The false positive rate with our case detection testing of plasma metanephrines about 15%. So based on how rare pheochromocytoma is and a 15% false positive rate with plasma metanephrines, 97% of patients with elevated plasma normetanephrines do not have pheochromocytoma.
So we have a real problem with case detection testing. The 24-hour urine metanephrines and catecholamines using appropriate reference ranges are probably a better way to do case detection testing for pheochromocytoma, but there’s still a false positive rate with urinary normetanephrine.
Never mistake a benign adrenal adenoma for a pheo. In terms of the imaging phenotype, pheos are dense and vascular. As they enlarge, they get cystic hemorrhagic areas within them.
FMN: What goes on with other paragangliomas?
Dr. Young: Pheochromocytoma is the term we use when you have a catecholamine-secreting tumor in the adrenal gland itself. It develops in the adrenal medulla. Paraganglioma is an identical tumor, but it’s outside of the adrenal gland. It’s somewhere in the pelvis, could be in the chest, could be in the skull base, or neck. Most commonly it’s in the abdomen. So the case detection testing is the same.
But patients we should consider testing for pheochromocytoma and paraganglioma are those with paroxysmal symptoms like episodes of pounding heartbeat, sweating, headache, tremor, and pallor. Young people with new onset hypertension, hypertension that’s poorly controlled, and vascular adrenal masses should also be tested for pheochromocytoma.
FMN: Are there things that can confound any of these tests we discussed or any drugs that should be noted that could get in the way?
Dr. Young: For pheochromocytoma, the good news is now that most reference labs use tandem mass spectrometry technology, the hypertension drugs that potentially interfered in the past like labetalol and sotalol no longer interfere. So these days the clinician doesn’t need to stop any blood pressure–related medications.
The medications that can cause false positive testing are primarily tricyclic antidepressants. Flexeril, which is cyclobenzaprine, is commonly used to treat fibromyalgia, and that is a tricyclic antidepressant, and that will cause false positive testing ... with norepinephrine and normetanephrine. Tricyclic antidepressants can increase those levels three, four, or fivefold. Levodopa, which is in Sinemet, can cause false positive testing. Antipsychotics can cause false positive testing, and MAO inhibitors ... So the clinician shouldn’t worry about blood pressure medications but should worry about the other medications the patient is taking.
FMN: When someone looks at laboratory values, should you be comparing these values to people with hypertension who do not have these conditions, and do labs have adjusted values?
Dr. Young: That’s a good question, and in the Mayo medical lab, our reference range that we use is based on patients who were tested for pheochromocytoma [and] proved not to have it. So our cutoffs are 50% to 100% higher than some other reference labs.
These other reference labs use normal laboratory volunteers who have normal blood pressure and who are taking no medications, and I’ve never tested such a patient for pheochromocytoma, so why would we use that group of people to determine our reference range? So we should use reference ranges based on patients tested for pheo but who prove to not have pheo. And that leads to higher accuracy of our case detection tests.
FMN: What are the treatments for these conditions and follow-up? I take it if there’s an adrenal mass, you get a surgeon, and I think you also noted that you need an experienced endocrine surgeon.
Dr. Young: For primary aldosteronism, if the patient has a unilateral aldosterone-producing adenoma, the outstanding treatment is laparoscopic adrenalectomy. Patients are in the hospital one night, [and] they’re back at work in 7-10 days, but that does require an expert laparoscopic adrenal surgeon. And in the United States we have a 1-year endocrine surgery program. It’s optimal that patients are referred to surgeons who have done that unique training.
For pheochromocytoma less than 8-9 cm, laparoscopic adrenalectomy with an experienced endocrine surgeon is an excellent treatment option. When the adrenal pheochromocytoma is larger than 8 or 9 cm, especially if it’s cystic, the surgeon may want to do it as open [surgery] because it’s critical that the capsule of the pheochromocytoma is not ruptured intraoperatively. If it is ruptured, a benign pheochromocytoma has just been transformed to malignant, incurable disease.
If it’s a paraganglioma, typically that requires an open operation whether it’s in the neck or the chest or the pelvis or lower abdomen.
FMN: What is the follow-up to any of these conditions?