Download PDF
Horm Metab Res 2010; 42(6): 429-434
DOI: 10.1055/s-0029-1243257
Review

© Georg Thieme Verlag KG Stuttgart · New York

Comorbidities in Primary Aldosteronism

M. Quinkler1 , E. Born-Frontsberg1 , V. G. Fourkiotis1
  • 1Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany
Further Information

Publication History

received 31.08.2009

accepted 17.11.2009

Publication Date:
04 January 2010 (online)

Also available at
   Permissions and Reprints
Preview

Abstract

Patients presenting with primary aldosteronism experience more cardiovascular events than patients with essential hypertension independent of blood pressure. Therefore, the presence of primary aldosteronism should be detected, not only to determine the cause of hypertension, but also to prevent such complications. This review focuses on human data regarding increased end-organ damage and comorbidities in primary aldosteronism. Special emphasis is put on the effects of aldosterone excess on blood vessels, the heart, the kidney, and the brain. The data reviewed in our article demonstrate that primary aldosteronism is associated with a prevalence of cerebro-, cardiovascular and renal complications that are out of proportion to the blood pressure and benefits substantially from treatment in the long term. In this view, adrenalectomy and aldosterone antagonist treatment seem to be of considerable therapeutic value to control and limit the progression of comorbidities in primary aldosteronism.

