Why are the repeat test results different?

Happy Holidays!

For a serious diagnosis like pheo, repeat testing of pheo markers is generally a good idea. Pheo test results from the same patient even within a few days or weeks can be quite different at times. Patients having acute illness, anxiety attack, or any emotional or physical stress would have higher pheo marker levels than when they are healthy and restful. The position (sitting or lying) of patients getting blood draw matters. Random variations are always possible. Laboratory errors do happen as well. If the two test results are concordant (which fortunately are more common), we can confidently say whether the patient has normal or abnormal pheo marker levels. If, however, the two test results are discordant (one abnormal and one normal, or one very high and one only slightly high), what shall we do?

There are several factors to consider. First, we need to see the quantitative differences between the two results. If one result is in the high normal range and the other slightly abnormal, they are essentially similar and concordant results. Second, we need to delve into the details on the patient’s mental and physical condition when the tests are done. If the patient is seriously ill when one test is taken, the result is likely higher and does not necessarily suggest pheo. Third, we need to ask ourselves the likelihood of this patient’s having pheo is high or not, based on the grounds why we test for pheo in the first place. Of course the more suspicion we have, the more likely the abnormal result is true. Fourth, past research has shown that if there are no laboratory errors, a single normal test result rules out pheo in most patients. Thus a negative pheo test result should be given more weight in general. Last, when we are really not sure, imaging is needed to give us more information.

Dr. Pheo

Ten years and going strong!

I started the Dr. Pheo blog on March 19, 2009. At that time, I was not certain how long the blog would last. Today, exactly 10 years later, I am pleased to see the blog is still going and going strong! I thank my family, friends, colleagues, patients, and especially readers for your support and encouragement in all these years.

      Pheo is a fascinating but challenging disease. In the last 10 years, we witnessed the explosive growth in pheo genetics and pathogenesis. Genetic tests for pheo are now widely available. We also observed the unraveling of the natural history of pheo and the understanding of pheo-induced heart problems. More doctors now recognize that small pheos exhibit features distinct from those of large pheos. The diagnosis of pheo progressed right in front of our eyes. Metanephrines are now accepted by most doctors as the best tests and are more available world-wide. The imaging characteristics of pheo were firmly established with the emergence of many nuclear imaging tools. In spite of the advancements, two major challenges still face us: misdiagnosis of pheo and management of malignant pheo.

      I will continue the blog as long as I can. I will remain anonymous.  

   

Dr. Pheo

Plasma or urine metanephrines?

I have discussed plasma versus urine metanephrines in the past. Recently a few doctors asked me this question again. I figure that if some doctors are not clear whether to order plasma or urine metanephrines, patients probably also want to know the pros and cons of plasma and urine metanephrines.

      First of all, both tests are great. If your local area only offers one of them, take it. If your local area offers both tests, which one is better? Shall you do both? My personal preference is plasma metanephrines. The plasma test is convenient and can be done to any patient at any time. The only small drawback is the blood draw itself. If you really hate needles, the plasma test could be an issue. The urine test offers no practical advantage over the plasma test. In theory and in earlier reports, the urine test is less prone to false positive results. In real clinical practice, the urine test and the plasma test perform similarly. The urine test is laborious to collect (24-hour urine is required), not reliable in patients with kidney problems, and hard to do in children. Lastly, the urine test results have to be corrected by urine creatinine. I have seen patients who passed ~5 liters of urine in 24 hours; of course the metanephrines levels are higher simply because of the large urine volume. The results usually are more accurate after they are divided by the total amount of creatinine in the urine. Again I want to emphasize that I personally don’t see why one would need the urine metanephrines for pheo diagnosis if plasma test is available. There is also no need to do both tests.

       

Dr. Pheo

In case I missed your questions...

Only a few days ago, did I realize that I had missed several questions from the Dr. Pheo blog. I have not received any email alerts on new questions since late May 2018. Initially I thought perhaps it was summer time or perhaps readers found answers from previous posts. Then I saw a few comments on the blog a few days ago. That was strange because I was supposed to get email alters on new comments. I certainly did not change any settings and I checked again and found all the settings were the same.

