How should I screen, diagnose, and manage an adult with unexplained labile hypertension and the classic triad of headache, sweating, and palpitations suggestive of pheochromocytoma?

Screening, Diagnosis, and Management of Suspected Pheochromocytoma

Immediate Biochemical Testing

In an adult presenting with labile hypertension and the classic triad of headache, sweating, and palpitations, you should immediately order plasma free metanephrines or 24-hour urinary fractionated metanephrines, as this triad has 93.8% specificity and 90.9% sensitivity for pheochromocytoma. 1

• The American College of Cardiology and American Heart Association mandate immediate biochemical testing when this classic presentation occurs, as undiagnosed pheochromocytoma can cause syncope, cardiac arrest, myocardial infarction, hypertensive crisis, stroke, or sudden death 2, 1
• This presentation warrants urgent evaluation because pheochromocytoma, though rare (0.1-0.6% of hypertensive patients), is present in up to 4% of patients with resistant hypertension 1

Optimal Biochemical Testing Strategy

Order plasma free metanephrines as the first-line test, collected from an indwelling venous catheter after the patient has been lying supine for 30 minutes to minimize false positives. 1

• Plasma free metanephrines have the highest sensitivity (96-100%) and specificity (89-98%) for diagnosing pheochromocytoma 1
• 24-hour urinary fractionated metanephrines are an acceptable alternative with sensitivity of 86-97% and specificity of 86-95% 1
• If you cannot use the ideal collection method (indwelling catheter, 30 minutes supine), proceed with standard venipuncture, but repeat under ideal conditions if results are marginally elevated 1

Critical Pre-Testing Requirements

Before testing, ensure the patient has discontinued interfering medications for at least 2 weeks, including: 1

• Tricyclic antidepressants
• Sympathomimetics and decongestants
• Certain neuropsychiatric agents

Note: Common antihypertensive medications, including alpha-1 blockers like doxazosin, do NOT interfere with plasma free metanephrine measurements and should be continued. 3

Interpretation Algorithm Based on Metanephrine Levels

Levels ≥4 Times Upper Limit of Normal

Proceed immediately to imaging with MRI of the abdomen and pelvis (preferred over CT due to risk of hypertensive crisis with IV contrast). 1

• These levels are diagnostic for pheochromocytoma/paraganglioma 1
• Never perform fine needle biopsy of a suspected pheochromocytoma—this is absolutely contraindicated and can trigger fatal hypertensive crisis 1, 4

Levels 2-4 Times Upper Limit of Normal

• Repeat testing in 2 months using proper collection technique (indwelling catheter, 30 minutes supine) 1
• Consider genetic testing for hereditary syndromes, especially in younger patients 1
• Assess for hyperadrenergic symptoms: sustained or intermittent palpitations, tachycardia, diaphoresis, tremors, or new-onset hypertension 4

Levels 1-2 Times Upper Limit of Normal (Marginally Elevated)

• Repeat testing in 6 months using ideal collection conditions 1
• Consider clonidine suppression test if clinical suspicion remains high—this test has 100% specificity and 96% sensitivity for distinguishing true pheochromocytoma from false positives 1, 3

Physical Examination Findings to Document

Look specifically for: 2

• Orthostatic hypotension (paradoxical finding due to volume depletion)
• Skin stigmata of neurofibromatosis (café-au-lait spots, neurofibromas)
• Fine tremor, tachycardia during symptomatic episodes
• Blood pressure variability between visits

Critical Management Pitfalls to Avoid

Never initiate beta-blockade alone before alpha-blockade in suspected pheochromocytoma—this can precipitate severe hypertensive crisis due to unopposed alpha-adrenergic stimulation. 1, 3

Additional contraindications until pheochromocytoma is excluded: 1

• Contrast-enhanced CT (use MRI instead)
• Fine needle biopsy of adrenal masses
• Any invasive procedures without proper alpha-blockade

Preoperative Management if Pheochromocytoma Confirmed

Start alpha-adrenergic blockade (phenoxybenzamine or doxazosin) 7-14 days preoperatively with gradually increasing dosages until blood pressure targets are achieved. 1, 4, 5

• Only add beta-blockers after adequate alpha-blockade is established to control tachyarrhythmias 5
• Ensure adequate volume repletion before surgery 6

Imaging Localization Strategy

Once biochemical diagnosis is confirmed: 1, 4

• MRI of abdomen/pelvis is preferred over CT (avoids contrast-related hypertensive crisis risk)
• Consider functional imaging with MIBG scintigraphy for high-risk features: tumor ≥5 cm, extra-adrenal location, SDHB mutation, or plasma methoxytyramine >3-fold elevated 4, 7
• Extend imaging to chest and neck if initial abdominal imaging is negative despite positive biochemistry 3

Genetic Testing Indications

Order genetic testing for: 4, 3

• All patients with extra-adrenal tumors (paragangliomas)
• Bilateral adrenal tumors
• Age <30 years at diagnosis
• Family history of pheochromocytoma or hereditary syndromes (MEN2, VHL, NF1, SDHx mutations)
• Approximately 30-35% of pheochromocytomas are hereditary with autosomal dominant inheritance 3

Post-Surgical Follow-Up

All patients require lifelong surveillance due to 10-15% recurrence risk and 10-12% malignancy rate: 4

• Repeat biochemical testing 14 days post-surgery to confirm complete resection 4
• Follow-up every 3-4 months for 2-3 years, then every 6 months 4
• More intensive surveillance required for SDHB mutations (higher malignancy risk) 4, 3