Adrenal tumors are fairly common. Diagnosis and follow-up of adrenal tumors can be costly and inconvenient. So a reasonable question is "why don't we biopsy an adrenal mass to get a definitive diagnosis?" Here I will try to convince the readers that adrenal biopsy is seldom necessary or useful except in one situation. Most important to me is the one particular safety issue of adrenal biopsy: biopsy of a pheo can be catastrophic.
The one situation where we need adrenal biopsy is to determine the staging of a cancer. For example, one unfortunate patient has lung cancer and an adrenal mass. If the adrenal mass is benign, then the patient's lung cancer is of a lower stage. If the adrenal mass is lung caner metastasis, then the same lung cancer is of an advanced stage. Only biopsy of the adrenal mass will give definitive staging information of the patient's cancer.
Adrenal biopsy is not needed for the vast majority of adrenal masses because the diagnosis of adrenal mass can be confidently made in most patients without biopsy. Let me explain why. How do we know someone has an adrenal mass? Either the patient has clinical symptoms (e.g. paroxysmal hypertension) with suggestive biochemical test results (e.g. elevated plasma metanephrines) so that a functioning adrenal mass (e.g. pheo) is suspected, or CT or MRI is done on the abdomen for some other purposes (such as abdominal pain or cancer staging). In both cases, the imaging characteristics of the adrenal mass tell a lot about it. The size, density, enhancement, and appearance on various MRI protocols all matter. With additional biochemical testing, a good doctor is able to make the correct diagnosis of the adrenal mass.
One may wonder, OK, adrenal biopsy probably is not needed, but will it give important additional information? This issue is a little complicated for non-specialists. For the most common clinical question whether an adrenal mass is adenoma or carcinoma, adrenal biopsy can not answer. Regarding pheo, we just simply do not biopsy a pheo to confirm the diagnosis because doing so is too risky without any benefits.
Although generally very safe, adrenal biopsy can be potentially lethal if done to an unappreciated (or worse, suspected) pheo because of the risk of hypertensive crisis. Here are the basic facts: 5% of all incidentally identified adrenal masses are pheo and the percentage is higher if the mass is pheo-like on imaging. In addition, 6-24% of adrenal masses suspected to be malignancy or metastasis are actually pheo. It is not that every attempted biopsy of a pheo will result in hypertensive crisis. It happens in about 15% of times. Although this number does not sound very high, the extreme danger and the total avoidability of hypertensive crisis makes adrenal biopsy unacceptable in any patients without negative pheo test results.
To prevent hypertensive crisis from happening, ask these following questions before adrenal biopsy:
1. Is this adrenal biopsy really needed? (Answer: only needed for cancer staging.)
2. If adrenal biopsy is needed, have pheo markers been tested? (Answer: please test pheo markers and only do biopsy if the markers are considered negative.)
Dr. Pheo
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Dr. Pheo: Why is it that some pheo's respond to chemo and others do not? This too is true for NB, as you may recall, my son is a NB patient and my family has a big history of pheo/para's. In my aunt's case, where her pheo was malignant, they attempted to treat with chemo, various concoctions but it never responded.
ReplyDeleteKate
Dear kate,
ReplyDeleteMost chemo is based on that tumor cells grow faster than normal counterparts. Same here for pheo. If the pheo cells grow faster, they tend to respond to chemo. If not, they do not respond. That is not to say faster-growing pheos are better--they are not. Another factor is that tumor cells gain resistance to chemo over time.
Dr. Pheo
Hi again. Can you tell me if man and woman who are both SDH mutants would be able to have a child? Someone told me that a pregnancy would always fail if both parents had SDH mutations, that the mother would always have a miscarriage. Can you confirm or deny? Thanks for your time.
ReplyDeletePam
Are you aware of the Pheo Para Trooper newsletter? We just sent out our second issue and are looking for topics and articles. I'd like to use some of your blogs to help educate our readers. Can you contact me and let me know what you think, either by posting, or sending me a message through Blogspot? You have helped me so much over the last two years by answering all my questions and everyone else's. Thank you!
ReplyDeleteDear Pam,
ReplyDeleteI am aware of the Pheo Para Tooper newsletter. Please feel free to use the materials in the blog. Please do acknowledge my blog as the source.
Regarding the miscarriage question. I am not aware of any studies on this issue. In theory, if both parents are carriers of SDH mutation(the situation is very rare anyway), the baby has a 25% chance to carry two defective copies of the SDH genes. This will be a problem, based on experience of homozygous mutations of SDHA. (Baby mice with homozygous SDHD deletion do not survive to term.) If two carriers of SDH mutations consider having children, they should seek a formal genetic counseling.
Dr. Pheo
Dear Dr. Pheo
ReplyDeleteI sent this to an earlier post instead of to the most recent post
I have spells of paroxysmal hypertension, tachycardia, and palpitations (no other symptoms) with varying frequency. Results of initial test of 24 hr Urine Cathecholamines, Total Metanephrines, VMA were normal except for Epinephrine abnormal at 35mcg . A repeat test was normal except for Epi abnormal at 38mcg . A subsequent 24 hr U Fractionated Metanephrines test was normal: Normetanephrine at 189 mcg (range normotensive 82-500) ; Metanephrine at 223mcg (range normotensive 45-290). Thus, there is a negative result for metanephrine in a highly sensitive test and a positive result for epinephrine in a highly specific test. In light of these conflicting results, how can the effects of these tests on the probability of a pheo be assessed?
Can one use a Bayesian analysis to determine the effect of these tests by deriving a joint likelihood ratio by multiplying the positive LR of the cathecholamines test by the negative LR of the metanephrines test? Or does the positive result of the Epi test (specificity of 99.6 % at >35 mcg according to the Oct 2003 article in J Clin Endocrinol Metab by Dr. Young of Mayo and others) warrant scanning without any further biochemical testing.?
An oddity of my case is that if the initial test had been the fractionated metanephrines test the negative result would have been held by some to virtually exclude a pheo, at least in cases of low suspicion (Eishenhofer, Lenders, Pacak).
Dear jhardy,
ReplyDeletePlease tell me your age and sex. The interpretation of conflicting lab test results is an interesting topic. The mathematical maneuvers may be of limited value in clinical settings.
Dr. Pheo
Dr. Pheo,
ReplyDeleteI am a 71 year old male.
Dear jhardy,
ReplyDeleteMy own research shows that any negative results will likely rule out pheo. I suggest that you try fractionated plasma metanephrines. In older individuals, renal function may not be perfect, which can cause false negative results. Overall your risk of pheo is not high.
Dr. Pheo
Dr Pheo,
ReplyDeleteThank you
Dr. Pheo,
ReplyDeleteSeveral members of my family were diagnosed with MEN2A last year, along with Medullary Thyroid Cancer. Before their thyroidectomies, a 24-hr urine test was performed to rule out pheo. All tests were negative and all surgeries went well. My 39 yr old sister has had high blood pressure for about ten years. She also has experienced random (every few months) episodes of fast heart rate along with palpitations, so her Endo ordered a Plasma Metanephrines test with the following results:
Metanephrine, Free: 80 (ref range <57)
Normetanephrine, Free: 156 (ref range <148)
Total: 236 (ref range <205)
These results are not extremely elevated, but they are elevated nonetheless. Local endo suggests another 24 hr urine collection when episodes of racing heart & palpitations return. Pheo is supposed to be rare for her MEN2A 609 codon, so what would you suggest based on this scenario? Could nervousness (white coat syndrome) contribute to these slightly positive results?
Dear bgirl_nw,
ReplyDeleteAlthough not frequently, pheo can still occur in patients with codon 609 mutations. The elevated metanephrine is also consistent with pheo in MEN2. Nervousness usually only causes elevation of normetanephrine. I think she has a real risk of pheo. She should get abdominal CT or MRI, instead of another test.
Dr. Pheo
Thank you, Dr. Pheo, I will suggest that she call her Endo at once! Please clarify for me...how could my sister sail through her thyroidectomy surgery last year and have a pheo? Shouldn't there have been some bp/heart rate complications? Also, could Adrenal Medulla Hyperplasia be playing a role here and can CT or MRI confirm it as well?
ReplyDeleteOne more question...as more family members are being confirmed positive for MEN2A, why is it that all seem to be initially given the 24 hr urine catecholamine test when it sounds as though the plasma metanephrines test is a better one? Should they all be having both tests done? Please note that not everyone in our family is being treated by an MEN expert endo.
ReplyDeleteDear bgirl_nw,
ReplyDelete1. Not all patients with pheo will have BP fluctuations during operations. Patients with small pheo often tolerate surgery well.
2. Adrenal medullary hyperplasia is present in most patients with MEN2. It is usually not assoicated with elevated markers. I would predict that your sister already has tumor(s) on her adrenal(s).
