Utility of Plasma Metanephrines in Adrenal Venous Sampling in Primary Aldosteronism

Abstract Introduction: Adrenal Venous Sampling (AVS) is the most reliable means of identifying surgically curable subtypes of primary aldosteronism (PA). Cortisol levels are used to determine cannulation success and lateralization. However, cortisol has a variable secretion pattern and long-half life, and can be co-secreted by adrenal adenomas, leading to misinterpretation of results. Plasma metanephrines (MN) are a possible alternative analyte. MN levels are unaffected by stress, have a short half-life of 3–6 minutes and are released continuously by the adrenals, resulting in very high concentration gradients between the adrenal veins (AV) and peripheral veins (PV), thus providing a sensitive means to determine cannulation success. Premise:The objective of this study was to see if MN can be used in lieu of cortisol in AVS. A secondary end-point was to see if the data was particularly useful in patients who are known co-secretors of cortisol. Methods: Data from AVS carried out without cosyntropin stimulation, from October 2018 to March 2020, were analysed retrospectively. Of these, 51 had additional samples drawn for MN at the time of the procedure and were recruited. Six patients were identified as having autonomous cortisol secretion as they failed an overnight dexamethasone suppression test (ONDST). The data was analysed using cortisol and MN separately and then compared with regards to their selectivity and lateralization index. Data was also analysed to see if known co-secretors had an elevated cortisol/MN ratio of more than 2 on the affected side as described in previous papers. Results: When compared to cannulation and lateralization outcomes using cortisol, similar results were obtained using, a MN AV/PV ratio of more than 12 to indicate successful cannulation and an aldosterone/MN ratios of greater than 5 to confirm lateralization. Contralateral suppression to less than 0.5 for aldosterone/MN below the PV was seen in unilateral disease. With regards to the six co-secretors, all had elevated cortisol/MN ratios of more than 2 on the affected side. Three had concordant results but the other three had discrepant results, with MN analysis suggesting unilateral disease and cortisol measurements suggesting bilateral disease. Two had undergone surgery with biopsy confirming unilateral disease that correlated with MN analysis. The third is under medical management. Conclusion: This is the first study evaluating the use of MN to determine lateralisation of aldosterone production in PA. Further studies are needed, but using MN may be a more reliable alternative to cortisol in the analysis of AVS before definitive surgery in particular in patients with cortisol co-secretion.

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OR34-04 Efficiency of Adrenal Venous Sampling in the Treatment Choice of Primary Aldosteronism (AVSTAT Study)

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.480 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Mitsuhide Naruse ◽

Felix Beuschlein ◽

Mirko Parasiliti Caprino ◽

Jaap Deinum ◽

William Drake ◽

...

Keyword(s):

Primary Aldosteronism ◽

Clinical Decision ◽

Pressure Control ◽

Primary Objective ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Bilateral Disease ◽

