Wednesday, September 25, 2013

Another "dopamine-producing" pheo

Some days ago, I got a call from a physician asking me for suggestions on how to proceed with a “dopamine-producing” pheo. The patient was an elderly man with labile blood pressure and varying heart rate. Pheo was suspected. Urine dopamine levels were >5000 mcg/24 hours (normal reference range: 60-450). But was it a pheo?

I usually get 1 or 2 calls on potential "dopamine-producing" pheo every year. True dopamine-producing pheos are extremely rare and do not cause clear symptoms. These tumors are usually localized outside the adrenal glands and may present as metastatic tumors. They are usually clinically silent until they grow very big and causing abdominal discomfort. Specifically they do not cause hypertension per se. Only about half of the patients have high dopamine only and the other half have high dopamine and high epinephrine or norepinephrine as well.

In any given situation, the most common cause of very high urine or plasma dopamine is the medication Carbidopa-Levodopa (Sinemet) for Parkinson disease. These patients usually have every high dopamine but normal or slightly elevated epinephrine or norepinephrine. Levodopa is presumably converted into dopamine which is then detected by the catecholamine measurement. Parkinson disease and related conditions such as multiple system atrophy often cause sympathetic instability in the forms of fluctuating blood pressure and heart rate, orthostatic hypotension, and syncope, all of which resemble pheo symptoms.

I therefore asked the physician if the patient had Parkinson disease. He was reasonably surprised and told me the patient did have Parkinson. I then asked if the patient took Sinemet. He checked the medication list but Sinemet was not on the list. I was not swayed. Many patients think Parkinson is a disease of old age and Sinemet some kind of food supplement so they do not tell their doctor they are taking it. Luckily the patient was still in the clinic. The physician told me he would ask the patient about Sinemet and call me back. He didn't call me back. I assumed the patient was taking Sinemet, as all of the patients I had been asked about are.

Dr. Pheo



P.S. I have not written about pheo for 7 months for various reasons. My job is more demanding, to be sure. Also, there has not been a major advancement in the pheo field in the last 7 months, in my opinion. 

56 comments:

  1. Hello Dr. Pheo

    I am 34 yrs female and had been diagnosed with hypertension in May 2013 (BP: 180/100). I had a 24 hr urine test for catecholamine done. Results: epinephrine is 12.87 ug/g creat; norepinephrine is 3754.64 ug/g creat and dopamine is 319.18 ug/g creat.

    Based on these results my endocrinologist recommended an MIBG scan which came up with no evidence of pheo found. Subsequently I underwent a PET/CT scan.

    i will quote the results : "No abnormal FDG uptake is seen in both adrenals. Nodule is noted on medial limb of right adrenal that measures 9X7 mm having fat density on CT - likely to represent an adenoma. Left adrenal is normal."

    Based on this my endocrinologist is still suspecting a very tiny pheo.

    i continue to monitor my BP on weekly basis. I had been taking some medication (Alphadopa 250 twice). BP was fine for few months. Started fluctuating again with frequent headaches. Rose to 160/110. My Dr. has added another medicine (nicardia Retard 20 - once) since 2 weeks now. BP has been normal till now.

    So what is your opinion on this- is this more likely to be a pheo? Could I have anything else? What should I do next?

    Thank you. Look forward to your response

    PS: I had posted this in your post on Very small pheos. Am reposting as there was no response.

    ReplyDelete
    Replies
    1. Dear Baljeet,

      I am sorry that I did not see your earlier question. You unlikely have pheo. Other causes of secondary hypertension, such as renal artery disease and primary hyperaldosteronism should be considered.

      Dr. Pheo

      Delete
  2. Dear Dr. Pheo,

    My 64 year old Father was diagnosed with a suspected dopamine secreting paraganglioma. He is not a Parkinsons patient and was a relatively healthy and active individual prior to the onset of flank & abdominal pain over the past 4 - 8 months. He experiences high level pain attacks that last 15 - 60 minutes but he does not appear to have the hypertension involved with the classical pheo. The CT Scan from 5 weeks ago indicates an abdominal mass that is 78mm wide, 61 mm deep and 105 mm tall. The CT also indicates the mass is adjacent to the upper pole left kidney, markedly increased in size now showing encasement of the aorta, with invasion of the crux of the left hemidiaphragm, left kidney, spleen and also likely tail of the pancreas. The tumour appears to be aggressive as there was such involvement on the CT from a couple of months prior.

