Unilateral Aldosterone-producing Adenoma Research Articles

A-056 Investigating Iodine Contrast Contamination in Cortisol and Aldosterone Samples

Abstract Background Primary aldosteronism (PA) is a condition characterized by hypertension resulting from excess secretion of aldosterone. PA caused by a unilateral aldosterone-producing adenoma can be treated with adrenalectomy but requires diagnosis by adrenal vein sampling (AVS). In this procedure, intravenous cosyntropin is administered to stimulate adrenal cortical secretion, followed by obtaining samples from the right and left adrenal veins and IVC. Laterization index is calculated by obtaining the aldosterone:cortisol ratio for each side, with a ratio cutoff ≥3 is used for confirmation. Iodinated contrast media facilitates visualization of catheter positioning during AVS and sometimes results in contamination of samples, evidenced by abnormal gel separator flotation (i.e. gel above plasma). This study had two aims: 1) to determine at what concentration contrast dye causes gel flotation and 2) discern whether contrast media interferes with our cortisol or aldosterone assays. Methods Gel flotation studies were performed by spiking pooled plasma samples with iohexol contrast media (Omnipaque 240, GE Healthcare) at concentrations ranging from 3%-10% v/v and aliquoting into fresh lithium heparin plasma separator tubes (BD, PSTs). Samples were then centrifuged and visually inspected for abnormal gel flotation. Contrast interference studies were performed using three pools of low (5 µg/dL), medium, (30 µg/dL), and high (55 µg/dL) cortisol concentrations. Sample pools were diluted with 20% contrast media or saline (control) and subsequently mixed at different ratios to create a range of dye concentrations (0.5%-18% v/v). Each mixture was assayed in triplicate for cortisol and aldosterone on a cobas e602 (Roche Diagnostics) and LIAISON XL (DiaSorin) immunoanalyzer, respectively. The total allowable error (TEa) was ±0.4 μg/dL or ±20% for cortisol and ±2 ng/dL or ±20% for aldosterone. Results Flotation of the gel separator was observed at a dye concentration of 4.5% v/v and greater. For the cortisol interference study, the bias was <5% for the three pools at all contrast media concentrations. Aldosterone was also measured in these pools, as bias could affect ratios calculated for PA. Aldosterone interference occurred at contrast dye concentrations ranging from 12%-20% v/v. An average positive bias of 34% was observed in aldosterone samples spiked with contrast media relative to the saline control. Compared to sample pool controls without added saline or dye, measurements for cortisol and aldosterone were 19%-22% and 16-25% lower in media- and saline-spiked samples (20% v/v), respectively, indicating a logical dilution effect. Conclusions Contrast dye contamination of AVS specimens can cause gel flotation in lithium heparin PSTs, preventing their analysis. The presence of contrast media at certain concentrations interfered with the DiaSorin aldosterone assay, leading to falsely elevated results. No cortisol assay interference occurred in the presence of contrast media but results were falsely decreased due to sample dilution. Samples collected during AVS may be contaminated with contrast dye causing gel flotation to occur. This is indicative of a minimum contrast media concentration of 4.5% v/v. Aldosterone:cortisol ratios may be inaccurate due to the positive aldosterone immunoassay bias with contrast media contamination. Care should be taken when reporting and interpreting AVS results with suspected contamination.

Primary aldosteronism and hypokalemia-induced rhabdomyolysis in a patient with aldosterone-producing adenoma: A case report and literature review.

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

Aldosterone-Cortisol co-secretion in different adrenal tumors: A case series

Primary aldosteronism is the most common cause of endocrine hypertension. It commonly presents as refractory hypertension, carrying an elevated risk of cardiac and renal complications. Concurrent hypercortisolemia exacerbates the susceptibility to metabolic disorders, including obesity, dyslipidemia, abnormal blood glucose levels, and cardiovascular and renal diseases. Among the reported patients with co-secretion of aldosterone, the majority are aldosterone producing adenoma. Cases of bilateral adrenal hyperplasia secreting both aldosterone and cortisol are rarely reported. In this study, we conducted a comparative analysis of the clinical manifestations, laboratory tests, and imaging findings in two cases involving unilateral aldosterone-producing adenomas and bilateral macronodular adrenal hyperplasia respectively. Notably, our patients exhibited a cortisol circadian rhythm during the initial screening, complicating the diagnosis of Cushing's syndrome. The incorporation of early or routine low-dose dexamethasone suppression tests may prove beneficial in identifying co-secretory lesions promptly, assessing the risk of perioperative adrenal insufficiency, and guiding subsequent treatment and prognosis evaluation.

