Download PDF
Horm Metab Res 2020; 52(12): 827-833
DOI: 10.1055/a-1236-4869
Review

Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension

George P. Piaditis
1   Department of Endocrinology and Diabetes Center, “G. Gennimatas” General Hospital, Athens, Greece
,
Gregory Kaltsas
2   Department of Pathophysiology, National University of Athens, Athens, Greece
,
Athina Markou
1   Department of Endocrinology and Diabetes Center, “G. Gennimatas” General Hospital, Athens, Greece
,
George P. Chrousos
3   University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Primary hyperaldosteronism (PA) is a well-known cause of hypertension although its exact prevalence amongst patients with apparent essential hypertension has been a matter of debate. A number of recent studies have suggested that mild forms of PA may be relatively common taking into consideration factors that were previously either overestimated or ignored when developing diagnostic tests of PA and when applying these tests into normotensive individuals. The performance characteristics and diagnostic accuracy of such tests are substantially increased when the adrenocorticotrophin effect, inappropriate potassium levels and their application in carefully selected normotensive individuals are considered. In the present review, we critically analyze these issues and provide evidence that several, particularly mild, forms of PA can be effectively identified exhibiting potentially important clinical implications.

Key words

primary aldosteronism - hypertension - ACTH - adrenal - aldosterone to renin ratio


