Management Of Primary Aldosteronism Research Articles

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

Effectiveness of adrenal venous sampling in the management of primary aldosteronism; single centered study at a tertiary care hospital in Sri Lanka

Effectiveness of adrenal venous sampling in the management of primary aldosteronism; single centered study at a tertiary care hospital in Sri Lanka

24 A Surgical Odyssey in Primary Aldosteronism Management

24 A Surgical Odyssey in Primary Aldosteronism Management

Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).

Retrospective evaluation of patients diagnosed with Primary Hyperaldosteronism

Primary hyperaldosteronism (PA), despite being a common disease, is grossly underdiagnosed and undertreated. Though in primary care prevalence of PA is 4–6% in patients with hypertension, it is much higher in specialized hypertensive clinics, especially in resistant hypertension (RH). PA is associated with higher morbidity rates than matched essential hypertension patients. PA is classified as unilateral and bilateral disease, with adrenalectomy considered for unilateral disease and medical management with mineralocorticoid receptor antagonists (MRA) for bilateral disease. There is gross underdiagnosis of PA across the world with very limited literature on PA from India. We wanted to retrospectively evaluate the profile of patients diagnosed with PA from case records, in outpatient settings in a tertiary care hospital. Primary outcomes of the study will be to evaluate the presenting features of PA patients. This includes clinical, biochemical, radiological aspects in different subgroups like unilateral vs bilateral disease, diabetes/ prediabetes vs non-diabetes, and chronic kidney disease (CKD) vs no significant CKD. We also want to evaluate the treatment preferences (both surgical and medical) and follow-up data (for treatment outcomes / effectiveness if relevant records were available). Our main objective is to highlight the current state of PA presentation and management so that we can develop a pragmatic diagnostic approach to improve screening, case detection and empiric management of PA.

Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia.

While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited health care access. We aimed to assess the availability and affordability of health care resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries. Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin ratio is performed in all countries, confirmatory testing is routinely performed in only 6 countries due to lack of facilities and local assays, and cost constraint. Assays are locally available in only 4 countries, and some centers have a test turnaround time exceeding 3 weeks. In 7 countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In 6 countries, the cost of AVS and adrenalectomy combined is more than 30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable. Large populations currently do not have access to the health care resources required for the optimal management of PA. Greater efforts are required to improve health care access and affordability. Future guideline revisions for PA may need to consider these limitations.

What We Know about and What Is New in Primary Aldosteronism.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.

Adrenal Vein Sampling in the Management of Primary Aldosteronism: The Added Value of Intraprocedural Cortisol Assessment.

Primary aldosteronism is the most common cause of secondary hypertension. Adrenal vein sampling is the gold standard for subtyping primary aldosteronism. However, this procedure is technically challenging and often has a low success rate. Our center is one of the very few performing this technique in our country with an increasing experience. The aim of this study was to evaluate the role of the cortisol intraprocedural assay in improving the performance of adrenal vein sampling. We enrolled all of the patients with primary aldosteronism that underwent adrenal vein sampling from February 2016 to April 2023. The cortisol intraprocedural assay was introduced in October 2021. We enrolled a total of 50 adrenal vein samplings performed on 43 patients with the diagnosis of primary aldosteronism. In this sample, 19 patients and 24 patients underwent adrenal vein sampling before and after intraprocedural cortisol measurement, respectively. The procedure was repeated in seven patients (one before and six after intraprocedural cortisol measurement), given the unsuccess of the first exam. Selectivity of the adrenal vein sampling was assumed if the serum cortisol concentration from the adrenal vein was at least five times higher than that of the inferior vena cava. Lateralization was assumed if the aldosterone to cortisol ratio of one adrenal vein was at least four times the aldosterone to cortisol ratio of the contralateral side. The mean age of the patients that underwent adrenal vein sampling (N = 43) was 55.2 ± 8.9 years, and 53.5% (n = 23) were female. The mean interval between the diagnosis of hypertension and the diagnosis of primary aldosteronism was 9.8 years (±9.9). At diagnosis, 62.8% of the patients (n = 27) had hypokalemia (mean value of 3 mmol/L (±0.34)), 88.4% (n = 38) had adrenal abnormalities on preprocedural CT scan, and 67.4% (n = 29) described as unilateral nodules. There were no statistically significant differences in the patients' baseline characteristics between the two groups (before and after intraprocedural cortisol measurement). Before intraprocedural cortisol measurement, adrenal vein sampling selectivity was achieved in 35% (n = 7) patients. Selectivity increased to 100% (30/30) after intraprocedural cortisol measurement (p < 0.001). With the exception of one patient who refused it, all patients with lateralized disease underwent unilateral adrenalectomy with normalization of the aldosterone to renin ratio postoperatively. The lack of effective alternatives in subtyping primary aldosteronism highlights the need to improve the success rate of adrenal vein sampling. In this study, intraprocedural cortisol measurement allowed a selectivity of 100%. Its addition to this procedure protocol should be considered, especially in centers with a low success rate.

2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism.

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

Success Rate of Adrenal Venous Sampling and its Determining Factors: Experience of a Single Center in Malaysia

Primary hyperaldosteronism has been regarded as the commonest and potentially curable cause of secondary hypertension in up to 80% of cases if this condition is detected early. Laparoscopic adrenalectomy proved to be a promising curable method for primary hyperaldosteronism secondary to aldosterone producing adenoma (APA), while primary hyperaldosteronism secondary to bilateral adrenal hyperplasia (BAH) requires optimization of medical treatment. Adrenal venous sampling (AVS) has been recommended by the Endocrine Society's guideline in addressing the subtypes of primary hyperaldosteronism. Therefore, determining success rate of AVS in our centre is crucial in the management of primary hyperaldosteronism and to prevent redundant procedures. The objectives of this study were to evaluate the success rate of AVS in our centre and the associated factors that correlate with the success rate. A retrospective study in a single centre, all adult patients who were diagnosed with primary hyperaldosteronism and underwent AVS in our centre between 2014 until 2022 were included. Successful samples defined by a selectivity index (SI) of ≥ 2, that is, the ratio of adrenal vein cortisol level to the peripheral vein cortisol level, were evaluated. The baseline demographic characteristics of each patient, technical parameters of AVS, and anatomical parameters of right adrenal vein from the venographic images were evaluated and analysed to correlate with the outcome of AVS. A p-value of <0.05 was considered statistically significant. The overall success rate of AVS in our centre was 61.3%. The success rate significantly increased to 80.6% in the trained IR group, which represents a single IR who had completed specific training in adrenal venous sampling (AVS), compared to non-trained IR group which consisted of a total of 10 IRs without specific AVS training (p=0.046). The right AVS had lower success rate than the left AVS (64% vs 94.6%). The type of right adrenal vein pattern showed significant association with the outcome of AVS (p=0.014). There were 6 types of right adrenal vein patterns observed in our study; Type 1 - gland-like pattern with numerous branches, Type 2 - delta pattern, Type 3 - triangular pattern with central "blush", Type 4 - no discernible pattern and Type 5 - spidery or stellate pattern. The sixth pattern was the hepatic radicles blush with hepatic drainage, for which blood sampling were also collected due to its appearance was frequently indistinguishable from the Type 1 pattern. The results showed Type 2 pattern had the highest incidence (30.5%; 32/105 samples) and Type 5 had the highest success rate (100%; 11/11 samples), while the hepatic radicles blush pattern had the highest incidence in fail samples resulting in the highest failure rate (94.7%; 18/19 samples). The visualisation of the inferior emissary vein from the venographic images during right AVS had a significant association with the successful AVS (97.5% success rate; 39/40 samples; p=0.003). Contrariwise, blood sampling withdrawn from the right adrenal vein in the presence of hepatic drainage communication associated with the failure AVS (86.7% failure rate; 26/30 samples; p=0.001). The overall success rate of both AVS in our centre was 61.3%, and the success rate was higher in the trained IR group than the non-trained IR group. The visualisation of inferior emissary vein and the type of right adrenal vein patterns were the key determining factors with significant association to the successful right AVS. Conversely, blood sampling withdrawn from the hepatic radicles and hepatic drainage had significant association with the failure right AVS.

