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DOI: 10.1055/s-0043-119755
Is Primary Aldosteronism Still Largely Unrecognized?
Publication History
received
03 August 2017
accepted
06 September 2017
Publication Date:
16 November 2017 (online)
Abstract
Primary aldosteronism (PA) was first reported by Jerome W. Conn in 1954 when it was considered a rare disorder, only suspected in cases of hypertension and spontaneous hypokalemia. Over the last 30 years, with the wide application of the plasma aldosterone to plasma renin activity ratio as screening test, the clinical spectrum of PA has dramatically changed. Different studies displayed significant differences in term of patients investigated, diagnostic criteria and hormonal assays; however, large prospective studies with robust diagnostic criteria indicated that the prevalence of PA is around 6% of the general hypertensive population and 11% of the patients referred to hypertension centers. In light of these epidemiological studies, the Endocrine Society Guideline recommends the screening for PA of around 50% of patients with hypertension, and identifies the categories of patients at high risk for the disease. However, clinical data obtained from “real-life” show that the screening rate is much lower and PA remains an under-diagnosed and under-treated cause of secondary hypertension with an associated increased risk of cardio- and cerebrovascular mortality and morbidity.
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References
- 1 Mulatero P, Monticone S, Bertello C, Viola A, Tizzani D, Iannaccone A, Crudo V, Burrello J, Milan A, Rabbia F, Veglio F. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism . J Clin Endocrinol Metab 2013; 98: 4826-4833
- 2 Milliez P, Girerd X, Plouin P-F, Blacher J, Safar ME, Mourad J-J. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism . J Am Coll Cardiol 2005; 45: 1243-1248
- 3 Prejbisz A, Warchoł-Celińska E, Lenders JWM, Januszewicz A. Cardiovascular risk in primary hyperaldosteronism. Horm Metab Res 2015; 47: 973-980
- 4 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr. WF, Montori VM. Endocrine Society . Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline . J Clin Endocrinol Metab 2008; 93: 3266-3281
- 5 Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline . J Clin Endocrinol Metab 2016; 101: 1889-1916
- 6 Mulatero P, Monticone S, Burrello J, Veglio F, Williams TA, Funder J. Guidelines for primary aldosteronism: Uptake by primary care physicians in Europe . J Hypertens 2016; 34: 2253-2257
- 7 Käyser SC, Dekkers T, Groenewoud HJ, van der Wilt GJ, Carel Bakx J, van der Wel MC, Hermus AR, Lenders JW, Deinum J. Study heterogeneity and estimation of prevalence of primary aldosteronism: A systematic review and meta-regression analysis . J Clin Endocrinol Metab 2016; 101: 2826-2835
- 8 Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, Gabetti L, Mengozzi G, Williams TA, Rabbia F, Veglio F, Mulatero P. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice . J Am Coll Cardiol 2017; 69: 1811-1820
- 9 Rossi E, Perazzoli F, Negro A, Magnani A. Diagnostic rate of primary aldosteronism in Emilia-Romagna, Northern Italy, during 16 years (2000-2015) . J Hypertens 2017; 35: 1691-1697
- 10 Williams TA, JWM Lenders, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF, Gomez-Sanchez CE, Funder JW, Reincke M. Primary Aldosteronism Surgery Outcome (PASO) investigators . Outcomes after adrenalectomy for unilateral primary aldosteronism: An international consensus on outcome measures and analysis of remission rates in an international cohort . Lancet Diabetes Endocrinol 2017; 5: 689-699
- 11 Sato M, Morimoto R, Seiji K, Iwakura Y, Ono Y, Kudo M, Satoh F, Ito S, Ishibashi T, Takase K. Cost-effectiveness analysis of the diagnosis and treatment of primary aldosteronism in Japan . Horm Metab Res 2015; 47: 826-832
- 12 Conn JW. Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome . J Lab Clin Med 1955; 45: 3-17
- 13 Gittler RD, Fajans SS. Primary aldosteronism (Conn’s syndrome). J Clin Endocrinol Metab 1995; 80: 3438-3441
