Subscribe to RSS
DOI: 10.1055/a-1134-4980
Hypokalemia and the Prevalence of Primary Aldosteronism
Authors

Abstract
Hypokalemia is closely linked with the pathophysiology of primary aldosteronism (PA). Although hypokalemic PA is less common than the normokalemic course of the disease, hypokalemia is of particular importance for the manifestation and development of comorbidities. Specifically, a growing body of evidence demonstrates that hypokalemia in PA patients is associated with a more severe disease course regarding cardiovascular and metabolic morbidity and mortality. It is also well appreciated that low potassium levels per se can promote or exacerbate hypertension. The spectrum of hypokalemia-related symptoms ranges from asymptomatic courses to life-threatening conditions. Hypokalemia is found in 9–37% of all cases of PA with a predominance in patients with aldosterone producing adenoma. Conversely, hypokalemia resolves in almost 100% of cases after both, specific medical or surgical treatment of the disease. However, to date, high-level evidence about the prevalence of primary aldosteronism in a hypokalemic population is missing. Epidemiological data are expected from the recently launched IPAHK+study (“Incidence of Primary Aldosteronism in Patients with Hypokalemia”).
Publication History
Received: 10 December 2019
Accepted: 02 March 2020
Article published online:
06 April 2020
© Georg Thieme Verlag KG
Stuttgart · New York
-
References
- 1
Byrd JB,
Turcu AF,
Auchus RJ.
Primary aldosteronism. Circulation 2018; 138: 823-835
Reference Ris Wihthout Link
- 2
Funder JW.
Primary aldosteronism. Hypertension 2019; 74: 458-466
Reference Ris Wihthout Link
- 3
Hannemann A,
Wallaschofski H.
Prevalence of primary aldosteronism in patient’s cohorts and in
population-based studies – A review of the current literature. Horm Metab Res 2012;
44: 157-162
Reference Ris Wihthout Link
- 4
Hannemann A,
Bidlingmaier M,
Friedrich N.
et al. Screening for primary aldosteronism in hypertensive subjects: Results from
two
German epidemiological studies. Eur J Endocrinol 2012; 167: 7-15
Reference Ris Wihthout Link
- 5
Pillai PR,
Griffith M,
Schwarcz MD.
et al. Primary aldosteronism: Cardiovascular risk, diagnosis, and management. Cardiol
Rev 2020; 28: 84-91
Reference Ris Wihthout Link
- 6
Milliez P,
Girerd X,
Plouin P-F.
et al. Evidence for an increased rate of cardiovascular events in patients with primary
aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
Reference Ris Wihthout Link
- 7
Wu X,
Yu J,
Tian H.
Cardiovascular risk in primary aldosteronism: A systematic review and
meta-analysis. Medicine 2019; 98: e15985
Reference Ris Wihthout Link
- 8
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: 1889-1916
Reference Ris Wihthout Link
- 9 [Anonymous] Clinical study of adrenal incidentaloma in Korea FAU - Kim, Hee Young
FAU - Kim,
Sin Gon FAU - Lee, Kye Won FAU - Seo, Ji A FAU - Kim, Nan Hee FAU - Choi, Kyung
Mook FAU - Baik, Sei Hyun FAU - Choi, Dong Seop. Korean J Intern Med 2005; 20: 303-309
Reference Ris Wihthout Link
- 10
Conn JW.
Presidential address: Part I. Painting background Part II. Primary
aldosteronism, a new clinical syndrome. J Lab Clin Med 1955; 45: 3-17
Reference Ris Wihthout Link
- 11
Conn JW,
Louis LH.
Primary aldosteronism: A new clinical entity. Trans Assoc Am Phys 1955; 68: 215
Reference Ris Wihthout Link
- 12
Ganguly A.
Primary aldosteronism. N Engl J Med 1998; 339: 1828-1834
Reference Ris Wihthout Link
- 13
Kaplan NM.
Hypokalemia in the hypertensive patient: With observations on the incidence of
primary aldosteronism. Ann Inter Med 1967; 66: 1079-1090
Reference Ris Wihthout Link
- 14
Gordon RD,
Ziesak MD,
Tunny TJ.
et al. Evidence that primary aldosteronism may not be uncommon: 12% incidence
among antihypertensive drug trial volunteers. Clin Exp Pharmacol Physiol 1993; 20:
296-298
Reference Ris Wihthout Link
- 15
Mulatero P,
Stowasser M,
Loh K-C.
et al. Increased diagnosis of primary aldosteronism, including surgically correctable
forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89: 1045-1050
Reference Ris Wihthout Link
- 16
Gordon RD,
Stowasser M,
Tunny TJ.
et al. High incidence of primary aldosteronism in 199 patients referred with
hypertension. Clin Exp Pharmacol Physiol 1994; 21: 315-318
Reference Ris Wihthout Link
- 17
Gallay BJ,
Ahmad S,
Xu L.
et al. Screening for primary aldosteronism without discontinuing hypertensive
medications: Plasma aldosterone-renin ratio. Am J Kidney Dis 2001; 37: 699-705
Reference Ris Wihthout Link
- 18
Calhoun DA,
Nishizaka MK,
Zaman MA.
et al. Hyperaldosteronism among black and white subjects with resistant hypertension.
hypertension. 2002; 40: 892-896
Reference Ris Wihthout Link
- 19
Acelajado MC,
Calhoun DA.
