In this issue of the JCEM, Kupers et al. (1) make a truly groundbreaking contribution to the management of primary aldosteronism (PA). In a retrospective study on consecutive patients investigated for PA over an 18-month period, they show that in 87 subjects with confirmed PA, adrenal venous sampling (AVS) lateralized hypersecretion in 49 of them. In this latter group, the adrenal oversecreting aldosterone could be predicted with 100% accuracy by the combination of a unilateral adrenal mass of at least 10 mm on imaging, plus a plasma [K ] on presentation of less than 3.5, and/or an effective glomerular filtration rate (eGFR) of at least 100 ml/min. In this way, 30% of patients with confirmed PA can confidently forego AVS and proceed directly to laparoscopic adrenalectomy. As the authors themselves note, this initial study needs to be validated on an independent sample. This should pose no great difficulty, given the potential availability of similarly curated (and importantly, recently derived) cohorts from other European countries and elsewhere. This accompanying editorial commentary will thus focus on two areas. The first is what follow-up studies might address, to extend as well as to validate the initial study by Kupers et al. (1). This is not meant to be picky and is a tribute tothestudy,rather thanacriticism; theadditional issuesstem largely from questions raised by the Kupers et al. (1) paper and may prompt subsequent investigators to build on, rather than merely repeat, the initial study. The second— quite different—area is to address the concerns about access to and cost of AVS voiced by Kupers et al. (1). The question there is whether, in addition to the substantial advance they have demonstrated, we need a radical reassessment of the management of PA as a whole and a truly fresh approach, on public health grounds, to what needs to be done. Thereareanumberofquestionsraisedbythe initial study. First, of those confirmed with PA, 49 of 87 subjects were lateralized, pointing to a prevalence of 56% of aldosteroneproducing adenoma (APA) as responsible for aldosterone hypersecretion—a percentage higher than in most other reports,with theexceptionof some fromJapan.What thismay reflect are the relatively strict criteria applied for a positive aldosterone to renin ratio (ARR). One is the requirement of a baseline sitting/standing plasma aldosterone concentration of 500–550 pmol/liter (17–19 ng/dl). This is in addition to a positiveARRonat least twooccasions,where the lower level of active renin concentration is taken as 5 mU/ml, and a positive ARR set at 64 pmol/mU. Taken together, those cutoffs may exclude a group of patients with bilateral adrenal hyperplasia (BAH), who are included on perhaps more relaxed criteria elsewhere, and contribute to the more commonly reported 2:1 ratio of BAH to APA. Second, when a unilateral mass—regardless of patient age—is used for lateralization, the authors report six “false positives.” Five of those six were when the lateralization index (LI) fell short of the cutoff of the required 4-fold difference in aldosterone/cortisol ratio. It would be interesting to know whether these LI values were in the 2–4 range, and in particular whether these subjects—any or all—had plasma [K ] below 3.5 mmol/liter, and/or eGFR of at least 100 ml/min. In addition, it would be comforting toknowthat the remaining false-positive (who lateralized to the contralateral side) was biochemically cured and had an improved blood pressure after laparoscopic adrenalectomy on the basis of the AVS. Third, further refinement of the diagnostic nomogram [see Table 3 in Kupers et al. (1)] may be possible. As it stands, the presence of a characteristic at least 10-mm mass on imaging scores3points, plasma [K ] of less than3.5mmol/liter