What is the role of a catecholamine (CAT) test in the management of hypertension (HTN)?

Role of Catecholamine Testing in Hypertension Management

Catecholamine testing should be performed in hypertensive patients with clinical features suggestive of pheochromocytoma, particularly those with paroxysmal hypertension, resistant hypertension, or classic symptoms such as headache, sweating, palpitations, and pallor. 1

When to Consider Catecholamine Testing

• Catecholamine testing is not indicated for all hypertensive patients but should be considered in specific clinical scenarios 1, 2:
  • Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive medications including a diuretic) 1
  • Paroxysmal hypertension with classic symptoms (headache, sweating, palpitations, pallor) 2, 3
  • Early-onset hypertension (<30 years) 2
  • Significant blood pressure variability 2, 3
  • Family history of pheochromocytoma 2

Recommended Testing Methods

• The test with the highest sensitivity (97-98%) is measurement of plasma free metanephrines, together with urinary fractionated metanephrines 1, 2
• For routine clinical practice, measurement of urinary fractionated metanephrines remains the diagnostic test of choice when plasma free metanephrines are not available 1
• Plasma free metanephrines have superior sensitivity (96-100%) and specificity (89-98%) compared to other tests 2, 4
• Urinary fractionated metanephrines have high sensitivity (86-97%) and specificity (86-95%) 1, 2

Interpretation of Results

• Very high values of metanephrines require no further testing 1, 2
• When plasma or urine values are only modestly elevated despite strong clinical suspicion:
  • Consider repeating the test 2
  • Proceed with stimulation or suppression tests (glucagon or clonidine) 1, 5
  • The clonidine suppression test is regarded as negative when there is a marked reduction of plasma catecholamines 1, 5

Potential False Positives

• Hypertensive patients may have elevated catecholamine metabolites, especially in the presence of:
  • Obesity 2
  • Obstructive sleep apnea 2
  • Use of certain medications (e.g., tricyclic antidepressants) 2
• False positive elevations are usually <4 times the upper limit of normal 2

Management Algorithm Based on Test Results

1. Initial screening: Measure plasma free metanephrines or urinary fractionated metanephrines 1, 2
2. If results are positive:
   • For levels ≥4 times upper limit of normal: Proceed to imaging to localize the tumor 2
   • For levels 2-4 times upper limit of normal: Repeat testing in 2 months and consider genetic testing 2
   • For marginally elevated levels: Repeat testing in 6 months and consider clonidine suppression test 1, 2

Clinical Relevance and Importance

• Pheochromocytoma is a rare cause of hypertension (0.2-0.4% of all hypertension cases) with an estimated annual incidence of 2-8 per million population 1
• Early diagnosis is crucial as there is typically a 3-year delay in diagnosis, and approximately one-third of cases are inherited 2
• Hypertension occurs in about 70% of all pheochromocytoma cases, being stable or paroxysmal in approximately equal proportions 1
• Untreated pheochromocytoma can lead to significant morbidity and mortality, including hypertensive crisis 6, 3

Special Considerations

• The glucagon test must be performed after the patient has been effectively treated with an alpha-adrenoreceptor antagonist to prevent marked blood pressure increases 1
• Beta-blockers should never be started before alpha-blockers in patients with suspected pheochromocytoma, as blockade of vasodilatory peripheral beta-adrenergic receptors with unopposed alpha-adrenergic receptor stimulation can lead to further elevation of BP 6
• For confirmed pheochromocytoma, surgical excision is the definitive treatment, requiring careful perioperative management 6