A 45-year-old patient with a family history of early stroke and hypertension, not responding to dual antihypertensive therapy, also has mild hypokalemia (3.2). What is the next step in management?

Aldosterone-Renin Ratio is the Next Step

The correct answer is A: Aldosterone-renin ratio. This patient presents with a classic triad for primary aldosteronism: resistant hypertension (not responding to dual therapy), hypokalemia (3.2 mEq/L), and a family history of early stroke—all of which are Class I indications for screening for primary aldosteronism 1.

Why Primary Aldosteronism Screening is Indicated

The 2017 ACC/AHA Hypertension Guidelines provide explicit Class I recommendations for screening primary aldosteronism in patients with 1:

• Resistant hypertension (hypertension not controlled on 2+ medications qualifies as treatment-resistant)
• Hypokalemia (spontaneous or substantial if diuretic-induced)
• Family history of early-onset hypertension or stroke at young age (<40 years)

This patient meets all three criteria, making primary aldosteronism screening mandatory rather than optional 1.

Why Not Metanephrines

Pheochromocytoma screening with metanephrines would be indicated if the patient presented with 1:

• Paroxysmal hypertension or "spells"
• Classic triad of headache, sweating, and palpitations
• BP lability with pallor
• Adrenal incidentaloma
• Family history of pheochromocytoma/paraganglioma

This patient has none of these features. The presentation is consistent with sustained hypertension with hypokalemia, not the episodic symptoms characteristic of catecholamine excess 1.

The Diagnostic Algorithm

Step 1: Obtain Plasma Aldosterone-Renin Ratio (Class I Recommendation)

• The plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is the recommended screening test for primary aldosteronism 1, 2
• Critical preparation: Correct hypokalemia before testing and withdraw aldosterone antagonists for 4-6 weeks 1
• An elevated PAC/PRA ratio plus an elevated absolute aldosterone level constitutes a positive screen 2

Step 2: Confirmatory Testing if Screening is Positive

If the aldosterone-renin ratio is elevated 1, 2:

• Oral sodium loading test with 24-hour urine aldosterone, OR
• IV saline infusion test with plasma aldosterone at 4 hours
• Adrenal CT scan to evaluate for adenoma vs. bilateral hyperplasia

Step 3: Specialist Referral (Class I Recommendation)

• Mandatory referral to a hypertension specialist or endocrinologist for further evaluation and treatment if screening is positive 1

Important Clinical Context

Prevalence Matters

Primary aldosteronism affects 1:

• 8% of general hypertensive population
• Up to 20% of patients with resistant hypertension
• This makes it the most common identifiable cause of resistant hypertension

Hypokalemia is NOT Required

Critical pitfall: Hypokalemia is absent in the majority of cases and has low negative predictive value for primary aldosteronism 1. However, when present (as in this patient), it significantly increases the likelihood of the diagnosis 1, 3.

Why This Matters for Outcomes

Early detection of primary aldosteronism is crucial because 4, 5:

• Curable hypertension: Unilateral aldosterone-producing adenomas can be surgically cured with adrenalectomy
• Targeted therapy: Bilateral hyperplasia responds to mineralocorticoid receptor antagonists (spironolactone)
• Cardiovascular protection: Primary aldosteronism causes disproportionate cardiovascular and kidney damage beyond BP elevation alone 1
• Stroke prevention: Particularly relevant given this patient's family history of early stroke 1

The Family History Connection

The family history of early stroke is particularly significant 1:

• Glucocorticoid-remediable aldosteronism (GRA) is a familial form that presents with early-onset hypertension and stroke
• This autosomal dominant condition should be considered if primary aldosteronism is confirmed 3

Practical Testing Considerations

Before ordering the aldosterone-renin ratio 1, 6:

• Correct the hypokalemia first (potassium <3.5 mEq/L can suppress aldosterone secretion)
• Review medications that interfere with testing: spironolactone (withdraw 4-6 weeks prior), beta-blockers, ACE inhibitors, ARBs
• Calcium channel blockers and alpha-blockers have minimal effect and can be continued
• Patient should be on normal sodium diet

Bottom Line

Order the plasma aldosterone-renin ratio now 1. This patient's presentation—resistant hypertension, hypokalemia, and family history of early stroke—represents a textbook indication for primary aldosteronism screening with the highest level of guideline support (Class I, Level C-EO) 1. Pheochromocytoma screening would be inappropriate given the absence of characteristic paroxysmal symptoms 1.