The 5 pheo tests are subjected to interferences by quite a few factors. I list those factors here according to their significance. The most important message, however, is that these factors are usually not a big deal and can be rather easily figured out by an expert. Reaching a pheo diagnosis requires all things considered, rather than any evidence in isolation.
Major interferences:
1. In many diseases, catecholamines and metanephrines levels are indeed genuinely elevated, and can be rather high. About 30 such diseases are known. Obstructive sleep apnea, severe anxiety, and essential hypertension are the most common ones.
2. Any major stress, such as stroke, severe infection, and bad pain, elevate catecholamines and metanephrines levels.
3. Some drugs such as cocaine, phenoxybenzamine, tricyclic antidepressants, and monoamine oxidase inhibitors can also elevate catecholamines and metanephrines levels. Sinemet elevates dopamine levels tremendously.
Minor interferences:
Eating, standing, the stress of venipuncture, and old age. These conditions usually elevate catecholamines and metanephrines levels only slightly.
Variable interferences:
These are caused by drugs (usually beta blockers) and they are assay-dependent. The clinicians and the lab should communicate about them.
Errors:
Clerical and lab errors are also realistic possibilities. They are rare but can happen.
When I order pheo tests, I actually tell the patients initially not to worry about any interferences. If the results are normal (which is the case in most patients), the patient does not have pheo. If the results are elevated (usually in 20% of cases), I will then decide on a case-by-case basis.
This will be the last post this year. Happy holidays! I will continue posting next year.
Dr. Pheo
Monday, December 7, 2009
Sunday, November 22, 2009
Happy Holidays
Dear readers,
The Dr. Pheo's blog has been running for 8 months. Since the very beginning, readers have been giving me very positive feedbacks. Up to now, the blog has covered almost all aspects of pheo and I hope that patients and families benefit from reading these posts.
As the holiday season is approaching, I want to take this opportunity to wish all patients, their families and friends, and all those interested in this disease a very happy holiday season.
Dr. Pheo
The Dr. Pheo's blog has been running for 8 months. Since the very beginning, readers have been giving me very positive feedbacks. Up to now, the blog has covered almost all aspects of pheo and I hope that patients and families benefit from reading these posts.
As the holiday season is approaching, I want to take this opportunity to wish all patients, their families and friends, and all those interested in this disease a very happy holiday season.
Dr. Pheo
Thursday, October 1, 2009
Pheo tests in the real world
Whenever a new test is reported, its performance is always great (why report it if not?). There are multiple reasons why the test performs well in the original reports. The diagnosis criteria are strict and clear, the tests are run by experts with strict quality control measures, the clerical errors are minimized, etc. When the test is used by more people, it usually becomes not as great. One example is the pheo test "plasma metanephrines."
In the first few studies of this test, the sensitivity (if you have pheo, the test will be positive) and specificity (if you don't have pheo, the test will be negative) both approach 100%. In a very well-designed, definitive study (published in 2002), the sensitivity and specificity are indeed close to 100% but only in people with family history of pheo. In patients without family history of pheo, the sensitivity is also nearly 100%, but the specificity is about 85%. That means, if you do not have a family history of pheo and if your doctors suspect you have pheo but you do not actually have pheo, the chance that the test will still be positive is 15% (false positive). In most cases, it is the normetanephrine that is false positive rather than metanephrine. I am sure you know what I am talking about if you have ever read a plasma metanephrines test report. The metanephrines test gives two values, metanephrine and normetanephrine.
How does the plasma metanephrines test perform in the real world? Earlier this year, a report was published comparing the performances of all 5 tests for pheo in a large US hospital. The 5 tests are plasma metanephrines, plasma catecholamines, urine metanephrines, urine catecholamines, and urine VMA. The study has quite a few limits; the major one being that not a lot of patients eventually prove to have pheo (which is also a strength because it reflects the fact that pheo is rare). With these limits, this study shows that the sensitivity and specificity of all 5 tests are about the same. The nicest thing about the study is that it gives positive predictive value (PPV) and negative predictive value (NPV) of the 5 tests in the real world.
The PPV and NPV are different from sensitivity and specificity because they depend on how the ordering physician selects patients to be tested. Let's not get entangled in technicality but the PPV of a test means that if you have a positive test for pheo, what the chance is that you actually have pheo. The NPV means that if your test result is negative, what the chance is that you actually do not have pheo. In this community-based study, the PPVs of all these tests range from 15-30%. That means if you have a pheo test at this hospital and it is positive, the chance that you indeed have pheo is about 15-30%. If the test is only moderately elevated, the PPVs are even much lower and range from 2-15%. The NPVs of all these tests are excellent: close to 100%. That means if you have a normal test result (from just any of the 5 tests) at this hospital, you are pretty sure that you do not have pheo.
Make no mistake. I do think that the plasma metanephrines is the best test for pheo. It is scientifically sound, highly reproducible, and not as interfered by medications as some other tests. I can also do clonidine suppression test based on the plasma metanephrines. I use it as the main test to diagnose pheo. It is just that the test results need to be interpreted by an expert.
Dr. Pheo
In the first few studies of this test, the sensitivity (if you have pheo, the test will be positive) and specificity (if you don't have pheo, the test will be negative) both approach 100%. In a very well-designed, definitive study (published in 2002), the sensitivity and specificity are indeed close to 100% but only in people with family history of pheo. In patients without family history of pheo, the sensitivity is also nearly 100%, but the specificity is about 85%. That means, if you do not have a family history of pheo and if your doctors suspect you have pheo but you do not actually have pheo, the chance that the test will still be positive is 15% (false positive). In most cases, it is the normetanephrine that is false positive rather than metanephrine. I am sure you know what I am talking about if you have ever read a plasma metanephrines test report. The metanephrines test gives two values, metanephrine and normetanephrine.
How does the plasma metanephrines test perform in the real world? Earlier this year, a report was published comparing the performances of all 5 tests for pheo in a large US hospital. The 5 tests are plasma metanephrines, plasma catecholamines, urine metanephrines, urine catecholamines, and urine VMA. The study has quite a few limits; the major one being that not a lot of patients eventually prove to have pheo (which is also a strength because it reflects the fact that pheo is rare). With these limits, this study shows that the sensitivity and specificity of all 5 tests are about the same. The nicest thing about the study is that it gives positive predictive value (PPV) and negative predictive value (NPV) of the 5 tests in the real world.
The PPV and NPV are different from sensitivity and specificity because they depend on how the ordering physician selects patients to be tested. Let's not get entangled in technicality but the PPV of a test means that if you have a positive test for pheo, what the chance is that you actually have pheo. The NPV means that if your test result is negative, what the chance is that you actually do not have pheo. In this community-based study, the PPVs of all these tests range from 15-30%. That means if you have a pheo test at this hospital and it is positive, the chance that you indeed have pheo is about 15-30%. If the test is only moderately elevated, the PPVs are even much lower and range from 2-15%. The NPVs of all these tests are excellent: close to 100%. That means if you have a normal test result (from just any of the 5 tests) at this hospital, you are pretty sure that you do not have pheo.
Make no mistake. I do think that the plasma metanephrines is the best test for pheo. It is scientifically sound, highly reproducible, and not as interfered by medications as some other tests. I can also do clonidine suppression test based on the plasma metanephrines. I use it as the main test to diagnose pheo. It is just that the test results need to be interpreted by an expert.
Dr. Pheo
Tuesday, September 1, 2009
Dr. Pheo's musings on health care cost
I usually do not pay much attention to political arguments. In these days, however, I cannot go a single day without hearing discussions on health care or health insurance reform. A lot of discussions, I feel, are not on the really important issues. Today, I'd like to share my thoughts on one of the key issues in health insurance reform: health care cost.
The one thing everyone seems to agree upon is that the health care cost is too high for our society to afford and "we" spend way too much money on health care in America but only to achieve the same levels of health that other developed countries achieve with much less cost. But who are "we"? Am I one of the "we"? Are the readers of this blog some of the "we"? Who are responsible for the high cost in health care? How do we cut down the cost?
I, as a physician, may contribute to the high cost. For example, although I know that the MIBG scan probably does not add much to the localization of pheo if CT or MRI already finds a clear adrenal tumor in a middle-aged patient with high markers, I order the MIBG scan anyway for this patient because I worry about the small possibility that there may be a second pheo somewhere that I may miss otherwise. Although the literature and my own research show that ordering multiple tests for pheo is not necessary, I sometimes do order 2 markers because there is a small chance that there may be a lab error.
As a patient, you may also contribute to the high cost. Yearly follow-up of pheo markers is sufficient after pheo resection; some patients, though, insist on testing every 3 months because they worry about the small chance that they may have a fast-growing pheo. Some patients demand to have an MRI even after CT shows clear results because MRI does have a small advantage over CT in describing the pheo.
All medically justified costs are not waste. But who determines if a test or a treatment is justified? In reality and in theory, the physicians are the ones who eventually determine if a cost is justified. The insurance clerk who declined the coverage of your MRI just acted on the recommendations made by physicians hired by the insurance company. Although physicians have the intellectual capacity to perform this function, the society as a whole has to decide on a few key issues to make physicians exercise their best judgment on cost justification.
1. Do we trust physicians to do this job at the first place? If we don't, who else do we trust?
2. If we trust physicians, how do we make sure that physicians always exercise their best judgment without playing favoritism?
3. What is the maximal acceptable risk? If there is a 1/million chance a pheo may be missed, most reasonable people don't worry about it. What if the chance is 1/1,000, or 1/100, or 1/10?
4. How much do we want to pay for "peace of mind" and how much physical discomfort is intolerable?
5. Who is responsible for the risk? If I do not order an MIBG on a patient who I feel rather sure only has a solitary pheo but it turns out that the patient does have metastasis, whose fault is it? Am I free of blame because I exercised my best judgment?
6. What is the appropriate mechanism to reward physicians so that physicians are motivated both to avoid unnecessary tests and treatments and to use all necessary tests and treatments?
7. Do the answers to the above questions depend on whether a patient pays everything by her/himself, has private insurance, has public insurance, or has no insurance at all?
Our society has to be reasonable and responsible to achieve an efficient, equitable, and satisfying health care system.
Dr. Pheo
The one thing everyone seems to agree upon is that the health care cost is too high for our society to afford and "we" spend way too much money on health care in America but only to achieve the same levels of health that other developed countries achieve with much less cost. But who are "we"? Am I one of the "we"? Are the readers of this blog some of the "we"? Who are responsible for the high cost in health care? How do we cut down the cost?
I, as a physician, may contribute to the high cost. For example, although I know that the MIBG scan probably does not add much to the localization of pheo if CT or MRI already finds a clear adrenal tumor in a middle-aged patient with high markers, I order the MIBG scan anyway for this patient because I worry about the small possibility that there may be a second pheo somewhere that I may miss otherwise. Although the literature and my own research show that ordering multiple tests for pheo is not necessary, I sometimes do order 2 markers because there is a small chance that there may be a lab error.
As a patient, you may also contribute to the high cost. Yearly follow-up of pheo markers is sufficient after pheo resection; some patients, though, insist on testing every 3 months because they worry about the small chance that they may have a fast-growing pheo. Some patients demand to have an MRI even after CT shows clear results because MRI does have a small advantage over CT in describing the pheo.
