scholarly journals SAT-556 Use of ACTH-Stimulated Lateralization Indices Underestimates Surgically Curable Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nicholas Yozamp ◽  
Barry Sacks ◽  
Jonathan Underhill ◽  
Tali Fudim ◽  
Anand Vaidya
Keyword(s):  
Primary Aldosteronism ◽  
Vena Cava ◽  
Adrenal Vein ◽  
Imaging Data ◽  
Acth Stimulation ◽  
Cross Sectional ◽  
Bilateral Disease ◽  
Discordance Rate ◽  
Repeated Sampling ◽  
Separate Cohort

Abstract Introduction: Adrenal venous sampling (AVS) is recommended to assess laterality in primary aldosteronism to determine whether a patient has unilateral, or surgically curable, disease. Institutional practices differ in whether ACTH stimulation is used or not and if so, whether values are obtained after a single injection of ACTH or during an ACTH infusion. Studies have demonstrated appreciable discordance between lateralization based on unstimulated versus stimulated AVS. Objective: To assess the influence of ACTH-stimulation on lateralization indices. Methods: We performed a retrospective cross-sectional analysis of 140 patients who underwent AVS between 2012–2019. We then validated these findings in a separate cohort of 233 patients who underwent AVS between 2008–2016. AVS was performed using simultaneous, unstimulated, and triplicate sampling from the inferior vena cava (IVC) and bilateral adrenal veins, followed by repeated sampling in duplicate or triplicate from each site following a bolus of 250 ug of ACTH (cosyntropin). The lateralization index (LI) was defined as the quotient of the aldosterone-to-cortisol ratios from each adrenal vein, and the categorical definition of lateralization was defined as a LI ≥ 2 (unstimulated) and LI ≥ 4 post-ACTH. Results: The median unstimulated LI was 8.7 compared to 8.9 post-ACTH. Seventy-one of 140 patients (51%) had a decrease in LI following the ACTH bolus. Overall lateralization discordance was 21.4%, with the majority of this discordance (90%) attributed to situations where there was an unstimulated LI ≥ 2 that became a post-ACTH LI < 4, thereby transforming a unilateral interpretation into one of bilateral disease. Comparing the group that had an increase in LI after ACTH to the group that had a decrease in LI, the latter had significantly higher rates of lateralization pre-ACTH (89% vs 74%, p=0.02) and significantly lower rates of lateralization post-ACTH (50% vs 78%, p=0.001). All of these general findings were validated in the separate cohort of 233 patients. The discordance rate between pre-ACTH lateralization and available imaging data was 32%; the same discordance rate was found when comparing post-ACTH lateralization to imaging. Conclusions: The administration of ACTH during AVS causes an increase in LI in half of patients and a decrease in LI in the other half. Using conventional cut-offs, pre-ACTH and post-ACTH lateralization indices disagree on laterality more than 20% of the time and almost always involve pre-ACTH unilateral disease that is classified as bilateral disease post-ACTH. These findings underscore that while ACTH stimulation may be useful for confirming adrenal vein selectivity, the decrease in post-ACTH LI may result in misclassification of surgically curable primary aldosteronism in a substantial proportion of patients.

Abstract 861: Comparison of Three Different Doses of ACTH Stimulation During AVS For Primary Aldosteronism

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
GianPaolo Rossi ◽  
Teresa M Seccia ◽  
Diego Miotto ◽  
Franco Mantero ◽  
Gisella Pitter ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Vena Cava ◽  
Adrenal Vein ◽  
High Dose ◽  
Correct Identification ◽  
Acth Stimulation ◽  
Four Corners ◽  
Wrong Identification ◽  
The Right ◽  
Different Doses