- 14 Conn JW, Cohen EL, Rovner DR. Suppression of plasma renin activity in primary aldosteronism . JAMA 1964; 190: 213-221
- 15 Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases . Am J Surg 1964; 107: 159-172
- 16 Kaplan NM. Hypokalemia in the hypertensive patient, with observations on the incidence of primary aldosteronism . Ann Intern Med 1967; 66: 1079-1090
- 17 Fishman LM, Kuchel O, Liddle GW, Michelakis AM, Gordon RD, Chick WT. Incidence of primary aldosteronism uncomplicated „essential“ hypertension. A prospective study with elevated aldosterone secretion and suppressed plasma renin activity used as diagnostic criteria . JAMA 1968; 205: 497-502
- 18 Kaplan NM. Diagnostics and techniques. Curr Opin Nephrol Hypertens 1994; 3: 627-628
- 19 Ganguly A. Primary aldosteronism. N Engl J Med 1998; 339: 1828-1834
- 20 Kaplan NM. Commentary on incidence of primary aldosteronism: current estimations based on objective data . Arch Intern Med 1969; 123: 152-154
- 21 Ledingham JGC. Secondary hypertension. In: Oxford textbook of medicine 2. Oxford University Press; 1987: 13382-13397
- 22 Biglieri EG, Kater CE. Internal Medicine. In: Disorder of the adrenal cortex. Brown 1991; 2188-2207
- 23 Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension . N Engl J Med 1991; 324: 1098-1104
- 24 Brunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT, Krakoff LR, Bard RH, Bühler FR. Essential hypertension: Renin and aldosterone, heart attack and stroke . N Engl J Med 1972; 286: 441-449
- 25 Bühler FR, Laragh JH, Sealey JE, Brunner HR. Plasma aldosterone-renin interrelationships in various forms of essential hypertension. Studies using a rapid assay of plasma aldosterone . Am J Cardiol 1973; 32: 554-561
- 26 Dunn PJ, Espiner EA. Outpatient screening tests for primary aldosteronism . Aust N Z J Med 1976; 6: 131-135
- 27 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
- 28 Gordon RD, Klemm SA, Stowasser M, Tunny TJ, Storie WJ, Rutherford JC. How common is primary aldosteronism? Is it the most frequent cause of curable hypertension? . J Hypertens Suppl 1993; 11: S310-S311
- 29 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
- 30 Mulatero P, Stowasser M, Loh K-C, 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
- 31 Gordon RD, Ziesak MD, Tunny TJ, Stowasser M, Klemm SA. Evidence that primary aldosteronism may not be uncommon: 12% incidence among antihypertensive drug trial volunteers . Clin Exp Pharmacol Physiol 1993; 20: 296-298
- 32 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
- 33 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
- 34 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
- 35 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
- 36 Westerdahl C, Bergenfelz A, Isaksson A, Wihl A, Nerbrand C, Valdemarsson S. High frequency of primary hyperaldosteronism among hypertensive patients from a primary care area in Sweden . Scand J Prim Health Care 2006; 24: 154-159
- 37 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
- 38 Fogari R, Preti P, Zoppi A, Rinaldi A, Fogari E, Mugellini A. Prevalence of primary aldosteronism among unselected hypertensive patients: A prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test . Hypertens Res 2007; 30: 111-117
- 39 Karashima S, Kometani M, Tsujiguchi H, Asakura H, Nakano S, Usukura M, Mori S, Ohe M, Sawamura T, Okuda R, Hara A, Takamura T, Yamagishi M, Nakamura H, Takeda Y, Yoneda T. Prevalence of primary aldosteronism without hypertension in the general population: Results in Shika study . Clin Exp Hypertens 2017; [Epub ahead of print]
- 40 Westerdahl C, Bergenfelz A, Isaksson A, Nerbrand C, Valdemarsson S. Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area . Scand J Prim Health Care 2011; 29: 57-62
- 41 Anderson GH, Blakeman N, Streeten DH. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients . J Hypertens 1994; 12: 609-615
- 42 Abdelhamid S, Muller-Lobeck H, Pahl S, Remberger K, Bonhof JA, Walb D, Rockel A. Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients . Arch Intern Med 1996; 156: 1190-1195
- 43 Brown MA, Cramp HA, Zammit VC, Whitworth JA. Primary hyperaldosteronism: a missed diagnosis in „essential hypertensives“? . Aust N Z J Med 1996; 26: 533-538