Key words

renin-angiotensin-aldosterone system - aldosterone - hypertension

References

  • 1 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. 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
  • 2 Rayner BL, Opie LH, Davidson JS. The aldosterone/renin ratio as a screening test for primary aldosteronism.  S Afr Med J. 2000;  90 394-400
    Search in Google Scholar
  • 3 Fardella CE, Mosso L, Gomez-Sanchez C, Cortes P, Soto J, Gomez 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
  • 4 Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young WF. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore.  J Clin Endocrinol Metab. 2000;  85 2854-2859
    Search in Google Scholar
  • 5 Gordon RD, Stowasser M, Tunny TJ, Klemm SA, Rutherford JC. High incidence of primary aldosteronism in 199 patients referred with hypertension.  Clin Exp Pharmacol Physiol. 1994;  21 315-318
    Search in Google Scholar
  • 6 Lim PO, Dow E, Brennan G, Jung RT, MacDonald TM. High prevalence of primary aldosteronism in the Tayside hypertension clinic population.  J Hum Hypertens. 2000;  14 311-315
    Search in Google Scholar
  • 7 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
  • 8 Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young 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
  • 9 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
  • 10 Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, Papadopoulos N, Vogiatzis K, Zamboulis C. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study.  Lancet. 2008;  371 1921-1926
    Search in Google Scholar
  • 11 Kaplan NM. Is there an unrecognized epidemic of primary aldosteronism?.  Con Hypertension. 2007;  50 454-458
    Search in Google Scholar
  • 12 Mosso L, Carvajal C, Gonzalez 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
  • 13 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
  • 14 Eide IK, Torjesen PA, Drolsum A, Babovic A, Lilledahl NP. Low-renin status in therapy-resistant hypertension: a clue to efficient treatment.  J Hypertens. 2004;  22 2217-2226
    Search in Google Scholar
  • 15 Strauch B, Zelinka T, Hampf M, Bernhardt R, Widimsky J. Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region.  J Hum Hypertens. 2003;  17 349-352
    Search in Google Scholar
  • 16 Umpierrez GE, Cantey P, Smiley D, Palacio A, Temponi D, Luster K, Chapman A. Primary aldosteronism in diabetic subjects with resistant hypertension.  Diabetes Care. 2007;  30 1699-1703
    Search in Google Scholar
  • 17 Marney AM, Brown NJ. Aldosterone and end-organ damage.  Clin Sci (Lond). 2007;  113 267-278
    Search in Google Scholar
  • 18 Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system.  Ann N Y Acad Sci U S A. 2002;  970 89-100
    Search in Google Scholar
  • 19 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
  • 20 Taddei S, Virdis A, Mattei P, Salvetti A. Vasodilation to acetylcholine in primary and secondary forms of human hypertension.  Hypertension. 1993;  21 929-933
    Search in Google Scholar
  • 21 Rizzoni D, Paiardi S, Rodella L, Porteri E, De CC, Rezzani R, Boari GE, Zani F, Miclini M, Tiberio GA, Giulini SM, Rosei CA, Bianchi R, Rosei EA. Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism.  J Clin Endocrinol Metab. 2006;  91 2638-2642
    Search in Google Scholar
  • 22 Rizzoni D, Muiesan ML, Porteri E, Salvetti M, Castellano M, Bettoni G, Tiberio G, Giulini SM, Monteduro C, Garavelli G, Gabiti-Rosei E. Relations between cardiac and vascular structure in patients with primary and secondary hypertension.  J Am Coll Cardiol. 1998;  32 985-992
    Search in Google Scholar
  • 23 Holaj R, Zelinka T, Wichterle D, Petrak O, Strauch B, Widimsky J. Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension.  J Hypertens. 2007;  25 1451-1457
    Search in Google Scholar
  • 24 Bernini G, Galetta F, Franzoni F, Bardini M, Taurino C, Bernardini M, Ghiadoni L, Bernini M, Santoro G, Salvetti A. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism.  J Hypertens. 2008;  26 2399-2405
    Search in Google Scholar
  • 25 Strauch B, Petrak O, Wichterle D, Zelinka T, Holaj R, Widimsky J. Increased arterial wall stiffness in primary aldosteronism in comparison with essential hypertension.  Am J Hypertens. 2006;  19 909-914
    Search in Google Scholar
  • 26 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
  • 27 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
    Search in Google Scholar
  • 28 Rocha R, Stier CT. Pathophysiological effects of aldosterone in cardiovascular tissues.  Trends Endocrinol Metab. 2001;  12 308-314
    Search in Google Scholar
  • 29 Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.  N Engl J Med. 1999;  341 709-717
    Search in Google Scholar
  • 30 Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.  N Engl J Med. 2003;  348 1309-1321
    Search in Google Scholar
  • 31 Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.  Circulation. 2003;  108 1831-1838
