Good afternoon, everyone. Thank you for taking the time to join us today. My name is Gedmisa Karyas. I'm from the University of Minnesota. I'd like to thank the Endocrine Society for the opportunity to speak today. Today, we'll be discussing primary aldosteronism, focusing on three critical aspects. First, examining our current screening practices and the potential role of clinical support tools in addressing that. Second, we'll work through the practical case-based diagnostic approaches. Finally, we'll discuss evidence-based treatment strategies and monitoring. I have no financial relationships to disclose. Let's start with a case here. Mr. Eby is a 28-year-old male with history of hypertension diagnosed in his early 20s. Past medical history of atrial fibrillation. Blood pressure remains uncontrolled on two antihypertensive medications, so reports medication compliance issue. Basic body mass index is normal. Potassium thyroid function test echocardiograms are normal. The question asks, would you screen Mr. Eby for primary aldosteronism? Go ahead and select yes or no if you choose to use a pulse. I don't see anything coming up, so let me share our learning objectives for today. At the end of this session, you will be able to assess the clinical gap in primary aldosteronism screening and evaluate the role of clinical decision support tools in addressing that, be able to apply primary aldosteronism diagnostic algorithms using case-based learning scenarios, and finally, outline evidence-based treatment options and monitoring protocols. Primary aldosteronism is the most common cause of treatable cause of hypertension. The hallmark is autonomous aldosterone production independent of renin and regardless of sodium status. It can arise from a single or multiple aldosterone-producing regions in one or both adrenal glands. Studies over the last decade has informed us that primary aldosteronism is largely a genetic disorder. More than 90% aldosterone-producing adenomas carry somatic mutations, and these key mutations are found in the genes like KCNJ5, CACNAA1D, and others. And irrespective of the mutations, directly or indirectly, they increase intracellular calcium, which leads to increased or stimulating Cp11 beta2 expression, leading to autonomous aldosterone production. And this increased aldosterone production within the principal cells of the collecting tubal cell and dysadenal tubules activates the mineralocorticoid receptor, leading to increased expression of the epithelial sodium channel and the sodium ATPase channel and cell membranes, leading to increased absorption of sodium tubular lumen on the left to the bloodstream on the right, with overall increased sodium reabsorption. Through electrogenic exchange, there is potassium and hydrogen ion loss, leading to increased urinary excretion of potassium and hydrogen ion. And this vicious cycle of increased sodium reabsorption and volume expansion and increased vascular systemic resistance leads to the hypertension we see in primary aldosteronism, hypokalemia, metabolic alkalosis. And patients with primary aldosteronism have disproportionately increased target organ damage for the degree of hypertension, which we'll be looking at in more detail later on. And when it comes to prevalence, there is no single point estimate regarding the prevalence among the general hypertension population, reflecting various disease definitions studies have used over the years. However, when it comes to resistant hypertension, the data seems to be consistent. About 20% or 25% or more individuals with resistant hypertension have primary aldosteronism. And at the bottom, we see that the prevalence of primary aldosteronism increases with the severity of hypertension. In patients with hypokalemia, this study reports 28% prevalence. And at the bottom, they show that the prevalence of primary aldosteronism increases with the severity of hypokalemia, approaching more than 80% among those with severe hypokalemia. So based on this, guidelines recommend all individuals with resistant hypertension and hypokalemia to be screened for primary aldosteronism. In addition, hypertension early onset, accelerated or malignant hypertension, when there is disproportionate target organ damage for the degree of hypertension, unexplained atrial fibrillation, hypertension adrenal nodules are also other indications for screening. This slide illustrates the pathophysiology cascade of aldosterone-mediated cardiovascular disease. Basic science studies informs us that in addition to the sodium retention and volume expansion we saw in the earlier slide, there is aldosterone excess at the cardiac and vascular level causes remodeling, inflammation, apoptosis, increased oxidative stress, leading to the increased cardiovascular morbidity and mortality in this group. Studies over the last two decades have shown that patients with primary aldosteronism have increased risk of atrial fibrillation, heart failure, coronary artery disease, cardiovascular mortality, and stroke compared