Primary aldosteronism (PA) is characterised by aldosterone concentrations that are inappropriately high in relation to the activity of the renin-angiotensin system and that are not adequately suppressible by sodium loading [1
]. Recent studies have shown that PA, with its two main subtypes aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia (BAH), is the most common cause of secondary hypertension with a prevalence of approximately 5–10% among all hypertensive patients and an even higher prevalence among selected patients with advanced stages of hypertension and resistant hypertension [1
]. Importantly, patients suffering from PA have, independent of blood pressure, an increased risk of cardiovascular diseases and renal damage when compared to patients with essential hypertension [4
]. Therefore, screening for PA is important for hypertensive patients because detection of PA offers the opportunity for a targeted and effective treatment that significantly reduces the excess cardiovascular risk in patients with PA [7
]. After removal of the affected adrenal gland, patients with APA are cured from hypertension in approximately half of the cases with an improvement of hypertension in the remainder [1
]. This surgical therapy is also considered cost-effective [9
]. Patients with BAH respond well to drug therapy with mineralcorticoid receptor antagonists [1
Despite a wide acceptance of the aldosterone to active renin ratio (AARR) and the aldosterone to renin activity ratio (ARR) in screening for PA, the accuracy of these tests is still not well documented [10
], leading to many controversies and discrepancies in the use of AARR and ARR as a screening tool for PA which can be attributed to several causes: (1) There exists no generally accepted "gold standard" or "reference standard" for the diagnosis of PA, mainly because APA but not BAH can be unambiguously diagnosed (APA can be diagnosed by cure or improvement of arterial hypertension after surgical removal of an histopathologically confirmed adrenal adenoma). (2) In most diagnostic studies in this field only patients with a positive result of the screening test were referred to the chosen "reference standard test", which may be responsible for a verification bias with an overestimated accuracy of the screening test[10
]. (3) The results of the AARR and/or ARR are hardly comparable between different laboratories. Comparative studies have partially shown significantly different inter-laboratory results, mainly depending on the laboratory methods (assays) used [1
]. (4) The AARR and/or the ARR are also influenced by several other factors including e.g. medications, age, time of blood sampling, posture and dietary salt intake. It still needs to be clarified whether these above mentioned factors, in particular the use of beta-blockers, that were shown to decrease renin levels, significantly alter the accuracy of the AARR and/or ARR in screening for PA [1
]. It should also be pointed out that dietary salt loading has a significant impact on the renin-angiotensin aldosterone system (RAAS) with complex interactions and is thus a potential confounder for diagnostic procedures for PA [14
], which are largely performed without considering dietary sodium intake [1
]. In summary, previous studies reveal great discrepancies concerning the blood sampling conditions and laboratory methods for the determination of the AARR and/or ARR. Hence there is an urgent need for further evaluation and development of standardised and practicable diagnostic procedures for the detection of PA.
In our study we apply a standardised diagnostic procedure for PA in hypertensive patients that was derived from the most valid currently available data about this topic [1
]. Our main study aims are (1) to test the accuracy of the AARR in screening for PA (primary outcome), (2) to test the accuracy of the saline infusion test (SIT) and (3) to evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR as a screening test for PA. (4) In the first 100 patients of our study we aim to compare our laboratory methods for aldosterone and renin with other widely used and validated assays and (5) we will calculate the accuracy of the ARR in diagnosing PA and compare it with the accuracy of the AARR. (6) We will also evaluate the test characteristics of the SIT in comparison with PA diagnosis based on 24 hours urine aldosterone levels.