All medically justified costs are not waste. But who determines if a test or a treatment is justified? In reality and in theory, the physicians are the ones who eventually determine if a cost is justified. The insurance clerk who declined the coverage of your MRI just acted on the recommendations made by physicians hired by the insurance company. Although physicians have the intellectual capacity to perform this function, the society as a whole has to decide on a few key issues to make physicians exercise their best judgment on cost justification.
1. Do we trust physicians to do this job at the first place? If we don't, who else do we trust?
2. If we trust physicians, how do we make sure that physicians always exercise their best judgment without playing favoritism?
3. What is the maximal acceptable risk? If there is a 1/million chance a pheo may be missed, most reasonable people don't worry about it. What if the chance is 1/1,000, or 1/100, or 1/10?
4. How much do we want to pay for "peace of mind" and how much physical discomfort is intolerable?
5. Who is responsible for the risk? If I do not order an MIBG on a patient who I feel rather sure only has a solitary pheo but it turns out that the patient does have metastasis, whose fault is it? Am I free of blame because I exercised my best judgment?
6. What is the appropriate mechanism to reward physicians so that physicians are motivated both to avoid unnecessary tests and treatments and to use all necessary tests and treatments?
7. Do the answers to the above questions depend on whether a patient pays everything by her/himself, has private insurance, has public insurance, or has no insurance at all?
Our society has to be reasonable and responsible to achieve an efficient, equitable, and satisfying health care system.
Dr. Pheo
Saturday, August 1, 2009
Chromogranin A
Chromogranin A (CGA) is one of the most important tests in the diagnosis of neuroendocrine tumors. Unfortunately, it is also one of the trickiest tests to interpret. I am asked very frequently by patients and colleagues on interpretation of CGA.
CGA is a protein. It is produced in neuroendocrine cells and released into the circulation. CGA is metabolized to fragments and cleared by the kidney. CGA is actually a hardy protein. It is very stable in serum at long incubation at 37°C, or even after repeated freezing and thawing. It reflects the cumulative secretory activity of all those cells. So CGA can be elevated by any of the many types of neuroendocrine cells. CGA indirectly reflects tissue or tumor mass. CGA is elevated in most patients with pheochromocytoma or paraganglioma.
Several issues need to be considered when interpreting the CGA results. One problem is that the reference range differs among labs. In Quest, the upper limit of normal is 36 ng/mL, while in Labcorp, it is 5 nmol/L (equivalent to 245 ng/mL). The Quest test is more useful. (Note added on July 26, 2010: One reader contests this point. Please see comment 25 and others.)
CGA can be elevated in benign and reversible conditions. In a type of gastritis (atrophic gastritis), acid production is decreased, which in turn stimulates CGA production from the stomach.
The most common cause of elevated CGA in clinical practice is anti-acid treatment, especially proton pump inhibitors for acid reflux. CGA will increase even after days of PPI in healthy volunteers. The prevalence of elevated CGA is common in patients on PPI, and more than 60% patients on PPI have elevated CGA after 4 years.
Because CGA is cleared by the kidney, CGA is elevated in kidney failure.
CGA can be elevated in several other diseases: hepatocellular carcinoma, prostate cancer, adrenal incidentaloma, pituitary tumors, and rheumatoid arthritis.
In summary, CGA is an important marker for neuroendocrine tumors. In routine clinical practice, the most common cause of high CGA is anti-acid treatment. Kidney failure and atrophic gastritis are also causes of high CGA. In a patient is not taking anti-acids or has chronic kidney failure, high CGA levels raise suspicion of neuroendocrine tumor or other tumors, including pheochromocytoma.
Obviously, CGA is not specific for pheochromocytoma and is less important than metanephrines in the diagnosis of pheochromocytoma. CGA can be used in combination with metanephrines to increase diagnostic accuracy for pheochromocytoma.
Dr. Pheo
CGA is a protein. It is produced in neuroendocrine cells and released into the circulation. CGA is metabolized to fragments and cleared by the kidney. CGA is actually a hardy protein. It is very stable in serum at long incubation at 37°C, or even after repeated freezing and thawing. It reflects the cumulative secretory activity of all those cells. So CGA can be elevated by any of the many types of neuroendocrine cells. CGA indirectly reflects tissue or tumor mass. CGA is elevated in most patients with pheochromocytoma or paraganglioma.
Several issues need to be considered when interpreting the CGA results. One problem is that the reference range differs among labs. In Quest, the upper limit of normal is 36 ng/mL, while in Labcorp, it is 5 nmol/L (equivalent to 245 ng/mL). The Quest test is more useful. (Note added on July 26, 2010: One reader contests this point. Please see comment 25 and others.)
CGA can be elevated in benign and reversible conditions. In a type of gastritis (atrophic gastritis), acid production is decreased, which in turn stimulates CGA production from the stomach.
The most common cause of elevated CGA in clinical practice is anti-acid treatment, especially proton pump inhibitors for acid reflux. CGA will increase even after days of PPI in healthy volunteers. The prevalence of elevated CGA is common in patients on PPI, and more than 60% patients on PPI have elevated CGA after 4 years.
Because CGA is cleared by the kidney, CGA is elevated in kidney failure.
CGA can be elevated in several other diseases: hepatocellular carcinoma, prostate cancer, adrenal incidentaloma, pituitary tumors, and rheumatoid arthritis.
In summary, CGA is an important marker for neuroendocrine tumors. In routine clinical practice, the most common cause of high CGA is anti-acid treatment. Kidney failure and atrophic gastritis are also causes of high CGA. In a patient is not taking anti-acids or has chronic kidney failure, high CGA levels raise suspicion of neuroendocrine tumor or other tumors, including pheochromocytoma.
