What are the possibilities for an adult patient with hypertension and an elevated aldosterone renin ratio (ARR) but a normal computed tomography (CT) adrenal scan?

Elevated Aldosterone-Renin Ratio with Normal CT Adrenal: Diagnostic Possibilities

The most likely diagnosis is bilateral idiopathic adrenal hyperplasia (IHA), which accounts for approximately 50-67% of primary aldosteronism cases and typically presents with normal or minimally abnormal adrenal imaging. 1, 2, 3

Understanding the Clinical Context

When you encounter an elevated aldosterone-renin ratio (ARR) but normal CT imaging, you are dealing with a common scenario in primary aldosteronism workup. The absence of a visible adenoma on CT does NOT exclude primary aldosteronism - in fact, the majority of cases will have normal-appearing adrenals on imaging. 2

Primary Diagnostic Possibilities

Bilateral Idiopathic Hyperplasia (Most Common)

• This represents approximately 60-67% of all primary aldosteronism cases and is the most likely diagnosis when CT is normal 2, 3
• The adrenal glands appear normal or show only minimal bilateral nodularity on CT imaging 2
• These patients require lifelong medical therapy with mineralocorticoid receptor antagonists rather than surgery 3

Microscopic Aldosterone-Producing Adenoma

• Small adenomas (<1 cm) may not be visible on standard CT imaging 2
• These represent approximately one-third of primary aldosteronism cases but can be missed on imaging 2, 3
• Adrenal venous sampling is essential to distinguish this from bilateral disease 2

Unilateral Adrenal Hyperplasia

• Less common variant that appears normal on CT but shows unilateral aldosterone hypersecretion on adrenal venous sampling 3
• Potentially curable with unilateral adrenalectomy 3

Critical Next Steps: Confirmatory Testing Required

You cannot proceed to subtype determination until autonomous aldosterone production is confirmed. 4, 1 The elevated ARR is only a screening test with low specificity due to common low-renin states from volume expansion or dietary salt. 4

Confirmatory Testing Options

Oral Sodium Loading Test (Preferred)

• Administer high-sodium diet (>200 mEq/day) for 3 days with measurement of 24-hour urine aldosterone 1, 2
• Failure to suppress urinary aldosterone below threshold confirms autonomous production 1
• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone and causes false-negatives 1

Intravenous Saline Suppression Test

• Infuse 2L normal saline over 4 hours 1
• Plasma aldosterone >5-10 ng/dL after infusion confirms primary aldosteronism 1

Subtype Determination: The Critical Decision Point

Once primary aldosteronism is biochemically confirmed, adrenal venous sampling (AVS) is MANDATORY before considering surgery, even with normal CT imaging. 1, 5 This is the single most important step that determines whether the patient receives surgery (potentially curative) versus lifelong medical therapy.

Why Adrenal Venous Sampling is Essential

• CT imaging alone is insufficient for treatment decisions - up to 25% of patients would undergo unnecessary adrenalectomy based on CT findings alone 1
• Normal-appearing adrenals on CT can harbor microscopic adenomas or unilateral hyperplasia 2
• Bilateral nodularity on CT may represent nonfunctioning incidentalomas with unilateral aldosterone production 2
• AVS is the only test that definitively distinguishes unilateral from bilateral aldosterone hypersecretion 1, 2

Exception to AVS requirement: Patients <40 years old with clear unilateral adenoma on imaging, as bilateral hyperplasia is rare in this population 1

Important Medication Considerations

Several antihypertensive medications interfere with ARR interpretation and confirmatory testing:

• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn for at least 4 weeks before any testing 4, 1
• Beta-blockers and direct renin inhibitors suppress renin and cause false-positive ARR 4
• ACE inhibitors and ARBs raise renin and can cause false-negative ARR, but paradoxically increase test sensitivity if renin remains suppressed despite these medications 4
• Diuretics should be stopped when feasible 4

If medications cannot be safely discontinued, interpret results in the context of the specific drugs being taken. 1

Uncommon but Important Alternative Diagnosis

Primary Aldosteronism with Secondary Renal Damage

• In patients with severe, longstanding hypertension, secondary kidney damage can cause renin to "escape" from suppression 6
• These patients have elevated ARR due to disproportionately high aldosterone despite non-suppressed renin 6
• They typically have elevated serum creatinine and may develop severe hyperkalemia when treated with spironolactone 6
• This represents a medical emergency requiring early specific treatment to prevent further renal deterioration 6

Treatment Algorithm Based on Subtype

For Unilateral Disease (Adenoma or Unilateral Hyperplasia):

• Laparoscopic unilateral adrenalectomy is the treatment of choice 1, 5, 7
• Improves blood pressure in virtually 100% of patients 5, 7
• Achieves complete cure of hypertension in approximately 50% of cases 5, 7
• Earlier diagnosis and treatment improves cure rates by preventing irreversible vascular remodeling 5

For Bilateral Disease (Idiopathic Hyperplasia):

• Lifelong medical therapy with mineralocorticoid receptor antagonists 5, 3
• Spironolactone 25-50 mg daily is first-line treatment 1, 5
• Eplerenone 50-100 mg daily is an alternative with fewer anti-androgenic side effects 5
• Monitor potassium within 1 week of initiation and regularly thereafter, especially in patients with renal dysfunction or concurrent ACE inhibitor/ARB use 1

Common Pitfalls to Avoid

• Never rely on presence or absence of hypokalemia - it is absent in approximately 50% of primary aldosteronism cases 1, 5, 7
• Never proceed to surgery based on CT findings alone without adrenal venous sampling (except in young patients <40 with clear unilateral adenoma) 1
• Never perform confirmatory testing while patient is on mineralocorticoid receptor antagonists - requires 4-week washout 1
• Never assume normal CT excludes primary aldosteronism - bilateral hyperplasia and microscopic adenomas are common 2, 3

Clinical Significance and Urgency

Primary aldosteronism carries dramatically worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels, including 3.7-fold increase in heart failure, 4.2-fold increase in stroke, and 12.1-fold increase in atrial fibrillation. 7 This makes accurate diagnosis and appropriate treatment essential, not optional.