Pheochromocytoma Diagnosis
Laboratory Tests
- 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
Imaging
- 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