Good afternoon, everyone. Thank you for joining us. My name is Andrea Quiles-Sanchez and I work at Endocrine Society as Digital Program Administration Coordinator. And welcome to ITE Live 22, Session 1. As many of you are likely aware, ITE Live has typically been hosted in person at Endo. In order to provide this resource to fellows and program directors, we've decided to host this yet again as a webinar. Please note that today's session is being recorded and will be available on the Center for Learning in a couple of weeks. Today we'll be focusing on reproduction, thyroid and adrenal questions from ITE 2022. And it is my pleasure to introduce today's moderator, Dr. Salila Khura, our ITE Chair. Dr. Khura, the floor is yours. Great, thank you so much and thank you to everyone for joining us and thank you to our presenters for taking time out of your busy schedules to come and speak today. So I think we can move on to the next slide. And thank you to our ITE 2022 faculty who are listed here. They put in a lot of work and designed a great exam that was very useful for the over 700 fellows that took the test. So thank you again for your participation and your hard work. Next slide. And these are just the disclosures. And we can move on to the next slide. And some important points about ITE that it should really be treated as a learning experience by programs rather than as a formal high stakes knowledge assessment. It really should be used to provide a general picture of the fellows knowledge base in general endocrinology and the questions can be reviewed to identify gaps in an individual fellows knowledge and also to guide the program if curricular changes are needed or if there are particular gaps that the program should focus on. But it really should not be viewed as a board exam in and of itself. It's really for educational purposes. Next slide. And this just goes over the fellow performance. As you can see over 700 fellows took the exam. The average score was around 60 and fellows got better with the test as they progressed in their training. And so this is a good thing to realize that if you're a first year fellow you're not supposed to have done as well or not have the knowledge base the same as a third year fellow. So this just reiterates that. And then performance by topic area. Today we'll be discussing reproduction, adrenal and thyroid. And the performance was pretty similar in most areas. Male reproduction is always tough because there's not as many clinical encounters with male reproduction and that this has been an issue in terms of most of our fellows don't have as much exposure clinically to this. But the other areas all seem to score around the same, which was around 60%. So without further delay, we'll have Dr. Alan Dalkin from the University of Virginia Health System present the reproduction questions to us. So thank you, Dr. Dalkin, for coming and speaking to us. Happy to do it. Can you go back one slide? Just go back one slide real quick. I promise I won't take your life. Just look at the denominator, the number of female and male reproduction questions is less. So missing one hurts considerably more. That's a very fair point. So while we're, of course, very tough and reproduction is a difficult topic, yeah, missing one of seven is worse than missing one of 21. So yeah, no, that's a good, that's an important point to bring up. So thank you. Anyway, all right, go forward. So I have two male and two female reproduction questions. I picked the ones where the performance was sort of the most confusing in the sense of, I think there needed to be some clarification in terms of the answer. So that's the basis for these. Obviously, there are more questions. So first one, 35-year-old guy, I'll just review these since you all read them de novo when the test came out. 35-year-old man is evaluated for azoospermian infertility. Critically important is that there's two years of unprotected intercourse without conception. Otherwise, normal, wife's normal, physical exam and laboratory. The physical exam is otherwise, as I said, normal, but in terms of the testicular size and such like that. But the labs have one specifically important result, which is that the FSH level is high, and that's in distinction to the LH level, which is normal. There's a karyotype that's already been done, and that's normal. And there's a couple of semen analyses. The second one documents a pH value that's normal and a normal volume, but there's azoospermia. Next slide. So the question was, which of the following genetic conditions does this patient most likely have? And you can see there's a range of options in terms of the selections there, with D being the most common selection and A being the second most common. But there's pretty much somebody who picked just about everything. Just take a look through those for one sec. All right, then go on. And the correct answer is A, Y chromosome microdeletion. Go ahead to the next slide. So the important points on this in terms of separating it out were the patient has non-obstructive azoospermia, and that's based on the semen analysis having normal pH, so all the various contributions to the semen are normal, the volume's normal. And most importantly, the LH and testosterone levels indicate that there's normal lating function. The elevated FSH would not occur were there obstructive issues. In other words, whether there's a problem with the delivery of sperm to the semen and then semen to the outside world, if you will. So the high FSH wouldn't fit with any obstructive pathology, really, in that regard. So what are microdeletions of the Y chromosome? It's the second most common cause of genetic male infertility after Klinefelter syndrome. You guys can read through this as you go through it. There's quite a bit known about the genetic mutation and the lesion itself. Next slide. But I want to go through why the other ones were wrong, because I think one could eliminate these pretty well. Obviously, Kalman syndrome is hypogonadotropic, hypogonadism associated with anosmia or hyposmia. And there really should be smaller, the patient having normal testicular size eliminates that as well. The mosaic Klinefelter, again, because of normal testicular size and normal karyotype, although theoretically, I guess we didn't say how many cells were analyzed. For choice D, congenital absence of the vas deferens, you would not have the high FSH. That can be seen in conditions such as cystic fibrosis. But again, we talked about why this isn't simply just obstructive vasospermia. In answer E, although gonadotropic adenomas are often non-functional associated with normal testosterone, they're really rare in young men of reproductive age. All right. So are we going to do questions at the end? Is that how this is rolling? Or do you want me to? Yeah, I think probably questions at the end would be the best way. Okay. All right. So if you have a question, fire it into the chat box, and we'll pull it back up and answer them at the back end of the session. Next one. So 16-year-old man is referred to discuss treatment options for hypogonadism. He doesn't want to use testosterone gel or patch. And he's read about testosterone decanoate, which is a depot formulation long-acting testosterone that's given every 10 weeks. So we asked about some additional safety information. Next slide. So which of the following is a potential adverse effect that you need to explain to the patient if they're going to use that regimen? And you can see there's marked fluctuations in energy levels and mood, abnormal liver enzymes, cough, shortness of breath, immediately following the injection, skin irritation, and injection site myopathy. And again, you can see that there's a pretty broad distribution of answers, which in my opinion, suggests that nobody really knows about this medication, which I admit is pretty new and very expensive and probably not used frequently. So it's worth putting it on the ITEs that you can all read about it. Next slide. The answer is C, right? So the FDA stipulated that all injections of testosterone decanoate must be administered in an office or hospital setting because of the injection side effects that occur. And there's some reasonable incidence, low but reasonable incidence of pulmonary oil microemboli. So you can get cough and shortness of breath, and hence these things have to be given in the physician's office. Generally speaking, my understanding is that none of these are particularly severe, but when they occur, they are certainly worrisome. Next slide. So answer A, the whole point of this formulation is that there's less variation in testosterone levels from day to day, and then less variation in terms of how the men are feeling. So it tends to be that there's not fluctuations in movement and that there are not fluctuations in energy level. So the answer B, oral testosterone is broken down in the liver and has potential to cause liver damage. The injectables do not. Answer D, which is skin irritation, is much more common with a patch and the adhesive from the patch. And answer E, injection site myopathy has not been associated or reported with testosterone decanoate. All right, let's do the two female cases. So female reproduction, this was question number 31. 17-year-old woman presents with primary amenorrhea. She is otherwise healthy and there is no family history of any reproductive disorders. On physical exam, she is notable for sparse axillary and pubic hair, but normal Tanner stage five breast development. And her pelvic examination reveals a blind vaginal vault and there is no uterus seen on transvaginal ultrasound. The laboratory studies, there's an undetectable HCG, so she's not pregnant. The FSH level is normal. The LH level is elevated and the prolactin level is likewise normal. All right, next slide. So which of the following is the most likely result if one were to do karyotype analysis? 45X, 46XX, 46XY, and 47XXY. And again, D wasn't picked particularly frequently, but Turner syndrome, normal female genetics, and male genetics. Those were the three choices. And next slide or forward. The correct answer is C, and this is going to be testicular feminization or androgen insensitivity. Next slide. So the patient is phenotypically female. There's normal breast development, but absent uterus and the high normal LH or above normal LH level. And this is the presentation that we see with androgen insensitivity. And her karyotype is going to be most likely male, XY. In androgen insensitivity syndrome, the karyotype, with this karyotype, the patients present as a female phenotype because testosterone is unable to activate its receptor. So there's an absence of the cervix as the malaria and ducts are needed for development of the upper one-third of the vagina, cervix, uterus, and fallopian tubes. So when you measure it, the testosterone levels are quite high, and the feedback to the pituitary and to LH specifically is diminished. Next slide. A is Turner syndrome, gonadal dysgenesis. That would have 45XO karyotype, ovarian failure, short statue, and a number of comorbidities that were not mentioned in the stem. Answer B, which is the rare congenital absence of the uterus and vagina, would present with absent menarche, but normal pubertal development and gonadotropin levels should be normal. Those patients would be 46XX. And finally, D, which was 46XXY, which is the underlying Klinefelter syndrome, which is in men with hypergonadotropic hypogonadism. All right, next slide. So the second female reproduction. So 25-year-old woman with congenital adrenal hyperplasia is referred for preconception counseling. Congenital adrenal hyperplasia was diagnosed shortly after birth with clitoromegaly and labial changes and treated with prednisone as a child and then after puberty changed to hydrocortisone, which she's currently taking, 15 milligrams in the morning and five in the evening. Birth control pills were started after menarche to manage the hirsutism and regulate demenses. She's also on Florinef and then the birth control pills. And she and her husband want to start attempting conception in the coming year. Next slide. So physical exam, blood pressure is normal. Height, five feet, four inches. Weight is normal, so BMI 24. And there's terminal hair growth on her chin, abdomen, and dyes and elevated Ferrimengaloy score of nine, which is quantification of hirsutism. The rest of her exam is unremarkable. There's her laboratory studies. The testosterone level is slightly above normal. The DHEA sulfate level is slightly above normal. The androstenedione level is similarly above normal. Next slide. So the question was, which of the following is the best next step in this patient's management? So choice A was switch the hydrocortisone back to the dexamethasone or back switch the hydrocortisone to dexamethasone. B, discontinue the oral contraceptive and start trying to conceive. C, refer for genetic counseling or testing for the parents of the fetus. D, measure 17-hydroxyprogesterone. Or E, measure progesterone in the follicular phase. So there were a fair number of choices for B, C, and E. And you can put advance. And the correct answer for this was C. I would say, I will admit here that we probably made a mistake in writing this question to a slight extent because there's no fetus yet. So if that's why you picked or you didn't pick C because they're not yet pregnant, I apologize. I guess in retrospect, we could have done a better job. But let's go through the other incorrect answers. So congenital adrenal hyperplasia is due to 21-hydroxyl deficiency is probably one of the more common autosomal recessive disorders. You guys can read about the CYP21A2 gene. Pregnancy rates, if properly treated, can be up to 60 to 80% in this population. Interestingly, many of the women with congenital adrenal hyperplasia do not attempt pregnancy in their lifetime. Androgens can appear with ovulation. So it's important to have glucocorticoid replacement and try and suppress hyperandrogenism. Next slide. So answer C, which is the correct answer, preconception counseling is very important. And it includes testing the father to see whether he is a carrier. Because lacking carrier status, there's no risk to the baby. It's all about managing the mom as well as making sure that if there's hyperandrogenism, and it's a female fetus that you're treating the hyperandrogenism in the presence of a male fetus, that would be less of an issue. Next slide. Last slide. So answer A, dexamethasone is typically associated with more adverse effects of cortisol excess, such as weight gain, worsening insulin resistance, it would need to be stopped as soon as pregnancy is diagnosed because it can cross the placenta into the fetal circulation. And that has adverse effects. Answer B, she should not discontinue the oral contraceptive and start trying to conceive until after the father's carrier status is known and then the risks are clear. Answer D, 17-hydroxyprogesterone does not need to be normalized when treating congenital hyperplasia. This leads to overtreatment and excess glucocorticoid exposure. So it's all about cyclicity, not so much the actual androgen levels. And answer E, ideally, after discontinuing oral contraceptives but before trying to conceive, treatment optimization can be monitored with measurement of progesterone in the follicular phase but it would not be helpful on the patients on birth control pills. All right, back to you, Zalula. Great, thank you so much, Dr. Dalkin. And if you have questions, please put them in the Q&A and we will have time at the end to review them. So next we'll move on to the thyroid section. So Dr. Sarah Mason is going to be presenting. She's from the University of Colorado School of Medicine. So thank you for joining us today. Good afternoon or evening, depending on where you are. Can go to the next slide. So I have three questions to run through today. The first is a 67-year-old man who was treated with ipilimumab and nivolumab therapy for melanoma. He has no personal or family history of thyroid disease. Three weeks after initiating therapy, thyroid function tests are performed. His TSH at that time measures 0.06, which is low. Total T3 is 240, which is elevated. Total T4 is 17.1, which is elevated. And free T4 is 3.2, which is also elevated. On exam, he has a pulse rate of 92 beats per minute, no ophthalmopathy. His thyroid's non-tender, firm, approximately 20 grams in size and without any nodules. Eight weeks later, findings on his thyroid exam are unchanged, and he has, you can go to the next slide, the following lab results. So the