The importance of novel histopathological classification and its association with outcomes of primary aldosteronism: What you need to know from a urologist’s perspective

Primary aldosteronism (PA), the most important cause of secondary endocrine hypertension, is hallmarked by excessive aldosterone secretion. There were 2 subtypes of PA—unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia, which are now outdated. Since conventional adrenal pathological reports only examined hematoxylin and eosin staining, the secretory function of the structural adenoma(s) could not be determined. Several enzymes produce aldosterone-related steroids, and 2 isoforms of 11β-hydroxylase, namely CYP11B1 and CYP11B2 (aldosterone synthase), are responsible for producing cortisol and aldosterone, respectively. Since the availability of specifically selective antibodies for targeting CYP11B1 and CYP11B2, the diagnosis/nomenclature of PA-related adrenal pathology has been revolutionized by using immunohistochemistry staining for CYP11B2 to identify the aldosterone production site in the human adrenal cortex. The significance of immunohistochemical staining of formalin-fixed paraffin-embedded adrenal tissue sections has become “mandatory” for precisely detecting the lesions responsible for PA. Recently, the histopathology of PA consensus, based on immunochemical findings, was established to define the nomenclature and adrenal histopathological features in unilateral PA. In this study, we further investigate the association between the pathological subtypes and the surgical outcomes of PA as per the criteria of the Primary Aldosteronism Surgery Outcome consensus. Unfortunately, a significant lag is seen in the adaptation of Taiwan’s pathologists to the histopathology of PA consensus. Furthermore, a strong push from all urologists across Taiwan and the governmental health care authorities is required to elevate the care level provided to all patients with PA in Taiwan to exceptional.

Unilateral Primary Aldosteronism: Long-Term Disease Recurrence After Adrenalectomy.

Primary aldosteronism (PA) is frequently caused by a unilateral aldosterone-producing adenoma with a PA-driver mutation. Unilateral adrenalectomy has a high probability of short-term biochemical remission, but long-term postsurgical outcomes are relatively undefined. Our objective was to investigate the incidence of long-term recurrence of PA in individuals with postsurgical short-term biochemical remission. Adrenalectomized patients for unilateral PA were included from a single referral center. Histopathology and outcomes were assessed according to international histopathology of unilateral primary aldosteronism and PASO (Primary Aldosteronism Surgical Outcome) consensuses. Genotyping was performed using CYP11B2 (aldosterone synthase)-guided sequencing. Classical adrenal histopathology, exemplified by a solitary aldosterone-producing adenoma, was observed in 78% of 90 adrenals, compared with 22% with nonclassical histopathology. The classical group displayed higher aldosterone-to-renin ratios (P=0.013) and lower contralateral ratios (P=0.008). Outcome assessments at both short (12 months [7; 12]) and long (89 months [48; 124]) terms were available for 57 patients. At short-term assessment, 53 (93%) displayed complete biochemical success (43 classical and 10 nonclassical), but long-term assessment demonstrated biochemical PA recurrence in 12 (23%) with an overrepresentation of the nonclassical histopathology (6 [60%] of 10 nonclassical histopathology versus 6 [14%] of 43 classical histopathology; P=0.005). PA-driver mutations were identified in 97% of 64 aldosterone-producing adenomas; there was no association of the aldosterone-producing adenoma genotype with PA recurrence. A substantial proportion of individuals display postsurgical biochemical recurrence of PA, which is related to the histopathology of the resected adrenal gland. These findings emphasize the role of histopathology and the requirement for continued outcome assessment in the management of surgically treated patients for PA.

Conn´s syndrome after kidney transplantation.

Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least atriple combination of antihypertensives, including adiuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria. In addition to arterial hypertension and hypokalaemia, the diagnosis of Conn's syndrome relies on examination of serum renin and aldosterone concentrations, plasma renin activity, exercise or furosemide stimulation tests, and imaging studies, preferably computed tomography. The method of treatment of Conn's syndrome is adrenalectomy. In patients with primary hyperaldosteronism with underlying bilateral adrenal cortical hyperplasia or patients contraindicated for surgery, mineralocorticoid receptor antagonists are administered in combination with antihypertensives targeted for optimal blood pressure control.In the group of patients after kidney transplantation, the exact incidence of primary hyperaldosteronism is unknown. Based on across-sectional study performed in 2020, it is estimated to be approximately 15% in the group of patients with unsatisfactorily compensated arterial hypertension; in the cohort of normotensive recipients, the incidence of primary hyperaldosteronism is not documented. Diagnosis of Conn's syndrome in patients in the early period after kidney transplantation is problematic, as the prevalence of arterial hypertension in transplanted patients is high (70-90%) according to the literature. Mineral abnormalities, including hypokalaemia, are also common in the early post-transplant period, mainly due to factors such as duration of cold ischaemia, onset of graft function, donor parameters, post-transplant tubulopathy, and diuretics, the effects of immunosuppressive drugs (especially calcineurin inhibitors and corticosteroids), and possibly potassium-restricted dietary habits that the patient brings from the pre-transplant period, which may mask the effect of hyperaldosteronism on potassium.We present the case of apatient who was diagnosed with Conn's syndrome 7 months after primary kidney transplantation from adeceased donor based on persistent hypokalaemia unresponsive to replacement therapy. At the time of the first manifestation of severe hypokalaemia, the patient was treated with adual combination of antihypertensives (amlodipine at adaily dose of 5 mg and carvedilol at adaily dose of 50 mg), without the need for adiuretics.We consider the case interesting because the spectrum of mineral and acid-base abnormalities in advanced renal failure and in the early post-transplant period, as well as acid-base and mineral imbalances, including hypokalaemia, and the high prevalence of arterial hypertension in the post-transplant period, may mask the picture of Conn's syndrome (Fig. 3, Ref. 19). Text in PDF www.elis.sk Keywords: kidney transplantation, primary hyperaldosteronism, hypokalaemia, metabolic alkalosis, secondary arterial hypertension.

Postoperative ACTH-stimulated aldosterone predicts biochemical outcome in primary aldosteronism.

Primary aldosteronism (PA) is the most common surgically curable cause of hypertension. Unilateral aldosterone-producing adenoma can be treated with adrenalectomy. Clinical and biochemical outcomes are assessed 6-12 months after adrenalectomy according to PASO consensus criteria. Earlier prediction of biochemical remission would be desirable as it could reduce cumbersome follow-up visits. We hypothesized that postoperative ACTH stimulated plasma aldosterone concentrations (PAC) measured shortly after adrenalectomy can predict PASO outcomes. Retrospective cohort study. We analyzed 100 patients of the German Conn's registry who underwent ADX and postoperative ACTH stimulation tests within the first week after adrenalectomy. 6-12 months after adrenelectomy we assessed clinical and biochemical outcomes according to PASO criteria. Serum cortisol and PAC were measured by immunoassay at baseline and 30 min after the intravenous ACTH infusion. We used receiver operating characteristics (ROC) curve analysis and matched the parameters to PASO outcomes. 81% of patients had complete, 13% partial and 6% absent biochemical remission. Complete clinical remission was observed in 28%. For a cut-off of 58.5pg/ml, stimulated PAC could predict partial/absent biochemical remission with a high sensitivity (95%) and reasonable specificity (74%). Stimulated PAC's area under the curve (AUC) (0.89; CI 0.82-0.96) was significantly higher than other investigated parameters. Low postoperative ACTH stimulated PAC was predictive of biochemical remission. If confirmed, this approach could reduce follow-up visits to assess biochemical outcome.

