Evaluation of right adrenal vein cannulation by trans-catheter contrast-enhanced ultrasonography: A retrospective comparative study

Detection of adrenal veins on selective retrograde CT adrenal venography in comparison with digital subtraction angiography in subjects with established diagnosis of one-sided adrenal aldosterone-producing tumor confirmed by adrenal vein sampling, histopathology and clinical course

Adrenal vein sampling (AVS) is integral to identifying surgically remediable unilateral primary aldosteronism (PA). However, right adrenal vein (AV) cannulation can be challenging, limiting its success. Intra-procedural cortisol assays can improve the reliability of AVS. The aim of this study was to validate the use of semi-quantitative cortisol estimates obtained utilizing a quick cortisol assay (QCA) during AVS procedures at our institution. Retrospective review of results of AVS procedures before and after the introduction of the QCA. Twenty-three AVS procedures were performed with the provisional success determined by intra-procedural QCA. Successful AV cannulation was defined by an AV to peripheral vein cortisol ratio ≥ 4.0 (the selectivity index) from laboratory measurements. The control cohort consisted of 23 consecutive procedures prior to introduction of the QCA. QCA correctly predicted all AV cannulation attempts. Successful bilateral AV cannulation increased from 52% to 91% of procedures when performed with the QCA (P=0.01) and adequate cannulation of the right AV increased from 61% to 91% (P=0.03). There was no increase in procedural time, number of AV cannulation or sampling attempts. Point-of-care, semi-quantitative cortisol estimates can be performed accurately during AVS with QCA, facilitating improvements in AVS success rates without increasing procedural time.

Background: Primary aldosteronism (PA) is characterized by excessive, autonomous secretion of aldosterone from one or both adrenal glands. Identification of unilateral disease and surgical resection can lead to cure, and is dependent on accurate criteria for lateralization of excess aldosterone during adrenal vein (AV) sampling (AVS). Current evidence for AVS lateralization cut-offs using plasma aldosterone concentration (PAC) measured by LC-MS/MS and post-surgical outcomes is limited. Aim: To determine optimal cut-off criteria to define lateralization of PA on AVS based on PAC measured by LC-MS/MS post-ACTH stimulation and post-surgical outcomes data. Methods: This study involved 60 subjects with PA who had PAC measured by LC-MS/MS post ACTH-stimulation during bilaterally-cannulated AVS, underwent unilateral adrenalectomy between July 2015-July 2021 and were followed up for ≥6 months. AVS lateralization parameters (lateralization index [LI; dominant PAC/cortisol(AV) ÷ non-dominant PAC/cortisol(AV)], contralateral suppression index [CSI; non-dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)], lateralization ratio [LR; dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)] and post-surgical outcome data were examined. Complete biochemical remission (CR) of PA post-surgery was defined using PASO International Consensus Criteria. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for LI, CSI and LR based on cases who achieved CR of PA post-surgery (n=55) vs those who did not (n=5). Results: Optimal cut-off LI during ACTH-stimulated AVS to identify unilateral PA cases who achieved CR post-surgery was 5.1 (AUC=0.92, P<0.001; 92.7% sensitivity, 80.0% specificity) while the optimal cut-off for CSI was 0.6 (AUC=0.887, P<0.001; 82.1% sensitivity, 100.0% specificity), and for LR was 3.3 (AUC=0.695, P=0.202; 80.0% sensitivity, 80.0% specificity). Cases with LR of 2.0-3.3 also achieved CR post-surgery if it was associated with CSI <0.6. Conclusion: LI of >5.1 provides high sensitivity and CSI <0.6 high specificity for identification of surgically curable unilateral PA during ACTH-stimulated AVS when PAC is analyzed by LC-MS/MS.