3. With all things considered, plasma metanephrines are the best test for all patients, including those with MEN2.
Dr. Pheo
Dr Pheo,
ReplyDeleteI conceptually think of adrenal pheos as being solitary tumors arising from the medulla. Not often giving consideration that multiple tumors within an adrenal could exist when a pheo is diagnosed. Maybe this is because when adrenal pheos are mentioned in medical literature they often don't report much about the physical pathology within the adrenal. Also when I have seen pheo in the plural form it often means bilateral adrenal, metastic, or extra-adrenal - which today would most likely be referenced as paragangliomas.
Based on your experience, how often are multiple pheos found in a single adrenal?
With VHL patients are multiples seen more often? What about the prevalence in other genetic syndromes?
When single tumors are seen, how often is abnormal cell biology present in the surrounding adrenal tissue?
With adrenal sparing surgery being done more often, what's the reported incidence of recurrance of pheos in the remaining portion of the adrenal? Is adrenal sparing surgery "kicking the can down the road"? Surgical management of a disease by addressing the immediate medical issue/crisis with the prospect of readdressing it again at a later date. The benefits to the patient is the is a hope that adrenal function can be preserved,
Dear DJPheo,
ReplyDeleteA pheo tumor in a patient with sporadic disease (no family history or stigmata of endocrine syndromes) is usually solitary.
In patients with endocrine tumor syndromes such VHL and MEN2, multiple tumors can be present in one adrenal gland. In this case, adrenal medulla hyperplasia precedes the pheos. In other words, the adrenal medulla cells around the pheos are not normal but pre-neoplastic.
Partial adrenalectomy (or adrenal-sparing adrenal tumor resection) is mostly used in young patients with familial pheo syndromes. The reason for partial adrenalectomy is to avoid the mandatory use of corticosteroids. Young people are often not compliant with medications (think of binge drinking in college) and they probably do not get the message that they have to take corticosteroid every day. Pheo will certainly recur in the remaining adrenal. Rather than "kicking the can down the road," it is better to think of partial adrenalectomy as buying time for young patients with familial pheos. Hopefully total adrenalectomy can be done when they are mentally mature enough.
Dr. Pheo
Dr Pheo,
ReplyDeleteMe again (sister with MEN2A)...Her Endo insisted on the 24 hr urine metanephrines test before ordering imaging, so she went along with it. She wasn't experiencing an episode during the collection, and results were normal. Now we are confused. Was the mildly elevated plasma metanephrines test a false positive? Is the wait and see approach acceptable for even small pheos or should they all be removed immediately regardless of size and symptoms? My sister says she feels fine and has not had any significant episodes for several months. Now what?
Dear bgirl_nw,
ReplyDeleteThe timing of adrenal surgery in patients with MEN2A is a bit subjective. Most people would agree that if there is a clear pheo on imaging, adrenalectomy should be done. There is a good chance that your sister already has a small pheo which should be seen on imaging. On the other hand, if the urine metanephrines are negative, the pheo should be really small (around 1 cm). She should repeat the test (either plasma or urine) in 6 months or whenever she has symptoms.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteI was I guess diagnosis with a so far showing benign or non cancerous adrenal tumor on my right side. They did blood urine and imaging work for it and could find little to no sign of it being a pheo. However I have taken amphetamines since I was 8 in second grade. Im now 19 and still take them.70 mg vyvanse. Highest dose and newest one. Howevr, it makes me normal and only awake and alert. If i skip even one day for that day i can not wale up and will sleep all day with no energy. Could this be my adrenal gland not producing any adrenaline or energy?
Dear katumor7,
ReplyDeleteFailure of the adrenal glands to produce adrenaline is very rare. Even people without adrenal glands (those after bilateral removal) usually do not complain of significant fatigue.
Dr. Pheo
I had a biopsy done on my adrenal gland and was told that it was needed to leter finding out that the ct scans showed that it did not like cancer and it was shrinking. also ever since i had the biopsy i have been having close to severe pain in my right kidney which is the side the tumor is on. ct scan showed it looked like a pheo but test results said it wasn't. I felt i was kind of pushed into having the biopsy because they said there was no other way to tell if it was cancer or not. not sure what i should do.?
ReplyDeleteDear Courtney,
DeleteComplications of adrenal biopsy are uncommon but can occur. You should talk to the doctor who did the biopsy about the pain.
What did the biopsy conclude on the nature of your adrenal tumor?
Dr. Pheo
Dr.pheo, I have a pheo. I have been fighting for my life with this tumor. I am 2 weeks away from having it surgically removed. my question is does this run in families?
ReplyDeleteDear Michaela,
DeleteAbout 30% of people with pheo have genetic mutations that could run in a family.
Dr. Pheo