Assays of the renin-angiotensin-aldosterone system in adrenal disease
- Michael Stowasser, MD
Michael Stowasser, MD
- Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute
- Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia
Assessment of the renin-angiotensin-aldosterone system has recently assumed a much greater role in clinical practice, particularly in the evaluation of patients with hypertension. This is mainly attributable to the growing appreciation that primary aldosteronism is a much more common cause of hypertension than previously thought, accounting for as many as 5 to 10 percent of cases, and that most patients lack hypokalemia as a clinical clue. As a result, guidelines advocate screening for primary aldosteronism by measurement of the plasma aldosterone/renin ratio rather than that of plasma potassium (which is much less sensitive) and among a much wider population of hypertensives than previously .
In addition, the renin-angiotensin-aldosterone system is often evaluated in patients with:
●Hypokalemia or hyperkalemia who may have hyperaldosteronism (or other forms of real or apparent mineralocorticoid excess) or hypoaldosteronism, respectively
●Adrenal insufficiency (to distinguish primary from secondary)
The use of renin, angiotensin, and aldosterone measurements will be reviewed here. The approach to the patient with potential mineralocorticoid excess or hypoaldosteronism is discussed separately. (See "Diagnosis of primary aldosteronism" and "Causes and evaluation of hyperkalemia in adults".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- 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.
- Haber E, Koerner T, Page LB, et al. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab 1969; 29:1349.
- Workman RJ, Sussman CR, Burkitt DW, Liddle GW. Circulating levels of angiotensin I measured by radioimmunoassay in hypertensive subjects. J Lab Clin Med 1979; 93:847.
- Sealey JE, Laragh JH. Radioimmunoassay of plasma renin activity. Semin Nucl Med 1975; 5:189.
- Ferrari P, Shaw SG, Nicod J, et al. Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism. J Hypertens 2004; 22:377.
- Ahmed AH, Gordon RD, Taylor PJ, et al. Effect of contraceptives on aldosterone/renin ratio may vary according to the components of contraceptive, renin assay method, and possibly route of administration. J Clin Endocrinol Metab 2011; 96:1797.
- Ahmed AH, Gordon RD, Ward G, et al. Effect of Combined Hormonal Replacement Therapy on the Aldosterone/Renin Ratio in Postmenopausal Women. J Clin Endocrinol Metab 2017; 102:2329.
- Ahmed AH, Gordon RD, Taylor PJ, et al. Are women more at risk of false-positive primary aldosteronism screening and unnecessary suppression testing than men? J Clin Endocrinol Metab 2011; 96:E340.
- Laragh JH, Sealey J, Brunner HR. The control of aldosterone secretion in normal and hypertensive man: abnormal renin-aldosterone patterns in low renin hypertension. Am J Med 1972; 53:649.
- Stowasser, M, Gordon, RD. The aldosterone-renin ratio for screening for primary aldosteronism. Endocrinologist 2004; 14:267.
- Michelakis AM, Yoshida H, Dormois JC. Plasma renin activity and plasma aldosterone during the normal menstrual cycle. Am J Obstet Gynecol 1975; 123:724.
- Weinberger MH, Kramer NJ, Grim CE, Petersen LP. The effect of posture and saline loading on plasma renin activity and aldosterone concentration in pregnant, non-pregnant and estrogen-treated women. J Clin Endocrinol Metab 1977; 44:69.
- Gordon RD, Wolfe LK, Island DP, Liddle GW. A diurnal rhythm in plasma renin activity in man. J Clin Invest 1966; 45:1587.
- Gordon RD. Primary aldosteronism. J Endocrinol Invest 1995; 18:495.
- Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93:3266.
- Ahmed AH, Gordon RD, Ward G, et al. Effect of Moxonidine on the Aldosterone/Renin Ratio in Healthy Male Volunteers. J Clin Endocrinol Metab 2017; 102:2039.
- Sever PS, Peart WS, Meade TW, et al. Ethnic differences in blood pressure with observations on noradrenaline and renin. 1. A working population. Clin Exp Hypertens 1979; 1:733.
