When should I test for epinephrine (adrenaline) levels?

When to Test Epinephrine Levels

Epinephrine (adrenaline) levels should primarily be tested as part of the diagnostic workup for suspected pheochromocytoma or paraganglioma (PPGL), not as an isolated test. Testing should focus on metanephrines rather than direct epinephrine measurement.

Primary Indications for Testing

• Suspected pheochromocytoma/paraganglioma: Testing is indicated in patients with clinical signs of catecholamine excess or adrenal masses ≥10 HU on non-contrast CT 1, 2
• Genetic predisposition: Individuals with hereditary syndromes associated with PPGL (MEN2, VHL, SDHx mutations) should undergo biochemical screening starting at age 6-8 years 1
• Adrenal incidentaloma evaluation: All patients with adrenal masses ≥10 HU on non-contrast CT should be screened for catecholamine excess 1, 2
• Pre-operative screening: Before any surgery in patients with suspected PPGL to prevent intraoperative hypertensive crisis 1
• Pregnancy planning: In patients with known genetic predisposition to PPGL 1

Preferred Testing Methods

• Plasma free metanephrines (normetanephrine and metanephrine) or 24-hour urinary fractionated metanephrines are the recommended first-line tests, NOT direct epinephrine measurement 1, 3
• Plasma free metanephrines have the highest sensitivity (99%) compared to other biochemical tests 3
• Urinary fractionated metanephrines have high sensitivity (97%) but lower specificity (69%) 3
• Plasma methoxytyramine (metabolite of dopamine) should be included when paraganglioma is suspected 1, 4

Testing Protocol for Optimal Results

• Collection conditions for plasma tests:

  • Patient should be supine for 30 minutes before blood collection 4
  • Blood should be collected after an overnight fast 4
  • Patient should avoid interfering medications and foods 1

• Interpretation of results:

  • Levels >2× upper limit of normal strongly suggest PPGL 1
  • Borderline elevations may require confirmatory testing with clonidine suppression test 5
  • Normal plasma metanephrine levels effectively exclude PPGL (100% negative predictive value) 6

Special Populations Requiring Screening

• SDHx mutation carriers: Begin screening at age 6-8 years with annual plasma metanephrines or 24-hour urinary fractionated metanephrines 1
• MEN2 syndrome carriers: Begin screening at age 11 years for "high" risk alleles and age 16 for "moderate" risk alleles 1
• Patients with hypertension and adrenal mass: Should undergo biochemical testing for PPGL 1, 2
• Patients with symptoms of catecholamine excess: Paroxysmal hypertension, headaches, sweating, palpitations 1

Follow-up Testing Recommendations

• Confirmed PPGL cases: After surgical treatment, measurement of plasma or urine metanephrines should be performed by 8 weeks post-treatment 1
• SDHD mutation carriers: Annual biochemical measurements regardless of surgical history 1
• Surveillance in genetic syndromes: Annual biochemical testing and imaging every 2-3 years 1

Important Caveats

• Direct epinephrine measurement has lower diagnostic accuracy than metanephrines 6, 3
• False positives can occur with certain medications, stress, or improper sample collection 1, 4
• In high-risk patients (familial syndromes), plasma metanephrines are preferred due to higher sensitivity 7
• In low-risk patients, 24-hour urinary tests may be preferred due to higher specificity 7

Remember that testing for epinephrine directly is not recommended; instead, focus on its metabolites (metanephrines) for more accurate diagnosis of catecholamine-producing tumors 3, 4.