Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Pathophysiology and clinical features of primary aldosteronism

William F Young, Jr, MD, MSc
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD


Nonsuppressible (primary) hypersecretion of aldosterone is an underdiagnosed cause of hypertension. The classic presenting signs of primary aldosteronism are hypertension and hypokalemia, but potassium levels are often normal in modern-day series of aldosteronomas.

The pathophysiology and clinical features of primary aldosteronism will be reviewed here. The treatment of this disorder and an approach to the diagnosis of hypertension and hypokalemia are discussed separately. (See "Treatment of primary aldosteronism" and "Diagnosis of primary aldosteronism".)


Renin-independent, incompletely suppressible (primary) hypersecretion of aldosterone is an increasingly recognized, but still underdiagnosed, cause of hypertension [1]; it is estimated to be responsible for 5 to 13 percent of hypertension in humans. Many subtypes of primary aldosteronism have been described since Conn's original report of the aldosterone-producing adenoma (APA) in 1954 [2-5].

The most frequent causes of primary aldosteronism include:

Bilateral idiopathic hyperaldosteronism (or idiopathic hyperplasia [IHA], 60 to 70 percent).


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jun 30, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101:1889.
  2. CONN JW. Aldosterone in clinical medicine; past, present, and future. AMA Arch Intern Med 1956; 97:135.
  3. Bravo EL, Tarazi RC, Dustan HP, et al. The changing clinical spectrum of primary aldosteronism. Am J Med 1983; 74:641.
  4. Mattsson C, Young WF Jr. Primary aldosteronism: diagnostic and treatment strategies. Nat Clin Pract Nephrol 2006; 2:198.
  5. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf) 2007; 66:607.
  6. Weisbrod AB, Webb RC, Mathur A, et al. Adrenal histologic findings show no difference in clinical presentation and outcome in primary hyperaldosteronism. Ann Surg Oncol 2013; 20:753.
  7. Masilamani S, Kim GH, Mitchell C, et al. Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney. J Clin Invest 1999; 104:R19.
  8. Bastl CP, Hayslett JP. The cellular action of aldosterone in target epithelia. Kidney Int 1992; 42:250.
  9. AUGUST JT, NELSON DH, THORN GW. Response of normal subjects to large amounts of aldosterone. J Clin Invest 1958; 37:1549.
  10. Gonzalez-Campoy JM, Romero JC, Knox FG. Escape from the sodium-retaining effects of mineralocorticoids: role of ANF and intrarenal hormone systems. Kidney Int 1989; 35:767.
  11. Hall JE, Granger JP, Smith MJ Jr, Premen AJ. Role of renal hemodynamics and arterial pressure in aldosterone "escape". Hypertension 1984; 6:I183.
  12. Yokota N, Bruneau BG, Kuroski de Bold ML, de Bold AJ. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest 1994; 94:1938.
  13. Wang XY, Masilamani S, Nielsen J, et al. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest 2001; 108:215.
  14. Guyton AC. Blood pressure control--special role of the kidneys and body fluids. Science 1991; 252:1813.
  15. Åkerström T, Crona J, Delgado Verdugo A, et al. Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter. PLoS One 2012; 7:e41926.
  16. Boulkroun S, Beuschlein F, Rossi GP, et al. Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. Hypertension 2012; 59:592.
  17. Azizan EA, Murthy M, Stowasser M, et al. Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. Hypertension 2012; 59:587.
  18. Xekouki P, Hatch MM, Lin L, et al. KCNJ5 mutations in the National Institutes of Health cohort of patients with primary hyperaldosteronism: an infrequent genetic cause of Conn's syndrome. Endocr Relat Cancer 2012; 19:255.
  19. Monticone S, Hattangady NG, Nishimoto K, et al. Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells. J Clin Endocrinol Metab 2012; 97:E1567.
  20. Azizan EA, Lam BY, Newhouse SJ, et al. Microarray, qPCR, and KCNJ5 sequencing of aldosterone-producing adenomas reveal differences in genotype and phenotype between zona glomerulosa- and zona fasciculata-like tumors. J Clin Endocrinol Metab 2012; 97:E819.
  21. Beuschlein F, Boulkroun S, Osswald A, et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 2013; 45:440.
  22. Williams TA, Monticone S, Schack VR, et al. Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. Hypertension 2014; 63:188.
  23. Azizan EA, Poulsen H, Tuluc P, et al. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet 2013; 45:1055.
  24. Scholl UI, Goh G, Stölting G, et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet 2013; 45:1050.
