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      The value of plasma metanephrine measurements during adrenal vein sampling

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          Abstract

          Objective

          The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS.

          Design

          This is a diagnostic accuracy study in a tertiary referral endocrinology department.

          Methods

          Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS.

          Results

          There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet–PVmet) of ≥12.0 to indicate successful cannulation of the AV ( n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet–AVnormet) of ≥2.0 to indicate successful cannulation ( n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization ( n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%).

          Conclusions

          Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy.

          Significance statement

          Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

          To develop clinical practice guidelines for the management of patients with primary aldosteronism.
            • Record: found
            • Abstract: found
            • Article: not found

            Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

            : By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas.
              • Record: found
              • Abstract: found
              • Article: not found

              Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis.

              There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with primary aldosteronism. We aimed to assess the association between primary aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                12 January 2024
                06 December 2023
                01 February 2024
                : 13
                : 2
                : e230300
                Affiliations
                [1 ]Endocrine , Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
                [2 ]Department of Medicine , University of Otago, Wellington, New Zealand
                [3 ]Department of Radiology , Wellington Regional Hospital, New Zealand
                [4 ]University of Otago , Wellington, New Zealand
                [5 ]Diabetes and Endocrinology Service , Hutt Hospital, New Zealand
                [6 ]Department of Biochemistry & Endocrinology , Awanui Labs, New Zealand
                [7 ]Department of Biochemistry , Awanui Labs, Dunedin, New Zealand
                [8 ]Department of Surgery & Anaesethesia , University of Otago, Wellington, New Zealand
                [9 ]Department of General Surgery , Wellington Regional Hospital, New Zealand
                [10 ]Centre for Endocrinology and Metabolism , Hudson Institute of Medical Research, Clayton, Victoria, Australia
                [11 ]Department of Medicine , Monash University, Clayton, Victoria, Australia
                Author notes
                Correspondence should be addressed to R W Carroll: richard.carroll@ 123456ccdhb.org.nz
                Author information
                http://orcid.org/0000-0003-4532-8336
                http://orcid.org/0000-0002-9628-9958
                Article
                EC-23-0300
                10.1530/EC-23-0300
                10831578
                38055778
                b1f99d9a-3621-4a4f-a4cf-199ccb6519df
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 06 August 2023
                : 06 December 2023
                Categories
                Research

                adrenal vein sampling,primary aldosteronism,metanephrines

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