Influence of somatic mutations on the lateralization index of adrenal vein sampling in aldosterone producing adenomas

2013 ◽  
Author(s):  
Andrea Oszwald ◽  
Evelyn Fischer ◽  
Martin Bidlingmaier ◽  
Anna Pallauf ◽  
Christoph Degenhart ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Adrenal Vein ◽  
Adrenal Vein Sampling ◽  
Lateralization Index

Abstract 277: Mutations in the KCNJ5 Gene Imply a Higher Lateralization Index at Adrenal Vein Sampling for Primary Aldosteronism

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Teresa M Seccia ◽  
Franco Mantero ◽  
Claudio Letizia ◽  
Maniselvan Kuppusamy ◽  
Marlena Barisa ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Somatic Mutations ◽  
Contralateral Side ◽  
Adrenal Vein ◽  
K Channel ◽  
Coding Region ◽  
Aldosterone Secretion ◽  
Adrenal Vein Sampling ◽  
Lateralization Index

Background. The mutations that affect the selectivity filter of the KCNJ5 K+ channel can play a role in triggering and/or maintaining aldosterone oversecretion in primary aldosteronism (PA). We therefore hypothesized that these somatic mutations can be associated with an increased aldosterone secretion from the APA, thus translating in raised plasma aldosterone concentrations (PAC) in the ipsilateral adrenal vein. Aim. To investigate if the lateralization index (LI) at adrenal vein sampling (AVS) is higher in the patients with an APA carrying the mutation (KCNJ5mut), as compared to those without the mutation (KCNJ5wt). Methods. Ninety-two consecutive PA patients who underwent AVS and received diagnosis of APA based on the four corners criteria were recruited. Unequivocal information on the presence or absence of the KCNJ5 mutations was available for each patient. The selectivity index (SI) was calculated as ratio between the right or left adrenal vein PCC (PCCside) and the infrarenal IVC PCC and a cutoff of 2.00 was used. The lateralization index (LI) was calculated in the bilaterally selective AVS as the ratio of PAC/PCC at the APA side to PAC/PCC at the contralateral side. We sequenced the KCNJ5 coding region spanning aminoacids 122 to 199, which include the selectivity filer. Results. The overall prevalence rate of KCNJ5 somatic mutations was 34%; G151R, L168R and T158A mutations were found in 19, 10 and 1 APA respectively. The G151E mutation was not found. The KCNJ5mut and KCNJ5wt groups were similar for gender, age, sK+ levels, while PAC and ARR were higher, and PRA lower (all p<0.05) in the KCNJ5 mut group. In the latter group the LI was higher than in the KCNJ5wt group (29.3± 6.7 vs 16.7±3.9, p< 0.02). This was due to a PAC/PCC ratio which was higher in the adrenal vein ipsilateral to the APA side and lower contralaterally in the KCNJ5mut group. Conclusions. These results provide direct in vivo evidence for a higher aldosterone secretion from APA carrying the KCNJ5 mutations, which translates into higher values of the LI, compared to the tumors without such mutations. Hence, the presence of these KCNJ5 mutations can affect the accuracy of the AVS-based diagnosis of the subtype of PA.

scholarly journals Somatic Mutations in the KCNJ5 Gene Raise the Lateralization Index: Implications for the Diagnosis of Primary Aldosteronism by Adrenal Vein Sampling

2012 ◽  
Vol 97 (12) ◽  
pp. E2307-E2313 ◽  
Author(s):  
Teresa M. Seccia ◽  
Franco Mantero ◽  
Claudio Letizia ◽  
Maniselvan Kuppusamy ◽  
Brasilina Caroccia ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Somatic Mutations ◽  
Adrenal Vein ◽  
Adrenal Vein Sampling ◽  
Lateralization Index

ADRENAL VEIN SAMPLING WITHOUT DISCONTINUATION OF MINERALOCORTICOID RECEPTOR ANTAGONIST THERAPY

2020 ◽  
Vol 26 (9) ◽  
pp. 953-959
Author(s):  
Malini Ganesh ◽  
Shabirhusain S. Abadin ◽  
Leon Fogelfeld
Keyword(s):  
Plasma Renin Activity ◽  
Mineralocorticoid Receptor ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Adrenal Vein ◽  
Adrenal Vein Sampling ◽  
Mineralocorticoid Receptor Antagonist ◽  
Plasma Aldosterone Concentration ◽  
Contralateral Suppression ◽  
Lateralization Index

