Pheochromocytoma and Paraganglioma Diagnosis and Management

Screening and Diagnosis

The American Urological Association recommends screening for pheochromocytoma/paraganglioma using 24-hour urine fractionated metanephrines in patients with adrenal incidentalomas displaying >10 HU on non-contrast CT, or in those with signs/symptoms of catecholamine excess 1, 2
The Endocrine Society suggests that early-onset hypertension (<30 years of age) is an indication for screening 2
Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive medications including a diuretic) is also an indication for screening 2
Paroxysmal hypertension with classic triad symptoms (headache, palpitations, sweating) has 93.8% specificity and 90.9% sensitivity for pheochromocytoma/paraganglioma 2
Significant blood pressure variability or episodic symptoms despite treatment is an indication for screening 2
Family history of pheochromocytoma or hereditary syndromes is an indication for screening 2
Adrenal incidentaloma with >10 HU on unenhanced CT is an indication for screening 1

24-hour urine fractionated metanephrines have sensitivity of 86-97% and specificity of 86-95% for diagnosing pheochromocytoma/paraganglioma 2

Before testing, confirm that interfering agents were avoided, as several medications and foods can cause false positive results 3, 2
Antidepressants (especially tricyclics) can decrease urinary metanephrine and cause false elevations in catecholamine metabolites 2
Doxazosin and other alpha-1 selective blockers used in preoperative management of pheochromocytoma do not need to be discontinued for testing 2

Verify pre-analytical factors, including interfering medications and correct urine volume 3, 2
Interpret results based on degree of elevation: ≥4 times upper limit of normal is consistent with pheochromocytoma/paraganglioma 3, 2
Proceed immediately to imaging to localize the lesion if results are ≥4 times upper limit of normal 3, 2
Repeat testing in 2 months if results are 2-4 times upper limit of normal 3, 2
Consider genetic testing for hereditary syndromes, especially in younger patients 3, 2
Assess for hyperadrenergic symptoms (sustained or intermittent palpitations, tachycardia, diaphoresis, tremors, new-onset hypertension) 2

Whole-body MRI (skull base to pelvis) is preferred over CT due to risk of hypertensive crisis with IV contrast 3, 2
For hereditary syndromes, begin whole-body MRI surveillance biennially starting at age 6-8 years 3
Consider functional imaging (FDG-PET or SSTR PET/CT) for high-risk features: tumor ≥5 cm, extra-adrenal location, SDHB mutation, or plasma methoxytyramine >3-fold above upper limit 4, 2

Measure plasma or urine metanephrines 2-8 weeks post-operatively to confirm complete resection 4, 2
Repeat imaging at 3-6 months post-operatively 4
All patients require lifelong surveillance due to risk of recurrence, metastasis, or new tumors 4, 2
Follow-up every 3-4 months for 2-3 years, then every 6 months 2
Annual blood pressure measurements and biochemical testing at minimum 3, 4

SDHB mutations (higher risk of malignancy and metastasis) require intensive surveillance 3, 4, 2
Extra-adrenal tumors require intensive surveillance 2
Tumors >5 cm require intensive surveillance 2
PASS score ≥4 requires intensive surveillance 2

For pediatric patients with hereditary paraganglioma/pheochromocytoma syndromes, begin annual surveillance at age 6-8 years with 24-hour urine fractionated metanephrines once continent of urine 3
Use plasma metanephrines before continence is achieved 3
Reference pediatric-specific intervals for interpretation 3
For von Hippel-Lindau syndrome, begin surveillance at age 2 years 2