Hi, good afternoon everyone and thanks for joining us today. I think Andrea you were going to start with the introduction. Yes, thank you. Okay. Hello everyone. My name is Andrea Willis Sanchez and I work at endocrine society as the digital program administration coordinator, and I'm so happy to welcome you all to it 2022 live session to please note that the sessions this week are being recorded. So if you weren't able to attend on Tuesday, or you just want to review this at a later date, you'll be able to access that via the Center for Learning and more information about that will be available in the next few weeks. So without further ado, I'd like to welcome our moderator, the IT chair, Dr. So we will correct. Thank you. Great. Thank you, Andrew and thank you for all your hard work putting all these sessions together. So welcome to everyone and this is our second session and today we'll be covering diabetes lipids and obesity pituitary and bone. Next slide please. Thank you to our wonderful faculty have put in a lot of hard work into making this test as successful as it is so thank you and thank you to everyone who came today to speak, and to present their slides. So next slide please. And these are our disclosures. Next slide. So just some important points about it, it should really be treated as a learning experience by programs rather than a formal high stakes knowledge assessment. The purpose of the test is really to give both fellows and programs an idea of where their gaps may be and the areas that they should focus on and the areas that they are in terms of their knowledge base already well versed in so it's just to give both fellows, some basic tools to move forward with their training and to determine which areas they should spend the most time learning about. So this is just the fellow performance and I went over this in the first it sessions I won't belabor these points but as you can see, progress, we did see progress with a program year with the second year and third year fellows doing better than the first year, which is exactly what we would expect and would want, because the purpose of the fellowship training is to gain clinical knowledge and thereby answer these questions a little more easily with time. Once you progress through the program, and at the average score is around 60 which is consistent with years past. So this just goes a breakdown by topic area and as Dr. Duncan pointed out in the last session, it's a little bit unfair and that some of these denominators are smaller for, you know, male reproduction adrenal so fellows may know these topics as well but did they have a less of a chance to get the questions right So I'm just going to go over a few questions and some of these topic areas, but overall, this really should just be a guide of what areas to focus on as you study for boards and as you move through your clinical practice. Next slide please. So, let's get started and we'll start with the diabetes team first so Dr. Derek Beckman from the San Antonio Uniformed Health Services, and Dr. Ganjan Gandhi from the University of Florida health Jacksonville we presenting this section. Thank you both for coming and speaking. So that's the first three questions and Dr. Gandhi's got the last couple there. So first one up. Question 12 here, and I won't read everything off the slide but 24 year old gentleman who ate a piece generous piece of cake had symptoms about 30 minutes later, including headache dizziness and sweating and noted a finger stick glucose of 220 and measured a once in seven percent and noting a normal BMI, and you can see who started on insulin but over time had reduced his insulin dose down to four units due to nocturnal hypoglycemia. And so he really looks at reducing his carbohydrate intake and mealtime insulin. No other relevant relevant history. Next slide. And you see the family history here which is particularly important with there is type two diabetes in the paternal grandfather, unknown if it was any diabetes related complications but the father did have diabetes type two diagnosed complicated by neuropathy and and you can see the labs down here with an A1C of 7.4% after being on insulin, a present C peptide there with the glucose elevated at 165, and negative GAD antibody or get 65. Next slide. So the question is, which, which this patient is most likely to have which pathogenic variant of the following genes and go ahead and hit the next one there for us. I don't need to read all those out for you. You can see the answers, who answered, or how many answer to the right there. The HNF1A is our right answer with the most selection and then the second was the GCK. Next slide. Our next. Our objective here is to classifying diabetes other than our normative and looking at patients with low BMI. Next slide. So looking at this again I won't get too much into this but really that middle section they're looking at, if you're thinking about Modi our young folks with sometimes can be normal BMI which will be some somewhat of an indicator under the age of 30, you can see that you're going to be a betting person that HNF1A is going to be the majority of your Modi genes. And then GCK is 15 to 32% with HNF4A being only 10% and that's going to catch 99% of your pathogenic variants and then there's a small subset of many others. So we can see that we did one and two HNF1A and GCK, but really looking at GCK generally doesn't have any complications and so you can see that highlighted in the second to last paragraph that the father was likely misclassified and he did have a diabetic neuropathy and so concerning less can less consistent with GCK so playing the odds, and then there's family history of complications makes it the most likely is HNF1A and not GCK, and you can read through all the other ones there about why they are not the correct answers. Next slide. Next question. 