    My Father had been Alpha Blocked and deemed fit for a surgery that was to have occurred one week ago. Unfortunately the surgeon finally got around to reading the new CT report and cancelled the surgery, deeming it too risky to operate. We are now in a situation where they have recommended getting him approved for Sutent. Our alternative plan is investigate a Radionuclide Therapy option.

    Dr. Pheo, I would like to know what treatment options you would recommend? Is it possible to shrink this tumour to the point where surgical resection is again an option?


    Thank You. Your Blog is a great wealth of information on a subject in which information can be difficult to find.

    ReplyDelete
    Replies
    1. Dear Para,

      Chemotherapy is probably the best option now. Sutent and MIBG radiotherapy can both be considered.

      Dr. Pheo

      Delete
  3. Dear Dr. Pheo,

    What would cause low dopamine? And what are your thoughts about an SDHB family with Carney Triad, Neuroblastoma, Paranglioma in one identical twin and very small bilateral pheos in the other identical twin? Would one gene cause all those different things in one family?

    Thank you again,
    Frances

    ReplyDelete
    Replies
    1. Dear Francis,

      Yes, SDHB mutation can cause all those. The penetrance (how the mutation will affect a person) is variable. So it is not uncommon that 2 siblings have tumors at different organs and at different ages.

      Dr. Pheo

      Delete
  4. Hello Dr Pheo,

    I just saw this blog in search for some information. Recently I had 24 hour urine catecholamines test done, my levels of Norepinephrine were mildly elevated above the reference range at a value of around 180 mcg/24h, while my dopamine levels seemed significantly more elevated at a value of around 900 mcg/24h. The Dr, decided this was likely the result of stress or anxiety and that was that. Could anxiety actually be the most likely explanation for the elevated results?


    I am not on any medication aside for ACE inhibitor and Beta Blocker.

    ReplyDelete
    Replies
    1. Dear Doug,

      Anxiety can cause mild elevation of norepinephrine levels. The elevated urine dopamine levels are unlikely related to anxiety. You can measure plasma catecholamines. If the plasma dopamine levels are normal, then the elevated urine dopamine levels do not mean much.

      Dr. Pheo

      Delete
  5. I recently had serum catecholamines, supine norepinephrine was at 650, standing was at 800 and my dopamine was elevated on both readings at 23 and 24. I had negative metanephrines back in January but was fairly asymptomatic when urine and serum collected. I have bouts of tachycardia up in 170s that seems to be aggravated by even something such as bending over, hypertension that is labile, and sweats. Could it still be pheo despite negative labs January? Thanks.

    ReplyDelete
    Replies
    1. Pheo is unlikely. Other causes of your symptoms should be sought after.

      Dr. Pheo

      Delete
  6. Sometime over the previous 6 months, my blood pressure went from normal ranges to grade 2 hypertension; doctor 165/110; home testing in early AM 180/115, even to 200/118; after 2 weeks medicine; 145/90. Highly variable, checking many times per day.
    blood plasma:
    CATECHOLAMINES 928
    DOPAMINE <30
    EPINEPHRINE 35
    NOREPINEPHRINE 893

    Other blood tests showed only
    GLUCOSE 59

    I have no symptoms. I am thin, eat no red meat, do not salt food, drink maximum one wine evening, do not smoke, etc.

    I have noticed that, for previous 4 months, I do not sleep more than 6 hours and wake up wide awake. Blood pressure was highest at this time, immediately on rising.

    I can think of no other change in my health. I am not stressed. I get moderate exercise every day.

    I am scheduled for CT scan. I had ultra sound no renal artery stenosis. Trabeculated bladder (I have EP), scheduled for urology.

    I see another test for Metanephrines in medical literature. Is this an important additional test?

    ReplyDelete
    Replies
    1. The metanephrines are indeed better than catecholamines in pheo diagnosis.

