In a 13-year-old obese boy with persistent hypertension, acanthosis nigricans, and paroxysmal headache, sweating, and palpitations, what is the next step to establish the diagnosis?

Measure Plasma Free Metanephrines or 24-Hour Urinary Fractionated Metanephrines

In this 13-year-old obese boy with persistent hypertension, acanthosis nigricans, and the classic triad of headache, sweating, and palpitations, the next step to establish diagnosis is to measure catecholamines (Option A) - specifically plasma free metanephrines or 24-hour urinary fractionated metanephrines - to screen for pheochromocytoma. 1, 2

Clinical Reasoning

The combination of symptoms in this patient creates a compelling clinical picture:

• The classic triad of headache, palpitations, and sweating in a hypertensive patient has 93.8% specificity and 90.9% sensitivity for pheochromocytoma, with an exclusion value of 99.9% when absent 1, 2
• The American College of Cardiology and American Heart Association recommend immediate biochemical testing when this classic presentation occurs 3, 1, 2
• Although pheochromocytoma is rare (0.01-0.2% of general hypertensive population), it can be present in up to 4% of patients with resistant hypertension 1, 2

The presence of acanthosis nigricans indicates insulin resistance and metabolic syndrome, which commonly causes hypertension in obese children 4, 5, 6. However, the paroxysmal symptoms (headache, sweating, palpitations) are the critical distinguishing feature that mandates ruling out pheochromocytoma first 3, 1.

Recommended Biochemical Testing

First-line testing should include either:

• Plasma free metanephrines (sensitivity 96-100%, specificity 89-98%) 1, 2, 7
• 24-hour urinary fractionated metanephrines (sensitivity 86-97%, specificity 86-95%) 1, 2, 7

For plasma collection, ideally use an indwelling venous catheter after the patient has been lying supine for 30 minutes to minimize false positives 1, 8, 2. However, in pediatric patients, 24-hour urine collection may be more practical once the child is continent 8.

Interpretation Algorithm

Based on metanephrine levels:

• If ≥4 times the upper limit of normal: Results are consistent with pheochromocytoma/paraganglioma - proceed immediately to imaging (MRI preferred over CT due to risk of hypertensive crisis with IV contrast) 1, 8, 2
• If 2-4 times the upper limit of normal: Repeat testing in 2 months and consider genetic testing for hereditary syndromes 1, 8
• If marginally elevated (1-2 times upper limit): Repeat testing in 6 months using proper collection technique or consider clonidine suppression test (100% specificity, 96% sensitivity) 1, 8

Why Not the Other Options?

Option B (Cortisone level and ACTH): While Cushing's syndrome can cause hypertension and obesity, the paroxysmal triad of symptoms (headache, sweating, palpitations) is pathognomonic for catecholamine excess, not cortisol excess 3. The American College of Cardiology specifically recommends catecholamine testing for this presentation 3, 1.

Option C (Renal US): While renovascular hypertension should be considered in pediatric hypertension, the European Society of Hypertension recommends suspecting renovascular disease in patients with stage 2 hypertension, significant diastolic hypertension, or discrepant kidney sizes 3. The paroxysmal symptoms in this case point specifically to pheochromocytoma 3, 1.

Option D (Ambulatory BP Monitoring): While ABPM is useful for evaluating high-risk patients with obesity for potential masked hypertension 3, it does not establish the underlying diagnosis. The American Heart Association recommends ABPM after initial evaluation, not as the diagnostic test for secondary causes 3.

Critical Pitfalls to Avoid

• Never initiate beta-blockade alone before alpha-blockade in suspected pheochromocytoma, as this can precipitate severe hypertensive crisis due to unopposed alpha-adrenergic stimulation 1, 2
• Avoid contrast-enhanced CT until pheochromocytoma is excluded - use MRI preferentially 1, 2
• Never perform fine needle biopsy of adrenal masses before excluding pheochromocytoma - this is absolutely contraindicated and can trigger fatal hypertensive crisis 1, 8
• Discontinue interfering medications before testing, including tricyclic antidepressants, sympathomimetics, and decongestants 1, 2

Additional Considerations

While this patient's obesity and acanthosis nigricans suggest metabolic syndrome (which increases hypertension risk twofold 6), life-threatening complications of undiagnosed pheochromocytoma include syncope, cardiac arrest, myocardial infarction, hypertensive crisis, stroke, or sudden death 1, 2. This makes ruling out pheochromocytoma the immediate priority before attributing hypertension solely to obesity 3, 9.

Approximately 30-35% of pheochromocytomas are hereditary, so genetic counseling should be considered if the diagnosis is confirmed 2, 7.