Good Blood Pressure Control ◽

Number Of Patients ◽

Unilateral Disease

Abstract BACKGROUND: Adrenal venous sampling (AVS) is strongly recommended for a subtype diagnosis of primary aldosteronism (PA) if adrenalectomy (ADX) is desired by the patient. Given various issues related to AVS such as technical demand, invasive nature, expensive cost and radiation exposure, AVS is expected to lead efficiently to the subtype diagnosis and ADX. Aim: Primary objective was to assess the performance of AVS to determine treatment of PA by investigating the ratio of unilateral disease and rate of ADX following AVS in patients with unilateral disease. Methods: Sixteen major referral centers in ENS@T (n=10) and Japan (n=6) participated in the study. Study period was from 2006 to 2018. Data on total number of PA patients, AVS (total number and number of successful procedures), number of patients with unilateral diseases, and number of patients that underwent ADX were collected by a questionnaire-based survey. In addition, reasons for not proceeding to ADX in patients with a unilateral diagnosis were investigated. The diagnosis of PA was based on the positive case detection and at least one positive result in confirmatory testing. Results: Total number of confirmed PA patients and conducted AVS showed a dramatic increase during the past decade (PA: 1061 pts/ 2006–2011 to 3718 pts/ 2012–2018; AVS: 720/ 2006–2011 to 2448/ 2012–2018). Success rate of AVS was improved from 79.0% (2006–2011) to 92.5% (2012–2018). Both rate of unilateral PA and ADX of successful procedures decreased from 42.7% (2006–2011) to 37.3% (2012–2018) and from 40.8% (2006–2011) to 34.9% (2012–2018), respectively. Of the patients with successful AVS, bilateral disease was diagnosed in 63.5% (1812/2854 pts). Of the unilateral PA patients, 11.9% (125/ 1054 pts) were not subjected to ADX. The rate of the patients not subjected to ADX was significantly higher in Japan than in ENS@T centers both in patients with successful AVS (75.8% vs. 53.4%) and with unilateral disease (19.9% vs. 8.6%). Clinical decision against ADX in unilateral disease was made by the physicians in 33.3%, the patients in 33.3%, and both in 33.3%. Medical factors for Dr.’s decision against ADX in unilateral disease included good blood pressure control, normokalemia, comorbidities (e.g. DM, CKD), non-lateralized CT findings (e.g. no tumor, contralateral tumor), and discordant results among different criteria of AVS. Conclusions: High prevalence of bilateral disease and change of treatment policy after implementation affected the efficiency of AVS as an essential diagnostic procedure prior to ADX. Development of non-invasive procedures to exclude bilateral PA and more strict indication of AVS are warranted.

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Application of strict criteria in adrenal venous sampling increases the proportion of missed patients with unilateral disease who benefit from surgery for primary aldosteronism

Journal of Hypertension ◽

10.1097/hjh.0000000000001693 ◽

2018 ◽

Vol 36 (6) ◽

pp. 1407-1413 ◽

Cited By ~ 8

Author(s):

Gregory Kline ◽

Alexander Leung ◽

Benny So ◽

Alex Chin ◽

Adrian Harvey ◽

...

Keyword(s):

Primary Aldosteronism ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Unilateral Disease

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Adrenal Venous Sampling in Young Patients with Primary Aldosteronism. Extravagance or Irreplaceable?

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab047 ◽

2021 ◽

Author(s):

Eleftheria Gkaniatsa ◽

Augustinas Sakinis ◽

Magnus Palmér ◽

Andreas Muth ◽

Penelope Trimpou ◽

...

Keyword(s):

Primary Aldosteronism ◽

Clinical Guidelines ◽

Clinical Success ◽

Adrenal Adenoma ◽

Young Patients ◽

Adrenal Venous Sampling ◽

Imaging Studies ◽

Venous Sampling ◽

Unilateral Adrenalectomy ◽

Aldosterone Production

Abstract Context Current clinical guidelines suggest that adrenal venous sampling (AVS) may not be mandatory in young patients with primary aldosteronism (PA) and a solitary adrenal adenoma on imaging. Objective The aim of this study was to further elucidate whether conventional imaging alone is sufficient to distinguish unilateral from bilateral PA among patients aged 40 years or younger. Methods This was a retrospective study where data from 45 patients with PA, aged between 26 and 40 years, who underwent successful AVS between 2005 and 2019, were analyzed. Results concerning laterality on imaging studies and AVS were recorded. Outcome in surgically treated patients was assessed according to the Primary Aldosteronism Surgical Outcomes criteria. Results In 4 of 25 patients with unilateral aldosterone production according to AVS, computed tomography inaccurately suggested bilateral disease. Following unilateral adrenalectomy, all 4 patients showed complete clinical success. Five of 20 patients with bilateral aldosterone production according to AVS had a solitary adrenal nodule (8-19 mm) on imaging. Two of these 5 patients were treated with unilateral adrenalectomy, neither having complete biochemical and/or clinical success postoperatively. Two of 16 patients younger than 35 years had discordant results, 1 with unilateral and 1 with bilateral aldosterone production, according to AVS. Conclusion Imaging studies inaccurately predicted laterality in a significant number of young patients with PA. In contrast to current clinical guidelines, our results support AVS for subtype evaluation in young adults with PA, including patients 35 years or younger.

