Which medications may influence the results of aldosterone-to-renin ratio (ARR) in the workup of hyperaldosteronism?

Updated: Oct 19, 2018
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Answer

Spironolactone and diuretics should be withheld for 6 weeks before testing.

If necessary to maintain hypertension control, patients should be treated with other antihypertensive medications that have lesser effects on the ARR (ie, verapamil slow-release, hydralazine [with verapamil slow-release, to avoid reflex tachycardia], prazosin, doxazosin, terazosin). See Table above. It is a shared opinion that dihydropyridinic calcium channel blockers do not significantly affect aldosterone secretion, causing mainly an increase in PRA, which rarely gives false negatives. [34, 35]

Βeta-blockers, ACE inhibitors, selective-serotonin reuptake inhibitors, and oral contraceptives have been shown to influence the results of the test. Ideal testing conditions involve discontinuation of such medications 2 weeks prior.

Patients should also eliminate products derived from the licorice root because these can interfere with 11beta-hydroxysteroid dehydrogenase, producing a state of apparent mineralocorticoid excess.

Renal impairment can lead to a high ARR in patients without primary hyperaldosteronism because fluid retention suppresses PRA and hyperkalemia stimulates aldosterone secretion.

Renin assays should be sufficiently sensitive to measure levels as low as 0.2–0.3 ng/mL/h (DRC 2 mU/L).

Recent data suggest that the random urinary aldosterone-to-creatinine ratio (UACR) might enable the diagnosis of PA in concordance with the 24-hour urinary aldosterone level (Uald-24 h). The thresholds with the best sensitivity for a specificity of 90.6% of the UACR were 3 ng/mg and that of the Uald-24 h was 20.3 mcg, in a single study. [36]

After a positive screening test result, subsequent testing is directed at confirming aldosterone secretory autonomy and differentiating an APA, for which surgery is currently first-line treatment, from idiopathic hyperaldosteronism (IHA), which is usually treated medically. The possibility of GRA, which accounts for approximately 1% of cases of primary hyperaldosteronism, should be kept in mind.

Table 1. Factors affecting interpretation of ARR results (Open Table in a new window)

False Negative Results

Factor

Aldosterone

Renin

ARR

Medications

 

 

 

K-sparing diuretics

↑↑

K-wasting diuretics (Non-K-sparing diuretics, such as thiazides, induce renal potassium losses and reduce plasma potassium concentrations, leading to decreased aldosterone secretion.)

→↑

↑↑

ACE inhibitors

↑↑

Angiotensin receptor blockers

↑↑

DHPs (It is a shared opinion that dihydropyridinic calcium channel blockers do not significantly affect aldosterone secretion, mainly causing an increase in PRA, which rarely gives false negatives.)

→↓

Other conditions

Hypokalemia

→↑

Sodium-restricted diet

↑↑

Pregnancy

↑↑

Renovascular hypertension

↑↑

Malignant hypertension

↑↑

False Positive Results

Beta-adrenergic blockers

↓↓

Central alpha-2 agonists (eg, clonidine, alpha-methyldopa)

↓↓

NSAIDS

↓↓

Other conditions

Potassium loading

→↓

Sodium-loaded diet

↓↓

Advancing age

↓↓

Renal dysfunction

→↑

PHA-2

Luteal phase of menstrual cycle

PRA: Unchanged

Antihypertensive Medications With Minimal Effect on the ARR

Prazosin, doxazosin, terazosin

 

←→

Verapamil, hydralazine

 

←→

Other medications

Renin inhibitors (Renin inhibitors raise the ARR if renin is measured as PRA [false positive] and lower it if measured as DAR concentration [false negative.])

↑↓

↑↓

SSRIs

OCPs (OCPs have little effect on ARR when renin is measured as PRA. Use of immunometric measurements of DAR rather than PRA may give false positive results. Subdermal etonogestrel has no effect on ARR.)

↓DAR

Liddle syndrome

Normal

 

ARR, aldosterone-renin ratio; NSAIDs, non-steroidal anti-inflammatory drugs; K, potassium; ACE, angiotensin converting enzyme; ARBs, angiotensin II type 1 receptor blockers; DHPs, dihydropyridines; PHA-2, pseudohypoaldosteronism type 2; PRA, plasma renin activity; DAR, direct active renin; OCPs, oral contraceptive agents; SSRIs, selective serotonin reuptake inhibitors


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