We'll give folks a few, a little bit to join. For those that are returning from last week, welcome back. And for those that were not able to join us last week, welcome to ITE Live. My name is Hannah Gittner. I'm the Director of Education Development and Learning Technology for the Endocrine Society. If you were not able to join us last week, hopefully you were able to find the recording and the slide deck, which is actually available in the same course activity that you used probably to access today's program. So just head to the content tab and you will see both the recording as well as a PDF of the slide deck. In terms of the flow of today, you're going to see a few kind of performance data points in regards to the clinical practice areas we're covering today, which will be adrenal, diabetes, pituitary, and thyroid. For question and answers, we are going to hold those until the end, but please do submit them in real time so that, you know, when they're in your head, please make sure to pop them in. You're just going to click on the Q&A section and you're just going to submit your question. Note that the questions are going to be public, so all of our attendees will be able to see them, and we will do our best to answer them at the end of the program. Madeline, would you mind advancing the slides? We're going to go straight to probably the clinical practice area data. All right, if you could just do one more and then we'll go. Perfect. All right, so without further ado, I'd like to introduce the chair of the in-training exam, Dr. Nick Tritos. Thanks so much, Hannah, and good afternoon and welcome to everyone, to all our participants, fellows. I would like to really extend my gratitude to our talented faculty and also endocrine society staff members who have all worked tirelessly, you know, tirelessly in order to bring this to fruition. So it's a real pleasure to be with you and, you know, for this session of the IDE Live. Just a couple of minutes to show you some of the performance data, as you can see. Some areas, you know, the performance was higher than others, certainly diabetes and bone, you know, people did very well, even male reproduction. There were some other areas, female repro, perhaps pituitary, that were not as well subscribed. But nonetheless, this is really, you know, for our fellows, you know, it serves as feedback for our fellows and we hope that this information and the participation in the exam will help our fellows do better and better in the future, not only in their exams, but certainly in real life in their careers. So this is meant to be constructive feedback that will hopefully lead to improvement. So next slide, please. So without further ado, I would like to call upon Dr. Alan Chang and Ricardo Correa to discuss some of the adrenal questions. And please save your own questions, put them in the chat, and we will discuss them at the end as much as possible. Thank you, Dr. Chang. Thank you so much, Dr. Tritos. Hi, everyone. Welcome to IT Live, the adrenal section at least. Alan Chang from Sloan Brook University. Next slide, please. All right. So our first question of the day. So we have a 32-year-old female who underwent a successful left laparoscopic adrenalectomy for a 2.1-centimeter aldosterone-secreting adenoma four months ago. She had presented initially with hypokalemia with a potassium of 2.9 molecules per liter and severe hypertension. Initial blood pressure was 162 over 102 millimeters per mercury. After her surgery, the hypokalemia resolved and blood pressure normalized without any medications. However, since her operation, she has been more easily fatigued, has had a decreased appetite, and has lost about 6.5 pounds or 3 kilograms. Her only medication is an oral contraceptive. On physical exam, she's healthy, appearing female with a BMI of 31.3, her blood pressure is 124 over 82, and her pulse rate is 92. She has upper body obesity with some increase in cervical vascular and dorsal cervical fat. The rest of her examinations are normal. Next slide, please. So these are the lab results. So her sodium was 134 over, sorry, 134 milligrams per liter. Potassium was 4.7. I'm just going to read the actual numbers now. Glucose was 91. Creatinine was 0.8. Cortisol was 2.8. Plasma ACH was 98. Aldosterone was 5. And plasma renin activity was 0.4 milligrams per milliliter. Next slide, please. In addition to initiating hydrocortisone replacement therapy, which of the following is the best recommendation? So we have A, DHEAS measurement. B, MRI of the pituitary gland. C, no further diagnostic studies. And D, 21-hydroxylase antibody measurement. So the answer is C. Thank you. No further diagnostic studies. And most of the fellows did choose this. Oh, there was a decent amount that also chose D, the 21-hydroxylase antibody measurement. All right. So next one, please. Next slide, please. All right. So rationales list. So about 15%, 20% of aldosterone-producing adenomas for APHD greater than 1.5 centimeters also co-secrete cortisol. And this cortisol secretion is usually mild. However, when the aldosterone-producing adenoma grows, the glucocorticoid hypersecretion may become more apparent. And as a result, post-adrenalectomy, the patient may have suppression of cortisol production on the contralateral side. And that's what's happened in this patient. Adrenal adrenal production is decreased in both primary and secondary AI, adrenal sufficiency. So DHEAS may be a good idea to check an impaired adrenal function. However, in this case, well, the cortisol was already low. And hypoadrenalism is already apparent. So not really needed. B, pituitary imaging would not provide any insight into the recovery of the ACTH cortisol function access. No further diagnostic studies are needed in this patient, which is C, because, well, you have an elevated ACTH with a suppressed cortisol. And given the clinical scenario of the surgery, APA, and the likelihood of it being co-secreting cortisol, that's very likely the ideology of those adrenal sufficiency. And in this case, the hypoadrenalism can also be managed conservatively by encouraging liberal salt intake and a low potassium diet in addition to the steroids. And finally, the antibodies to the 21-hydroxylase, answer D, yes, it's for classic autoimmune condition, adrenolitis. In this case, it's unlikely, given the clinical situation, the clinical scenario. The high ACTH and the low serum cortisol at this point tells us that this patient does have a low cortisol production, does need some help with replacement, and eventually, hopefully, the HPA access will recover. So yes. Next slide, please. So next question. 