In a 13-year-old obese male with persistent hypertension documented on multiple visits and acanthosis nigricans of the neck and axillae, which is the most appropriate initial laboratory test? A. Plasma catecholamines B. Plasma renin activity C. Cortisol D. Ambulatory blood pressure monitoring

Most Appropriate Initial Laboratory Test

The most appropriate initial laboratory test is B. Plasma renin activity (as part of an aldosterone-to-renin ratio), not ambulatory BP monitoring, plasma catecholamines, or cortisol alone.

Clinical Context and Reasoning

This 13-year-old obese boy presents with a constellation of findings that strongly suggests insulin resistance syndrome/metabolic syndrome rather than a primary endocrine cause of hypertension:

• Obesity with acanthosis nigricans is a dermatologic marker of insulin resistance and metabolic syndrome 1
• Persistent hypertension in the setting of obesity and acanthosis nigricans represents the metabolic syndrome phenotype 2
• Acanthosis nigricans has a strong association with metabolic syndrome (p=0.003), with 27.7% of patients having both conditions 1

Why Plasma Renin Activity (Aldosterone-to-Renin Ratio) is Most Appropriate

While this clinical picture suggests metabolic syndrome, secondary causes of hypertension must be excluded, particularly primary aldosteronism:

• Primary aldosteronism affects 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension 3
• The aldosterone-to-renin ratio (ARR) is the recommended screening test for all pediatric patients with confirmed hypertension 3
• Obesity itself is associated with increased plasma renin activity, making this measurement diagnostically important to distinguish obesity-related hypertension from primary aldosteronism 4
• In obese hypertensive subjects, plasma renin activity correlates directly with diastolic blood pressure and plays an important role in obesity-induced hypertension 4

Test Interpretation Parameters

• A positive ARR requires both ARR ≥20-30 AND plasma aldosterone ≥10-15 ng/dL 3
• Blood should be collected in the morning with the patient seated for 5-15 minutes 3
• Patient should be potassium-replete before testing, as hypokalemia suppresses aldosterone production 3

Why Other Options Are Less Appropriate

D. Ambulatory BP Monitoring

• While ABPM is useful for confirming hypertension and excluding white coat hypertension 5, the question states hypertension is already documented on multiple visits
• ABPM becomes more useful as children age and is less well tolerated by younger children 5
• ABPM is a confirmatory tool, not a diagnostic laboratory test for the underlying cause 5

A. Plasma Catecholamines

• Plasma catecholamines screen for pheochromocytoma, which is rare in children
• This patient lacks typical features of catecholamine excess (paroxysmal symptoms, severe/labile hypertension)
• Obesity itself increases sympathetic activity and plasma norepinephrine, making interpretation difficult 6
• Not indicated as initial testing without suggestive clinical features

C. Cortisol

• Screens for Cushing syndrome, which typically presents with central obesity, striae, moon facies, and buffalo hump
• Acanthosis nigricans is not a typical feature of Cushing syndrome
• The clinical picture of truncal obesity with acanthosis nigricans beginning at age 6-7 years suggests metabolic syndrome with autosomal dominant inheritance pattern rather than hypercortisolism 2

Clinical Pitfalls to Avoid

• Do not assume all obesity-related hypertension is benign - up to 20% of resistant hypertension cases have primary aldosteronism 3
• Do not rely on presence or absence of hypokalemia - it is absent in approximately 50% of primary aldosteronism cases 3
• Acanthosis nigricans is strongly associated with insulin resistance, hypertension, and metabolic syndrome (prevalence 14.5% in adolescents, with 61.54% occurring in obese individuals) 7
• Patients with obesity and acanthosis nigricans follow a detrimental sequence: truncal obesity at age 6-7 years → hypertension in young adulthood → diabetes type 2 in late adulthood 2

Next Steps After Initial Testing

If ARR is positive (≥20-30 with aldosterone ≥10-15 ng/dL):

• Confirmatory testing required (saline suppression test or oral sodium loading) 3
• Referral to pediatric endocrinology/hypertension specialist 3

If ARR is normal:

• Focus on lifestyle modification for metabolic syndrome (weight reduction, increased physical activity) 5
• Pharmacologic treatment if blood pressure remains ≥95th percentile after 3-6 months of lifestyle intervention 5
• Consider ACE inhibitor or ARB as initial pharmacologic therapy 5