All right, so why don't we go ahead and get started. Good afternoon, everyone. And welcome to our second ITE Live session. And today, we have a jam-packed agenda with the presentation of the diabetes, lipid, and obesity, adrenal, and thyroid questions. And I'm the moderator and ITE chair, Salil Akura. And I am at the Columbia University Medical Center in New York. Next slide, please. So thank you to our ITE 2024 faculty. They worked very hard to put together the ITE. And thank you for coming today to present the questions that you think are important for review. Next slide, please. And these are the disclosures, which you can also see on our website. So I'll move quickly to the next slide. And then the important points about ITE is that it really should be treated as a learning exercise by programs. It's not and should not be a formal high-stakes knowledge assessment. Rather, it should be used as a guide for fellows to assess their own knowledge base and areas of focus and then for programs to review areas in their curriculum that may need further attention. Next slide, please. And this is just to go over fellow performance. And as you can see, about over 760, almost 770 fellows. Oh, sorry. Do you mind going back to the other? Yeah, 770 participants. And as you can see, the average score, as you would expect, went up with years of training. And folks did about the same as they've done in prior years on the ITE. Next slide, please. And here, it just goes to the breakdown of the questions. And today, we'll focus on some of the questions that people found challenging as well as those that are important learning points. And as you can see, the average correct did not differ statistically from year to year. So just to move on to the questions, since we have a lot, I didn't want to spend too much time on the introduction. But moving on to the diabetes sections, which will be presented by Dr. Beckman and Dr. Gandhi. And I'll just turn it over to you both. Hi, I'm Derek Beckman with endocrinology at the San Antonio Uniformed Health Services Education Consortium, or SAWSHEC, i.e. the Air Force and Army Program, or Army and Navy down in San Antonio. And Dr. Gunjan Gandhi, if you want to go ahead and introduce yourself. Hi, I'm Gunjan Gandhi. I'm here at the University of Florida in Jacksonville. Glad to be with all of you today. Awesome. And Madeline, next slide. All right. So the first question here, a 65-year-old male with 20-year history of type 2 diabetes, hypertension, complicated by neuropathy, and suboptimal glycemic control. On premixed insulin, 40 units of breakfast, and 30 at dinner. Checks his glucose a couple of times a day with uncontrolled glucoses, 200 to 300 milligrams per deciliter, 11.1 to 16.7 millimoles per liter. A1c has been ranging 8.5% to 10%, and is on ramipril, amlodipine, metoprolol, resubastatin, and biotin. And looking at the labs, A1c is 9% or 75 millimoles per mole. And serum creatinine 2.2. And the big kicker here, urinary albumin to creatinine ratio, 3,886 milligrams per gram of creatinine. Liver function was normal. TSH mildly elevated at 7.5. And a serum fructosamine noted to be normal at 210. Next slide. And so what's likely are the discrepancy between this patient's hemoglobin A1c and fructosamine level is most likely caused by which of the following? And go to the next slide. And so biotin and hemolysis were kind of the next two in line behind the correct answer of proteinuria, which was the majority answer. And so I do want to highlight why it was proteinuria and not biotin and hemolysis, and not too many people jumped onto hypothyroidism and laboratory error. Mostly, we're looking at the complications related to nephrotic syndrome and interpreting labs. So next slide. And so we've all been kind of buzzed over the past few years of biotin. I really like this 2017 article, really just kind of looking at the different radioimmune assays that we have and what happens when we introduce external biotin into the system and how it can give us false elevations or false lowering of a lot of our assays. However, hemoglobin A1c is not typically one of those assays that is complicated by biotin. Next slide. And so just I always think about hemoglobin A1c as a product of the lifespan of a red blood cell times the average glucose. Things that increase red blood cell turnover or shorten the lifespan are going to give us a shorter or falsely lower A1c, which is the case for hemolytic anemias or hemolysis, things that consume your red blood cells. And so you have a faster turnover. And so hemolysis would be likely to give you a falsely lower A1c. Next slide. And so when you're looking at this, always remembering your average glucose, he said he's being 200 to 300, that you should estimate that the A1c would be somewhere around 8% to 10% there based on an average glucose. These are two different charts with an average glucose compared to fructosamine. And the one on the right has the A1c. Just noting that the Raden 2014 article is a little bit off on the fructosamine. But this patient's fructosamine was normal at 210, but his glucoses are running a lot higher. So we are tending not to believe the fructosamine. And just noting that fructosamine refers to all ketoamine linkages between that result from the glycation of serum proteins. And because albumin is the lion's share, when you're losing a lot of that, you can get a falsely low fructosamine. So that's the reason for the low fructosamine was because of the proteinuria from his nephrotic syndrome. Next slide. So this is the next question. This is looking at cystic fibrosis related diabetes. 20 year old woman with cystic fibrosis affecting your lungs and liver is referred after following laboratory results are documented. And so you note that hemoglobin A1c three months ago and current are mildly elevated at 6.2% and 6.1% or 44 and 43 millimoles per mole. However, the two-hour plasma glucose on an OGTT were both elevated above 200 at 245 and 260 milligrams per deciliter. No family history of diabetes and a BMI of 23 kilograms per meter squared. Next slide. So which of the following therapeutic options should be started as the next best step? So you have metformin, pioglitazone, acetylglyptin, rapid acting insulin and referral to nutritionists. Next slide. And so the lion's share got was rapid acting insulin and that is the best recommended treatment in cystic fibrosis related diabetes. However, we did have a good component of people referencing back to metformin and referral to nutritionists were the number two and three answers. Next slide. And so really kind of highlighting those that looking at the correct answer here, the cystic fibrosis related diabetes often has normal fasting glucoses. So don't always bank on a fasting glucose or even an A1c can be falsely lower comparatively. And so insulin is the recommended to jump on before treating it because of these other reasons that IE, the oral medications haven't been really shown to be effective. So looking at metformin, it's not expected to work and it's actually maybe not be safe with the liver involvement of the cystic fibrosis. And then a referral to nutritionists, while not wrong, it's not the therapeutic intervention that is very necessary at this point given how high the glucoses were that we need to initiate therapy, but you should still refer to a nutritionist for good dietary guidelines within cystic fibrosis related diabetes and cystic fibrosis in general. Next slide. So these are the guidelines by Dr. Moran in 2010 that are still referenced by the American Diabetes Association Standards of Care. And there is a 2014 update or partial update from Dr. Moran as well, but ultimately just noting that I highlighted there at the bottom there, number three, patients with cystic fibrosis related diabetes should be treated with insulin therapy. And then number four, oral diabetes agents are not as effective as insulin in improving nutritional metabolic outcomes in cystic fibrosis related diabetes and not recommended outside of clinical trials. And so you should be thinking about those alternatively in trials if that's the avenue to go down. Next slide. And my last question here is about a 37 year old man presenting for