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Horm Metab Res 2010; 42(6): 382-391
DOI: 10.1055/s-0030-1248326
Review

© Georg Thieme Verlag KG Stuttgart · New York

Aldosterone to Renin Ratio – A Reliable Screening Tool for Primary Aldosteronism?

A. Tomaschitz1 [*] , S. Pilz1 [*]
  • 1Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria
Further Information

Publication History

received 29.09.2009

accepted 02.02.2010

Publication Date:
11 March 2010 (online)

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Abstract

Primary aldosteronism (PA) is defined as inappropriately high and (relatively or absolutely) autonomous aldosterone secretion, which is not adequately suppressible by sodium loading. Recent evidence shows that the PA prevalence ranges from 3 to 32%. This high prevalence of PA is suggested to be the result of both more intense screening for PA and improvement of laboratory procedures. Inappropriate high aldosterone secretion is paralleled by severe target organ damage, underlining the importance for the identification of PA at an early stage. The aldosterone to renin ratio (ARR), which reflects aldosterone hypersecretion in regard to its principal trophin renin, is currently considered the most reliable tool for PA screening. Accumulating evidence, however, points to a considerable intra-individual variation of this ratio, emphasizing the importance of standardized screening procedures. In particular, laboratory methods, posture, antihypertensive medication, and dietary salt intake are significant effectors of ARR variation. Furthermore, differentiation between low-renin essential hypertension and PA is difficult and probably arbitrary. It is the purpose of the present review to issue the reliability of the ARR as a screening tool for PA. This review also provides an overview about the physiology of the renin-angiotensin-aldosterone system, highlights current laboratory methods for aldosterone and renin determination, and addresses potential influence factors on the ARR.

Key words

aldosterone to renin ratio - primary aldosteronism - adrenal adenoma - adrenal cortex

