What is the most appropriate initial laboratory test for a patient with persistent hypertension and acanthosis nigricans?

Most Appropriate Initial Laboratory Test

The most appropriate initial laboratory test is B. Plasma renin activity (or plasma aldosterone-to-renin ratio), as acanthosis nigricans in the context of persistent hypertension strongly suggests insulin resistance and metabolic syndrome, which are commonly associated with primary aldosteronism—a leading cause of secondary hypertension that requires screening with plasma aldosterone and renin levels. 1, 2

Clinical Reasoning

Recognition of Acanthosis Nigricans as a Key Clinical Clue

• Acanthosis nigricans is a hyperpigmented, velvety skin change that serves as a visible marker of insulin resistance and metabolic syndrome 3, 4
• In patients with hypertension, the presence of acanthosis nigricans indicates multiple metabolic abnormalities including obesity, hyperinsulinemia, dyslipidemia, and increased risk for secondary causes of hypertension 4, 5
• The combination of persistent hypertension with acanthosis nigricans significantly increases the likelihood of secondary hypertension, particularly primary aldosteronism, which affects 8-20% of resistant hypertension cases 2

Why Plasma Renin Activity (Aldosterone-to-Renin Ratio) is the Priority

• The American Heart Association recommends that laboratory examination of patients with resistant hypertension should include a paired morning plasma aldosterone and plasma renin activity (PRA) to screen for primary aldosteronism 1
• The aldosterone-to-renin ratio (ARR) has a high negative predictive value for screening primary aldosteronism, making it an effective initial test 1
• The 2024 ESC guidelines now recommend measuring renin and aldosterone in all adults with confirmed hypertension (Class IIa recommendation), representing a significant shift toward broader screening 2
• A high ratio (>20) when serum aldosterone is >16 ng/dL and PRA is <0.6 ng/mL per hour is suggestive of primary aldosteronism 1

Why Other Options Are Less Appropriate Initially

• Plasma catecholamines (Option A) and urinary metanephrines (Option C) are appropriate for screening pheochromocytoma, but this condition presents with episodic symptoms and labile hypertension—not the clinical picture described here 1
• The American Heart Association states that measurement of plasma or urinary metanephrines is indicated only when pheochromocytoma is specifically suspected based on clinical features 1
• Cortisol level (Option D) would be appropriate if Cushing syndrome were suspected, which typically presents with obesity, abdominal striae, moon facies, and intrascapular fat deposition—features not mentioned in this case 1

Comprehensive Initial Workup Context

While the aldosterone-to-renin ratio is the most specific test for this clinical presentation, the complete initial evaluation should include:

• Basic metabolic profile (serum sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, and creatinine) 1, 6
• Hypokalemia, if present, would further support the diagnosis of primary aldosteronism 1, 2
• Fasting blood glucose and HbA1c to assess for diabetes mellitus, given the strong association between acanthosis nigricans and insulin resistance 7, 6, 3
• Urinalysis and urinary albumin-to-creatinine ratio to assess for kidney damage 1, 7, 6
• Lipid profile for cardiovascular risk stratification 7, 6

Important Clinical Pitfalls to Avoid

• Do not delay screening for primary aldosteronism in patients with persistent hypertension and metabolic features like acanthosis nigricans 2
• Interpretation of the aldosterone-to-renin ratio can be affected by certain antihypertensive medications: mineralocorticoid receptor antagonists raise aldosterone levels, while beta-blockers and direct renin inhibitors lower renin levels 1
• The ratio is most sensitive when the patient is taking an ACE inhibitor or ARB, as these drugs elevate PRA; if renin remains suppressed despite these medications, it increases diagnostic sensitivity 1
• Even with a positive screening test, confirmatory testing (such as saline infusion test) and adrenal imaging are required before definitive diagnosis 2