32-year-old female is referred for further evaluation for recurrent hypokalemia. She has a two-year history of treatment-resistant hypertension, initially diagnosed during her routine medical assessment. Her current medications are amlodipine, 10 milligrams daily, doxazosin, 8 milligrams daily, and Ramipro, 10 milligrams daily. She also takes potassium chloride, two tablets of 470 milligrams of potassium per tablet, twice a day. Her medical history is otherwise unremarkable, and there is no relevant family history. On physical exam, her height is 66 inches, or 167.6 centimeters, and her weight is 154 pounds, 70 kilograms. Her BMI is 25. Her blood pressure is 155 over 92 millimeters per mercury, and pulse is 74 beats, and regular. Physical exam is normal. Next slide, please. Here are the results. Serum potassium, 3.2 milligrams per liter. Plasma-running activity is 0.05 milligrams per milliliter. Serum aldosterone, 39.5 milligrams per DL. And the serum cortisol following a low-dose 1-milligram dexamethasone suppression test was 1.0 micrograms per deciliter. She had a cascading of the adrenal glands, triple phase, which shows a 2.5-centimeter nodule in the right adrenal gland with nine hansel units baseline. And the left adrenal gland has a normal appearance. Next slide, please. Which of the following is the most appropriate next step in a patient's evaluation and management? Do you A, send the patient for adrenal venous sampling, or AVS? B, aldosterone suppression test? C, genetic testing for glucocorticoid remediable aldosteronism, or GRA? D, MRI of the adrenal glands? Or E, right adrenalectomy? And the answer is E, right adrenalectomy. And it's pretty much, you know, looking at the percentages, it's pretty much between A and E. Now, it's about half and half. All right. So next slide, please. OK. So this is the reason why. So this patient has primary hyperaldosteronism. I think everyone agrees to that. And as per Adrenal Society Consensus Statement Guidelines, these are the steps that they recommend. Number one is screening. Number two is confirmation, which is usually via salt loading and 24-hour urine collection. Three is imaging. Four is adrenal vein sampling. And five is treatment. So that's the basic steps. However, there are caveats. So caveat one, if the aldosterone level is above 20, with a plasma-ridden activity level being suppressed, which is below one, with spontaneous hypokalemia, it is suggested or recommended that the confirmation testing can be skipped. So in this case, checking the salt loading test is not needed under this situation. And number two, caveat number two, if the patient is under the age of 35, has spontaneous hypokalemia, marked hyperaldosterone excess, and a unilateral adrenal lesion with radiological features consistent with a critical adenoma, adrenal vein sampling may not be needed. Next slide. Next slide, please. OK. So once surgery is being considered for primary hyperaldosteronism, adrenal vein sampling performed by an experienced interventional radiologist is usually recommended to distinguish between unilateral and bilateral adrenal disease. In this case, as we just kind of mentioned, this case, this patient has several characteristics that justify just proceeding directly to surgery. So in this case, for example, aldosterone suppression testing or salt loading test is not required, as the aldosterone was 39.5, with a suppressed PRA of 0.05, and the patient did have spontaneous hypokalemia. So we could skip the aldosterone suppression, the confirmation, as per the recommendations, the guidelines. Genetic testing, genetic testing for glucocorticoid-remediable aldosteronism is usually reserved for patients when the primary hyperaldosteronism comes on set very young, under age of 20, with a family history of hyperaldosteronism and stroke in the young age, under 40 years, years old, and usually the stroke is a hemorrhagic. So this patient does not have any of that. The CAT scan demonstrated a 2.5, less than 10, household units adrenal lesion. And given the fact that this patient is young, under the age of 35, has very prominent labs demonstrating primary hyperaldosteronism with a unilateral lesion, no further imaging is necessary, and adrenal vein sampling is not recommended as per the endocrine society guidelines. And I actually just said the last bullet point. It's reasonable to proceed directly to surgery, given the virtues of the following, age less than 35, spontaneous hypokalemia, hyperaldosteronism with a unilateral adrenal lesion. So yeah, that's why the answer is proceed directly to surgery. And next slide. I believe it's my colleague, Dr. Ricardo Correa. Thank you, Dr. Chan. So our final question and adrenal for this live is a 31-year-old woman of Mediterranean heritage, present for evaluation of infertility. She and her husband has been trying to conceive for the past year. She report irregular periods every 30 to 60 days. She has struggled to lose weight most of her life. She has type 2 diabetes and is treated with 1000 milligrams of metformin twice a day. She also takes prenatal multivitamins. She has occasional acne, particularly before menses, and has a cyclical breast tenderness before menses. No electrorea or visual defects. And she's physically active. Her blood pressure is 115 over 75, pulse 78. Her BMI is 30.1. She has an olive skin complexion and dark hair. Her autism is not present in examination. However, she bleaches her upper lips hair and report plucking minimal dark hair on her chest and perioral area. She has uniform distribution of excess adiposity. Muscle strength is normal. Her skin is warm without pleura or bruises. She has thin, pale abdominal strea and two acne lesions on her chin. Next slide, please. Here you can see the lab work. So a TSH on 2.6 with an A1C of 6.3% and a 54 of 1.1. Prolactin of 10. Total testosterone, 37 nanograms per deciliter. A DHES of 580 and a DHEA of 37. And racinidione of 60. 