Adrenal Vein Sampling Lateralization Research Articles

FRI148 Adrenal Vein Sampling: Intra-protocol Hormonal Variability

Abstract Disclosure: C. Lee: None. Z. Salman: None. J. Shields: None. A.F. Turcu: None. Background: Primary aldosteronism (PA) might arise from one or both adrenal glands. Treatment of PA relies on determining the relative contribution of aldosterone from the two adrenal glands. Adrenal vein sampling (AVS) is essential to identifying patients with lateralized PA (LPA), who benefit from surgery. AVS procedure and interpretation protocols differ between centers. Variability in AVS lateralization has been primarily attributed to cosyntropin use and lateralization index (LI) thresholds. However, data on intra-protocol variability are lacking. Methods: We retrospectively reviewed the clinical records of patients with PA who underwent AVS at University of Michigan between January 2015 and December 2022. In our center, AVS is performed both before and after cosyntropin stimulation, and 6 sets of paired adrenal vein and peripheral serum are obtained: 3 at baseline, and 3 between 5-30 min after cosyntropin stimulation. We included patients who had successful adrenal vein catheterization and valid data from 6 time points. A LI≥4 was considered indicative of LPA. We assessed the rates of inconsistent AVS results within baseline and cosyntropin stimulated samples as proportion of sets in which 1/3 LIs provided different subtyping results than the other 2/3. Results: Of 361 patients included, 107 (29.6%) patients had at least one inconsistent LI. Of these, 74 (20%) patients had an inconsistent LI within the basal sets, 45 (12%) within the cosyntropin stimulated sets, and 12 (3.3%) patients had a discrepant result in both baseline and cosyntropin stimulated sets. The highest outlier rates were observed in the first basal sample (30.3%), followed by the third basal sample (21.9%), the first post-cosyntropin sample (16.0%), and the last post-cosyntropin sample (13.5%). Patients with one intra-protocol outlier were younger (mean age 52.2 ± 11.5 vs. 56.2 ± 10.8 years), but there were no sex, race distribution, or BMI differences between the two groups. Conclusions: The intra-procedural AVS data variability is almost twice as high in basal vs. post-cosyntropin stimulation sampling, particularly in the initial set, likely mediated by acute ACTH fluctuations during the procedure. Our results emphasize the importance of obtaining multiple AVS data sets, in order to best inform the decision for or against surgery. Presentation: Friday, June 16, 2023

Adrenal Vein Sampling Without Discontinuation of Mineralocorticoid Receptor Antagonist Therapy

Objective: Guidelines recommend withdrawing mineralocorticoid-receptor antagonists (MRAs) for 4 weeks prior to adrenal vein sampling (AVS), but this is not always feasible because of hypertension and hypokalemia. This retrospective study of primary aldosteronism (PA) patients who underwent AVS between 2008 and 2018 assessed the effect of continuing MRA on the AVS procedure.Methods: Clinical data including antihypertensive regimen defined by the World Health Organization Daily Defined Dose (DDD) system were collected for 19 patients with adequate cannulation and lateralization during AVS. Results were compared between 5 patients who continued and 14 patients who discontinued MRA therapy (MRA and non-MRA groups).Results: At diagnosis, plasma renin activity, plasma aldosterone concentration (PAC), potassium (K) doses, and DDD were not significantly different between groups. Aldosterone-renin ratio was significantly higher in the MRA group (median, 375.0; interquartile range [IQR], 224.8 to 544.3 vs. 148.7, 118.4 to 192.1; P = .034). No difference was found in lateralization index (median 48.3; IQR, 23.6 to 52.1 vs. 8.7; 4.9 to 20.2; P = .10). Contralateral suppression, defined as aldosterone-cortisol ratio of unaffected adrenal to periphery, trended lower in the MRA group (median, 0.17; IQR, 0.03 to 0.39 vs. 0.51; 0.27 to 1.1; P = .056). All five MRA patients underwent successful adrenalectomy with at least 50% reduction in DDD and PAC and normal K postoperatively. One MRA patient did not lateralize, which was confirmed on repeat AVS, after MRA withdrawal.Conclusion: Continuation of MRA may not interfere with AVS lateralization or affect contralateral adrenal suppression. Continuation of MRA in preparation for AVS may be considered, especially in patients with severe PA, to avoid uncontrolled hypertension and severe hypokalemia.

