Pheochromocytoma Detection and Diagnosis

Diagnostic Approaches

The American College of Radiology recommends CT scanning as a first-line imaging modality for localizing pheochromocytoma after biochemical confirmation, but it has limitations in detecting all cases 1
Pheochromocytomas typically appear as heterogeneously enhancing masses with irregular margins on CT, but their appearance can vary significantly 1
Small pheochromocytomas or those in atypical locations may be missed on conventional CT imaging 2, 3
The European Journal of Nuclear Medicine and Molecular Imaging suggests that extra-adrenal paragangliomas can occur in various atypical locations that might not be included in standard abdomen/pelvis CT imaging fields 2, 4

MRI offers superior soft tissue contrast and can detect some lesions missed on CT, according to the Annals of Oncology and Genetics in Medicine 1, 5
Functional imaging with 123I-MIBG scintigraphy, 18F-FDOPA PET, or 18F-FDG PET provides higher sensitivity for detecting small or atypically located tumors 2, 4
Combined anatomical and functional imaging (SPECT/CT or PET/CT) significantly improves diagnostic accuracy, as reported by the European Journal of Nuclear Medicine and Molecular Imaging 2, 3

Initial biochemical confirmation with plasma free metanephrines or 24-hour urinary fractionated metanephrines is recommended by Genetics in Medicine 5
First-line anatomical imaging with CT or MRI of abdomen and pelvis is suggested by the Annals of Oncology 1
If initial imaging is negative but biochemical evidence is positive, extend imaging to include chest and neck, and consider functional imaging with 123I-MIBG, FDOPA-PET, or FDG-PET, as recommended by the European Journal of Nuclear Medicine and Molecular Imaging and Genetics in Medicine 2, 5

Biopsy of suspected pheochromocytoma is contraindicated due to risk of hypertensive crisis, according to the Annals of Oncology 1
Biochemical testing should always precede imaging for suspected pheochromocytoma, as recommended by the Annals of Oncology and Genetics in Medicine 1, 5
Even with negative imaging, if biochemical evidence strongly suggests pheochromocytoma, further investigation is warranted 5

Relying solely on CT imaging without biochemical confirmation is a common pitfall, as reported by the Annals of Oncology 1
Failing to consider extra-adrenal locations when adrenal imaging is negative is another common pitfall, according to the European Journal of Nuclear Medicine and Molecular Imaging 2, 4
Not recognizing that some pheochromocytomas may have atypical imaging appearances is a pitfall, as reported by the European Journal of Nuclear Medicine and Molecular Imaging 2
Overlooking the need for specialized imaging protocols optimized for adrenal evaluation is a pitfall, as recommended by the Annals of Oncology and the Journal of the American College of Radiology 1, 6

If plasma testing is equivocal (less than fourfold elevation), a follow-up 24-hour urine collection for catecholamines and metanephrines should be performed, as recommended by the Genetics in Medicine society 7, 8
Plasma free metanephrines (normetanephrine and metanephrine) should be included in a complete hormonal work-up for suspected pheochromocytoma, according to the Annals of Oncology society 9, 10
Plasma methoxytyramine (when available, helps assess likelihood of malignancy) should be considered in the hormonal work-up, as suggested by the Annals of Oncology society 9, 11

After positive biochemical testing, localization of the pheochromocytoma is generally done by CT or MRI, as recommended by the Genetics in Medicine and Annals of Oncology societies 7, 12
Functional imaging, such as Meta-iodobenzylguanidine (MIBG) scintigraphy, 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine positron emission tomography (FDOPA-PET), and FDG-PET, is helpful to detect multifocal disease, according to the Genetics in Medicine and Annals of Oncology societies 7, 11, 10

In patients with confirmed pheochromocytoma, long-term follow-up should include annual surveillance with plasma metanephrines, as recommended by the Genetics in Medicine society 7, 8
Screening asymptomatic patients without clinical suspicion is not recommended due to low yield, according to the Genetics in Medicine society 7, 8
Fine needle biopsy of suspected pheochromocytoma is contraindicated due to risk of hypertensive crisis, as warned by the Annals of Oncology society 11, 13

The European Journal of Nuclear Medicine and Molecular Imaging recommends CT or MRI of the abdomen and pelvis as the initial imaging step after biochemical diagnosis is established, to capture adrenal and extra-adrenal locations 14.

For apparently sporadic non-metastatic pheochromocytoma, 123I-MIBG scintigraphy is the first-line functional imaging modality, providing whole-body screening to rule out extraadrenal disease and guide additional anatomical imaging 14, 15.
Reserve PET tracers for MIBG-negative cases, multifocal tumors on MIBG, or patients taking drugs that interfere with MIBG accuracy, according to the European Journal of Nuclear Medicine and Molecular Imaging 14, 15, 16.

For head and neck paragangliomas, 18F-FDOPA PET is the most sensitive imaging tool, with sensitivity approaching 100%, as recommended by the European Journal of Nuclear Medicine and Molecular Imaging 14, 16, 17.
For SDHB-related metastatic disease, 18F-FDG PET is the imaging modality of choice, while for non-SDHB metastatic disease or unknown genetic status, 18F-FDOPA PET/CT is preferred, according to the European Journal of Nuclear Medicine and Molecular Imaging 14, 15, 18.
For MEN2-related pheochromocytoma, many patients do not need functional imaging if the tumor is confined to the adrenal gland with characteristic metanephrine elevation, but if needed, 18F-FDOPA PET is useful due to absent uptake in normal adrenal glands 14, 19, 18.

123I-MIBG alone significantly underestimates metastatic disease and should not be used as the sole modality, as stated by the European Journal of Nuclear Medicine and Molecular Imaging 14, 15, 18.
Consider SPECT/CT or PET/CT hybrid imaging to improve diagnostic accuracy by combining anatomical and functional data, as recommended by the European Journal of Nuclear Medicine and Molecular Imaging 20.