question is, which of the following thyroid function test patterns is now the most likely in this patient eight weeks later? And so just to summarize, I can let you look through these. They have various TSH and free T4 or T3 levels and also different antibody patterns. And you can see, looking at the distribution of answers, most commonly people chose A, but there were also a fair number of people who chose B and C, which is why we thought it was a good question to review. And you can click forward. So the correct answer is A, which is an elevated serum TSH, a low free T4, a low total T3, and positive TPO antibodies with negative TRAB. And our objective was to just, well, that's fine, we'll move forward. To the next slide. Sorry, these are small. So immune checkpoint inhibitors, also called immunotherapy. These are cancer therapies that are commonly, I should say, that are more commonly prescribed in various solid tumors. And these promote T cell-mediated anti-tumoral responses. And some of the first studies showing their benefit was with melanoma, as in this patient. These drugs target either CTLA-4, which is involved in that immune checkpoint. The common therapies include ipilimumab, which this patient was on. There's also PD-1 inhibitors, again, involved in the checkpoint, including nivolumab, which this patient was taking. And then PD-L1 inhibitors, which is the ligand for PD-1. And those are also used in some solid tumors. So immunotherapies have been associated with endocrinopathies throughout various endocrine organs, but most commonly are associated with thyroid dysfunction. And rates are as high as 35% with monotherapy and up to affecting two-thirds of patients in combination therapy, as in the case we described here. You can also see other endocrinopathies like hypophysitis, less commonly primary adrenal insufficiency or type 1 diabetes. So the most frequent form of immune checkpoint inhibitor-related thyroid dysfunction is a painless, destructive thyroiditis. And this encompasses transient thyrotoxicosis that's rapidly followed by primary hypothyroidism, which is answer A. And in the majority of patients, TPO antibodies are positive. The thyrotoxic phase, as I mentioned, is brief and self-limited. And the median time from the start of therapy is short to thyrotoxicosis about five weeks. Thyrotoxicosis lasts a medium of six weeks and hypothyroidism develops in most patients at a medium of 10 weeks. And this can be transient or permanent, but often will require treatment with levothyroxine. Patients, not uncommonly, will really have very mild symptoms despite very abnormal thyroid function tests. The other answer, central hypothyroidism from hypothyroidism is answer B, occurs in 6% of patients treated with immune checkpoint inhibitors. It's less common and would not follow a thyrotoxic phase. So that's why that answer is incorrect. Immune checkpoint inhibitor-induced graves, hyperthyroidism can occur, but it's much less common. In this context, you'd expect to see a higher T3 to T4 ratio. And of course, more commonly, you would see a positive trap as well. Euthyroidism answer C is less likely than the rapid development of hypothyroidism. That's why that answer is incorrect. And given that immune checkpoint inhibitor, thyroid dysfunction is so common, we do, our oncologist colleagues do closely monitor for thyroid dysfunction in patients taking immunotherapy. Can go to the next one. So this is our next question. A 38-year-old woman who's presenting for follow-up of a 1.6-centimeter right thyroid cancer. She'd undergone an ultrasound-guided FNA, which showed a follicular neoplasm Bethesda 4 cytopathology. And she subsequently had molecular testing, which demonstrated abnormal gene expression with a risk of a malignancy of approximately 60%. I should say risk of malignancy or NFP of approximately 60%. The patient had no abnormal lymph nodes or contralateral thyroid nodules on ultrasound. And she thus proceeded with a right lobectomy for management with isthmosectomy. And that was four weeks ago. Her pathology shows a 2.4-centimeter minimally invasive follicular thyroid cancer with capsular invasion, no extra thyroid extension or angioinvasion and negative surgical margins. At this visit today, she feels tired. Her exam is unremarkable. However, her laboratory tests demonstrate a TSH of 1.9, which is within the normal range, thyroglobulin of 15.9, and thyroglobulin antibodies that are negative. You can go to the next slide. So the question is, which of the following should be recommended now as the most appropriate next step in this patient's management? A, no additional testing or treatment. B, repeated neck ultrasonography. C, completion thyroidectomy. D, completion thyroidectomy and radioactive iodine. Or E, initiation of levothyroxine. And you can look again at the selections by the people who took the exam, which are fairly spread across the board, which is why we chose this as one of the questions to review. But the majority, the largest number, I should say, of respondents did indicate answer A. You can move forward, which was the correct answer. And you can go to the next slide. So in terms of follicular thyroid cancer, the WHO in 2017 adjusted the histological classification. There are now three subtypes according to the WHO, which include minimally invasive follicular thyroid cancer, which this patient had. That's where you only see capsular invasion. Encapsulated angioinvasive follicular thyroid cancer, where you would just see blood vessel invasion. And then widely