59 year old woman with type two diabetes, five years duration, and having diabetic neuropathy or peripheral neuropathy. Over the past three months, however, is complaining of polyuria and unintentional weight loss of 10 pounds. Poor adherence to recommendations for lifestyle modifications, and she's having issues with joint discomfort so not doing a lot of activity or exercise. Next slide. Blood pressure a little elevated, BMI elevated at 32.3, no acanthosis, niagara cans, facial plethora, dorsal cervical fat pad, kind of ruling out her Cushing's concern, peripheral pulses and findings on foot exam were normal, but there is loss of Achilles tendon reflexes, but normal vibratory and monofilaments, or sorry they're both impaired, vibratory and monofilament impaired. A1C still elevated at 9.2%. Next slide. So what would be the, in addition to lifestyle changes here, what's the best medication to add on here? Next slide. Next iteration there. And so insulin detriment, you can actually see that that's our second most commonly chosen answer and loraglutide was the winner here. So we're really looking at determining when to add insulin as a better choice than other non-insulin agents. And so that's why we really chose this one is for this little edification piece, which is important. Next slide. While she still is obese, I really got to be concerned again, suboptimal glycemic control, we see that a lot and has complications, but most importantly here that she's having hyperglycemia and catabolism, unintentional weight loss. And so that's why insulin is the best answer here, despite she still has an obese BMI that she's in catabolism. Over time, likely being able to add those other non-insulin agents on board would be very reasonable. But the fourth bullet there noting that the presence of polyuria and unintentional weight loss suggesting catabolism, noting that loraglutide and impagliflozin combination is not the best choice currently. However, in the future would probably be reasonable. We don't generally like sulfonylureas, no other significant benefits and unlikely to meet its criteria, i.e. reducing the A1C enough. And similarly, loraglutide alone or impagliflozin alone, in addition to catabolism would not benefit there, probably wouldn't alone meet the target A1C for the patient of less than 7%. Next slide. And so this question here is getting more at neuropathy. So a 66-year-old male with type 2 diabetes, he's well controlled over the past five years. He's on exanatide, long-acting and insulin glargine and A1C doing very well at 6.5%. So no hypoglycemia and weight is stable. Has had peripheral neuropathy for years and treated with gabapentin currently on 300 milligrams three times a day. However, over the past years has some changes, increasing numbness and decreased sensation in his feet. But notice that he's having some weakness in his hands, as well as difficulty getting dressed and getting up from a seated position. He's experiencing falls at home and he's getting more worsening of his burning sensation. Of note, has a history of Crohn's disease and underweight colectomy 20 years ago. On the physical examination, he's having some decreased sensation on the monofilament. Of note, he's having atrophy of his thenar eminence, as well as the dorsal web space of the hands. He has to push while using his arms to get up from a seated position and noting the decreased muscle strength. Next slide. Here are his labs. I won't extensively go through those as well. Controlled A1C, no significant protein gap, calcium is normal, no anemia on there, B12 is normal, and undetectable antibodies. Next slide. So which of the following is the next best step for this patient's management? Next slide. We do have the majority here, but we really like this one because there was a good smattering of alternative selections in regards to the next highest one was looking. For using an SPEP, UPEP to look for multiple myeloma. But remember, kind of really noting that nothing else was pointing in that direction. Next slide here. So really looking at there's different etiologies for peripheral neuropathies and patients with diabetes don't just anchor on this. We do see this a lot in clinical practice. Oh, you have diabetes, you have neuropathy, has to be diabetic neuropathy. And so make sure to keep your spidey sense up to look for alternative reasons. Next slide. So most common patterns are distal symmetric axonal sensory motor neuropathy, we very commonly see that and then second most common is small fiber painful neuropathy for diabetes. And as time goes on evolve into autonomic fibers are also common in diabetes are very infrequently or multifocal neuropathies cranial nerves model neuropathies asymmetric proximal motor neuropathy diabetic a myotrophy and symmetric proximal motor neuropathy is very uncommon. And this patient was manifesting with wasting a muscle motor deficiency that are not common. And so this patient was referred to neurology, this was a real case. The patient was eventually diagnosed with chronic inflammatory demyelinating demyelinating polyneuropathy, as I've emphasized that there's nothing else really pointing towards the second most common answer with multiple myeloma, no anemia no hypercalcemia no significant protein gap gap for this patient. Next slide, and I'll turn it over to Dr. Gunjan. Thank you, Dr. Beckman good afternoon everyone. Thank you for hanging out with us on a late Friday afternoon, at least here on the east coast. Next slide, please. So this is the largest topical area within endocrine, and roughly 22-23% of all your questions not only for the IT remember the IT follows the ABIM endocrine subspecialty exam blueprint very closely so you will still get a large chunk of your questions in the test from from diabetes. So let's go over this one. So this is a 42 year old woman who has a long standing history of type one diabetes. She comes to you on routine follow up. She has non proliferative retinopathy and proteinuria. When you start talking to her more she mentions that she has had some more fatigue and notice that she becomes lightheaded when she stands up quickly. On digging deeper, she does mention that the number of hypoglycemia episodes have increased, and not all of them are because she skips meals, and her night sleep is disrupted and she has noticed that she wakes up at times with low blood sugars. So, you know, having had this for a long time she reduces her basal insulin dose by 10% and she has done so several times, but still is troubled by hypoglycemia. Lifestyle habits have not really changed for her. You do some orthostatic vitals, note that she is significantly orthostatic with her blood pressure dropping significantly when she stands, and then her heart rate goes up when she stands significantly as well. On neurological exam, you note that on 10 gram monofilament testing, there's increased hyperesthesia and her ankle reflexes are somewhat delayed in that recovery. Next slide please. So pertinent labs to point out here her sodium level is normal but at the low end of normal range. Her potassium is mildly high. Kidney function is intact. She has mild microalbuminuria. Of note, her TSH is slightly high as well. And her A1c, the last one, is 7.8%. Next slide. So the question for you is, which of the following is the most likely cause of her orthostatic hypotension? And the options are, as you can see, the one that was chosen by most of you is adrenal insufficiency, which