In a hypertensive patient, does a plasma aldosterone concentration of 19.5 ng/dL and plasma renin activity of 3.5 ng·mL⁻¹·h⁻¹ (aldosterone‑to‑renin ratio ≈5.6) rule out primary aldosteronism?

Analysis of Aldosterone and Renin Results

Direct Interpretation

These values do NOT suggest primary aldosteronism and effectively rule out the diagnosis in a hypertensive patient. The aldosterone-to-renin ratio (ARR) of approximately 5.6 (19.5 ÷ 3.5) falls far below the screening threshold of ≥20–30 required to suspect primary aldosteronism, and both the aldosterone and renin values are within or near normal ranges 1.

Detailed Analysis

Aldosterone-to-Renin Ratio Calculation

• ARR = 19.5 ng/dL ÷ 3.5 ng·mL⁻¹·h⁻¹ = 5.6 1
• This ratio is dramatically below the screening cutoff of ≥20–30 recommended by the American College of Cardiology and American Heart Association 1
• For primary aldosteronism screening to be positive, both criteria must be met: ARR ≥20–30 AND plasma aldosterone concentration ≥10–15 ng/dL 1

Individual Component Assessment

Plasma Aldosterone (19.5 ng/dL):

• This value is mildly elevated above the minimum threshold of 10–15 ng/dL required for a positive screen 1
• However, aldosterone elevation alone without an elevated ARR does not indicate primary aldosteronism 1
• Mild aldosterone elevation can occur in essential hypertension, particularly with diuretic use, high dietary sodium intake, or physiologic stress 1

Plasma Renin Activity (3.5 ng·mL⁻¹·h⁻¹):

• This value is normal to elevated, not suppressed 1
• In primary aldosteronism, renin is characteristically suppressed (typically <0.5–1.0 ng·mL⁻¹·h⁻¹) due to aldosterone-mediated volume expansion 1, 2
• The presence of non-suppressed renin essentially excludes classical primary aldosteronism 2

Clinical Significance

Why This Rules Out Primary Aldosteronism

• Primary aldosteronism is characterized by autonomous aldosterone production with suppressed renin 1, 2
• The hallmark finding is a high ARR (≥20–30) with suppressed renin activity 1
• Your patient has neither of these features—the ARR is low (5.6) and renin is not suppressed (3.5) 1, 2
• The specificity for primary aldosteronism improves when using a minimum plasma renin activity cutoff of 0.5 ng/mL/h; your patient's renin of 3.5 is seven times higher than this threshold 1

Alternative Explanations for These Values

Most likely diagnoses:

• Essential (primary) hypertension with normal renin-angiotensin-aldosterone system activity 2
• Secondary aldosteronism (if aldosterone were higher)—where both renin and aldosterone are elevated due to renal artery stenosis, heart failure, or volume depletion 3
• Medication effects—ACE inhibitors, ARBs, or diuretics can elevate both renin and aldosterone 1

Medication Considerations

Factors That May Affect Interpretation

• Beta-blockers suppress renin and can cause false-positive ARR (low renin, normal aldosterone) 1
• ACE inhibitors and ARBs increase renin and can cause false-negative ARR 1
• Diuretics increase both renin and aldosterone 1
• If your patient is on any of these medications, the non-suppressed renin makes primary aldosteronism even less likely, as these drugs would need to be causing a massive renin elevation to mask underlying suppression 1

Clinical Recommendations

No Further Testing Needed for Primary Aldosteronism

• Do not proceed with confirmatory testing (saline suppression test, oral salt loading) as the screening test is clearly negative 1
• Do not order adrenal imaging for primary aldosteronism evaluation 1
• Do not refer to endocrinology specifically for primary aldosteronism workup 1

Focus on Alternative Causes of Hypertension

• Evaluate for other secondary causes if hypertension is resistant (uncontrolled on ≥3 medications including a diuretic): renal artery stenosis, obstructive sleep apnea, chronic kidney disease, pheochromocytoma, Cushing syndrome 1
• Optimize essential hypertension management with standard antihypertensive therapy 1
• If the patient has resistant hypertension, consider adding a mineralocorticoid receptor antagonist (spironolactone 25–50 mg daily) empirically, as this provides significant blood pressure reduction (25/12 mmHg) regardless of primary aldosteronism status 1

Common Pitfalls to Avoid

• Do not assume that any elevation in aldosterone indicates primary aldosteronism—the ARR and suppressed renin are essential diagnostic features 1, 2
• Do not rely on hypokalemia as a screening criterion; it is absent in approximately 50% of primary aldosteronism cases, but its absence does not change the interpretation of a negative ARR 1
• Do not repeat ARR testing unless clinical circumstances change dramatically (development of severe hypokalemia, adrenal incidentaloma, or worsening resistant hypertension) 1