to those with central hypertension for the same degree of hypertension. And that's why it's important that even if blood pressure is controlled, diagnosing primary aldosteronism for targeted treatment to prevent these complications is important. And treatment reverses or prevents this complication. This is a long-term mortality in cardiovascular event study among patients with unilateral primary aldosteronism after targeted treatment. Those that are represented in the red and blue graph are those who have underwent adrenal leptomy. And this group, whether they had hypertension cured or not, had all lower all-cause mortality compared to those with primary or essential hypertension represented here in the orange line. So going back to the earlier question, the young age at onset or the onset of hypertension at a young age, early onset unexplained atrial fibrillation are indications for screening for primary aldosteronism in this individual. The normal potassium does not exclude primary aldosteronism. And current medication adherence needs to be addressed, but that should not delay primary aldosteronism screening. But the reality for this individual and most others is primary aldosteronism is a diagnosis is reached if at all after people have developed multiple complications. And studies show that less than 2% of high-risk patients undergo screening for primary aldosteronism. So given the significant implication of delayed diagnosis, let's look at the role of clinical decision support tools in addressing this screening gap. This is a best practice alert quality improvement implementation, which the alert identified multiple risk factors for primary aldosteronism screening, about 14,000 plus candidates. And they report that at the end of 18 months, 14% received primary aldosteronism screening orders following best practice alert implementation. Another study here, which targeted treatment-resistant hypertension group, reports that the primary aldosteronism screening orders placed on the y-axis doubled after introducing the best practice alert, this is comparison of 12 months before and after implementation, though the overall screening rate was still low. In this slide, I will examine details of the best practice alert in action. It first identifies the patients at risk and displays how that for providers. And then if screening has not been done previously in real time, it triggers or alerts providers to order screening orders for primary aldosteronism screening. It can incorporate embedded screening orders. It can include information for providers. For example, in this case, it says screening can be performed without discontinuing antihypertensive medications. Screening interpretation guides can be incorporated within it or with an EMR. For example, in this case, under aldosterone labs, comments can be incorporated to aid up to level of interpret to help actually with interpreting the labs when they are available. So in general, the clinical decision support tools, my take is the initial experience suggests maybe potential utility in primary aldosteronism screening. It certainly represents one approach to implementing systematic screening. The overall screening rate still remains low, but every screening effort contributes to patient detection. Now I will transition to my next objective for this session to apply current diagnostic algorithms. Case two is a 68-year-old male with hypertension, has persistent hypokalemia despite supplements. Blood pressure is uncontrolled on a triple therapy, has cardiovascular, cerebrovascular accident, atrial fibrillation, obstructive sleep apnea. Potassium is low normal. Plasma renine activity is 0.2 nanogram per ml per hour. Aldosterone is 7.8 nanogram per deciliter. All these are given in conventional units. Has normal methanephrines and cortisol. The question asks, what is the most likely diagnosis? Low renine hypertension, syndrome of apparent mineralocorticoid excess, primary aldosteronism, idiopathic resistant hypertension. I don't think that our polls are working, so I'll proceed. So in this study, which checked aldosterone levels multiple times among people with confirmed primary aldosteronism, showed that the aldosterone levels were below this traditional cutoff of 10 nanogram per deciliter or below in 14% of this cohort. Another cohort also shows 29% of primary aldosteronism patient confirmed PA patients had aldosterone levels below the traditional screening method threshold of less than 10. So the key point is there is intra-individual variation of aldosterone secretion due to the pulsatile aldosterone secretion, especially in high-risk population. We should consider repeating the test multiple measurements. And this is a study which looked at the established prevalence at the different states of hypertension using 24-hour urine collection or 24-hour urine aldosterone levels. And they report that the prevalence using aldosterone-to-renin ratio in the most right column, they show that underestimated the prevalence of primary