is option A. The second most common answer was cardiovascular autonomic neuropathy. Some of you chose hypothyroidism. Some picked sensorimotor neuropathy. And a handful of you chose salt-based stengnephropathy as the cause of her orthostatic hypotension. And the correct answer, and I think this is a reasonably straightforward question, but I think it has important educational points. So the correct answer here is adrenal insufficiency, which is option A. The learning objective is to identify and consider adrenal insufficiency in a patient with type 1 diabetes. Next slide, please. And I think this is fairly clear to most of you, and it should be, is that this person has a predisposition for autoimmune conditions. She has type 1. She likely seems to have Hashimoto's thyroiditis based on her elevated TSH. She likely has at least subclinical hypothyroidism from what we can tell. So there is increased propensity for her to develop another autoimmune condition, such as adrenal insufficiency. And this really is the classic presentation. You know, there are a few things we need to consider when glycemic control either worsens significantly, or in this case, where her insulin requirements for no good reason seem to be going down. On the other hand, there are other clues that are given. So she's orthostatic. She has hyperkalemia. She has low normal sodium. And the important point here also is they may not always have the orthostatic hypotension or the electrolyte abnormality. So even if those were not as significant as in this patient, I still think your suspicion for adrenal insufficiency has to be heightened with her clinical presentation. I think another reasonable one to consider would have been autonomic neuropathy because of the orthostatic hypotension. But remember, the first manifestation for autonomic neuropathy, at least cardiovascular-wise, is they tend to get resting tachycardia. And that resting tachycardia becomes a fixed tachycardia. So even on standing up, you would not see a reflex increase in their heart rate as was seen in this patient. So I think that is a clue that it's unlikely to be autonomic neuropathy. And then typically, these have advanced microvascular complications, including peripheral neuropathy. And in her case, the neuropathy seems fairly mild. Hypothyroidism, I don't think there is much given here that would suggest that. Certainly not orthostatic hypotension as a manifestation of hypothyroidism. And then because her sodium level is not, frankly, low, I don't think salt-wasting nephropathy is necessarily higher up in her differential diagnosis as well. So just a good basic question of think of adrenal insufficiency with falling insulin requirements in a patient with strong autoimmune predisposition. All right, next question, please. All right, so this will be the last diabetes question. So 32-year-old woman who presents to you for a six-week postpartum follow-up visit. So she was diagnosed with gestational diabetes during her pregnancy. And she had a screening oral glucose tolerance test at 22 weeks. Remember, routinely at 24 to 28 weeks, an oral glucose tolerance test is performed to screen for diabetes in pregnant patients. And that was abnormal in her case. So she started with lifestyle changes and went on to require insulin therapy during her third trimester. The delivery was uneventful. And really, she had a healthy daughter who was normal in terms of her weight. And to credit the patient since delivery, she has intentionally lost 10 pounds, but has continued a basal bolus insulin treatment regimen since her hospital discharge. Her blood sugars on her log seem good. They are all in a good normal range. And she's been experiencing occasional hypoglycemia. So she wonders and she questions, she poses a question to you whether she can stop insulin therapy. Next slide, please. Which of the following is the best recommendation for the patient's question. So option A is to continue current treatment. And I guess you just want to maybe inflict more pain on your patients, but you tell her to continue current therapy and only a small minority of you chose that option. Option B is change from insulin to metformin. Option C is you stop insulin therapy and you perform an oral glucose tolerance test in one month. And this was the most popular option chosen by most of you. And the last option was stop insulin therapy and measure A1C in three months, which seems like a possibly a reasonable option to consider as well. The correct answer here, and again, you know, most of you got this correct is option C, which is stop insulin therapy and perform an oral glucose tolerance test in one month. And the objective for this question is to know what the appropriate follow-up should be for gestational diabetes patients, especially in the postpartum period. Next slide, please. So, you know, one comment I'll make is that as adult endocrinologists, we don't commonly order oral glucose tolerance tests very often, but for boards, and I guess for practical purposes as well, for pregnant patients and in the postpartum period is one time when there are merits to doing an oral glucose tolerance test. And sometimes in PCOS patients, there may be merit to doing oral glucose tolerance testing as well. I think one important point to remember is, well, there's two points. One is a lot of patients with gestational diabetes will revert to normal glucose levels postpartum. However, as you all know, these patients are at particularly increased future risk of developing diabetes and impaired glucose tolerance. So they do need close follow-up. And a standard test that is recommended is the one step. So it's not the two step 50 and 100 gram. This is a 75 gram OGTT, and you do it six to 12 weeks postpartum. And the reason for that is it has been shown in studies to be more sensitive at detecting glucose intolerance. And, you know, some of you may ask, well, is A1C not an easier test to do given that you can diagnose diabetes and prediabetes based on that. But in this situation, remember, if you do an A1C, one is it might still reflect the higher blood sugar she had pre-delivery. Second, there is increased red blood cell turnover, especially in that peripartum period. And there is some blood loss during delivery so that A1C may not be completely reliable. So because of these reasons, and because OGTT is superior and more sensitive at detecting glucose intolerance, and OGTT is the way to go to screen for diabetes in the postpartum period. And one last point I'll make is, let's assume the OGTT comes back normal in this patient. Remember, we know they're at higher risk for diabetes in the future, so they do need