      Dr. Pheo

      Delete
  7. Dear Dr. Pheo,
    I was diagnosed with POTS that has been getting progressively worse over the past few years. I recently had plasma catecholamines checked:
    Dopamine: 82 pg/ml (normal range 0-20)
    Norepinephrine: 671 (80-520)
    Epinephrine: 11 (10-200)
    Do you think this could be pheo? What else do you think could be creating high dopamine and NE yet low E?

    ReplyDelete
    Replies
    1. Dear Anonymous,

      It is unlikely pheo. The slightly elevated dopamine and NE but low E mostly points to nerve release of dopamine and NE (rather than released by pheo).

      Dr. Pheo

      Delete
  8. I have had increased Dopamine on 24 hour urine tests. Epinephrine and Norepinephrine are normal. I've had sudden onset of high blood pressure 170/ 124, heart rate only 65- 70. I can not breath when I have those onsets of high blood pressure. I've seen Endo 4 times in last few months. Two 24-hour urine tests were positive, one negative (Metanephrines Free 24 h 0.233 both times, Dopamine 24 h first time 3764 nmol/d. second time 3474 nmol/d). I am doing forth 24 h urine test next week. I have 1,5 cm visible adrenal adenomaon few MRI's. I do not drink smoke or use any kind of drugs. I have puffy ankles, like 3 golf balls arounf each ankle and gain about 25 lb in last 1,5 year. All other adrenal disorders except Pheochromocytoma are ruled out by my Endo. Kidneys, lungs, liver and heart are ruled out as causes of my high blood pressure. Any thoughts, suggestions? Thanks

    ReplyDelete
  9. I have elevated plasma dopamine of 138 (ref range 0-20) and all other catecholamines/metanephrines in normal range. I am very anxious and recently was very ill and stressed with thyroiditis. Is this from stress, or a possible tumor?

    ReplyDelete
  10. Dear Anonymous,

    The slightly elevated dopamine levels are unlikely caused by a pheo. It is often not clear why dopamine levels are elevated in patients without pheo. I suppose anxiety and stress may contribute. I usually recheck dopamine levels in 3 months to make sure they are normal then.

    Dr. Pheo

    ReplyDelete
    Replies
    1. Dear Dr. Pheo,

      Thank you so very much for writing! I was under the impression that my dopamine was very high, and it's reassuring to hear you refer to it as "slightly elevated." Your response just lowered my stress level, and I am very grateful for your input.

      I've been researching other possible causes of elevated dopamine (as a currently unmedicated person), and coming up empty except for stress. My thyroid levels are still very slightly low and my body is recovering from months of inactivity and soaring/plunging thyroid hormone levels. Is there anything other than pheo testing you would recommend pursuing, or is it safe to let this go if further testing shows dopamine at this level or lower?

      I just had more testing done which will hopefully clear things up, and I will let you know how this plays out. Have a great week!

      All best,
      Anonymous

      Delete
    2. Dear Anonymous,

      Let's see what repeat test will show.

      Dr. Pheo

      Delete
  11. Dear Dr. Pheo,

    Happily, I tested in the normal range on both blood and urine tests. I am being told to assume the initial blood test was a false positive. Would you advise a retest at a later date, or does this sound like a straightforward false positive to you?

    Thanks so much,
    Anonymous

    ReplyDelete
    Replies
    1. Dear Anonymous,

      I would not worry about it any more.

      Dr. Pheo

      Delete
    2. Great, thank you! I am honestly not sure why I was tested for it in the first place. Thank you again for taking the time to write. I hope this is useful to someone else who may be scared by a false positive.

      Happy holidays!