    Search in Google Scholar
  • 32 Suzuki T, Abe H, Nagata S, Saitoh F, Iwata S, Ashizawa A, Kuramochi M, Omae T. Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism.  Am J Cardiol. 1988;  62 1224-1227
    Search in Google Scholar
  • 33 Rossi GP, Sacchetto A, Visentin P, Canali C, Graniero GR, Palatini P, Pessina AC. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism.  Hypertension. 1996;  27 1039-1045
    Search in Google Scholar
  • 34 Rossi GP, Sacchetto A, Pavan E, Palatini P, Graniero GR, Canali C, Pessina AC. Remodeling of the left ventricle in primary aldosteronism due to Conn's adenoma.  Circulation. 1997;  95 1471-1478
    Search in Google Scholar
  • 35 Tsioufis C, Tsiachris D, Dimitriadis K, Stougiannos P, Missovoulos P, Kakkavas A, Stefanadis C, Kallikazaros I. Myocardial and aortic stiffening in the early course of primary aldosteronism.  Clin Cardiol. 2008;  31 431-436
    Search in Google Scholar
  • 36 Shigematsu Y, Hamada M, Okayama H, Hara Y, Hayashi Y, Kodama K, Kohara K, Hiwada K. Left ventricular hypertrophy precedes other target-organ damage in primary aldosteronism.  Hypertension. 1997;  29 723-727
    Search in Google Scholar
  • 37 Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, Sechi LA. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism.  Hypertension. 2007;  50 911-918
    Search in Google Scholar
  • 38 Muiesan ML, Salvetti M, Paini A, Gabiti-Rosei C, Monteduro C, Galbassini G, Belotti E, Aggiusti C, Rizzoni D, Castellano M, Gabiti-Rosei E. Inappropriate left ventricular mass in patients with primary aldosteronism.  Hypertension. 2008;  52 529-534
    Search in Google Scholar
  • 39 Giacchetti G, Ronconi V, Turchi F, Agostinelli L, Mantero F, Rilli S, Boscaro M. Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study.  J Hypertens. 2007;  25 177-186
    Search in Google Scholar
  • 40 Porodko M, Auer J, Eber B. Conn's syndrome and atrial fibrillation.  Lancet. 2001;  357 1293-1294
    Search in Google Scholar
  • 41 Conn JW, Knopf RF. Clinical characteristics of primary aldosteronism from analysis of 145 cases.  Am J Surg. 1964;  107 159-172
    Search in Google Scholar
  • 42 Abdo A, Bebb RA, Wilkins GE. Ventricular fibrillation: an extreme presentation of primary hyperaldosteronism.  Can J Cardiol. 1999;  15 347-348
    Search in Google Scholar
  • 43 Nishimura M, Uzu T, Fujii T, Kuroda S, Nakamura S, Inenaga T, Kimura G. Cardiovascular complications in patients with primary aldosteronism.  Am J Kidney Dis. 1999;  33 261-266
    Search in Google Scholar
  • 44 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
  • 45 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. Cardio- and cerebrovascular comorbidites of hypo- and normokalemic primary aldosteronism: results of the German Conn's Registry.  J Clin Endocrinol Metab. 2009;  94 1124-1130
    Search in Google Scholar
  • 46 Fallo F, Veglio F, Bertello C, Sonino N, Della MP, 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
    Search in Google Scholar
  • 47 Duprez DA, Bauwens FR, De Buyzere ML, De Backer TL, Kaufman JM, Van HJ, Vermeulen A, Clement DL. Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension.  Am J Cardiol. 1993;  71 17A-20A
    Search in Google Scholar
  • 48 Lawes CM, Vander HS, Rodgers A. Global burden of blood-pressure-related disease, 2001.  Lancet. 2008;  371 1513-1518
    Search in Google Scholar
  • 49 Miro O, Pastor P, Pedrol E, Mallofre C, Grau JM, Cardellach F. Cerebral vascular complications in Conn's disease: report of two cases.  Neurologia. 1995;  10 209-211
    Search in Google Scholar
  • 50 Takeda R, Matsubara T, Miyamori I, Hatakeyama H, Morise T. Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension The Research Committee of Disorders of Adrenal Hormones in Japan.  J Endocrinol Invest. 1995;  18 370-373
    Search in Google Scholar
  • 51 Mulatero P, Caserta M, Bertello C, Schiavone D, Verhovez A, Giraudo G, Morello F, Veglio F. Aldosterone as an independent factor in cerebrovascular damage.  Clin Exp Hypertens. 2008;  30 785-797
    Search in Google Scholar
  • 52 Rocha R, Chander PN, Khanna K, Zuckerman A, Stier CT. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats.  Hypertension. 1998;  31 451-458
    Search in Google Scholar
  • 53 Stowasser M, Gordon RD. Familial hyperaldosteronism.  J Steroid Biochem Mol Biol. 2001;  78 215-229
    Search in Google Scholar
  • 54 Halimi JM, Mimran A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension.  J Hypertens. 1995;  13 1801-1802
    Search in Google Scholar
  • 55 Danforth DN, Orlando MM, Bartter FC, Javadpour N. Renal changes in primary aldosteronism.  J Urol. 1977;  117 140-144
    Search in Google Scholar
  • 56 Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, Kanashiki M, Saito Y, Ota H, Nose T. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population.  Kidney Int. 2006;  69 1264-1271