17-hydroxyprogesterone of 238. Estradiol of 19. LH of 8. FSH of 4.1. Corisol of 16. And ACDH of 77. Next slide. So the question is, which of the following is the next best step in this patient management? And the answer is B. Next slide. Calcitropin simulation test. So here the distribution of the participants were a little bit even between A, B, and D with an E, sorry, with a less amount on C. So it was a very, if we see psychometric, it was a very well distributed answer. So let's look why B is the correct answer. So next slide. So if we think about A, that is the adrenal CT, it will be instrumental when we are thinking about adrenocortical carcinomas. In those cases, the DHEA is extremely high. Her DHEA was in the 500. So it's not extremely high. And she didn't have any other clinical features of excess of hyperandrogenism that will think us that this is a malignancy. The answer B, that is the calcitropin stim test, is for amplification of some steroids, which elevated when you have some type of congenital adrenal hyperplasia. So if we do a stimulation test with measuring 17-hydroxyperc-neuron and the concentration is more than 5,000, it's very suggestive. I'm back or still cut off? You're back now, but I don't think we heard the rational, right, the stem test. Okay, sorry, let me repeat it again. Sorry, the connection. I don't know what happened. So if we think about the answer B, the stipulation tests usually amplify the elevation of steroids. So in cases where congenital adrenal hyperplasia is suspected, like this one, having a stimulation test and measuring 17-hydroxypregnenolone greater than 5,000 confirmed the diagnosis. So this is one of the type of congenital adrenal hyperplasia. Why not the genetic testing? Usually genetic testing is used in cases where there is an ambiguous hormonal data. In these cases, the 17-hydroxyprogesterone was more than 200. So that was very suggestive that we have to do the next step instead of jumping immediately to genetic testing. So the next slide. What about ovarian ultrasonography? This is when you suspected that the patient has some ovarian pathology. In those cases, the adrostenidin and testosterone will be extremely high. In this case, the patient didn't have any hyperandrogenism symptoms and the levels were in the normal range for a woman. An epitetal MRI is indicated when you are thinking about Cushing, ACTH-dependent Cushing. In this case, the ACTH values were disproportionate with her serum cortisol value, which is subjective of a non-classic congenital adrenal hyperplasia. So with this, this is the slide. Now we go to diabetes. Thanks so much, Dr. Chang and Dr. Correa, and apologies to our participants. We had a minor technical glitch. So without further ado, I'd like to call upon the diabetes team. I believe we have Dr. Derek Beckman and Dr. Brianna Johnson-Rabbit, who will take over and will educate us regarding diabetes. Brianna? Hello. Thank you. Thank you. Again, Brianna Johnson-Rabbit. Nice to meet you all. All right. So the first diabetes question that's included here, a 67-year-old woman presents with questions about new treatments for type 2 diabetes. Since her diagnosis six years ago, she's been treated with a sulfonylurea because of intolerance to metformin. She's now taking glipizide 10 milligrams twice daily, and she documents blood glucose values that are generally less than 150 with her home glucose monitoring. However, since she started therapy, she's gained 15 pounds and is frustrated with her inability to lose weight. Findings on hepatic ultrasonography performed last year were consistent with steatosis. She recently saw an ad in a magazine touting epiglosin and is very interested in a diabetes pill that causes weight loss. She takes HCTZ and lisinopril for hypertension and atorvastatin for elevated cholesterol. She has no history of diabetes-related complications. On physical exam, her weight is 208 with a BMI of 35 and blood pressure is 136 over 84. She doesn't have any signs of neuropathy. Her results are significant for an A1c of 8.4%, a creatinine of 1.9, and an estimated GFR of 38 amongst other abnormalities, including a urinary albumin to creatinine ratio of 110 milligrams per gram creatinine. She would really like to start an SGLT2 inhibitor. Next slide. In this patient, epiglosin's main limitation would be that it would, A, cause only transient weight loss with weight regain in one to two months, B, exacerbate hepatic steatosis, C, improve proteinuria but worsen estimated GFR in the long term, D, interfere with the effectiveness of her antihypertensive regimen, or E, not sufficiently decrease blood glucose levels. So the answer is E, not sufficiently decrease blood glucose levels. And the majority of test takers did select that as the correct answer. Next slide. So SGLT2 inhibitors do result in weight loss as monotherapy and in combination. There's thought to be multiple mechanisms, though it's not fully clarified. One of them is glucoseuria, of course. In clinical trials, the weight loss has been demonstrated to persist for at least six to 12 months and often longer. It's usually around two to three kilograms or so, so I know that that was the most commonly selected distractor, so just to talk about that a little bit more. No adverse effects on blood pressure, her hepatic function had been described. Blood pressure actually improves systolic, approximately five millimeters mercury on average or so. As we know, SGLT2 inhibitors can transiently worsen the EGFR, but in the longer term, provide kidney protection. For the actual key to answer, so the addition of ampicliflozin is unlikely to achieve her hemoglobin A1c goal, which is the main problem. She has an estimated GFR of 38, and the glucose lowering effects of SGLT2 inhibitors are dependent on the estimated GFR, so basically, with an EGFR of 45 to 59 or so, the A1c lowering effect goes down to about 0.3 to 0.4. With an EGFR of 30 to 44 or so, the decrease in A1c is down to 0.2 to 0.3, and then generally doesn't have an effect on A1c or glucose lowering with an EGFR below 30. All right, we can move on to the next item. Thank you. I'm Derek Beckman from Rook Army Medical Center in San Antonio. To the next two questions, so question diabetes, question 