appropriate follow-up. And this may be a patient who, if she decides to become pregnant, you may either screen preconception or screen with OGTT early on in her pregnancy rather than waiting for 24 to 28 weeks. So she would be considered a high risk for developing diabetes in the future pregnancies and over her lifetime as well. So with that, I will end my part of the presentation, and I think, I believe we have lipids next, lipids and obesity. Great, thank you, Dr. Beckman and Dr. Gandhi. And then now we'll move on to lipids and obesity. And Dr. Rashmi Srinath from the ICANN School of Medicine in Mount Sinai will be presenting. And if you have questions, please put them into the Q&A section and we will address them at the end of the talk. Great, welcome everyone, good afternoon. So I'm gonna start with our first question. This is lipid obesity question 10. So this is a 36 year old female who has been attempting to lose weight to improve her health. Her current height is 67 inches. Her weight is 245 pounds with a BMI of 38.4 kilograms per meter squared. She does have type two diabetes and dyslipidemia. She was recommended to start a low glycemic index reduced calorie diet inducing a 500 calorie deficit per day and is currently eating about 1800 calories daily. In addition, she has been exercising, walking on a treadmill for about an hour, five days a week and incorporating some resistance training. She's been keeping her daily food diary on an app and she's lost 40 pounds, tremendous over two years. Over the last few months, she's regained a little bit of the weight, approximately eight pounds or 3.6 kilos. Her food diary indicates she's consuming about 1200 to 1400 calories a day and doing well in maintaining her exercise regimen. But she's frustrated and really worried about all of this weight regain. Next slide. So the question here is, which of the following is the main cause of this patient's weight regain? Your answer choices are A, increased energy expenditure, B, decreased satiety, C, decreased energy expenditure or D, increased appetite. Next one. And the answer here, which majority, 573 people chose here is answer C, decreased energy expenditure. And we'll talk a little bit about why that is. Next slide. So the rationale here is, yes, this patient clearly has lost significant weight over the last few years, but she has experienced a plateau with regain. And we know that this is very common. I see patients with this every day almost. What we need to counsel patients and understand is that the body's adapting to this. In several ways. So as we lose the weight, there is a shift in the hormones and such that it favors the hunger hormones, such as ghrelin over the hormones that suppress your appetite. And what we also know is that to maintain stable weight, we have to keep our daily expenditure stable. So your intake must match your output. And I actually put the equation in here to review. So your total energy expenditure is equivalent to your, what we call basal metabolism or basal metabolic rate, which is your resting energy expenditure, plus thermogenesis, which is approximately 10% of the total, and plus your activity level, which is about 20 to 30%. So what we know is that when people do lose weight, there is a drop in the resting energy expenditure. And we do have to keep that in mind as patients are losing weight. Remember also to keep in mind that your resting energy expenditure is actually dependent on lean muscle mass. So this will fall as people lose weight because of a loss of both lean body mass and fat mass. So again, the key point here is that as patients lose weight, their metabolism is changing. There is a hormonal shift. We call this metabolic adaptation. And we need to counsel patients that yes, it does get harder. And that's where, again, they have to continue to work hard, eating well, exercising, and doing their best. And if they're regaining, this might be an option to consider pharmacotherapy. Next slide, please. Great, so we're gonna go to the next question. We're gonna shift gears a little bit. So this is a question about lipids. So this is a 45-year-old presenting with hyperlipidemia and seeking advice for secondary prevention of cardiovascular disease. He had a myocardial infarction approximately six months ago, complicated by a stroke. He has not smoked cigarettes. He is exercising now and is now taking a torpostatin 80 milligrams every day. His LDL cholesterol has improved. It's now under 100 milligrams per deciliter. However, he develops a second heart attack three months ago. And his twin brother actually passed away suddenly of a myocardial infarction at age 44. On examination, you note that his blood pressure is 126 over 74. As you can see, his heart rate is normal. His BMI is 27 kilos per meter squared and his waist circumference is 36 inches. Next slide. In terms of reviewing his labs, you note that his total cholesterol is 155. His LDL is 85, his HDL is 44 and his triglycerides are 128 in the normal range. His A1C is normal at 5.3. Thyroid function tests are normal and ALT of 24. Next slide. And so the question here is which of the following most likely explains this patient's high cardiovascular disease risk despite his response to statin therapy? So we have our options A here, apolipoprotein A1 deficiency, B, elevated lipoprotein A, B, I'm sorry, this is option C, ABCA1 deficiency, or option D, elevated apolipoprotein B. And next slide, please. Our next iteration. The answer here is answer B, elevated lipoprotein A. And this is a really good question because it highlights patients clearly who have high risk, what is the etiology and clearly patients on a high dose statin, what else is going on? Next slide, please. So the rationale here is that yes, we do have more markers for evaluating cardiovascular risk. In a traditional office patient, you're gonna get a lipid panel, but in someone here who's had multiple cardiac events, has family history, you wanna go up and beyond that. So in someone who has these risk factors, lipoprotein A we know is highly atherogenic. It can be associated with increased cardiovascular disease, particularly premature, meaning at an early age. We know that lipoprotein A is an LDL particle. It is a large protein attached to apolipoprotein B and can contribute to atherosclerosis. It can be slightly elevated in some conditions such as familial hypercholesterolemia. But when we see levels being very, very high, we know that this person's at very, very high risk for future events. Next slide. And so we know that in certain patients, there are certain indications for when you want to consider this. So someone who has premature