The Concordance Between Imaging and Adrenal Vein Sampling Varies With Aldosterone-Driver Somatic Mutation

Correct subtyping of primary aldosteronism (PA) is critical for guiding clinical management. Adrenal imaging is less accurate than adrenal vein sampling (AVS); nonetheless, AVS is invasive, technically challenging, and scarcely available. To identify predictors of concordance between cross-sectional imaging and lateralized AVS in patients with PA that could help circumvent AVS in a subset of patients. We retrospectively studied all patients with PA who underwent AVS in a tertiary referral center from 2009 to 2019. AVS was performed before and after cosyntropin stimulation. Patients with lateralized AVS in at least one condition were included. Aldosterone synthase-guided next-generation sequencing was performed on available adrenal tissue. Logistic regression was implemented to identify predictors of imaging-AVS lateralization concordance. A total of 234 patients (62% men), age 20 to 79 years, 73% white, 23% black, and 2% Asian were included. AVS lateralization was found: 1) both pre- and post-cosyntropin (Uni/Uni) in 138 patients; 2) only at baseline (Uni/Bi) in 39 patients; 3) only after cosyntropin stimulation (Bi/Uni) in 29 patients. Catheterization partially failed in 28 patients. AVS-imaging agreement was higher in patients with KCNJ5 versus other aldosterone-driver somatic mutations (90.3% versus 64.6%; P < 0.001); in Asian and white versus black Americans (75%, 70%, and 36%, respectively); in younger patients; and those with left adrenal nodules and contralateral suppression. Conversely, AVS-imaging agreement was lowest in Uni/Bi patients (38% vs. 69% in Uni/Uni, and 62% in Bi/Uni; P = 0.007). While AVS-imaging agreement is higher in young white and Asian patients, who have KCNJ5-mutated aldosterone producing adenomas, no predictor confers absolute imaging accuracy.

SAT-065 Adrenal Vein Sampling Without Discontinuation Of Mineralocorticoid-Receptor Antagonist Therapy

In primary hyperaldosteronism (PA), adrenal vein sampling (AVS) is a critical step in determining if the source of aldosterone is unilateral or bilateral. Guidelines recommend withdrawing mineralocorticoid-receptor antagonists (MRA) for 4 weeks prior to testing as unsuppressed renin levels may stimulate the contralateral normal adrenal gland and mask the lateralization of aldosterone secretion. However, it is not always feasible to withdraw these drugs in patients with severe hypertension and hypokalemia. We conducted a retrospective study of PA patients who underwent AVS at our institution between 2008-2018 to assess the effect of MRA on the AVS procedure. We analyzed demographics, laboratory results, pathology and follow-up data. Antihypertensive regimen between groups was compared using the WHO Defined Daily Dose (DDD) system. Nineteen patients with adequate adrenal vein cannulation during AVS using cortisol corrected selectivity index, as well as lateralization were studied. Five continued MRA therapy and in 14 MRA therapy was discontinued. At diagnosis, plasma renin activity, plasma aldosterone concentration and potassium (K) doses, and DDD were not significantly different between MRA and non-MRA groups. Aldosterone renin ratio was significantly higher in the MRA group compared to the non-MRA group (375.0, IQR 224.8-544.3 vs 148.7, IQR 118.4-192.1; p 0.034). The dose of MRA when continued ranged from 25-100mg of spironolactone. The results of the AVS showed that there was no difference in lateralization index (LI) between both groups (48.3, IQR 23.6-52.1 vs 8.7, IQR 4.9-20.2; p 0.10). Contralateral suppression index of the unaffected adrenal was not different between the groups (0.17, IQR 0.03-0.39 vs 0.51, IQR 0.27-1.1; p 0.056). Seventeen out of 19 patients with AVS lateralization had unilateral adrenalectomy (5 patients on MRA and 12 patients off MRA). Two patients were not deemed surgical candidates. All 5 patients in the MRA group and 7/12 patients in the non-MRA group had at least 50% reduction in DDD postoperatively. All 17 patients had normal K postoperatively off supplements. All 5 patients on MRA and 11/12 patients off MRA had at least 50% reduction in postoperative PAC. One patient on MRA did not lateralize on AVS, which was confirmed on repeat AVS after withdrawal of MRA for four weeks. Conclusion: The current study shows that continuation of MRA therapy does not interfere with AVS lateralization, nor does it affect the contralateral unaffected adrenal suppression index. Continuation of MRA in preparation for AVS may be considered especially in patients with high ARR to avoid uncontrolled BP and significant hypokalemia.