invasive follicular thyroid cancer, which is grossly invasive. The American Thyroid Association 2015 Thyroid Cancer and Nodule Guidelines classify risk of recurrence for all types of differentiated thyroid cancer. But as you can see that the subset of patients who have follicular thyroid cancer with extensive vascular invasion, so that's that widely invasive group per WHO, have a very high risk of recurrence between 30 and 55%. Whereas patients who have minimally invasive follicular cancer, like the patient described here, have a low risk of recurrence of only two to 3%. So very different. So when you're determining patient's risk of recurrence, you'll also look at their age, tumor size, again, whether it's widely invasive, presence of extrathyroidal extension, and of course, lymph node or distant metastases. In this particular case, the patient had minimally invasive follicular cancer, as I mentioned, no risk factors for an adverse outcome as described. And her post-op thyroglobulin was 15 after a lobectomy, which is an appropriate level. Generally, a thyroglobulin of less than 30 is expected after a hemothyroidectomy. So this patient's expected long-term survival is similar to that of the general population. Next slide. And that's the most appropriate next step in her management is to do nothing at this point, but to continue to follow the patient over time. Completion thyroidectomy, answer C, or completion thyroidectomy with radioiodine, answer D would be incorrect given her low risk for structural recurrence and she doesn't need additional treatment now. She has an excellent predicted long-term survival and thus any risks of further surgical intervention or radioiodine therapy would outweigh potential benefits for this person. Prescribing Lodos levothyroxine is also incorrect. Her initial TSH goal is approximately 0.5 to two given low risk for recurrence. And so there's no need to prescribe levothyroxine at this time. And repeating another ultrasound now is both costly and unnecessary in this patient. Again, the American Thyroid Association guidelines recommend doing a repeat neck ultrasound post-op at six to 12 months after initial treatment for most patients. Next slide. Last question in thyroid. 67-year-old man is admitted to the intensive care unit with hypotension due to sepsis. Despite aggressive therapy, the patient's condition continues to deteriorate. And one month earlier, the patient had had a normal thyroid laboratory panel. Next slide. Which of the following patterns is expected in this patient? So we have TSH, T4, total T4, total T3, and free T4 levels that are variously elevated and low, which I really don't feel compelled to read. But I will highlight that most folks answered answer C and then the second most popular answer was answer B. Next. And the majority of people did get this right. Can go to the next slide. So this is a critically ill patient who's in the ICU and is clinically deteriorating. And they have what's called non-thyroidal illness syndrome, which was formerly referred to commonly as youth thyroid six syndrome. And the changes in the patient's TFTs are classic for this syndrome and represent what we would be expecting in the case of severe medical illness. So what we typically see with non-thyroidal illness syndrome most commonly is a low total T3 level, and that's frequent in hospitalized patients. Total T4 values are also frequently low in non-thyroidal illness and a very low T4 per 10s of poor prognosis. Free T4 levels generally remain normal in most patients, but in a patient such as this one where they're critically ill and declining, you can see a frankly low free T4 as well. And early on with non-thyroidal illness, TSH is either normal or can be low, but generally measurable, so not undetectable. And then during recovery phase, the TSH value is generally elevated, but below 20. So if it was higher than that, you'd be more concerned about primary hypothyroidism. Next slide. So only answers B and C had a low total T3, making answers A, D and E wrong. Answer B had a slightly elevated TSH, but the patient, based on the description of their clinical trajectory actually declining, makes it incompatible with the recovery phase. And therefore answer C with a very low T3, a low T4 and a low free T4 with a low TSH is the most likely pattern to see in this context. And that's all I have. Great, thank you, Dr. Mason. And now we'll move on to the adrenal section. So Dr. Alan Chang from Stony Brook and Dr. Ricardo Correa from the University of Arizona, Phoenix will be presenting this section. Thank you both. Thank you. Great to be here. Hello everyone. So we have three questions for the adrenals. I'll be doing the first and third one and Dr. Correa will be doing the second one. So thank you for that. So first question, we have a 67 year old female who presents to the clinic with a six month history of weakness and edema. She's been referred for further evaluation and management of a suspected neuroendocrine tumor. On physical exam, her blood pressure is 145 over 90 millimeters per mercury, heart rate's 80 beats per minute. She has large but superclavicular and mild dorsal cervical fat pads with slight facial plethora and one plus pedium edema bilaterally. She has several ecchymosis on her arms and legs, significant dermal atrophy and no striae and she has decreased proximal and distal muscle strength. Next slide, please. Thank you. So on labs, we have a potassium of 3.1, which is on the lower side, plasma ACTH is 40, which is quote unquote normal. Urinary