diabetes management. His mother told him that he was diagnosed with diabetes shortly after birth. He reports that his mother and two siblings also have diabetes. Mom is on insulin therapy, just not sure how long she was diagnosed before receiving insulin therapy or when she was diagnosed. And the two siblings were diagnosed with type one diabetes. He hasn't had good control. A1C elevated nine to 11%, most recent 10.5%. And CKD4 has neuropathy, macroalbuminuria, or albuminuria and uncontrolled hypertension. He's currently on insulin with Lispro 5 before each meal on a correctional scale and 22 units of Glargine. And just noting kind of on the physical exam, a normal weight BMI, 22 BMI, and no lipohypertrophy or absence of fat tissue. I'll get into some of the answers here and just noting some neuropathy with decreased sensation. So looking at the labs, an A1C of 10.5%, creatinine elevated at 2.8, random glucose of 275, and a C-peptide that was undetectable at the same time that that glucose was drawn. And the antibodies for glutamic acid, D-carboxylase and islet-cell are both undetectable or negative. Next slide. So ordering the genetic tests for which pathogenic variants and which of the following genes would most likely confirm this patient's diagnosis. And these are just ones that you gotta go back and memorize. So we'll go to the next slide here. So KCNJ11 is the correct answer. A lot of people jumped on the MODIs, the HNF1A and the HNF4A. Noted that it was a genetic issue. And we typically thinking MODI more typically in our setting, but you gotta remember the neonatal diabetes. And then we'll talk about the first couple of answers as well. Next slide. So just noting the physical exam are these two variants are most common causes for congenital generalized lipodystrophy. And so that wasn't noted in the STEM. So looking at your MODI cases versus KCNJ11, looking at neonatal diabetes. More people jumped on the HNF1A, which is more common comparatively to HNF4A. However, we gotta think about the time of diagnosis. KCNJ11 is one of the more common variants for permanent neonatal diabetes. And so we'll go to the next slide. And so this is a nice breakout from the ADA standards of care, looking at the difference between MODIs versus your neonatal diabetes. And we'll show on the next slide here, but neonatal diabetes is diagnosed within the first six months. And I will always keep in the back of my mind that KCNJ11 and ABCC8 in particular. However, you can see the difference. Some of them are permanent versus transient neonatal diabetes. Next slide. So remember that neonatal diabetes is onset within the first six months. So that's what they were heavily hinting at here. And there was a genetic predisposition noted within the whole family. And that it generally just affects some part of your processing within the beta cell function. And one third of these cases are permanent. So the KCNJ11, notice it hits the cure 6.2 part of the sulfonylurea receptor here. And then your ABCC8 hits the SOR1 component of that channel. And so you can see over on the right side that you have dysfunction there that can lead to neonatal diabetes. And that can be overcome with sulfonylurea sometimes. And so just noting that any of those processes can be complications. And then just remembering about that time of diagnosis within the first six months. Next slide. I think that's it. Over to you. And sorry, before Dr. Gandhi starts, if folks have questions, they can put them in the Q&A section and we can review them. So feel free to type in any questions that you may have. All right, so our next diabetes question is a 32-year-old woman with a five-year history of suboptimally controlled type 2 diabetes is concerned about a right lower extremity lesion that started small and has grown over time. And you can focus on the photograph, the image given to you. The lesion is solitary, it's not raised, and it itches but does not hurt. Her diabetes treatment regimen includes metformin, glimepiride, and liraglutide. And she's also on lisinopril and atorvastatin. So the lesion in question here is located on the right lower extremity. It is erythematous with some yellowing in the center. There's visible blood vessels within the lesion. The border is regular, and no other lesions are observed on careful skin examination. Next slide, please. So the question is, which of the following diagnosis most likely characterizes the skin finding? Is it a diabetic bully? Is it diabetic dermopathy? Option C is granuloma annulari. D is necrobiosis lipoidica. And option E is scleroderma diabeticorum. And the correct answer is option D, necrobiosis lipoidica. And the main objective of this question is to look at skin findings and identifies those that are associated with diabetes. And the vast majority of you did get this answer correct. The second most common option chosen was diabetic dermopathy. If you can go back one slide to the picture, just a couple words on necrobiosis lipoidica. So it is more common in women, classically described as being associated with both type one and type two. You know, I have seen it in a handful of patients, and most of them have had type one diabetes. Tends to affect the pre-tibial areas, could be bilateral. And it starts out as this small lesion that can get quite large. And the main thing to think about is even with minimal trauma, you can get ulceration and there is risk of secondary infection. Why it occurs is not quite clear. There doesn't seem to be a definitive correlation with suboptimal glycemic control. It is a granulomatous disorder where there is collagen disruption. And dermatologists who you will send these patients to will frequently biopsy it. No great treatment options. You know, they might try topical or intralesional corticosteroids. You know, they might sometimes give them a calcineurin inhibitor such as tecrolimus. I've seen them use systemic treatments like TNF alpha inhibitors, UVA treatment. None of these treatments really work that well. And the typical course is this will progress, be indolent over time, can be fairly disfiguring. And, you know, you'll see this repeatedly with some waxing, waning over time. So a difficult lesion to treat. All right, we can move forward to the next couple slides. And I just wanted to, yep, this is good. So the other options given, I thought, you know, showing you pictures would be much more worthwhile than a description. So granuloma annulari can fairly uncommon, is associated rarely with diabetes, can be localized, can be diffused, can be seen in sun-exposed areas. So extremities or sun-exposed areas of trunk are common locations. You know, lesions will resolve, new lesions will come on. Again, a difficult condition to treat. And there is a predominance of females. They have tried UVA treatment, they've tried Dapsone, sometimes systemic retinoids or topical retinoids are used with variable effects. Scleroderma diabeticorum is more common in men. This is one where suboptimal glycemic control does seem to play a role. And the posterior neck, upper back, shoulders are a common location. You know, you'll see this induration of skin. It's fairly classical. It's hard to miss scleroderma in this location. Next slide, please. Diabetic bully, you can see them typically in the lower extremities. Starts out as a small blister, tends to get larger, get tense, can perforate, can heal by secondary intention over two to six weeks. The key is to make sure you prevent secondary infection of these lesions. The most common diabetic skin lesion likely is diabetic dermopathy. And these can be seen in up to 40% of people with type 2 diabetes. The pre-tibial area tends to be a common location. It can start out as a red papule that ultimately becomes a flat brownish atrophic macula type lesion, as you can see in the image. Typically does not merit any treatment, and you can reassure the patient. There have been small studies where they've seen this as a harbinger of increased risk of cardiovascular disease. Just keep that in mind. Next slide, please. The next couple slides that I will not go into any detail because I've highlighted the main findings, but when you get the answers and these are, you know, will be available on the