SAT-061 Determinants of Cosyntropin Effect on Adrenal Vein Sampling Lateralization in Primary Aldosteronism

Background: Although adrenal vein sampling (AVS) is the gold standard for subtyping primary aldosteronism (PA), consensus regarding the optimal protocol and data interpretation is lacking. Advantages of cosyntropin stimulation during AVS include enhancing the rate and confidence of successful cannulation, and circumventing the intra-procedure hormonal fluctuations. While it has been suggested that cosyntropin might stimulate aldosterone secretion from non-autonomous areas, aldosterone-producing adenomas are also responsive to cosyntropin. The relative effect of cosyntropin on autonomous vs. normal aldosterone-producing cells remains poorly understood. Objectives: To define the major patterns of time-dependent AVS lateralization response to cosyntropin and the determinants of these patterns. Methods: We retrospectively studied all patients with confirmed PA who underwent AVS in our institution between 2009-2018. Simultaneous adrenal vein (AV) and peripheral samples were obtained before, 10 and 20 minutes after cosyntropin administration. Only patients who had successful catheterization on all 3 time points were included. Unilateral (U) or bilateral (B) PA were defined based on a lateralization index (LI) ≥ or < 4, respectively. Demographic, laboratory, imaging, and pathological data were reviewed. Aldosterone synthase (CYP11B2)-guided genetic analysis was performed on available adrenal tissue by next generation sequencing. Linear mixed effects model was used to identify factors influencing LI patterns across the three time points. Results: Study criteria were met in 220 patients. Based on pre-and post-cosyntropin data, AVS lateralization was concordant in 163 (74%) patients (UU, 104; BB, 59) and discordant in 57 (26%) patients (UB, 35; BU, 22). Baseline and stimulated LI in the UU group were significantly higher than in the UB and BU group, respectively (~2.3 fold, p<0.001). Three major patterns of LI response to cosytropin were identified: increasing, decreasing, and stable. Baseline peripheral and dominant AV aldosterone concentrations were strong predictors for LI pattern across the 3 time points (p=0.03 and p<0.001, respectively) while cortisol, age, sex or race did not predict LI response to cosyntropin. The mutation status has been analyzed in 50 patients who underwent adrenalectomy and revealed: 21 KCNJ5, 17 CACNA1D, 8 ATP1A1 and 4 ATP2B3 somatic mutations. For tumors harboring KCNJ5 mutations, LI was highest at baseline compared with all other groups (35.5 vs.12.9; p<0.001), and LI declined across the three time points studied. In contrast, for tumors with ATP1A1 and ATP2B3 mutations, LI increased with cosyntropin stimulation. Conclusions: The cosyntropin impact on aldosterone secretion and LI varies in PA patients. Predictors of LI patterns of response to cosyntropin include baseline aldosterone concentrations and aldosterone-driver mutations.

Adrenal Vein Sampling Lateralization Despite Mineralocorticoid Receptor Antagonists Exposure in Primary Aldosteronism.

Many antihypertensive medications modulate the renin-angiotensin-aldosterone system, possibly skewing the diagnosis and subtyping of primary aldosteronism (PA). Particularly, mineralocorticoid receptor antagonists (MRA) might raise renin and stimulate aldosterone synthesis from nonautonomous areas, potentially obscuring lateralization on adrenal vein sampling (AVS). Withdrawal of MRA in severe PA, however, can precipitate hypokalemia and/or hypertension and therefore is not always practical. To assess the effects of MRA on the interpretation of AVS data. A cohort study of all PA patients who underwent AVS at University of Michigan between January 2009 and January 2018 was conducted. Demographics, diagnostic, AVS, surgical pathology, and follow-up data were collected retrospectively. Of 191 patients who underwent AVS, 51 (27%) were exposed to MRA at the time of the procedure. Plasma aldosterone concentration and the daily defined dose of antihypertensives were higher in patients taking vs those not taking MRA. Unilateral PA was more frequent in the MRA group, both precosyntropin and postcosyntropin (P < 0.05). The MRA group included two patients with unsuppressed renin, who demonstrated unequivocal AVS lateralization. To date, 86 patients underwent unilateral adrenalectomy, including 30 patients taking MRA during AVS. The proportion of clinical and biochemical success was not statistically different between patients exposed to and those not exposed to MRA during AVS (P = 0.17 and 0.65, respectively). Our data suggest that conclusive AVS lateralization is often achieved in patients with severe PA despite MRA use.

Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism.

Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures. We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α-hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation. Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT-detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2-negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava. Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA.