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Special Features: John W. Funder, Robert M. Carey, Carlos Fardella, Celso E. Gomez-Sanchez, Franco Mantero, Michael Stowasser, William F. Young, Jr., and Victor M. Montori Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2008; 93: 3266-3281 [Abstract] [Full text] [PDF]

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Eplerenone for the treatment of primary aldosteronism

Asterios Karagiannis, Panagiotis Anagnostis, Konstantinos Tziomalos, Vasilios G. Athyros, Dimitri P. Mikhailidis   (8 January 2009)

About suppression tests

Pierre-Francois PLOUIN, Laurence Amar   (30 October 2008)

Eplerenone for the treatment of primary aldosteronism 8 January 2009
Asterios Karagiannis, M.D. Aristotle University of Thessaloniki, Greece, Panagiotis Anagnostis, Konstantinos Tziomalos, Vasilios G. Athyros, Dimitri P. Mikhailidis Send letter to journal: Re: Eplerenone for the treatment of primary aldosteronism astkar{at}med.auth.gr Asterios Karagiannis, et al.	Funder et al. (1) state in their clinical practice guidelines for the diagnosis and treatment of patients with primary aldosteronism (PA) that there is lack of current clinical trial evidence for the use of eplerenone in PA. In a prospective, randomized, open-label, blinded-endpoint study, we showed, for the first time, that eplerenone is as effective as spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA) (2). Thirty-four patients were assigned to either spironolactone (50-400 mg/day) or eplerenone (50-200 mg/day) for 24 weeks. If the patients’ blood pressure (BP) was not at goal (<140/90 mmHg) at week 16, a daily dose of hydrochlorothiazide 12.5 mg was added, which was doubled if the BP remained uncontrolled at week 20. The primary endpoint was BP control (<140/90 mmHg) at 16 weeks (i.e. with aldosterone antagonist monotherapy). The majority of patients in both groups (82.4% of those assigned to eplerenone and 76.5% of those assigned to spironolactone; P = 1.00) reached the primary endpoint. There was no case of severe hyperkalemia. Two patients in the spironolactone group and 3 patients in the eplerenone group developed mild hyperkalemia, which resolved after decreasing the drug dose. In addition, 2 patients in the spironolactone group presented with bilateral painful gynaecomastia, which completely resolved after switching to eplerenone. In conclusion, eplerenone appears to have comparable antihypertensive efficacy with spironolactone and the reduced rate of endocrine side effects may improve compliance. However, more extensive studies are required to confirm these findings. The positive features of eplerenone should be weighed against its higher cost and the scarcity of data on its long-term effects in patients with IHA. References 1. Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young WF Jr, Montori VM 2008 Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 93:3266-3281 2. Karagiannis A, Tziomalos K, Papageorgiou A, Kakafika AI, Pagourelias ED, Anagnostis P, Athyros VG, Mikhailidis DP 2008 Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. Exp Opin Pharmacother 9:509-515
About suppression tests 30 October 2008
Pierre-Francois PLOUIN , Laurence Amar Send letter to journal: Re: About suppression tests Pierre-Francois.plouin{at}egp.aphp.fr Pierre-Francois PLOUIN, et al.	The Clinical Practice Guideline for case detection, diagnosis, and treatment of patients with primary aldosteronism (PA) published in the September 27th issue recommends that "patients with a positive aldosterone to renin ratio (ARR) undergo testing, by any of four confirmatory tests, to definitively confirm or exclude the diagnosis". The four confirmatory tests are suppression tests using oral sodium loading, oral fludrocortisone, oral captopril, and the saline infusion test (SIT). Evidence concerning this recommendation is discussed in Section 2.1, which reports three references, all from the same group. The most relevant of these papers is a careful analysis of the optimal cut-off values for plasma aldosterone concentrations determined after the SIT to confirm the diagnosis of PA (1). This analysis however does not compare the diagnostic performance of plasma aldosterone concentrations determined before and after the SIT. Therefore, it does not establish that post-SIT aldosterone concentrations provide a more effective reference for diagnosing PA than pre-test values. Besides, the sensitivity and the specificity of the post- SIT aldosterone values were 73 and 76% respectively, indicating that approximately one test in four may lead to a false positive or false negative result. Table 6 of the Guideline refers to many variants of the four suppression tests but does not address their diagnostic performances. The guideline does not mention recent reports showing that the SIT does not aid the diagnosis of PA in the majority of cases (2, 3). A conclusive evaluation of suppression tests in patients with presumed PA should compare how effective pre-test and post-test aldosterone concentrations are at predicting an outcome independent of peripheral hormone determinations, such as the presence of a lateralized aldosterone hypersecretion or a favorable hormonal or blood pressure outcome of adrenalectomy. Until such an evaluation is available, PA should not be excluded in patients with a high ARR and a hypersecretion of aldosterone that is reduced by a suppression test. Excluding patients with suppressible aldosterone hypersecretion from further work-up - as indicated in the guideline’s algorithm - precludes the diagnosis of "angiotensin-responsive" or "renin-responsive" aldosterone-producing adenomas, conditions that can be cured by unilateral adrenalectomy (4, 5). This exclusion is a loss of opportunity for the patients concerned, which may have severe hypertension. We agree that costly or invasive tests should not be undertaken on the basis a single positive ARR. Further work-up could be limited to patients with a positive ARR and sustained, absolute hypersecretion of aldosterone established without treatment (or on medications that have minimal effects on renin and aldosterone) who would benefit from the diagnosis, i.e. patients with severe or resistant hypertension who would accept an adrenalectomy if indicated. References 1. Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Montemurro D, Palumbo G, Rizzoni D, Rossi E, Semplicini A, Agabiti-Rosei E, Pessina AC, Mantero F; PAPY Study Investigators. Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone-producing adenoma. J Hypertens 2007; 25:1433-1442 2. Juutilainen AM, Voutilainen ET, Mykkanen L, Niskanen L Plasma aldosterone to renin ratio predicts treatment response in primary aldosteronism: is volume loading needed? Blood Press. 2005;14:245-250 3. Schirpenbach C, Seiler L, Maser-Gluth C, Rüdiger F, Nickel C, Beuschlein F, Reincke M. Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites. Eur J Endocrinol. 2006;154:865-873 4. Gordon RD, Gomez-Sanchez CE, Hamlet SM, Tunny TJ, Klemm SA. Angiotensin-responsive aldosterone-producing adenoma masquerades as idiopathic yperaldosteronism or low-renin essential hypertension. J Hypertens Suppl. 1987;5:S103-s106 5. Irony I, Kater CE, Biglieri EG et al. Correctable subsets of primary aldosteronism. Primary adrenal hyperplasia and renin responsive adenoma. Am J Hypertens 1990;3:576-582