Aldosteronism and resistant hypertension. Int J Hypertens 2011; 2011: 837817
Reference Ris Wihthout Link
- 20
Dudenbostel T,
Calhoun DA.
Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens
2012; 26: 281-287
Reference Ris Wihthout Link
- 21
Ekmekcioglu C,
Elmadfa I,
Meyer AL.
et al. The role of dietary potassium in hypertension and diabetes. J Physiol Biochem
2016; 72: 93-106
Reference Ris Wihthout Link
- 22
Vaidya A,
Mulatero P,
Baudrand R.
et al. The expanding spectrum of primary aldosteronism: Implications for diagnosis,
pathogenesis, and treatment. Endocr Rev 2018; 39: 1057-1088
Reference Ris Wihthout Link
- 23
Zacchia M,
Abategiovanni ML,
Stratigis S.
et al. Potassium: From physiology to clinical implications. Kidney Dis (Basel, Switzerland)
2016; 2: 72-79
Reference Ris Wihthout Link
- 24
Gennari FJ.
Hypokalemia. N Engl J Med 1998; 339: 451-458
Reference Ris Wihthout Link
- 25
Clausen T,
Everts ME.
Regulation of the Na, K-pump in skeletal muscle. Kidney Int 1989; 35: 1-13
Reference Ris Wihthout Link
- 26
Palmer BF.
Regulation of potassium homeostasis. Clin J Am Soc Nephrol 2015; 10: 1050-1060
Reference Ris Wihthout Link
- 27
Udensi UK,
Tchounwou PB.
Potassium homeostasis, oxidative stress, and human disease. Int J Clin Exp Physiol
2017; 4: 111-122
Reference Ris Wihthout Link
- 28
Field MJ,
Giebisch GJ.
Hormonal control of renal potassium excretion. Kidney Int 1985; 27: 379-387
Reference Ris Wihthout Link
- 29
Cannavo A,
Bencivenga L,
Liccardo D.
et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology
and pathophysiology. Oxid Med Cell Longev. 2018 1204598.
Reference Ris Wihthout Link
- 30
Atlas SA.
The renin-angiotensin aldosterone system: Pathophysiological role and
pharmacologic inhibition. J Manag Care Pharm 2007; 13 (8 Suppl B) 9-20
Reference Ris Wihthout Link
- 31
Balakumar P,
Anand-Srivastava MB,
Jagadeesh G.
Renin-angiotensin-aldosterone: An inclusive, an invigorative, an interactive and
an interminable system. Pharmacol Res 2017; 125: 1-3
Reference Ris Wihthout Link
- 32
Kawai T,
Forrester SJ,
O’Brien S.
et al. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res
2017; 125: 4-13
Reference Ris Wihthout Link
- 33
Larsen PR,
Kronenberg HM,
Melmed S.
et al. Williams textbook of endocrinology. Saunders; Philadelphia: 2003
Reference Ris Wihthout Link
- 34
El Ghorayeb N,
Bourdeau I,
Lacroix A.
Role of ACTH and other hormones in the regulation of aldosterone production in
primary aldosteronism. Front Endocrinol 2016; 7: 72
Reference Ris Wihthout Link
- 35
Shibata S,
Rinehart J,
Zhang J.
et al. Mineralocorticoid receptor phosphorylation regulates ligand binding and renal
response to volume depletion and hyperkalemia. Cell Metab 2013; 18: 660-671
Reference Ris Wihthout Link
- 36
Arroyo JP,
Ronzaud C,
Lagnaz D.
et al. Aldosterone paradox: Differential regulation of ion transport in distal. Nephron
Physiology (Bethesda) 2011; 26: 115-123
Reference Ris Wihthout Link
- 37
Choi M,
Scholl UI,
Yue P.
et al. K+channel mutations in adrenal aldosterone-producing adenomas and
hereditary hypertension. Science 2011; 331: 768-772
Reference Ris Wihthout Link
- 38
Azizan EAB,
Poulsen H,
Tuluc P.
et al. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal
hypertension. Nat Genet 2013; 45: 1055-1060
Reference Ris Wihthout Link
- 39
Daniil G,
Fernandes-Rosa FL,
Chemin J.
et al. CACNA1H mutations are associated with different forms of primary
aldosteronism. EBioMedicine 2016; 13: 225-236
Reference Ris Wihthout Link
- 40
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: 440-444
Reference Ris Wihthout Link
- 41
Fernandes-Rosa FL,
Boulkroun S,
Zennaro M-C.