12, 26-year-old man with a five-year history of type 1 diabetes is interested in insulin pump therapy. He travels often for work and has an erratic eating schedule. However, he has good glycemic control, and he no longer wants to administer multiple daily injections. His current insulin regimen consists of insulin, glargine, 22 units at bedtime, and Lispro, six units with each meal, a total daily dose of 40 units. He self-monitors his blood glucose values ranging between 80 to 130 and rarely has hypoglycemic events. His BMI is 24, and the exam is otherwise unremarkable with an A1c of 6.9%. Next slide. And so which of the following parameters are most appropriate for his initial insulin pump setting? Next slide. And so B is the answer. We'll walk through how we got the calculation, and there was some between A and C and why we landed with B as the answer. Next slide. And so just remembering that if somebody is well-controlled when they move from MDI, multiple daily injections, to an insulin pump, they will need less insulin doing anywhere, you know, I've seen anywhere between 20 to 30%, 25% is kind of the most quoted, and so doing a 25% reduction, he was well-controlled with his glucoses as well as his hemoglobin A1c. And so his total daily dose was 40 units, multiplying that by 0.75 gives us a new total daily dose of 30 units, half of that would be your basal insulin, that would lead us to 15 units. And then you need to extrapolate that into an hourly rate, so dividing that by the 24 hours in a day gets you the 0.6 units per hour. Once you get there, then you can delineate from there. The carbohydrate ratio, people will use either 450 or 500, and divide that by your new total daily insulin to get your carbohydrate ratio of 15. And the insulin sensitivity factor, you can use 1700 to 1800, again, there are some variations of what people will use, those are pretty, again, pretty typical. And so 55 was the new sensitivity factor based on your new total daily insulin on somebody that is well-controlled switching from MDI to an insulin pump. Next slide. Now to question 16, 36-year-old woman with a history of type 1 diabetes and sickle cell disease presents to the diabetes clinic for follow-up. She is treated with insulin glargine, 18 units daily at 12 p.m. at her lunchtime, and she also received short-acting insulin, 6 units with each meal, and a correctional insulin of 1 unit for every 50 milligrams per deciliter above 150. She usually has breakfast at 8, lunch at noon, and dinner at 6.30 p.m. Her only medication is hydroxyurea that she started almost one month ago, which she takes in the morning just before breakfast, 8 a.m. The patient has recently started to experience marked hyperglycemia. She explains that her glucose concentration, as monitored by her real-time continuous glucose monitor, starts rising from approximately 140 around 1.30 to 2 p.m., and it becomes significantly elevated, 300 milligrams per deciliter. Her glucose management indicator is now up to 7.5%, which is higher than the value that the patient had three months ago, 6.8%. The continuous glucose monitor report shows a pattern of hyperglycemia around 2 p.m. that usually persists until 6 to 6.30 p.m. Next slide. Which of the following is the best next step in this patient's management? And next slide. And so the correct answer was asking the patient to do point-of-care POC finger stick blood glucose values several times between the time where she has that excursion. And there was a larger percentage of people that went ahead and increased their pre-lunch And another good portion of people that recommended an automated insulin delivery system or insulin pump initiation. And so we'll go to the next slide. And so just noting that hydroxyurea, so if you look at answer B, the hydroxyurea is one of those medications, while they're overall relatively rare, that can interfere with your CGM sensor that can give you a pseudo hyperglycemia. And so she may not be actually experiencing a true hyperglycemia. And so measuring actual pain of care glucose that would not be interfered by the hydroxyurea is the correct answer. Just kind of noting our other inappropriate answers or incorrect answers that continuing her just a current regimen, obviously the significant hyperglycemia would not be the correct answer and not chosen well. Just make sure to, again, look out for those things that may give us false readings. And so just increasing the insulin dose may not be based on true values. While typically we can trust the CGM, especially with medications that can interfere, be careful with that. Recommending an AID system could potentially cause dangerous glucose values because it would just actually talk to the CGM. And so if the CGM is reading incorrectly, it could start dumping in insulin and actually cause true hypoglycemia. And so that's the reasons. And then our answer E, so before switching the glargine, that sometimes we can see that, but this is not the iteration or reason for hyperglycemia with her Lantus at the noon timeframe. Next slide. I'll turn it over to Dr. Johnson for a bit again. So for diabetes number 15, a 48-year-old woman has new onset type 2 diabetes. Metabolic dysfunction associated steatohepatitis was recently suspected after routine testing showed abnormal liver function. Subsequent workup, including a liver biopsy, revealed MASH with pathologic evidence of steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. There's no evidence of cirrhosis. Her BMI is 32. The hepatologist suggests prescribing an anti-diabetes agent that would also improve her liver histology. Next slide. Her laboratory results include an A1C of 8.0, a creatinine of 0.8, an ALT of 89, and a TSH of 2.5. Next slide. Which of the following medications would be the best choice given these concerns? A, dapaglifazine, B, dulaglutide, C, metformin, D, pioglitazone, or E, citagliptin? So the answer for this item is pioglitazone, which the majority – sorry, not the majority. The majority did choose dulaglutide instead of pioglitazone, so we can talk that through. Next slide. So there isn't significant available data on changes in specifically liver histology in patients with MASH and type 2 diabetes with dapaglifazine, dulaglutide, or citagliptin. There is some data looking at changes with liraglutide, semaglutide, truzepatide, but not dulaglutide. The effectiveness of metformin for the treatment of MASH was evaluated in a meta-analysis, but there was no difference between patients who received metformin and controls in the histologic response or changes in ELT levels. Certain diabetes agents have been shown to improve liver histology, which includes thiazolidinediones. There have been – there is data to support improvement, so there was a meta-analysis that demonstrated that glitazones, which did include both pioglitazone and rosiglitazone, but glitazones resulted in improved hepatocyte ballooning in ELT, though not inflammation or fibrosis in patients with diabetes, but in patients without diabetes, glitazones also significantly improved all histologic and biochemical outcomes, including fibrosis. Next item. A 52-year-old woman presents for evaluation of type 2 diabetes. Diabetes was diagnosed at age 32 in the setting of class 3 obesity and approximately five years after pregnancy, during which she had gestational diabetes. Since diagnosis, hemoglobin A1C values have been between 9 and 10 percent, and BMI has been between 38 and 42. She has moderate to severe non-proliferative retinopathy in both eyes and distal polyneuropathy affecting her feet. Eight months ago, she underwent a gastric sleeve and has lost 90 pounds since then. She feels well and bikes 30 minutes per day. On physical exam, her BMI is 32, blood pressure is 128 over 72, and pulse is 84. Her current medications include dulaglutide, 1.5 milligrams per week, losartan, 100 milligrams per day, and simvastatin, 20 milligrams per day. She reports that she is unable to tolerate SGLT2 inhibitors because of recurrent severe vaginal yeast infections. Next slide. Laboratory results include a point-of-care hemoglobin of 6.7, a creatinine of 1.68, an EGFR of 42, a urinary albumin to creatinine ratio of 280, and other lipids as shown. Next slide. Which of the following is the best next step to slow progressive kidney disease? A, adfenerinone, 10 milligrams per day, B, add insulin-clargene, 0.15 units per kilogram per day, C, increase the dulaglutide dosage to 3 milligrams per week, D, increase, there's actually a small typo there, but losartan dosage to 50 milligrams per day, or E, increase the simvastatin dosage to 40 milligrams per day? So the answer is A, adfenerinone. So the most significant distractor in this item was C, increase the dulaglutide dosage to 3 milligrams per week. Next slide. So SGLT2 inhibitors and the mineralocorticoid receptor A, adfenerinone, have been effectively shown, found effectively to lower the risk of kidney failure. Increasing insulin would most likely be excessive and could be problematic, given that her A1c is already below 7. Dulaglutide 1.5 has been shown to modestly reduce progression to kidney failure in a CV outcomes trial and so on, but it's less likely that a specific dosage increase would augment that risk reduction. So those are the, again, the distractors. In regards to this item, so the FIDELO-DKD study, sorry, yes, okay, we can hold there on that slide, there were over 5,000 patients with type 2 diabetes and chronic kidney disease with microalbuminuria and diabetic retinopathy or macroalbuminuria and an EGFR of 25 to 75 already taking an ACE inhibitor, this patient's on an R, but, and they were randomly assigned to taking adfenerinone or placebo and there was an 18% reduction in the primary composite endpoint of time to kidney failure, which included a sustained decrease of 40% or greater in baseline EGFR or death from kidney-related causes. All right, thank you very much. Thanks so much, Dr. Johnson and Dr. Beckman. Without further ado, I'd like to ask Dr. Brandon Gaunt from the pituitary team to discuss the pituitary questions and please be reminded to put any questions in the chat and we will get to them at the end. Thank you. Brandon? Thank you very much, Dr. Tritos, for the introduction. So I will be going over three pituitary questions for today. Next slide, please. So this is question number one. So this is a 35-year-old man who is interested in fertility. He has a history of a clinically non-functioning pituitary macroadenoma with surgical removal at age 31 years of age. Following the surgery, he developed hypopituitarism and he currently takes libothyroxine, hydrocortisone, growth hormone, and transdermal testosterone. He has good energy levels and he states that he has a normal libido and erectile function. Upon physical examination, he is well virilized with 10 cc's testes bilaterally that have normal consistency and a subsequent semen analysis documents azoospermia. Next slide, please. So which of the following is the best next step in this patient's management? So A, add an aromatase inhibitor. B, refer for microdissection, testicular sperm extraction. C, switch from transdermal testosterone to clomiphene citrate. D, switch from transdermal testosterone to HCG injections three times per week. Or E, switch from transdermal testosterone to HCG injections three times per week as well as FSH injections twice per week. Next slide, please. So the correct answer in this case was D, which is switch from transdermal testosterone to HCG injections three times per week. So you can see here that most people did get this question correct with the second most common selection being E, switching to both HCG and FSH injections twice per week. Next slide, please. So the purpose here is to recognize that this patient has hypogonadotropic hypogonadism with infertility from that related to this pituitary surgery in the past. And this has been demonstrated by azoospermia on a semen analysis. And in this setting, a treatment of infertility or infertility induction requires stopping the parenteral testosterone and using gonadotropin therapy for intra-testicular testosterone production to generate sperm. And so the first answer, aromatase inhibitor, works by reducing estrogen production and thus at the level of the hypothalamus and pituitary, would increase gonadotropin concentrations. But that would occur in someone with an intact hypothalamic-pituitary axis, which we do not have in this case. So this would not be expected to be useful. Answer B, micro-TC would not be usually our first step in this situation as typically we would go to gonadotropin therapy first. It's unlikely that a blockage in the patient's testicular duct system is the cause of the azoospermia given history. Clomiphene citrate, so that would be answer C, which is an estuarine receptor antagonist. Similarly to the aromatase inhibitor, answer A would reduce native feedback at the level of the hypothalamus and pituitary. But again, this patient does not have intact hypothalamic-pituitary access, and thus you would not expect that it would be effective in this case. So the correct answer here is to switch from transdermal testosterone to HCG injections three times per week, and this would be to give the patient back LH. Now, the other commonly selected response was to use HCG as well as FSH. Typically, the way that this is done is HCG would be tried first for a period generally of about six months, aiming for normal testosterone levels, and if an adequate sperm count has not been reached after about six months, then typically FSH would be added after that. Sometimes FSH will be added first in the setting of a small testes, typically less than four to six ccs, but the stem in this question did actually tell you that the testicular size was about 10 ccs. So in this case, we would use HCG first. So that's why answer E is not the correct answer in this question. Okay, next slide, please. So the second question here is a 63-year-old man who reports a gradual bilateral loss of vision over two years. An ophthalmologic evaluation shows optic neuropathy. His past medical history is notable for pre-diabetes, hypertension, hyperlipidemia, a remote transient ischemic stroke, and nephrolithiasis. Medications are rosuvastatin, lysinopril, and aspirin. On physical examination, he has non-inflammatory arthritic nodules on the distal interphalangeal joints and bitemporal superior quadrantinopia. Next slide, please. So here are the MRI results shown. This reveals a 4.3 by 3.6 by 2.5 centimeter pituitary mass with supracellular extension and bilateral cavernous sinus invasion. Next slide, please. So here are the laboratory results drawn at eight in the morning while fasting. So prolactin of 1609 nanograms per mil, TSH of 1.04, 3T4 of one nanogram per deciliter, FSH of four, TSH of 3.7, total testosterone of 135 nanogram per deciliter, cortisol of 9.7 microgram per deciliter, ACTH of 69.2 picogram per mil, growth hormone of 1.99 nanogram per mil, hemoglobin A1C of 5.9%, and the remainder of his general chemistry panel was normal. Next slide, please. So which of the following is the best next step in managing this patient's pituitary tumor? So answer A, measure growth hormone 120 minutes after oral administration of 75 grams of glucose, or B, measure IGF-1, insulin-like growth factor one, C, measure 24-hour urinary cortisol, or D, refer for transphenoidal pituitary surgery, or E, start carbarguling 0.5 milligrams twice per week. Next slide. So the correct answer in this question was to measure IGF-1. The stem actually had a growth hormone level, but did not have an IGF-1 level. The other two commonly selected answers in this question were to refer for transphenoidal surgery or to start carbarguling. Next slide, please. So the key point in this question is to recognize that this patient actually has acromegaly. The laboratory testing did show high prolactin levels, but the stem did not include an IGF-1 level, just a fasting growth hormone level. And it's important always in a patient with high prolactin levels, where you think there is production of prolactin to also evaluate for growth hormone co-secretion. And so answer A was measuring growth hormone 120 minutes after oral administration of 75 gram glucose. Typically, if you're gonna do an oral glucose tolerance test to look at growth hormone levels in the setting of acromegaly, you would be doing growth hormone every 30 minutes after the glucose administration, not just the 120 minutes. And typically, your first investigation looking for acromegaly would be an IGF-1 level, which is answer B and the correct answer in this situation. And in fact, this patient's IGF-1 level was elevated, confirming a diagnosis of acromegaly with prolactin co-secretion. The answer C was a measurement of 24-hour urinary cortisol, which is not necessary in this specific scenario. The clinical presentation that was given in the stem was not necessarily suggestive of Cushing's. And with the prolactin elevation in this stem, this was indicative of prolactin secretion, not a stock effect. And you would not expect corticotrophin lactotroph cells to arise from a similar tumor. So that would not be your next step here. So answer D and E were treatment options. Answer D would be surgery, which you have not completely worked up this tumor yet with an IGF-1 level. And in fact, if the IGF-1 level returned normal and this was just prolactin secretion, you would not typically send this patient for surgery, at least not as a first step. You would treat them with a dopamine agonist versus answer E, cabergoline treatment only. Your evaluation, again, was not complete yet at this stage as the IGF-1 was not performed and this patient actually had to acromegaly. And so surgery would typically be your first line treatment. Okay, next question, please. Next slide. So this is the last pituitary question. So we have a 57-year-old male with a history of hypertension and nephrolithiasis referred for possible hypercortisolism. He has been experiencing weight gain and his blood pressure has been more difficult to control than in the past. His medical history is remarkable for a seizure disorder since childhood, as well as depression. His current medications include aspirin, alfusosin, amlodipine, carbamazepine, fluoxetine, and an over-the-counter prostate health supplement. On physical exam, he is in no apparent distress. His blood pressure is 121 over 85 and his pulse rate is 79. His heart height is 69.5 inches and weight of 304 pounds, yielding a BMI of 44.2. His abdomen is protuberant with some abdominal striae. Next slide, please. So his primary care physician has considered the diagnosis of Cushing syndrome and has ordered the following laboratory tests prior to his endocrinology visit. So a lab test drawn at 8 a.m. after one milligram of dexamethasone given at 11 p.m. at night. His cortisol that morning was 3.9 micrograms per deciliter, which would be considered abnormal. The CTH was 15 picograms per mil and his urinary free cortisol was 63 micrograms per day above the reference range shown there. Next slide, please. So which of the following is the best next step in this patient's evaluation? So A, adrenal-directed CT scan. B, another dexamethasone suppression test after stopping the prostate supplement. C, late-night salivary cortisol measurements. D, low-dose dexamethasone suppression test with measurement of 24-hour urinary cortisol excretion. Or E, pituitary-directed MRI. Next slide, please. So the correct answer in this question was to perform a late-night salivary cortisol measurements, which the majority of respondents did correctly identify, with B being the second most selected answer, performing another dexamethasone suppression test after stopping the prostate supplement. Next slide, please. So this question was to highlight drawbacks and downsides. So this question was to highlight drawbacks and downsides with some of the tests that we use to diagnose Cushing's syndrome. And so answer A and E, imaging of either the adrenal or pituitary glands would not be the next best step as you have not yet established the diagnosis of Cushing's syndrome. Do not proceed to imaging yet until you've made that diagnosis. When stopping the supplements, so the second answer was to stop the prostate health supplements, but actually the stem was to illustrate that the patient was actually taking carbamazepine, which is a strong CYP3A4 inducer, which enhances dexamethasone clearance, and thus leading to a false positive in dexamethasone suppression test. So the answer was actually to, if the answer included carbamazepine, that would be included here. The correct answer was to measure bedtime salivary cortisol, which is not influenced by carbamazepine, and that's the next appropriate step. And the final answer, D here, the two-day dexamethasone suppression test, again, because the patient's taking carbamazepine would have the same limitations as the overnight one milligram dexamethasone suppression test. That's it. Thank you very much. Thanks so much, Dr. Galm. I would like to call upon Drs. Traver Angel and Dr. Kristen Kobaly of the thyroid team to educate us on thyroid questions, please. And please be reminded to put questions in the chat, and we'll try to get to them at the end of the session. Thank you. All right, so I'm gonna lead us off today with our final topic, if we can advance the slides. All right, so we have a 74-year-old woman with fatigue and weight gain who is referred for evaluation of subclinical hypothyroidism. The patient has gained 10 pounds since she retired two years ago, and is frequently requiring a midday nap. Her medical history is notable for hyperlipidemia, which has been managed by diet alone. And on exam, she has a normal-sized thyroid gland without nodules, and the rest of her exam findings are normal. Next slide. Laboratory results show a serum TSH of 8.9, which is elevated, a free T4 of 1.3 in the normal range. Her LDL is 160, HDL is 38, and she has positive TPO antibodies. Three months later, TSH is repeated and is similar. Next slide. So the question is, which potential effect of initiating levothyroxine treatment for this patient is most strongly supported by current evidence? A, iatrogenic subclinical hypothyroidism, B, improved cognitive function, C, increased HDL cholesterol, and D, less fatigue. Are those the correct answers? So the correct answer is iatrogenic subclinical hyperthyroidism, which was slightly, answered most commonly 29%, but there was a pretty even split overall. So let's go through the reasoning. So for the rationale, so iatrogenic subclinical hyperthyroidism is actually, you know, first of all, detrimental and is quite common. So studies show that about 14 to 21% of individuals who take levothyroxine are overtreated. So, you know, it is certainly possible that even in treating a patient with mild abnormalities, they can be overtreated and develop hyperthyroidism. However, there's been no intervention trial that's shown consistent improvement in cognitive function or inner energy in treating patients who have subclinical hypothyroidism with a TSH less than 10. And HDL is typically not altered in patients with subclinical hypothyroidism. We do see improvements in treating patients with subclinical hypothyroidism and LDL cholesterol. So I'm gonna hand it over to Dr. Angel for the next question. Great, Kirsten, thank you. I will pick up the baton here. 57 year old man was diagnosed with Graves' disease 24 months ago. At that time his free T4 and total T3 levels were approximately threefold elevated. Free T4 of 6.1, total T3 of 635 nanograms per deciliter. And his TRAB levels were significantly elevated at 5.1. Patient was treated with methimazole 30 milligrams daily and subsequent resolution of his hyperthyroid symptoms decreased in his goiter size. He tolerates the methimazole without significant adverse effects and without worsening of some mild thyroid eye disease. Six months ago, he was euthyroid on methimazole dose of five milligrams daily with a mildly elevated TRAB concentration of now 2.2 and elected to discontinue methimazole. Treatment options, including radioactive iodine therapy, resumption of methimazole and thyroidectomy are discussed with the patient. He states that his greatest concerns are protecting his quality of life, ensuring his professional activities as a news show host, that those are not affected and preventing further hyperthyroid symptoms. Let's go forward. So his hyperthyroid symptoms have returned as TSH is fully suppressed. Free T4, 3.5 nanograms per deciliter. Total T3, 460 nanograms per deciliter and TRAB positive at 3.5. Let's go ahead. Which of the following treatment options is the most suitable for this patient? Long-term methimazole therapy, one-year retrial of methimazole, radioactive iodine therapy or thyroidectomy. See the right answer. Right, so the right answer is long-term methimazole therapy. Again, between three answers, pretty neutral spread across those. Let's go forward. So what's the rationale? So for the right answer, long-term methimazole treatment would be a reasonable approach. Firstly, long-term therapy has had some evidence now for greater remission rates and quality of life in creating stable thyroid hormone levels and avoiding one of his priorities, which was not having a return of any hyperthyroid symptoms. A one-year retrial of methimazole may be less suitable given the persistent TRAB elevation and the unlikelihood of remission and the risk of recurrent hyperthyroidism. Radioactive iodine therapy here may not be the best choice because of mentioning both quality of life given that it can exacerbate thyroid eye disease and additionally imbalance thyroid hormone levels for a time. And then total thyroidectomy has a small but relevant risk of damage to recurrent or superior laryngeal nerve, which could lead to voice impairment, which would be significant enough to affect his job performance, which he wants to definitely avoid. Let's go forward again and I'll give it back to Kristen. Great, all right, so our last question of the day. So we have a 26-year-old woman who presents for follow-up of hypothyroidism that was diagnosed several years ago. And she's currently treated with levothyroxine 88 micrograms per day and lyothyronine 10 micrograms daily. And she's on combination therapy because two years ago she had persistent fatigue on levothyroxine alone. Symptoms improve with the change and she feels well. A recent serum TSH value measured three weeks ago was 1.23. However, her period is two weeks late and an in-office urine pregnancy test is positive. Next slide. So which of the following is the best option for this patient's thyroid hormone therapy now? Continue current treatment, increase both the levothyroxine and lyothyronine doses by 25%, increase the levothyroxine dosage to 112 micrograms daily and continue the current lyothyronine dose or stop lyothyronine and increase the levothyroxine dosage to 150 micrograms per day. And the answer? So 56% shows the correct answer, which was to stop lyothyronine and increase the levothyroxine. And the second most common choice was to continue the T3 and increase the levothyroxine dosage to 112. So let's see the rationale. So first of all, not on this slide, but most hypothyroid women do need an increase in the levothyroxine by about 25 to 30%. And that's largely due to the increase in TBG that we see in pregnancy related to increases in estrogen. However, levothyroxine and lyothyronine combination therapy is not a recommended treatment for pregnant women. It's T4 that predominantly crosses the placenta. And so T3 could potentially render the fetus hypothyroid. And so therefore normalizing maternal TSH on combination therapy, which are the first three answers is not correct. So why are we gonna go from 88 to 150 micrograms in this patient, which was the correct answer? It may seem like a large gap or a large increase. So first of all, the patients on 10 micrograms of lyothyronine a day, T3 treatment is about three to four times more potent. So you take your 10 micrograms of T3 is worth about 30 to 40 of levothyroxine. So let's say it's 30, we can add that to her 88 of levothyroxine gets us to about 120 micrograms per day. However, we still need to do that 25% increase for the pregnancy. And that's how the 150 microgram dose is achieved. All right. Thanks so much to our thyroid team. We have a few minutes and a few questions in the chat. One question pertains to the adrenal section. Why would ACTH level be elevated in case 38? This is the patient with the suspected partial three beta HSD deficiency. So this is a question for the adrenal team. Would one of our adrenal- Sorry, Ricardo, Dr. Correa, you there? Either Dr. Chang or Dr. Correa. Sorry, so I was typing in, I apologize. I was answering the question actually to another question. Okay, you answered it online. Okay, thank you. Thanks, Dr. Chang. No, no, no. The question actually, I think, are we talking about question 38? Is that the first question? Sorry, I don't have in front of me. What question is that from? Yes, that was the first one. Oh, okay. Yeah, about the adrenalectomy. Yes, yes. I didn't answer that in the thing, but I can say it right now though. So basically the patient had a left adrenalectomy and it was co-secreting cortisol. And then, so once they removed it, the contralateral cortisol secretion from the right gland was suppressed. And basically the patient would have had secondary adrenal deficiency at that time with a low cortisol and low ACTH because of the hypersecretion of cortisol from the left gland that was removed. However, over time, the HPA axis was hard to recover. The pituitary will start revving up, starting making more ACTH, and it would stimulate, try to stimulate the remaining right side adrenal gland to start making cortisol, which eventually it probably will, but it will just take time. I need support. And does that make sense? Yes, no, thank you. I think the question was pertaining though to the patient with suspected late onset congenital adrenal hyperplasia, but it's still compensatory, right? I mean, I think, I don't know if you want to elaborate on that, but it's still a compensatory rise in ACTH. Yes, yes. So in this case, the ACTH is elevated. So the question is, does the patient have 21 hydroxylase deficiency? You know, hence that's why the whole test was being done to do a co-centric stimulation test. So yes, it is a compensatory state where the body is going to be trying to make more, more, there is a, what do you call it? A deficiency of 21 hydroxylase, which is part of the cascade of the cortisol metabolism. So patients will not make enough cortisol. Hence the body will make more ACTH to be elevated. We don't have a diagnosis yet in this question because we need to confirm whether the patient has 21 hydroxylase deficiency, which most likely the patient does. Thank you so much. And there were two other diabetes question and one P2 question that were answered in the chat. I think that was covered very well. So I would like to thank our panelists, our endocrine staff members and endocrine staff and all our participants and fellows for your participation and wish you a happy, a good weekend and all the best. Thank you.

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