aldosteronism in their cohort, as we see in the table here. And this is a study we saw earlier in the report that among confirmed primary aldosteronism patients, aldosterone ratio was below 30 in 57% of, or 57% had aldosterone ratio less than 30 to one point. So this, the traditional threshold of aldosterone-to-renin ratio above 30 as provided in the guideline demonstrated limited diagnostic accuracy with suboptimal sensitivity and negative predictive value. So in recent years, there has been widespread adoption of more sensitive screening cutoffs to define positive test results, plasma aldosterone concentration 10 or above in a setting of suppressed renin activity or concentration, or aldosterone-to-renin ratio 20 or above in a setting of aldosterone concentration at least six or above. In clinical practice, I find it helpful to look at both numbers and ratios. They both give me information. These revised, or even these cutoffs aim to balance diagnostic sensitivity with practical clinical implementation, particularly as screening becomes widely available. However, as the studies showed earlier in the earlier slides, even these screening thresholds have limitations. Therefore, if clinical suspicion for primary aldosteronism remains high despite initial negative testing, repeat screening is warranted. As with any medical condition, interpretation of biochemical results should also consider or take into account the previous probability of disease in that individual. Therefore, when in doubt of a high-risk group, we have to repeat the screening testing. This is a study which looked at, well, what other management strategy do we have in those individuals? Screening is negative, particularly in individuals with resistant hypertension. In this study, they looked at, if they screened patients for primary aldosteronism, or their cohort is patients with resistant hypertension, they ruled out secondary causes, including primary aldosteronism, based on the cutoff at the time. And then they randomized them to different modalities of therapy. And first, they demonstrate that spironactone is the most effective drug in lowering blood pressure, as shown here in the red graph. And then they show further that the most lower blood pressure approaching negative 20 was among those with suppressed reining level, as we see in the x-axis. Patients with resistant hypertension showed the greatest BP reduction when treated with spironactone, particularly those with low plasma reining levels. Another more recent study looked at low reining hypertension and mineralocorticoid therapy use and titration in that group. And I have their conclusion here. Empiric mineralocorticoid antagonist therapy in patients with low reining hypertension or probable primary aldosteronism targeting unsuppressed reining can safely and effectively improve blood pressure control and reduce proteinuria. Therefore, the key point is negative primary aldosteronism screening in resistant hypertension individuals, low reining or suspected primary aldosteronism, mineralocorticoid therapy reduces blood pressure, and also proteinuria based on this smaller study. So in summary of this primary aldosteronism screening, high clinical suspicion plus negative initial screening, repeat primary aldosteronism screening, secondly, plan B, negative primary aldosteronism screening in resistant hypertension, low reining or suspected primary aldosteronism, mineralocorticoid antagonist therapy is indicated. And this is an argument with hypertension guideline as well, adding mineralocorticoid receptor antagonist as a false drug in the treatment of resistant hypertension. So going back to case two, in this individual, we see a lot of red flux, adjustive of primary aldosteronism risk and the resistant hypertension, persistent hypokalemia, complications that are commonly seen in people with primary aldosteronism and has suppressed reining. And we've seen earlier that even though the traditional aldosterone cutoff is 10, for case detection, studies demonstrated hourly bursts of aldosterone secretion with levels falling below 10 in 20 to 30% of cases. Therefore, the likely diagnosis in this individual is primary aldosteronism. In this case, we proceeded with a 24-hour correlation for aldosterone, which confirmed the diagnosis of primary aldosteronism. So case three, a 56-year-old male with hypertension, hypokalemia, five class of antihypertensive medications. Laboratory findings show reining activity of 0.1, plasma aldosterone concentration 28 nanogram per deciliter in conventional units both, and then serum potassium low at 3.2. CT adrenal findings show bilateral nodularity of adrenal glands, no discrete nodules identified. What is the best next step? Proceed with dynamic confirmatory test with oral salt loading or selenium suppression test. Stop interfering medications and repeat aldosterone and reining measurements. Diagnose by bilateral primary aldosteronism, start myelocorticoid receptor antagonist, or proceed with adrenal venous sampling. So, the endocrine