References

  • 1 Conn JW. Primary aldosteronism.  J Lab Clin Med. 1955;  45 661-664
    Search in Google Scholar
  • 2 Young WF. Primary aldosteronism: renaissance of a syndrome.  Clin Endocrinol (Oxf). 2007;  66 607-618
    Search in Google Scholar
  • 3 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr WF, Montori VM. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline.  J Clin Endocrinol Metab. 2008;  93 3266-3281
    Search in Google Scholar
  • 4 Mosso L, Carvajal C, González A, Barraza A, Avila F, Montero J, Huete A, Gederlini A, Fardella CE. Primary aldosteronism and hypertensive disease.  Hypertension. 2003;  42 161-165
    Search in Google Scholar
  • 5 Fardella CE, Mosso L, Gómez-Sánchez C, Cortés P, Soto J, Gómez L, Pinto M, Huete A, Oestreicher E, Foradori A, Montero J. Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology.  J Clin Endocrinol Metab. 2000;  85 1863-1867
    Search in Google Scholar
  • 6 Olivieri O, Ciacciarelli A, Signorelli D, Pizzolo F, Guarini P, Pavan C, Corgnati A, Falcone S, Corrocher R, Micchi A, Cressoni C, Blengio G. Aldosterone to Renin ratio in a primary care setting: the Bussolengo study.  J Clin Endocrinol Metab. 2004;  89 4221-4226
    Search in Google Scholar
  • 7 Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young Jr WF. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents.  J Clin Endocrinol Metab. 2004;  89 1045-1050
    Search in Google Scholar
  • 8 Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension.  Hypertension. 2002;  40 892-896
    Search in Google Scholar
  • 9 Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F. PAPY Study Investigators . A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients.  J Am Coll Cardiol. 2006;  48 2293-2300
    Search in Google Scholar
  • 10 Vasan RS, Evans JC, Larson MG, Wilson PW, Meigs JB, Rifai N, Benjamin EJ, Levy D. Serum aldosterone and the incidence of hypertension in nonhypertensive persons.  N Engl J Med. 2004;  351 33-41
    Search in Google Scholar
  • 11 Tanabe A, Naruse M, Naruse K, Hase M, Yoshimoto T, Tanaka M, Seki T, Demura R, Demura H. Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension.  Hypertens Res. 1997;  20 85-90
    Search in Google Scholar
  • 12 Sechi LA, Novello M, Lapenna R, Baroselli S, Nadalini E, Colussi GL, Catena C. Long-term renal outcomes in patients with primary aldosteronism.  JAMA. 2006;  295 2638-2645
    Search in Google Scholar
  • 13 Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA. Cardiovascular outcomes in patients with primary aldosteronism after treatment.  Arch Intern Med. 2008;  168 80-85
    Search in Google Scholar
  • 14 Ritz E, Tomaschitz A. Aldosterone, a vasculotoxic agent – novel functions for an old hormone.  Nephrol Dial Transplant. 2009;  24 2302-2305
    Search in Google Scholar
  • 15 Born-Frontsberg E, Reincke M, Beuschlein F, Quinkler M. Tumor size of Conn's adenoma and comorbidities.  Horm Metab Res. 2009;  41 785-788
    Search in Google Scholar
  • 16 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism.  J Am Coll Cardiol. 2005;  45 1243-1248
    Search in Google Scholar
  • 17 Tomaschitz A, Pilz S, Ritz E, Meinitzer A, Boehm BO, Maerz W. Plasma aldosterone levels are associated with increased cardiovascular mortality.  Eur Heart J. 2010;  ; doi:10.1093/eurheartj/ehq019
    Search in Google Scholar
  • 18 Rossi GP, Pessina AC, Heagerty AM. Primary aldosteronism: an update on screening, diagnosis and treatment.  J Hypertens. 2008;  26 613-621
    Search in Google Scholar
  • 19 Sukor N, Gordon RD, Ku YK, Jones M, Stowasser M. Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year single center experience.  J Clin Endocrinol Metab. 2009;  94 2437-2445
    Search in Google Scholar
  • 20 Pilz S, Tomaschitz A, März W. Diagnostic procedures for primary aldosteronism.  J Lab Med. 2009;  33 ((4)) 202-209
    Search in Google Scholar
  • 21 McKenna TJ, Sequeira SJ, Heffernan A, Chambers J, Cunningham S. Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism.  J Clin Endocrinol Metab. 1991;  73 952-957
    Search in Google Scholar
  • 22 Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C, Smithers BM. High rate of detection of primary aldosteronism, including surgically treatable forms, after ‘non-selective’ screening of hypertensive patients.  J Hypertens. 2003;  21 2149-2157
    Search in Google Scholar
  • 23 Tiu SC, Choi CH, Shek CC, Ng YW, Chan FK, Ng CM, Kong AP. The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling.  J Clin Endocrinol Metab. 2005;  90 72-78
    Search in Google Scholar
  • 24 Hirohara D, Nomura K, Okamoto T, Ujihara M, Takano K. Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives.  J Clin Endocrinol Metab. 2001;  86 4292-4298
    Search in Google Scholar
  • 25 Dunn PJ, Espiner EA. Outpatient screening tests for primary aldosteronism.  Aust N Z J Med. 1976;  6 131-135
    Search in Google Scholar
  • 26 Hiramatsu K, Yamada T, Yukimura Y, Komiya I, Ichikawa K, Ishihara M, Nagata H, Izumiyama T. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients.  Arch Intern Med. 1981;  141 1589-1593
    Search in Google Scholar
  • 27 Montori VM, Young Jr. WF. Use of plasma aldosterone concentration-to-plasma renin activity ratio as a screening test for primary aldosteronism A systematic review of the literature.  Endocrinol Metab Clin North Am. 2002;  31 619-632 xi
    Search in Google Scholar
  • 28 Pilz S, Tomaschitz A, Stepan V, Obermayer-Pietsch B, Fahrleitner-Pammer A, Schweighofer N, Portugaller HR, Sourij H, Dobnig H, Meinitzer A, Pieber TR. Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism.  BMC Endocr Disord. 2009;  9 11
    Search in Google Scholar
  • 29 Persson PB. Renin: origin, secretion and synthesis.  J Physiol. 2003;  552 667-671
    Search in Google Scholar
  • 30 Hackenthal E, Paul M, Ganten D, Taugner R. Morphology, physiology, and molecular biology of renin secretion.  Physiol Rev. 1990;  70 1067-1116
    Search in Google Scholar
  • 31 Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.  J Clin Invest. 2002;  110 229-238
    Search in Google Scholar
  • 32 Pilz S, Tomaschitz A, Ritz E, Pieber TR. Vitamin D status and arterial hypertension: a systematic review.  Nat Rev Cardiol. 2009;  6 621-630
    Search in Google Scholar
  • 33 Wagner C, Jensen BL, Kramer BK, Kurtz A. Control of the renal renin system by local factors.  Kidney Int Suppl. 1998;  67 S78-S83
    Search in Google Scholar
  • 34 Schweda F, Kurtz A. Cellular mechanism of renin release.  Acta Physiol Scand. 2004;  181 383-390
    Search in Google Scholar
  • 35 Todorov V, Muller M, Schweda F, Kurtz A. Tumor necrosis factor-alpha inhibits renin gene expression.  Am J Physiol Regul Integr Comp Physiol. 2002;  283 R1046-R1051
    Search in Google Scholar
  • 36 Vinck WJ, Fagard RH, Vlietinck R, Lijnen P. Heritability of plasma renin activity and plasma concentration of angiotensinogen and angiotensin-converting enzyme.  J Hum Hypertens. 2002;  16 417-422
    Search in Google Scholar
  • 37 Brandenberger G, Follenius M, Muzet A, Ehrhart J, Schieber JP. Ultradian oscillations in plasma renin activity: their relationships to meals and sleep stages.  J Clin Endocrinol Metab. 1985;  61 280-284
    Search in Google Scholar
  • 38 Modlinger RS, Sharif-Zadeh K, Schneider G, Gutkin M. Circadian rhythm of plasma renin activity in primary hyperaldosteronism.  J Clin Endocrinol Metab. 1976;  42 361-364
    Search in Google Scholar
  • 39 Hurwitz S, Cohen RJ, Williams GH. Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest.  J Appl Physiol. 2004;  96 1406-1414
    Search in Google Scholar
  • 40 Brand E, Chatelain N, Mulatero P, Féry I, Curnow K, Jeunemaitre X, Corvol P, Pascoe L, Soubrier F. Structural analysis and evaluation of the aldosterone synthase gene in hypertension.  Hypertension. 1998;  32 198-204
    Search in Google Scholar
  • 41 Davies E, Holloway CD, Ingram MC, Inglis GC, Friel EC, Morrison C, Anderson NH, Fraser R, Connell JM. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2.  Hypertension. 1999;  33 703-707
    Search in Google Scholar
  • 42 Lim PO, Macdonald TM, Holloway C, Friel E, Anderson NH, Dow E, Jung RT, Davies E, Fraser R, Connell JM. Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio.  J Clin Endocrinol Metab. 2002;  87 4398-4402
    Search in Google Scholar
  • 43 Tanahashi H, Mune T, Takahashi Y, Isaji M, Suwa T, Morita H, Yamakita N, Yasuda K, Deguchi T, White PC, Takeda J. Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas.  J Clin Endocrinol Metab. 2005;  90 6226-6231
    Search in Google Scholar
  • 44 Tomaschitz A, Pilz S, Ritz E, Obermayer-Pietsch B, Pieber TR. Aldosterone and arterial hypertension.  Nat Rev Endocrinol. 2010;  6 83-93
    Search in Google Scholar
  • 45 Davies E, MacKenzie SM. Extra-adrenal production of corticosteroids.  Clin Exp Pharmacol Physiol. 2003;  30 437-445
    Search in Google Scholar
  • 46 Lemarie CA, Paradis P, Schiffrin EL. New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone.  J Mol Med. 2008;  86 673-678
    Search in Google Scholar
  • 47 Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA. The adrenal gland and ACTH.  Eur J Endocrinol. 1996;  135 739
    Search in Google Scholar
  • 48 Connell JM, MacKenzie SM, Freel EM, Fraser R, Davies E. A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function.  Endocr Rev. 2008;  29 133-154
    Search in Google Scholar
  • 49 Freel EM, Ingram M, Wallace AM, White A, Fraser R, Davies E, Connell JM. Effect of variation in CYP11B1 and CYP11B2 on corticosteroid phenotype and hypothalamic-pituitary-adrenal axis activity in hypertensive and normotensive subjects.  Clin Endocrinol (Oxf). 2008;  68 700-706
    Search in Google Scholar
  • 50 Reynolds RM, Walker BR, Phillips DI, Dennison EM, Fraser R, Mackenzie SM, Davies E, Connell JM. Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure.  Hypertension. 2009;  53 932-936
    Search in Google Scholar
  • 51 Quack I, Vonend O, Sellin L, Stegbauer J, Dekomien G, Rump LC. A tale of two patients with Mendelian hypertension.  Hypertension. 2008;  51 609-614
    Search in Google Scholar
  • 52 Reincke M, Beuschlein F, Latronico AC, Arlt W, Chrousos GP, Allolio B. Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical neoplasms: correlation with P450scc expression.  Clin Endocrinol (Oxf). 1997;  46 619-626
    Search in Google Scholar
  • 53 Oelkers W, Brown JJ, Fraser R, Lever AF, Morton JJ, Robertson JI. Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man.  Circ Res. 1974;  40 69-77
    Search in Google Scholar
  • 54 Fliser D, Veldhuis JD, Dikow R, Schmidt-Gayk H, Ritz E. Effects of acute ACE inhibition on pulsatile renin and aldosterone secretion and their synchrony.  Hypertension. 1998;  32 929-934
    Search in Google Scholar
  • 55 Spat A, Hunyady L. Control of aldosterone secretion: a model for convergence in cellular signaling pathways.  Physiol Rev. 2004;  84 489-539
    Search in Google Scholar
  • 56 Willenberg HS, Schinner S, Ansurudeen I. New mechanisms to control aldosterone synthesis.  Horm Metab Res. 2008;  40 435-441
    Search in Google Scholar
  • 57 Emanuele E, Geroldi D, Minoretti P, Coen E, Politi P. Increased plasma aldosterone in patients with clinical depression.  Arch Med Res. 2005;  36 544-548
    Search in Google Scholar
  • 58 Katz FH, Romfh P, Smith JA. Episodic secretion of aldosterone in supine man; relationship to cortisol.  J Clin Endocrinol Metab. 1972;  35 178-181