Cosyntropin [ACTH (1-24)] stimulation during adrenal vein (AV) sampling (AVS) enhances the confidence in the success of AV cannulation and circumvents intraprocedure hormonal fluctuations. Cosyntropin's effect on primary aldosteronism (PA) lateralization, however, is controversial. To define the major patterns of time-dependent lateralization, and their determinants, after cosyntropin stimulation during AVS. We retrospectively studied patients with PA who underwent AVS before, 10, and 20 minutes after cosyntropin stimulation between 2009 and 2018. Unilateral (U) or bilateral (B) PA was determined on the basis of a lateralization index (LI) value ≥4 or <4, respectively. Available adrenal tissue underwent aldosterone synthase-guided next-generation sequencing. PA lateralization was concordant between basal and cosyntropin-stimulated AVS in 169 of 222 patients (76%; U/U, n = 110; B/B, n = 59) and discordant in 53 patients (24%; U/B, n = 32; B/U, n = 21). Peripheral and dominant AV aldosterone concentrations and LI were highest in U/U patients and progressively lower across intermediate and B/B groups. LI response to cosyntropin increased in 27% of patients, decreased in 33%, and remained stable in 40%. Baseline aldosterone concentrations predicted the LI pattern across time (P < 0.001). Mutation status was defined in 61 patients. Most patients with KCNJ5 mutations had descending LI, whereas those with ATP1A1 and ATP2B3 mutations had ascending LI after cosyntropin stimulation. Patients with severe PA lateralized robustly regardless of cosyntropin use. Cosyntropin stimulation reveals intermediate PA subtypes; its impact on LI varies with baseline aldosterone concentrations and aldosterone-driver mutations.

Background and aims:Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side.Methods:Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side.Results:Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity.Conclusion:In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.

Utility of Epinephrine Levels in Determining Adrenal Vein Cannulation During Adrenal Venous Sampling for Primary Aldosteronism

Intraprocedural Cortisol Measurement Increases Adrenal Vein Cannulation Success Rate in Primary Aldosteronism: A Systematic Review and Meta-analysis.

Disclosure: N. Yagishita: None. M. Kometani: None. K. Aiga: None. R. Mizoguchi: None. T. Yoneda: None. Context: Adrenal vein sampling (AVS) is recognized as the gold standard method to distinguish subtypes of primary aldosteronism (PA), helps differentiating the pathogenic side and determining the appropriate treatment strategies. The Selectively Index (SI) and Lateralization Index (LI), which are based on aldosterone and cortisol levels, are used to determine the success rate of AVS and to diagnose PA subtypes. On the other hand, determining the success of adrenal vein insertion and disease type remains controversial, and various methods to improve its accuracy are still being reported. Objective: Evaluate the impact of performing multiple blood samplings from the inferior vena cava (IVC) and each adrenal vein (AV) during a single AVS session and its impact on the success rate of said AVS and the consequent accuracy of PA subtype diagnosis. Patients: A total of 48 patients who were diagnosed as PA and underwent multiple AVS procedures at Kanazawa University Hospital or Houju Memorial Hospital. Protocol: This study involved 48 patients diagnosed with PA. AVS was performed using the following procedure. A catheter is inserted into the IVC through the right or left femoral vein. A sample is first taken from the IVC (IVC-1). AVS was then performed in the order of right adrenal vein and left adrenal vein or vice versa. After cannulation of each adrenal vein, samples were taken three times before switching to the other adrenal vein. After the collection of each adrenal vein was completed, samples were taken again from the IVC (IVC-2). Results: Of the 48 patients, 44 patients were included in the study, for whom all sets of AVS samples were available. For each patient, six SI's were calculated per AV. Multiple AV samples did not affect the success rate of AVS. Regardless of the cortisol level in the AV, the SI calculated using the cortisol level in IVC -2 was significantly higher in most patients (P &amp;lt; 0.0001). Only patients in whom AVS was successful in all cases were selected to determine lateralization. Since nine different LI’s could be calculated, there were nine chances to determine subtypes for each patient. 18 patients in IVC-1 (left: 2, right: 4, bilateral: 12), 17 patients in IVC-2 (left: 3, right 2, bilateral: 12) all exhibited consistencies in lateralization. Except four patients which in both cases exhibited inconsistencies in lateralization. Conclusions: These results revealed that multiple blood samplings resulted in lateralization discrepancies that could not be determined with a single blood sampling. Although it was not possible to confirm that multiple blood samplings influence the success rate of AVS, it was newly confirmed that the timing of blood sampling from IVC impacts it. Presentation: 6/1/2024