society guideline suggests that if a patient recommends that if a classic trial of aldosterone above 20 in a setting of suppressed training and low potassium additional workup is not needed, primary aldosteronism is confirmatory in that case, and subsequent studies have also supported this recommendation. But in all others, the guideline recommends performing confirmatory testing for further confirmation of primary aldosteronism, mostly employed being saline infusion test, oral salt loading, and captopril challenge. However, in the next slides, we'll see studies which looked at is confirmatory testing necessary for all patients with positive PA screening who don't present with necessarily with this classic trial. One of that study is this ACQUIRE study, which looked at aldosterone-renin ratio for detection of aldosterone-producing adenoma. In their cohort, they report that aldosterone-renin ratio of 100 or above had 100% specificity with zero false positive rate. Even at the aldosterone-renin ratio cutoff of 50 or above, they report in their cohort 0.98% to 100% specificity. And they conclude that high aldosterone-renin ratio value suggests the undertaking of any further confirmatory testing, redundant and unnecessary. Another study which looked at absolute value of the plasma aldosterone concentration reports that in their cohort, plasma aldosterone concentration of 30 or above had 100% diagnostic value with or without hypokalemia for primary aldosteronism. And a systematic review and meta-analysis, which included 55 studies, first, they show the evidence that use of confirmatory tests in a setting of high probability or feature of primary aldosteronism is based on very low quality evidence. And further, the clinical impact being, they mentioned that use of confirmatory tests has led to excess missed cases. And they conclude that the use of confirmatory tests should be reconsidered for patients with high probability of primary aldosteronism features and abnormal screening results. Another study which followed patients with negative confirmatory tests for up to five years report that about 1 5th or 20% of patients with a negative confirmatory test develop overt primary aldosteronism over time, develop primary aldosteronism over time. So the guideline was already outlined that when aldosterone is above 20 in a setting of suppressed screening, low potassium, we don't need additional confirmatory tests. But studies has also challenged the role of confirmatory tests in a setting of a strong clinical features plus abnormal screening test results, or when we have high screening values. But most importantly, a negative confirmatory test result does not exclude primary aldosteronism definitively. And if clinically indicated, if clinical presentation deteriorates, we need to think about rechecking. Or as a management option, we should consider mineralocorticoid antagonist therapy again in a setting of all those resistant hypertension, low renin, or probable primary aldosteronism. After primary aldosteronism diagnosis, imaging, adrenal imaging is recommended. And older studies show that imaging studies correctly identify the source of the aldosterone excess or primary aldosteronism of 50% of the time. Even a more recent systematic review reports sensitivity and specificity of 68% and 57% respectively. They add further that even in young patients, 21% risk of unnecessary surgery if relying on imaging alone. So the key point here is adrenal venous sampling remains the gold standard for surgical decision making and management of primary aldosteronism. Adrenal venous sampling involves catheterization of the bilateral veins and the inferior vena cava. And then the first step is verifying correct placement of the catheter by looking at cortisol step-up or selectivity index. In a case of ACTH stimulation, if the cortisol is five times more than the adrenal veins, more than the periphery, we say the catheters are at the right place. And then we look at lateralization by looking at aldosterone to cortisol ratio on each side of the adrenal veins. And in the case of ACTH stimulation, if the ratio is four or more, we say that it has lateralized to one side. And then further, we look at contralateral separation by looking at aldosterone to cortisol ratio on the contralateral side compared to the periphery. And if it is less than one, it suggests contralateral separation. There are emerging approaches in primary aldosteronism subtyping, one of them being metomidate PET CT scan versus adrenal venous sampling. In this study, looking at biochemical success and clinical success rate provided here right in the middle, they report that metomidate was non-inferior to adrenal venous sampling. So we might be seeing some other options of subtyping down the line. So going back to case one, case three, what is the best next step? A, proceed with dynamic confirmatory testing. That is not the best next step, as aldosterone is clearly very high in the setting of suppressed renin and low potassium, as we've seen earlier. Second, it says stop interfering medications and repeat. This is not the best next step, because most antihypertensive medications cause false negative results. But this individual has positive results, despite multiple medications that are causing false negative results. So further just checking by stopping medication not indicated. C, diagnose bilateral primary aldosteronism. This assumes bilateral disease, which is not correct. CT findings alone are insufficient for making this conclusion. We cannot determine lateralization. We cannot determine lateralization from imaging only. And then the best next step in this individual would be the proceeding with adrenal venous sampling if surgical management is indicated as desired. I'll move to my final, my last objective here, outline evidence-based treatment options and monitoring protocols. So unilateral laparoscopic adrenalectomy is recommended for confirmed lateralizing disease. Preoperative optimization of blood pressure and potassium are recommended. And the treatment with myelocorticoid antagonists prior to surgery serves two purposes. One, it will help to achieve blood pressure optimization by chemical control of potassium and other values. Secondly, it informs post-surgical outcome based on the response to the myelocorticoid antagonist. Post-operatively, we discontinue myelocorticoid antagonist after surgery and monitor potassium for a few weeks due to a risk of transient hyperkalemia due to hypoaldastronism. And we adjust anti-ather, anti-pertensive medications based on the blood pressure response we see clinically in the subsequent days or during hospitalization. The primary aldosteronism surgical outcome group suggests follow-up of patients to assess clinical outcome and biochemical outcome within three months and then six to 12 months later. And they have clinical outcomes are established by looking at blood pressure measurements and use of anti-pertensive medications. And we say that it's complete clinical remission if blood pressure is at goal in a setting of no anti-pertensive medication. Biochemical outcome looks at potassium reading in aldosterone measurements. And if all these values are within the normal range, we say complete biochemical remission. So we're going back to case number three. He has lateralizing adrenal venous sampling to the left. And it's being referred for left adrenalectomy. But he's asking, what is my chance of having complete clinical success or remission? A, 30% to 40%. B, 55% to 60%. C, 60% to 70%. And D, more than 80%. So this is a study which looked at clinical and biochemical success rate after adrenolectomy and using 705 cohorts, they report complete clinical remission and 37% of their cohort and complete biochemical success in 94%. More recent data reports complete clinical success of 39%. Therefore, we should advise this individual that his chance is 30-40% and setting this expectation prior to surgery is helpful. What are predictors of favorable surgical outcomes? Our clinical predictors of cure are young age, female sex, lower BMI, but most importantly, short history of hypertension, absence of vascular remodeling, and chronic kidney disease are predictors of complete clinical remission, again, highlighting the importance of early intervention. The international consensus classifies histopathology into two broad categories. Classical histopathology involves when using, actually, the classification is using the morphologic examination and the CYP11β2 immunochemistry staining. The classical refers to the CYP11β2 activity in one area in the form of adenoma, microadenoma, or hyperplasia, whereas non-classical refers to multiple areas of activity, the CYP11β2 activity in the form of microadenoma or hyperplasia. And studies have shown that histopathology informs outcome, and this study of 60 patients with primary aldosteronism, they report that those with classical histopathology had 97, 98% biochemical success rate, whereas those with non-classical had 67%. And another study which looked at long-term recurrence, they report 23% recurrence among their cohort, and further, they classify that the most of this recurrence, out of which 60% was happened in the non-classical histopathology after a follow-up period of nine years. A more larger study of 262 primary aldosteronism patients first report that no biochemical remission, first they report in 16% of their cohort. This was after the fact that all had lateralization index of four or above, and then they showed that this no biochemical remission happened in 73% had multiple CYP11β2 positive areas. So non-classical histopathology, based on the current data, has higher disease persistence and recurrence, which suggests long-term monitoring. So this is a case we saw earlier with resistant hypertension and hypokalemia. Had primary aldosteronism confirmed, adrenal venous sampling showed non-lateralizing result, and medical treatment was started. Before primary aldosteronism diagnosis, amlodipine 10 milligram, benzapryl, clortalidone, all