Fibrin clot properties and fibrinolysis in patients with endocrine hypertension due to aldosterone or catecholamines excess.

OBJECTIVE: The aim of the study was to investigate a new possible background of increased risk of cardiovascular events in two forms of endocrine hypertension: in primary aldosteronism (PA) and pheochromocytoma/paraganglioma (PPGL) in comparison to essential hypertension (EHT). CONTEXT: Prothrombotic properties of the fibrin clot structure, impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk. DESIGN: Patients with PA and PPGL were evaluated at baseline and re-evaluated 3 months after causative treatment. At baseline PA and PPGL patients were compared to matched EHT patients and to healthy controls. PATIENTS: The study included 35 patients with PA, 16 patients with PPGL and two reference groups of patients with EHT (32 and 22 patients) and healthy controls (35 and 23 subjects). MEASUREMENTS: All subjects underwent evaluation according to the study protocol that included plasma fibrin clot permeability (Ks), clot lysis time, endogenous thrombin potential. RESULTS: There were no differences in clot structure and fibrinolytic activity in PA and PPGL patients as compared to matched patients with EHT, whereas all hypertensive groups were characterized by more compact fibrin clot structure, faster clot formation and enhanced thrombin generation in comparison to healthy controls. Both in PA and PPGL patients, fibrin clot properties and fibrinolytic parameters remained stable after the causative treatment. CONCLUSIONS: Patients with PA and PPGL are at a prothrombic state comparable to patients with EHT. The results suggest the higher risk of cardiovascular events observed in hypertensive PA and PPGL as compared to EHT is not mediated through investigated prothrombic mechanisms.

A single-centre experience of the implementation of adrenal vein sampling procedure: the impact on the diagnostic work-up in primary aldosteronism.

BACKGROUND: Primary aldosteronism is one of the most common causes of secondary hypertension. Adrenal vein sampling (AVS) remains a "gold standard" procedure in differentiation between unilateral (adenoma) and bilateral (hyperplasia) disease. AIM: The aim of this study was to present our single-centre experience in establishing and implementating the AVS procedure. METHODS: All patients had primary aldosteronism confirmed in a salt-infusion test. AVS was performed sequentially during a continuous intravenous infusion of cosyntropin and was preceded by multislice contrast-enhanced computed tomography (CT) examination of adrenal glands performed a few weeks before AVS in the majority of patients. AVS was regarded as successful if the ratio of each adrenal vein cortisol to inferior vena cava cortisol levels (selectivity index [SI]) was higher than 3.0. In the case of failure, a second attempt was considered in a few weeks. Patients were divided into four groups according to the order of the procedure by quartiles. RESULTS: Between 31 May, 2012 and 5 May, 2016, AVS was performed in 124 patients (69% males, aged 55.3 ± 10.3 years) and was successful in 120 (96.8%) patients. All failed cases were due to the failure of cannulation of the right adrenal vein. The first-attempt success rate was 94.3% (117 of 124 patients) and increased from 83.9% in the first 31 patients to 100% in the last 31 patients. Similarly, the overall success rate increased from 93.5% to 100%. The right SI was significantly higher than the left one (26.4 vs. 11.0, p < 0.0001). Both indices did not differ across quartiles of patients. No complications occurred during the procedure. CONCLUSIONS: The AVS procedure, preceded by adrenal CT, may be implemented into daily diagnostic practice safely with an excellent success rate.

Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.

BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52·7 [IQR 43·9-56·8] vs 53·2 [44·0-56·8], p=0·83; RAND-36 mental scores 49·8 [43·1-54·6] vs 52·7 [44·9-55·5], p=0·17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0·25). A non-significant mean difference of 0·05 (95% CI -0·04 to 0·13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of €2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of €30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0·2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. INTERPRETATION: Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism. FUNDING: Netherlands Organisation for Health Research and Development-Medical Sciences, Institute of Cardiology, Warsaw.

Primary aldosteronism - recent progress and current concepts.

Primary aldosteronism is the commonest form of hormone-related hypertension, with an estimated prevalence of 6-13% in the generalpopulation of hypertensive patients. Among patients with resistant hypertension, the proportion of PA is even higher. Through intensiveresearch in the field of basic science and the creation of large registries of patients with PA, it is possible to understand the effect ofexcess aldosterone not only on the cardiovascular system but also on the morphology and function of the other organs. Recent researchhas highlighted the differences in the regulation of calcium metabolism in patients with adrenal adenomas and PA. A lot of attention hasbeen paid to the improvement of diagnostic methods, with particular emphasis on adrenal vein sampling, which is becoming increasinglyimportant. In recent years there have been many publications on the prevalence of mutations in the potassium channel in patients withadrenal tumours and PA. A new form of familial hyperaldosteronism - FIII, has also been distinguished. Treatment of patients with PAstill relies on the use of mineralocorticoid receptor antagonists or adrenalectomy, preferably preceded by a confirmation of aldosteronesecretion lateralisation by adrenal vein sampling.