PDF herunterladen
Horm Metab Res 2010; 42(6): 406-410
DOI: 10.1055/s-0029-1246186
Review

© Georg Thieme Verlag KG Stuttgart · New York

Confirmatory Tests in the Diagnosis of Primary Aldosteronism

P. Mulatero1 , S. Monticone1 , C. Bertello1 , G. Mengozzi2 , D. Tizzani1 , A. Iannaccone1 , F. Veglio1
  • 1Division of Internal Medicine and Hypertension Unit, Department of Medicine and Experimental Oncology, University of Torino, Torino, Italy
  • 2Clinical Chemistry Laboratory, AOU San Giovanni Battista, Torino, Italy
Weitere Informationen

Publikationsverlauf

received 29.09.2009

accepted 14.12.2009

Publikationsdatum:
29. Januar 2010 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Primary aldosteronism is the most common form of secondary hypertension and patients with hyperaldosteronism are more prone to premature cardiovascular complications compared to essential hypertensives. The diagnostic flow-chart for the diagnosis of PA is performed in three steps: a) screening; b) confirmation; and c) subtype differentiation. Instead of proceeding directly to subtype classification, the recently published Endocrine Society Guidelines recommend that patients with a positive ARR should undergo a confirmatory test, in order to definitively confirm or exclude the diagnosis of PA. The Guidelines recognize four testing procedures: oral sodium loading, saline infusion, fludrocortisone suppression, and captopril challenge. Herein we discuss the diagnostic protocols for these confirmatory tests and highlight both the advantages and contraindications and we discuss studies in which these confirmatory tests have been compared.

Key words

saline load - aldosterone - captopril test - fludrocortisone - hyperaldosteronism

References

  • 1 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
    Google Scholar
  • 2 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
    Google Scholar
  • 3 Kaplan NM. The current epidemic of primary aldosteronism: causes and consequences.  J Hypertens. 2004;  22 863-869
    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
    Google Scholar
  • 5 Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension.  Hypertension. 2002;  40 892-896
    Google Scholar
  • 6 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
    Google Scholar
  • 7 Mulatero P, Bertello C, Verhovez A, Rossato D, Giraudo G, Mengozzi G, Limerutti G, Avenatti E, Tizzani D, Veglio F. Differential diagnosis of primary aldosteronism subtypes.  Curr Hypertens Rep. 2009;  11 217-223
    Google Scholar
  • 8 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourard JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism.  J Am Coll Cardiol. 2005;  45 1243-1248
    Google Scholar
  • 9 Born-Frontsberg E, Reincke M, Rump LC, Hahner S, Diederich S, Lorenz R, Allolio B, Seufert J, Schirpenbach C, Beuschlein F, Bidlingmaier M, Endres S, Quinkler M. Participants of the German Conn's Registry. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry.  J Clin Endocrinol Metab. 2009;  94 1125-1130
    Google Scholar
  • 10 Mulatero P, Milan A, Williams TA, Veglio F. Mineralocorticoid receptor blockade in the protection of target organ damage.  Cardiovasc Hematol Agents Med Chem.. 2006;  4 75-91
    Google Scholar
  • 11 Mulatero P, Verhovez A, Morello F, Veglio F. Diagnosis and treatment of low-renin hypertension.  Clin Endocrinol (Oxf). 2007;  67 324-334
    Google Scholar
  • 12 Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M, Rabbia F, Federspil G, Mulatero P. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism.  J Clin Endocrinol Metab. 2006;  91 454-459
    Google Scholar
  • 13 Fallo F, Della Mea P, Sonino N, Bertello C, Ermani M, Vettor R, Veglio F, Mulatero P. Adiponectin and insulin sensitivity in primary aldosteronism.  Am J Hypertens. 2007;  20 855-861
    Google Scholar
  • 14 Maule S, Mulatero P, Milan A, Leotta G, Caserta M, Bertello C, Rabbia F, Veglio F. QT interval in patients with primary aldosteronism and low-renin essential hypertension.  J Hypertens. 2006;  24 2459-2464
    Google Scholar
  • 15 Fallo F, Federspil G, Veglio F, Mulatero P. The metabolic syndrome in primary aldosteronism.  Curr Hypertens Rep. 2007;  9 106-111
    Google Scholar
  • 16 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
    Google Scholar
  • 17 Rossi GP, Sechi LA, Giacchetti G, Ronconi V, Strazzullo P, Funder JW. Primary aldosteronism: cardiovascular, renal and metabolic implications.  Trends Endocrinol Metab. 2008;  19 88-90
    Google Scholar
  • 18 Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM. A chimaeric 11β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.  Nature. 1992;  355 262-265
    Google Scholar
  • 19 Stowasser M, Gordon RD. Primary aldosteronism: from genesis to genetics.  Trends Endocrinol Metab. 2003;  14 310-317
    Google Scholar
  • 20 Sukor N, Mulatero P, Gordon RD, So A, Duffy D, Bertello C, Kelemen L, Jeske Y, Veglio F, Stowasser M. Further evidence for linkage of familial hyperaldosteronism type II at chromosome 7p22 in Italian as well as Australian and South American families.  J Hypertens. 2008;  26 1577-1582
    Google Scholar
  • 21 Geller DS, Zhang J, Wisgerhof MV, Shackleton C, Kashgarian M, Lifton RP. J A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism.  Clin Endocrinol Metab. 2008;  93 3117-3123
    Google Scholar
  • 22 Mulatero P. A new form of hereditary primary aldosteronism: familial hyperaldosteronism type III.  J Clin Endocrinol Metab. 2008;  93 2972-2974
    Google Scholar
  • 23 Mulatero P, Dluhy RG, Giacchetti G, Boscaro M, Veglio F, Stewart PM. Diagnosis of primary aldosteronism: from screening to subtype differentiation.  Trends Endocrinol Metab. 2005;  16 114-119
    Google Scholar
  • 24 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
    Google Scholar
  • 25 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
    Google Scholar
  • 26 Letavernier E, Peyrard S, Amar L, Zinzindohoué F, Fiquet B, Plouin PF. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma.  J Hypertens. 2008;  26 1816-1823
    Google Scholar
  • 27 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
    Google Scholar
  • 28 Pizzolo F, Corgnati A, Guarini P, Pavan C, Bassi A, Corrocher R, Olivieri O. Plasma aldosterone assays: comparison between chemiluminescence-based and RIA methods.  Clin Chem. 2006;  52 1431-1432
    Google Scholar