Somatic and inherited mutations in primary aldosteronism. J Mol Endocrinol 2017; 59:
R47-R63
Reference Ris Wihthout Link
- 42
Aburto NJ,
Hanson S,
Gutierrez H.
et al. Effect of increased potassium intake on cardiovascular risk factors and disease:
Systematic review and meta-analyses. BMJ (Clinical Research Ed) 2013; 346: f1378
Reference Ris Wihthout Link
- 43
Kardalas E,
Paschou SA,
Anagnostis P.
et al. Hypokalemia: A clinical update. Endocr Connect 2018; 7: R135-r146
Reference Ris Wihthout Link
- 44
Paice BJ,
Paterson KR,
Onyanga-Omara F.
et al. Record linkage study of hypokalaemia in hospitalized patients. Postgrad Med
J 1986; 62: 187-191
Reference Ris Wihthout Link
- 45
Marti G,
Schwarz C,
Leichtle AB.
et al. Etiology and symptoms of severe hypokalemia in emergency department
patients. Eur J Emerg Med 2014; 21: 46-51
Reference Ris Wihthout Link
- 46
Chaker Ben S,
Houssem H,
Kamel B.
Drug-induced hypokalaemia. Curr Drug Safety 2009; 4: 55-61
Reference Ris Wihthout Link
- 47
Macdonald JE,
Struthers AD.
What is the optimal serum potassium level in cardiovascular patients?. J Am Coll Cardiol
2004; 43: 155-161
Reference Ris Wihthout Link
- 48
Schulman M,
Narins RG.
Hypokalemia and cardiovascular disease. Am J Cardiol 1990; 65: E4-E9
Reference Ris Wihthout Link
- 49
Tran TTT,
Pease A,
Wood AJ.
et al. Review of evidence for adult diabetic ketoacidosis management protocols. Front
Endocrinol 2017; 8: 106
Reference Ris Wihthout Link
- 50
Schilbach K,
Junnila RK,
Bidlingmaier M.
Aldosterone to renin ratio as screening tool in primary aldosteronism. Exp Clin Endocrinol
Diabetes 2019; 127: 84-92
Reference Ris Wihthout Link
- 51
Stowasser M,
Ahmed AH,
Pimenta E.
et al. Factors affecting the aldosterone/renin ratio. Horm Metab Res 2012; 44: 170-176
Reference Ris Wihthout Link
- 52
Brown JJ,
Chinn RH,
Davies DL.
et al. Falsely high plasma potassium values in patients with hyperaldosteronism. Br
Med J 1970; 2: 18-20
Reference Ris Wihthout Link
- 53
Don BR,
Sebastian A,
Cheitlin M.
et al. Pseudohyperkalemia caused by fist clenching during phlebotomy. N Engl J Med
1990; 322: 1290-1292
Reference Ris Wihthout Link
- 54
Fischer E,
Beuschlein F,
Bidlingmaier M.
et al. Commentary on the endocrine society practice guidelines: Consequences of
adjustment of antihypertensive medication in screening of primary
aldosteronism. Rev Endocr Metab Disord 2011; 12: 43-48
Reference Ris Wihthout Link
- 55
Krogager ML,
Torp-Pedersen C,
Mortensen RN.
et al. Short-term mortality risk of serum potassium levels in hypertension: A
retrospective analysis of nationwide registry data. Eur Heart J 2016; 38: 104-112
Reference Ris Wihthout Link
- 56
Krishna GG.
Effect of potassium intake on blood pressure. J Am Soc Nephrol 1990; 1: 43-52
Reference Ris Wihthout Link
- 57
Binia A,
Jaeger J,
Hu Y.
et al. Daily potassium intake and sodium-to-potassium ratio in the reduction of blood
pressure: A meta-analysis of randomized controlled trials. J Hypertens 2015; 33: 1509-1520
Reference Ris Wihthout Link
- 58
Whelton PK,
He J,
Cutler JA.
et al. Effects of oral potassium on blood pressure: Meta-analysis of randomized
controlled clinical trials. JAMA 1997; 277: 1624-1632
Reference Ris Wihthout Link
- 59
Oberleithner H,
Callies C,
Kusche-Vihrog K.
et al. Potassium softens vascular endothelium and increases nitric oxide release.
Proc Natl Acad Sci USA 2009; 106: 2829-2834
Reference Ris Wihthout Link
- 60
Liu Z,
Peng J,
Lu F.
et al. Salt loading and potassium supplementation: effects on ambulatory arterial
stiffness index and endothelin-1 levels in normotensive and mild hypertensive
patients. J Clin Hypertens (Greenwich) 2013; 15: 485-496
Reference Ris Wihthout Link
- 61
Haddy FJ,
Vanhoutte PM,
Feletou M.
