What follow-up blood work is recommended for a patient with a history of an adrenaline-producing tumor (pheochromocytoma) removed from the adrenal gland?

Follow-up Blood Work After Pheochromocytoma Resection

After surgical removal of a pheochromocytoma, you need lifelong biochemical surveillance with plasma or urinary metanephrines (metanephrine, normetanephrine), along with chromogranin A, starting approximately 14 days post-surgery and continuing at specific intervals for at least 10 years, with lifelong monitoring recommended. 1

Initial Post-Operative Testing (14 Days After Surgery)

• Measure plasma free metanephrines or 24-hour urinary fractionated metanephrines approximately 14 days following surgery to confirm complete tumor removal and check for residual disease 1
• Include chromogranin A measurement at this initial post-operative assessment 1, 2
• For plasma free metanephrines, ideally collect from an indwelling venous catheter after 30 minutes of supine rest to minimize false positives 3

Surveillance Schedule for First 2-3 Years

• Repeat biochemical testing every 3-4 months for the first 2-3 years after surgery 1
• This intensive early surveillance is critical because recurrence risk is highest during this period 1
• Each testing cycle should include:
  • Plasma free metanephrines (normetanephrine and metanephrine) OR 24-hour urinary fractionated metanephrines 1
  • Chromogranin A 1, 2

Long-Term Surveillance (After 2-3 Years)

• Continue biochemical testing every 6 months after the initial 2-3 year intensive surveillance period 1
• Maintain this 6-month interval for at least 10 years total 1
• Lifelong surveillance is strongly recommended, particularly for high-risk patients 1

High-Risk Features Requiring More Intensive Lifelong Monitoring

You need particularly vigilant lifelong surveillance if any of these features are present:

• Extra-adrenal primary tumor location (paraganglioma) 1
• Tumor size >5 cm at diagnosis 1
• SDHB gene mutation (if genetic testing was performed) 1, 4
• Proven malignant disease (metastases identified) 1
• Pheochromocytoma without relevant preoperative hormone secretion (rare cases) 1

For these high-risk patients, imaging should be repeated at least every 6 months during the first year and yearly afterward, regardless of biochemical test results 1

Clinical Monitoring Alongside Blood Work

• Monitor blood pressure levels at each follow-up visit 1
• Assess for adrenergic symptoms: headaches, palpitations, sweating, pallor 1, 4
• Any new onset of these symptoms should prompt immediate biochemical testing and imaging, even if not scheduled 1

When to Obtain Imaging

Proceed to imaging (CT chest/abdomen/pelvis and functional imaging like PET-FDG) if any of the following occur during follow-up:

• Elevated plasma or urinary metanephrines on surveillance testing 1
• Elevated chromogranin A levels 1, 2
• New or recurrent hypertension 1
• Return of adrenergic symptoms (palpitations, headaches, sweating) 1
• New pain 1

Important Caveats About Chromogranin A

• Proton pump inhibitors (PPIs) can cause false elevations in chromogranin A, so consider discontinuing these medications before testing if clinically appropriate 2
• Renal failure can also falsely elevate chromogranin A levels 2
• Despite these limitations, chromogranin A remains valuable for long-term surveillance when interpreted in clinical context 2

Genetic Testing Considerations

• If not already performed, consider genetic testing for hereditary syndromes (MEN2, VHL, NF1, SDHB/SDHD mutations), as approximately 25-33% of pheochromocytomas are hereditary 4
• Genetic results directly impact surveillance intensity and family screening needs 1, 4

Practical Testing Approach

For plasma free metanephrines (preferred method with 96-100% sensitivity):

• Use indwelling venous catheter when possible 3
• Patient should be supine for 30 minutes before collection 3
• If marginally elevated, repeat under ideal conditions 3

For 24-hour urinary fractionated metanephrines (alternative with 86-97% sensitivity):

• May be more practical for some patients 3
• Particularly useful if plasma results are equivocal 3

The rationale for lifelong surveillance is that pheochromocytomas carry a 10-15% risk of malignancy (defined only by presence of metastases), and recurrence can occur many years after initial surgery 1, 4. This prolonged follow-up protocol prioritizes early detection of recurrence to prevent the life-threatening complications of unrecognized catecholamine excess, thereby reducing both morbidity and mortality.