endosociety, the fellows training series part, you know, there'll be more description of these lesions. So you can look at them in more detail. Next slide, please. And this highlights the treatment options and the clinical presentation of these lesions. All right, next question. So this is the last question in the diabetes subsection. And this is an interesting one. A 26-year-old man with an 11-year history of type 1 diabetes has difficulty with hypoglycemia during exercise. No known microvascular complications. And really he has done quite well with his A1C values ranging from 6.7 to 7.5% over the last four years. And his most recent values have been less than 7% on the A1C. He does use an insulin pump with continuous glucose monitoring. And the pump does have predictive low glucose suspend feature. He typically jogs three times a week. Although he aims to jog for 30 to 60 minutes, but almost always develops hypoglycemia 15 to 30 minutes after starting to run and thus has to stop. He typically jogs in the morning before eating or in the late afternoon, about four to five hours after lunch. On his own, he has tried reducing his basal insulin rate during the period of exercise, but then finds that he experiences hypoglycemia after his workouts. Which of the following suggestions would be most appropriate to help this patient avoid hypoglycemia during aerobic exercise? A, consume 45 to 60 grams of carbs just before exercise. B, engage in resistance exercise before starting aerobic exercise. Option C is increased protein and fat consumption in the meal before exercise. Should you reduce basal insulin by 50% at the beginning of exercise? And option E is reduce pre-exercise meal bolus by 30 to 50%. And the most appropriate answer here is option B, which is engage in resistance exercise before starting aerobic exercise. And again, you all did a great job. Most of you got this correct. The other options that were chosen were consuming carbs before exercise and increasing protein and fat consumption in the meal before exercise. Next slide, please. So this patient has hypoglycemia during aerobic exercise. And why do blood sugars drop during exercise, especially aerobic exercise? Obviously, current treatment regimens, even the sophisticated automated insulin delivery and hybrid closed-loop systems are unable to match the normal physiologic decrease in insulin that would normally occur. Because of exercise, there can be increased subcutaneous blood flow, which can lead to increased insulin absorption. There could be increased uptake of glucose in the muscles via the GLUT4 transporters. And the counter-regulatory hormone responses that prevent hypoglycemia are impaired during exercise. As a result, blood sugars in general will tend to drop during aerobic exercise. I think one thing to consider as you approach these patients is to find out when are they exercising. Are they exercising in a so-called high insulin state, which would be soon after consuming a meal? Or are they exercising several hours after a meal, as in our patient, which is a low insulin state? And remember, our patient was exercising in the recommended time frame, which would be in a low insulin state, either early in the morning or several hours after eating. Now, if in this case, he's not exercising soon after eating, so reducing the pre-exercise meal bolus by 30% to 50% would really not help. Only if he was exercising soon after eating would cutting down on pre-meal bolus be a helpful recommendation. Reducing basal insulin by 50%, and our patient had tried something similar and found that it led to post-exercise hyperglycemia, so that was not ideal as well. Next slide, please. One reasonable consideration would be consuming 45 to 60 grams of carbs before exercise. But again, the amount of carbs that was given as an option is a little too much. In general, we think of 0.5 to 1 gram of carb per kilogram per hour of exercise. And again, that's a general recommendation. It varies on the intensity, duration, exercise tolerance, variety of factors affected. But this probably is a little too much, which will lead to hyperglycemia, likely. And then consumption of fat and protein has been suggested. There's some data in adolescents where if they were given protein before exercise, it reduced post-exercise hypoglycemia, but it's not been consistently shown. And so the most reasonable answer here is resistance exercise, which is interesting. So resistance exercise, think of it as being an anaerobic mode of exercise. So this could be lifting heavy weights. This could be sprinting. This could be high-intensity interval training. And what has been noted is this will typically raise counter-regulatory hormones, and that reduces glucose uptake into muscle, preventing hypoglycemia, and actually can cause hyperglycemia. And doing resistance training before aerobic exercise has led to much stable glucose levels over the period of exercise duration. Next slide, please. And this is a nice paper by Zaharieva and colleagues that came out in the Diabetes Spectrum in 2023. And for those that plan to do this quite a bit in their practices, I would highly recommend you refer to this, because it gives you nice strategies, especially now with automated insulin delivery systems with pumps and how the different pumps and the automated delivery modes vary. You can do a variety of different things. One is all of them have some sort of exercise or activity mode, which is also called a temporary target in some pumps. And that sets the glucose threshold higher, 150, 160, rather than 110. And it typically will shut off the microboluses to counter hyperglycemia. So all of that will help reduce hypoglycemia during exercise. If it's a planned, unplanned spontaneous exercise, then increasing carb intake at exercise intake may be your only option. Next slide, please. And this is a nice cartoon of what we've been discussing. So when you break down exercise, think of aerobic exercise, typically lowering glucose. Anaerobic exercise, like weightlifting, jiu-jitsu, taekwondo, whatever it might be, raising blood glucose in general. And when you have a mix of anaerobic and aerobic exercise, you tend to have more glucose stability. Great, thank you, Dr. Gandhi and Dr. Beckman. I think we'll move on now to the lipids and obesity section, which Dr. Srinath will present. Thanks, Lila. Can everyone hear me? So, yes, my name is Rae Srinath from Mount Sinai here in New York, and I also want to welcome my colleague, David Saxon. Oh, I'm sorry, I didn't introduce Dr. Saxon. My apologies. So welcome to Dr. Srinath and Dr. Saxon. Thanks for having me. Of course. So next slide, please. Okay. Okay. So this is the first question. So this is a 32-year-old man who's referred for assistance with weight loss. So 10 years ago, he was in a motor vehicle accident and has since really struggled with weight gain. He previously followed a meal replacement program and lost about 20 pounds, equivalent to 9.1 kilograms, but unfortunately then regained. In terms of diet and exercise, he reports an intake of breakfast, about two sausage biscuits, skips lunch, and for dinner has a double portion of protein, vegetables, limited carbohydrate. In terms of activity, he's taking about 6,000 to 7,000 steps every day. On physical examination, he is 72.5 inches. He is approximately 286 pounds, which is 130 kilograms, and his BMI is 38 kilograms per meter squared. His waist circumference is 51 inches or 129.5 centimeters. Next slide. So the question here is, which of the following adipokines is most likely decreased in this patient? Next slide, please. So our options here, I forgot to read them, adiponectin, leptin, plasminogen activator inhibitor and resistance, and tumor necrosis factor alpha. So the answer here is adiponectin, which the majority of you, excuse me, significant portion of people did choose. We'll talk a little bit about what changes occur. Next slide. So the big important fact to note is our cells, our fat cells specifically are metabolically active. And as we do gain weight, those fat cells of the adipocytes are getting bigger. They are secreting more and more adipokines, more and more hormones. So in a state where patients are gaining weight, we