Abstract
In primary aldosteronism (PA) the differentiation of unilateral aldosterone-producing adenomas (APA) from bilateral adrenal hyperplasia (BAH) is usually performed by adrenal venous sampling (AVS) and/or computed tomography (CT). CT alone often lacks the sensitivity to identify micro-APAs. Our objectives were to establish if steroid profiling could be useful for the identification of patients with micro-APAs and for the development of an online tool to differentiate micro-APAs, macro-APAs and BAH. The study included patients with PA (n = 197) from Munich (n = 124) and Torino (n = 73) and comprised 33 patients with micro-APAs, 95 with macro-APAs, and 69 with BAH. Subtype differentiation was by AVS, and micro- and macro-APAs were selected according to pathology reports. Steroid concentrations in peripheral venous plasma were measured by liquid chromatography-tandem mass spectrometry. An online tool using a random forest model was built for the classification of micro-APA, macro-APA and BAH. Micro-APA were classified with low specificity (33%) but macro-APA and BAH were correctly classified with high specificity (93%). Improved classification of micro-APAs was achieved using a diagnostic algorithm integrating steroid profiling, CT scanning and AVS procedures limited to patients with discordant steroid and CT results. This would have increased the correct classification of micro-APAs to 68% and improved the overall classification to 92%. Such an approach could be useful to select patients with CT-undetectable micro-APAs in whom AVS should be considered mandatory.
Highlights
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension characterized by aldosterone overproduction relative to suppressed plasma renin [1,2,3]
Complete clinical and biochemical success were less frequent in the micro-aldosterone-producing adenomas (APA) than in the macroAPA group (12.1% vs 40.0%, P=0.003, 84.8% vs 96.8%, P=0.023, respectively) whereas absent biochemical success was more prevalent in the micro-APA group (9.1% vs 1.1%, P=0.036)
We focussed on using this approach to identify patients with micro-APAs which are often missed by computed tomography (CT) in those centres that rely on CT for the differentiation of APA from bilateral adrenal hyperplasia (BAH)
Summary
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension characterized by aldosterone overproduction relative to suppressed plasma renin [1,2,3]. Patients with PA have an increased risk of cardiovascular and cerebrovascular events and renal disease progression relative to patients with primary hypertension including those with similar cardiovascular risk profiles [4,5,6,7]. Unilateral PA is mainly caused by an aldosterone-producing adenoma (APA) and is potentially curable by laparoscopic unilateral adrenalectomy whereas bilateral PA (bilateral adrenal hyperplasia [BAH]) is usually treated with a mineralocorticoid receptor antagonist (MRA). These specific treatment options emphasize the central role of an accurate differentiation of APA from BAH in the diagnostic work up of PA which is usually performed by computed tomography (CT) and adrenal venous sampling (AVS) [8]. AVS is a technicallydemanding and invasive procedure with non-standardized protocols and variable interpretation of results, and alternative approaches to reduce or even replace AVS for subtype differentiation in PA are currently sought [11,12,13,14,15,16]
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