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)

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.

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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 11 Kaplan NM. Is there an unrecognized epidemic of primary aldosteronism?.  Con Hypertension. 2007;  50 454-458
  • 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
  • 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
  • 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
  • 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
  • 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
  • 17 Marney AM, Brown NJ. Aldosterone and end-organ damage.  Clin Sci (Lond). 2007;  113 267-278
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 28 Rocha R, Stier CT. Pathophysiological effects of aldosterone in cardiovascular tissues.  Trends Endocrinol Metab. 2001;  12 308-314
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 40 Porodko M, Auer J, Eber B. Conn's syndrome and atrial fibrillation.  Lancet. 2001;  357 1293-1294
  • 41 Conn JW, Knopf RF. Clinical characteristics of primary aldosteronism from analysis of 145 cases.  Am J Surg. 1964;  107 159-172
  • 42 Abdo A, Bebb RA, Wilkins GE. Ventricular fibrillation: an extreme presentation of primary hyperaldosteronism.  Can J Cardiol. 1999;  15 347-348
  • 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
  • 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
  • 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
  • 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
  • 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
  • 48 Lawes CM, Vander HS, Rodgers A. Global burden of blood-pressure-related disease, 2001.  Lancet. 2008;  371 1513-1518
  • 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
  • 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
  • 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
  • 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
  • 53 Stowasser M, Gordon RD. Familial hyperaldosteronism.  J Steroid Biochem Mol Biol. 2001;  78 215-229
  • 54 Halimi JM, Mimran A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension.  J Hypertens. 1995;  13 1801-1802
  • 55 Danforth DN, Orlando MM, Bartter FC, Javadpour N. Renal changes in primary aldosteronism.  J Urol. 1977;  117 140-144
  • 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
  • 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
  • 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
  • 59 Ribstein J, Du CG, Fesler P, Mimran A. Relative glomerular hyperfiltration in primary aldosteronism.  J Am Soc Nephrol. 2005;  16 1320-1325
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 66 Sonino N, Fallo F, Fava GA. Psychological aspects of primary aldosteronism.  Psychother Psychosom. 2006;  75 327-330
  • 67 Khurshid KA, Weaver ME. Conn's syndrome presenting as depression.  Am J Psychiatry. 2005;  162 1226
  • 68 Malinow KC, Lion JR. Hyperaldosteronism (Conn's disease) presenting as depression.  J Clin Psychiatry. 1979;  40 358-359
  • 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
  • 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
  • 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
  • 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
  • 73 Sechi LA, Melis A, Tedde R. Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.  Metabolism. 1992;  41 1261-1266
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 80 Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose.  Diabetes. 2000;  49 1751-1760

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