      Delete
  12. Hi,
    I am a 29 year old female. when i was 21 they found an adrenal adenoma, and after several tests deemed it fine. Recently they decided due to underlying systems to start checking it again. I received blood tests/urine tests back that showed an elevated level of Dopamine, however the rest of my catecholamine’s were fine. On the 24h urine my results were:
    Dopamine: 2891.00 nmol/d (ref range: <2600)
    Epinepherine: <10 nmol/d (RR: <100)
    Norepinephrine 269 nmol/d (RR: <500)

    I also have elevated:
    Creatinine: 18.4 mmol/d (rr 4.2-15.3)
    DHEA: 13.6 unol/l (rr 2.68-9.23)
    Testosterone Bioavailable: 1.2 nmol/L (rr 0-0.8)
    Testosterone, Free: 2.3 nmol/L (rr 0-1.9)
    Plus high cholesterol 5.12 mmol/l (rr 0-4.59)

    As well as low:
    MVP
    SHBG 15 nmol.l (rr 25-122)

    We also did a 24 hour cortisol test which came back fine to rule out Cushing’s.

    Is there any chance it’s a PHEO?

    Thank you,

    ReplyDelete
    Replies
    1. Sorry, forgot to mention my metanephrines came back fine as well.

      Delete
    2. Dear Anonymous,

      Urine dopamine is mostly made by the kidney. The plasma dopamine is more accurate for pheo diagnosis. With all things considered, you unlikely have pheo.

      Dr. Pheo

      Delete
  13. Hi Dr Pheo
    I was extensively investigated for a pheo in 2011 after suffering from initially prolonged elevated bp (between 240/160 and 180/110) which settled to labile bp (ranging between 220/150 to 80/40) (all readings taken manually). Numerous 24hr collections showed normal cat and met for adrenaline, slightly elevated both for noradrenaline and levels of over 8000 for dopamine (ref <2500). CT, numerous MRI, MIBG and one other nuclear med scan negative. Was discharged.

    Recently had ?anaphylaxis/??pheo crisis episode, facial swelling/wheeze/flushing. Relieved with piriton 8mg and epipen x2. BP again very labile, ranged 70/30 to 260/180 with as little as 3 minutes between vastly changed readings (done manually in ER). 24hr urine again for catecholamines and metanephrines showed normal adrenaline, noradrenaline unfortunately able to be recorded and dopamine 5317.

    I appreciate having been extensively investigated 4 years ago that a pheo is unlikely. I am awaiting rv by endocrinology again now 24hr urine results back. I wondered what your thoughts on Page's syndrome are? I have Ehlers-danlos syndrome, no chiari malformation have been mentioned following MRIs (would it always be mentioned?) but my understanding is that dopamine pheos are silent without affecting bp? Is Page's syndrome therefore a possibility and/or could it be connected to the Ehlers-danlos syndrome? I suffer also from pulsatile tinnitus and POTS and severe, brittle asthma (which is currently behaving since starting xolair injections, I have been out of hospital for 5 months!). Any thoughts gratefully received. Thank you so much.

    ReplyDelete
    Replies
    1. Dear Anonymous,

      I am sorry but I don't know much about Page's syndrome.

      Dr. Pheo

      Delete
    2. Thank you for taking the time to reply, it is much appreciated. Is Page's syndrome therefore not very common?

      Delete
    3. Dear Anonymous,

      Page's syndrome is one of the syndromes mimicking pheo. The term is often used loosely.

      Dr. Pheo

      Delete
  14. My 17 y.o. son had a pheo and his left adrenal gland removed in July; he subsequently lost his kidney due to occlusion in the artery (not addressed quickly enough to put in a stent). At the 3 month 24 hour urine test, his norepinephrine was slightly below range (9 instead of 15-57), his epinephrine at the bottom of the range (1 instead of 1-9) but his dopamine much lower (59 instead of 137-393). Ratios were similar too.

    I know he doesn't have a pheo now. My questions is what causes low dopamine and is it something that needs to be addressed in any way?

    Thank you.

    ReplyDelete
  15. Dear Wendy,

    The urine dopamine is mostly made by the kidney. The meaning of low urine dopamine is not clear.

    Dr. Pheo

    ReplyDelete
  16. Dear Anonymous,

    You can see Dr. Fitzgerald in San Francisco. I have to delete your post to protect your personal information.

