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Determination of lateralization of aldosterone excess
Source publication
Adrenal vein sampling (AVS) is considered the gold-standard test to demonstrate unilateral aldosterone excess in primary aldosteronism, yet no single approach to interpretation of AVS has been externally validated.
There may be significant inter-observer variability in the final diagnosis of unilateral vs. bilateral aldosterone excess depending on...
Context in source publication
Context 1
... the full cohort, the AVS results were interpreted according to each published set of lateralization criteria and sensitivity and specificity calculated (Table 4). There are important assumptions regarding cases of bilateral aldosterone excess inherent in this analysis, but the true-positive and false-negative rates are not subject to any diagnostic biases, since they represent the surgically confirmed cases. ...
Similar publications
Background:
We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice.
Methods:...
To determine factors associated with lateralization in primary aldosteronism (PA). The clinical data for PA patients hospitalized at the First Affiliated Hospital of Guangxi Medical University from October 2016 to March 2021 were included in this study. They were classified according to results derived from computed tomography (CT): bilaterally nor...
Context:
Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were found to be associated with higher plasma aldosterone concentrations in the patients with an aldosterone-producing adenoma (APA).
Objective:
We investigated whether plasma aldosterone levels and the lateralization index are higher from the side with the APA with the...
Adrenal venous sampling (AVS) is the gold standard for identifying curable unilateral aldosterone excess in primary aldosteronism (PA). Studies have demonstrated the value of steroid profiling through liquid chromatography–tandem mass spectrometry (LC–MS/MS) in AVS interpretation. First, the performance of LC–MS/MS and immunoassay in assessing sele...
Objectives
To clarify the differences between two left sampling sites (left adrenal central vein [LCV] and common trunk [CMT], conjunction with LCV and inferior phrenic vein) and their impact on adrenal venous sampling (AVS) in primary aldosteronism by analyzing the results of segmental AVS (sAVS).
Methods
We retrospectively analyzed a final cohor...
Citations
... 16 Substantial heterogeneity in AVS procedural protocols and data interpretation exists even among referral centers, 17 and these differences impact the recommendation for or against surgery. 18 Data on long-term postoperative follow-up are limited and include variability in PA subtyping tests and criteria used. 19,20 Nevertheless, because AVS relies on comparative adrenal aldosterone production, with limited applicability of absolute hormonal concentrations within each adrenal vein, we hypothesized that even robust aldosterone lateralization cannot exclude bilateral PA. ...
BACKGROUND
Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy.
METHODS
We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue.
RESULTS
The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45–17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00–26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20–6.31]).
CONCLUSIONS
Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.
... Finally, the marked variety of protocols and indices leads to variable subtype classification, treatments and outcomes. In a study by Klein et al. (Kline et al. 2008), only 17% (11/63) patients would be classified the same across the all the various protocols and indices. Lethielleux et al. (Lethielleux et al. 2015) repeated a similar analysis by retrospectively analyzing data from 537 nonstimulated simultaneous AVS procedures. ...
Primary aldosteronism is the leading cause of secondary hypertension worldwide. Its deleterious effects outstrip those due to blood pressure elevation alone. An essential part of the work-up of a patient with primary aldosteronism is determining if aldosterone production is unilateral or bilateral. With the former, surgery offers a potential cure and better overall outcomes. Adrenal vein sampling is considered the most reliable method to determine whether production is unilateral or bilateral. Sampling may be non-diagnostic when the vein cannot be properly cannulated. But with proper knowledge and experience as well as the utilization of certain techniques, procedure success can be high. Multiple protocols exist; their rationale and drawbacks are reviewed here. This article will give the reader an overview of techniques for improving procedural success as well as background, rationale and evidence to guide one in choosing the appropriate procedural and interpretation protocol.
... An accurately performed and analyzed computed tomography scan can add volumes to the diagnosis of PA and eliminate the need for AVS (7). Although AVS is the gold standard for localization of the source of PA, it is highly operator dependent and associated with high failure rates, leading to a variety of difficulties in interpreting the findings (8). ...
To the editor,
We read with interest the article titled “Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades—Yet an Underdiagnosed Disorder “by Gkaniatsa et al (1) in the September 2021 issue of The Journal of Clinical Endocrinology & Metabolism, in which the investigators estimated the notified incidence of primary aldosteronism (PA) in the general population. The article highlights the cryptic and underdiagnosed problem of PA in a cohort of the Swedish population. Diagnosis and management of PA, which is the most common cause of secondary hypertension, can offer a permanent surgical or medical cure for hypertension (2).
