Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling

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.

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Comparison of Cortisol, Androstenedione and Metanephrines to Assess Selectivity and Lateralization of Adrenal Vein Sampling in Primary Aldosteronism

Journal of Clinical Medicine ◽

10.3390/jcm10204755 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4755

Author(s):

Giulio Ceolotto ◽

Giorgia Antonelli ◽

Brasilina Caroccia ◽

Michele Battistel ◽

Giulio Barbiero ◽

...

Keyword(s):

Decision Making ◽

Primary Aldosteronism ◽

Inferior Vena ◽

Clinical Decision Making ◽

Vena Cava ◽

Clinical Decision ◽

Selectivity Index ◽

Adrenal Vein ◽

Adrenal Vein Sampling ◽

The Right

Success of adrenal vein sampling (AVS) is verified by the selectivity index (SI), i.e., by a step-up of cortisol levels between the adrenal vein and the infrarenal inferior vena cava samples, beyond a given cut-off. We tested the hypothesis that androstenedione, metanephrine, and normetanephrine, which have higher gradients than cortisol, could increase the rate of AVS studies judged to be bilaterally successful and usable for the clinical decision making. We prospectively compared within-patient, head-to-head, the selectivity index of androstenedione (SIA), metanephrine (SIM), and normetanephrine (SINM), and cortisol (SIC) in consecutive hypertensive patients with primary aldosteronism submitted to AVS. Main outcome measures were rate of bilateral success, SI values, and identification of unilateral PA. We recruited 136 patients (55 + 10 years, 35% women). Compared to the SIC, the SIA values were 3.5-fold higher bilaterally, and the SIM values were 7-fold and 4.4-fold higher on the right and the left side, respectively. With the SIA and the SIM the rate of bilaterally successful AVS increased by 14% and 15%, respectively without impairing the identification of unilateral PA. We concluded that androstenedione and metanephrine outperformed cortisol for ascertaining AVS success, thus increasing the AVS studies useable for the clinical decision making.

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Rapid Cortisol Assay during Adrenal Vein Sampling in Patients with Primary Aldosteronism

Clinical Chemistry ◽

10.1373/clinchem.2007.092080 ◽

2007 ◽

Vol 53 (11) ◽

pp. 1968-1971 ◽

Cited By ~ 65

Author(s):

Giulio Mengozzi ◽

Denis Rossato ◽

Chiara Bertello ◽

Corrado Garrone ◽

Alberto Milan ◽

...

Keyword(s):

Primary Aldosteronism ◽

Vena Cava ◽

Cost Effective ◽

Secondary Hypertension ◽

Sampling Procedure ◽

Standard Test ◽

Adrenal Vein ◽

Adrenal Vein Sampling ◽

Bilateral Adrenal Hyperplasia ◽

Service Oriented

Abstract Background: Adrenal vein sampling is considered the gold standard test to identify primary aldosteronism, the most frequent form of secondary hypertension. Technical difficulties with this procedure may be overcome by monitoring cortisol concentrations in the different sampling sites during catheterization. Methods: We applied a rapid automated cortisol assay performed on a benchtop immunoassay analyzer near the operating suite during the catheterization procedures in 5 hypertensive patients. A mean of 7.8 samples (range, 5–13) were collected from the vena cava as well as from right and left adrenal veins. Results: Cortisol concentrations measured by the rapid assay and by our routine method were comparable. Two of 5 patients were found to be affected by an aldosterone-producing adenoma and 3 of 5 by a bilateral adrenal hyperplasia. Cortisol determination during the adrenal vein sampling procedure allowed a successful cannulation in all patients, including a patient in whom it was necessary to cannulate 9 different candidate right adrenal veins before finding the correct one. Conclusions: Intraoperative cortisol assays appeared safe, reproducible, simple to perform, rapid, and cost-effective. The approach represents a service-oriented model for the laboratory and can provide valuable and timely information for improving the success rate of adrenal vein catheterization.

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Laterality Diagnosis of Adrenal Vein Sampling for Primary Aldosteronism Using Aldosterone Alone

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.592 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A291-A291

Author(s):

Norio Wada ◽

Shuhei Baba ◽

Hajime Sugawara ◽

Arina Miyoshi ◽

Shinji Obara ◽

...