Publication History

Received: 28 May 2020

Accepted after revision: 05 August 2020

Article published online:
03 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Conn JW, Louis LH. Primary aldosteronism: A new clinical entity. Trans Assoc Am Physicians 1955; 68: 215-231
    PubMedGoogle Scholar
  • 2 Schirpenbach C, Reincke M. Primary aldosteronism: Current knowledge and controversies in Conn’s syndrome. Nature clinical practice. Endocrinol Metab 2007; 3: 220-227
    PubMedGoogle Scholar
  • 3 Gordon RD, Gomez-Sanchez CE, Hamlet SM. et al. Angiotensin-responsive aldosterone-producing adenoma masquerades as idiopathic hyperaldosteronism (IHA: Adrenal hyperplasia) or low renin essential hypertension. J Hypertens (Suppl) 1987; 5: S103-S106
    PubMedGoogle Scholar
  • 4 Stowasser M, Gordon RD, Rutherford JC. et al. Diagnosis and management of primary aldosteronism. JRAAS 2001; 2: 156-169
    PubMedGoogle Scholar
  • 5 Staruschenko A. Regulation of transport in the connecting tubule and cortical collecting duct. Compr Physiol 2012; 2: 1541-1584
    CrossrefPubMedGoogle Scholar
  • 6 Briet M, Schiffrin EL. The role of aldosterone in the metabolic syndrome. Curr Hypertens Rep 2011; 13: 163-172
    CrossrefPubMedGoogle Scholar
  • 7 Rossi GP, Sacchetto A, Pavan E. et al. Left ventricular systolic function in primary aldosteronism and hypertension. J Hypertens 1998; 6: 2075-2077
    CrossrefPubMedGoogle Scholar
  • 8 Rossi GP, Di Bello V, Ganzaroli C. et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 2002; 40: 23-27
    Google Scholar
  • 9 Rossi GP, Bernini G, Desideri G. et al. Renal damage in primary aldosteronism: Results of the PAPY Study. Hypertension 2006; 48: 232-238
    CrossrefPubMedGoogle Scholar
  • 10 Rossi GP, Sechi LA, Giacchetti G. et al. Primary aldosteronism: Cardiovascular, renal and metabolic implications. Trends Endocrinol Metab 2008; 19: 88-90
    Google Scholar
  • 11 Fritsch Neves M, Schiffrin EL. Aldosterone: A risk factor for vascular disease. Curr Hypertens Rep 2003; 5: 59-65
    CrossrefPubMedGoogle Scholar
  • 12 Gilbert KC, Brown NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes 2010; 17: 199-204
    CrossrefPubMedGoogle Scholar
  • 13 Carey RM. Aldosterone and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 2010; 17: 194-198
    CrossrefPubMedGoogle Scholar
  • 14 Huang BS, Leenen FH. Mineralocorticoid actions in the brain and hypertension. Curr Hypertens Rep 2011; 13: 214-220
    CrossrefPubMedGoogle Scholar
  • 15 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
    Google Scholar
  • 16 Piaditis G, Markou A, Papanastasiou L. et al. Progress in aldosteronism: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. Eur J Endocrinol 2015; 172: R191-R203
    Google Scholar
  • 17 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Col Cardiol 2006; 48: 2293-2300
    CrossrefPubMedGoogle Scholar
  • 18 Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab 2009; 94: 3623-3630
    CrossrefPubMedGoogle Scholar
  • 19 Douma S, Petidis K, Doumas M. et al. Prevalence of primary hyperaldosteronism in resistant hypertension: A retrospective observational study. Lancet 2008; 371: 1921-1926
    CrossrefPubMedGoogle Scholar
  • 20 Stowasser M, Gordon RD, Gunasekera TG. et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ‘non-selective’ screening of hypertensive patients. J Hypertens 2003; 21: 2149-2157
    CrossrefPubMedGoogle Scholar
  • 21 Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol 2007; 66: 607-618
    CrossrefPubMedGoogle Scholar
  • 22 Gouli A, Kaltsas G, Tzonou A. et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Inves 2011; 41: 1227-1236
    CrossrefPubMedGoogle Scholar
  • 23 Piaditis GP, Kaltsas GA, Androulakis II. et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol (Oxf) 2009; 71: 772-778
    CrossrefPubMedGoogle Scholar
  • 24 Markou A, Sertedaki A, Kaltsas G. et al. Stress induced aldosterone hyper-secretion in a substantial subset of patients with essential hypertension. J Clin Endocrinol Metab 2015; 100: 2857-2864
    CrossrefPubMedGoogle Scholar
  • 25 Luger A, Deuster PA, Debolt JE. et al. Acute exercise stimulates the renin-angiotensin-aldosterone axis: Adaptive changes in runners. Horm Res 1988; 30: 5-9
    CrossrefPubMedGoogle Scholar
  • 26 Luger A, Deuster PA, Kyle SB. et al. Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training. N Engl J Med 1987; 316: 1309-1315
    CrossrefPubMedGoogle Scholar
  • 27 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 Article 72
    PubMedGoogle Scholar
  • 28 Seely EW, Conlin PR, Brent GA. et al. Adrenocorticotropin stimulation of aldosterone: prolonged continuous versus pulsatile infusion. J Clin Endocrinol Metab 1989; 69: 1028-1032
    CrossrefPubMedGoogle Scholar
  • 29 Turchin A, Guo CZ, Adler GK. et al. Effect of acute aldosterone administration on gene expression profile in the heart. Endocrinology 2006; 147: 3183-3189
    CrossrefPubMedGoogle Scholar
  • 30 Schmidt BM, Georgens AC, Martin N. et al. Interaction of rapid nongenomic cardiovascular aldosterone effects with the adrenergic system. J Clin Endocrinol Metab 2001; 86: 761-767
    CrossrefPubMedGoogle Scholar
  • 31 Winter C, Kampik NB, Vedovelli L. et al. Aldosterone stimulates vacuolar H+-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway. Am J Physiol Cell Physiol 2011; 301: C1251-C1261
    CrossrefPubMedGoogle Scholar
  • 32 Hiramatsu K, Yamada T, Yukimura Y. et al. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med 1981; 141: 1589-1593
    PubMedGoogle Scholar
  • 33 Schwartz GL. 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
    CrossrefPubMedGoogle Scholar
  • 34 Papanastasiou L, Markou A, Pappa T. et al. Primary aldosteronism in hypertensive patients: Clinical implications and target therapy. Eur J Clin Invest 2014; 44: 697-706
    CrossrefPubMedGoogle Scholar
  • 35 Montori VM, Young WF. Use of plasma aldosterone concentration to plasma renin ratio as a screening test for primary aldosteronism: A systematic review of the literature. Endocrinol Metab Clin North Am 2002; 31: 619-632
    CrossrefPubMedGoogle Scholar
  • 36 Pappa T, Papanastasiou L, Kaltsas G. et al. Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension. J Clin Endocrinol Metab 2012; 97: E537-E545
    CrossrefPubMedGoogle Scholar
  • 37 Mansmann G, Lau J, Balk E. et al. The clinically inapparent adrenal mass: Update in diagnosis and management. Endocr Rev 2004; 25: 309-340
    CrossrefPubMedGoogle Scholar
  • 38 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
    Google Scholar
  • 39 Baudrand R, Guarda FJ, Fardella C. et al. A continuum of renin-independent aldosteronism in normotension. Hypertension 2017; 69: 950-956
    Google Scholar
  • 40 Brown JM, Siddiqui M, Calhoun DA. et al. The unrecognized prevalence of primary aldosteronism. Ann Inter Med 2020; 173: 10-20
    CrossrefPubMedGoogle Scholar
  • 41 Himathongkam T, Dluhy RG, Williams GH. Potassium-aldosterone-rennin interrelationships. J Clin Endocrinol Metab 1975; 41: 153-159
    CrossrefPubMedGoogle Scholar
  • 42 Bauer JH, Gauntner WC. Effect of potassium chloride on plasma rennin activity and plasma aldosterone during sodium restriction in normal man. Kidney Int 1979; 15: 286-293
    CrossrefPubMedGoogle Scholar
  • 43 Hattangady N, Olala L, Bollag WB. et al. Acute and chronic regulation of aldosterone production. Mol Cell Endocrinol 2012; 350: 151-162
    CrossrefPubMedGoogle Scholar
  • 44 Tsiavos V, Markou A, Papanastasiou L. et al. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol 2016; 175: 21-28
    CrossrefPubMedGoogle Scholar