traditionally find increased leptin levels, increased resistance levels, increased apalin, bisaptin, and decreased adiponectin. Similarly, when patients are lower in weight, we find lower leptin and higher adiponectin. And it's key to note that adiponectin actually plays a huge role in glucose metabolism, cardiovascular disease risk, and overall metabolic disease risk. Next slide, please. And so what I sort of highlighted earlier in terms of our answer choices, answer A, leptin. So in fact, leptin is a hormone that does go up when we have greater adipose tissue. And it is most likely proportional to body fat. So therefore, higher levels of obesity are prevalent with more higher levels of leptin. The second choice, adipocyte secretion of tumor necrosis factor alpha. So this is actually a pro-inflammatory molecule that also goes up in patients with weight or obesity. And it actually can correlate with increased insulin resistance, changes in glucose metabolism, and diabetes risk. Resistance, on the other hand, can also contribute to insulin resistance. It is a pro-inflammatory molecule, and it works on the adipocytes, the liver, and the muscle and can promote diabetes risk. So again, going up with weight gain and obesity. And plasminogen activator inhibitor one is also a pro-inflammatory molecule that really works on fibrinolysis, and it is involved in both energy balance and insulin resistance. So again, this also goes up with weight gain. So keeping in mind, these are all pro-inflammatory molecules. They go up when patients gain weight, and adiponectin is the one that goes down. Next slide, please. Okay. So the next question we're going to move on to is a different case. Actually, David, you're going to take over here. Yeah, no problem. I'll take over here, and thanks for having me. This is a 58-year-old male, former smoker. He's seen for optimization of lipid-lowering therapy after coronary artery bypass graft. He's symptomatic with exertional angina now. His meds are atorvastatin 80 milligrams daily, ezetimibe 10 milligrams daily, evolacumab 140 milligrams every two weeks. He also has onomatopoeia, aspirin, and clopidogrel. On exam, nothing remarkable there. BMI is 22. He does have faint corneal arcus, but no tendons and thomas. Increasing lipid panel is significant for total cholesterol of 122, triglycerides of 90, HDL of 38, and LDL of 66. Next slide. Before recommending any treatment changes for further cardiovascular risk reduction, which of the following would be beneficial to measure? A, apolipoprotein B, B, high-sensitivity CRP, C, LDL particle number by nuclear magnetic resonance, D, lipoprotein A, and E, plasma phytosterols. And the answer, which most people got right, is lipoprotein A, which is in the news a lot, and I'll talk a little bit about that. Next slide. So this is a figure showing what the structure of lipoprotein A looks like. I like to think about this as essentially an LDL particle that's ApoB-containing, but it has this fancy extra thing hanging off the side of it that makes its structure and function in the body completely different than LDL cholesterol. And that's what you see here is this ApoA moiety at the bottom, and the Ks there represent what are called kringles, and there are repeats of this that vary in size even within an individual. So it makes it difficult sometimes to measure LPA historically, because even within an individual, lipoprotein A can weigh a different amount depending on how many kringles are in the ApoA moiety. So that's what lipoprotein A looks like, and it's important to remember that it's been determined now through many different types of studies that it's an independent and causal risk factor for ASCVD. We should think about measuring this in the following scenarios. There's a personal or family history of premature ASCVD. There's suspected familial hypercholesterolemia, because we know that patients with FH have a higher rates of lipoprotein A as an extra independent causal risk factor for ASCVD. And then you could think about measuring it when there's suboptimal response to traditional lipid-lowering therapy, meaning that the LDL cholesterol did not go down with statin therapy as expected. It may be that a lot of the LDL cholesterol being measured is actually lipoprotein A. I'll also mention that there are international guidelines that say that lipoprotein A should be checked once in everyone in their lifetime. American guidelines have really not moved in that direction until recently when the National Lipid Association said, we should probably think about doing this as well. But a lot of our society guidelines have not promoted measuring lipoprotein A in everyone quite yet. A little bit more. Statins do not lower LPA levels, and in fact, can often raise them by 5% to 10%. But we don't usually measure lipoprotein A, again, after we start a statin in someone with high lipoprotein A, because the benefit of LDL lowering tends to outweigh this minimal increase that you might see in lipoprotein A levels when a statin is started. If your patient is on a PCSK9 inhibitor, you should know that it can lower lipoprotein A levels by up to 25% to 30%, although specifically lowering lipoprotein A with PCSK9 inhibitors is not an FDA-approved therapy. The only FDA-approved therapy there is specifically for LPA is lipid apheresis, which is essentially kind of like a dialysis for lipid disorders. Patients tend to come in every two to four weeks and have their cholesterol removed from their serum. And specifically, the FDA criteria is that you can get apheresis if you have established ASCVD, a lipoprotein A level that's over 60 milligrams per deciliter, and also an LDL cholesterol over 100 milligrams per deciliter. You'll hear a lot more in the future about lipoprotein A, because I'm aware of at least five drugs that are in trials for lipoprotein A-specific lowering. Helicarcin is an antisense oligonucleotide that's being tested in the HORIZON trial, and that trial is the furthest along with possibly results as early as sometime in 2025. But there are four drugs in total that have either entered phase three trials or will be entering phase three trials soon, and then a fifth drug, which is an oral agent, that is under experiment in phase one trials. Next. The other options, which were the incorrect options, apolipoprotein B or apob, an LDL particle number, those aren't going to add much here for helping differentiate whether this patient needs more intensive therapy or whether they have extra risk factors that are present. But you can think about measuring these things in patients with significant hypertriglyceridemia, because there can be discordance in the calculated LDL cholesterol on a standard lipid panel and these potential values. With regards to high-res CRP, it's usually used in patients at intermediate risk of cardiovascular disease to help decide on whether you should initiate statin therapy. In this example, this patient already had established coronary artery disease. And then lastly, measurement of plasma phytosterols. That should be considered when the disease cytostilaremia is suspected. That's a rare autosomal disorder that's characterized by tendons and thomas and premature ASCVD. Sometimes those patients will have elevated cholesterol levels and sometimes they will not. Next slide. Great. So this is a 26-year-old presenting for evaluation for weight gain and obesity. He reports being overweight as a child, was placed on his first diet in kindergarten. He has constant hunger, continued weight gain. On past medical history, you report congenital unilateral hydronephrosis, legal blindness due to retinitis pigmentosa. On examination, he is 65.7 inches. His weight is 254 pounds, which is 115.2 kilograms, and his BMI is 41. He also has polydactyly of the right hand. On laboratory tests, his fasting blood sugar is 109, which is significantly elevated. His TSH is 5.5, and his total testosterone is 210 milligrams per deciliter. Next slide. So the question here is, which of the following treatments is most appropriate to address obesity in this patient? A, recombinant leptin. B, semaglutide. C, setanilatide. D, somatotropin. And E, testosterone. Next slide. So the answer here is C, setanilatide, and