    Search in Google Scholar
  • 57 Tonelli M, Jose P, Curhan G, Sacks F, Braunwald E, Pfeffer M. Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial.  BMJ. 2006;  332 1426
    Search in Google Scholar
  • 58 Rossi GP, Mantero F, Pessina AC. Response to Renal Function in Primary Aldosteronism: Is Glomerular Hyperfiltration a Hallmark of Primary Aldosteronism Further Results from the Primary Aldosteronism? Prevalence in Hypertension (PAPY) Study.  Hypertension. 2006;  48 e111-e112
    Search in Google Scholar
  • 59 Ribstein J, Du CG, Fesler P, Mimran A. Relative glomerular hyperfiltration in primary aldosteronism.  J Am Soc Nephrol. 2005;  16 1320-1325
    Search in Google Scholar
  • 60 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
  • 61 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. Risk Factors Associated with a Low Glomerular Filtration Rate in Primary Aldosteronism.  J Clin Endocrinol Metab. 2009;  94 869-875
    Search in Google Scholar
  • 62 Fox CS, Larson MG, Hwang SJ, Leip EP, Rifai N, Levy D, Benjamin EJ, Murabito JM, Meigs JB, Vasan RS. Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample.  Kidney Int. 2006;  69 2064-2069
    Search in Google Scholar
  • 63 Novello M, Catena C, Nadalini E, Colussi GL, Baroselli S, Chiuch A, Lapenna R, Bazzocchi M, Sechi LA. Renal cysts and hypokalemia in primary aldosteronism: results of long-term follow-up after treatment.  J Hypertens. 2007;  25 1443-1450
    Search in Google Scholar
  • 64 Calhoun DA, Nishizaka MK, Zaman MA, Harding SM. Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea.  Chest. 2004;  125 112-117
    Search in Google Scholar
  • 65 Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, Cofield SS, Harding SM, Calhoun DA. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension.  Chest. 2007;  131 453-459
    Search in Google Scholar
  • 66 Sonino N, Fallo F, Fava GA. Psychological aspects of primary aldosteronism.  Psychother Psychosom. 2006;  75 327-330
    Search in Google Scholar
  • 67 Khurshid KA, Weaver ME. Conn's syndrome presenting as depression.  Am J Psychiatry. 2005;  162 1226
    Search in Google Scholar
  • 68 Malinow KC, Lion JR. Hyperaldosteronism (Conn's disease) presenting as depression.  J Clin Psychiatry. 1979;  40 358-359
    Search in Google Scholar
  • 69 Murck H, Held K, Ziegenbein M, Kunzel H, Koch K, Steiger A. The renin-angiotensin-aldosterone system in patients with depression compared to controls – a sleep endocrine study.  BMC Psychiatry. 2003;  3 15
    Search in Google Scholar
  • 70 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
  • 71 Colussi G, Catena C, Lapenna R, Nadalini E, Chiuch A, Sechi LA. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients.  Diabetes Care. 2007;  30 2349-2354
    Search in Google Scholar
  • 72 Marigliano A, Tedde R, Sechi LA, Pala A, Pisanu G, Pacifico A. Insulinemia and blood pressure. Relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment.  Am J Hypertens. 1990;  3 521-526
    Search in Google Scholar
  • 73 Sechi LA, Melis A, Tedde R. Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.  Metabolism. 1992;  41 1261-1266
    Search in Google Scholar
  • 74 Shimamoto K, Shiiki M, Ise T, Miyazaki Y, Higashiura K, Fukuoka M, Hirata A, Masuda A, Nakagawa M, Iimura O. Does insulin resistance participate in an impaired glucose tolerance in primary aldosteronism?.  J Hum Hypertens. 1994;  8 755-759
    Search in Google Scholar
  • 75 Ishimori M, Takeda N, Okumura S, Murai T, Inouye H, Yasuda K. Increased insulin sensitivity in patients with aldosterone producing adenoma.  Clin Endocrinol (Oxf). 1994;  41 433-438
    Search in Google Scholar
  • 76 Haluzik M, Sindelka G, Widimsky J, Prazny M, Zelinka T, Skrha J. Serum leptin levels in patients with primary hyperaldosteronism before and after treatment: relationships to insulin sensitivity.  J Hum Hypertens. 2002;  16 41-45
    Search in Google Scholar
  • 77 Catena C, Lapenna R, Baroselli S, Nadalini E, Colussi G, Novello M, Favret G, Melis A, Cavarape A, Sechi LA. Insulin sensitivity in patients with primary aldosteronism: a follow-up study.  J Clin Endocrinol Metab. 2006;  91 3457-3463
    Search in Google Scholar
  • 78 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
    Search in Google Scholar
  • 79 Matrozova J, Steichen O, Amar L, Zacharieva S, Jeunemaitre X, Plouin PF. Fasting plasma glucose and serum lipids in patients with primary aldosteronism: a controlled cross-sectional study.  Hypertension. 2009;  53 605-610
    Search in Google Scholar
  • 80 Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose.  Diabetes. 2000;  49 1751-1760
    Search in Google Scholar

Correspondence

M. QuinklerMD 

Clinical Endocrinology Charité Campus Mitte

Charité University Medicine

Berlin Charitéplatz 1

10117 Berlin

Germany

Phone: +49 30 450 514152

Fax: +49 30 450 514952

Email: marcus.quinkler@charite.de