Context: Adrenal vein sampling (AVS) is the standard method for subtype diagnosis in primary aldosteronism (PA), while success rate of its procedures, especially in right adrenal vein (AV), has limited. However, unilateral subtype of PA can be completely cured by surgical treatment and hence diagnostic approach for PA should be established especially when patients with apparent adrenal disease on computed tomography (CT) lack complete AVS result. In recent years, segmental AVS demonstrates that apparent aldosterone gradient in each adrenal vein branch is specific finding in aldosterone producing adenoma. Since we have reported that plasma aldosterone concentrations different in the proximal and distal regions of the left AV in some of the patients with PA, we hypothesized that solo finding of adrenal aldosterone gradient in the left AV (left AV gradient) should be the clue for unilateral subtype of PA.Objective: The aim was to investigate whether left AV gradient indicate the left unilateral subtype of PA.Design and Setting This study was a part of the Kyushu Adrenal Network Database for Advanced medicine (Q-AND-A) study, a cross-sectional and retrospective study in a single referral center.Participants and AVS procedure: Of 194 PA patients who underwent AVS with cosyntropin stimulation between January 2007 and April 2019, 111 patients had available and successful AVS data. Blood samples in left adrenal veins were obtained from following two positions; the common trunk and the central adrenal vein. We calculated left AV gradient by the ratio of aldosterone-to-cortisol ratio on the higher position in left AV to that on the lower position. We determined the presence of left AV gradient if it was greater than four.Main outcome measures: Prevalence of unilateral subtype in patients with left AV gradient who had unilateral disease on CT.Results: Of 111 patients with complete AVS data, 43 who had left unilateral disease on CT were analyzed in present study. Twenty-nine patients were diagnosed as left unilateral subtype on AVS and 14 were bilateral subtype. Aldosterone gradient was observed only in patients with unilateral subtype (41% [12/29]), not in patients with bilateral subtype (0% [0/14]). Of 29 patients with unilateral subtype on AVS, clinical parameters, including plasma aldosterone concentrations, plasma renin activity, and serum potassium levels, were not different in those with and without left AV gradient. The receiver operative curve analysis for the diagnosis of unilateral subtype on AVS showed that the optimal cutoff value of left AV gradient was 3.3 with a sensitivity of 45% and specificity of 100%.Conclusion: The presence of left AV gradient is the reliable finding for the diagnosis of left unilateral subtype in patients with PA who have unilateral disease on CT. However, further study in a larger number of cases is required to validate this finding.

Disclosure: S. Mohan: None. O.A. Shariq: None. J.C. Andrews: None. W.F. Young: None. Background: Adrenal vein sampling (AVS) is performed in patients with primary aldosteronism (PA) to subtype surgically curable unilateral disease. During AVS, iodinated contrast is used to confirm catheterization of adrenal veins for accurate sampling. However, in patients with severe contrast allergy, the optimal method of safely and effectively confirming localization is debatable. Premedication with oral corticosteroids has raised concern for suppression of cortisol and confounding of AVS results. We therefore investigated our experience of AVS after corticosteroid premedication in patients with PA and iodine contrast allergy. Methods: Patients with PA who underwent AVS at our center under continuous cosyntropin infusion (50 mcg/hr started 30 minutes before sampling) between September 1990 - October 2023 were identified. Individuals with documented allergy to iodinated contrast who received corticosteroid premedication were matched 1:1 for age and sex with control patients without contrast allergy or premedication. Baseline demographics, biochemical variables, AVS results, and follow-up data were compared between groups. Results: 1273 AVS studies were performed in 1255 patients with PA and 35 (2.8%) patients received corticosteroid premedication for contrast allergy. Methylprednisolone was used in 32 (91.4%) patients while dexamethasone was used in the rest. No patients experienced a severe breakthrough allergic reaction. Mean age was similar in cases vs. controls (53.9 vs. 54.1 years, P=0.92) with 16 females (45.7%) per group. There were no significant differences in baseline aldosterone-to-renin ratios (57.7 vs. 49.3, P=0.57) or daily defined doses of antihypertensives (5.5 vs. 4.4, P=0.21) between the two groups. Absolute cortisol levels (mcg/dL) from both adrenal veins (AV) and the inferior vena cava (IVC) were similar between cases and controls (right AV: 752.5 vs. 813.7, P=0.48; left AV: 527.2 vs. 462.7, P=0.33; IVC: 23.1 vs. 24.5, P=0.18). The ratio of cortisol in the corresponding AV to the IVC (selectivity index) was &amp;gt;5 in all patients, confirming appropriate cannulation, with similar mean selectivity indices between groups (right AV: 33.0 vs. 33.7, P=0.86; left AV: 22.8 vs. 19.0 P=0.17). Unilateral disease (indicated by a lateralization index &amp;gt;4) was present in 20 (57.1%) patients who received premedication compared with 16 (45.7%) controls (P=0.34). Surgery for unilateral disease was performed in 16 cases and 12 controls, with similar post-op day 1 aldosterone levels in both groups (3.8 vs. 3.3, P=0.36), consistent with surgical cure. Conclusion: In patients with PA and iodine contrast allergy, premedication with corticosteroids prior to cosyntropin-stimulated AVS does not significantly suppress cortisol levels or affect interpretation of AVS results, with comparable rates of disease subtyping and surgical outcomes when compared to a control group. Presentation: 6/3/2024

