In a young adult with resistant hypertension despite two antihypertensive agents, which screening test is most appropriate?

Screening for Secondary Hypertension in Young Adults with Resistant Hypertension

In a young adult with resistant hypertension on two antihypertensive agents, the plasma aldosterone-to-renin ratio (Option B) is the most appropriate initial screening test.

Rationale for Primary Aldosteronism Screening

Primary aldosteronism is the most common and most important secondary cause to screen for in this clinical scenario, affecting up to 20% of patients with resistant hypertension and representing a potentially curable cause with dramatically higher cardiovascular risk than essential hypertension 1, 2.

Why the Aldosterone-Renin Ratio is First-Line

• The 2017 ACC/AHA guidelines give a Class I recommendation for screening with the plasma aldosterone-to-renin ratio in adults with resistant hypertension 1.
• The ARR has excellent sensitivity (>90%) and specificity (>90%) for detecting primary aldosteronism when properly performed 2.
• A positive screen requires both an ARR ≥20-30 AND plasma aldosterone concentration ≥10-15 ng/dL 1, 2.

Clinical Impact of Early Detection

Primary aldosteronism causes markedly worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels 2:

• 3.7-fold increase in heart failure
• 4.2-fold increase in stroke
• 6.5-fold increase in myocardial infarction
• 12.1-fold increase in atrial fibrillation

Early diagnosis and targeted treatment—either unilateral adrenalectomy or mineralocorticoid receptor antagonist therapy—can reverse aldosterone-mediated target organ damage and mitigate this excess cardiovascular risk 2.

Why Other Tests Are Not First-Line

24-Hour Urine Cortisol (Option A)

• Cushing syndrome is a much less common cause of resistant hypertension and typically presents with distinctive clinical features (central obesity, facial plethora, proximal muscle weakness, wide purple striae) that should prompt this specific test 1, 3.
• Without these characteristic features, screening for Cushing syndrome is not the priority in young adults with resistant hypertension 3.

Plasma or Urinary Fractionated Metanephrines (Options C & D)

• Pheochromocytoma is uncommon (affecting <1% of hypertensive patients) and typically presents with episodic symptoms: paroxysmal hypertension, headaches, palpitations, diaphoresis, and pallor 1, 4, 3.
• Plasma free metanephrines have 96-100% sensitivity and are the screening test of choice when pheochromocytoma is specifically suspected based on clinical features 4, 5.
• However, in the absence of episodic symptoms or labile hypertension, screening for pheochromocytoma is not the initial priority 4, 3.
• The 2017 ACC/AHA guidelines do not recommend routine pheochromocytoma screening in resistant hypertension without suggestive clinical features 1.

Practical Testing Considerations

Patient Preparation for ARR Testing

• Ensure potassium repletion (target 4.0-5.0 mEq/L) before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1, 2.
• Discontinue interfering medications when clinically feasible 1, 2:
  • Beta-blockers and diuretics should be stopped (they suppress renin and cause false-positives)
  • Mineralocorticoid receptor antagonists must be withdrawn ≥4 weeks before testing
  • Long-acting calcium channel blockers and alpha-receptor antagonists are safe alternatives that minimally interfere with ARR
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 1, 2.

Blood Collection Technique

• Collect blood in the morning (0800-1000 hours) with the patient out of bed for ≥2 hours and seated for 5-15 minutes immediately before collection 1, 2.
• Blood should be drawn with the patient in a seated position 1, 2.

Next Steps After Positive Screening

• All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading 1, 2.
• Confirmatory test options include intravenous saline suppression test or oral sodium loading with 24-hour urine aldosterone measurement 1, 2.
• Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination via adrenal venous sampling and treatment planning 1, 2.

Common Pitfalls to Avoid

• Do not rely on hypokalemia as a screening trigger—it is absent in approximately 50% of primary aldosteronism cases 1, 2.
• Do not proceed to expensive imaging studies before completing basic biochemical screening 3.
• Do not skip confirmatory testing after a positive ARR—the screening test alone has limited specificity due to common low-renin states 1, 2.
• Do not proceed to surgery based on CT findings alone—adrenal venous sampling is mandatory to distinguish unilateral from bilateral disease, as up to 25% of patients might undergo unnecessary adrenalectomy based on imaging alone 2.

Additional Evaluation

While screening for primary aldosteronism is the priority, a comprehensive evaluation for resistant hypertension should also include 1, 3:

• Basic metabolic panel (assess for spontaneous hypokalemia)
• Serum creatinine and eGFR (evaluate for renal parenchymal disease)
• Urinalysis and urinary albumin-to-creatinine ratio (detect proteinuria and kidney damage)
• Assessment for medication nonadherence and white coat effect
• Review of substances that impair BP control (NSAIDs, decongestants, herbal products)
• Consideration of obstructive sleep apnea (present in 25-50% of resistant hypertension cases) 3, 6