Keyword(s):

Primary Aldosteronism ◽

Roc Analysis ◽

Vena Cava ◽

Area Under The Curve ◽

Adrenal Vein ◽

Acth Stimulation ◽

Adrenal Vein Sampling ◽

Left And Right ◽

Lateralization Index

Abstract Background: In adrenal vein sampling (AVS) for primary aldosteronism (PA), cortisol concentration is used to determine successful AVS, and laterality diagnosis is performed using a combination of aldosterone and cortisol concentrations. In this study, we examined the comparison with the conventional method when AVS was determined by aldosterone alone. Subjects and methods: We studied the data from 277 patients with PA who underwent AVS in Sapporo City General Hospital from July 2007 to April 2020. The patients with autonomous cortisol production were excluded. Using the blood samples from adrenal veins and inferior vena cava (IVC) after ACTH stimulation, the predicting ability of the left and right ratio of aldosterone concentration (aldosterone ratio, AR) for lateralization Index (LI) was examined by Receiver operating characteristic (ROC) analysis. The predicting abilities of the ratio of aldosterone concentration between adrenal vein and IVC (aldosterone index, AI) and aldosterone concentration for selectivity index (SI) and contralateral ratio (CR) were also examined by ROC analysis. Results: Six samples (0.01%) with SI <5 after ACTH stimulation those were determined unsuccessful AVS. The results of the area under the curve (AUC) in ROC analysis of aldosterone concentration and AI for prediction of SI>5 was 0.998, 0.990, respectively, p=0.39. The optimal cut-off values of aldosterone concentration and AI for prediction successful AVS were 1700 pg/ml (sensitivity 99.5%, specificity 100%), 7.44 (sensitivity 94.0%, specificity 100%), respectively. Seventy-two patients (27.3%) had LI >4 who were diagnosed as unilateral aldosterone excess. AR had 0.94 of AUC for prediction of LR >4. The optimal cut-off value of AR was 3.53 (sensitivity 86.1%, specificity 94.8%). Eighty-two patients (31.1%) had unilateral CR<1. The AUC of aldosterone concentration and AI for prediction of CR<1 was 0.96, 0.98, respectively, p=0.07. The optimal cut-off values of aldosterone concentration and AI were 13600 pg/ml, 42, respectively. The sensitivity and the specificity at the optimal cut-off points of aldosterone concentration and AI were 91.5%, 91.5% and 91.5%, 94.8%, respectively. Conclusions: The determination of successful AVS and unilateral result in AVS can be predicted using aldosterone alone. It was suggested that AR is useful for tentative interpretation in the cases where the results of aldosterone were previously reported and lateralizing diagnosis of the cases with autonomous cortisol production.

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Adrenal vein sampling for primary aldosteronism: a 15-year national referral center experience

Radiology and Oncology ◽

10.2478/raon-2020-0052 ◽

2020 ◽

Vol 54 (4) ◽

pp. 409-418

Author(s):

Tomaz Kocjan ◽

Mojca Jensterle ◽

Gaj Vidmar ◽

Rok Vrckovnik ◽

Pavel Berden ◽

...

Keyword(s):

Primary Aldosteronism ◽

Initial Period ◽

Treatment Options ◽

Vena Cava ◽

Cross Sectional Study ◽

Adrenal Vein ◽

Adrenal Vein Sampling ◽

Cross Sectional ◽

Referral Center ◽

Unilateral Disease

Abstract Background Adrenal vein sampling (AVS) is essential for diagnostics of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. We reviewed the performance of AVS for primary aldosteronism at our center during first 15 years, comparing the initial period to the period after the introduction of a dedicated radiologist. Additionally, AVS outcomes were checked against CT findings and the proportion of operated patients with proven unilateral disease was estimated. Patients and methods A retrospective cross-sectional study conducted at the national endocrine referral center included all patients with primary aldosteronism who underwent AVS after its introduction in 2004 until the end of 2018. AVS was performed sequentially during Synacthen infusion. When the ratio of cortisol concentrations from adrenal vein and inferior vena cava was at least 5, AVS was considered successful. Results Data from 235 patients were examined (168 men; age 32–73, median 56 years; BMI 18–48, median 30.4 kg/ m2). Average number of annual AVS procedures increased from 7 in the 2004–2011 period to 29 in the 2012–2018 period (p < 0.001). AVS had to be repeated in 10% of procedures; it was successful in 77% of procedures and 86% of patients. The proportion of patients with successful AVS (92% in 2012–2018 vs. 66% in 2004–2011, p < 0.001) and of successful AVS procedures (82% vs. 61%, p < 0.001) was statistically significantly higher in the recent period. Conclusions Number of AVS procedures and success rate at our center increased over time. Introduction of a dedicated radiologist and technical advance expanded and improved the AVS practice.

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Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

Acta Endocrinologica ◽

10.1530/eje-11-0246 ◽

2011 ◽

Vol 165 (1) ◽

pp. 85-90 ◽

Cited By ~ 4

Author(s):

Teresa M Seccia ◽

Diego Miotto ◽

Renzo De Toni ◽

Valentina Gallina ◽

Matteo Vincenzi ◽

...