free cortisol is 400 micrograms per over 24 hours. That's quite high. And the serum cortisol after a low dose dexamethasone suppression test was 17 micrograms per deciliter, which is above the caught up on 1.8. And they did a dexamethasone level, which was 300 milligrams, which is appropriate. Next slide, please. All right, so we have a, they did an MRI pituitary T1 with gadolinium and it was red as normal. Yeah, it's the image. So take a look. Yep. And then they did a CAT scan of the chest and abdomen of the pelvis, which showed enlarged adrenal glands and the nine millimeter vascular mass in the pancreas, which was interpreted as being consistent with a neuroendocrine tumor. And there's the arrow, the positive arrow sign. Yep, and that's it. Next slide, please. So which of the following is the best next step in this patient's evaluation and management? So we have five. We have A is octreotide scan. B is the PET CT. C is late night salivary cortisols. D is inferior pituitary sinus sampling. And E is chest CT. Now of all these five answers, answers A and D seem to have gotten the most choices. And the correct answer is D, D as in delta. So it's IPSS, inferior pituitary sinus sampling. And so next, can you, next. So the whole purpose of this question was to evaluate for ACTH dependent hypercortisolism. So next one. So I mean, this patient has ACTH, basically has, well, so we think ACTH dependent hypercortisolism. She definitely looks on exam and her biochemical workup was definitely positive. And her ACTH was appropriately normal. It was not suppressed. Given all those facts, we did not need to undergo more testing such as the late night salivary. So statistically, you know, Cushing's, the most common cause of Cushing's syndrome is a pituitary adenoma and the Cushing's disease, aka pituitary adenoma secreting ACTH is much more likely than ectopic ACTH syndrome. In this case, factors that favor Cushing's disease are the modest magnitude of the ACTH. So it's not very high, the elevated urinary cortisol levels, and basically just the fact that it's most likely to be the cause of this. Factors that favor ectopic ACD syndrome are the hypokalemia, myopathy, and rapid onset. Incidental pituitary adenomas are found in up to 10% of imaging studies, and up to half of patients with Cushing's disease do not have a tumor visible on MRI. Hence, if you see a clean MRI or even a pituitary adenoma that's below 6 millimeters, it doesn't mean that that may or may not be the cause. So further testing will be needed, such as IPSS. Next one. So IPSS can consistently distinguish Cushing's disease from ectopic ACD syndrome, and this is the next best stop. It was a clean MRI, so hence we need to find out whether there is a microscopic adenoma up there that is called secreting ACD. In this case, somastand receptor imaging might be used as further evidence that the pancreatic mass is a neuroendocrine tumor, but it's very common to have these incidental findings, and this study, this imaging, will not help us determine whether the tumor is producing ACTH. Finally, well not finally, PET-CT actually images tumors of high metabolic activity, but neuroendocrine tumors do not have this. And again, this study will not help us localize the source of ACTH access. And finally, a chest CT will be performed after ruling out Cushing's disease. So basically, if the IPSS is negative, that's when you would go for a chest CT. So that's out. Next one, please. Okay, so Dr. Correa. Thank you so much, Dr. Chen. This is amazing because when you're talking about one of the two most important glands in the body, you have two people talking about them, so adrenal is one of them. So let's talk about a 52-year-old man with hypertension and hypokalemia that is completing evaluation for primary hyperaldehyde. The sodium is 147, the potassium is 3.2, so in the low side, the aldosterone is 30, and the plasma renin activity is less than 0.6, and you perform a CT with fine cuts, and you demonstrated that there was normal appearance. So the next slide. The next step to do is an AVS. So next slide. So these are the results of the AVS. You can see the aldosterone, cortisol, and the ratio. You can see the right adrenal vein with an aldosterone of 3,000, the left of 456, and the inferior vena cava of 20. You can see the cortisol and the ratio. So next slide. So which of the following is the most accurate interpretation of the adrenal vena sampling? And really, we choose this topic because this is a high-yield topic that will come in every single AVIM exam. So you will get one of this in the exam. You will get an AVS, so that's why we try to put this in every IIT exam. So if you see here, there is the distribution between successful study. Both adrenal glands are successful. The second one was unsuccessful study. However, there is enough information to localize the source in the right side, and unsuccessful study unable to localize. Really, the answer is C. Next click. So let's talk about next slide. So basically, when we look at an AVS, we have to first look at the cortisol concentration. So the cortisol concentration will tell us if we are really in the area that we need to be. We need to be in the right adrenal vein and in the left adrenal vein, and we compare that with the central or what we call mixed venous blood, that is the IVC. The ratio between the venous blood and in the cortisol in the venous blood and in the right and the left and in the IVC is called selectivity index. And the selectivity index has to be greater than two if you