Treatment of malignant (metastatic) pheo is a big challenge.
Malignant pheo has a very variable clinical course; some patients live with it
for many years with high quality of life while some other patients can have a
rapid deterioration of their conditions. Malignant pheo is exceedingly rare,
making it hard for clinical trials to recruit patients. There have been no
approved therapies for malignant pheo so far.
Two recent advances may offer hope. They are both “targeted
internal radiotherapies”. The radiopharmaceuticals only go into certain cells
of the body, malignant pheo cells in particular (hence “targeted”). The
patients would receive intravenous infusions of the radiopharmaceuticals rather
than getting radiation from an external source (hence “internal”).
The first one is carrier-free MIBG radiotherapy. We don’t
have to go into the technical details of what is carrier-free but this new form
of MIBG radiotherapy supposedly deliver more radiation to the tumors. The
manufacturer released a press announcement this year, showing the effects of
carrier-free MIBG radiotherapy in patients with malignant pheo. Older forms of
MIBG radiotherapy have been used for years in clinical practice and in some
clinical trials. It is hard to compare the therapeutic effects of the old and
new MIBG radiotherapies. Generally the effects are comparable in my eyes. The
carrier-free MIBG radiotherapy is tested in a prospective and more controlled
manner, thus more convincing.
The second one is PRRT. Although the completed US clinical
trial of PRRT is only for carcinoid, PRRT has been used in Europe and Australia
for all kinds of neuroendocrine tumors, including malignant pheo. A recently
published paper showed that PRRT helps control hypertension and reduce the size
of malignant pheo. This study is a retrospective one so it is even harder to
compare the carrier-free MIBG radiotherapy and PRRT. My own cursory reading
convinces me that they have roughly similar efficacy.
The carrier-free MIBG radiotherapy is seeking US approval. PRRT
should be close to approval in the US but will very likely be approved for
carcinoid only. Assuming both will be approved eventually, I imagine it will be
interesting to how they are used for patients with malignant pheo. The use of
PRRT will be “off-label”. Besides efficacy, availability, comorbidities, side
effects, cost, and insurance coverage will also be factors that influence the
decision to use one over the other. More interestingly, can the two
radiotherapies be used in succession? The
best indication of the two radiotherapies should be assessed on a case-by-case
basis.
Dr. Pheo
Hello. So my story begins 3 yrs ago. I was in the kitchen when i started feeling a burning in my chest, then it rised up to throat, then face. My face turned extremely red( hubby told me), i felt like i couldn't breathe, i had nausea and sometimes vomitting, I get really hot with extreme sweating. I get a headache after. I also felt dizzy. It felt like my head was going to explode. After a few more of those episodes, i decided to go get bloood work from my primary doc. Everything was normal. I proceeded to get these episodes, i was advised to go to a cardiologist bc of extreme high heart rate and tremors. Again everything normal. I have been also to a neurologist. Normal. My primary said anxiety attacks. I just knew it wasn't that. I continued to get the "episodes". I always know when they are coming. Last yr, for my routine blood work, my test tested positive for hyperthyroidism. I was sent to an endocrinologist who diagnosed me with graves disease. My symptoms seemed to fit graves and i had a family history of Hyperthyroidism. But i continued to get these episodes even tho my thryoid levels became normal. She finally said she thought it was pheo. The only thing is that everytime my BP is normal. Tho i suspect it is NOT during these episodes. So i guess my question is do these symptoms seem like pheo? The episodes last no more than seconds to a couple of minutes. But I do feel like crap for about 1 after these spells...Bad headaches and still some burning in my stomach or chest. During the episode, my head feels like it's going to explode. I can't really breathe and my chest n throat burns
ReplyDeleteDear Anonymous,
DeleteYour symptom is best described as flushing. Flushing is not a common symptom of pheo. You can test for pheo to be sure.
Dr. Pheo
Adrenal incidentaloma found during CT for abdominal pain 3 years ago. 2.6cm at that time. Annual scans, one an MRI, showed growth but other than one episode of extremely high blood pressure, sweating, severe feelings of doom... Nothing. Serum tests showed slightly elevated norepinephrine, but just over normal, so assumed it was non functioning. Last scan (last year) had grown to 3.6cm on MRI. Didn't "light up" so again, just watchful waiting and tracking. I was ok with that.
ReplyDeleteFast forward to 6 weeks ago, I was very very ill with severe laryngitis. Cold went away, but laryngitis persisted. PCP prescribed prednisone. Ended up in ER with palpitations, headaches... But they were more concerned with laryngitis. Prescribed longer course of prednisone... On last day of taper I had a major sweating episode at the grocery store. By major I mean dripping wet, soaking through my dress, with pallor, palpitations. Home, checking BP and heart rate, both were elevated, 170/90ish and 110BPM. Sweating resolved after a few hours, BP and heart rate? Not so much. Couldn't get heart to just calm down! Now I'm sitting here with a resting heart rate averaging 110, spiking to as high as 155. Extremelying frightening, and I know it's happening because I start sobbing uncontrollably, then sweating, tremors, teeth chattering uncontrollably... Then BP is up to 180/120ish. Then the excruciating headache. Excruciating!!
I've had sweating episodes without the other symptoms with some frequency over the years, but I'm fat and they always excused that away.
My questions: can an adenoma just switch on? Could the prednisone trigger this?
We are all looking at this as if it were a pheo, but I also have Hashimoto's and an extremely painful thyroid nodule on my isthmus. Have always been euthyroid, but now have both TpoAb and TgAb elevated (54 and 5 respectively)
I can't drive now because of the frequency and severity of the episodes. Started with sweating Saturday. Today is Wednesday. Seems really fast to be pheo.
Drs at Walter Reed endocrinology put me on the phenoblahblah meds today, but waiting to see if it can help with the palpitations and BP issues. Hopefully it will but one dose did nothing. Teeth chattering is the only thing that is better.
Sorry, forgot flank pain on both sides, even tho unilateral. Also microscopic hematuria that was thoroughly worked up with no answers.
DeleteDear Janis,
DeleteThe MRI feature is not consistent with those typical for pheos. There are of course exceptions.
Dr. Pheo
Drs agree, norepinephrine elevated only to 189. I'm happy getting off the alpha blocker, but terrified to wait with tremors tachycardia, crying episodes, sweating, etc. 3.6 cm Adenoma getting rescanned CT. Waiting on urine results.
DeleteDr. Pheo:
ReplyDeleteThank you for your informative blog.
Five years ago I was diagnosed with pheo after an adrenalectomy. Last month my urinary fractionated normetanephrines came back 2x elevated on two different tests. (Plasma free metanephrines did not have any increased levels). I then had a abdominal/pelvis CT with the only remarkable finding being "low-attenuation foci in the right hepatic lobe." In your opinion, would this finding be something to further explore?
A CT of the neck/head has also been ordered. These are the first scans in the 5 years since the pheo resection.
Thank you for your time and consideration.
Dear Marita,
DeleteAn MIBG scan or FDG PET or DOTATATE PET will be helpful to see if you have recurrent or metastatic pheo.
Dr. Pheo
Thank you for the response, Dr. Pheo.
DeleteHello Sir!
ReplyDeleteI was ordered to do 24h urine test and plasma test for pheo. In short my blood test came back ok, but the urine one didn't. So the question is pheo execluded in this case?
Is there any other test I can do?
In case you are wondering about the exact levels, here they are:
URINE/24h (I was on diet during/2days before the test)
- normetanephrine (ELEVATED! 1194 - norm: 105-354 µg/24h)
- metanephrine (169 - norm: 74-297 µg/24h)
- methoxytyramine (133 - norm: <220 µg/24h)
BLOOD:
- free metanephrine (22 - norm: <90 ng/ml)
- free normetanephrine (49 - norm: <180ng/ml)
As for the symptoms (male 33 here):
- I do not have hypertenstion, I have face&chest flushing, anxiety, fatigue, abdominal pain.
Thanks for your time.
- Mike
Dear Mike,
DeletePheo is very unlikely.
Dr. Pheo
Hi Dr. Pheo,
ReplyDeleteI am a 36 year old female with a history of new onset hypertension 170s/100s. I also have headaches, tachycardia, sweating, and facial flushing at times with high elevated BP. I am a healthy, active, not overweight 36 year old. My family history includes my father had an adrenalectomy for an adrenal gland tumor thought to not be "hormonal". Pathology is unknown. My grandmother passed from an inter cranial hemorrhage from a hypertensive crisis (240s/140s) after induction of anesthesia for cataract surgery. She had difficult to control HTN, as does my father. My PMD performed an echocardiogram which showed left ventricular hyperplasia, and elevated urine/plasma metanephrines in May. An adrenal CT scan showed mild left adrenal thickening with no discrete mass. I was referred to endocrine, who thought the elevated metanephrines were from low dose TCA Pamelor taken for IBS. I discontinued the medication and redrew labs and urine. They continue to be elevated. Hypertension continues to be difficult to control despite high doses of double anti hypertensives. The plan from endocrinology is to repeat labs/urine in 3-6 months, and repeat adrenal MRI in 6 months. Please see labs below:
Plasma normetanephrine 1.79(May) down to 0.98 (July)
Urine norepinephrine/crt (0-45) 68 (July lab)
Urine norepinephrine/day (16-71) 83 (July lab)
Urine normetanephrine/crt (0-400) 532 (May) down to 421 (July)
Urine normetanephrine/day (109-393) 632 (May) down to 515 (July).
Thank you for any advice!!
Sorry I meant to say mild left ventricular hypertrophy on echocardiogram.
DeleteAlso repeat plasma normetanephrine went from 0.98 back up to 1.23 (under 0.89 is range)
Dear Anonymous,
DeletePheo is unlikely. I agree with your endocrinologist's approach.
Dr. Pheo
Hi Dr. Pheo,
ReplyDeleteMy friend was in car accident a few months ago and has since started having acute episodes of very elevated blood pressure and orthostatic hypertension. He complains of headaches and tachycardia, though intermittent, and profuse sweating as a prominent symptom. His pupils get very dilated when he has these episodes and his moods are poor.
He's had two strokes so far, so I am very worried. He doesn't have insurance, so I don't want to recommend unnecessary tests.
His back was injured, so I was thinking probably the hospital missed autonomic hyperreflexia, but he is normotensive normally and doesn't have orthostatic hypotension or bradycardia.
He is a young man and also doesn't have diabetes or pre-existing vascular disease.
Is it is a good use of money to test for pheo or should he be tested for something else first?
Thank you so much!
Dear Anonymous,
DeleteIt is very hard to answer. If he had been in perfect health before the accident and he has no family history of pheo, he probably can wait a little to see if other causes are possible.
Dr. Pheo
Thank you so much for your advice. It's a very difficult situation.
DeleteDear Dr. Pheo, thanks so much for all of the time and effort you've put into making this blog. The information is invaluable and very well presented. One topic I did not see in your writings is pseudo pheochromocytoma. (http://www.revespcardiol.org/en/pseudopheochromocytoma-as-cause-of-resistant/articulo/90192448/) What are your thoughts on this? I am asking after my pheo "work up" came back normal, yet I still have no explanation for my symptoms. Thanks in advance!
ReplyDeleteDear MW,
DeleteThere are many conditions that mimic pheo. I have a post
"If not pheo, what do I have?" on WEDNESDAY, JULY 28, 2010.
Dr. Pheo
Dear Dr. Pheo, my cousin removed a right adrenal gland tumor fifteen years ago. In July 2017, he was given the enhanced CT scanning on the chest and abdomen due to the intermittent back pain for a week. The CT identified increased lung markings on both sides and several intrapulmonary nodular shadows with different sizes in the pulmonary parenchyma. He underwent a series of tests including tracer agent (131I-MIBG). The test results and clinical presentations indicate the pheochromocytoma recurrence as well as ectopia and pulmonary metastasis. The whole family is devastated by this rare disease. The surgery is not recommended in his case. What treatments would you recommend? Which hospital and doctor would you recommend? Thanks a lot!!
ReplyDeleteDear Anonymous,
DeleteTreatment of metastatic pheo requires experience and expertise. Please check one of my early posts on a list of pheo specialists.
Dr. Pheo
Dr Pheo,
ReplyDeleteI am so grateful to have run across your blog. When I was running with my dog three weeks ago, I took quite a fall and was taken to the emergency room. To check my ribs, they did a CT scan. During the scan, they had an incidental finding of a mass on my adrenal gland. It was low density and rounded, so there was no thought for concern, but wanted an MRI to follow up to be sure. After the MRI, there was more concern requiring now a 24 hour urine, blood draw and PET scan. The impression said, "T1, T2 hyperintense lesion in the left adrenal which demonstrates contrast enhancement, and essentially necrotic. This is favored to be a pheochromocytoma, although additional considerations include solitary metastasis, or an early presentation of Richard a cortical carcinoma." I am very scared. I have never had high blood pressure a day in my life, nor any of the other symptoms. I went through menopause early, so some symptoms may be due to that as far as libido...but that has gotten better with medication. Confused and hopeful for your thoughts. Are PET scans only ordered if they think you for sure have cancer? Thank you so much!!
Also, if I did have to have something done, I am from Michigan, so would you recommend anyone from the U of M Hospital?? If I had to have a theo removed, what is recovery time? I am a teacher and school is starting soon!!! Thank you!! (This is an add on from above!)
DeleteDear Anonymous,
DeleteIncidentally identified adrenal mass like what you have is a common issue. Your adrenal mass likely will need to be removed. Pheo markers also need to be tested. U of Michigan Ann Arbor has a great center for adrenal tumors. There are a number of doctors there (Drs. Auchus, Else, Hammer, etc) who specialize in adrenal tumor.
Dr. Pheo
Dr Pheo,
DeleteThank you for the reply...my lesion is measuring
3 X 2.6 and was not seen in my last scan in 2012. Wondered your thoughts on the size as far as being worried about cancer. If it is a pheo, what is recovery time from a surgery like that? Thank you so very much!
Dear Anonymous,
DeleteSize alone cannot tell whether it is cancer. Recovery from a pheo surgery is usually quick. You probably need to rest for 1-2 weeks before you can work full time.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteMy symptoms started almost a year ago. My usual bp is around 105/75. One day I began to feel unwell at work (in a clinic). My bp was 160/110. I had bad headaches, felt faint, and had chest pain/pressure and sob. I had these episodes off and on throughout the week, and one day it just stopped. I had a few good weeks, until I took prednisone for a tough case of sinusitis. The following week, I was miserable. All my symptoms returned. My doctor prescribed hydroxyzine, which did not help. Episodes were intermittent through the winter, until in January I took another dose of prednisone for bronchitis. Mid-way through that treatment, my episodes started again - blood pressures in the 150/110 range, terrible headaches, sweating (I was sleeping with the windows open in -40 weather). Several days that month, my feet were numb. It was a strange numbness that lasted all day. At that time, I chalked everything up to side effects of prednisone. My episodes stopped in February and I had a pretty healthy spring. In early May, they returned. I had them at least several times per week, sometimes lasting 15 minutes, other times all day long. I went back to my doctor who said it was anxiety. Up until this point, I was feeling pretty well mentally. The episodes were very scary, but I was getting through them. She asked me to try hydroxyzine again, which again didn't help. I found info on pheo and asked her to explore it. My first 24 hr urine was abnormal, and they said they were just going to call it inconclusive as something must have interfered (I hadn't taken any medicine other than advil for weeks prior to the test). I went through 6 weeks of worsening attacks, and eventually started to develop some anxiety on top of it. My doctor had me start prozac, which I reacted very badly to. Then she had me try propranolol and hydroxyzine for several weeks. I still had bad attacks during that time. I am now taking ativan to deal with the anxiety that comes on top of the physical symptoms, and seeing a counselor for support, but no amount of deep breathing exercises takes away the chest pain, palpitations, or blood pressure issues. I've had a cardiac workup with normal stress echo and 48 hr holter. Abdominal CT didn't find anything on adrenals, but did find a large cyst on one ovary, areas of colitis, and prominent venous structures in my pelvis. Ultrasound found a mass in my gallbladder that can't be determined if it is a stone vs. some sort of polyp. I often have pain in my right kidney/flank during these episodes, and pain in the left side of my neck. I have been told that I have sponge kidney. My repeat 24 hr urine just came back with metanephrines 188 (39-143). What would you recommend as next steps?
Dear Anonymous,
DeleteWhat is the value and normal range of the normetanephrine and metanephrine components?
Dr. Pheo
Meta: 188. Reference (39-143)
DeleteNormeta: 335 Reference (109-393)
Dear Anonymous,
DeleteMost likely you don't have pheo. To be safe, you should repeat the test in 6 months.
Dr. Pheo
I have all the classic symptoms of a pheo, and my urinary normetanephrine levels were measured at about 5x normal. My dr was convinced I had a pheo, but an abdominal ct scan and a full body I123-MIBG scan showed nothing. Is it likely that both could have a false negative result? Where do I go from here? I just don't know what else to do.
ReplyDeleteDear CJ,
DeleteThe bladder, the pelvis, and the heart are the potential locations of pheo that are not seen by abdominal CT and sometimes not even by MIBG scan. You may do chest and pelvic CT, and/or FDG PET, Ga68 DOTATATE PET, or octreotide scan to see if a pheo can be found.
Dr. Pheo
Hello,
ReplyDeleteMy son is 18 and has become ill in the past six months, until this he was perfectly healthy, athlete, never sick. He lost 25+ pounds in the past six months and has been having intermittent elevated bp and heart rate, generally feeling poor off and on, sweats a lot, nausea off and on, definitely worse when he eats a lot. He had a few "episodes" and ended up in the ER, every test known to man was performed including an abdominal CT, nothing showed up everything is normal. The only test that was even slightly elevated was 24 hr urine epinephrine of 22 (0-18 normal) and most recently plasma epinephrine of 119 (normal 0-60). His plasma metanephrines were normal, so.... Late last week he had another episode, much more severe than any other and was taken from campus by ambulance, and is now in the hospital, his heart rate was 170 resting and bp 170/110, he has every classic symptom of pheo. With this episode he said he could feel what he described as an adrenaline surge just out of nowhere. He has been tested for every other adrenal/endocrine issue, all normal. He has had a full cardiac workup, heart is good, kidneys are fine. Prior to this his bp was typically 110/60 and heart rate was 50-55. Now even when he isn't even having an episode his bp is 130/90 and heart rate is 90. Clearly something is wrong, have you seen patients with this type of symptoms but nothing showing up in the metanephrines/catecholamines but they end up with a pheo/paraganglioma diagnosis? He also complains frequently that his eyes feel weird, vision is different, but he can still see, he says its hard to explain. The nurse told him his eyes were very dilated when they admitted him, is this consistent with pheo or does it mean anything in your opinion? They are going to start him on medication, but I fear this is only going to mask the problem and he is so young and was so healthy. Any suggestions for us??
Dear Kll,
ReplyDeleteYour son does NOT have pheo. Other causes of his symptoms should be considered.
Dr. Pheo
I had an adrenalectomy four years ago for an incidental adrenal tumor which was found to be a benign pheochromocytoma with a PASS score of 11.
ReplyDeleteTwo years later on a screening MRI, nodules were found in my lungs. Had an MIBG scan which was negative and then a VATS surgery which confirmed malignant pheochromocytoma with lung mets. Had a negative octreoscan, but was started on Sandostatin injections, then Captem oral chemo, neither of which were effective. Was switched to CVD chemo for six months, but still had slow progression. Had another negative MIBG scan.
Started Keytruda which has kept me stable for nearly a year now. By the way, I also have Lynch syndrome and my original tumor was MSI high. There is now a question as to whether my diagnosis is correct. One of my doctors believes it to be an adrenal cortical carcinoma while several other believe it is a metastatic composite pheochromocytoma. All blood and urine tests have been negative.
Is there any way to confirm my diagnosis?
Dear AJ,
DeleteIn most cases, pheo and adrenocortical carcinoma are quite different on histology. Immunostaining of chromogranin A and synaptophysin is also helpful. You may also want to have the slides read by a specialist pathologist.
Dr. Pheo
My tumors were negative for chromogranin A and positive for synaptophysin. I have had my slides read by specialist pathologists and unfortunately, they do not agree on my diagnosis.
DeleteDear AJ,
DeleteYour tumor is quite unique then. The best way forward is to have a conference in which several specialist doctors attend and discuss your case.
Dr. Pheo
Dear Dr Pheo
ReplyDeletePlease help me.....
Is this possible to make an appointment with you to discuss my case? I live in SF
Please let me know if it is possible
Natasha
Dear Anonymous,
DeleteYou can see Dr. Quan-Yang Duh at UCSF.
Dr. Pheo