OR02-05 Differences In Genomic Characteristics Of Small Aldosterone-producing Lesions Between Normal And Pathologic Adrenals

Abstract Disclosure: J. Lim: None. S. Plaska: None. &. Liu: None. J. Baker: None. A. Blinder: None. W.E. Rainey: None. A.M. Udager: None. Introduction: Primary aldosteronism (PA) – the most common form of secondary hypertension – is characterized by inappropriate adrenal aldosterone production under suppressed renin conditions. The majority of PA is caused by unilateral aldosterone-producing adenomas (APA) and bilateral hyperaldosteronism (BHA). Emerging evidence suggests that BHA is associated with the accumulation of small aldosterone-producing lesions (less than 1 cm in diameter), including aldosterone-producing micronodules (APM) and/or aldosterone-producing nodules (APN). However, previous studies have shown that APM may also be observed in normal adrenals, and thus, the impact of APM and APN on the development and progression of aldosterone overproduction is not well established. In this study, we compare the frequency and distribution of somatic aldosterone-driver mutations in small aldosterone-producing lesions from normal and pathologic adrenals. Methods: Twenty-eight normal adrenals from deceased renal donors (n=24) and patients undergoing radical nephrectomy for renal cell carcinoma (n=4) were compared with 24 pathologic adrenals from patients with PA who underwent adrenalectomy at the University of Michigan. CYP11B2 immunohistochemistry-guided capture was performed to selectively obtain APM and APN DNA from formalin-fixed paraffin embedded tissue, and mutation status for all known aldosterone-driver genes was determined by Ion Torrent-based targeted next-generation sequencing. Results: From normal adrenals, 57 APM from 12 female and 16 male subjects (median age = 49 years) were analyzed, and approximately 46% of these lesions harbored an aldosterone-driver mutation. The most commonly mutated gene in normal samples was CACNA1D (n = 23; 40.4%), but no KCNJ5 mutations were identified, and no significant sex differences were observed. From pathologic adrenals, 56 APM and 7 APN from 17 female and 7 male subjects (median age = 46.5 years) were analyzed, and the frequency of aldosterone-driver mutations (approximately 70%) was significantly higher than normal adrenals (p-value < 0.05). Although CACNA1D mutations were still predominant in pathologic adrenals (n = 33; 52.4%), a number of KCNJ5 mutations were also observed (n = 5; 7.9%) – particularly in APN. Finally, there was a higher rate of aldosterone-driver mutations in small aldosterone-producing lesions in pathologic adrenals from men compared to women (93.3% vs. 62.5%; p-value = 0.051). Conclusions: The frequency and distribution of aldosterone-driver mutations in small aldosterone-producing lesions (APM and APN) in pathologic adrenals are different from those in normal adrenals and may also vary by sex. Further research is needed on how these different APM patterns affect autonomous aldosterone production in patients with PA. Presentation: Thursday, June 15, 2023

Fluorinated aldosterone synthase (CYP11B2)-inhibitors for differential diagnosis between bilateral and unilateral conditions of primary aldosteronism

The enzyme aldosterone synthase (CYP11B2) is specifically expressed in aldosterone-producing tissue of the adrenal cortex and is overexpressed in aldosterone-producing adenomas (APA). It therefore represents an ideal target for molecular imaging, particularly for the differential diagnosis between bilateral hyperplasia and unilateral APA in primary aldosteronism. However, the presence of the cortisol-producing enzyme 11β-hydroxylase (CYP11B1) in the adrenal cortex remains very challenging owing to its high homology to CYP11B2. Within this study, we efficiently synthesized a variety of disubstituted fluorinated pyridines and pyrazines by Suzuki coupling reactions. These compounds were evaluated for their ability to inhibit CYP11B1 and CYP11B2 in transfected Y1 cells and in NCI-h295 cells. Several compounds were found to exhibit excellent affinity (IC50 < 10 nM) to CYP11B2 as well as strong selectivity (up to 125-fold) over CYP11B1. These findings support the further development of an analogous 18F-labelled PET tracer.

Identifying KCNJ5 Mutation in Aldosterone-Producing Adenoma Patients With Baseline Characteristics Using Machine Learning Technology