- 44 Rossi GP, Rossi E, Pavan E, Rosati N, Zecchel R, Semplicini A, Perazzoli F, Pessina AC. Screening for primary aldosteronism with a logistic multivariate discriminant analysis . Clin Endocrinol Oxf 1998; 49: 713-723
- 45 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
- 46 Rossi E, Regolisti G, Negro A, Sani C, Davoli S, Perazzoli F. High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among Italian hypertensives . Am J Hypertens 2002; 15: 896-902
- 47 Trenkel S, Seifarth C, Schobel H, Hahn EG, Hensen J. Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism . Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc 2002; 110: 80-85
- 48 Martell N, Rodriguez-Cerrillo M, Grobbee DE, López-Eady MD, Fernández-Pinilla C, Avila M, Fernández-Cruz A, Luque M. High prevalence of secondary hypertension and insulin resistance in patients with refractory hypertension . Blood Press 2003; 12: 149-154
- 49 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
- 50 Strauch B, Zelinka T, Hampf M, Bernhardt R, Widimsky Jr. J. Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region . J Hum Hypertens 2003; 17: 349-352
- 51 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
- 52 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
- 53 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
- 54 Morillas P, Castillo J, Quiles J, Núñez D, Guillén S, Bertomeu-González V, Pomares F, Bertomeu V. Prevalence of primary aldosteronism in hypertensive patients and its effect on the heart . Rev Esp Cardiol 2008; 61: 418-421
- 55 Ribeiro MJS, Figueiredo Neto JA, de Memória EV, Lopes M de C, Faria M dos S, Salgado Filho N, de Oliveira TC. Prevalence of primary hyperaldosteronism in a systemic arterial hypertension league . Arq Bras Cardiol 2009; 92: 39-45
- 56 Di Murro A, Petramala L, Cotesta D, Zinnamosca L, Crescenzi E, Marinelli C, Saponara M, Letizia C. Renin-angiotensin-aldosterone system in patients with sleep apnoea: Prevalence of primary aldosteronism . J Renin-Angiotensin-Aldosterone Syst JRAAS 2010; 11: 165-172
- 57 Matrozova JA, Zacharieva SZ, Kirilov GG, Boyanov MA. Prevalence of primary aldosteronism among bulgarian hypertensive patients . Cent Eur J Med 2010; 5: 399-405
- 58 Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LKG, Amaro ACS, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: The most common secondary cause of hypertension associated with resistant hypertension . Hypertension 2011; 58: 811-817
- 59 Ríos MC, Izquierdo A, Sotelo M, Honnorat E, Rodríguez Cuimbra S, Catay E, Popescu BM. Aldosterone/renin ratio in the diagnosis of primary aldosteronism . Medicina (Mex) 2011; 71: 525-530
- 60 Sigurjonsdottir HA, Gronowitz M, Andersson O, Eggertsen R, Herlitz H, Sakinis A, Wangberg B, Johannsson G. Unilateral adrenal hyperplasia is a usual cause of primary hyperaldosteronism. Results from a Swedish screening study . BMC Endocr Disord 2012; 12: 17
- 61 Yin G, Zhang S, Yan L, Wu M, Xu M, Li F, Cheng H. Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups . Endocrine 2012; 42: 182-189
- 62 Sang X, Jiang Y, Wang W, Yan L, Zhao J, Peng Y, Gu W, Chen G, Liu W, Ning G. Prevalence of and risk factors for primary aldosteronism among patients with resistant hypertension in China . J Hypertens 2013; 31: 1465-1471
- 63 Jansen PM, van den Born B-JH, Frenkel WJ, de Bruijne ELE, Deinum J, Kerstens MN, Smulders YM, Woittiez AJ, Wijbenga JAM, Zietse R, AHJ Danser, van den Meiracker AH. Test characteristics of the aldosterone-to-renin ratio as a screening test for primary aldosteronism . J Hypertens 2014; 32: 115-126
- 64 Noilhan C, Barigou M, Bieler L, Amar J, Chamontin B, Bouhanick B. Causes of secondary hypertension in the young population: A monocentric study . Ann Cardiol Angeiol (Paris) 2016; 65: 159-164
- 65 Galati S-J, Cheesman KC, Springer-Miller R, Hopkins SM, Krakoff L, Bagiella E, Zhuk RA, Ying TK, Amer C, Boyajian MK, Inabnet WB, Levine AC. Prevalence of primary aldosteronism in an urban hypertensive population . Endocr Pract 2016; 22: 1296-1302