Disclosure: A. Boisvert: None. J. Coll: None. N. Gagnon: None. A. Lamarre: None. Background: Adrenal vein sampling (AVS) is the gold-standard test to assess for lateralization in primary aldosteronism (PA). In case of unsuccessful right adrenal vein (RAV) cannulation, our tertiary care centre (CHU de Québec-UL) uses a multinomial regression model to extrapolate the RAV cannulation results. Objectives: 1) To determine the proportion of successful RAV cannulation during AVS at the CHU de Québec-UL; 2) To evaluate the management and clinical evolution of patients with PA who underwent AVS at the CHU de Québec-UL, including those who were treated based on the multinomial regression model results. Methods: This retrospective cohort study included patients aged ≥18 years with a diagnosis of PA who underwent AVS between January 2017 and September 2022 at the CHU de Québec-UL. Epidemiological data at diagnosis were collected, as well as data on AVS cannulation, AVS complications and PA clinical evolution. Successful RAV cannulation was determined by the interventional radiologist and by cortisol ratios. Results are presented as percentage or mean±SD. Results: 39 patients were included (33,3% women; mean age 51,1±11,5 years; 89,7% with hypertension treated with a mean of 2,5±1,1 antihypertensive drugs; 74,4% with hypokalemia), for a total of 40 AVS procedures. 3 procedures (7,5%) selectively cannulated both adrenal veins. 3 procedures (7,5%) led to complications (subcutaneous hematoma). Of the 33 incomplete AVS procedures, the clinical management after 6 of these procedures was unavailable due to follow-up in other hospital centres. Among the remaining 27 patients, 5 (18,5%) had a second complete AVS in another tertiary care center, 12 (44,4%) were medically treated, 1 (3,7%) had an adrenalectomy and 11 (40,7%) were treated according to the multinomial regression model results. The model lateralized aldosterone secretion in 5 patients, who then all had adrenalectomy, after which 4 were diagnosed adrenal adenomas and one was diagnosed adrenal hyperplasia on pathology. The 8 complete AVS procedures led to 6 diagnoses of unilateral disease and 2 diagnoses of bilateral disease. Applying the multinominal regression model to the initial AVS procedure of these 8 cases would have correctly predict aldosterone lateralization in 7 cases (87,5%). Conclusion: AVS success rate in our tertiary care centre was low. The multinominal regression model appeared to adequately detect unilateral disease in our small sample. It is necessary to reevaluate our AVS technical protocol to increase our AVS successful cannulation rate. Presentation: 6/1/2024

The aim of this study is to determine the accuracy of adrenal vein sampling (AVS) with and without adrenocorticotropic hormone (ACTH) stimulation to distinguish between unilateral and bilateral primary hyperaldosteronism (PA). Retrospective analysis of a prospective database from a referral center between 1984 and 2009, 76 patients had simultaneous cannulation of bilateral adrenal veins and AVS with and without ACTH stimulation. All patients had adrenalectomies. The selectivity index (SI, cut-off value ≥2) was used for confirmation of successful cannulation of the adrenal vein. The lateralization index (LI, cut-off value >2 and >4) was used for distinguishing between unilateral and bilateral PA. The SI ratio was higher with ACTH stimulation compared to without for the right adrenal vein (p = 0.027). The LI > 2 ratio was higher with ACTH stimulation compared to without (p = 0.007). For the LI > 4 ratio, there was no difference between with and without ACTH stimulation (p = 0.239). However, for a LI > 4, 7 patients (9.2%) were not lateralized with ACTH stimulation, but they did lateralize without ACTH stimulation. AVS with ACTH stimulation is associated with a higher SI ratio compared to AVS without ACTH stimulation. However, when using LI > 4 for AVS, samples without ACTH stimulation should also be included to detect a subset of patients with unilateral disease that are not detected with ACTH stimulation.

Adrenal vein sampling (AVS) is required to distinguish unilateral from bilateral aldosterone sources in primary aldosteronism (PA), and cortisol is used for AVS data interpretation, but cortisol has several pitfalls. In this study, we present the utility of several other steroids in PA subtyping, both during AVS, as well as in peripheral serum. We included patients with PA who underwent AVS at University of Michigan between 2012 and 2018. We used mass spectrometry to simultaneously quantify 17 steroids in adrenal veins (AV) and periphery, both at baseline and after cosyntropin administration. PA was classified as unilateral or bilateral based on a lateralization index ≥ or <4, respectively, separately for baseline and post-cosyntropin administration. Of 131 participants, AV catheterizations was deemed failed in 28 (21 %) patients (36 AVs) at baseline. Eight steroids demonstrated higher AV/periphery ratios than cortisol (P<0.01 for all); 11β-hydroxyandrostenedione, 11-deoxycortisol, and corticosterone rescued most failed baseline catheterizations. Lateralization was generally consistent when using these alternative steroids. Based on pre- and post-cosyntropin data, the remaining 103 patients were classified as: U/U, 37; B/B, 32; U/B, 20; B/U, 14. Discriminant analysis of multi-steroid panels from peripheral serum showed distinct profiles across the 4 groups, with highest aldosterone, 18-oxocortisol and 11-deoxycorticosterone in U/U patients. In conclusion, 11β-hydroxyandrostenedione and 11-deoxycortisol are superior to cortisol for AVS data interpretation. Single assay multi-steroid panels measured in peripheral serum are helpful in stratified PA subtyping and have the potential to circumvent AVS in a subset of patients with PA.

Disclosure: J.K. Waraich: None. G. Kline: None. M.Y. Choi: None. R.J. Sigal: None. C. Caughlin: None. S.J. Przybojewski: None. A. Leung: None. Background: Primary aldosteronism (PA) is a condition characterized by excessive aldosterone secretion, and accounts for at least 10% - 20% of all cases of hypertension. Determination of PA subtype (i.e., unilateral vs. bilateral aldosterone hypersecretion) is clinically important to inform targeted treatment. We hypothesized that pathogenesis of PA is immune-mediated and autoantibodies to angiotensin receptor type 1 (AT1) may determine PA subtype. Aims: The aim of this study was to examine whether AT1 autoantibodies predict PA subtype. Methods: We conducted a cross-sectional study of patients with PA who were referred for adrenal vein sampling (AVS) for subtyping. AT1 autoantibody titres were measured using an enzyme-linked immunosorbent assay. AT1 antibodies were defined as present when the titre was &amp;gt;17 U/mL, negative if &amp;lt;10 U/mL, and indeterminate if between 10-17 U/mL. AVS was used as a gold standard to determine lateralization and PA . The frequency of positive AT1 autoantibodies was determined according to PA subtype and clinical predictors of lateralization. Baseline patient characteristics were reported as means (and standard deviations) for normally distributed variables, and medians (and interquartile ranges) for non-normally distributed variables. Fisher’s exact test was performed for categorical variables and Kruskal-Wallis test for continuous variables. Results: 54 patients had successful cannulation of both adrenal veins (mean age, 52.7 years; 46.3% male; mean body mass index, 31.2 kg/m2). AT1 antibodies were detected in 14 (25.9%) of the patients, absent in 32 (59.3%), and indeterminate in 8 (14.8%). Among the 25 patients with unilateral PA, 8 (32.0%) had positive AT1 antibodies, 15 (60.0%) negative, and 2 (8.0%) indeterminate. Similarly, among the 29 patients with bilateral PA, 6 (20.7%) had positive AT1 antibodies, 17 (58.6%) negative, and 6 (20.7%) indeterminate. There was no significant association detected between AT1 antibody status and lateralization (p=0.39). There were no associations between AT1 autoantibody status and any of the clinical factors traditionally predictive of PA, including sex (p=0.94), older age (p=0.76), hypokalemia (p=0.91), higher estimated glomerular filtration rate (p=0.46), or magnitude of aldosterone-to-renin ratio elevation (p=0.58). There was also no association between AT1 titres and these factors. Conclusion: AT1 autoantibodies are common in patients with PA; over a quarter of patients who underwent AVS in our study. Although they were not predictive of PA subtype, these results may still suggest that PA is immune-mediated. Future studies comparing AT1 autoantibodies in PA to other controls are underway. Presentation: 6/1/2024

BackgroundAdrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling.MethodsA total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=124). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5.ResultsWith C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (P<0.001), with substantial decreases in failure rates (43.7% to 0.8%, P<0.001). There were significant increases in adequate sampling rates from right (43.7% to 91.9%, P<0.001) and left adrenal veins (53.1% to 95.9%, P<0.001) as well as decreases in catheterization failure from right adrenal vein (9.3% to 0.0%, P<0.001). Net improvement of SI on right side remained significant after adjustment for left side (adjusted SI, 1.1 to 9.0; P=0.038). C-AVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; P<0.001).ConclusionC-AVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein.