What is the next step to establish a diagnosis for an obese boy with persistent hypertension, acanthosis nigricans, and symptoms including headache, sweating, and palpitations?

Measure Plasma Free Metanephrines or 24-Hour Urinary Fractionated Metanephrines

The next step is to measure catecholamines (plasma free metanephrines or 24-hour urinary fractionated metanephrines) to screen for pheochromocytoma, as this patient presents with the classic triad of headache, sweating, and palpitations in the setting of persistent hypertension. 1, 2

Clinical Reasoning

This obese adolescent presents with a constellation of findings that requires systematic evaluation:

Primary Concern: Pheochromocytoma

• The 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 1, 2
• Pheochromocytoma, though rare (0.01-0.2% of general hypertensive population), can be present in up to 4% of patients with resistant hypertension 1
• Life-threatening complications can occur, including syncope, cardiac arrest, myocardial infarction, hypertensive crisis, stroke, or sudden death 1

Biochemical Testing Options

First-line testing should include either: 1, 2

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

For plasma collection, ideally use an indwelling venous catheter after the patient has been lying supine for 30 minutes to minimize false positives 1, 2

Interpretation Algorithm

If levels are ≥4 times the upper limit of normal: 1, 2

• Results are consistent with pheochromocytoma/paraganglioma
• Proceed immediately to imaging (MRI preferred over CT due to risk of hypertensive crisis with IV contrast)

If levels are 2-4 times the upper limit of normal: 1

• Repeat testing in 2 months
• Consider genetic testing for hereditary syndromes

If marginally elevated (1-2 times upper limit): 1

• Repeat testing in 6 months using proper collection technique
• Consider clonidine suppression test (100% specificity, 96% sensitivity)

Secondary Consideration: Insulin Resistance Syndrome

The acanthosis nigricans indicates underlying insulin resistance, which is commonly associated with obesity and can contribute to hypertension 3, 4, 5:

• Acanthosis nigricans is a cutaneous marker of hyperinsulinemia and insulin resistance 3, 5
• Children with acanthosis nigricans are at risk for metabolic syndrome, dyslipidemia, and type 2 diabetes 3, 6, 7
• However, insulin resistance alone does not explain the classic catecholamine-excess symptoms (headache, sweating, palpitations)

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 these procedures until pheochromocytoma is excluded: 1

• Contrast-enhanced CT (use MRI preferentially)
• Fine needle biopsy of adrenal masses (absolutely contraindicated—can trigger fatal hypertensive crisis)

Discontinue interfering medications before testing: 2

• Tricyclic antidepressants
• Sympathomimetics and decongestants
• Certain neuropsychiatric agents

Additional Evaluation After Catecholamine Testing

While pursuing pheochromocytoma workup, complete standard hypertension evaluation 1:

• Serum electrolytes and creatinine with eGFR
• Fasting glucose or HbA1c (given acanthosis nigricans and obesity)
• Lipid profile
• ECG for left ventricular hypertrophy
• Urinalysis with albumin/creatinine ratio

If pheochromocytoma is confirmed and surgery is planned, alpha-adrenergic blockade must be started 7-14 days preoperatively with gradually increasing dosages until blood pressure targets are achieved 1, 2