atherosclerotic disease or personal history of these events without other risk factors, not smoking, no alcohol use, nothing else significant. And what we know is that if the value is above 50 or greater, this is something that should be evaluated. I've listed here on the table below some other risk factors that may favor statin therapy in someone who has mild to moderate risk of heart disease. And I won't read through that below, but I think the key point here is that in someone who may not have diabetes but has increased risk, multiple events or family history events, you may want to go up and beyond the standard lipid panel to evaluate their cardiac risk. And there are some reasons here that are listed for when you might want to pursue that option. Next slide, please. Great, I think actually we skipped one. Sorry, go back. Yeah, so this is just a summary of the different apolipoproteins. Just talking about what are the other options. We have apolipoprotein B. Which is another protein found on atherogenic lipid particles. We have apolipoprotein A1 and ABCA1 or ATP binding cassette deficiency. Again, not the main contributor here in this question. Next slide. So this is question 81. So this is a 45 year old man who is interested in starting a weight loss medication for weight loss and obesity. He has already started reducing his caloric intake but is having difficulty because of cravings and hunger. He's already gained approximately 20 pounds or 9.1 kilograms in the last year. In the last three years, he unfortunately has had worsening spinal stenosis. So he has limited his mobility. He can ambulate about 10 minutes before he experiences leg and back pain. And he's taking narcotics, particularly oxycodone as needed. He also has high blood pressure, hypertension for which he takes hydrochlorothiazide, hydralazine, and nalopril. And he has CKD stage three, which has been stable for the last few years with an estimated GFR around 45. He does smoke cigarettes. On your evaluation, on examination, he is 65 inches. His weight is 196 pounds, giving him a BMI of around 33 kilograms per meter squared. His blood pressure is slightly elevated, 156 over 88. You notice on exam that he does have truncal obesity and some mild pinning edema of the lower extremities. Next slide. Next slide. In terms of lab results, you have a hemoglobin of 12.1 in the normal range. Creatinine is elevated at 1.9 milligrams per deciliter. Fasting glucose is elevated at 105, normal under 100. His LDL is 110. His HDL is 53 milligrams per deciliter, and his triglycerides are elevated at 185 milligrams per deciliter. Next slide. So the question here is which of the following would be an appropriate weight loss prescription for this patient? And our options here are A, extended-release fentramine to Pyramate, of which 31 people responded yes. B, fentramine monotherapy, of which nine people responded. C, naltrexone bupropion. D, liraglutide. And E, metformin. Next slide. So the answer here is D, liraglutide for multiple reasons here. Next slide, please. And so it's important to note that we have multiple FDA-approved weight loss medications for use as adjuncts to lifestyle therapy. We consider that calorie restriction, engaging in moderate intensity activity. And so for patients who have a BMI over 27 with complications such as hypertension, hyperlipidemia, or sleep apnea, or type 2 diabetes, or if they have a BMI over 30, they would qualify for these drugs. And what's important to note here is this is a patient who clearly is limited in terms of ability. He's on narcotics, so his exercise may be slightly limited. He does have from his labs a slightly elevated blood sugar of 105 and some mild CKD. We also note that he has hypertension, multiple other comorbidities. So when you're weighing your choice of medication or pharmacotherapy, you want to look at not only what is their weight, what are their comorbidities, and how are they gonna respond given potential medication interactions. Next slide. So here I've sort of listed out all the medications. Again, this question was a little bit old in that we don't have the newest drug available, which is Wagovi. But here, you know, loraglutide or sexthenda is the best option here. This is a GLP-1 agent, which titrated can contribute to both helping this patient with weight loss and lowering glucose and diabetes risk. We know that thentamine monotherapy is not ideal, especially given his ongoing hypertension. His blood pressure is uncontrolled at your current visit, and he's on multiple agents. We don't typically use Orlistat anymore, but this was an agent that was approved, one of the older agents, which works as a lipase inhibitor and can be effective for some patients, but again, a very mild agent. In this patient who's already on oxycodone having ongoing pain issues, you don't want to give him naltrexone bupropion given the interaction between the naltrexone and his ongoing opiates. That would reduce the effectiveness of those. And then the other options are Wagovi, which probably would be a good option here as well to consider if available. And in terms of his using phentermine to pyramid, again, the concern would be use of phentermine ongoing in someone who has ongoing hypertension, ongoing comorbidities, not ideal. So again, the answer here would be loraglutide or sexthenda. If Wagovi were available, that would be another option. Next slide. Oh, I think that's it. Thank you guys. Celila, you're muted. Oh, sorry. I was having a conversation with myself, apologies. So thank you, Dr. Srinath, and thank you to the people that submitted questions. We will address those questions at the end of the talk. And now we'll move on to the pituitary section. So Dr. Nicholas Tuitos from the Mass General Hospital and Harvard Medical School will be presenting the pituitary section. Thank you. Thank you. Good afternoon and welcome to everyone. Next slide, please. So I'd like to go over three pituitary questions. Here's the first one. A 31-year-old woman with a history of prolactinoma is now pregnant in the 34th week of pregnancy. At presentation two years ago, she had secondary amenorrhea and galactorrhea. At that time, her prolactin was 320 nanograms per ml and a pituitary MRI examination showed a macrolanoma 14 millimeters in diameter, which was not impinging on the chiasm. She was treated with bromocryptin 2.5 milligrams daily and her symptoms resolved. Menses resumed, prolactin normalized, and the tumor measured five millimeters in diameter on follow-up MRI. Bromocryptin was stopped when a positive pregnancy test was obtained. Currently, she reports no headache or visual symptoms. Visual field testing is normal. Serum