we're going to talk about this more in terms of options of how we treat obesity here. Next slide. So the key point here in this case is this is actually a presentation of a monogenic form of obesity called Bardet-Bidel. So this is an autosomal recessive condition. It has multiple congenital conditions that are associated with it, including what you noted, which was polydactyly of the right hand. It also is associated with increased hunger, appetite, which starts from beginning of life. There is significant kidney dysfunction. There is degenerative eye changes, secondary to retinitis pigmentosa that can lead to blindness. And there's also intellectual disability. Unfortunately, the hunger, these cravings are driven by abnormalities in the melanoportin-4 receptor pathway. So this is a G-coupled protein, which works on both driving energy balance, glucose homeostasis, and significantly can impact weight gain. Next slide. So this was a key gain in our care for patients with Bardet-Bidel syndrome, which is a monogenic form of weight gain and obesity. So set melanotype was approved just within the last few years. There have been multiple phase 3 multicenter randomized control trials. And I've presented some of the data here on the right. But as you can see, the significance is there is significant weight loss on the order of up to 10% over 52 weeks. So this is really great. And almost more than a third or almost a third of patients reach that 10% weight loss threshold. In addition, patients tolerate these medications quite well. It is an injectable that patients are giving themselves. It is approved for patients over 6, so can be administered by the patient or a parent. Most common side effects do include skin changes, hyperpigmentation, injection site reactions, possibly mild GI side effects initially. But otherwise, it's really well tolerated. So this is something really exciting. What it points to is that patients need to be identified early and potentially genetically tested and then potentially followed by the right provider so they can get this medication moving forward. Next slide. Going through our other options, so recombinant leptin, remember that leptin treatment has been approved for use in congenital or acquired generalized lipodystrophy. Again, a very different presentation than this patient. Or in leptin deficiency, we also have some aglutide, which many of you are familiar with as Ozempic or Wolgobi. Again, used for patients with obesity, type 2 diabetes, a GLP-1 agonist. Again, may help, but not the ideal agent here. We have somatropin, which is not the right answer here. This is actually used to treat growth hormone deficiency. And lastly, testosterone. So we know that there are multiple studies showing testosterone replacement can actually contribute to weight loss or improve this patient's symptoms. So again, not the right treatment for us here. Next slide. Great, thank you. David, I believe you're answering some of the questions in the chat. And if there's any further questions after, we can address it at the end. But thank you both for presenting. And then we'll move on to the, in the interest of time, to Dr. Cheng, who will discuss the adrenal questions. Hi, how are you? Sorry about that. So I'm Dr. Chang, Alan Chang, I'm from Stony Brook University on Long Island. And unfortunately, Dr. Ricardo Correa cannot join us today, so I'll be presenting his slides as well. Next slide. So first question, we have a 52-year-old male with hypertension and hypokalemia being seen for primary hyperaldosteronism. So the screening tests are below. Sodium is 147, potassium is 3.2, serum bosterone is 34 nanograms per deciliter, and serum renin activity is suppressed at below 0.6 nanograms per milliliter. Next slide. Okay, so adrenal cascade demonstrates normal appearing glands with slight thickening of the central part of the right adrenal gland. So he undergoes adrenal vein sampling with a continuous infusion of cosentropin at 50 nanograms per hour. And the results are below. I mean, I can read it to you. So right adrenal vein, aldosterone is 3,000, left adrenal vein, aldo is 456, and IBC is 40. Going to the cortisol, the right adrenal vein is 750, left adrenal vein is 120, and the ferravena cava is 20. And the right adrenal vein, aldosterone, the cortisol ratio is 4.0, left adrenal vein is 3.8, and IBC is 2.0. Yes, please, next slide. So which of the following is the best interpretation of the results of the adrenal venous sampling study? And so successful study, both adrenal glands are sources, so bilaterally, B, successful study, left adrenal gland is the source, left side, C, unsuccessful, there's not enough information to localize, thank you, and finally, D is unsuccessful, unable to localize the source. So answer is A, as you can tell, and the majority of the fellows got it correct. Next slide. So there's a few things one needs to interpret in AVS, adrenal vein sampling. So basically, during the sampling, cortisol concentrations are used to determine which side it's from, and it needs to be accounted for, for the dilution of the left adrenal vein. And the ratio of this cortisol in the adrenal vein to the cortisol in the mixed venous blood is called the selectivity index. Basically selectivity index basically tells you whether the catheters are correct when they actually do the procedure. So the selectivity index on both sides should be over 2 if the AVS is done without cosintropin. And it should be greater than 5 if it's underperformed under cosintropin stimulation. And technically, the study should not be interpreted unless both selectivity indexes are greater than these values. And that is generally what is recommended at this time. The right side is more difficult because it's shorter, actually. And usually the cortisol levels in the right side samples are more concentrated because it is shorter. So that's why there is the need to do this calculation, which we'll talk about. Next slide. So in this case, the selectivity index on the right side is 37.7. So that was the cortisol of the right adrenal vein over the cortisol of the IVC. And the selectivity index on the left side is only 6, so that's the left adrenal vein cortisol over the IVC cortisol. But even though it's only 6, it's still valid, still above 5. So that tells us that it is a good, a catheter is in place correctly. So at this point, you know it's done correctly. You have to now find out which side it's coming from. So now you have to calculate the lateralization index. And this is done by calculating the cortisol corrected ratio. So it's the aldosterone to cortisol ratio of both adrenal veins. And basically it's defined as the ratio of the higher over the lower. So basically it doesn't matter which side is higher or lower, you just take the higher side of whichever adrenal vein and divide it by the lower side. Yes. And that gives you the lateralization index. Under co-centripetal stimulation, the cutoff is above 4. So if it's above 4 and the higher side, let's say is the top, the top numbers on the right, that means that it's the right, it's the right adrenal gland. And yeah, so it's above 4. And if it's below 3, however, that means it's bilateral. If it's between 3 and 4, it's actually quite difficult to, to determine. It's thankfully hasn't happened to me personally yet. But usually if that happens, it's recommended, well, you have to go back and reevaluate maybe doing your ABS. It's the, you know, there's no right answer in that case. Without concentripin, however, without ACT stimulation, the ratio should be greater than 2 for lateralization. Okay. And while below that, it's both sides. So in a way it's kind of simple, simpler. So basically if the patient select selectivity index, it should be greater than 2 without concentripin and it should be greater than 2 with lateralization index. So in this case, let's say the cortisol, the cortisol correct, it got a loss on ratio of less than 4, thus answer A is correct. The answer B is incorrect. All right. So next one, primary care physician refers a 45 year old male from Southern Illinois with bilateral adrenal enlargement. The physician is concerned about the possibility of bilateral field chromocytoma as plasma metamorphism measured in his office by venipuncture were elevated. The cat's, the patient's CT is shown below demonstrating adrenal enlargement. See image arrows. There's the positive white arrow sign bilaterally. Next one. So the patient's appetite has been poor. He has lost 11 pounds or 5 kilograms in the past three months. He has no family history of endocrinopathies and he takes no medications. When seated, his blood pressure is 100 over 68 milligrams per mercury, sorry, millimeters per mercury with a pulse rate of 96 and when standing, his blood pressure sinks to 88 over 50 with a pulse of 120. So he's sort of static. The rest of the exam findings are unremarkable. Next slide. So initial laboratory results. So you have your plasma nor-metanephrine 225, slightly elevated, plasma metanephrines, which is below 40. And then you order, well, it was ordered additional labs at 8 a.m. So sodium was 131, potassium is 4.4, creatinine is 0.6, aldosterone level is 4, plasma renin activity is 17, plasma ACTH is 212, and cortisol is 3.2. Next slide, please. So which of the following diagnostic tests is most likely to be helpful in the further diagnosis and management of this patient? So you have A, bilateral adrenal venous sampling for cortisol, aldosterone, and catecholamines. B, you want to do a biopsy, CD guided pertaneous adrenal biopsy. C, measurement of 21 hydroxylase antibodies. D, measurement of 24-hour urinary free cortisol. And E, pituitary directed MRI. Excellent. So the answer is B, as in beta, which, you know, a good majority of the answer choices were worthless, but C actually took the cake on this one. Next slide. Okay. So this patient has adrenal insufficiency, and specifically has primary adrenal insufficiency as demonstrated by the elevated ACTH level and the low cortisol level. Okay. Plus, also the patient presented very classically with the hyponatremia, hyperkalemia, vomit and yeah. So this patient has primary AI. So a few things. When ACTH levels are high, and when they exceed 80 to 100 milligrams per milliliter, some studies say 60, 66, you have the maximum stimulation of the adrenal glands in this ability to make cortisol. Okay. And usually, when it's that high, we want the cortisol to be elevated, at least 18, you know, at least on the lower, I'm sorry, the older assays. Just so it's out there. So now, nowadays, newer assays are coming online. There's one called this Roche that uses a low cortisol cut point for ACTH stimulation tests such as 13 to 15. Here at Stony Brook, we do use the Roche Alkasis 2, and our cut point is 13.5, not the 18. But regardless, this patient has an elevated ACTH value, and his cortisol is quite low, and also his plasma activity is quite high. So yeah, so it's primary AI. Next slide, please. So the question is why, right? Oh, can you go back? So the question is why. So, okay. So in this case, the adrenal glands are large, you know, bilaterally, which is unusual. Usually with primary adrenal insufficiency due to autoimmune conditions, it should be small, it should be tiny. So when one sees an enlarged adrenal gland with adrenal insufficiency, one should start thinking about infiltration, you know, cancer, lymphoma, infiltration, metastasis. So as a result, the best way to diagnose it in this patient is a CT-guided adrenal biopsy. Let's just continue for now. So yes, one can biopsy the adrenals. As long as pheochromocytoma is ruled out, you can biopsy as many times as you want, in theory. I'm not advocating for that. But that's the whole point. You have to rule out pheos. So in this case, the patient had a slightly elevated normal and different levels. It wasn't that elevated. And usually, when it's mildly elevated, less than two times, traditionally, it's three times upper normal. But now a newer assay says two times upper normal. One should not think automatically it's a pheo, but perhaps it's a secondary cause. So it could be medications, phlegm depletion, something, but not a true pheochromocytoma. Other false positives could be medications such as TCAs, serotonin, norepinephrine replic inhibitors, clonidine withdrawal, state biopsy, and there's quite a few other options, causes, I should say. So in this patient, the CT-guided percutaneous biopsy demonstrated findings consistent with histoplasmosis. I believe he is from Ohio, I think. Regardless, that's where histoplasmosis is endemic. Next slide. Okay. So, as I said earlier, patients with autoimmune adrenal insufficiency, they have small adrenal glands. So, you know, most fellows answer tonic hydroxylase antibodies, which it's not a bad answer. However, the question was the diagnosis and management as well. So the diagnosis is adrenal insufficiency, you know, and management will be, well, in this case also, you should probably treat the underlying cause as well. That is the histoplasmosis. So even if it was positive, it would not really change the aid in the treatment, I would argue. Urinary free cortisol, we don't use it to diagnose adrenal insufficiency, that's out. And because this patient has primary, not secondary, one does not need pituitary imaging. Adrenal venous sampling, adrenal vein sampling is just not done overall in the evaluation of AI, adrenal insufficiency. Next slide. Okay. And this is the last question. 36-year-old female presents with a one-year history of worsening anxiety, palpitations, and sweating. She describes episodic anxiety with feeling of heart racing, pounding, has not drenching night sweats on her upper body and face. Symptoms are not provoked by physical or emotional triggers. These episodes are unpredictable. They resolve within a wild interval of time, 15 to 60 minutes. And during her episodes, her blood pressure ranges from 154 over 80 to 210 over 100 millimeters per mercury. So a few chromocytomas diagnosed. After plasma, normal and different levels were found to be six-fold elevated and abdominal cascand imaging reveals an eight-centimeter left adrenal mass with high attenuation characteristics, basically high Hansel units, 45 Hansel units pre-contrast. Of note, her father died of a metastatic gastrointestinal stromal tumor, and her mother and sister have had breast cancer. Next slide. So the pathogenesis of the patient's field chromocytoma is most likely attributable to a pathogenic variant in which of the following genes. You have A, EPAS1, B, RET, C, SDHB, T, TMEM127, and E, VHL. So the answer is, as most fellows got it correct, C, SDHB, succinate dehydrogenase B. Although VHL is actually quite close behind as well. Next slide, please. So the patient, she presented very classically for a feo, a chromocytoma, with her palpitations, tremors, the diaphoresis, and her imaging showed that it was non-lipid rich, basically Hansel units above 10, actually, and in her case, it was 45. So very suspicious of a being a feo, or at least not an adrenal lipid rich adenoma. Okay, so at least a third of all feos in Paris are attributed to a known germline variant. For all intents and purposes, nowadays, all patients with a feo or paraganglioma should undergo genetic testing, because obviously, it would shed more light on the prognosis and also of genetic testing for the family members as well. So this patient's family history of a metastatic gastrointestinal stromal tumor should raise concerns for a pathogenic variant of one of the SDH, A, B, C, D, or AF2 genes. The variants in this SDHX gene can cause a patient to have a lifetime risk of developing a feo, paraganglioma, and there's more, there's a renal cell carcinoma, gastrointestinal stromal tumor, pituitary adenoma, and SDHB is most likely culprit gene in this case, SDHB, it is unfortunately, the most aggressive and B is B for bad, it can cause abdominal and thoracic tumors, actually, VHL genes are also common. It's also a common cause of feos. However, and usually the patients they do have cerebellar hemangiomas, retinal angiomas and neuroendocrine tumors. It's not a bad, it's not a bad, bad question, bad answer. It's just that the probability wise, SDHB should definitely be tested first before testing VHL. And I do think time is running out. So I think that's well, next slide, next slide, please. I'll go quickly over lists. Let's see now, the red gene, you know, MEN type two, it can cause, it can be the cause of feochromocytomas. However, they also have other causes, other symptoms such as high calcium. Let's see now. And TMEM 127 and EPA S1, they're very rare causes for feo. And they're, yeah, that's not technically what we see, what we're concerned about. Next slide. So I apologize for running over time. And please. No worries. Thank you, Dr. Chang. And we'll move on to our final section, which is Dr. Loh covering the thyroid. Okay. Thank you, Dr. Kura. Hi everyone. I'm sure you're dying to get outside because it is a gorgeous day on the East coast. So I'll try to get you guys out of here, but just hang on for a couple more minutes. We have three questions and they're pretty high yield, we think. First one, 48 year old female, she felt right thyroid nodule a month ago. She's had a whole year of symptoms such as difficulty sleeping, anxiety and palpitations. She has had no neck pain, compressive symptoms or voice changes. She's got no history of radiation exposure or family history of thyroid cancer. On exam, you can feel the nodule. It's on the right hand side, four centimeters. There is no cervical lymphadenopathy. She does have a fine tremor and the rest of the exam is normal. Lab shows suppressed TSH of 0.01. The free T4 is normal, 1.56, as is the total T3, 172. Here's some pictures. You get an ultrasound and there's the nodule on your left. So the right sided nodule is the leftmost picture. It's 4.5 by 2.9 by three centimeters. You can see it's solid isoechoic. And then you see a left-sided nodule. Sorry, this is not the same level of magnification. And in case the left-sided nodule is solid hypoechoic and it measures 2.7 by 1.6 by 1.7 centimeter. Because she has a low TSH, you went ahead and gotten thyroid uptake and scan. And you can see that result right here. The uptake at six hours is 12.5%, which is in the normal range. And you can see the distribution of the radioactive iodine uptake. And it is mainly distributed within that right lower thyroid nodule. Question is, what is the most appropriate management to recommend next? Would you, A, refer her for right lobectomy. B, check a TRAB. C, biopsy the left nodule. D, biopsy both nodules. E, biopsy the right thyroid nodule. And the answer is, biopsy the left thyroid nodule. So she came in, remember, with the palpable right thyroid nodule. She didn't even know about the left side. But as you know, she had iodine uptake in that right-sided nodule. And on the left side, it was just either ISO uptake or it wasn't cold, but it wasn't hot. So it was sort of like a warm area. So once again, you see that she had subclinical hyper and a multinodular thyroid. Again, she had a hot right-sided nodule. That's the one that you could feel and that we could see. And this one, we're not gonna biopsy because they have a very rare, not zero, but in general, for your purposes, it is very rare risk of malignancy. So in general, it's not necessarily recommended to biopsy a hot nodule. On the other hand, on the left side, the nodule should be biopsied based on its sonographic risk characteristics. So you saw that it was hypoechoic and solid. There were no calcifications. The margins were okay. And so in the absence of other high suspicion features, this would qualify as TIRADS-4 or ATA intermediate risk. And so basically being 2.4 centimeters, it does qualify by both criteria. They are a little bit different with those two risk stratification systems, but for intermediate risk, the cutoffs are one centimeter for a hypochoic solid nodule for ATA and 1.5 for a TIRADS-4 nodule. So we would biopsy the left nodule. All right, next question. Yeah, so for all those reasons, we would biopsy the left nodule. So the question choice B, measurement of the TRAB, would not necessarily help us in diagnosis here. We know that she has a hot right nodule. And so measuring to see if she also has Graves concurrently would not necessarily be the next best step. Okay, next question, please. Okay, next one. This is a 34-year-old female. Gravita 1, para-zero. She is currently pregnant, 31 weeks. She was diagnosed with Graves' disease. Sorry, that's a typo. It's 14 weeks ago she was diagnosed. And at the time she had had palpitations and weight loss and dyspnea, and she was started on methimazole five milligrams a day. Since that time, she seems to be doing very well on methimazole. Her symptoms have gotten better. She's regained some of that weight and she has no eye symptoms of thyroid eye disease. You see her today at 31 weeks. Her blood pressure is good, 110 over 60. Her pulse is 80. Her weight is 155 pounds and her BMI is 24. Her thyroid exam shows mild symmetric enlargement without nodules and gravid uterus. Her labs. So at 17 weeks when she was first diagnosed, she had a fully suppressed TSH. The total T4 was elevated at 21 with the upper limit of normals you can see all the way at the right-hand side. Total T3 was 340 and the TSI was elevated at 140. And now today the TSH is suppressed. The total T4 is 17. The total T3 is 290. Just wanted to pay attention to the upper limits of the reference ranges for the total T4 and T3 because that's sort of the point of this question here. Okay, so it looks high, but is it within the upper limit of normal for pregnancy? Next slide, please. Question is, in addition to checking her labs again in one month, what would you do next? Would you A, keep going? Same dose methimazole, five milligrams. B, stop the methimazole and switch to PTU. C, would you increase the methimazole? Or D, would you now refer her for thyroidectomy? And the answer is, keep going. She's doing great. Most of you got that right, except for not really. So a lot of people thought maybe the methimazole dose should be increased. So this is an important point is because it looked like her thyroid hormones were still elevated. It looked like she was still hyperthyroid. I think that was the reason that many of you felt that the methimazole dose should increase. So we're gonna tell you why she's actually fine the way she is right now. So as you know, the antithyroid drugs are teratogenic and the highest risks occur in early pregnancy. This is why, and one of the only main reasons why we would use PTU is that it is preferred in first trimester because methimazole has more severe associated birth defects in early pregnancy, like aplasia acutis, et cetera. So the goal of all antithyroid drugs is to use the lowest possible effective dose to maintain euthyroidism or actually even run patients slightly hot. So the patients, so the TSH, we're not actually looking at the TSH too much because we know that the TSH will lag behind and normalizing the TSH may not be the goal that you're looking for. You're really looking and micromanaging that three or total T4 level and also the T3 level as well concurrently. Bear in mind that the upper limit of total T4, what should it actually be? Well, after 16 weeks, you're basically looking for your total T4 upper limit of normal to be about one and a half times the upper limit of the non-pregnant reference range. So that's just sort of an easy way to think about it is just look at the upper limit of normal and go one and a half times that. And that's sort of around where you wanna keep people maintained. Prior to 16 weeks, there's a quick calculation. You can do an elevation of 5% per week of the upper limit of normal. And that's basically because the HCG affects the total T4. The free T4 is a little bit less accurate to follow. You can have some spurious low levels of free T4, especially in the latter half of pregnancy due to the direct free T4 assays, even though we're only supposed to be looking at free T4 with these assays, there is still some dilution there. And so sometimes we just measure a total T4 if we're worried about a discrepancy. Next slide. All right, so the whole point there is measure the total T4 and then calculate your own. Unless you have it given to you, some of the labs will already give you a pregnancy-specific reference range. But if they don't, then you can calculate your own, just go with one and a half times above the upper limit of normal. All right, the other choices are not as good or wrong. And this is the reason why. To change