Obviously, CGA is not specific for pheochromocytoma and is less important than metanephrines in the diagnosis of pheochromocytoma. CGA can be used in combination with metanephrines to increase diagnostic accuracy for pheochromocytoma.
Dr. Pheo
Wednesday, July 1, 2009
A sexual side effect of phenoxybenzamine
As the cliché goes, the best teacher of a doctor is the patient. There is nothing more true about it, especially on side effects of a drug.
Years ago, I had the opportunity of seeing a very pleasant 30-something male patient. He had been diagnosed with pheo by another doctor and saw me for a second opinion. He had been on phenoxybenzamine for the alleged specific anti-pheo effects for more than a year. His blood pressure was well controlled by phenoxybenzamine. After reviewing the numerous tests and imaging studies, I determined that he did not have pheo. I recommended using a diuretic medication for blood pressure control, instead of using the expensive phenoxybenzamine. He was so relieved once he learned that he would not absolutely need phenoxybenzamine—but not due to financial reasons. He told me that he could not have children while on the drug but his wife and he so much wanted to start a family. An inquisitive soul, I asked him to elaborate. The patient shyly told me that he had not had ejaculates after he was on phenoxybenzamine.
That was the first time I learned this very common side effect of phenoxybenzamine in men. We all know the standard common side effects such as nasal stuffiness, orthostatic hypotension, and fatigue. Ejaculatory failure happens in almost every man taking phenoxybenzamine. Most men do not complain of this side effect, probably because the treatment is usually short-term and patients have anxiety before operation so that they do not attempt sexual activity. Men may also be embarrassed to talk about this what is perceived by some as a sensitive but trivial symptom.
The mechanism of ejaculatory failure is not retrograde ejaculation, rather, patients simply do not transfer seminal fluid (the bulk of ejaculates) to be ejaculated. The good news is that this sexual side effect is completely reversible in 1-2 days after discontinuing phenoxybenzamine. And phenoxybenzamine does NOT affect libido, potency, or orgasm.
Prazosin and doxazosin usually do not cause ejaculatory problems but sometimes they do.
After I learned this side effect from that patient, I always inform my male patients of this unique side effect of phenoxybenzamine. Most of them appreciate my warning. Some would say “Doc, sex is the last thing I am thinking of now.” Hey, you never know. Sexual activity is generally not contraindicated in patients with pheo, provided that it is not particularly violent.
Dr. Pheo
Years ago, I had the opportunity of seeing a very pleasant 30-something male patient. He had been diagnosed with pheo by another doctor and saw me for a second opinion. He had been on phenoxybenzamine for the alleged specific anti-pheo effects for more than a year. His blood pressure was well controlled by phenoxybenzamine. After reviewing the numerous tests and imaging studies, I determined that he did not have pheo. I recommended using a diuretic medication for blood pressure control, instead of using the expensive phenoxybenzamine. He was so relieved once he learned that he would not absolutely need phenoxybenzamine—but not due to financial reasons. He told me that he could not have children while on the drug but his wife and he so much wanted to start a family. An inquisitive soul, I asked him to elaborate. The patient shyly told me that he had not had ejaculates after he was on phenoxybenzamine.
That was the first time I learned this very common side effect of phenoxybenzamine in men. We all know the standard common side effects such as nasal stuffiness, orthostatic hypotension, and fatigue. Ejaculatory failure happens in almost every man taking phenoxybenzamine. Most men do not complain of this side effect, probably because the treatment is usually short-term and patients have anxiety before operation so that they do not attempt sexual activity. Men may also be embarrassed to talk about this what is perceived by some as a sensitive but trivial symptom.
The mechanism of ejaculatory failure is not retrograde ejaculation, rather, patients simply do not transfer seminal fluid (the bulk of ejaculates) to be ejaculated. The good news is that this sexual side effect is completely reversible in 1-2 days after discontinuing phenoxybenzamine. And phenoxybenzamine does NOT affect libido, potency, or orgasm.
Prazosin and doxazosin usually do not cause ejaculatory problems but sometimes they do.
After I learned this side effect from that patient, I always inform my male patients of this unique side effect of phenoxybenzamine. Most of them appreciate my warning. Some would say “Doc, sex is the last thing I am thinking of now.” Hey, you never know. Sexual activity is generally not contraindicated in patients with pheo, provided that it is not particularly violent.
Dr. Pheo
Tuesday, June 16, 2009
Pheo growth speed
One important feature of pheos is that they always grow. The growth speed of pheo, however, is only known for patients with von Hippel Lindau disease. For people with true sporadic pheo (~70% of all pheos), we have little knowledge on the growth speed of their pheos. The reason is that familial pheos can be monitored but sporadic pheos are usually resected once they are diagnosed. Only under two conditions, patient's choice of delaying surgery and omission of pheo testing of incidentally-identified adrenal mass, the growth speed of sporadic pheos can be assessed.
I recently took care of a patient with likely sporadic pheo. This patient's adrenal pheo increased from 0.6 x 1.2 cm to 3.0 x 3.6 cm in 6 years. This patient is among the few I know with recorded growth speed of a sporadic pheo.
The information on pheo growth speed is much needed to tell patients what they will expect of their tumor. I would like to do a survey of the growth speed of pheo, whether with genetic mutations or not. If you have a pheo that was imaged multiple times, please let me know the size of the tumor, the time interval in-between imaging, and whether you have a pheo syndrome (with mutations) or not. I thank you in advance.
Dr. Pheo
I recently took care of a patient with likely sporadic pheo. This patient's adrenal pheo increased from 0.6 x 1.2 cm to 3.0 x 3.6 cm in 6 years. This patient is among the few I know with recorded growth speed of a sporadic pheo.