BackgroundPrimary aldosteronism is characterized by inappropriate aldosterone production, and unilateral aldosterone-producing adenoma (uPA) is a common type of PA. KCNJ5 mutation is a protective factor in uPA; however, there is no preoperative approach to detect KCNJ5 mutation in patients with uPA. ObjectivesThis study aimed to provide a personalized surgical recommendation that enables more confidence in advising patients to pursue surgical treatment. MethodsWe enrolled 328 patients with uPA harboring KCNJ5 mutations (n = 158) or not (n = 170) who had undergone adrenalectomy. Eighty-seven features were collected, including demographics, various blood and urine test results, and clinical comorbidities. We designed 2 versions of the prediction model: one for institutes with complete blood tests (full version), and the other for institutes that may not be equipped with comprehensive testing facilities (condensed version). ResultsThe results show that in the full version, the Light Gradient Boosting Machine outperformed other classifiers, achieving area under the curve and accuracy values of 0.905 and 0.864, respectively. The Light Gradient Boosting Machine also showed excellent performance in the condensed version, achieving area under the curve and accuracy values of 0.867 and 0.803, respectively. ConclusionsWe simplified the preoperative diagnosis of KCNJ5 mutations successfully using machine learning. The proposed lightweight tool that requires only baseline characteristics and blood/urine test results can be widely applied and can aid personalized prediction during preoperative counseling for patients with uPA.

CXCR4-DIRECTED [68GA]GA-PENTIXAFOR PET/CT AS A NOVEL DIAGNOSTIC MODALITY IN PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is caused by autonomous production of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction (‘subtyping’) is crucial, PA is cured by adrenalectomy in unilateral PA and is treated by medication in bilateral PA. Subtyping is currently done by adrenal vein sampling (AVS). We propose a new diagnostic imaging modality employing the PET-tracer [68Ga] Ga-PentixaFor. This tracer reportedly has high uptake in APAs, whereas uptake is low in BAH or normal adrenals. The goal of this study is to determine concordance of [68Ga] Ga-PentixaFor PET/CT and AVS. Secondary outcomes are optimal timepoint for scanning and quantitative criteria for lateralization at the optimal timepoint. Design and method: This study is step 1 of a two-step randomized controlled diagnostic trial. We included patients with PA from Radboudumc Nijmegen and UMC Utrecht, confirmed by an intravenous salt-loading test. Patients underwent AVS and [68Ga]Ga-PentixaFor PET/CT. A dynamic scan was performed to determine optimal timepoint for scanning in the first 6 patients. The main outcome was the concordance of AVS and [68Ga]Ga-PentixaFor PET/CT. The SUVmax was used to determine lateralization in [68Ga]Ga-PentixaFor PET/CT. Results: Nineteen patients underwent adrenal vein sampling and a [68Ga]Ga-PentixaFor PET/CT. The optimal timepoint of scanning was 1h post injection. AVS showed lateralization in 13/19 patients. Using a cut-off of SUV¬max-ratio of 1.4, concordance was 68%. (figure 1) Using a Bayesian prediction model, the predicted concordance is: 67% (CI80% = 53 - 79). Figure 1: Scatter dot plot of the SUVmax Ratio in patients who had lateralization or no lateralization on AVS with a cut-off value of 1.4. Conclusions: [68Ga]Ga-PentixaFor PET/CT is a new imaging modality with high concordance with AVS. It is safe, readily available and as an out-patient procedure has the potential to improve subtyping in PA. With these preliminary results we have sufficient evidence of concordance to proceed to step 2 of the two-step trial: A pragmatic randomized controlled diagnostic trial, in which patients will be randomized in either [68Ga]Ga-PentixaFor PET/CT or AVS.

Feasibility of single-port laparoscopic partial adrenalectomy with selective adrenal venous sampling and high-resolution ultrasound for unilateral aldosterone-producing adenomas

BackgroundThe surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy for patients with aldosterone-producing adenomas are unknown. Precise diagnosis of intra-adrenal aldosterone activity and a precise surgical procedure may improve outcomes. In this study, we aimed to determine the surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy with preoperative segmental selective adrenal venous sampling and intraoperative high-resolution laparoscopic ultrasound in patients with unilateral aldosterone-producing adenomas. We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. MethodsA single-center, retrospective cohort study. All patients with unilateral aldosterone-producing adenomas diagnosed by selective adrenal venous sampling and treated surgically between January 2012 and February 2015 were included. Follow-up with biochemical and clinical assessments was set at 1 year after surgery for short-term outcomes and was performed every 3 months after surgery. ResultsWe identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. Single-port surgery was associated with shorter operative and laparoscopic times (odds ratio, 0.14; 95% confidence interval, 0.039–0.49; P = .002 and odds ratio, 0.13; 95% confidence interval, 0.032–0.57; P = .006, respectively). All single-port and multi-port partial adrenalectomy cases showed complete short-term (median 1 year) biochemical success, and 92.9% (26 of 28 patients) who underwent single-port partial adrenalectomy and 100% (13 of 13 patients) who underwent multi-port partial adrenalectomy showed complete long-term (median 5.5 years) biochemical success. No complications were observed with single-port adrenalectomy. ConclusionSingle-port partial adrenalectomy is feasible after selective adrenal venous sampling for unilateral aldosterone-producing adenomas, with shorter operative and laparoscopic times and a high rate of complete biochemical success.