Role of potassium in regulating blood flow and blood pressure. Am J Physiol Regul
Integr Comp Physiol 2006; 290: R546-R552
Reference Ris Wihthout Link
- 62
Terker AS,
Zhang C,
McCormick JA.
et al. Potassium modulates electrolyte balance and blood pressure through effects
on
distal cell voltage and chloride. Cell Metab 2015; 21: 39-50
Reference Ris Wihthout Link
- 63
Rengarajan S,
Lee DH,
Oh YT.
et al. Increasing plasma [K+] by intravenous potassium infusion reduces NCC
phosphorylation and drives kaliuresis and natriuresis. Am J Physiol Renal Physiol
2014; 306: F1059-F1068
Reference Ris Wihthout Link
- 64
Rossi GP,
Rossi E,
Pavan E.
et al. Screening for primary aldosteronism with a logistic multivariate discriminant
analysis. Clin Endocrinol (Oxf) 1998; 49: 713-723
Reference Ris Wihthout Link
- 65
Fogari R,
Preti P,
Zoppi A.
et al. 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
Reference Ris Wihthout Link
- 66
Monticone S,
Burrello J,
Tizzani D.
et al. Prevalence and clinical manifestations of primary aldosteronism encountered
in
primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820
Reference Ris Wihthout Link
- 67
Rossi GP,
Bernini G,
Caliumi C.
et al. A prospective study of the prevalence of primary aldosteronism in 1125
hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300
Reference Ris Wihthout Link
- 68
Käyser SC,
Deinum J,
de Grauw WJ.
et al. Prevalence of primary aldosteronism in primary care: A cross-sectional
study. Br J Gen Pract 2018; 68: e114-e122
Reference Ris Wihthout Link
- 69
Ito Y,
Takeda R,
Takeda Y.
Subclinical primary aldosteronism. Best Pract Res Clin Endocrinol Metab 2012; 26:
485-495
Reference Ris Wihthout Link
- 70
Markou A,
Pappa T,
Kaltsas G.
et al. Evidence of primary aldosteronism in a predominantly female cohort of
normotensive individuals: A very high odds ratio for progression into arterial
hypertension. J Clin Endocrinol Metab 2013; 98: 1409-1416
Reference Ris Wihthout Link
- 71
Baudrand R,
Guarda FJ,
Fardella C.
et al. Continuum of renin-independent aldosteronism in normotension. Hypertension
(Dallas, Tex: 1979) 2017; 69: 950-956
Reference Ris Wihthout Link
- 72
Schirpenbach C,
Segmiller F,
Diederich S.
et al. The diagnosis and treatment of primary hyperaldosteronism in Germany: Results
on
555 patients from the German Conn Registry. Dtsch Arztebl Int 2009; 106: 305-311
Reference Ris Wihthout Link
- 73
Cohn JN,
Kowey PR,
Whelton PK.
et al. New guidelines for potassium replacement in clinical practice: A contemporary
review by the national council on potassium in clinical practice. Arch Inter Med 2000;
160: 2429-2436
Reference Ris Wihthout Link
- 74
Crop MJ,
Hoorn EJ,
Lindemans J.
et al. Hypokalaemia and subsequent hyperkalaemia in hospitalized patients. Nephrol
Dial Transplant 2007; 22: 3471-3477
Reference Ris Wihthout Link
- 75
Williams TA,
Lenders JWM,
Mulatero P.
et al. 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
Reference Ris Wihthout Link
- 76
Fischer E,
Hanslik G,
Pallauf A.
et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary
aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97: 3965-3973
Reference Ris Wihthout Link
- 77
Mattsson C,
Young WF.
Primary aldosteronism: Diagnostic and treatment strategies. Nat Clin Pract Nephrol
2006; 2: 198-208
Reference Ris Wihthout Link
- 78
Karagiannis A,
Tziomalos K,
Papageorgiou A.
et al. Spironolactone versus eplerenone for the treatment of idiopathic
hyperaldosteronism. Exp Opin Pharmacother 2008; 9: 509-515
Reference Ris Wihthout Link
- 79
Karashima S,
Yoneda T,
Kometani M.
et al. Comparison of eplerenone and spironolactone for the treatment of primary
aldosteronism. Hypertens Res 2015; 39
Reference Ris Wihthout Link
- 80
Parthasarathy HK,
Ménard J,
White WB.
et al. A double-blind, randomized study comparing the antihypertensive effect of
eplerenone and spironolactone in patients with hypertension and evidence of
primary aldosteronism. J Hypertens 2011; 29: 980-990
Reference Ris Wihthout Link