The information on pheo growth speed is much needed to tell patients what they will expect of their tumor. I would like to do a survey of the growth speed of pheo, whether with genetic mutations or not. If you have a pheo that was imaged multiple times, please let me know the size of the tumor, the time interval in-between imaging, and whether you have a pheo syndrome (with mutations) or not. I thank you in advance.
Dr. Pheo
Tuesday, May 26, 2009
A familial pheo risk calculator
Two papers on risks of familial pheo appear in the May, 2009 issue of the Journal of Clinical Endocrinology and Metabolism. One Paper describes experience in about 500 Italian patients, the other over 200 Spanish patients. The paper on Italian patients is particularly informative. With the three large studies now available (the original landmark study in 2002 published in the New England Journal of Medicine and these two new papers), I feel it is time to quantify the probability of having familial pheo. I have prepared a calculator of risks for familial pheo. The calculator is based on the 3 above large studies. The calculator has only five input variables:
1) Primary location of your pheo/paraganglioma
2) Age at diagnosis
3) Family history of pheo or paraganglioma (Yes/No)
4) Single or multiple pheo/paraganglioma (Single/Multiple)
5) Do you have any of the following diseases in addition to pheo/paraganglioma (Yes/No): medullary thyroid cancer, hyperparathyrodism, hirschsprung's disease, mucosa neuroma, hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumor, and skin neurofibroma?
As this is a blog format, I can not post the calculator on line. If you tell me the answer to the 5 variables, I will tell you your risk of having a familial pheo. The calculator has its intrinsic limitations and perhaps even errors; and the results are only as good as the accuracy of the 5 variables. Also I can not tell you the chances of any particular mutated genes.
Of course, the calculator only gives you an estimate of risk and only your doctor and you shall decide whether to do genetic testing. You should use the results of the calculator responsibly and at your own risk; I can not be held liable for any adverse consequences.
Dr. Pheo
1) Primary location of your pheo/paraganglioma
2) Age at diagnosis
3) Family history of pheo or paraganglioma (Yes/No)
4) Single or multiple pheo/paraganglioma (Single/Multiple)
5) Do you have any of the following diseases in addition to pheo/paraganglioma (Yes/No): medullary thyroid cancer, hyperparathyrodism, hirschsprung's disease, mucosa neuroma, hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumor, and skin neurofibroma?
As this is a blog format, I can not post the calculator on line. If you tell me the answer to the 5 variables, I will tell you your risk of having a familial pheo. The calculator has its intrinsic limitations and perhaps even errors; and the results are only as good as the accuracy of the 5 variables. Also I can not tell you the chances of any particular mutated genes.
Of course, the calculator only gives you an estimate of risk and only your doctor and you shall decide whether to do genetic testing. You should use the results of the calculator responsibly and at your own risk; I can not be held liable for any adverse consequences.
Dr. Pheo
Monday, May 11, 2009
Silent? No way!
You may have heard the term “silent pheo”. The sole purpose of this post is to convince you that “silent pheo” is a dangerous term and should be avoided at all cost. So next time you hear someone mentioning “silent pheo”, you tell the person there is no such a thing. Every time I hear the term, I get goose bumps and try to correct the person.
The term “silent pheo” or “subclinical pheo” apparently refers to a pheo in a patient who does not have hypertension or paroxysmal attacks. There are quite a few situations where a patient indeed has a pheo or paraganglimoa but does not have classical symptoms of pheo. Most paragangliomas in the neck and chest do not produce significant amounts of catecholamines. I would rather call these tumors "nonfunctional" rather than "silent". Very small pheos produce only small amounts of catecholamines so that they do not cause clinical symptoms. In the above two situations, blood tests for pheo show normal results. Most pheos in adrenal glands, retroperitoneal space, and bladder do produce catecholamines and are therefore "functional". The majority of patients with pheo have at least subtle symptoms that can be elicited by experienced physicians or realized in retrospect after removal of the tumor.
Some patients indeed have no apparent hypertension in spite of very functional pheos. These patients tend to be mismanaged and are at the highest risk of complications around surgery. Here are the reasons. These patients tend to be young and healthy before they have pheo. Their bodies try very hard to accommodate the bombardment of catecholamines by shrinking their blood volume. My experience is that their blood pressure may be normal while sitting or standing but rises when they lie down. An inexperienced doctor may think they have so-called "desensitization" of catecholamine receptors and can go ahead with surgery without preparation. Disaster happens if they do. They will have very high blood pressure while the tumor is manipulated and profound hypotension after the tumor is resected. Then they will get a lot of intravenous fluid their hearts can not handle. It will be a mess!
The bottomline is that if a patient has normal blood test results, whatever tumor the patient has may not be sufficiently functional. If the patient has elevated blood markers for pheo, the patient should be treated as having a functional pheo and undergo careful preoperative preparation, regardless of having hypertension or not. A young, otherwise healthy patient with a large pheo and high levels of markers but without hypertension is the most vulnerable one. That patient particularly deserves careful preoperative preparation.
Dr. Pheo
The term “silent pheo” or “subclinical pheo” apparently refers to a pheo in a patient who does not have hypertension or paroxysmal attacks. There are quite a few situations where a patient indeed has a pheo or paraganglimoa but does not have classical symptoms of pheo. Most paragangliomas in the neck and chest do not produce significant amounts of catecholamines. I would rather call these tumors "nonfunctional" rather than "silent". Very small pheos produce only small amounts of catecholamines so that they do not cause clinical symptoms. In the above two situations, blood tests for pheo show normal results. Most pheos in adrenal glands, retroperitoneal space, and bladder do produce catecholamines and are therefore "functional". The majority of patients with pheo have at least subtle symptoms that can be elicited by experienced physicians or realized in retrospect after removal of the tumor.
