Title: The Aldosterone-Renin Ratio and Primary Aldosteronism
Abstract: To the Editor: Montori and coworkers1Montori VM Schwartz GL Chapman AB Boerwinkle E Turner ST Validity of the aldosterone-renin ratio used to screen for primary aldosteronism.Mayo Clin Proc. 2001; 76: 877-882PubMed Scopus (85) Google Scholar have attempted to discredit the aldosterone-renin ratio (ARR) as a screening test for primary aldosteronism (PAL) by reporting that, in a group of 497 patients with "previously diagnosed essential hypertension," plasma aldosterone (PA) was only weakly dependent on plasma renin activity (PRA). The view is supported in an accompanying editorial by Kaplan.2Kaplan NM Caution about the overdiagnosis of primary aldosteronism [editorial].Mayo Clin Proc. 2001; 76: 875-876PubMed Google Scholar However, no one experienced in this area would have expected to find a simple relationship between PA and PRA, even in clinically normal individuals, because PA responds to potassium and corticotropin as well as to angiotensin II. It is for this reason that the ARR is only a screening test, which we measure at least twice before performing a fludrocortisone suppression test (FST) to confirm or exclude PAL.3Gordon RD Stowasser M Klemm SA Tunny TJ Primary aldosteronism and other forms of mineralocorticoid hypertension.in: Swales JD Textbook of Hypertension. Black-well Scientific Publications, London, England1994: 865-892Google Scholar, 4Gordon RD Stowasser M Rutherford JC Primary aldosteronism: are we diagnosing and operating on too few patients?.World J Surg. 2001; 25: 941-947Crossref PubMed Scopus (74) Google Scholar, 5Stowasser M Gordon RD Prevalence and diagnostic workup of primary aldosteronism: new knowledge and new approaches.Nephrology. 2001; 6: 119-126Crossref Scopus (18) Google Scholar Because Montori et al did not definitively exclude PAL (for example, by FST) in patients with elevated ARR, their cohort could have included many (even 50, based on recent reports) with PAL, in whom dependency of aldosterone on angiotensin II should be reduced or lost, contributing to a very high renin dependency of ARR values. Their study was also compromised by sampling after only 30 minutes of ambulation, insufficient time for PRA to maximally respond but sufficient time for the hepatic blow flow-mediated component of the rise in PA to be fully expressed. Early in the development of PAL, as autonomous aldosterone makes up a gradually increasing proportion of total production, the renin level declines progressively in an attempt to keep total aldosterone levels appropriate for the body's needs,4Gordon RD Stowasser M Rutherford JC Primary aldosteronism: are we diagnosing and operating on too few patients?.World J Surg. 2001; 25: 941-947Crossref PubMed Scopus (74) Google Scholar and ARR becomes more renin dependent. Montori et al postulate that the ARR would be of use only if it was a renin- independent measure of aldosterone, which of course it is not. In terms of patient management, does any of this matter if the ratio has proved useful in many hands to point to possible PAL, which is then confirmed by definitive testing and leading to cure of hypertension in many patients? The suggestion by Montori et al,1Montori VM Schwartz GL Chapman AB Boerwinkle E Turner ST Validity of the aldosterone-renin ratio used to screen for primary aldosteronism.Mayo Clin Proc. 2001; 76: 877-882PubMed Scopus (85) Google Scholar which is supported by Kaplan,2Kaplan NM Caution about the overdiagnosis of primary aldosteronism [editorial].Mayo Clin Proc. 2001; 76: 875-876PubMed Google Scholar to combine suppressed PRA with elevated PA to identify PAL will miss all those patients with PAL in whom PA levels have increased greatly but have not yet risen above the wide range of normal. A cutoff upright PA level of 20 ng/dL would have excluded one fifth of our patients with aldosterone-producing adenoma (APA). Kaplan2Kaplan NM Caution about the overdiagnosis of primary aldosteronism [editorial].Mayo Clin Proc. 2001; 76: 875-876PubMed Google Scholar suggests that inappropriate interpretation of the ARR may have led to overdiagnosis of PAL by groups (such as ours) reporting a marked increase in detection after its application to all (including normokalemic) hypertensive patients. However, he does not acknowledge our well-reported3Gordon RD Stowasser M Klemm SA Tunny TJ Primary aldosteronism and other forms of mineralocorticoid hypertension.in: Swales JD Textbook of Hypertension. Black-well Scientific Publications, London, England1994: 865-892Google Scholar, 4Gordon RD Stowasser M Rutherford JC Primary aldosteronism: are we diagnosing and operating on too few patients?.World J Surg. 2001; 25: 941-947Crossref PubMed Scopus (74) Google Scholar, 5Stowasser M Gordon RD Prevalence and diagnostic workup of primary aldosteronism: new knowledge and new approaches.Nephrology. 2001; 6: 119-126Crossref Scopus (18) Google Scholar cautious application and interpretation of the ARR when screening, or that we always perform FST in patients with raised ARR to definitively confirm or exclude PAL. We have repeatedly cautioned that computed tomographic scanning lacks reliability in differentiating APA from bilateral adrenal hyperplasia and can be frankly misleading by demonstrating nonfunctioning nodules.3Gordon RD Stowasser M Klemm SA Tunny TJ Primary aldosteronism and other forms of mineralocorticoid hypertension.in: Swales JD Textbook of Hypertension. Black-well Scientific Publications, London, England1994: 865-892Google Scholar, 4Gordon RD Stowasser M Rutherford JC Primary aldosteronism: are we diagnosing and operating on too few patients?.World J Surg. 2001; 25: 941-947Crossref PubMed Scopus (74) Google Scholar, 5Stowasser M Gordon RD Prevalence and diagnostic workup of primary aldosteronism: new knowledge and new approaches.Nephrology. 2001; 6: 119-126Crossref Scopus (18) Google Scholar Therefore we always perform adrenal venous sampling to differentiate unilateral from bilateral forms of PAL before recommending surgical or medical management. This approach has led to a 4-fold increase in our rate of removal of APAs. The Aldosterone-Renin Ratio and Primary Aldosteronism: In ResponseMayo Clinic ProceedingsVol. 77Issue 2PreviewMontori et al and I are aware that aldosterone production is not solely dependent on the renin-angiotensin mechanism. Nonetheless, virtually every proven case of autonomous PAL is associated with suppressed renin-angiotensin, even the 50 presumably renin-dependent cases. Full-Text PDF The Aldosterone-Renin Ratio and Primary Aldosteronism: In ResponseMayo Clinic ProceedingsVol. 77Issue 2PreviewBefore addressing performance characteristics of the ARR as a screening test, our study asked a more fundamental question: Is the assumption underlying its calculation valid?1 Several of the points raised by Stowasser and Gordon serve to further discredit the ARR. Their comment that "no one experienced in this area would have expected to find a simple relationship" between PA concentration and PRA is the essence of the argument against the ARR. The concomitant effects of potassium and corticotropin also underscore the advocates' disconnect in logic, since they do not propose dividing PA concentration by these other influential covariates. Full-Text PDF