- CONN JW. PLASMA RENIN ACTIVITY IN PRIMARY ALDOSTERONISM. IMPORTANCE IN DIFFERENTIAL DIAGNOSIS AND IN RESEARCH OF ESSENTIAL HYPERTENSION. JAMA 1964; 190:222.
- Arai K, Chrousos GP. Syndromes of glucocorticoid and mineralocorticoid resistance. Steroids 1995; 60:173.
- Irony I, Biglieri EG, Perloff D, Rubinoff H. Pathophysiology of deoxycorticosterone-secreting adrenal tumors. J Clin Endocrinol Metab 1987; 65:836.
- Walker BR, Campbell JC, Fraser R, et al. Mineralocorticoid excess and inhibition of 11 beta-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1992; 37:483.
- Simpoulos AP, Marshall JR, Delea CS, Bartter FC. Studies on the deficiency of 21-hydroxylation in patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 1971; 32:438.
- Shizuta Y, Kawamoto T, Mitsuuchi Y, et al. Inborn errors of aldosterone biosynthesis in humans. Steroids 1995; 60:15.
- Warnock DG. Liddle syndrome: genetics and mechanisms of Na+ channel defects. Am J Med Sci 2001; 322:302.
- Stewart PM. 11 beta-Hydroxysteroid dehydrogenase: implications for clinical medicine. Clin Endocrinol (Oxf) 1996; 44:493.
- White PC, Speiser PW. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am 1994; 23:325.
- Geller DS, Farhi A, Pinkerton N, et al. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 2000; 289:119.
- Gordon RD, Geddes RA, Pawsey CG, O'Halloran MW. Hypertension and severe hyperkalaemia associated with suppression of renin and aldosterone and completely reversed by dietary sodium restriction. Australas Ann Med 1970; 19:287.
- Wilson FH, Disse-Nicodème S, Choate KA, et al. Human hypertension caused by mutations in WNK kinases. Science 2001; 293:1107.
- Boyden LM, Choi M, Choate KA, et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 2012; 482:98.
- McKenna TJ, Sequeira SJ, Heffernan A, et al. Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism. J Clin Endocrinol Metab 1991; 73:952.
- Mayes D, Furuyama S, Kem DC, Nugent CA. A radioimmunoassay for plasma aldosterone. J Clin Endocrinol Metab 1970; 30:682.
- Perschel FH, Schemer R, Seiler L, et al. Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays. Clin Chem 2004; 50:1650.
- Schirpenbach C, Seiler L, Maser-Gluth C, et al. Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps. Clin Chem 2006; 52:1749.
- Taylor PJ, Cooper DP, Gordon RD, Stowasser M. Measurement of aldosterone in human plasma by semiautomated HPLC-tandem mass spectrometry. Clin Chem 2009; 55:1155.
- Al-Dujaili EA, Edwards CR. The development and application of a direct radioimmunoassay for plasma aldosterone using 125I-labeled ligand--comparison of three methods. J Clin Endocrinol Metab 1978; 46:105.
- Pratt JH, Jones JJ, Miller JZ, et al. Racial differences in aldosterone excretion and plasma aldosterone concentrations in children. N Engl J Med 1989; 321:1152.
- Katz FH, Romfh P, Smith JA. Diurnal variation of plasma aldosterone, cortisol and renin activity in supine man. J Clin Endocrinol Metab 1975; 40:125.
- Tuck ML, Dluhy RG, Williams GH. Sequential responses of the renin-angiotensin-aldosterone axis to acute postural change: effect of dietary sodium. J Lab Clin Med 1975; 86:754.
- Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J Clin Endocrinol Metab 1983; 56:222.
- D'Armiento M, Reda G, Kater C, et al. 17 alpha-hydroxylase deficiency: mineralocorticoid hormone profiles in an affected family. J Clin Endocrinol Metab 1983; 56:697.
- Plasma renin activity
- Plasma renin concentration
- Which is the preferred assay?
- Normal values
- - Factors that affect renin
- Interpretation in adrenal disease
- Interpretation in nonadrenal conditions
- Normal values
- Interpretation in adrenal disease
- Interpretation in other (nonadrenal) conditions
- Urine aldosterone excretion
- Aldosterone secretory rate
- SOCIETY GUIDELINE LINKS