What is the diagnosis and treatment approach for a high aldosterone (aldosterone) to renin (renin) ratio (ARR)?

High Aldosterone-to-Renin Ratio: Diagnosis and Treatment

Immediate Next Steps

A positive aldosterone-to-renin ratio (ARR) screening test requires confirmatory testing before establishing the diagnosis of primary aldosteronism, followed by referral to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 2

Understanding Your ARR Result

What the Numbers Mean

• An ARR >30 (when aldosterone is measured in ng/dL and renin activity in ng/mL/h) with plasma aldosterone concentration ≥10 ng/dL is considered a positive screening test 2, 3
• An ARR >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 2
• The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2

Important Caveat About Low Renin

• Low renin can artificially elevate the ARR even without truly elevated aldosterone levels 3
• Other conditions causing low renin include low-renin essential hypertension (particularly common in Black patients), chronic kidney disease, Cushing syndrome, and excessive sodium intake 3

Confirmatory Testing Protocol

Before Testing: Medication Management

• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before confirmatory testing 2, 3
• Stop beta-blockers, centrally acting drugs, and diuretics when feasible 2
• Use long-acting calcium channel blockers and alpha-receptor antagonists as alternatives during the testing period, as they minimally interfere with results 2
• If medications cannot be safely discontinued, proceed with testing but interpret results in the context of current medications 2, 4

Testing Conditions

• Ensure serum potassium is normal before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 2, 4
• Maintain unrestricted salt intake during the testing period 2, 3

Confirmatory Test Options

• Intravenous saline suppression test: Administer 2L of 0.9% saline over 4 hours with aldosterone measurement before and after 2, 4
• Oral sodium loading test: High sodium diet (>200 mEq/day for 3 days) with 24-hour urine aldosterone measurement on day 4 2, 4

Subtype Determination After Confirmation

Imaging First

• Obtain non-contrast CT scan of the adrenal glands to identify potential adenomas 2
• Critical pitfall: CT findings alone are insufficient for treatment decisions, as adenomas on imaging can represent hyperplasia, and false positives are common due to nodular hyperplasia 2

Adrenal Venous Sampling (AVS)

• AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease 2, 3
• Without AVS, up to 25% of patients undergo unnecessary adrenalectomy based on CT findings alone 2
• May reasonably exclude AVS only in patients <40 years when imaging shows a single affected gland, as bilateral hyperplasia is rare in this population 1

Treatment Based on Subtype

Unilateral Disease (Aldosterone-Producing Adenoma)

• Laparoscopic unilateral adrenalectomy is the treatment of choice 2, 3
• Improves blood pressure in virtually 100% of patients 3
• Results in complete cure of hypertension in approximately 50% of patients 3
• Complete biochemical success achieved in most patients 2

Bilateral Disease (Idiopathic Hyperaldosteronism)

• Medical therapy with mineralocorticoid receptor antagonists is the cornerstone of treatment 3
• Spironolactone is first-line treatment at 100-400 mg daily 3, 5
• Eplerenone is an alternative option with fewer anti-androgenic side effects (gynecomastia, sexual dysfunction) 3

Clinical Context and Prevalence

• Primary aldosteronism is present in up to 20% of individuals with resistant hypertension 1, 2
• Common pitfall: Not screening high-risk patients—only ~2-4% of eligible patients get screened 2
• Major misconception: Primary aldosteronism does not require hypokalemia for diagnosis; it is absent in the majority of cases 1, 2, 3

Referral Recommendation

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for further evaluation and treatment 1, 2, as multidisciplinary review by endocrinologists, surgeons, and radiologists is recommended for optimal management 2