Though oceans apart, we in India also firmly believe that the problem of PA is largely underdiagnosed and late diagnosed, and a lot needs to be done in this aspect (3).
The investigators declare that this is the first study to evaluate the incidence of PA in the general population. Though it seems attractive and promising, the feasibility and cost-effectiveness of this approach is a serious question. The Endocrine Society (ES) guidelines have clearly outlined the case detection criteria for PA (4), and adhering to these will be more clinically oriented and resource intensive. Particularly in a resource-constrained setup like India, evaluation at the population level will strain existing resources.
... There are several diagnostic criteria reported for PA confirmation and AVS interpretation. 18 We adopted the widely used diagnostic criteria from clinical guidelines 14 as follows: (1) PA confirmation: post-saline infusion plasma aldosterone concentration (PAC) >5 ng/dL, (2) successful AV cannulation during AVS with cosyntropin stimulation by selectivity index (SI), the cortisol ratio of each AV to the IVC (C AV /C IVC ) ⩾ 5, (3) PA lateralization subtyping by LI, the side-to-side ratio of ACR >4 for unilateral, <3 for bilateral, and 3-4 for indeterminate cases. LIR [= ACR of LAV (ACR LAV )/ACR of IVC (ACR IVC )] and RIR [= ACR of right AV (RAV; ACR RAV )/ACR IVC ] were used to establish new cutoffs for ipsilateral or contralateral disease. ...
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.
... AVS requires at least 3 expert parties: the radiologist who performs the technical procedure, the laboratorian who performs the biochemical assays, and the clinician who interprets the results, so theoretically, there is the potential for error at each level. Much attention has been paid to the problem of clinical adrenal vein interpretation criteria and the extent to which the final subtype diagnosis may vary, depending on which biochemical interpretation protocol is applied (12,13). Additionally, the effects of laboratory assay variation on clinical interpretation (within one interpretive regimen) has recently been reported (14). ...
Context
The reproducibility of adrenal vein sampling(AVS) is unknown.
Objective
Determine reproducibility of biochemical results and diagnostic lateralization in patients undergoing repeat AVS.
Design
Retrospective chart review of single-center, single-operator AVS procedures.
Setting
Tertiary care center.
Patients
Patients with confirmed PA undergoing repeat AVS due to concerns about technical success or discordant diagnostic results.
Intervention
Simultaneous AVS by an experienced operator using a consistent protocol of both pre-and post-cosyntropin infusion.
Main Outcome Measures
Among successfully catheterized adrenal veins(selectivity index ≥ 2) the correlation of the adrenalaldosterone/cortisol ratio between the first and second AVS. Secondary outcome measure was diagnostic agreement in repeat AVS lateralization(lateralization index ≥ 3).
Results
There were 46 sets of AVS from 23 patients, median 3 months apart. There was moderate correlation in aldosterone/cortisol ratios in adrenal veins and IVC(Spearman r = 0.49-0.59, p<0.05) pre-cosyntropin. Post-cosyntropin, the correlation was better(Spearman r=0.67-0.76, p<0.05). In technically successful AVS, there was moderate correlation between the repeated lateralization indices(Spearman r=0.53, p<0.05). In 15 patients where repeat AVS was done due to apparent lateralization discordance with CT imaging, the final diagnosis was the same in the second AVS procedure. Initial failed AVS was successful 75% of the time upon repeat attempt.
Conclusions
Repeat AVS was feasible and usually successful when an initial attempt failed. There was modest correlation between individual repeat adrenal aldosterone/cortisol ratios and lateralization indices when AVS was done twice. Final lateralization diagnosis was identical in all cases. This demonstrates that AVS is a reliable and reproducible localizing test in PA.
... According to a systemic review of 950 patients [1], if the adrenal CT finding was only regarded, unnecessary adrenalectomy would be performed in 19% and opposite adrenalectomy in 4%. Several studies reported that AVS is a reliable diagnostic tool for localization [11,[18][19][20]. Moreover, one study insisted that routine AVS should be performed because 25% of APA patients presented a negative CT finding [21]. ...
Background:
We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice.