Some patients indeed have no apparent hypertension in spite of very functional pheos. These patients tend to be mismanaged and are at the highest risk of complications around surgery. Here are the reasons. These patients tend to be young and healthy before they have pheo. Their bodies try very hard to accommodate the bombardment of catecholamines by shrinking their blood volume. My experience is that their blood pressure may be normal while sitting or standing but rises when they lie down. An inexperienced doctor may think they have so-called "desensitization" of catecholamine receptors and can go ahead with surgery without preparation. Disaster happens if they do. They will have very high blood pressure while the tumor is manipulated and profound hypotension after the tumor is resected. Then they will get a lot of intravenous fluid their hearts can not handle. It will be a mess!
The bottomline is that if a patient has normal blood test results, whatever tumor the patient has may not be sufficiently functional. If the patient has elevated blood markers for pheo, the patient should be treated as having a functional pheo and undergo careful preoperative preparation, regardless of having hypertension or not. A young, otherwise healthy patient with a large pheo and high levels of markers but without hypertension is the most vulnerable one. That patient particularly deserves careful preoperative preparation.
Dr. Pheo
Tuesday, April 28, 2009
Dr. Pheo's Pheo Dr.
I have two criteria for entering doctors into this list: 1) great clinicians, and 2) clinical researchers with >=3 papers on pheo. Both criteria have to be met to be on this list. You will see that the list is pretty short. Pheo is a rare disease, and a doctor usually has to practice at a metropolitan area to see enough patients to become an expert. I need the readers to send me more names and I will check them and select those who meet my criteria. These doctors are mostly endocrinologists and I know personally quite a few of them. They are real experts on pheo.
The list is by no means comprehensive and will be updated frequently based on reader feedback. For example, at least one or two doctors in the list are semi-retired and I don’t know how long they will practice. In addition, if I have missed a great clinician who also does clinical research on pheo, please let me know.
California
Paul Fitzgerald, University of California San Francisco
Run Yu, University of California Los Angeles
Iowa
Thomas O'Dorisio, University of Iowa
Massachusetts
Robert Dluhy, Brighams & Womans Hospital
Michigan
Richard Auchus, University of Michigan
Minnesota
William Young, Mayo Clinic
Missouri
Ruth Decker, St. Lukes Hospital
Ohio
Charis Eng, Cleveland Clinic
Pennsylvania
Raymond Townsend, University of Pennsylvania
Texas
Camilo Jimenez, MD Anderson Cancer Center
DC
Karel Pacak, National Institute of Health
Constantine Stratakis, National Institute of Health
Canada
Shereen Ezzat, University of Toronto
UK
Ashley B. Grossman, St. Bartholomew’s Hospital
France
Pierre-Francois Plouin, Hopital Europeen Georges Pompidou
Germany
Hartmut Neumann, University of Freiburg
Graeme Eisenhofer, University of Dresden
Netherlands
Jacques Lenders, St Radboud University
Sweden
Barbro Eriksson, Uppsala University
China
Zhengpei Zeng, Peking Union Medical College
Japan
Yukio Hirata, Tokyo Medical and Dental University
Mitsuhide Naruse, Kyoto Medical Center
Australia
Bruce Robinson, Sir Charles Gairdner Hospital
Roderick Clifton-Bligh, Royal North Shore Hospital
The list is by no means comprehensive and will be updated frequently based on reader feedback. For example, at least one or two doctors in the list are semi-retired and I don’t know how long they will practice. In addition, if I have missed a great clinician who also does clinical research on pheo, please let me know.
California
Paul Fitzgerald, University of California San Francisco
Run Yu, University of California Los Angeles
Iowa
Thomas O'Dorisio, University of Iowa
Massachusetts
Robert Dluhy, Brighams & Womans Hospital
Michigan
Richard Auchus, University of Michigan
Minnesota
William Young, Mayo Clinic
Missouri
Ruth Decker, St. Lukes Hospital
Ohio
Charis Eng, Cleveland Clinic
Pennsylvania
Raymond Townsend, University of Pennsylvania
Texas
Camilo Jimenez, MD Anderson Cancer Center
DC
Karel Pacak, National Institute of Health
Constantine Stratakis, National Institute of Health
Canada
Shereen Ezzat, University of Toronto
UK
Ashley B. Grossman, St. Bartholomew’s Hospital
France
Pierre-Francois Plouin, Hopital Europeen Georges Pompidou
Germany
Hartmut Neumann, University of Freiburg
Graeme Eisenhofer, University of Dresden
Netherlands
Jacques Lenders, St Radboud University
Sweden
Barbro Eriksson, Uppsala University
China
Zhengpei Zeng, Peking Union Medical College
Japan
Yukio Hirata, Tokyo Medical and Dental University
Mitsuhide Naruse, Kyoto Medical Center
Australia
Bruce Robinson, Sir Charles Gairdner Hospital
Roderick Clifton-Bligh, Royal North Shore Hospital
Sunday, April 19, 2009
Name a good pheo doctor
I am compiling a list of doctors and medical centers that are experienced in pheo. I hope readers will share their PERSONAL experience with their own doctors and medical centers that they feel do a great job with pheo. Please indicate only the doctor's name and state, and the medical center's name. No other information please. I don't want any physician ad here at all.
I would ask you to only list a doctor who actually diagnosed or treated you. Name the doctor or center as comments to this post. Please only list if you are a pheo patient yourself. I hope we can come up with an accurate list of good pheo doctors voted by patients.
I may or may not list the doctors or centers in my own list, depending on the investigative work I will do to check. I have my own angle: from a fellow physician.
Dr. Pheo
I would ask you to only list a doctor who actually diagnosed or treated you. Name the doctor or center as comments to this post. Please only list if you are a pheo patient yourself. I hope we can come up with an accurate list of good pheo doctors voted by patients.