prolactin, however, is 427 nanograms per ml. Next slide, please. So which is the next best step in this patient's management? A, restart bromocryptin now. B, deliver the baby. C, start cabergoline. D, perform pituitary-directed MRI. And E, continue to monitor clinical progress. And the correct answer is E, continue to monitor clinical progress, which is what most of you chose. Next slide, please. So here's why. Serum prolactin levels rise during pregnancy, including both in healthy women and in those with prolactinomas. So measuring serum prolactin is of no diagnostic or prognostic value during pregnancy and should not be done in this setting. Tumor growth may, of course, occur in about 2% of women with microprolactinomas and 20% of patients with microprolactinomas during pregnancy. However, in the absence of symptoms or evidence of visual compromise, neither pituitary imaging nor treatment for hyperprolactinemia per se are indicated. Next slide, please. So here's the second question. A 21-year-old woman with history of optic-nerve glioma diagnosed at age 11 presents in follow-up. She underwent surgery and radiotherapy for degree at age 11. She has partial complex epilepsy, treated with Lamotrigine, and was treated with growth hormone replacement between ages 12 and 19. Her menses are regular. She's currently normotensive and of normal weight. Her body mass index is 20.8 kilograms per meter square. Serum IGF-1 level is low, 72 nanograms per ml. You can see the normal range on the screen. H3T4, morning cortisol, FSH, LH estradiol are within their respective normal ranges. Next slide, please. So the question is, which of the following is the best management strategy for this patient? A, annual evaluation of full pituitary function indefinitely. B, evaluation of pituitary function if symptomatic of endocrine deficiency. C, annual evaluation of gonadotropins, that is the gonadal axis only. D, thyrotropin-releasing hormone stimulation test. And E, insulin tolerance test. And the correct answer is A, annual evaluation of full pituitary function indefinitely. As you see, it was a little close. So most of you chose A, but there were some who chose B. Let's talk why. Next slide, please. So radiation therapy to the cell or paracellar structures is associated with a high risk, about 80% you see on your screen of anterior hypopituitarism in the long-term. It's actually time dependent. It's about 50% at five years and about 70 to 80% at 10 years. So it increases over time. Annual monitoring of the pituitary function is recommended for patients who have received radiation exposure. You can see there it's indicated over 30 gray to the cellular region, even if not obviously symptomatic. The reason being that some of these patients may have relatively few symptoms, especially for example, if they have partial hypoadrenalism, they may not have specific or obvious symptoms at the time of their presentation, yet they may be at risk for adrenal crisis if not diagnosed and treated. So an insulin tolerance test, although it would be diagnostically helpful with regards to evaluation of adrenal function and of course growth hormone, it is actually contraindicated in this patient who has a history of seizures. In addition, in older patients or those with cardiovascular disease, it would also be contraindicated. And the TRH stimulation test is actually not helpful from diagnostic standpoint to evaluate the thyroid axis. And in addition, TRH is no longer available in the U.S. Okay, so next slide, please, which is the last pituitary question. This is a 76 year old man who was diagnosed with a 3.2 centimeter macroprolactinoma with a prolactin 3,200 nanograms per mL at presentation that was about a year ago. He also was found to have central hypoadrenalism, central hypothyroidism and hypogonadism at that time. He began treatment with cabergolin 0.5 milligrams twice weekly, as well as hydrocortisone replacement 15 and five milligrams, levothyroxine 125 micrograms daily. After six months, his prolactin is now normal, 14 nanograms per mL. MRI shows a decrease in the tumor size. His testosterone is low and he begins at this point testosterone replacement. Follow-up testing shows free thyroxine of 1.9 nanograms per deciliter, which is borderline high, as you can see. Testosterone is within the normal range at 632 nanograms per deciliter. By mistake, he switched to prednisone at the same dose as hydrocortisone. So he's receiving 15 milligrams in the morning and five in the afternoon. And this was apparently an error. Several months later, his wife reports that he has been spending too much money and he has been visiting prostitutes, both of which were quite uncharacteristic of him. Next slide, please. So which of the following is the most likely cause for his behavior? A, excessive thyroid hormone replacement. B, excessive glucocorticoid dosage. C, cabergoline therapy. D, excessive testosterone dosage. And E, new presentation of bipolar disorder. And the correct answer is actually C, which is what most of you chose. Next slide, please. So impulse control disorders, which is what this patient has now developed, may occur in those patients who have received dopamine agonist therapy. And therefore, all patients who are receiving such therapy, bromocritin or cabergoline, should be monitored for the possible emergence of impulse control disorders. And the medication should be stopped if these develop. And the patient should be referred to a psychiatrist as well. Mild hyperthyroidism can certainly cause anxiety, but it's unlikely to cause impulsive behaviors. Excessive glucocorticoid replacement is, of course, of concern in general for many reasons. But in addition, it can precipitate psychosis in addition to anxiety, but it's unlikely to cause impulsive behaviors. In addition, his testosterone replacement by the measures that we have is appropriate, so it's unlikely to induce impulsivity in itself. And finally, bipolar disorder usually presents in much younger patients, so typically young adults, so it would be an unlikely explanation for the patient's symptoms. So thank you. I'd like to stop here, and I'll be happy to answer any questions at the end. Great, thank you so much, Dr. Fritos. And then we'll move on to the bone section, which is our last section. And Dr. Alan Malaban from the Boston Medical Center will be presenting this. And I love the background of the osteoporotic bone. Thank you very much. And thank you all for staying late on a Friday afternoon. This question is a 52-year-old man presenting with symptomatic hypocalcemia beginning about two months ago. Four months prior, he underwent Roux-en-Y gastric bypass. Before