    Search in Google Scholar
  • 59 Cugini P, Scavo D, Cornelissen G, Lee JY, Meucci T, Halberg F. Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake.  Horm Res. 1981;  15 7-27
    Search in Google Scholar
  • 60 Ahokoski O, Virtanen A, Kairisto V, Scheinin H, Huupponen R, Irjala K. Biological day-to-day variation and reference change limits of serum cortisol and aldosterone in healthy young men on unrestricted diets.  Clin Chem. 1999;  45 1097-1099
    Search in Google Scholar
  • 61 Lieb W, Larson MG, Benjamin EJ, Yin X, Tofler GH, Selhub J, Jacques PF, Wang TJ, Vita JA, Levy D, Vasan RS, Mitchell GF. Multimarker approach to evaluate correlates of vascular stiffness: the Framingham Heart Study.  Circulation. 2009;  119 37-43
    Search in Google Scholar
  • 62 Beevers DG, Brown JJ, Cuesta V, Davies DL, Fraser R, Lebel M, Lever AF, Morton JJ, Oelkers W, Robertson JI, Schalekamp MA, Tree M. Inter-relationships between plasma angiotensin II, arterial pressure, aldosterone and exchangeable sodium in normotensive and hypertensive man.  J Steroid Biochem. 1975;  6 779-784
    Search in Google Scholar
  • 63 Mulatero P, Verhovez A, Morello F, Veglio F. Diagnosis and treatment of low-renin hypertension.  Clin Endocrinol (Oxf). 2007;  67 324-334
    Search in Google Scholar
  • 64 Warnock DG. Low-renin and nonmodulating essential hypertension.  Hypertension. 1999;  34 395-397
    Search in Google Scholar
  • 65 Mulatero P, Schiavone D, Fallo F, Rabbia F, Pilon C, Chiandussi L, Pascoe L, Veglio F. CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism.  Hypertension. 2000;  35 694-698
    Search in Google Scholar
  • 66 Griffing GT, Wilson TE, Melby JC. Alterations in aldosterone secretion and metabolism in low renin hypertension.  J Clin Endocrinol Metab. 1990;  71 1454-1460
    Search in Google Scholar
  • 67 Drayer JI, Weber MA, Sealey JE, Laragh JH. Low and high renin essential hypertension: a comparison of clinical and biochemical characteristics.  Am J Med Sci. 1981;  281 135-142
    Search in Google Scholar
  • 68 Lim PO, Young WF, MacDonald TM. A review of the medical treatment of primary aldosteronism.  J Hypertens. 2001;  19 353-361
    Search in Google Scholar
  • 69 Sowers JR, Whaley-Connell A, Epstein M. Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension.  Ann Intern Med. 2009;  150 776-783
    Search in Google Scholar
  • 70 Weinberger MH, Fineberg NS. The diagnosis of primary aldosteronism and separation of two major subtypes.  Arch Intern Med. 1993;  153 2125-2129
    Search in Google Scholar
  • 71 Phillips JL, Walther MM, Pezzullo JC, Rayford W, Choyke PL, Berman AA, Linehan WM, Doppman JL, Gill Jr Jr JR. Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma.  J Clin Endocrinol Metab. 2000;  85 4526-4533
    Search in Google Scholar
  • 72 Schirpenbach C, Seiler L, Maser-Gluth C, Beuschlein F, Reincke M, Bidlingmaier M. Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps.  Clin Chem. 2006;  52 1749-1755
    Search in Google Scholar
  • 73 Hartman D, Sagnella GA, Chesters CA, Macgregor GA. Direct renin assay and plasma renin activity assay compared.  Clin Chem. 2004;  50 2159-2161
    Search in Google Scholar
  • 74 Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E, Ménard J. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement.  Clin Chem. 2009;  55 867-877
    Search in Google Scholar
  • 75 Montori 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;  76 877-882
    Search in Google Scholar
  • 76 Derkx FH, de Bruin RJ, van Gool JM, van den Hoek MJ, Beerendonk CC, Rosmalen F, Haima P, Schalekamp MA. Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity.  Clin Chem. 1996;  42 1051-1063
    Search in Google Scholar
  • 77 Deinum J, Derkx FH, Schalekamp MA. Improved immunoradiometric assay for plasma renin.  Clin Chem. 1999;  45 847-854
    Search in Google Scholar
  • 78 Dessì-Fulgheri P, Cocco F, Glorioso N, Bandiera F, Madeddu P, Rappelli A. Immunoradiometric assay of active renin in human plasma: comparison with plasma renin activity.  Clin Exp Hypertens A. 1987;  9 1383-1390
    Search in Google Scholar
  • 79 Sealey JE, Gordon RD, Mantero F. Plasma renin and aldosterone measurements in low renin hypertensive states.  Trends Endocrinol Metab. 2005;  16 86-91
    Search in Google Scholar
  • 80 Sealey JE, Moon C, Laragh JH, Alderman M. Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects.  Am J Med. 1976;  61 731-738
    Search in Google Scholar
  • 81 Sealey JE, Laragh JH. Aliskiren fails to lower blood pressure in patients who have either low PRA levels or whose PRA falls insufficiently or reactively rises.  Am J Hypertens. 2009;  22 112-121
    Search in Google Scholar
  • 82 Ismail AA, Walker PL, Cawood ML, Barth JH. Interference in immunoassay is an underestimated problem.  Ann Clin Biochem. 2002;  39 366-373
    Search in Google Scholar
  • 83 Herold DA, Fitzgerald RL. Immunoassays for testosterone in women: better than a guess?.  Clin Chem. 2003;  49 1250-1251
    Search in Google Scholar
  • 84 Turpeinen U, Hamalainen E, Stenman UH. Determination of aldosterone in serum by liquid chromatography-tandem mass spectrometry.  J Chromatogr B Analyt Technol Biomed Life Sci. 2008;  862 113-118
    Search in Google Scholar
  • 85 Ceglarek U, Kortz L, Leichtle A, Fiedler GM, Kratzsch J, Thiery J. Rapid quantification of steroid patterns in human serum by on-line solid phase extraction combined with liquid chromatography-triple quadrupole linear ion trap mass spectrometry.  Clin Chim Acta. 2009;  401 114-118
    Search in Google Scholar
  • 86 Taylor PJ, Cooper DP, Gordon RD, Stowasser M. Measurement of aldosterone in human plasma by semiautomated HPLC-tandem mass spectrometry.  Clin Chem. 2009;  55 1155-1162
    Search in Google Scholar
  • 87 Manolopoulou J, Mulatero P, Maser-Gluth C, Rossignol P, Spyroglou A, Vakrilova Y, Petersenn S, Zwermann O, Plouin PF, Reincke M, Bidlingmaier M. Saliva as a medium for aldosterone measurement in repeated sampling studies.  Steroids. 2009;  74 853-858
    Search in Google Scholar
  • 88 Fraser CG. Data on biological variation: essential prerequisites for introducing new procedures?.  Clin Chem. 1994;  40 1671-1673
    Search in Google Scholar
  • 89 Schwartz GL, Turner ST. Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity.  Clin Chem. 2005;  51 386-394
    Search in Google Scholar
  • 90 Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough.  Nat Clin Pract Nephrol. 2007;  3 486-492
    Search in Google Scholar
  • 91 Snoep JD, Hovens MM, Pasha SM, Frölich M, Pijl H, Tamsma JT, Huisman MV. Time-dependent effects of low-dose aspirin on plasma renin activity, aldosterone, cortisol, and catecholamines.  Hypertension. 2009;  54 1136-1142
    Search in Google Scholar
  • 92 Gallay BJ, Ahmad S, Xu L, Toivola B, Davidson RC. Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio.  Am J Kidney Dis. 2001;  37 699-705
    Search in Google Scholar
  • 93 Seifarth C, Trenkel S, Schobel H, Hahn EG, Hensen J. Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism.  Clin Endocrinol (Oxf). 2002;  57 457-465
    Search in Google Scholar
  • 94 Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.  Hypertension. 2002;  40 897-902
    Search in Google Scholar
  • 95 Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, Beuschlein F, Reincke M. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication.  Eur J Endocrinol. 2004;  150 329-337
    Search in Google Scholar
  • 96 Nishizaka MK, Pratt-Ubunama M, Zaman MA, Cofield S, Calhoun DA. Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension.  Am J Hypertens. 2005;  18 805-812
    Search in Google Scholar
  • 97 Komiya I, Yamada T, Takasu N, Asawa T, Akamine H, Yagi N, Nagasawa Y, Ohtsuka H, Miyahara Y, Sakai H, Sato A, Aizawa T. An abnormal sodium metabolism in Japanese patients with essential hypertension, judged by serum sodium distribution, renal function and the renin-aldosterone system.  J Hypertens. 1997;  15 65-72
    Search in Google Scholar
  • 98 Tanabe A, Naruse M, Takagi S, Tsuchiya K, Imaki T, Takano K. Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism.  J Clin Endocrinol Metab. 2003;  88 2489-2494
    Search in Google Scholar
  • 99 Lamarre-Cliche M, de Champlain J, Lacourcière Y, Poirier L, Karas M, Larochelle P. Effects of circadian rhythms, posture, and medication on renin-aldosterone interrelations in essential hypertensives.  Am J Hypertens. 2005;  18 56-64
    Search in Google Scholar
  • 100 Radke KJ, Izzo Jr. JL. Seasonal variation in haemodynamics and blood pressure-regulating hormones.  J Hum Hypertens. 2009 Sep 24;  [E Pub ahead of print]
    Search in Google Scholar
  • 101 Tsunoda K, Abe K, Goto T, Yasujima M, Sato M, Omata K, Seino M, Yoshinaga K. Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma.  J Clin Endocrinol Metab. 1986;  62 384-389
    Search in Google Scholar
  • 102 Fommei E, Ghione S, Ripoli A, Maffei S, Di Cecco P, Iervasi A, Turchi S. The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women.  J Hum Hypertens. 2009;  23 130-135
    Search in Google Scholar
  • 103 Pizzolo F, Raffaelli R, Memmo A, Chiecchi L, Pavan C, Guarini P, Guidi GC, Franchi M, Corrocher R, Olivieri O. Effects of female sex hormones and contraceptive pill on the diagnostic work-up for primary aldosteronism.  J Hypertens. 2010;  28 135-142
    Search in Google Scholar
  • 104 Hew-Butler T, Noakes TD, Soldin SJ, Verbalis JG. Acute changes in endocrine and fluid balance markers during high-intensity, steady-state, and prolonged endurance running: unexpected increases in oxytocin and brain natriuretic peptide during exercise.  Eur J Endocrinol. 2008;  159 729-737
    Search in Google Scholar
  • 105 Newton-Cheh C, Guo CY, Gona P, Larson MG, Benjamin EJ, Wang TJ, Kathiresan S, O'Donnell CJ, Musone SL, Camargo AL, Drake JA, Levy D, Hirschhorn JN, Vasan RS. Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample.  Hypertension. 2007;  49 846-856
    Search in Google Scholar
  • 106 Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ. Diagnosis and management of primary aldosteronism.  J Renin Angiotensin Aldosterone Syst. 2001;  2 156-169
    Search in Google Scholar
  • 107 Stowasser M, Gordon RD. Primary aldosteronism – careful investigation is essential and rewarding.  Mol Cell Endocrinol. 2004;  217 33-39
    Search in Google Scholar
  • 108 Jansen PM, Boomsma F, van den Meiracker AH. Aldosterone-to-renin ratio as a screening test for primary aldosteronism--the Dutch ARRAT Study.  Neth J Med. 2008;  66 220-228
    Search in Google Scholar
  • 109 Stowasser M. Update in primary aldosteronism.  J Clin Endocrinol Metab. 2009;  94 3623-3630
    Search in Google Scholar
  • 110 Celen O, O’Brien MJ, Melby JC, Beazley RM. Factors influencing outcome of surgery for primary aldosteronism.  Arch Surg. 1996;  131 646-650
    Search in Google Scholar
  • 111 Sawka AM, Young WF, Thompson GB, Grant CS, Farley DR, Leibson C, van Heerden JA. Primary aldosteronism: factors associated with normalization of blood pressure after surgery.  Ann Intern Med. 2001;  135 258-261
    Search in Google Scholar

1 Both authors contributed equally to the manuscript.

Correspondence

A. TomaschitzMD S. Pilz, MD 

Medical University of Graz

Department of Internal Medicine

Division of Endocrinology and Nuclear Medicine

Auenbruggerplatz 15

8036 Graz

Austria

Phone: +43/316/385 2383

Fax: +43/316/385 3428

Email: andreas.tomaschitz@gmx.at

Email: stefan.pilz@chello.at