I may or may not list the doctors or centers in my own list, depending on the investigative work I will do to check. I have my own angle: from a fellow physician.
Dr. Pheo
Friday, April 17, 2009
Pheo imaging: now you see it, now you don't
Today I will go over some intricacies of pheo imaging. The post is suggested by readers and I will answer some particular questions they have.
For most patients with real pheo, finding the tumor is rather straightforward. Most pheos are about 4-6 cm in diameter and have unique features. CT or MRI describes pheo well. An MIBG scan is then done to see whether there are other pheos lurking in the dark somewhere in the body. Unfortunately for some patients with real pheo and for a lot of patients who do not really have a pheo, imaging can be confusing.
First, for Peep, let's discuss how radiologists make a diagnosis. I work closely with quite a few great radiologists and begin to know their mindset. Radiologists are great at seeing things most other doctors don't see. But they will never be completely sure what the things are because many things can appear the same way. They need clinical information to make a judgment. So Peep, when your urine test results were very high, they will search your body from neck to pelvis trying to find something that might be pheo. A lymph node, or an uncommon normal variation of the shape of a normal organ, can be interpreted as potential pheo. Now the urine results are normal, radiologists will think you probably don't have pheo and take the same findings as what they normally are: lymph node or normal variations. So the same radiological finding in two patients can be read by radiologists as two different diseases. Think this way, the same red liquid in a fancy glass in an expensive restaurant probably is some great wine, while it must be melt lollipop if you see it on the pavement with a stick in the middle. Therefore, Peep, you may have some structures that are not exactly common but can be normal. What they are depends on the risk of your really having a pheo.
Second, for Dennis, let's discuss about MIBG scan. This is the single most misinterpreted imaging for pheo. MIBG scan itself is a great test. It is just some doctors do not know what to make of it. Technically, as Dennis points out, there is an I-131 MIBG, and there is an I-123 MIBG. In a nutshell, don't use the I-131 MIBG for diagnosis (it is used for treatment of pheo). Only use the I-123 MIBG which has a much better signal/background ratio. I-123 just gives much sharper pictures. Second, MIBG scan does not diagnose anyone with pheo, it just shows where the pheo is. As I discussed in a comment before, normal folks often have one adrenal taking more MIBG than the other but they don't have pheo. Nuclear medicine doctors, like radiologists (and any other doctors), will try to find a pheo if they are told there is really a pheo in a patient. If you use photoshop, Dennis, you will know that you can find something you like by adjusting the threshold, the contrast, or the color. If they know the patient has low risk, they will think a little spot might be just a fluke.
The key thing is communication between the endocrinologist and the radiologist. I used to routinely discuss with radiologists on every single case. Now that I know a little about pheo imaging, I still read every patient's images and I will call the radiologists when I feel something is not right. A pheo specialist should be a mini-radiologist on the adrenal gland, at least. My radiologist friends will call me as well if they feel something is not right.
Back to Dennis' point, the most likely place where endocrinologists and radiologists communicate to each other is an academic center with experience on pheo.
Dr. Pheo
For most patients with real pheo, finding the tumor is rather straightforward. Most pheos are about 4-6 cm in diameter and have unique features. CT or MRI describes pheo well. An MIBG scan is then done to see whether there are other pheos lurking in the dark somewhere in the body. Unfortunately for some patients with real pheo and for a lot of patients who do not really have a pheo, imaging can be confusing.
First, for Peep, let's discuss how radiologists make a diagnosis. I work closely with quite a few great radiologists and begin to know their mindset. Radiologists are great at seeing things most other doctors don't see. But they will never be completely sure what the things are because many things can appear the same way. They need clinical information to make a judgment. So Peep, when your urine test results were very high, they will search your body from neck to pelvis trying to find something that might be pheo. A lymph node, or an uncommon normal variation of the shape of a normal organ, can be interpreted as potential pheo. Now the urine results are normal, radiologists will think you probably don't have pheo and take the same findings as what they normally are: lymph node or normal variations. So the same radiological finding in two patients can be read by radiologists as two different diseases. Think this way, the same red liquid in a fancy glass in an expensive restaurant probably is some great wine, while it must be melt lollipop if you see it on the pavement with a stick in the middle. Therefore, Peep, you may have some structures that are not exactly common but can be normal. What they are depends on the risk of your really having a pheo.
Second, for Dennis, let's discuss about MIBG scan. This is the single most misinterpreted imaging for pheo. MIBG scan itself is a great test. It is just some doctors do not know what to make of it. Technically, as Dennis points out, there is an I-131 MIBG, and there is an I-123 MIBG. In a nutshell, don't use the I-131 MIBG for diagnosis (it is used for treatment of pheo). Only use the I-123 MIBG which has a much better signal/background ratio. I-123 just gives much sharper pictures. Second, MIBG scan does not diagnose anyone with pheo, it just shows where the pheo is. As I discussed in a comment before, normal folks often have one adrenal taking more MIBG than the other but they don't have pheo. Nuclear medicine doctors, like radiologists (and any other doctors), will try to find a pheo if they are told there is really a pheo in a patient. If you use photoshop, Dennis, you will know that you can find something you like by adjusting the threshold, the contrast, or the color. If they know the patient has low risk, they will think a little spot might be just a fluke.
The key thing is communication between the endocrinologist and the radiologist. I used to routinely discuss with radiologists on every single case. Now that I know a little about pheo imaging, I still read every patient's images and I will call the radiologists when I feel something is not right. A pheo specialist should be a mini-radiologist on the adrenal gland, at least. My radiologist friends will call me as well if they feel something is not right.
Back to Dennis' point, the most likely place where endocrinologists and radiologists communicate to each other is an academic center with experience on pheo.