are using without ACTH infusion. If you are using with ACTH infusion, then it's more than three. If you don't achieve that, then it's uninterpretable the study. So the study should not be interpreted, as I mentioned, if you don't achieve these numbers. So in the next slide, you can see that in this case, you compare that one was 750 compared to 10. So when you divide it, it's 75. So more than three for sure, this was with ACTH. And the other was 120 compared to 10. This was 12, more than three definitely. So this was the selectivity index is positive. So then you can go and look at cortisol, adductor and cortisol ratio. So then the answers were not predictability or not interpretability, then definitely you delete it. So A, D and E. So the next step is to calculate the lateralization index that in this case, you have to do it between the adductor and cortisol ratio. And the adductor and cortisol ratio under ACTH stimulation have to be above four to say that it's lateralization and below three is when we consider bilateral. So the next slide. In our case, when you see the ratio, you can see that the ratio of one side was 4.0 and the ratio of the other side was 3.8. When you divide it, the dominant versus the probably non-dominant, it goes to 1.05. This is less than three. So this is bilateral. Another characteristic of when it's not bilateral is that there is suppression from the non-dominant side. So there will be an elevation in the dominant side, but suppression in the non-dominant side. In this case, you can see that there was non-suppression. Both of them were very similar ratios. So this is how you answer this question. Now, Dr. Shang again. Thanks a lot. All right. Last question, guys. So 32-year-old female, referred for further investigation of recurrent hypokalemia. She has a two-year history of hypertension, initially diagnosed during a routine medical assessment. Her current medications are amlodipine, 10 milligrams daily, doxazosin, 8 milligrams daily, ramipril, 10 milligrams daily, and potassium chloride, two tablets, about 470 milligrams potassium per tablet, twice daily. Her medical history is otherwise unremarkable. There is no relevant family history. Her height is 66 inches, weight is 154 pounds, BMI is 25 kilograms per meter squared. Her blood pressure is 135 over 92 millimeters per mercury, and heart rate is 74 beats per minute and regular. Her physical exam findings are unremarkable. Next one, please. So labs. So potassium, 3.4, so on a mildly low side. Plasma-rendering activity is 0.05, so that's definitely suppressed. Serum aldosterone is 39.5 milligrams per deciliter, so that's quite high, elevated. Her low-dose dexamethasone suppression test was one, so that's probably suppressed. Cascades of the adrenal glands, triple phase, shows 2.5-centimeter nodule in the right adrenal gland with the following details. Base plant is 20 household units. One minute following contrast is 50 household units, and 15 minutes following contrast is 25 household units. And the left adrenal gland has a normal appearance. Next one, please. Okay, which of the following is the most appropriate next step in this patient's evaluation and management? So you have A, adrenal-adrenal sampling. We have B, genetic testing for glucocorticoid-remediable hyperaldosteronism. So you have C, MRI of the adrenal glands, D, saline suppression test, and E, right adrenalectomy. So the reason why we chose this question, actually, is because this question actually encompasses a lot in the workup for primary hyperaldosteronism, as well as the adrenal mass imaging characteristics, what we have to know. So then the correct answer is, I believe, E, right adrenalectomy. So it was pretty much between, as you can tell, A or E. And that's a pretty good difference. So the purpose of this question is just to basically walk through the steps. Okay, so next slide, please. So this patient, I mean, she has, her history is very suggestive of primary hyperaldosteronism. And basically, when, so basically, we worry about this when just resistant hypertension, which is basically uncontrolled blood pressure, despite treatment with at least three agents at reasonable doses, and one of which will usually be a diuretic. But in this case, was previously discontinued here because of the hypokalemia. And also, when there's persistent hypokalemia, despite treatment with ramipuril and potassium supplementation. So basically, we start worrying about primary hyperaldo when these two characteristics are there. So when the plasma renin activity is suppressed, and aldosterone concentration is greater than 20 nanograms per deciliter, in a patient with the history of spontaneous hypokalemia, you don't need confirmatory testing, actually. So normally, a confirmatory testing would be a 24-hour urine collection for salt and aldosterone. But when there's spontaneous hypokalemia, although it's above 20 with suppressed renin, we don't need it. We can go to the next step. So this patient has a CAT scan, which documented a right 2.5 centimeter adrenal lesion. The baseline household units are above the threshold expected usually of an adenoma. So when it's before the contrast, if it's a rich adenoma, it should be below 10 household units. In this case, the post contract findings are reassuring, washout 50%. So there is no indication for further imaging with adrenal MRI. Okay, so the washout in this case was good. So only for MRI. Next one, please. Okay. So when surgery is being considered for treatment of primary hyperaldo, normally, an AVS would