Pheochromocytoma is diagnosed through a combination of blood or urine tests that measure hormone byproducts, followed by imaging to locate the tumor. The process typically starts with biochemical screening, since these tumors produce excess adrenaline-like hormones that leave a detectable chemical trail. A plasma free metanephrine test catches virtually 100% of cases, making it the recommended first-line screening tool.
Biochemical Testing Comes First
The cornerstone of diagnosis is measuring metanephrines, which are breakdown products of the stress hormones adrenaline and noradrenaline. These tumors continuously produce and metabolize these hormones, so metanephrine levels stay elevated even between symptomatic episodes. Two testing options exist: a blood draw measuring plasma free metanephrines, or a 24-hour urine collection measuring urinary fractionated metanephrines.
Plasma free metanephrines are the more reliable option. In head-to-head comparisons, the blood test shows 100% sensitivity and 97.6% specificity, meaning it catches every true case while producing very few false alarms. The urine test is less sensitive at about 86%, though it remains a reasonable alternative when blood testing isn’t available. The Endocrine Society recommends either test as an acceptable first step, with a preference for plasma metanephrines in high-risk patients.
For the blood test, you’ll need to lie down for at least 15 minutes before the draw. This matters because standing up activates your sympathetic nervous system and raises catecholamine levels, which can push results into the abnormal range even without a tumor. Drawing blood while you’re resting in a supine position reduces false positives significantly.
Medications That Interfere With Results
A surprisingly long list of common substances can cause falsely elevated metanephrine levels. Tricyclic antidepressants are among the worst offenders, as they block the reuptake of noradrenaline and directly raise the hormones being measured. Other culprits include certain blood pressure medications (particularly phenoxybenzamine, some beta-blockers, and alpha-methyldopa), MAO inhibitors, levodopa, and acetaminophen.
Dietary factors also play a role. Caffeine, nicotine, alcohol, and catecholamine-rich foods like bananas and walnuts can all nudge results upward. Your doctor will typically ask you to avoid these for a set period before testing, or will factor them into the interpretation of borderline results. If you’re on any of these medications, don’t stop them on your own. Your medical team will decide which ones to pause and for how long.
What Happens With Borderline Results
When metanephrine levels come back mildly elevated but not dramatically so, the diagnosis gets trickier. Levels more than three to four times the upper limit of normal almost certainly indicate a tumor. Mildly elevated results, on the other hand, could be a false positive caused by stress, medications, or testing conditions.
In these gray-zone cases, a clonidine suppression test can help sort things out. Clonidine is a blood pressure medication that dampens sympathetic nervous system activity. In a healthy person, clonidine will bring hormone levels down. In someone with a pheochromocytoma, the tumor keeps pumping out hormones regardless. The test involves measuring plasma catecholamines before and three hours after taking a dose of clonidine. If levels of normetanephrine stay above normal and don’t drop by more than 40%, pheochromocytoma becomes much more likely. Any sympathetic-blocking medications need to be stopped at least 48 hours beforehand.
Imaging to Locate the Tumor
Once biochemical testing confirms excess hormone production, imaging identifies where the tumor is. CT scanning of the abdomen and pelvis is the standard first step because most pheochromocytomas sit in or near the adrenal glands. These tumors have a distinctive appearance on CT: they tend to be dense, with an unenhanced attenuation above 10 Hounsfield units (a measure of tissue density). They also hold onto contrast dye longer than benign adrenal nodules, which wash out the dye more quickly. An adrenal mass that measures 10 HU or less on an unenhanced scan, or washes out contrast by 60% or more within 10 to 15 minutes, is more likely a harmless adenoma than a pheochromocytoma.
MRI is an alternative, particularly useful for patients who can’t receive CT contrast dye, for pregnant patients, or when imaging needs to be repeated frequently. Pheochromocytomas characteristically appear very bright on certain MRI sequences.
Functional Imaging for Complex Cases
Standard CT or MRI shows anatomy, but functional imaging shows whether tissue is metabolically active like a pheochromocytoma. This becomes critical when tumors are outside the adrenal glands (called paragangliomas), when there’s concern about spread, or when CT and MRI findings are ambiguous.
The traditional functional scan uses a radioactive tracer called MIBG, which is taken up by the same cells that produce adrenaline. It has been a workhorse for decades, but newer PET-based imaging is proving superior. A tracer called DOTATATE, which targets receptors on the surface of these tumor cells, detected 100% of cases in comparative studies versus 78% for MIBG. The advantage was especially pronounced for tumors that had spread to bone, where DOTATATE found nearly three times as many lesions. For metastatic or extra-adrenal disease, DOTATATE PET/CT is increasingly the preferred functional imaging study.
Why Genetic Testing Matters
Pheochromocytoma was long considered the “tumor of tens,” with roughly 10% of cases thought to be hereditary. That number is outdated. Population-based studies now estimate that up to 32% of patients carry an inherited gene mutation, and specialized centers report mutation detection rates as high as 41%.
At least ten genes are known to increase the risk. Three are linked to well-known cancer syndromes: VHL (von Hippel-Lindau disease), RET (multiple endocrine neoplasia type 2), and NF1 (neurofibromatosis type 1). Another group involves the SDH complex, a set of genes (SDHA, SDHB, SDHC, SDHD, and the cofactor SDHAF2) involved in cellular energy production. Mutations in SDHB carry a particularly high risk of malignant disease. Two more recently identified genes, TMEM127 and MAX, round out the list.
Genetic testing has practical consequences beyond the individual patient. An SDHB mutation, for example, means lifelong surveillance for recurrence and metastatic disease, while a RET mutation may prompt screening for thyroid cancer. It also triggers screening for blood relatives who may carry the same mutation without knowing it. Current expert opinion holds that all patients diagnosed with pheochromocytoma should be offered genetic testing, regardless of family history or age at diagnosis.
The Typical Diagnostic Sequence
In practice, the diagnostic workup follows a predictable path. It usually begins because someone has symptoms (episodic headaches, sweating, rapid heartbeat, high blood pressure) or because an adrenal mass turns up incidentally on imaging done for another reason. The first step is always biochemical: plasma free metanephrines or 24-hour urine metanephrines. If results are clearly elevated, imaging follows to pinpoint the tumor’s location. CT of the abdomen is the usual starting scan. If the tumor is confirmed, functional imaging may be added to check for additional tumors or metastatic spread. Genetic testing is then recommended for all confirmed cases.
The entire workup, from first blood test to confirmed diagnosis, often takes a few weeks. The timeline depends on how quickly test results return and whether borderline results require repeat testing or a clonidine suppression test. Once the tumor is localized and characterized, the focus shifts to preparing for surgery, which involves carefully managing blood pressure and heart rate before the operation to reduce the risk of a dangerous hormone surge during tumor removal.