from PTU to methimazole, this is actually something we recommend you do. So if you had to start an antithyroid drug in early pregnancy in the first trimester, then we would recommend PTU because of the birth defect risk. We would then change to methimazole at 16 weeks, basically because of the risk of severe liver toxicity that are associated with PTU. The question choice here was whether you should change from methimazole to PTU. Never would we do this, all right? Unless there was a severe allergy or something like that. But at this point, this would not be indicated. Would we increase the methimazole dose here? Well, so the reason that we wouldn't is that this could actually lead to fetal hypothyroidism. The fetal thyroid is actually more sensitive to antithyroid drugs. And so you really don't want to over-treat. And so again, like my mentor used to tell me, run them a little bit hot or slightly undertreated, and this will not lead to any adverse pregnancy outcomes. Last answer choice is thyroidectomy. Yes, you could consider thyroidectomy as definitive treatment of grave. So generally we would reserve that for early in the second trimester, which is around 23 weeks or less. And that's mainly if we're having a lot of trouble maintaining control or if there is an allergy or contraindication to the antithyroid drugs. Here we are at 31 weeks. She seems to be doing just fine. So we would not necessarily think of that as the next best choice. All right, onward to the last one, over this one. Okay, 52 year old man. He presents with palpitations. He lost some weight recently. He was 237 and now he's 211. And he's been otherwise just fine and healthy. He's had no recent illnesses. He takes no meds and no supplements. On exam, his pulse is 97. He has no eye findings of thyroid eye disease. His thyroid is non-enlarged and non-tender. And he does have a fine tremor of his outstretched hands. Labs are obtained and they show a suppressed TSH, a free T4 elevated at 4.3, a total T3 elevated at 290. Because he's hyperthyroid, a radioactive iodine uptake is obtained and it shows less than 1% uptake at 24 hours. A spot urinary iodine is also obtained and this is non-elevated. So which of these things would you do next to properly reveal this patient's diagnosis? Would you check a SED rate? Would you check or repeat a radioactive iodine uptake and scan after a low iodine diet? Would you check a thyroglobulin? Or would you check a TSI? The answer is to check a thyroglobulin. There's quite a spread of answer choices here. So I just wanted to go through the differential diagnosis of low radioactive iodine thyrotoxicosis. Okay, so when you have thyrotoxicosis with low iodine uptake, that means that the thyroid cells are not avid for iodine. So the main etiologies of this would be all your thyroiditis, right? So non-avid, your thyroid is just kind of, it's like a volcano that's erupting, erupted, right? So you have painless thyroiditis, subacute thyroiditis, postpartum thyroiditis, struma. The thyroid cells here are avid for iodine, but you just can't see them. When you're doing an iodine uptake, usually you just have a neck scan. You would see avid iodine uptake in the pelvis. But in this case, it would show a negative iodine uptake in the neck. Factitious thyroiditis, of course, because your thyroid is not making additional thyroid hormone you're just getting it from the outside. Amiodarone use, basically because of the high iodine ingestion. And again, also any recent high iodine dose, iodine exposure. So in this case, we can rule out postpartum thyroiditis, struma and amiodarone. He's a male, so he can't have any of those two thyroiditis. And he was not taking any medication, so it's not amio. Next one. He had no viral prodrome, fever, thyroid fullness or tenderness, so we can knock out subacute thyroiditis. We can also knock out recent high dose iodine at the bottom because his spot urinary iodine was non-elevated. So this leaves us only with painless thyroiditis or factitious thyroiditis. How are we gonna tell the difference? We are going to check a thyroglobulin level. That will basically tell us the difference between these two idealities. So in painless thyroiditis, the thyroglobulin should be high. In factitious thyrotoxicosis, the thyroglobulin should be low. So remember there's endogenous thyroid hormone being liberated in painless thyroiditis, high TG. There is exogenous thyroid coming in from the outside in factitious, so your own endogenous thyroglobulin should be low. So a quick thing on the clinical course of painless thyroiditis, usually it resolves 50% of these people will also have a concurrent TPO antibody. Not all of those will move on to become permanently hypothyroidism, but there will be a proportion of those people with permanent hypo to follow. Some patients you should know will also have some recurrent thyroiditis years later. Factitious thyroiditis, some of the clues were that there was no goiter at all. And then the doses of thyroid hormone that would be associated with weight loss. So this person lost like 20 pounds or something. At those doses, you're probably going to get hypothyroid because that's the kind of thyroid dose that you would need to result in some weight loss. So he had the tremor. And I think that was my last slide. The reason the other ones were wrong real quick, why would you not check a SED rate? So he didn't have symptoms of subacute thyroiditis. So we, and also the SED rate is not helpful in painless thyroiditis. It's usually non-elevated. Would you repeat the radioactive iodine scan after low iodine diet? No, basically we would only do that if we were worried that he had a huge iodine ingestion and we didn't know. And so then we would have to ask him to do it over again, but we have a good urinary iodine. It's not so high iodine. And D, would you check a TSI? So, you know, not necessarily wrong in real life. We might check it anyway, except that we now have clearly an iodine scan that is not consistent with Graves. And so the radioactive iodine should be very high in Graves' disease. So checking a TSI would probably not be helpful here. And I think that is it. Yeah. We do have two questions about the first question about the uptake and scan. And the question was the thyroid uptake scan was normal. So how did we know that it was a hot module? Yeah, good question. So for some reason they didn't give us the 24 hour uptake. And so the 24 hour uptake should be a little bit higher. It may not actually be frankly elevated. And you can see that on the labs, if you remember back, they only had subclinical hyperthyroidism. So you may not actually have frankly elevated iodine uptake, but the distribution of the scan should be the thing that gives you the clue as to what to biopsy and what the cause of subclinical hyperthyroidism is. Great. And then the last question is if the patient with both nodules on neck ultrasound, if they had a positive TRAB before doing uptake and scan, would you assume directly that both nodules should undergo FNA and not do the uptake and scan? Ooh, so there's something called Marine Lenhardt syndrome where you have Graves and you have nodules. And sorry, Graves and hot nodule. And so in that case, I wouldn't necessarily not do the uptake and scan. In real life, you probably would get an ultrasound first, or at least in my office, we'd get that done in the office right away. So we'd know that the person has nodules and the person actually presented with nodules. So you'll have that ultrasound, you know they have nodules. You're looking for underlying Graves, not a bad idea because Graves underlying is actually quite common. And so in that case, I think you would still proceed with the iodine uptake to look for which one was autonomous so that you could guide which one to biopsy. Great, thank you. And thank you to all of our panelists for coming and presenting today and for all of the participants. So the slides will be posted in the next few weeks along with the recording. So thanks again to our panelists.

obesity treatment

semaglutide

GLP-1 receptor agonist

weight loss

BMI 27

hypertension

type 2 diabetes

recombinant leptin

congenital leptin deficiency

setanilatide

hyperthyroidism