at optimal doses, and high-dose potassium. After diagnosis of primary aldosteronism, currently on spironolactone 100 milligram, and amlodipine 10 milligram daily. Then we see the blood pressure parameter before and after here has improved, reading activity 0.2, and potassium has normalized to 4.3 from 3.2, and GFR has dropped from 81 to 57 here. Question asks, what is the next best step? Reduce spironolactone due to GFR, reduce GFR, no medication adjustment needed, increase spironolactone dose, and reduce amlodipine, stop spironolactone due to reduced GFR. So medical treatment of primary aldosteronism involves, first, dietary salt restriction, which leads to decrease in the sodium delivery to the distal nephron, thereby limiting the enact-mediated sodium absorption, reabsorption, rather, and also blocking the mineralocorticoid receptor antagonists using spironolactone or eplerenone. Spironolactone is a non-selective mineralocorticoid antagonist, it's long-lasting, it's cheaper, and it has more effective blood pressure control than eplerenone, based on an older randomized control trial. Eplerenone is a more selective mineralocorticoid antagonist, it has to be dosed twice daily because of its lower plasma-protein binding affinity. When we start medication and uptitrate doses, it is recommended to monitor potassium, particularly in a setting of renal impairment. If hyperkalemia develops during treatment course, we have the option to stop the other antihypertensive medications which causes hyperkalemia, like antigen receptor blockers or ACE inhibitors, option of adding a loop diuretics, or adding SGLT2 inhibitors based on current recent data, or using potassium binders. If there is intolerance of this medication, amyloride can be used, which blocks the epithelial sodium channel and prevents the reabsorption of sodium, however, there is no cardiovascular protection when using amyloride. And there are medications under investigation, particularly the aldosterone synthase inhibitors, which blocks the CYP11 beta-2, mediated conversion of 11-deoxycortisone to aldosterone, so we might have more options down the line. So in this study, which looked at the incidence of atrial fibrillation and mineralocorticoid receptor activity in patients with medically and surgically treated primary aldosteronism, they show that the incidence of atrial fibrillation was higher among those medically treated with mineralocorticoid antagonists, but their renin remained suppressed, represented here by the orange graph, compared to those, for example, renin is no longer suppressed. And similarly, another study looking at cardiovascular incidence of cardiovascular events, similarly demonstrate that those treated medically, but renin is still suppressed, had a higher cardiovascular events compared to those renin is no longer suppressed or essential hypertension, or primary hypertension group. So the key point here is, if renin is remained suppressed, that's a proxy for insufficient mineralocorticoid blockade. And in these two cases, had a significant, this group had a significant higher risk of incident cardiovascular events and atrial fibrillation. Another more recent study, a Swedish nationwide study, which had 2,400 plus patients with primary aldosteronism, they report increased risk of cardiovascular mortality and cardiovascular mortality and all-cause mortality among those with this higher listed out here. But among that was the treated with low-dose mineralocorticoid antagonists. Those treated with higher doses of mineralocorticoid did not have that increased risk of cardiovascular and all-cause mortality. Therefore, being on mineralocorticoid antagonists by itself is not enough in preventing morbidity and mortality in this patient population. Therefore, the parameters of follow-up when we are treating medically are normalizing blood pressure within the target range, also looking at normal potassium without supplement, and targeting a non-suppressed renin level. So in this individual, breaking it down further, so blood pressure, key clinical findings are blood pressure has normalized, but renin has remained suppressed. And we've seen that that's an indication or a proxy for inadequate mineralocorticoid receptor blockade and risk of increased cardiovascular morbidity and mortality. So we need to increase the spironolactone dose. We see that the blood pressure is already has normalized, so we have to create a room by reducing aminodipine. Actually when we have primary endocrine patients on targeted treatment approach like this, typically this allows us to reduce or eliminate other anti-pregnancy medications, ultimately decreasing the overall medication burden. I find it rewarding actually this way. And it not only simplifies their treatment regimen, but reduces medication-related side effects and improves patient adherence. Other options reduce spironolactone due to reduced GFR or stop spironolactone due to reduced GFR are not the best next step, because after initiating treatment for