Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

Seccia, Teresa Maria; Miotto, Diego; Toni, Renzo De; Gallina, Valentina; Vincenzi, Matteo; Pessina, Achille C.; Rossi, Gian Paolo

doi:10.1530/eje-11-0246

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…7,10 All the above factors likely contribute to the consistently high gradients in PV to AV plasma concentrations of metanephrine, which provide an opportunity for more accurate and sensitive detection of selective AV catheterization than the smaller gradients for cortisol or other substances evaluated for this purpose, such as chromogranin. 8,20 Additional consideration of the much higher ratios of metanephrine to normetanephrine in AV than PV plasma provides a further means for confirming correct positioning of AV catheters. Because measurements of metanephrine are commonly performed together with normetanephrine, the additional use of metanephrine to normetanephrine ratios offers another advantage of measuring these metabolites not possible with measurements of cortisol.…”

Section: Discussionmentioning

confidence: 99%

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

et al. 2013

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A drenal hypertension caused by primary aldosteronism comprises the most common curable form of secondary hypertension. In the analytic workup of patients with primary aldosteronism, adrenal venous sampling (AVS) is recommended for establishing the origins of excess production of hormones.1 AVS is a technically demanding procedure in which correct cannulation of the adrenal veins, especially the right, can pose significant difficulty. 2,3 Correct positioning of the catheter is verified by measurement of plasma cortisol concentrations. High cortisol concentrations in adrenal blood compared with peripheral blood ascertain correct catheter placement and thus selective sampling. Because cortisol has a long circulating halflife (100 minutes), increases in adrenal vein (AV) blood above levels of peripheral venous (PV) blood are relatively minor and subsequently subject to interpretative error. Furthermore, as a result of physiological corticotropin fluctuations, cortisol is secreted in a variable fashion so that fluctuating levels can interfere with the interpretation of AVS selectivity. [4][5][6] This problem can be overcome using cosyntropin stimulation. 7 Cosyntropin stimulation, however, adds to the complexity of the procedure and for this reason is not always used.With the above considerations in mind, there seems a need for more reliable parameters than cortisol in assessing the correct positioning of catheters during AVS.8 Plasma metanephrine, the O-methylated metabolite of epinephrine, represents one such alternative analyte. More than 90% of plasma metanephrine is produced within the adrenal medulla, with <10% produced from epinephrine after release from the adrenals. 7 Compared with cortisol, plasma metanephrine has a short circulating half-life of 3 to 6 minutes, resulting in close to 90-fold increases of AV compared with PV concentrations in situations where catheters are correctly positioned.7 Such large Abstract-Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative parameter. The objective of our study was to determine the use of plasma metanephrine concentrations to establish correct catheter positioning during adrenal vein sampling with and without cosyntropin stimulation. We included 52 cosyntropin-stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and metanephrine concentrations were measured in adrenal and peripheral venous samples. Success rates of sampling, using an adrenal to peripheral cortisol selectivity index of 3.0, were compared with success rates of metanephrine using a selectivity index determined by receiver operating characteristic curve analysis. Among procedures assessed as selective using cortisol, the adrenal to peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol (94.0 versus 15.5; P<0.0001). Ther...

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Section: Discussionmentioning

confidence: 99%

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

et al. 2013

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“…This furnished the opportunity for a paired within-patient-within-AVS comparison. Metoclopramide was only used in one center, as already described (19,24); the results obtained with metoclopramide are reported here simply for comparison with the cosyntropin-stimulated AVS.…”

Section: Study Populationmentioning

confidence: 99%

Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization

Rossitto

Amar

Azizi

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. Objectives To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. Design and settings In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. Results AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. Conclusion Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020)

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“…Metoclopramide has long been known to stimulate aldosterone secretion in man through a renin-angiotensin system-independent mechanism [13][14][15][16]. Conversely, metoclopramide has no influence on plasma cortisol levels [15][16][17][18]. Because metoclopramide is a powerful dopamine antagonist, it is classically considered that metoclopr-…”

Section: Introductionmentioning

confidence: 99%

l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man

et al. 2017

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In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT receptors.

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Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

Cited by 7 publications

References 24 publications

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization

l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man

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