Then I googled the problem. Wow, so many other bloggers had similar problems. It looked like Google Blogger required bloggers to re-consent receiving email alerts. The bottom line is that I can now receive email alerts of your questions. If you posted questions in late May or after, and did not receive answers from me, please post your questions again if you still need the answers.

Dr. Pheo

Incidental pheo (?) found by DOTATATE PET

Whenever a new imaging method is used widely, incidental findings from it are encountered. The new Ga-68 DOTATATE PET is no exception. It is well known that DOTATATE signals are normally found in the pituitary, salivary glands, thyroid, liver, spleen, and adrenal glands. Some people may also have signals in the pancreas.
      Although the adrenal glands are known to be lit up by DOTATATE PET, the signal from normal adrenal glands is usually low. A technical jargon called the standard uptake value (SUV) quantitatively describes the intensity of PET signals. Unfortunately, different machines give out different SUVs on the same organ of the same patient. The SUV thus has relative importance only in the same patient using the same machine.
      I saw a patient recently. She had another kind of neuroendocrine tumor and did a DOTATATE PET. The PET showed she had strong signal on one adrenal gland (SUV ~8) while the other adrenal gland had normal signal (SUV ~2). CT showed a tiny nodule in the adrenal gland with strong PET signal. Is this a metastatic lesion of the other neuroendocrine tumor? Or is it a tiny pheo that is incidentally found by the DOATATE PET? Either adrenal metastasis from neuroendocrine tumor or pheo is rare. Based on a variety of factors, I favor she has a tiny pheo. There are no convincing ways to prove either diagnosis. Only time will tell.

Dr. Pheo

Pheo still kills

Pheo very rarely causes death in modern times. Whenever a patient dies of pheo, the diagnosis and management of the patient’s pheo require detailed analysis. The lessons learned from such an unfortunate death are invaluable.

I run into a case report published earlier this year. A 61-year-old male suddenly developed fatigue, nausea, vomiting, and shortness of breath. He came to an emergency room 6 hours later. At the emergency room, he initially had high blood pressure and heart rate. His condition deteriorated quickly so that he was intubated. His markers of heart attack were elevated but his coronary arteries were normal. His left heart ventricle exhibited abnormal movement. He was diagnosed with takotsubo cardiomyopathy (a heart disease caused by extreme stress). Chest X-ray showed signs of heart failure and CT showed changes consistent with certain kind of pneumonia. 2 hours later, his blood pressure suddenly dropped and he suffered from cardiac arrest. He died shortly after. It was only 12 hours between the start of symptoms and death. Autopsy found a 4-cm hemorrhagic pheochromocytoma in the right adrenal gland.

This case is typical for pheo-related sudden death. He was apparently healthy before the onset of symptoms. He had no known pheo. His symptoms suggested heart or lung diseases. He initially had high blood pressure and heart rate. Testing and imaging showed he had normal coronary arteries but with other heart and lung abnormalities. He then suddenly developed low blood pressure and cardiac arrest and died quickly.

Was his death avoidable? It is hard to say. Were there potential opportunities to make an early diagnosis of pheo and to institute therapies? There probably were. In any patients with acute heart problems with normal coronary arteries, pheo should be considered. Pheo is a rare cause of heart problems but pheo-related heart problems are reversible. The probability of pheo is much higher after the coronary arteries are shown to be normal. Takotsubo cardiomyopathy cannot be reliably diagnosed without ruling out pheo. Therefore, pheo should be considered in this patient. A particularly odd thing in this case was that the chest CT did not mention the adrenal tumor. Chest CT should clearly see a 4-cm adrenal mass. A large adrenal mass and acute heart and lung problems without other plausible explanations only point to one disease, pheo-induced cardiomyopathy and pulmonary edema. He should have been diagnosed earlier and been treated with alpha blockade and aggressive cardiac support with all available devices. Believe it or not, even the sickest patient with pheo-induced cardiomyopathy can survive with early diagnosis and appropriate treatment.

Dr. Pheo

Targeted internal radiotherapies for malignant pheo

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