primary aldosteronism, medically or even surgically, one of the things actually that improves is normalization of this hyperfiltration state, because excessive aldosterone was driving abnormally high filtration rate. And then when we block the action of aldosterone with myocorticoid antagonist or even after surgical treatment, there is unmasking of underlying kidney impairment that was previously masked by the aldosterone-mediated hyperfiltration. So understanding this mechanism helps why the GFR decline is unexpected finding and should not be necessarily interpreted as treatment-related kidney injury. Therefore, A and D are not the best next step. And then clarifying this actually with patients is helpful. And then B is not the best next step, no medication adjustment, as we've seen earlier. So we have a critical, clinical, and even public health gap, less than 2% of high-risk patients for primary aldosteronism are screened for primary aldosteronism. I think best practice alerts show potential to enhance screening. It's one option as a one option. Screening considerations should take into account that there's intra-individual aldosterone variability. So if screening is negative, particularly in a setting of clinical, high clinical suspicion, we have to repeat screening. Confirmatory testing is not needed when the classic thread of aldosterone above 20, and low renin, and suppressed renin. But even current evidence challenges among those strong clinical features plus abnormal screening or high screening values, if we need confirmatory testing. But most importantly, negative confirmatory testing does not definitively exclude primary aldosteronism. And at every step of our diagnostic workup, we can have the use of mineralocorticoid antagonists, and titrating that as a management strategy. And that negative screening test result or negative confirmatory test, and a setting of particularly resistant hypertension, low renin, or probable PA mineralocorticoid antagonists, based on the recent data, even titrating up to other target non-suppressed renin might be the best next step. Adrenal various sampling remains a gold standard. If there's no lateralizing or non-lateralizing disease, it's treated medically with spironolactone and plurinone, along with salt restriction. And medical treatment titrate to optimize blood pressure potassium, and non-suppressed renin to ensure adequate mineralocorticoid receptor blockade, and reduce morbidity and mortality. And then complete clinical remission after surgery does not happen for majority, based on the current data. But favorable predictors for complete clinical remission are short history of hypertension and absence of vascular remodeling, and absence of CKD, again, taking us back to this identify patients early for targeted treatment. Histopathology informs long-term prognosis and monitoring. Thank you. And questions here, I will open up. I will read the first question. How do you manage someone with labs concerning for primary aldosteronism, but no hypertension? Example, a screening in patient with unilateral adenoma. Currently, I think it's my understanding that we don't have data in this group, if treatment actually is helpful. Therefore, in those group, I would not, there's no data to suggest that treatment has an impact. How long should an MRA be held, and are any other medical adjustments necessary in order to diagnose primary aldosteronism on labs? And honestly, we can actually screen patients without discontinuing any antihypertensive medications. In fact, we can do most of the workup without discontinuing antihypertensive medications, as long as renin is suppressed. And because most people are on low-dose mineralocorticoid antagonists anyway, we find that renin is suppressed more. So I would screen without adjusting antihypertensive medications. But if screening is negative, then in that case, I will hold the most offending medications, like mineralocorticoid antagonists or diuretics, for two to four weeks, and then screen again. And during that time, we can use alpha blockers, hydralazine, or calcium channel blockers as an alternative to management. How to counsel patients regarding surgery versus medical management? I'm not sure if I'm going in the right order. But how to counsel patients regarding the, I think that there is clear evidence that for lateralizing disease, if there is no contraindication to surgery, undergoing surgery is the best next step. That is our current understanding, even though there is no direct, well-studied, randomized control trial comparing the two. So that's how I will pose the discussion. Let me see. Going back to the actually. Thank you so much. OK. And then, how can we interpret cortisol in adrenal venous sampling in patients with cortisol co-secretion? So there is a recent data actually support. So if in a setting of mild, autonomous cortisol secretion, the adrenal venous sampling can be performed. And also, the lateralization, or in other words, it should not affect the interpretation of adrenal venous sampling, particularly as long as DHA sulfate is not suppressed, or an acetate is not suppressed. I'm considering that you're talking about the mild, you're talking about the mild cortisol secretion in a setting of primary aldosterolism, up to 20% to 25% can have mild autonomous cortisol secretion. And in that group, based on recent data, we can still interpret adrenal venous sampling results is how I look at it. So can you clarify the role of 24-hour urine collection of aldosterone, potassium, in the diagnosis of primary aldosterolism? So the 24-hour collection of urine aldosterone is done as a part of confirmatory test. We ask individuals if there is no contraindication to load salt orally for three days, three to five days. And starting from the third day, we collect a 24-hour collection to assess aldosterone value, together with the urine sodium. And if aldosterone value is above a certain threshold, I think 12 is what is recommended in the guideline, and in a setting of high sodium load in the urine, above 200 millimole, then we say that the diagnosis of primary aldosterolism is confirmed. But I don't know if I got your question. Another question here, primary aldosterolism in CKD, especially adrenal venous sampling with CKD stage 4, concern for worsening kidney disease due to die. Primary aldosterolism workup management in CKD can be challenging. It's challenging, actually. And yeah, that's a concern. But there is recent data from multiple institutions, which compare it's a retrospective data, but they could look at medically treated patients with CKD and primary aldosterolism compared to those surgically treated CKD and primary aldosterolism, and they show that other than the bottom line outcome, there was no difference between the two groups, which helps me in terms of when I think about workup and, again, management in this group. But yeah, that is a concern. Is there any role for using FinREN to treat primary aldosterolism? I don't think we have data regarding that yet. How can we do the workup in patients receiving several antihypertensive drugs? How should we discontinue the drugs? I would not discontinue the medications, antihypertensive medications, especially when I do initial screening. I would not screen them with no adjustment of antihypertensive medications. But again, if the screening result is negative, then we might need to stop the mostly diuretics and MRA. And then during that time, we have multiple medications, including alpha blockers, hydralazine, and others to fill in the gap during when they are off. When aldosterone-producing adenoma is isolated, resection of the adenoma feasible, I think it's my understanding that that's not a recommended approach. Laparoscopic adrenolectomy is a current recommendation. And we've seen, yeah, that's a current. So that's not the approach actually currently recommended. Let's see. In patients with stage 3 to 4 CKD, aldosterone is already raised. How do we interpret and screen such patients? Yeah, CKD is, again, a difficult workup. Renin would be low because of the kidney function, or high due to problem with excreting the renin. And then so it's difficult. There is no one answer to it, is the way I look at it. So how to proceed with resistant hypertension patients with bilateral nodules? In 1 to 2 centimeters. I guess in this case, the workup is the same. I would work them up the way I would work any other patients for primary aldosteronism perform adenovirus sampling. But if there is an adenoma more than, I think, 1.5 centimeters, I will do a cortisol suppression test or the dexamethasone suppression test to make sure that there is no autonomous cortisol secretion. Because if there is autonomous cortisol secretion, then actually taking care of the nodule or the adenoma that is producing that precedes from before treating the primary aldosteronism. Otherwise, in bilateral cases, bilateral adenoma, I think we do adenovirus sampling and take care of actually the source of if lateralizes, we take care of the source. So we have one minute. And again, I just want to leave you best practice alert. Some potential there. Consider repeat screening, MRA, if I clinical suspicion. If the screening is negative, as plan B, we can't treat. And the negative confirmatory test is not definitive P exclusion. And MRA treatment should be optimizing all these parameters, not only blood pressure, but looking at non-suppressed training, because it prevents complications and mortality. And then again, shortest three, no vascular damage is the key. No vascular remodeling and kidney damage is the key for a complete clinical remission. So early diagnosis is critical. Thank you so much. It's, I think, time to stop. Thank you so much again for joining us today. Bye, everyone. Dr. Sakaris, have a wonderful day. Thank you. You too. Bye.

primary aldosteronism

hypertension

screening practices

diagnostic approaches

treatment strategies

adrenalectomy

mineralocorticoid receptor antagonists

adrenal venous sampling

early diagnosis