July 7, 2020
Aldosterone Sampling Protocols - 1 - First Line Tests Minimize

Aldosterone sampling protocols - 1 - first line tests


Conventional practice suggests that the diagnosis of hyperaldosteronism should be considered in hypertensive patients with spontaneous or diuretic-induced hypokalaemia. However data from clinics which routinely screen hypertensive indicates that a number of patients would be undiagnosed on this basis since approximately 50% of patients with aldosterone secreting adenoma are normokalaemic.




The renin-aldosterone axis is primarily regulated by renal blood flow. Subjects under investigation should, therefore, not be taking any drugs that interfere with fluid balance or potassium. Neither bethanidine nor Doxazosin or Prazosin interfere and those subjects requiring hypotensive therapy should ideally be transferred to one of these agents. Secondly, it is essential that subject should be normally hydrated and have an adequate oral intake of sodium. Hypokalaemia must be avoided since it suppresses aldosterone secretion. It is important to note that the effect of increasing oral sodium will be to considerably increase urinary potassium excretion.

Side effects



Give potassium replacement (Slow K tabs) sufficient to raise plasma potassium into the reference range (3.5-5.5 mmol/L). Replacement should be stopped on the day of the test.

Spironolactone must be stopped for 6 weeks to be certain that any elevation in plasma renin activity is not due its inhibition of aldosterone.

Ideally all interfering drugs should be stopped, but if this is impractical, a best pragmatic approach is to stop ACE inhibitors, beta-blockers for 2 weeks and to avoid Ca-channel blockers on the day of the test; although Valloton states that the aldosterone/renin ratio is robust and antihypertensive therapy does not need to be stopped when the ratio is used as a first line test.

The optimal approach is to use either Doxazosin or Prazosin as none appear to affect the renin-aldosterone axis.


Physiological effect

Time to remove interference

ACE inhibitors

increase PRA & reduce aldosterone

2 weeks


reduce PRA more than aldosterone

2 weeks

Calcium channel blockers

reduce aldosterone and stimulate renin production

2 weeks


increase PRA and aldosterone

2 weeks


inhibits aldosterone secretion



retain sodium & reduce PRA, ? effect on aldosterone

2 weeks


increase renin substrate

6 weeks


increase PRA, variable effect on aldosterone

6 weeks


  • Lithium heparin tube
  • Blood samples should be taken rapidly to the laboratory but not on ice as PRA is measured by the activity of renin and at 4C the inactive renin precursor is maximally converted to active renin.


  • The patient should remain seated for 10 min prior to venepuncture.
  • Random blood sample (10 mL lithium heparin tube) for plasma renin activity (PRA), aldosterone (PA) and potassium.
  • This sample should optimally be taken at 8 am when aldosterone is physiologically high.


High aldosterone and suppressed plasma renin activity indicates primary hyperaldosteronism. Some patients with renal disease may give similar results.

Sensitivity and Specificity

This test can only be a first line guide to the diagnosis of hyperaldosteronism. If the diagnosis is still unclear return to the hyperaldosteronism flow chart for second line dynamic tests.


  • Cartledge S, Lawson N. Aldosterone and renin measurements. Ann Clin Biochem 2000;37:262-78.
  • Edwards CRW. Primary mineralocorticoid excess syndromes. In: DeGroot LJ et al (eds). Endocrinology. Saunders: Philadelphia. 3rd edit 1995;1775-1803.
  • Gordon RD. Mineralocorticoid hypertension. Lancet 1994;344:240-3.
  • McKenna TJ, Sequeira SJ, Heffernan A, Chambers J, Cunningham S. Diagnosis under random conditions of all disorders of the renin-aldosterone axis, including primary hyperaldosteronism. J Clin Endocrinol Met 1991;73:952-7.
  • Valloton MB. Primary hyperaldosteronism. Part I Diagnosis of primary hyperaldosteronism. Clin Endocrinol (Oxf) 1996;45:47-52. 

JHB 22 Mar 2014


Home|Paediatric|Endocrinology|Renal & electrolytes|Metabolic|Investigation protocols|Misc
Comments about this site to julian.barth@nhs.net Terms Of Use Privacy Statement