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Adrenal Venous Sampling–Guided Adrenalectomy Rates in Primary Aldosteronism: Results of an International Cohort (AVSTAT)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa706 ◽

2020 ◽

Author(s):

Youichi Ohno ◽

Mitsuhide Naruse ◽

Felix Beuschlein ◽

Florentine Schreiner ◽

Mirko Parasiliti-Caprino ◽

...

Keyword(s):

Blood Pressure ◽

Clinical Reasoning ◽

Primary Aldosteronism ◽

Pressure Control ◽

Adrenal Venous Sampling ◽

Diagnostic Efficiency ◽

Venous Sampling ◽

Good Blood Pressure Control ◽

Unilateral Disease ◽

Current Criterion

Abstract Context Adrenal venous sampling (AVS) is the current criterion standard lateralization technique in primary aldosteronism (PA). Japanese registry data found that 30% of patients with unilateral PA did not undergo adrenalectomy, but the reasons for this and whether the same pattern is seen internationally are unknown. Objective To assess the rate of AVS-guided adrenalectomy across an international cohort and identify factors that resulted in adrenalectomy not being performed in otherwise eligible patients. Design, Setting, and Participants Retrospective, multinational, multicenter questionnaire-based survey of management of PA patients from 16 centers between 2006 and 2018. Main Outcome Measures Rates of AVS implementation, AVS success rate, diagnosis of unilateral PA, adrenalectomy rate, and reasons why adrenalectomy was not undertaken in patients with unilateral PA. Results Rates of AVS implementation, successful AVS, and unilateral disease were 66.3%, 89.3% and 36.9% respectively in 4818 patients with PA. Unilateral PA and adrenalectomy rate in unilateral PA were lower in Japanese than in European centers (24.0% vs 47.6% and 78.2% vs 91.4% respectively). The clinical reasoning for not performing adrenalectomy in unilateral PA were more likely to be physician-derived in Japan and patient-derived in Europe. Physician-derived factors included non-AVS factors, such as good blood pressure control, normokalemia, and the absence of adrenal lesions on imaging, which were present before AVS. Conclusion Considering the various unfavorable aspects of AVS, stricter implementation and consideration of surgical candidacy prior to AVS will increase its diagnostic efficiency and utility.

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Adrenocorticotropic Hormone–Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies

Hypertension ◽

10.1161/hypertensionaha.121.17248 ◽

2021 ◽

Author(s):

Nicholas Yozamp ◽

Gregory L. Hundemer ◽

Marwan Moussa ◽

Jonathan Underhill ◽

Tali Fudim ◽

...

Keyword(s):

Primary Aldosteronism ◽

Adrenocorticotropic Hormone ◽

Adrenal Venous Sampling ◽

Original Research ◽

Venous Sampling ◽

Acth Stimulation ◽

The Past ◽

Unilateral Disease ◽

The Impact ◽

Lateralization Index

Guidelines recommend adrenal venous sampling to determine disease laterality in primary aldosteronism. Adrenocorticotropic hormone (ACTH) stimulation clearly improves the likelihood of successful adrenal vein catheterization but may lead to a decrease in lateralization rates. To examine the impact of ACTH on lateralization, we performed a retrospective analysis of 340 patients with confirmed primary aldosteronism who underwent adrenal venous sampling with a single interventional radiology team using a protocol of sampling both before and after an ACTH bolus. In addition to this original research, we conducted a review of similar studies from the past 5 years to develop a consensus on the impact of ACTH on lateralization for primary aldosteronism. In the original research analysis, following a bolus of ACTH, 58% of patients had a decline in lateralization index which led to discordance between the pre-ACTH and post-ACTH classifications of lateralization in up to 26% of cases. The majority of discordant cases were due to reclassification from unilateral disease pre-ACTH to bilateral disease post-ACTH. In patients who already lateralized with unstimulated sampling, the response to ACTH did not have any impact on surgical outcomes. In a review of contemporary studies, we identified 11 similar studies in the past 5 years, of which 10 reported either no change or a decrease in lateralization index following ACTH, resulting in ≈25% discordance between unstimulated and stimulated lateralization rates. We conclude that ACTH stimulation during adrenal venous sampling can underestimate surgically remediable primary aldosteronism and recommend that the role of ACTH be limited primarily to enhancing selectivity.

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