Despite carrying a minimal risk of adrenal vein rupture and at variance with the guidelines, AVS is not used systematically at major referral centers worldwide. These findings represent an argument for defining guidelines for this clinically important but technically demanding procedure.

Abstract-Primary aldosteronism is the most common form of secondary hypertension. Mutations in the KCNJ5 gene have been described recently in aldosterone-producing adenomas (APAs). The aim of this study was to investigate the prevalence of KCNJ5 mutations in unselected patients with primary aldosteronism and their clinical, biological and molecular correlates. KCNJ5 sequencing was performed on somatic (APA, nϭ380) and peripheral (APA, nϭ344; bilateral adrenal hyperplasia, nϭ174) DNA of patients with primary aldosteronism, collected through the European Network for the Study of Adrenal Tumors. Transcriptome analysis was performed in 102 tumors. Somatic KCNJ5 mutations (p.Gly151Arg or p.Leu168Arg) were found in 34% (129 of 380) of APA. They were significantly more prevalent in females (49%) than males (19%; PϽ10 Ϫ3) and in younger patients (42.1Ϯ1.0 versus 47.6Ϯ0.7 years; PϽ10 Ϫ3 ) and were associated with higher preoperative aldosterone levels (455Ϯ26 versus 376Ϯ17 ng/L; Pϭ0.012) but not with therapeutic outcome after surgery. Germline KCNJ5 mutations were found neither in patients with APA nor those with bilateral adrenal hyperplasia. Somatic KCNJ5 mutations were specific for APA, because they were not identified in 25 peritumoral adrenal tissues or 16 cortisol-producing adenomas. Hierarchical clustering of transcriptome profiles showed that APAs with p.Gly151Arg or p.Leu168Arg mutations were indistinguishable from tumors without KCNJ5 mutations. In conclusion, although a large proportion of sporadic APAs harbors somatic KCNJ5 mutations, germline mutations are not similarly causative for bilateral adrenal hyperplasia. KCNJ5 mutation carriers are more likely to be females; younger age and higher aldosterone levels at diagnosis suggest that KCNJ5 mutations may be associated with a more florid phenotype of primary aldosteronism. H ypertension is a major cardiovascular risk factor that affects between 10% and 40% of the population in industrialized countries. Detection of secondary forms of hypertension is particularly important because it allows for the targeted management of the underlying disease. Primary aldosteronism (PA) is the most common form of secondary hypertension, with an estimated prevalence between 6% and 12% of hypertensives and as high as 20% in patients with resistant hypertension. 1-5 PA occurs as the result of a dysregulation of the mechanisms controlling adrenal aldosterone production, ultimately leading to hypertension with low plasma renin and elevated aldosterone sometimes associated with hypokalemia. Among subtypes of PA, aldosteroneproducing adenoma (APA) and bilateral adrenal hyperplasia (BAH; also known as idiopathic hyperaldosteronism) together account for Ϸ95% of cases. [1][2][3] Aldosterone production from the adrenal zona glomerulosa is tightly controlled to maintain electrolyte and fluid homeostasis by the kidney. Thus, the two most important physiological stimuli of aldosterone secretion are angiotensin II and serum potassium. Glomerulosa cell membrane depolarization leads to openi...

Abstract-Adrenocorticotropic hormone administration was proposed to overcome the biases associated with pulsatile aldosterone secretion during adrenal venous sampling, but the usefulness of different protocols of stimulation was never systematically assessed. We, therefore, compared the effects of a high dose (HD; 250 g IV as a bolus), a very low dose (VLD; 250 pg IV), and an intermediate dose (ID; 50 g/h) of adrenocorticotropic hormone on the selectivity index (SI) and the lateralization index in primary aldosteronism patients, using the diagnosis of aldosterone-producing adenoma, based on pathology and follow-up data, as a reference. The HD (nϭ47) significantly increased plasma cortisol concentration in infrarenal inferior vena cava (ϩ79%) blood and the SI on both sides (SI RIGHT ϩ113% and SI LEFT ϩ131%), as compared with baseline values. The ID (nϭ14) also markedly increased both plasma cortisol concentration inferior vena cava (ϩ93%) and the SI (SI RIGHT ϩ690% and SI LEFT ϩ410%); the very low dose (nϭ6) had no effect on either the plasma cortisol concentration or SI. In the patients with unilateral aldosterone-producing adenoma, the increase of selectivity with the HD and ID was counterbalanced by a confounding effect on the correct identification of the aldosterone-producing adenoma side, which was attributed to the wrong side in 3.0% and 12.5% with HD and ID, respectively. In conclusion, the HD and the ID, but not the very low dose, adrenocorticotropic hormone stimulation protocol facilitated the ascertainment of selectivity of adrenal vein catheterization. However, this favorable effect was overridden by a confounding effect on the identification of lateralized aldosterone excess to the aldosterone-producing adenoma side. Hence, we do not recommend adrenocorticotropic hormone stimulation.