his surgery, his calcium was perfectly normal, and he was asymptomatic. He did have, notably, a history of subtotal thyroidectomy 10 years prior due to a large multinodular goiter. And on exam, he is overweight and has a positive Shlostek's sign, but no Trousseau. His corrected serum calcium was 7.7, clearly low, with a slightly high phosphate. PTH is normal, 25-hydroxy-D is 10, and urinary calcium is quite low, and the magnesium was 2.0. Next slide, please. So the question asks, in addition to optimizing calcium supplementation, which of the following is the best recommendation for this patient? A, ergocalciferol, vitamin D2, 50,000 units weekly. B, cholecalciferol, 5,000 units daily. C, cholecalciferol, 5,000 units daily, plus calcitriol, 0.5 micrograms twice daily. D, calcitriol, 0.5 micrograms twice daily. And E, magnesium gluconate, 500 milligrams orally, three times daily. And the answer is C, cholecalciferol. And the majority of the people taking the exam got that question correct. So next slide, please. So the clues to the answer of this question is the history of the subclinical, I'm sorry, the prior thyroidectomy, and the inappropriately normal PTH in the setting of low calcium. So that suggests that there has been some hypoparathyroidism, some damage to the parathyroid glands, and you're not getting an adequate response to the hypocalcemia. In addition, you have some problems with malabsorption and overt vitamin D deficiency because of the gastric bypass surgery with subsequent calcium malabsorption. So really you need to address both issues. In addition, with the inadequate parathyroid levels, you are not converting the 25-hydroxy D to the active 125-dihydroxy vitamin D. And so to address this, you really need a high dose of vitamin D by the Endocrine Society guidelines. They recommend 3,000 to 6,000 units daily in patients who have had gastric bypass surgery or who have malabsorption. And you also need to address the hypoparathyroidism for which the CALCITRIOL will help. So A and B are not correct. Vitamin D alone will not be adequate. You really need to add the CALCITRIOL as well. And the CALCITRIOL by itself is not helpful because it doesn't address the vitamin D deficiencies. So that's why choice D is incorrect. And magnesium, sometimes if you have magnesium deficiency because of malabsorption, that can impair PTH release. But in this case, this is probably related to the prior thyroid surgery. And if you gave this patient magnesium, it may cause diarrhea, exacerbating the problem. Okay, next slide, please. So the next question is a 71-year-old male who is referred for a chronic mild alkaline phosphatase elevation for at least five years. He had an abdominal pelvic CT, which showed extensive cortical and trabecular thickening at the right iliac and pubic bones, a consistence with Padgett's disease. He has intermittent low back pain exacerbated by excessive activity. He has a past medical history of hypertension and osteoarthritis involving the left knee and the right spine. His medications include hydrochlorothiazide, etanol and ibuprofen. He has no family history. Exam is notable only for a flattened lordotic curve at the spine without tenderness on the right hip. He has no tenderness over the right lateral pelvis or inguinal region. His lab testing is primarily normal with the exception of a modestly elevated alkaline phosphatase, a 25D that may be slightly suboptimal at 25 and an elevated bone specific alkaline phosphatase at 26. Next slide, please. So which of the following is the best next step in the evaluation and management of this order? A, treatment with zologenic acid. B, treatment with alendronate. C, serum C-Teal peptide measurement. D, serum and urine electrophoresis. And E, reassurance and repeated alkaline phosphatase measurement in 12 months. The correct answer, next slide please, is E. And unfortunately, the majority of the patients unfortunately, the majority of you had chosen A. Next slide, please. While it's not an absolute incorrect answer, it does fit in with the prior endocrine society guidelines. The most recent data comes from the PRISM-EZ study. And the big question here in the consideration of the elevated alkaline phosphatase is whether it's of liver source or bone source. 80% of the alkaline phosphatase comes from either liver or bone. So if you're able to rule out liver with a normal GGT, it's likely coming from bone. And then from there, you have to ask whether it's related to osteomalacia slash hyperparathyroidism versus malignancy versus Padgett's disease of bone. And in this patient, the plain x-rays showed classic changes consistent with Padgett's disease of bone. At this point, you have to ask whether to treat. And the PRISM and PRISM-EZ study, PRISM was a study in which patients were randomized to either intensive treatment, trying to normalize alkaline phosphatase versus a symptomatic treatment in which they initiated nonsteroidals and pain-related medications for symptomatic patients. And in that study, which was followed for a median of three years, there was really no difference in clinical outcomes between the two treatment arms. One of the criticisms of the study was it was quite short and maybe we need to follow them longer to find a benefit. And that's where the PRISM-EZ study came into place. The EZ, actually, they gave the patient zoledronic acid to normalize the alkaline phosphatase in the intensive treatment arm. And in the other arm, they treated symptomatically once again. And again, they found no clinical benefit of intensive bisphosphonate therapy over symptomatic therapy. In fact, there was a trend towards adverse effects with the intensive bisphosphonate therapy. So a non-significant increase in the risk for fractures, orthopedic events, and severe adverse events, such as osteonecrosis of the jaw, uveitis, arrhythmias, and delayed fracture healing. So there has been some shift to be a little bit more conservative about bisphosphonate therapy in these patients. So there are some circumstances in which case you can push forward to consider more aggressive therapy. You can consider bisphosphonates if there's skull involvement, in which case those patients may be at higher risk for developing cranial neuropathies, particularly a hearing loss or spine involvement. They may get some impingement neuropathies, or if there's orthopedic surgery planned at the pediatric site, and you need to have adequate control to help minimize bleeding and minimize complications during the surgery. In terms of the other choices, choice C is not correct. While bone turnover markers are increased in active pageants, it may be helpful in preparation, rapid