FRI124 Insights From The Incidence Of Primary Aldosteronism In Patients With Hypokalemia (IPAHK+) - Study

Abstract Disclosure: S. Gruber: None. E. Stasi: None. A. Boan Pion: None. R. Steiner: None. I. Sudano: None. F. Beuschlein: None. Background: Hypokalemia plays an important role in the diagnosis and management of primary aldosteronism (PA). The hypokalemic variant of the disease accounts for about one third of all cases. However, little is known about the incidence of PA in a hypokalemic population. Design: The IPAHK+ study is an epidemiological, monocentric, cross-sectional trial to provide evidence on the incidence of PA in a hypokalemic outpatient population. Methods: Recruitment of outpatients with hypokalemia ≤3 mmol/l is carried out on a continuous referral-basis through an automated data delivery system at the University Hospital Zurich (USZ). Todate, 69 patients underwent the study protocol, which includes guideline-compliant workup for PA. Results: The mean age of the participants was 52.5±1.5 years with a sex ratio of 35:34 women to men, a mean potassium value of 2.77±0.03 mmol/l [1.8; 3.0] and a prevalence of arterial hypertension of71%. PA was diagnosed in 45.9% of all participants, all of whom had a history of hypertension. The incidence of PA increased continuously with decreasing potassium level with proportions of 26.7%,45.8% and 59.1% in the subgroups of 3.0 mmol/l (n=15), 2.8-2.9 (n=24) and ≤2.7 mmol/l (n=22),respectively. In the subgroup of hypertensives the incidence of PA was as high as 65.1%. Prior testing,60.9% of all patients presented at least with one plausible other cause for their hypokalemia with potential drug triggers accounting for the largest portion (33.3%). Among participants on diuretics the incidence of PA was 57.9%. Conclusions: The incidence of PA in the investigated outpatient population was more than 4 out of 10and inversely correlated with baseline potassium levels. Moderate or severe hypokalemia, regardless of its cause, should therefore prompt evaluation for PA in hypertensive individuals. Normotensive PA was not observed in our cohort. The significance of the study is limited by the still low number of enrolled patients with a potential selection bias. Presentation: Friday, June 16, 2023

FRI416 Primary Hyperaldosteronism in Pregnancy

Abstract Disclosure: S.M. Seav: None. M. Basina: None. Background: Primary hyperaldosteronism is extremely rare in pregnancy. Since 1962, only approximately 30 cases have been reported in the literature.1 Clinical Case: A 40-year-old female was referred for work-up of primary hyperaldosteronism (PHA). She was first diagnosed with hypertension (HTN) at age 29 during her first pregnancy. Laboratory work-up was consistent with PHA: serum aldosterone 22.6 ng/dL, renin activity 0.1 ng/mL/hr, aldosterone:renin ratio of 226. Post-saline infusion aldosterone level was 10.7 ng/dL. Adrenal CT scan showed a 6mm left-sided adenoma. Surgery was not recommended because adrenal vein sampling did not show lateralization. She was started on Spironolactone 25 mg/day. Despite the significant pregnancy risks, patient continued to desire conception and was switched to Labetolol. She was lost to follow-up and returned to the emergency room for dizziness at 26 weeks pregnant with twins with BP 180/109 mmHg. She had not been taking any anti-hypertensives and there was evidence of severe fetal growth restriction in both babies. After a goals of care discussion, patient deferred emergent C-section and suffered intrauterine fetal demise on hospital day 9. Conclusion: PHA in pregnancy is rare and difficult to diagnose and manage. Newer studies estimate that &amp;gt; 5-10% of patients with HTN have PHA.2 Hence, maintaining high vigilance of this disease in pregnant patients is even more imperative, including screening for PHA during pre-conception period in hypertensive women. A systematic review of 38 cases of PHA in pregnancy showed that 19% of cases were diagnosed with HTN prior to pregnancy without PHA screening.1 The average age of women in this study was 29.8 years. Additionally, there is a correlation in women with younger age at diagnosis and having unilateral PHA, in which case adrenalectomy should be performed prior to conception.3 In pregnancy, first line anti-hypertensive therapies include alpha methyl dopa, labetolol, and nifedipine. In PHA, diuretics such as amiloride and mineralocorticoid receptors should also be considered if BP is not at goal. Spironolactone and eplerenone have been safely used in pregnancy with both male and female fetuses.1,4 If surgery is not an option and medical therapy is ineffective, then physicians should have a low threshold to admit patients for close BP monitoring. 1Landau, et al. Primary Aldosteronism and Pregnancy. Annales d’Endocrinologie. 2016;77:148–160 2Funder, et al. Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916 3Akasaka, et al. Sex Difference in the Association Between Subtype Distribution and Age at Diagnosis in Patients With Primary Aldosteronism. Hypertension. 2019;74(2):368-374 4Cabassi, et al. Eplerenone Use in Primary Aldosteronism in Pregnancy. Hypertension. 2012;59:e18-e19 Presentation: Friday, June 16, 2023

FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Abstract Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

FRI136 Adrenal Venous Sampling Criteria For Chemiluminescent Enzyme Immunoassay

Abstract Disclosure: K. Nakai: None. Y. Tsurutani: None. K. Irie: None. K. Teruyama: Employee; Self; Fujirebio Inc. J. Saito: None. M. Omura: None. T. Nishikawa: None. Objective: In primary aldosteronism (PA), plasma aldosterone concentration (PAC) was measured by radioimmunoassay (RIA), but the supply of the RIA kit was discontinued in March 2021 in Japan. The Japan Endocrine Society's 2021 Clinical Practice Guideline for the Diagnosis and Management of PA recommends that PAC measured by chemiluminescent enzyme immunoassay (CLEIA), which yields standardized LC-MS/MS compliant measurements, be used for clinical judgment. Because CLEIA shows a lower PAC than RIA, various cutoff values for PA need to be revised. Although conversion formulas for RIA and CLEIA for various kits have been provided, these conversions were studied mainly using samples representing aldosterone concentrations in peripheral blood; thus, it is unclear whether the same conversion formula can be used for samples obtained by adrenal venous sampling (AVS). In this study, we examined PAC conversion in AVS samples and the criteria for AVS when measured using CLEIA. Methods: PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) from 63 patients with PA, were measured using RIA and CLEIA methods. The established conversion formula for PAC in peripheral blood samples was PAC (CLEIA) = 0.852 × PAC (RIA) − 36.0. PAC and aldosterone/cortisol ratio (A/C ratio) conversion formulas were determined between the two assays for AVS samples. Moreover, the CLEIA conversion value, which corresponds to the AVS criteria of conventional RIA, was obtained. Results: The median [interquartile range] PAC (CLEIA) in the samples was 9823.3 [3659.8-20600.5]. PAC measured using CLEIA was significantly correlated with RIA, and the correlation coefficient was 0.971. The PAC conversion formula determined was PAC (CLEIA) = PAC (RIA) × 0.7723 - 1199 pg/mL. PAC at 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. The correlation coefficient for the A/C ratio was 0.997, and the conversion formula was A/C (CLEIA) = A/C (RIA) × 0.7864 - 2.427. Discussion: Samples obtained from AVS had a much higher level of PAC than those obtained from peripheral blood. The PAC conversion formula for samples in AVS has a very large intercept compared with those in peripheral blood. Thus, the results of AVS tested by CLEIA should be interpreted with care because of the differences in the conversion formula. A different cut-off value may also be needed when evaluating the lateralization ratio because of the large intercept. Conclusion: PAC conversion formulas for AVS samples using CLEIA and RIA methods were obtained. The study outcomes are useful for interpreting AVS results using the CLEIA. Presentation: Friday, June 16, 2023

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

Advances in the molecular imaging of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. It predisposes to adverse outcomes such as nephrotoxicity and cardiovascular damage, which are mediated by direct harm from hypertension to the target organs. Accurate subtype diagnosis and localization are crucial elements in choosing the type of treatment for PA in clinical practice since the dominant side of aldosterone secretion in PA affects subsequent treatment options. The gold standard for diagnosing PA subtypes, adrenal venous sampling (AVS), requires specialized expertise, the invasive nature of the procedure and high costs, all of which delay the effective treatment of PA. Nuclide molecular imaging is non-invasive and has wider applications in the diagnosis and treatment of PA. This review aims to provide a summary of the application of radionuclide imaging in the diagnosis, treatment management and prognostic assessment of PA.

Contrast medium free selective adrenal vein sampling in the management of primary aldosteronism

BackgroundTo analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA). MethodsConsecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists. ResultsIn total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52–0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01). ConclusionContrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy.

NP-59 Scintigraphy for Primary Aldosteronism Lateralization in a Patient With Polycystic Kidney Disease

A 65-year-old-male presented to the endocrine clinic for further evaluation and treatment of primary aldosteronism (PA). His past medical history was notable for polycystic-kidney-disease (PCKD) leading to a kidney-transplantation at age 48, as well as a diagnosis of PA at the age of 52. The patient had initially elected for medical management of PA; thus, PA sub-type-classification was not pursued. Despite treatment with spironolactone and potassium supplements, subsequent blood-pressure control was poor, with progressive renal failure and persistent hypokalemia. Currently, the patient was being prepared for a staged-bilateral-nephrectomy to relieve some of the mass-effect from the giant polycystic-kidneys. The upcoming surgery gave rise to the option of a concomitant adrenalectomy as a potential cure for PA. However, at this point, PA-sub-type classification was quite challenging. Anatomically, the large cysts grossly distorted the retroperitoneum, hiding the adrenal glands from view on CT imaging ( Figure A). Biochemically, adrenal-vein-sampling (AVS) seemed both technically difficult due to the distorted vascular anatomy as well as potentially risky due to the expected prolonged exposure to radio-contrast in a kidney transplant patient pre-existing advanced chronic kidney disease (CKD). Following a multidisciplinary consultation, NP-59 SPECT/CT was performed (Figure B-D). Very few case reports of PA in patients with PCKD have been reported thus far ((1)Hoorn E.J. Hesselink D.A. Kho M.M. Roodnat J.I. Weimar W. Van Saase J.L. Van Den Meiracker A.H. Zietse R. A case of primary aldosteronism revealed after renal transplantation.Nature Reviews Nephrology. 2011; 7: 55-60Crossref PubMed Scopus (8) Google Scholar). In the setting of PCKD, a diagnosis of PA may be delayed or missed entirely due to pre-existing alternative explanations for resistant hypertension and CKD. Furthermore, adrenal adenomas may be overlooked on planar imaging due to their small size and distorted abdominal anatomy associated with PCKD. In general, AVS is considered the gold-standard For PA sub-type classification, but in complex cases such as with PCKD, alternative diagnostic methods may be useful. NP-59 (I-131-iodo-cholesterol) is a marker of adrenocortical cholesterol uptake. Dexamethasone-suppression NP-59 scintigraphy has been suggested for the differentiation of PA sub-types, but its use is limited by low resolution allowing for false negatives as well as limited tracer availability ((2)Nomura K, Kusakabe K, Maki M, Ito Y, Aiba M, Demura H. Iodomethylnorcholesterol uptake in an aldosteronoma shown by dexamethasone-suppression scintigraphy: relationship to adenoma size and functional activity. J Clin Endocrinol Metab. 1990 Oct;71(4):825-830. doi: 10.1210/jcem-71-4-825. PMID: 2401712.Google Scholar). The addition of SPECT/CT over planar imaging NP-59 scintigraphy, has been shown to increase sensitivity to 82%, including the detection of aldosterone producing adenomas smaller than 1.5 cm ((3)Yen R.F. Wu V.C. Liu K.L. Cheng M.F. Wu Y.W. Chueh S.C. Lin W.C. Wu K.D. Tzen K.Y. Lu C.C. TAIPAI Study Group131I-6β-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results.Journal of Nuclear Medicine. 2009; 50: 1631-1637Crossref PubMed Scopus (94) Google Scholar). In our patient, NP-59 SPECT/CT clearly identified a functional left-adrenal cortical adenoma (Figures B-D). Subsequent left adrenalectomy and nephrectomy resulted in normalization of potassium levels and improved blood-pressure control allowing for a reduction in the number of his anti-hypertensive medications. Pathological evaluation identified a 3cm cortical adenoma. Thus, NP-59 SPECT/CT should remain a part of the diagnostic armamentarium, especially for challenging cases of PA sub-type classification.

PS-BPC08-1: VALIDATION OF PRIMARY ALDOSTERONISM DIAGNOSIS DURING THE TRANSITIONAL PERIOD OF ALDOSTERONE ASSAY AND GUIDELINE CHANGES IN JAPAN

Objectives and Methods: In Japan, the plasma aldosterone concentration (PAC) measurement method was changed from RIA to CLEIA method in April 2021. From then until August 2021, when the 2021 clinical practice guidelines for the diagnosis and management of primary aldosteronism (PA) were published, we diagnosed PA using the RIA-converted PAC value (conversion formula from CLEIA (X) to RIA (Y): Y = 1.174X + 42.3) and the conventional positive decision criteria of the screening and confirmatory tests in PA diagnosis. The new criteria were then used to re-determine and confirm the agreement. Results: PAC(CLEIA) and renin activity (PRA) or active renin concentration (ARC) were measured simultaneously for PA screening at our hospital from April to August 2021 in 122 patients (135 measurements in total). PAC values (CLEIA) were less than 4 pg/mL in 21 measurements (16%). This value was converted to PAC(RIA) at 47 pg/mL based on the formula. (i) PA screening tests: 10% of the measurements were found to be ‘not excluded’ by the conventional criteria and negative by the new criteria. This was due to the fact that the calculated PAC(RIA) values were higher than they should be when the conversion formula to RIA was applied to cases with low PAC(CLEIA) values, resulting in higher estimated ARR values (PAC(RIA)/PRA or PAC(RIA)/ARC ratio). (ii) PA confirmatory tests: In the captopril challenge test, one case was found to be positive by the conventional criteria and negative by the new criteria due to the same reason as that on point (i). In the saline infusion test, PAC(CLEIA) of 12–15 pg/mL was determined to be less than PAC(RIA) 60 pg/mL by the conversion formula, which was deemed negative by the conventional criteria but borderline by the new criteria. (iii) PA diagnosis using the confirmatory tests: In one case, the diagnosis did not match the positive (borderline) classification based on the new criteria, although the patient was deemed negative by the conventional criteria. This was due to discrepancies of the saline infusion test results. Conclusion: During the transition period of PA diagnosis from the RIA to CLEIA method, it was necessary to review the data and retest the patients according to their symptoms because of possible inconsistencies between the new and conventional criteria-based diagnostic results. PA diagnosis and treatment should be judged comprehensively on a case-by-case basis, without relying entirely on the values of the criteria.

Anatomical and functional remodeling of left ventricle in patients with primary aldosteronism and concomitant albuminuria.

Primary aldosteronism (PA) is the leading cause of secondary hypertension globally and is associated with adverse cardiovascular outcomes. However, the cardiac impact of concomitant albuminuria remains unknown. To compare anatomical and functional remodeling of left ventricle (LV) in PA patients with or without albuminuria. Prospective cohort study. The cohort was separated into two arms according to the presence or absence of albuminuria (>30 mg/g of morning spot urine). Propensity score matching with age, sex, systolic blood pressure, and diabetes mellitus was performed. Multivariate analysis was conducted with adjustments for age, sex, body mass index, systolic blood pressure, duration of hypertension, smoking, diabetes mellitus, number of antihypertensive agents, and aldosterone level. A local-linear model with bandwidth of 2.07 was used to study correlations. A total of 519 individuals with PA were enrolled in the study, of whom 152 had albuminuria. After matching, the albuminuria group had a higher creatinine level, at baseline. With regard to LV remodeling, albuminuria was independently associated with a significantly higher interventricular septum (1.22 > 1.17 cm, p = 0.030), LV posterior wall thickness (1.16 > 1.10 cm, p = 0.011), LV mass index (125 > 116 g/m2, p = 0.023), and medial E/e' ratio (13.61 > 12.30, p = 0.032), and a lower medial early diastolic peak velocity (5.70 < 6.36 cm/s, p = 0.016). Multivariate analysis further revealed that albuminuria was an independent risk factor for elevated LV mass index (p < 0.001) and medial E/e' ratio (p = 0.010). Non-parametric kernel regression also demonstrated that the level of albuminuria was positively correlated with LV mass index. The remodeling of LV mass and diastolic function under the presence of albuminuria distinctly improved after PA treatment. The presence of concomitant albuminuria in patients with PA was associated with pronounced LV hypertrophy and compromised LV diastolic function. These alterations were reversible after treatment for PA. Cardiac Impact of Primary Aldosteronism and Albuminuria Primary aldosteronism and albuminuria has been, respectively, demonstrated to bring about left ventricular remodeling, but the aggregative effect was unknown. We constructed a prospective single-center cohort study in Taiwan. We proposed the presence of concomitant albuminuria was associated with left ventricular hypertrophy and compromised diastolic function. Intriguingly, management of primary aldosteronism was able to restore these alterations. Our study delineated the cardiorenal crosstalk in the setting of secondary hypertension and the role of albuminuria for left ventricular remodeling. Future interrogations toward the underlying pathophysiology as well as therapeutics will facilitate the improvement of holistic care for such population.