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. Abbreviations: ACTH = adrenocorticotropic hormone; APA = aldosterone-producing adenoma; ARR = aldosterone-renin ratio; AV = adrenal vein; AVS = adrenal vein sampling; CS = contralateral suppression; DDD = daily defined dose; IQR = interquartile range; K = potassium; LI = lateralization index; MRA = mineralocorticoid receptor antagonist; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity

scholarly journals Effect of Adrenocorticotropic Hormone Stimulation During Simultaneous Bilateral Adrenal Vein Sampling in Primary Aldosteronism

2021 ◽  
Vol 53 (06) ◽  
pp. 364-370
Author(s):  
Wei Liu ◽  
Jingjing Zhang ◽  
Yaling Yang ◽  
Yinxin Jin ◽  
Zaizhao Li ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Adrenocorticotropic Hormone ◽  
Base Excess ◽  
Serum Potassium Level ◽  
Adrenal Vein ◽  
Acth Stimulation ◽  
Adrenal Vein Sampling ◽  
Before And After ◽  
Carbon Dioxide Combining Power ◽  
Lateralization Index

AbstractThe aim of the study was to investigate the significance and influence of adrenocorticotropic hormone (ACTH) stimulation in primary aldosteronism (PA) patients with simultaneous bilateral adrenal vein sampling (AVS). All patients diagnosed with PA underwent simultaneous bilateral AVS with ACTH. In 95 patients, the post-ACTH SI significantly increased (p<0.001), and it gradually decreased from t10–t30 after ACTH stimulation (p<0.001). The unsuccessful catheterization decreased after ACTH stimulation. Time points within 20 min after ACTH stimulation were better for sampling, and the selectivity did not increase over longer periods. According to lateralization before and after ACTH stimulation, the patients could be divided into 3 groups (U, unilateral; B, bilateral): U/U , U/B or B/U, and B/B. Compared with the U/U group, in the U/B or B/U and B/B groups, the lateralization index (LI) was lower both at baseline and after ACTH stimulation (p<0.0001), the contralateral index (CLI) was higher after ACTH stimulation (p<0.003), the serum potassium level was higher (p<0.001), and the carbon dioxide combining power (CO2CP) and base excess (BE) levels were lower. In conclusion, in simultaneous bilateral AVS, ACTH stimulation had significant effects on increasing the catheterization selectivity. Lateralization change was observed after stimulation. After ACTH stimulation, fewer patients could be diagnosed with lateralized PA. Patients with consistent lateralized PA showed a more serious phenotype.

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 to Distinguish Between Unilateral and Bilateral Primary Hyperaldosteronism: To ACTH Stimulate or Not?

2020 ◽  
Vol 9 (5) ◽  
pp. 1447
Author(s):  
Tae-Yon Sung ◽  
Wilson Mawutor Alobuia ◽  
Monica Varun Tyagi ◽  
Chandrayee Ghosh ◽  
Electron Kebebew
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Primary Hyperaldosteronism ◽  
Adrenal Vein ◽  
Acth Stimulation ◽  
Adrenal Vein Sampling ◽  
Successful Cannulation ◽  
Unilateral Disease ◽  
The Right ◽  
Lateralization Index ◽  
Prospective Database

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.

scholarly journals Three Discrete Patterns of Primary Aldosteronism Lateralization in Response to Cosyntropin During Adrenal Vein Sampling

2019 ◽  
Vol 104 (12) ◽  
pp. 5867-5876 ◽  
Author(s):  
Taweesak Wannachalee ◽  
Lili Zhao ◽  
Kazutaka Nanba ◽  
Aya T Nanba ◽  
James J Shields ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Primary Aldosteronism ◽  
Time Dependent ◽  
Adrenal Vein ◽  
Driver Mutations ◽  
Adrenal Vein Sampling ◽  
Mutation Status ◽  
Hormonal Fluctuations ◽  
Lateralization Index ◽  
Generation Sequencing

Abstract Context 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. Objectives To define the major patterns of time-dependent lateralization, and their determinants, after cosyntropin stimulation during AVS. Methods 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. Results 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. Conclusion 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.

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