Background. ACTH stimulation was proposed to overcome the potential biases associated with pulsatile aldosterone secretion during AVS. Different protocols and doses of synthetic ACTH have been used but no systematic comparison between them was available. Aim. To compare the effects of 3 different doses of ACTH on the selectivity (SI) and the lateralization index (LI). Patients and Methods. We prospectively tested the effect of a high dose (HD; 250 μg as an i.v. bolus, n=41), a very low dose (VLD, 250 pg as an i.v. bolus followed by 0.5 pg/min infusion, n=6) and an intermediate dose (ID 50 μg/hr; n=7) on the SI and LI in patient referred for primary aldosteronism. Blood sampling for the measurement of plasma aldosterone (PAC) and cortisol (PCC) concentration were obtained at baseline and 30 minutes after ACTH stimulation, using bilaterally simultaneous AVS. The SI was calculated as the ratio between cortisol levels in the right (C RAV ) or left (C LAV ) adrenal vein and the infrarenal inferior vena cava (C IVC ); the LI was assessed as the ratio of aldosterone to cortisol on the side with the higher ratio (A/C SIDE ) over the contralateral aldosterone to cortisol (A/C CTRL ). The diagnosis of APA was based on pathology and follow-up data. Results. The HD induced a highly significant increase of PCC in IVC (+83%, P<0.003) and on the SI on both sides (SI RIGHT +120%; SI LEFT +122%, P<0.001), as compared to baseline values. By contrast, no significant change of PCC in IVC and of the SI was seen with the VLD. The ID elicited a significant increase of PCC in the infrarenal IVC (+82%, P<0.001), which was not significantly different from that seen with the HD. Likewise, the ID increased the SI (SI RIGHT +177%, P<0.001; SI LEFT + 727%, P<0.001). In the patients with an unequivocal diagnosis or APA based on the ‘four corners’ criteria, the HD and the ID led to wrong identification of the APA side in 28 and 25%, respectively. Conclusions. The HD and the ID improve the ascertainment of the selectivity of adrenal vein catheterization during AVS; by contrast, no significant effect of the VLD on either PAC or PCC was seen. The improvement in the assessment of selectivity with both the HD and the ID should be weighed against the confounding effect on correct identification of lateralized aldosterone excess to the APA side.

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

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 &lt;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&gt;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 &gt;4 who were diagnosed as unilateral aldosterone excess. AR had 0.94 of AUC for prediction of LR &gt;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&lt;1. The AUC of aldosterone concentration and AI for prediction of CR&lt;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.

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

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.

scholarly journals Adrenal Venous Sampling in Primary Aldosteronism: The Usefulness of Contralateral Suppression Index

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Natalia Treistman ◽  
Aline Barbosa Moraes ◽  
Stéphanie Cozzolino ◽  
Patrícia de Fatima dos Santos Teixeira ◽  
Leonardo Vieira Neto
Keyword(s):  
Primary Aldosteronism ◽  
Vena Cava ◽  
Adrenal Vein ◽  
Adrenal Venous Sampling ◽  
Venous Sampling ◽  
Successful Cannulation ◽  
Contralateral Suppression ◽  
The Right ◽  
Cortisol Ratio ◽  
Suppression Index

Adrenal venous sampling (AVS) is the gold standard test to differentiate the unilateral from the bilateral form in patients with primary aldosteronism (PA) although it may be a difficult procedure, especially the successful cannulation of the right adrenal vein. In this report, we describe a 49-year-old female patient diagnosed with PA, after investigating resistant hypertension and refractory hypokalemia. Abdominal computed tomography scan revealed a 2.5 cm adenoma on the right adrenal vein. AVS was performed under cosyntropin infusion. Aldosterone and cortisol concentrations were obtained from the right and left adrenal veins and inferior vena cava (IVC). Cortisol on each adrenal vein divided by cortisol on IVC confirmed successful cannulation of the left side only, which makes it impossible to calculate the lateralization index (LI). From the data on the left adrenal vein and IVC, the aldosterone-to-cortisol ratio divided by the IVC aldosterone-to-cortisol ratio was less than 1.0, suggesting that the left adrenal vein was suppressed with the excess aldosterone originating from the contralateral side (contralateral suppression index (CSI)). Right adrenalectomy was performed; postoperative hypoaldosteronism was confirmed. This report highlights the importance of CSI obtained in AVS when technical difficulties occur making it impossible to obtain LI, which is most commonly used to decide between surgical and clinical management of PA.

scholarly journals OR34-03 Variable and Pulsatile Circulating Aldosterone Levels in Primary Aldosteronism: Implications for Diagnosis and Sub-Type Differentiation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nicholas Yozamp ◽  
Barry Sacks ◽  
Jonathan Underhill ◽  
Tali Fudim ◽  
Anand Vaidya
Keyword(s):  
Primary Aldosteronism ◽  
Vena Cava ◽  
Adrenal Vein ◽  
Anesthesia Induction ◽  
Lower Systolic Blood Pressure ◽  
Supine Posture ◽  
Variable Nature ◽  
The Mean ◽  
The Absolute ◽  
Absolute Decrease

Abstract Introduction: Considerable intra-individual variability in circulating aldosterone levels has been observed in patients with primary aldosteronism (PA). The magnitude and implications of this phenomenon are not well characterized. Objective: To evaluate the acute variability in aldosterone in patients with confirmed PA. Methods: 373 patients with confirmed PA underwent adrenal venous sampling (AVS) after appropriate catheterization of bilateral adrenal veins. Peripheral venous aldosterone levels were measured 2 hours prior to AVS while in supine posture. After anesthesia induction with fentanyl and midazolam, AVS was performed while in the same supine posture, and aldosterone levels were drawn from the inferior vena cava (IVC) and in triplicate from the bilateral adrenal veins over 10 minutes. Differences between the pre-AVS and intra-AVS IVC aldosterone levels were analyzed, and regression models used to identify independent predictors of change. Coefficients of variation (COV) between triplicate aldosterone levels in each adrenal vein were calculated. Results: 81% of patients demonstrated a decrease in aldosterone concentration from pre-AVS to the intra-AVS IVC measurement. The mean decrease in aldosterone was 10.5 ng/dL (95% CI: 7.6–13.3) and the mean relative decrease in aldosterone was 39% (95% CI: 27–51%, P&lt;0.0001). The absolute decrease in aldosterone was striking, with 48% of patients who had a decrease in aldosterone exhibiting an IVC aldosterone of less than or equal to 5 ng/dL. The absolute decrease in aldosterone was significantly associated with a higher aldosterone level (p&lt;0.001) and lower systolic blood pressure at diagnosis (p=0.02). A wide variation in triplicate aldosterone values was seen in the span of 10-minute sampling, ranging from 1–300%, with COV of 21.0% in the left adrenal vein and 25.0% in the right adrenal vein. If the lowest of three aldosterone-to-cortisol (A/C) ratios on the dominant side and highest of three A/C ratios on the contralateral side were used instead of the average of the three values, the interpretation of the AVS would have changed from unilateral PA to bilateral PA in 15.9% of cases. Conclusions: These findings underscore the pulsatile and variable nature of circulating aldosterone levels in patients with bona fide PA. Aldosterone levels substantially declined in 81% of patients within a period of 2 hours while maintaining a fixed and supine posture. In half of these patients, aldosterone levels declined to 5 ng/dL or below, a threshold typically considered incompatible with PA. Further, adrenal venous aldosterone levels exhibited large variations on repeated sampling within a 10-minute span that could have influenced the interpretation of sub-type differentiation in nearly 16% of cases. Single circulating aldosterone values lack precision and reproducibility and may result in incorrect diagnosis and sub-type differentiation.

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

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.

scholarly journals Physiologic variance of corticotropin affects diagnosis in adrenal vein sampling

2009 ◽  
Vol 160 (3) ◽  
pp. 459-463 ◽  
Author(s):  
Masayuki Tanemoto ◽  
Takehiro Suzuki ◽  
Michiaki Abe ◽  
Takaaki Abe ◽  
Sadayoshi Ito
Keyword(s):  
Low Dose ◽  
Standard Dose ◽  
Vena Cava ◽  
Adrenal Vein ◽  
Acth Stimulation ◽  
Adrenal Vein Sampling ◽  
High Prevalence ◽  
Design And Methods ◽  
Diagnostic Step ◽  
Cortisol Ratio

ObjectiveDifferentiating unilateral form from bilateral is a critical diagnostic step in primary aldosteronism (PA), for which adrenal vein sampling (AVS) is accepted to be the most reliable. However, variance of corticotropin could affect the diagnosis in AVS.Design and methodsWe conducted simultaneous bilateral AVS on ten biochemically diagnosed PA cases, and used the aldosterone-to-cortisol ratio (A/C) of the samples for the diagnosis. The diagnosis by AVS after a low-dose (0.1 μg) ACTH stimulation, which can provoke maximum-physiologic corticotropic response, was compared with those before the stimulation and after the standard-dose (250 μg) ACTH stimulation.ResultsIn half of the cases, the low-dose pre-stimulation affected the diagnosis. In four out of ten cases, the side-to-side ratios of A/C were changed in the basal/low-dose/standard-dose AVS as 6.62/2.46/0.63, 2.13/0.41/0.14, 1.88/2.38/2.40, and 1.96/2.27/1.90 respectively. In three out of ten cases, the adrenal vein to the matching inferior vena cava ratio of A/C was also changed across 1, the cut-off to indicate suppression of aldosterone secretion. Additionally, the confirmation of successful sampling was difficult in five out of ten and two out of ten cases of the basal and low-dose AVS respectively, whereas it was easy in all the cases of the standard-dose AVS.ConclusionsThe diagnosis in the basal AVS could be affected by the physiologic fluctuation of ACTH at relatively high prevalence. The basal AVS would be unreliable to differentiate two forms of PA.

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