Clinical background:
Aldosterone is the principal mineralcorticoid secreted by the zona glomerulosa of the adrenal cortex and is an important regulator of electrolyte homeostasis. The interaction of aldosterone, renin and angiotensin is important in the regulation of extracellular fluid volume, blood pressure and the balance of sodium and potassium ions.
The major application of the measurement of aldosterone is in the investigation of primary hyperaldosteronism. Primary hyperaldosteronism (also known as Conn’s syndrome) can be defined as the inappropriate hypersecretion of aldosterone in the absence of activation of the renin-angiotensin system. Overproduction is usually due to autonomous production by an adenoma or hyperplasia in both adrenals but can also be due to adrenal carcinoma or familial glucocorticoid-suppressible aldosteronism.
The aldosterone to renin ratio (ARR) is considered the best first line investigation of suspected hyperaldosteronism. However, the ARR is influenced by a range of factors and appropriate patient preparation and potentially interfering medications should be accounted for.
The ARR is considered to be a screening or case-detection test, rather than diagnostic due to its limited positive predictive value. Confirmatory testing (e.g. saline infusion test, fludrocortisone suppression test) is recommended in cases where the ARR is raised. These tests involve measurement of plasma aldosterone to determine if appropriate suppression has occurred.
Specimen container paediatric:
Plasma-EDTA
Specimen container adult:
Plasma-EDTA
Minimum volume paediatric:
2 mL blood
Minimum volume adult:
3 mL blood
Special requirements:
Please include details of any hypertensive medication as this may affect interpretation of the aldosterone/renin ratio (ARR). Endocrine Society Guidelines recommend the following patient preparation:
Attempt to correct any underlying hypokalaemia.
Encourage liberal (rather than restricted) sodium intake.
Withdraw agents that markedly affect ARR for at least 4 weeks (e.g. spironolactone, amiloride, K-wasting diuretics).
Withdrawal of other agents should be considered in cases of a non-diagnostic ARR and if hypertension can be controlled on relatively non-interferring medications.
Blood should ideally be collected mid-morning after the patient has been ambulant for at least 2 hours and then seated for 5-15 minutes.
If renin has also been requested, note that the sample should not be stored at refrigerator temperature at any point (to avoid cryo-activation of renin) and should be separated immediately on receipt and stored frozen.
Sample stability:
Unseparated: Same day (6 hrs if renin requested)
Separated: 4 days at room temperature, 4 days at 4-8°C (unless renin requested), 1 month at -20°C
Transport requirements:
Ambient (frozen if renin requested)
Availability:
Available during full access hours
Assayed weekly
Site of analysis: RVI
Interpretation:
The ARR cut-off for exclusion of primary aldosteronism is 30 pmol/mIU. In addition to a raised ARR the aldosterone concentration should also be taken into account. Aldosterone is typically >400 pmol/L in primary aldosteronism, although an aldosterone between 250 and 399 pmol/L has been reported in some cases.
It is important to take into account possible effects of anti-hypertensive medication that can alter the ARR. Some medications may raise the ARR (e.g. beta-blockers, NSAIDs, central alpha-2 agonists) or lower it (e.g. diuretics, ACEi, ARB, dihydropyridine Ca channel-blockers) potentially leading to false positives or false negatives, respectively.
Reference ranges:
Upright: 103 to 1197 pmol/L
Supine: 103 to 859 pmol/L
Factors affecting result:
Gross haemolysis, icterus or lipaemia may interfere.
N.B. Heterophilic antibodies can interfere with immunoassays.