We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men ( P <0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P =0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications ( P <0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P <0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01234220.

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 &lt;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 &lt; 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)

Background Portal vein thrombosis (PVT) is the most common thrombotic complication in cirrhosis; however, local risk factors involved in its pathogenesis are still not fully investigated. The aim of the study was to evaluate hemostasis and endothelial damage in the portal vein in patients with cirrhosis and portal hypertension. Methods Adult cirrhotics undergoing transjugular intrahepatic portosystemic shunt were consecutively enrolled. Rotational thromboelastometry (ROTEM), dosage of total circulating glycosaminoglycans (GAGs), and endotoxemia levels (lipopolysaccharide [LPS]), along with evaluation of endothelial dysfunction by quantification of circulating endothelial microparticles (MPs), were performed on citrated peripheric and portal venous blood samples from each enrolled patient. Results Forty-five cirrhotics were enrolled. ROTEM analysis revealed the presence of a significant heparin-like effect in portal blood (median ɑ angle NATEM 50° vs. HEPTEM 55°, p = 0.027; median coagulation time NATEM 665 s vs. HEPTEM 585 s, p = 0.006), which was not detected in peripheral blood, and was associated with a higher concentration of circulating GAGs. Even though total annexin V-MP circulating MPs were less concentrated in the splanchnic district, the proportion of MPs of endothelial origin, with respect to annexin V-MP, was significantly increased in the portal district (p = 0.036). LPS concentration was higher in portal (197 pg/mL) compared with peripheral blood (165 pg/mL) (p < 0.001). Conclusion Evidences of a damage of glycocalyx along with increased concentration of endothelial MPs suggest the presence of a significant endothelial alteration in the portal vein with respect to peripheral veins. Portal site-specific endothelial damage could hamper its antithrombotic properties and may represent an important local risk factor in the pathogenesis of PVT.

Background: A stress reaction involving increased cortisol release, which has not been documented thus far, might affect the assessment of selectivity of catheterization during adrenal venous sampling (AVS). Objective: To investigate whether an ACTH-driven cortisol release occurs during AVS and whether it influences the assessment of selectivity by the step-up of cortisol (plasma cortisol concentrations, PCC) between the adrenal vein blood (PCC SIDE ) and the inferior vena cava (PCC IVC ), e.g. the selectivity index (SI). Design and methods: We determined the SI in samples obtained simultaneously at starting AVS (t-15) and again after 15 min (t0) in 34 consecutive patients with proven aldosterone-producing adenoma. We then calculated the SI with PCC SIDE obtained at t-15 and at t0, and the PCC IVC values obtained at the different time point, thus simulating sequential AVS. Results: The PCC SIDE and the SI fell significantly from t-15 to t0 on both the sides. When PCC SIDE obtained at t-15 was combined with PCC IVC at t0, the SI values were higher than those obtained with simultaneously drawn samples. This led to label as selective more AVS studies than with bilaterally simultaneous data, especially when using higher cutoffs for the SI. Conclusions: A transient increase in cortisol release from both adrenal glands occurs in the majority of the patients who undergo AVS. This stress reaction can influence the assessment of both the selectivity of the catheterization during the sequential AVS technique and the lateralization of aldosterone excess.

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