  • 29 Stowasser M, Gordon RD. Aldosterone assays: an urgent need for improvement.  Clin Chem. 2006;  52 1640-1642
    Google Scholar
  • 30 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
    Google Scholar
  • 31 Mosso LM, Carvajal CA, Maiz A, Ortiz EH, Castillo CR, Artigas RA, Fardella CE. A possible association between primary aldosteronism and a lower beta-cell function.  J Hypertens. 2007;  25 2125-2130
    Google Scholar
  • 32 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
    Google Scholar
  • 33 Mulatero P, Milan A, Fallo F, Regolisti G, Pizzolo F, Fardella C, Mosso L, Marafetti L, Veglio F, Maccario M. Comparison of confirmatory tests for the diagnosis of primary aldosteronism.  J Clin Endocrinol Metab. 2006;  91 2618-2623
    Google Scholar
  • 34 Giacchetti G, Mulatero P, Mantero F, Veglio F, Boscaro M, Fallo F. Primary aldosteronism, a major form of low renin hypertension: from screening to diagnosis.  Trends Endocrinol Metab. 2008;  19 104-108
    Google Scholar
  • 35 Sechi LA, Di Fabio A, Bazzocchi M, Uzzau A, Catena C. Intrarenal hemodynamics in primary aldosteronism before and after treatment.  J Clin Endocrinol Metab. 2009;  94 1191-1197
    Google Scholar
  • 36 Reincke M, Rump LC, Quinkler M, Hahner S, Diederich S, Lorenz R, Seufert J, Schirpenbach C, Beuschlein F, Bidlingmaier M, Meisinger C, Holle R, Endres S. Participants of German Conn's Registry. Risk factors associated with a low glomerular filtration rate in primary aldosteronism.  J Clin Endocrinol Metab. 2009;  94 869-875
    Google Scholar
  • 37 Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young Jr WF. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore.  J Clin Endocrinol Metab. 2000;  85 2854-2859
    Google Scholar
  • 38 Young WF. Primary aldosteronism: renaissance of a syndrome.  Clin Endocrinol (Oxf). 2007;  66 607-618
    Google Scholar
  • 39 Williams JS, Williams GH, Raji A, Jeunemaitre X, Brown NJ, Hopkins PN, Conlin PR. Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia.  J Hum Hypertens. 2006;  20 129-136
    Google Scholar
  • 40 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
    Google Scholar
  • 41 Lyons DF, Kem DC, Brown RD, Hanson CS, Carollo ML. Single dose captopril as a diagnostic test for primary aldosteronism.  J Clin Endocrinol Metab. 1983;  57 892-896
    Google Scholar
  • 42 Agharazii M, Douville P, Grose JH, Lebel M. Captopril suppression versus salt loading in confirming primary aldosteronism.  Hypertension. 2001;  37 1440-1443
    Google Scholar
  • 43 Castro OL, Yu X, Kem DC. Diagnostic value of the post-captopril test in primary aldosteronism.  Hypertension. 2002;  39 935-938
    Google Scholar
  • 44 Mulatero P, Bertello C, Garrone C, Rossato D, Mengozzi G, Verhovez A, Fallo F, Veglio F. Captopril test can give misleading results in patients with suspect primary aldosteronism.  Hypertension. 2007;  50 e26-e27
    Google Scholar
  • 45 Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Palumbo G, Rizzoni D, Rossi E, Agabiti-Rosei E, Pessina AC, Mantero F. Primary Aldosteronism Prevalence in Italy Study Investigators. Comparison of the captopril and the saline infusion test for excluding aldosterone-producing adenoma.  Hypertension. 2007;  50 424-431
    Google Scholar
  • 46 Omura M, Saito J, Yamaguchi K, Kakuta Y, Nishikawa T. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.  Hypertens Res. 2004;  27 193-202
    Google Scholar
  • 47 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
    Google Scholar
  • 48 Giacchetti G, Ronconi V, Lucarelli G, Boscaro M, Mantero F. Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: need for a standardized protocol.  J Hypertens. 2006;  24 737-745
    Google Scholar
  • 49 Wu VC, Chang HW, Liu KL, Lin YH, Chueh SC, Lin WC, Ho YL, Huang JW, Chiang CK, Yang SY, Chen YM, Wang SM, Huang KH, Hsieh BS, Wu KD. TAIPAI Study Group . Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests.  Am J Hypertens. 2009;  22 821-827
    Google Scholar
  • 50 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
    Google Scholar
  • 51 Gordon RD, Laragh JH, Funder JW. Low renin hypertensive states: perspectives, unsolved problems, future research.  Trends Endocrinol Metab. 2005;  16 108-113
    Google Scholar
  • 52 Sealey JE, Gordon RD, Mantero F. Plasma renin and aldosterone measurements in low renin hypertensive states.  Trends Endocrinol Metab. 2005;  16 86-91
    Google Scholar
  • 53 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
    Google Scholar

Correspondence

P. Mulatero

Medicina Interna 4 e Centro Ipertensione

AOU S. Giovanni Battista

Via Genova 3

10126 Torino

Italy

Telefon: +39 011 6336959/20

Fax: +39 011 6336931

eMail: paolo.mulatero@libero.it