Ketosis, Salt, and Water: Novel Mechanistic Insights into Diet and Mineralocorticoid Metabolism.

The association between dietary macronutrient composition and cardiovascular health has been studied extensively for decades (1, 2). High dietary sodium intake has traditionally been linked with cardiovascular disease and mortality, although recent data suggest that this association may be negligible where mean intake is less than 5 g/day. The renin-angiotensin-aldosterone system (RAAS) is a key regulator of circulating blood volume, as well as sodium and potassium homeostasis. Renin production from the renal juxtaglomerular apparatus is stimulated by reduced circulating blood volume, thereby stimulating aldosterone secretion from zona glomerulosa cells of the adrenal cortex. Primary aldosteronism, due to a unilateral aldosterone-producing adenoma (Conn's syndrome) or bilateral hyperplasia of the glomerulosa, is an important cause of secondary hypertension and has independent associations with cardiovascular disease (3). In the absence of autonomous aldosterone production, antagonism of the mineralocorticoid receptor is a key therapeutic approach in hypertension and heart disease by lowering blood pressure and improving cardiac remodeling.

An Ancillary Method for Adrenal Venous Sampling in Cases in Which Right Adrenal Vein Sampling Is Difficult

Catheterization of the right adrenal vein (rt.AdV) to obtain blood samples can often be difficult. The aim of the present study was to investigate whether blood sampling from the inferior vena cava (IVC) at its juncture with the rt.AdV can be an ancillary to sampling of blood directly from the rt.AdV. This study included 44 patients diagnosed with primary aldosteronism (PA) in whom AVS with adrenocorticotropic hormone (ACTH) was performed, resulting in a diagnosis of idiopathic hyperaldosteronism (IHA) (n = 24), and patients diagnosed with unilateral aldosterone-producing adenoma (APA) (n = 20; rt.APA = 8, lt.APA = 12). In addition to regular blood sampling, blood was also sampled from the IVC, as the substitute rt.AdV [S-rt.AdV]. Diagnostic performance with the conventional lateralized index (LI) and the modified LI using the S-rt.AdV were compared to examine the utility of the modified LI. The modified LI of the rt.APA (0.4 ± 0.4) was significantly lower than those of the IHA (1.4 ± 0.7) (p < 0.001) and the lt.APA (3.5 ± 2.0) (p < 0.001). The modified LI of the lt.APA was significantly higher than those of the IHA (p < 0.001) and rt.APA (p < 0.001). Likelihood ratios to diagnose rt.APA and lt.APA using the modified LI with threshold values of 0.3 and 3.1 were 27.0, and 18.6, respectively. The modified LI has the potential to be an ancillary method for rt.AdV sampling in cases in which rt.AdV sampling is difficult. Obtaining the modified LI is extremely simple, which might complement conventional AVS.

Bipolar Radiofrequency Ablation of the Adrenal Gland: In Vivo and Ex Vivo Experiments.

Laparoscopic adrenalectomy is currently the standard treatment modality for unilateral aldosterone-producing adenoma (APA); however, a less-invasive treatment is needed for its treatment. A new bipolar ablation system that poses a lower risk of complications has been recently developed. This study aimed to evaluate the safety and performance of a novel bipolar radiofrequency ablation (RFA) system for the treatment of APAs. Ablations were performed in an ex vivo study using bovine adrenal glands [group A: n = 6, single-probe; group B: n = 6, two probes, interprobe distance (ID) = 12 mm; group C: n = 6, two probes, ID = 20 mm]. The in vivo study was conducted in groups A and B (n = 2 each) using porcine adrenal glands. For the ex vivo study, the mean vertical diameter (Dv) of the coagulative necrosis area and the mean transverse diameter (Dt) values were 11.99 mm and 10.96 mm for group A, 12.66 mm and 10.0 mm for group B, and 23.37 mm and 22.10 mm for group C, respectively. For the in vivo study, the mean Dv and Dt values were 12.23 mm and 9.03 mm for group A, and 16.38 mm and 9.52 mm for group B, respectively. No heat-induced damage to the adjacent organs was observed. To our best knowledge, this is the first study to evaluate the performance of the bipolar system in RFA of the adrenal gland. RFA using the new bipolar ablation system is safe and produces a sufficient coagulation area to treat APAs.