- 66 Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension . Hypertension 2002; 40: 892-896
- 67 Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: Theory and therapy . Hypertension 2004; 43: 518-524
- 68 Gonzaga CC, Gaddam KK, Ahmed MI, Pimenta E, Thomas SJ, Harding SM, Oparil S, Cofield SS, Calhoun DA. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension . J Clin Sleep Med 2010; 6: 363-368
- 69 Barceló A, Piérola J, Esquinas C, de la Peña M, Arqué M, Alonso-Fernández A, Bauçà JM, Robles J, Barceló B, Barbé F. Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: effect of continuous positive airway pressure treatment . PloS One 2014; 9: e84362
- 70 Huby A-C, Antonova G, Groenendyk J, Gomez-Sanchez CE, Bollag WB, Filosa JA, Belin de Chantemèle EJ. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis . Circulation 2015; 132: 2134-2145
- 71 Sim JJ, Yan EH, Liu ILA, Rasgon SA, Kalantar-Zadeh K, Calhoun DA, Derose SF. Positive relationship of sleep apnea to hyperaldosteronism in an ethnically diverse population . J Hypertens 2011; 29: 1553-1559
- 72 Conn JW. Hypertension, the potassium ion and impaired carbohydrate tolerance . N Engl J Med 1965; 273: 1135-1143
- 73 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
- 74 Reincke M, Meisinger C, Holle R, Quinkler M, Hahner S, Beuschlein F, Bidlingmaier M, Seissler J, Endres S. Participants of the German Conn’s Registry . Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn’s Registry . Horm Metab Res 2010; 42: 435-439
- 75 Williams TA, Monticone S, Urbanet R, Bertello C, Giraudo G, Vettor R, Fallo F, Veglio F, Mulatero P. Genes implicated in insulin resistance are down-regulated in primary aldosteronism patients . Mol Cell Endocrinol 2012; 355: 162-168
- 76 Whaley-Connell A, Sowers JR. Aldosterone and Risk for Insulin Resistance. Hypertension 2011; 58: 998-1000
- 77 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
- 78 Mukherjee JJ, Khoo CM, Thai AC, Chionh SB, Pin L, Lee KO. Type 2 diabetic patients with resistant hypertension should be screened for primary aldosteronism . Diabetes Vasc Dis Res 2010; 7: 6-13
- 79 Murase K, Nagaishi R, Takenoshita H, Nomiyama T, Akehi Y, Yanase T. Prevalence and clinical characteristics of primary aldosteronism in Japanese patients with type 2 diabetes mellitus and hypertension . Endocr J 2013; 60: 967-976
- 80 Tancredi M, Johannsson G, Eliasson B, Eggertsen R, Lindblad U, Dahlqvist S, Imberg H, Lind M. Prevalence of primary aldosteronism among patients with type 2 diabetes . Clin Endocrinol (Oxf) 2017; 87: 233-241
- 81 Rossi GP, Cesari M, Cuspidi C, Maiolino G, Cicala MV, Bisogni V, Mantero F, Pessina AC. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism . Hypertension 2013; 62: 62-69
- 82 Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates . Am J Cardiol 1998; 82: 2N-9N
- 83 Seccia TM, Caroccia B, Adler GK, Maiolino G, Cesari M, Rossi GP. Arterial hypertension, atrial fibrillation, and hyperaldosteronism: The triple trouble . Hypertension 2017; 69: 545-550
- 84 Reil J-C, Hohl M, Selejan S, Lipp P, Drautz F, Kazakow A, Münz BM, Müller P, Steendijk P, Reil G-H, Allessie MA, Böhm M, Neuberger H-R. Aldosterone promotes atrial fibrillation. Eur Heart J 2012; 33: 2098-2108
- 85 Rossi GP, Seccia TM, Gallina V, Muiesan ML, Leoni L, Pengo M, Ragazzo F, Caielli P, Belfiore A, Bernini G, Cipollone F, Cottone S, Ferri C, Giacchetti G, Grassi G, Letizia C, Maccario M, Olivieri O, Palumbo G, Rizzoni D, Rossi E, Sechi L, Volpe M, Mantero F, Morganti A, Pessina AC. Prospective appraisal of the prevalence of primary aldosteronism in hypertensive patients presenting with atrial flutter or fibrillation (PAPPHY Study): Rationale and study design . J Hum Hypertens 2013; 27: 158-163
- 86 Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas . Eur J Endocrinol 2003; 149: 273-285
- 87 Terzolo M, Stigliano A, Chiodini I, Loli P, Furlani L, Arnaldi G, Reimondo G, Pia A, Toscano V, Zini M, Borretta G, Papini E, Garofalo P, Allolio B, Dupas B, Mantero F, Tabarin A. Italian Association of Clinical Endocrinologists . AME position statement on adrenal incidentaloma. Eur J Endocrinol 2011; 164: 851-870