Diagnostic Use
Plasma aldosterone and renin values are dependent on posture, and sodium intake, being higher with low salt intake and in the upright position.
Hypokalaemia decreases aldosterone and should be corrected before testing for primary aldosteronism.
Interpretation
| Renin |
Aldosterone |
Interpretation |
|
<10
|
>400
|
Suggestive of primary aldosteronism, especially if hypokalemia is present.
A saline suppression test can be done to confirm this. This can be arranged with the Dept. of Endocrinology. |
|
<10
|
<400
|
Low-renin, low aldosterone hypertension. Likely to be salt-sensitive and to respond well to diuretic therapy and salt restriction.
Consider Liddle’s syndrome, especially if hypokalemia is present. |
|
10-60
|
0-1000
|
Compatible with essential hypertension. |
|
10-60
|
>1000
|
Hyperaldosteronism is present; it is unclear from the renin level whether this is primary or secondary. |
|
>60
|
0-1000
|
Compatible with ACE inhibitor or angiotensin receptor blocker therapy, high renin essential hypertension, or renovascular hypertension. |
|
>60
|
>1000
|
Indicates secondary hyperaldosteronism. Causes include renovascular disease, malignant hypertension, diuretics, spironolactone |
The interpretive guide above applies only to patients with hypertension without heart failure, and does not apply to a saline suppression test.
Renal impairment : falsely high levels of aldosterone may be seen in renal impairment, because of cross reaction with aldosterone metabolites (see below).
The plasma aldosterone/renin ratio is a better screening test for primary aldosteronism than either test alone. It can usually be confidently interpreted despite the effect of most continued medications (see below) or other suboptimal conditions of testing. It can be measured on usual unrestricted salt intake. No specific dietary requirements are needed.
However, It is best performed in the morning (before 10AM), in the sitting position, at least one hour after rising. For further background visit Endocrine Society Clinical Practice Guideline on Primary Aldosteronism
A positive screening test is an aldosterone/renin ratio > 55, together with aldosterone > 400 pmol/L. Typically, the renin is suppressed to < 10 mU/L and the plasma aldosterone is > 600 pmol/L.
A negative screening test is a ratio < 25, especially if renin is > 20 mU/L.
Drug effects: Beta-blockers and NSAIDs decrease renin and can cause a false positive (high) A/R ratio.
Spironolactone, drospirenone, amiloride, and angiotensin receptor blockers (ARBs) increase renin and can cause a false negative (low) A/R ratio. Spironolactone no longer cross-reacts with the new aldosterone assay (since July 2013).
The above drugs should be stopped for 4 weeks prior to testing if possible. If it is not possible to stop these drugs, the test can still be performed, but the result must be interpreted with regard to the false positive or negative results as described above.
ACE inhibitors, alpha-blockers, thiazides and calcium channel blockers interfere minimally with the diagnostic value of the A/R ratio, and can be continued.
Primary hyperaldosteronism (Conn’s syndrome): Suspect in hypertensive patients typically with unprovoked or diuretic-induced hypokalaemia or resistant to ACE inhibitor treatment. Hypokalaemia is a strong pointer to the presence of hyperaldosteronism; however, normokalaemia is just as common and does not exclude the diagnosis.
A confirmatory saline suppression test is suggested before proceeding to adrenal imaging by MRI or CT scan (which will pick up about 85% of aldosterone secreting adenomas) or trials of Aldactone treatment. Aldactone monotherapy may be all that is required in older patients. In patients with zona glomerula hyperplasia, blood pressure control may be achieved with 100 mg/day rather than the 200-400 mg/day that may be needed in adenoma patients. Adrenal catheterisation is infrequently required. The 4-hour upright posture test to distinguish adenoma from hyperplasia has a low specificity and is seldom indicated.
Secondary hyperaldosteronism: The combination of elevated renin and aldosterone suggests renal disease, particularly reno-vascular hypertension. However, baseline renin and aldosterone values may be normal, with exaggerated increases in plasma renin after Captopril. The diagnosis of reno-vascular hypertension usually requires either renal scintigraphy combined with a Captopril challenge test or Doppler ultrasound of the renal arteries.
Low-renin, low aldosterone hypertension: The combination of low renin (< 10 mU/L) and low aldosterone (< 225 pmol/L) may be due to a high salt diet, Liddle’s syndrome, liquorice ingestion, or 11-HSD deficiency.
Hypoaldosteronism: May be suspected in the presence of hyperkalaemia as part of primary adrenal insufficiency, when plasma aldosterone fails to increase after synacthen stimulation ; or secondary to hyporeninemic hypoaldosteronism when both renin and aldosterone are low and fail to rise after 2 hr upright posture
Renal failure : Falsely high aldosterone levels may be seen in renal failure, due to crossreaction with aldosterone metabolites in the non-extracted immunoassay. The degree of over-estimation is typically: 1.5-fold for eGFR 30-60 mL/min, 4-fold for end-stage renal failure (eGFR less than 30 mL/min), and 2.3-fold for patients on dialysis.
Saline Suppression Test
A positive test for adrenal autonomy is when the plasma aldosterone remains greater than 200 pmol/L after 2L saline infusion over 4 hours. This is the preferred test, which can be arranged by phoning the Endocrinology Department via Lablink , and written referral to the Endocrinology Nurse, Green Lane Clinical Centre.
Test Method
Principle: Competitive chemiluminescent immunoassay
Assay: Diasorin
Analyser: Diasorin Liaison XL