  25. Albiger NM, Sartorato P, Mariniello B, et al. A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion? Eur J Endocrinol 2011; 164:405.
  26. Zwermann O, Suttmann Y, Bidlingmaier M, et al. Screening for membrane hormone receptor expression in primary aldosteronism. Eur J Endocrinol 2009; 160:443.
  27. Saner-Amigh K, Mayhew BA, Mantero F, et al. Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas. J Clin Endocrinol Metab 2006; 91:1136.
  28. Lacroix A, Bourdeau I, Lampron A, et al. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf) 2010; 73:1.
  29. Teo AE, Garg S, Shaikh LH, et al. Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations. N Engl J Med 2015; 373:1429.
  30. Wisgerhof M, Carpenter PC, Brown RD. Increased adrenal sensitivity to angiotensin II in idiopathic hyperaldosteronism. J Clin Endocrinol Metab 1978; 47:938.
  31. Clore J, Schoolwerth A, Watlington CO. When is cortisol a mineralocorticoid? Kidney Int 1992; 42:1297.
  32. Pedrinelli R, Bruschi G, Graziadei L, et al. Dietary sodium change in primary aldosteronism. Atrial natriuretic factor, hormonal, and vascular responses. Hypertension 1988; 12:192.
  33. Blumenfeld JD, Sealey JE, Schlussel Y, et al. Diagnosis and treatment of primary hyperaldosteronism. Ann Intern Med 1994; 121:877.
  34. Zarifis J, Lip GY, Leatherdale B, Beevers G. Malignant hypertension in association with primary aldosteronism. Blood Press 1996; 5:250.
  35. Douma S, Petidis K, Doumas M, et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008; 371:1921.
  36. Vantyghem MC, Ronci N, Provost F, et al. Aldosterone-producing adenoma without hypertension: a report of two cases. Eur J Endocrinol 1999; 141:279.
  37. Vasan RS, Evans JC, Larson MG, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004; 351:33.
  38. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89:1045.
  39. Fraser R, Murray GD, Connell JM. Conn's syndrome: no longer a needle in a haystack? Clin Endocrinol (Oxf) 1998; 49:709.
  40. Loh KC, Koay ES, Khaw MC, et al. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocrinol Metab 2000; 85:2854.
  41. Rossi GP, Bernini G, Caliumi C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48:2293.
  42. Young DB. Quantitative analysis of aldosterone's role in potassium regulation. Am J Physiol 1988; 255:F811.
  43. George JM, Wright L, Bell NH, Bartter FC. The syndrome of primary aldosteronism. Am J Med 1970; 48:343.
  44. Shigematsu Y, Hamada M, Okayama H, et al. Left ventricular hypertrophy precedes other target-organ damage in primary aldosteronism. Hypertension 1997; 29:723.
  45. Rossi GP, Sacchetto A, Visentin P, et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension 1996; 27:1039.
  46. Yoshihara F, Nishikimi T, Yoshitomi Y, et al. Left ventricular structural and functional characteristics in patients with renovascular hypertension, primary aldosteronism and essential hypertension. Am J Hypertens 1996; 9:523.
  47. Milliez P, Girerd X, Plouin PF, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45:1243.
  48. Stowasser M, Sharman J, Leano R, et al. Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I. J Clin Endocrinol Metab 2005; 90:5070.
  49. Catena C, Colussi G, Nadalini E, et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168:80.
  50. Pimenta E, Gordon RD, Ahmed AH, et al. Cardiac dimensions are largely determined by dietary salt in patients with primary aldosteronism: results of a case-control study. J Clin Endocrinol Metab 2011; 96:2813.
  51. Pitt B, Zannad F, Remme WJ, et al. 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.
  52. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309.
  53. Williams JS, Williams GH. 50th anniversary of aldosterone. J Clin Endocrinol Metab 2003; 88:2364.
  54. Young WF Jr. Minireview: primary aldosteronism--changing concepts in diagnosis and treatment. Endocrinology 2003; 144:2208.
  55. Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res 2005; 96:643.
  56. Leopold JA, Dam A, Maron BA, et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med 2007; 13:189.
  57. Ribstein J, Du Cailar G, Fesler P, Mimran A. Relative glomerular hyperfiltration in primary aldosteronism. J Am Soc Nephrol 2005; 16:1320.
  58. Sechi LA, Novello M, Lapenna R, et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295:2638.
  59. Reincke M, Rump LC, Quinkler M, et al. Risk factors associated with a low glomerular filtration rate in primary aldosteronism. J Clin Endocrinol Metab 2009; 94:869.
  60. Gregoire JR. Adjustment of the osmostat in primary aldosteronism. Mayo Clin Proc 1994; 69:1108.
  61. Quamme GA. Control of magnesium transport in the thick ascending limb. Am J Physiol 1989; 256:F197.