSH receptor peptide, and neonatal FC receptor blockers. So in summary, the main management options in hyperthyroidism are ATDs, uh, RAI, and thyroidectomy. A shift in practice in the US favoring anti-thyroid drugs as initial management of radioactive iodine. Relapse has been observed in more than 50% of patients treated with the traditional 12 to 24 months duration of ATD. So I think it's fair to look into longer duration. Definitive treatment options for radioactive iodine and surgery, they carry the risk of lifelong hypothyroidism and surgical complications, so we have to be mindful of referring to the surgical skills, proper surgical skills. Long-term ATDs has proven to be safe and effective. Trap titers can help predict risk of recurrence, so it's worth to use it. Low doses of anti-thyroid drugs are safe in pregnancy and lactation. The mainstay in treatment of Graves' ophthalmopathy, or TED, include glucocorticoids, antipasa, surgery reserved for certain individuals when those don't work and it's not in the active setting. Radiofrequency ablation is a promising treatment option in select cases of thyroid nodules. Thank you very much for listening and this is my information if you guys have any questions and open for any questions. Thank you.
