Aldosterone sampling protocols - 2 - postural studies
Postural studies used to be the mainstay for the differential diagnosis between aldosterone producing adenomas and adrenal hyperplasia; with the latter producing a rise in aldosterone on standing whereas tumours show a fall. However, it is now recognised that about one-third of aldosterone producing adenomas are angiotensin sensitive and will respond to upright posture by a rise in the concentration of aldosterone, whereas the remainder will not. In view of this factor, few authorities now recommend their use.
Ideally all interfering drugs should be stopped, but this is impractical and a best pragmatic approach is to stop ACE inhibitors and beta-blockers for 2 weeks. Spironolactone must be stopped for 6 weeks to be certain that any elevation in plasma renin activity is not due to antagonism of aldosterone action. The optimal approach is to use bethanidine, Doxazosin or Prazosin neither of which appear to affect the renin-aldosterone axis.
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, prorenin, is maximally converted to active renin.
Subjects should be placed on a diet containing an adequate quantity of sodium (100-150 mmol/d) and potassium (75-125 mmol/d). This should be assessed by at least one 24h urine collection prior to the investigation.
The subject should not rise from bed after 2200 h on the night prior to investigation not even to go to the toilet. This is essential to ensure that basal levels of hormones are measured in the first sample.
0830 before breakfast
take 10 mL blood into a lithium heparin tube (orange top for cortisol, PRA and aldosterone). After venesection, patient should either sit, stand or walk until the midday sample is taken.
0900 before breakfast
take 10 mL blood into a lithium heparin tube (orange top for PRA).
1200 before midday meal
The baseline sample is taken to confirm the presence of hyperaldosteronism and to evaluate the aldosterone-PRA ratio under the controlled conditions on which the reference data has been collected.
The second sample is taken to establish that the effect of posture is to cause a physiological rise in PRA. No change in PRA suggests that aldosterone secretion is autonomous.
The midday sample is taken to help classify the nature of the adenoma. Aldosterone producing adenoma are either angiotensin dependent or ACTH dependent. The former is suggested by a midday concentration of aldosterone which is rises to twice the 0830h value whereas a fall in aldosterone to half the morning concentration suggests ACTH dependence. The latter requires confirmation by assessment of the physiological fall in ACTH at midday by a fall in plasma cortisol from 0830 to 1200 noon.
The aldosterone secretion in bilateral adrenal hyperplasia is generally angiotensin dependent and will rise in the midday sample.
Aldosterone producing adenoma are typically described as showing a fall in aldosterone between the recumbent and ambulant samples. This is consistent with the ACTH dependent, or angiotensin-unresponsive, adenoma.
Patients with Familial hyperaldosteronism type 1 (glucocorticoid suppressible) also show a fall in aldosterone in the midday sample.
- Feltynowski T, Ignatowska-Switalska H, Wocial B, Lewandowski J, Chodakowska J, Jaruszewic W. Postural stimulation test in patients with aldosterone producing adenomas. Clin Endocrinol (Oxf) 1994;41:309-314
- Gordon RD, Hamlet SM, Tunny TJ, Klemm SA. Aldosterone-producing adenomas responsive to angiotensin pose problems with diagnosis. Clin Exp Pharmacol Physiol 1987;14:175-179.
- Gordon RD. Mineralocorticoid hypertension. Lancet 1994,344:240-243.
- Short F, James VHT. Primary hyperaldosteronism in England and Wales: a review of the use of a supraregional assay service laboratory for the measurement of aldosterone and plasma renin activity. Ann Clin Biochem 1991;28:218-25.