    Dr. Pheo

    ReplyDelete
  17. Dr pheo. I have been experiencing high anxiety and have been hospitalized 7 times in the past 2 years for "anxiety attacks" resulting in fast afib heart beat, shortness of breath, and dizziness. Finally my endocrinologist tested my urine levels 3 times. catechomolines levels resulting in my dopamine levels to be 678 the first time, 874 2 weeks later and 690 2 weeks later with normal ranges on my nonepinephrine and epinephrine levels . My doctor suspects a tumor but I had a colored ct of my abdomen down to pelvis, colored ct of chest to neck , and a regular ct of head. Nothing has been found. What are your thoughts Dr pheo and could this be caused only because of stress?

    ReplyDelete
    Replies
    1. Dear Unknown,

      Unlikely you have a dopamine-producing tumor. Most of urine dopamine is made by the kidney. An isolated urine dopamine has unclear significance.

      Dr. Pheo

      Delete
  18. Dr. Pheo-
    Last year I had sudden onset resistant hypertension, diziness, tachycardia (history of PSVT that was ablated in 2001 and under control since then)

    I've seen two endocronoligists who state I am outside of their area of expertise and to go to Mayo but insurance doesn't cover.

    My hx is as follows
    ER visit for headache, tachy, BP 180/110
    CT shows advanced brain loss (I think hypertensive crisis)
    Follow up brain MRI normal
    Renal US normal
    Echo-diastolic dysfunction (normal ejection fraction)
    While monitoring my blood pressure I sporadically get trousseau sign despite my calcium being normal

    Urine tests have all been normal for cathec, metanephrines, dopamine etc

    Blood abnormalities
    Slightly elevated cortisol multiple times
    metanephrine elevated to 84/pg and 61 pg with normal normeteneprine

    Most recent labs plasma
    Epinephrine 55
    Normepinephrine 326
    Dopamine 38
    NM 64
    NMN 83

    I honestly don't know where to go from here. I'm in AZ if you have any ideas of what to look into or know a doc that may take me on.

    I do currently take adderall, however, for some of these tests I had quit taking it for months to rule out that as a cause.

    Thank you SO much

    ReplyDelete
  19. Wanted to edit my above post to note
    I am 37
    One endo found a highly vascular nodule on my thyroid that we are going to "watch"
    I'd love to know if you would recommend any other scans at this point

    thyroid tests have all been normal as well as PTH

    ReplyDelete
  20. Dear Unknown,

    Pheo is ruled out. Please see my post in July 2010 on other possible causes of pheo symptoms.

    Dr. Pheo

    ReplyDelete
  21. Thank you. Can you explain why you believe it’s completely ruled out due to sudden onset of symptoms and two different abnormal scans (brain ct and diastolic dysfunction) I am positive I did not have any issues with hypertension previous to Jan of last year along with moderately elevated other blood work. I am consistently tachy even during sleep with POTS like reactions but haven’t been formally tested. I also truly don’t believe this is anxiety related despite knowing the negative connotation associated with it. Just trying to figure what you mean by ruled out and what specifically makes you believe so. (Just elevations aren’t high enough). Thank you again for all
    Your help. (Anonymous/ Erin Rinny). :)

    My resting heart rate now averages 125 (I have confirmed this via Apple Watch and 21 day halter but nobody can seem to explain. It bounces everywhere as well as bp etc

    ReplyDelete
  22. Dear rinny,

    The normal urine markers and slightly abnormal blood markers are not consistent with a pheo causing your symptoms.

    Dr. Pheo

    ReplyDelete
  23. Dr. Pheo ,
    Would Dopamine levels of 598mcg on a 24 hour urine test be considered very elevated ? Ephineprine was 22mcg and noephinenphrine was 67mcg. VMA was 6 everything was normal except that dopamine level. Could that be indicative of pheo or a dopamine producing tumor?

    ReplyDelete
  24. Dear Unknown,

    I would check the plasma dopamine level (blood test). It is better than urine dopamine for pheo diagnosis.

    Dr. Pheo

    ReplyDelete
  25. Hello dr pheo, Patient 28 year old male presents with episodes of tachyardia and high blood pressure readings and is screen for pheochromcytoma. patient also has a suspected core myopathy based on a muscle biopsy, has had sudden severe headachs, acute abdominal pain, episodes of lightheadness, and intoxicated like feelings as well as sudden sexual urges and visual disturbances

    The pheo screening showed everything in the normal range expect for Dopamine which came back significantly at 3750.

    based on the symptoms and urine test do you think a dopamine producing tumor could be possible?

    ReplyDelete
    Replies
    1. Dear Unknown,

      I think pheo is still not very likely. I would also measure a plasma catecholamines to see if the urine dopamine is mostly from kidney.

      Dr. Pheo

      Delete
  26. hello dr. pheo sorry to bother you but i was wondering what your take on this is, i currently take meds for slightly elevated blood pressure, tachycardia( results in breathing and chest pain), raynauds phenomenon. I also have muscle weakness, bizarre posturing, excessive blinking, food triggers included bananas, chocolate, vanilla coffee creamer(results in stomach upset and rapid heartrate). As a child i couldn't take cough medicine because it caused hyper activity and unpleasant feelings. CT scan of abdomen normal.

    Pheo screening results are the following:

    catecholamine fract 24h urine,

    Volume 24h: 1800- range 600-1800ml/d
    Creatinine 24h: 17.2 range 6.3-22.7 mmol/d
    epinephrine: 78 - range <100 nmol/d
    norepinephrine: 395 -range <500 nmol/d
    Dopamine: 3710 - range< 2600 nmol/d
    normetanephrine- 1.5 range <3.3 umol/d
    metanephrine : 1.1 - Range 1.7 umol/d

    ReplyDelete
    Replies
    1. Dear Dopey,

      Pheo is ruled out. If you worry about your urine dopamine, you can measure plasma catecholamines. The urine dopamine is mostly made by the kidney rather than pheo.

      Dr. Pheo

      Delete
  27. Dr. Pheo

    I have now had 3 24 hour urine collections and 1 plasma metanephrines test due to a dopamine level that continues to be a little bit out of the reference range. Are those numbers high enough to suggest a dopamine producing Pheo? Please let me know if you think Pheo is ruled out based off the numbers below. AThank you.

    24 Urine ( first, second, third time)

    Epinephrine, 22 mcg, 14, mcg, 22 mcg ( reference range goes to 24)

    Norephinenrine: 67, 71, 42 mcg ( range 15-100)

    Dopamine, 598 mcg, 700 mcg, 613, mcg ( range to 450mcg).

    Plasma Metanephanrin 43pg/ml/ (range less than 57)Nometanephrine 66 pg/ml (range less than 148) all normal

    ReplyDelete
    Replies
    1. I also forgot to mention that the results of an abdominal CT scan with and without contrast was unremarkable

      Delete
  28. I have been diagnosed with POTS but got the 24 hour urine test. Everything came back normal with the exception of the dopamine. This was at 518. Should I be concerned about pheo? Should I ask to get a blood test to show it instead.

    ReplyDelete
  29. Dear Malisa Abrahams,

    The risk of pheo is low. You may want to do a blood test to measure catecholamines (including dopamine).

    Dr. Yu

    ReplyDelete
  30. HElko Dr. Pheo I've been having chest pain palpitations at rest and a day after exercise the chest pain was worse once while running for a year now. I did CT scan which came out normal I also take risperidone and have high blood pressure at 148 over 90 something my plasma catecholamines showed my dopamine high at 52 all other catecholamines were normal. How should I proceed? is it possible I have a pheo and dopamine is that low because it's only been a year since presentation?

    ReplyDelete
  31. It's me doctor with the 52 dopamine level the chest pain also happens more often when anxious it has decreased a lot in frequency I would say 80 percent since a year ago it started to decrease after taking metaprolol

    ReplyDelete
  32. Dear Unknown,

    Dopamine secreting pheos usually do not cause any symptoms other than those related to tumor compressing on normal organs. Overall you unlikely have a pheo.

    Dr. Pheo

    ReplyDelete
    Replies
    1. Can risperidone cause high dopamine levels? are they likely to be that high in dopamine pheo even at early stages?

      Delete
    2. Dear Unknown,

      I could not find any report on risperidone and dopamine levels. So I don't know.

      Dr. Pheo

      Delete