Methods:
We retrospectively reviewed 48 patients who had resistant hypertension (HTN) or hypokalemia with a biochemical diagnosis of primary aldosteronism and who underwent AVS from January 2009 to June 2017 at a tertiary referral hospital. Selection index (SI), lateralization index (LI), and contralateral suppression index (CSI) were calculated based on AVS results and the final clinical outcomes were evaluated.
Results:
The catheterization of both adrenal veins was successful in 43 of 48 (89.6%) patients. The lateralization based only on LI was performed in 23 out of 43 (53.5%) patients. When CSI and LI were combined in decision making, the concordance between adrenal computed tomography scan and AVS for unilateral lesion improved from 59.3% (19/32) to 75.0% (24/32). CSI also correlated well with unilateral adrenal disease in the catheterization failure group. The final outcomes of HTN were better in the contralateral suppression group.
Conclusion:
CSI combined with LI could be a supplementary diagnostic tool in patients with non-lateralization or catheterization failure and predict the clinical outcomes of HTN in patients with primary aldosteronism.
... The overall success rates of AVS without CB-CT range from 30 % to 95 % [10,12,18,19]. This difference might be due to the definitions of SI and types of AVS procedures that the authors used. ...
... In our study, since patients were under unstimulated conditions and to minimize the risk of false negatives, we used a SI > 2 as recommended by consensus [20,21]. Regarding the use of CB-CT, recent studies suggest that it might promote successful cannulation and lateralization of the RAV, thereby increasing the success rate [13][14][15][16][17][18][19][20][21][22][23][24]. In two Asian studies, the success rates were 95.2 % and 95.7 % [23,24]. ...
Purpose:
The aim of this study in a group of patients with primary aldosteronism was to evaluate the contribution of CB-CT (cone beam CT) to the overall success rate of adrenal vein sampling (AVS), and in particular to the selective cannulation of the right adrenal vein (RAV).
Method:
This was a retrospective single-center study including 91 AVS procedures performed by our consultant radiologist between March 2011 and January 2017. Fifty cases were performed with CB-CT and 50 were performed without. Angiography with CB-CT was carried out after RAV cannulation to check the accurate catheter position. For each patient, we collected technical and biochemical success rates, as well as irradiation data.
Results:
The overall success rate of AVS with CB-CT was 80 %, vs. 44 % without (p = 0.00046), with right-sided selectivity of 88 % vs. 49 % (p < 0.0001). There was no significant increase in radiation exposure with CB-CT (p = 0.8206). Fluoroscopy time and quantity of iodine injected were significantly lower with CB-CT than without (p = 0.0039 and p < 0.0001).
Conclusion:
CB-CT allows a better evaluation of the selectivity of right-sided adrenal catheterization and greatly increases the overall success rate of AVS.
... All referred cases had a clinical diagnosis of PA using published criteria (12,13). These were based on an elevated aldosterone/renin ratio (ARR) in conjunction with highprobability features of PA (i.e., resistant hypertension, spontaneous or diuretic-induced hypokalemia, and/or an adrenal nodule) (14). ...
... (strictest), comparing the dominant vs nondominant sides to identify the presence of unilateral aldosterone hypersecretion. This range was selected as representative of the most commonly used thresholds among major centers (8,12,20). For patients who underwent multiple AVS procedures, only the first successful attempt was considered for the analysis. ...
Background
Subtyping of primary aldosteronism (PA) using imaging and adrenal vein sampling (AVS) may yield discordant results, causing confusion in management. Interpretation criteria for AVS lateralization may affect discordance rates.
Methods
We identified consecutive patients with PA who underwent AVS at a quaternary care centre between January 2006 and May 2018. Patient demographics, laboratory results, diagnostic imaging, and AVS results were retrieved. Adrenal cross-sectional imaging was compared with AVS findings. The presence of lateralization was defined using varying thresholds for the lateralization index (LI) from >2:1 to >5:1. Discordance was defined by a unilateral lesion on imaging with contralateral or non-lateralization on AVS.
Results
A total of 342 patients were included and 68.7% had hypokalemia. With cross-sectional imaging, 191 (55.6%) patients had unilateral lesions, 47 (13.7%) had bilateral lesions, and 104 (30.4%) had normal imaging. Overall discordance rates were high, ranging from 22% to 28% for LI thresholds of >2:1 and >5:1, respectively. Discordance between imaging and AVS was positively correlated with LI threshold stringency (P<0.001). Patients with normal or bilateral lesions on imaging frequently lateralized on AVS. Lateralization, when present, was approximately equal between left and right sides, irrespective of LI thresholds.
Conclusions
Discrepancies between imaging and AVS were common, even among patients with nonspecific imaging. Discordance was greatest with the strictest AVS interpretation criteria. Even under the most lenient thresholds, apparent discordance between imaging and AVS still exceeded 20% and may limit the ability to make surgical decisions. Reliance on imaging alone for detecting lateralization may be misleading.
... Three papers were recorded through reference list reviews, and 20 potential studies were ultimately included for full text view after reviewing the titles and abstracts. With further screening, a total of 14 studies met the inclusion criteria (4,19,20,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). A flowchart of study selection is shown in Fig. 1. ...
... In seven studies, AVS with ACTH stimulation was compared with AVS without ACTH stimulation based on unsuccessful cannulations in both left and right adrenal veins (4,20,(25)(26)(27)(28)31). In four other studies, there was a comparison between AVS with ACTH and AVS without ACTH based on unsuccessful cannulations of LAV or RAV (4,19,27,29). ...
... In all of the studies, intravenous bolus and/or infusion of 250 mg ACTH were administered (4,19,20,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). However, in one study, an intermediate dose and a very low dose of ACTH were used in some patients (50 mg/ hour and 250 pg IV, respectively) (19). ...
Context
Adrenal venous sampling (AVS) with or without adrenocorticotropic hormone (ACTH) stimulation is the test of choice to identify patients with a surgically curable subtype of primary aldosteronism (PA). Whether AVS with ACTH stimulation is more effective than AVS without ACTH stimulation remains controversial.
Objective
To compare the effectiveness of AVS with ACTH stimulation and AVS without ACTH stimulation in patients with PA.
Methods
The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All cohort studies comparing the 2 techniques (AVS with ACTH stimulation and AVS without ACTH stimulation in patient with PA) were included in the analysis.
Results
A total of 14 studies met the inclusion criteria, and they were analyzed.
AVS with ACTH stimulation did not significantly reduce the number of incorrect lateralization more than AVS without ACTH stimulation in patients with PA [OR: 0.76, 95% confidence interval (CI): 0.36, 1.59; P=0.47].
AVS with ACTH stimulation significantly reduced the number of unsuccessful cannulations of both adrenal veins more than AVS without ACTH stimulation in patients with PA (OR: 0.26, 95% CI: 0.17, 0.40; P<0.00001). For subgroup analyses, it also significantly reduced the number of unsuccessful cannulations of left adrenal vein and right adrenal vein (OR: 0.14, 95% CI: 0.06, 0.33; P<0.00001 and OR: 0.30, 95% CI: 0.12, 0.71; P=0.007, respectively).
Conclusion
AVS with ACTH stimulation can significantly reduce the number of unsuccessful cannulations, without significantly reducing the number of incorrect lateralization. Further studies are still needed to verify these findings.
... The adrenal to peripheral vein cortisol ratio is typically more than 10:1, with the continuous cosyntropin infusion protocol [8] and more than 3:1 without the use of cosyntropin [9]. The criteria for biochemically confirming a successful adrenal vein catheterization remain debatable [10]. In some series, it is defined as the cortisol ratio of adrenal to peripheral veins >2 or >3:1 [11,12], but the use of cosyntropin remains controversial [13,14]. ...
Aim:
We aimed to compare the performance of nine adrenal steroids in confirming the correct catheter position during adrenal venous sampling (AVS) without cosyntropin in patients with primary hyperaldosteronism.
Materials & methods:
A successful adrenal vein catheterization without cosyntropin was defined as the ratio of steroids from adrenal to peripheral veins being >3:1. AVS samples from four patients with primary hyperaldosteronism were analyzed.
Results:
Compared with the mean ratio of cortisol without cosyntropin, the ratios of 11-deoxycortisol (p = 0.008), dehydroepiandrosterone (p = 0.01) and androstenedione (p = 0.008) were significantly higher. None of the ratios (n = 8) of cortisol from adrenal to peripheral veins exceeded 3:1, while all ratios of 11-deoxycortisol (p < 0.001) were >3.
Conclusion:
Cosyntropin infusion during AVS may not be necessary if 11-deoxycortisol is used to confirm catheter position.