probably be necessary, especially if they're above the ages of 35, of the older age. However, if the patient's young, aka below the age of 35, and on imaging, there is a unilateral unequivocal lesion there, then AVS usually is not needed. So in this case, is reason to proceed directly to surgery if age below 35, spontaneous hypokalemia, marked aldosterone excess, and unilateral lesion, adrenal lesion, with radiologic features of a cortical adenoma on adrenal CT. So this patient meets the criteria. And finally, genetic testing for glucocorticoid remediable aldosteronism is generally reserved for patients with primary hyperaldo with early onset, usually below the age of 20, and or family history of primary hyperaldo with stroke at a young age, and stroke is actually quite important. And that's usually below the age of 40. So that's why we don't actually pick that one for an answer. So in this case, the patient did not meet the criteria for confirmatory testing with 24 hour urine, she did not need an MRI, and she did not need an AVS because of her age and the unequivocal imaging on CAT scan. All right, and I believe that's it, right? Great, thank you. I find it depressing that young age is less than 40, but we'll talk about that. So there was one question about that last question, which was, you know, the importance of age, but I think that you've addressed that by saying that in patients younger than 35, with those other criteria, that you don't need to do AVS. I'm not sure if that's exactly what the Dr. Paul Volley was getting at, but I believe that was the question. And we'll give it another minute to see if there are any other questions, but there don't seem to be. So thank you to the presenters for so clearly delineating the answers. Okay, there seem to be a couple. The question was, what would be the cutoff for IPSS, for pituitary incidental loma? Cut off in what way, like in terms of like age or like? Yeah, I'm not sure exactly what that, I mean, oh, the person said, I mean size, Dr. Mittal. Oh, I see. So basically, on MRI, the pituitary gland, if there is a lesion, six millimeters and above, one does not need to undergo IPSS. However, if it's below six millimeters, then you cannot assume that that pituitary myocardial loma is the cause, and you still need to undergo IPSS. So six millimeters. The next question is, if ALDO is inappropriately normal, but the ALDO-Renin ratio is low with low potassium and marked hypertension and age less than 35, is AVS still not needed? One more time, sorry. If ALDO is inappropriately normal, but the ALDO-Renin ratio is low with low potassium and marked hypertension in a patient whose age is less than 35, is there still no need for AVS? So what I will recommend here is, if ALDO is inappropriately normal, let's see that the ALDO, it's a little bit above 12 with a suppressed Renin. The most important thing is a low Renin hypertension. So if the low Renin, it is suppressed Renin, and the ALDO is not more than 15, but more than 12, and the patient have hypokalemia and hypertension, yes, the patient is less than 35, I will not need an AVS. But the key here is low Renin, not just ALDO. It's the low Renin hypertension. That's the key. And might I add one more thing, is that the ALDO might be artificially lower. You have the potassium, it was run at the same time with a low potassium as well. So I would, we will need to repeat the potassium and see what the ALDO is before. Great, and thank you both. And this next question is a thyroid related question, is ipilimumab more commonly associated with thyroiditis? So the CTLA-4 inhibitors, which includes ipilimumab, if given as monotherapy, then that's where you'll see hypophysitis. It's with, actually with the PD-1 inhibitors that you'll more commonly see thyroid dysfunction or combination of the different classes, you'll see thyroid dysfunction. Most commonly hypothyroidism, then thyroiditis, then hyperthyroidism from Graves. Hopefully that answers the question. I don't, sometimes it's hard to know what they are, they mean that they're right. Yeah, well, we'll see if there's any follow-up, but I think that's a great answer. Oh, something just popped in. Thanks. Okay, yeah, cool. And so that, and I believe this is for the adrenal team. So it says, so if patient has a pituitary adenoma greater than six millimeters and ACTH-dependent Cushing's, would you forego IPSS and go straight to surgery? And then there's a follow-up to, and it's why not confirm with IPSS first to ensure pituitary surgery is required. So if Dr. Chen allowed me, so I will mark it myself. So I given me the professor at the endocrine society, so you can see it. And I addressed this question in that, in the endocrine society. But really, if I will say that between six and nine millimeters, I would consider that a gray zone and I will still perform IPSS. More than nine, definitely for surgery. Six and nine millimeters, so I will still do IPSS. So that's the only thing. There are some studies that say six, other studies in European says nine. So six and nine is still gray zone. So that's why I will just consider gray zone six and nine. More than nine go to surgery, definitely. Great, thank you. All right, well thank you to our panelists for joining us this evening afternoon depending on where you are, and thank you to all the participants.

reproduction

ITE 2022

azoospermia

Androgen Insensitivity Syndrome (AIS)

congenital adrenal hyperplasia

adrenal vein sampling (AVS)

primary hyperaldosteronism

cortisol concentration

neuroendocrine tumor