Keyword(s):

Primary Aldosteronism ◽

Chromogranin A ◽

Inferior Vena ◽

D2 Receptor ◽

Vena Cava ◽

Adrenal Vein ◽

Aldosterone Secretion ◽

Adrenal Vein Sampling ◽

Plasma Cortisol Concentration ◽

Design And Methods

BackgroundAdrenal vein sampling (AVS) is the gold standard for identifying the surgically curable forms of primary aldosteronism. Dopamine modulates adrenocortical steroidogenesis and tonically inhibits aldosterone secretion via D2 receptor. However, whether it could also affect the release of cortisol and chromogranin A (ChA), which can be used to assess the selectivity of AVS, is unknown.ObjectiveTo investigate whether metoclopramide increased the release of cortisol and ChA and could thereby improve assessment of the selectivity at AVS.Design and methodsWe investigated the effect of acute D2 antagonism with metoclopramide on cortisol and ChA release from the adrenal gland by comparing the adrenal vein and infrarenal inferior vena cava (IVC) hormone levels at baseline and after metoclopramide administration in 34 consecutive patients undergoing AVS.ResultsMetoclopramide increased plasma aldosterone in the IVC (P<0.00001) and in the adrenal vein blood (P<0.002) but failed to increase plasma cortisol concentration or ChA levels. Therefore, it did not increase the selectivity index based on the measurement of either hormone.ConclusionsThis study shows that the release of cortisol and ChA is not subjected to tonic D2 dopaminergic inhibition. Therefore, these findings lend no evidence for the usefulness of acute metoclopramide administration for enhancing the assessment of the selectivity of blood sampling during AVS with the use of either cortisol or ChA assay.

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The Impact of ACTH on Peripheral Steroids Differs between Unilateral and Bilateral Primary Aldosteronism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.645 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A316-A316

Author(s):

Yuta Tezuka ◽

Kae Ishii ◽

Lili Zhao ◽

Yuto Yamazaki ◽

Ryo Morimoto ◽

...

Keyword(s):

Logistic Regression ◽

Primary Aldosteronism ◽

Repeated Measures ◽

Dynamic Testing ◽

Roc Curves ◽

Adrenal Vein ◽

Rank Test ◽

Adrenal Vein Sampling ◽

Non Invasive ◽

The Impact

Abstract Background: ACTH is thought to contribute to aldosterone excess in primary aldosteronism (PA), possibly via aberrant melanocortin type 2 receptor (MC2R) expression in aldosterone producing adenomas (APAs). Dynamic manipulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a non-invasive tool for distinguishing unilateral PA (UPA) from bilateral PA (BPA), but existing data are minimal. Objective: To characterize the steroid responses to intrinsic ACTH variations and extrinsic HPA manipulation in UPA and BPA. Methods: We conducted comprehensive dynamic testing in PA patients, who were subtyped based on adrenal vein sampling. Peripheral plasma samples were collected from each patient at 6 time-points: morning; midnight; after 1 mg dexamethasone suppression (DST); and after cosyntropin stimulation (at 15’, 30’, and 60’). We quantified 15 steroids by mass spectrometry in each sample. Next generation sequencing was used to detect aldosterone-driver somatic mutations in APAs from 39 cases with available tissue. The Mann-Whitney test, Wilcoxon signed rank test, and repeated measures two-way ANOVA were employed, as appropriate. Penalized logistic regression was used to select steroids that best distinguished UPA from BPA. Receiver operating characteristic (ROC) curves were then plotted using the predicted score from the logistic regression model with the selected steroids, and area under the curves (AUC) were computed. Results: We included 80 PA patients, median age 51 (range, 26–76), 50% men, 40 with each subtype, both groups with similar age and sex distribution. Morning and midnight concentrations of 18-hydroxycortisol (18OHF), 18-oxocortisol (18oxoF), aldosterone, and 18-hydroxycorticosterone (18OHB) were higher in patients with UPA vs. BPA (p<0.001 for all). In response to cosyntropin stimulation, the UPA group had larger increments of aldosterone, 18oxoF, 11-deoxycorticosterone, corticosterone, and 11-deoxycortisol than the BPA group (p<0.05 for all). Following DST, aldosterone,18OHF, and 18oxoF were higher in UPA than in BPA patients (p<0.01 for all). Overall, cortisol and cortisone serum concentrations were similar between the two subtypes. Of the UPA cases, 27 (69%) had KCNJ5 mutations. Relative to UPA patients with other mutations, the KCNJ5 group had higher 18oxoF and 18OHF at baseline; higher 18oxoF and corticosterone after both dynamic tests; and lower aldosterone after DST. The highest AUC for PA subtyping was achieved using cosyntropin stimulated steroids (0.957), while baseline data reached an AUC of 0.909. Conclusions: Steroid responses to dynamic HPA testing differs between UPA and BPA: 18oxoF and 18OHF are less suppressible, while several steroids are disproportionally amplified by ACTH in patients with UPA vs. BPA. Such non-invasive tests could circumvent the need for adrenal vein sampling in a subset of PA patients.

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