11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA (NCT02945904) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = −6.5 to 24.1%) and 3.8% (95% confidence interval = −11.9 to 9.4) lay within the pre-specified −17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

PSUN61 Primary Aldosteronism Presenting as Chronic Hypokalemia in a Normotensive Patient

Abstract Introduction Conn first described the hallmark features of primary aldosteronism (PA) as a state of aldosterone excess in the setting of hypertension and hypokalemia. Recent work has shed light on a wide spectrum of disease that likely includes normotensive patients with elevated aldosterone and suppressed renin. Mineralocorticoid excess appears to be the main driver of disease progression; however, it is not known whether individual differences in intra-arterial plasticity and effective sodium potassium exchange alter the overt clinical presentation. Here, we describe a patient with chronic hypokalemia and normal blood pressure with the diagnosis of a unilateral aldosterone-producing adenoma. Clinical Case A 47-year-old woman with no significant medical history was referred to endocrinology for evaluation of isolated hypokalemia since 2012. Her potassium was 2.8mEq/L at its lowest a month prior to her visit and had numerous other values less than 3.5mEq/L over the past 10 years. She did not carry a diagnosis of hypertension nor was she hypertensive at the time of her initial and subsequent evaluations. Results on initial endocrinology evaluation demonstrated a potassium of 3.2mEq/L (3.5-5.0mEq/L), Plasma Aldosterone Concentration (PAC) of 29ng/dL (≤21ng/dL), Plasma Renin Activity (PRA) of 0.42ng/mL/h (0.25-5.82ng/mL/h), and Aldosterone Renin Ratio (ARR) of 69. PA was suspected based on hypokalemia with an ARR &amp;gt;30 and PAC &amp;gt;20ng/dL. Further work-up was pursued to confirm the diagnosis as the patient did not have hypertension. She underwent 3-day oral sodium loading. 24-hour urine collection at the conclusion revealed adequate sodium loading with a urine sodium content of 208mEq/24hr (&amp;gt;200mEq/24hr) and aldosterone secretion of 41.3mcg/24hr (&amp;lt;12mcg/24hr). She subsequently underwent a CT abdomen demonstrating a 1.3×0.8 cm right adrenal nodule. Adrenal venous sampling was performed (continuous cosyntropin infusion with simultaneous adrenal venous sampling) which revealed a cortisol-corrected aldosterone lateralization ratio (right to left) of 406 at -5 minutes, 368 at 0 minutes, 33 at 10 minutes and 85 at 15 minutes. Results were consistent with strong lateralization to the right with contralateral suppression. Diagnosis of a right-sided aldosterone-producing adenoma was confirmed and she was referred to surgery for right adrenalectomy. Conclusion This case highlights one of the many presentations of PA. The persistent hypokalemia for a decade suggests a history of longstanding untreated PA prior to eventual diagnosis, yet the patient has remained normotensive. Though normotensive PA is a recognized entity, most patients develop hypertension within 5 years. The ability to remain normotensive despite intravascular volume expansion may highlight the patient's highly compliant vasculature and kidneys that have likely adapted to excrete high sodium loads in the setting of sodium excess. This case emphasizes that isolated hypokalemia in patients without hypertension should prompt consideration of PA and that patients with PA may maintain normotension for multiple years. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS)

IntroductionPrimary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia...

Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism.

BackgroundOptimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision-making before engaging in AVS and surgery in clinical practice.MethodsWe conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression.ResultsWe developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53).ConclusionWe propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism.

Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism. Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients’ sections using immunohistochemistry technology and the relationship with clinical data was assessed. Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis. Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism.