Pheochromocytoma Diagnosis

• Evaluation using liquid chromatography w/ mass chromatography is preferred over laboratory methods
• Blood for plasma metanephrine measurement should be obtained w/ patient in supine position, w/ subsequent extractions done in the same position

Plasma Metanephrine

• Diagnostic test of choice
  
  • More suitable for high risk patients w/ a hereditary predisposition
  • Normal plasma levels excludes the diagnosis
  • Elevated plasma levels confirm the diagnosis

• Clonidine suppression test
  
  • Maybe done when plasma total cathecholamines concentration is elevated but not diagnostic
  • May distinguish elevated norepinephrine levels secondary to sympathetic nerves vs true pheochromocytoma
  • Failure to suppress norepinephrine levels by 50% suggests pheochromocytoma

• Glucagon stimulation test
  
  • Performed when plasma metanephrine levels are high but catecholamines are either normal or only moderately high
  • A 3-fold rise in norepinephrine levels in response to glucagon signify pheochromocytoma
  • Rarely used

Urine Biochemical Tests

• Alternative for excluding pheochromocytoma
  
  • May be preferred in those at low risk for pheochromocytoma

Accuracy is improved if at least 2 of the following are measured from urine sample:

• Unconjugated (free) catecholamines
  
  • Normal range: 590-885 nmol/24 hr (100-150 mcg/24 hr)
  • Diagnostic range: >1480 nmol/24 hr (>250 mcg/24 hr), or 2-fold elevation from normal level
  • Epinephrine should also be measured & may be high if multiple endocrine neoplastics (MEN) adrenal lesion is present

• Metanephrine/Normetanephrine
  
  • Upper limit of normal range: 7 micromol/24 hr (1.3 mg/24 hr)
  • Diagnostic range: Normetanephrine (>900 mcg/24 hr); Metanephrine (>400 mcg/24 hr)

24-Hr Urine Sample

• Analysis of urine sample should be done when patient is symptomatic eg hypertensive or during a crisis
• Full 24-hr sample is preferred
• CrCl should be measured to assess adequacy of collection
• If possible, patient is at rest, not taking medication & no recent exposure to radiographic contrast media
• Acidify & refrigerate urine during & after collection
• Tests may need to be repeated during attacks to exclude diagnosis
  
  • Pharmacologic tests may be helpful in difficult cases

• Once patient is diagnosed tumor localization & search for possible metastases should be undertaken
  
  • Maybe adrenal or extra-adrenal (paraganglioma)
  • Patient can be prepared pharmacologically at the same time

• CT scan & MRI are 1st-line diagnostic tools
  
  • Both provide localization & metastatic assessment
  • CT scan is preferred over MRI as 1st-line diagnostic tool for imaging of the thorax, abdomen & pelvic area
  • MRI is used best for detection of tumors in the skull base & neck, patients w/ contraindications for contrast dyes & radiation, & for patients w/ artifacts seen in CT

Anatomic Imaging

Magnetic Resonance Imaging

• Identify intraadrenal lesions
• Identify extraadrenal lesions in the abdomen
  
  • Look for von Hippel-Lindau disease neurofibromatosis or multiple endocrine neoplasia type 2 (MEN-II) if bilateral or extra-adrenal

• Detect intracardiac, juxtacardiac, juxtavascular pheochromocytoma
  
  • Reduces cardiac and respiratory motion-induced artifacts

• Initial evaluation for children, pregnant women or in cases of contrast allergy

CT Scan

• Detects adrenal pheochromocytoma of ≥0.5-1 cm or metastatic pheochromocytoma of ≥1-2 cm
• Extraadrenal tumors w/in the abdomen & pelvis (inital CT should visualize these areas); chest & neck
• Spiral CT preferred for small thoracic tumors
• CT w/ contrast can aggravate or precipitate crisis
  
  • Some consider CT as the most useful method to locate pheochromocytoma

Abdominal Aortography

• May be used to identify extraadrenal tumors in the abdomen since they are usually supplied by a large aberrant artery
• Alpha-adrenergic blockade must be completed before attempting aortography

Functional Imaging

Functional imaging techniques are not recommended as 1st-line procedures for localizing pheochromocytoma

Metaiodobenzylguanidine (MIBG) Scintigraphy

• May use I¹³¹ and I¹²³
  
  • I¹²³ is superior to I¹³¹, but is not approved by USFDA

• Useful in detecting recurrent or metastatic pheochromocytoma, tumors w/ fibrosis, extranodal tumors, tumors in unusual location or in areas w/ distorted anatomy
• Indicated when abdominal imaging results are negative, or if found pheochromocytoma is >10 cm in diameter

Positron Emission Tomography (PET) Imaging

• Advantages include low radiation exposure & superior spatial resolution
• Imaging is carried out immediately
  
  • Unlikely delays in scintigraphy

• Provides accurate information regarding the number & location of metastatic lesions
• Preferred over MIBG scintigraphy for patients w/ known metastatic lesions
• Limited availability among various centers
• Procedure is expensive

Somatostatin Receptor Scintigraphy

• Detects malignant/metastatic tumors better than primary/benign tumors
• Low sensitivity