preparation for surgery. The alkaline phosphates was already elevated and checking a C telopeptide would not offer any additional information. And then finally, choice D was not the correct answer because the biochemical and radiographic presentation were not consistent with myeloma. So next slide. So the final question is a 65-year-old man who was brought to the emergency room because of witness seizure. He started chemotherapy for aggressive lymphoma three days prior and was doing well until he developed nausea, vomiting, and weakness the day before admission. This morning, his wife found him unresponsive. His physical exam showed him to be lethargic. He was a febrile with a lowish blood pressure. His heart rate was elevated at 120 and irregular. Spastek and Trousseau signs are present. In terms of his labs, his sodium was low at 130, potassium elevated 8.4, calcium severely diminished at 5.4, uric acid was elevated, creatinine was increased, and CK was modestly increased at 550. Which of the following is the most likely cause of his severe hypocalcemia? Choice A, acute rhabdomyolysis. Choice B, splenic sequestration of calcium. Choice C, hyperphosphatemia. Choice D, acute renal failure. And choice E, severe metabolic acidosis. The correct answer is choice C, hyperphosphatemia. And the majority of you had answered that correctly. Next slide, please. So this is a case of tumor lysis syndrome in a patient with lymphoma. The lymphoma cells have quite a bit of potassium, phosphate, and purines. So with lysis of the cells, you see a marked increase in uric acid, marked potassium, and with the increased hyperphosphatemia, a marked drop in serum calcium. And the reason the calcium drops is because the phosphate complex into the calcium, and the calcium phosphate crystals precipitate in the renal tubules, causing renal failure. While acute rhabdomyolysis can produce many of the similar findings, usually the creatinine kinase is well over 1,000. So this is less than 1,000. And splenic sequestration of calcium, acute renal failure, and severe metabolic acidosis do not explain the hypocalcemia. Okay. So thank you, Dr. Malabanon, for your presentation. And I did want to go over some of the questions that were asked in the Q&A. And I'm going to go over some of the questions that were asked in the Q&A. And I did want to go over some of the questions. So the first question, actually, I think is for Dr. Srinath, regarding the PCSK9 inhibitors, and really when to add them, and what benefit they would have for CV risk. So those who I consolidated two of the questions that were here in the Q&A section, so. Sure. So for someone who has already been on statin, maximum dose, who has persistent LDL, either elevation or is not achieving goal, especially in patients who have underlying heart disease or who have cardiac risk, you want to get that LDL as low as possible under 70. So these are patients who you want to consider for a PCSK9 inhibitor. And it's safe to use those in conjunction together. Okay. Great, thank you. And then the next question is actually regarding, it's a pituitary question, and it was, would it help to decrease the dose of cobergeline if the patient develops impulse control disorder? Yeah, so the brief answer is sometimes, but not always. There's very limited, actually, information, limited evidence about the optimal approach to management of these patients. In case reports and observational studies, some patients have improved with dose reduction, but not always, so it's best to, and furthermore, there's no clear association between dosage and the risk of impulse control disorders in observational studies. So it's best because this can be quite serious and can really harm patients' and families' lives. So we recommend stopping dopamine agonist, of course. Then the question is what to do in these patients. And the answer is, it depends. If a patient has a large tumor, they may need surgery, they may need radiation therapy. If they have a small tumor, like a micro-adenoma, they could be treated, for example, with a sex steroid replacement. So it varies, but it's best to stop the medication. Thank you. Great, thank you. And then there's a question regarding Paget's disease. If Paget's disease affects a weight-bearing bone, i.e. the hip, pelvis, femur, et cetera, isn't there an indication to treat? So that is correct. If there is a long bone that's affected, it tends to deform more because of the weight, and it would be a reason to treat. In this particular patient, the involvement actually had been the iliac crest and not really the area that had been weight-bearing. Great, thank you. And then there's another lipid question regarding what would you do for a patient with elevated lipoprotein A? Is there a benefit for targeting a lower LDL? So I think the, I mean, using these markers helps evaluate risk. I personally am not that familiar with the literature at this point in terms of whether further LDL, I think generally we think LDL lowering is important, but I think in terms of how low to go, I'm not sure. I don't know that we have that data. I'm sure if any of the panelists know, I'm welcome to chime in, but I think that it's an important marker for assessing their risk. But I think in terms of sort of using that and determining how low to go, I don't think we know for sure. Great, and then last question is a follow-up regarding, for the boards, should you choose Zetia before the PCSK9 inhibitors? I think that's another one for you, Dr. Srinath. Oh, you're muted. Sorry, repeat that question one more time so that I can start. Sure, it was whether you should choose Zetia. There's a question on the boards, which should you always choose Zetia before moving to the PCSK9 inhibitors? I think that's a personalized choice. I think that, I think it depends on their cardiac risk. And I feel like Zetia, while it does have some mild LDL lowering ability, I think the PCSK9 inhibitors are much more potent. Obviously there are also side effect profiles. And so it's a discussion with the patient in terms of what they're willing to do. And I think both of them are helpful, but I think that definitely in someone who, for example, in the patient we discussed, who has underlying severe cardiac risk, multiple cardiac events, you wanna go with something that's a little bit more aggressive. Great, thank you so much. And I think we've addressed all of the questions in the Q&A. And thank you so much to our panelists for this wonderful talk. And thank you for all your hard work in developing this test. And thank you to the attendees. And have a good weekend, everyone.

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