Dr. Pheo
Saturday, April 11, 2009
Pheo and heart
Endocrine diseases seem to always affect the heart in some ways. Thyroid diseases certainly cause abnormal heart functions and diabetes causes atherosclerosis. The other day, I joked with a cardiologist that they should "steal one more disease from endocrinologists." This disease is pheochromocytoma.
The heart of a pheo patient is bombarded with catecholamines. Although most patients with pheo do not have obvious heart symptoms except for palpitation, ECG reveals subtle abnormalities in about half of the patients with pheo. In patients with large pheos, all kinds of severe heart problems can show up. I have seen myocardial infarction, congestive heart failure, and life-threatening arrhythmia in patients with pheo.
As patients with heart problems usually go to see cardiologists, and because pheo is so rare and not on the radar screen of cardiologists in the initial work-ups, delay in diagnosis is rather common. I am not here to say that all patients with common heart diseases should test for pheo. That would be impractical and common things are common. But if a relatively young patient without clear risk factors develops heart disease, pheo should be considered.
Surprisingly, little is known on why catecholamines cause heart damage. Another disease called Takotsubo cardiomyopathy has a lot in common with pheo. Takotsubo cardiomyopathy is a heart muscle diseases in patients with sudden and severe emotional or physical stress. If any colleagues have insights in heart diseases in pheo, please comment here.
The morals are: 1) if you have pheo but don't have heart symptoms, you should at least do an ECG to make sure you don't have a significant heart problem; 2) if you have heart problems and nobody knows why, consider pheo, at least as a long shot.
Dr. Pheo
The heart of a pheo patient is bombarded with catecholamines. Although most patients with pheo do not have obvious heart symptoms except for palpitation, ECG reveals subtle abnormalities in about half of the patients with pheo. In patients with large pheos, all kinds of severe heart problems can show up. I have seen myocardial infarction, congestive heart failure, and life-threatening arrhythmia in patients with pheo.
As patients with heart problems usually go to see cardiologists, and because pheo is so rare and not on the radar screen of cardiologists in the initial work-ups, delay in diagnosis is rather common. I am not here to say that all patients with common heart diseases should test for pheo. That would be impractical and common things are common. But if a relatively young patient without clear risk factors develops heart disease, pheo should be considered.
Surprisingly, little is known on why catecholamines cause heart damage. Another disease called Takotsubo cardiomyopathy has a lot in common with pheo. Takotsubo cardiomyopathy is a heart muscle diseases in patients with sudden and severe emotional or physical stress. If any colleagues have insights in heart diseases in pheo, please comment here.
The morals are: 1) if you have pheo but don't have heart symptoms, you should at least do an ECG to make sure you don't have a significant heart problem; 2) if you have heart problems and nobody knows why, consider pheo, at least as a long shot.
Dr. Pheo
Monday, April 6, 2009
Follow-up after pheochromocytoma resection
OK. Now you are diagnosed with pheochromocytoma, carefully prepared before resection, and operated by a great surgeon. Are you out of the loop yet? What shall you do next?
For patients with truly sporadic pheochromocytoma, 90% is the chance that they are cured. The remaining 10% may have recurrence or metastasis in the future. The problem is that the doctors can NOT predict who will be the lucky 90% and who will be the unlucky 10%. Therefore no patients should think that they are absolutely cured and all patients should have follow-up.
My own approach to patients with apparently sporadic pheochromocytoma is to measure plasma metanephrines 1 month after surgical resection to make sure there is no hidden tumor somewhere. Too early measurements can be false positive because I suspect based on my experience that there is some kind of depot of metanephrines in the body that is only depleted in a month. If the metanephrines are normal, I then measure them yearly or whenever they have symptoms suggestive of pheochromocytoma or when an adrenal or other mass is identified incidentally.
If a patient has familial form of pheochromocytoma or a gene mutation is identified, then the patient will have a much higher chance of recurrence or metastasis. Yearly plasma metanephrines are definitely needed. Imaging studies may be indicated depending on which form of familial pheochromocytoma or which gene mutations. Other components of the syndromes need to be screened; patients' family members need to be tested and carriers need to be regularly screened.
Now I have finished the basic topics on pheochromocytoma. I will write more on my personal experience and more interesting topics. If the contents of my blog are mostly based on my own experience and there is not much existing study on the topic, I will clearly state that at the beginning of the post. I welcome colleagues and patients to critique and to suggest. I will also just use "pheo", instead of the full name.
For patients with truly sporadic pheochromocytoma, 90% is the chance that they are cured. The remaining 10% may have recurrence or metastasis in the future. The problem is that the doctors can NOT predict who will be the lucky 90% and who will be the unlucky 10%. Therefore no patients should think that they are absolutely cured and all patients should have follow-up.
My own approach to patients with apparently sporadic pheochromocytoma is to measure plasma metanephrines 1 month after surgical resection to make sure there is no hidden tumor somewhere. Too early measurements can be false positive because I suspect based on my experience that there is some kind of depot of metanephrines in the body that is only depleted in a month. If the metanephrines are normal, I then measure them yearly or whenever they have symptoms suggestive of pheochromocytoma or when an adrenal or other mass is identified incidentally.
If a patient has familial form of pheochromocytoma or a gene mutation is identified, then the patient will have a much higher chance of recurrence or metastasis. Yearly plasma metanephrines are definitely needed. Imaging studies may be indicated depending on which form of familial pheochromocytoma or which gene mutations. Other components of the syndromes need to be screened; patients' family members need to be tested and carriers need to be regularly screened.
Now I have finished the basic topics on pheochromocytoma. I will write more on my personal experience and more interesting topics. If the contents of my blog are mostly based on my own experience and there is not much existing study on the topic, I will clearly state that at the beginning of the post. I welcome colleagues and patients to critique and to suggest. I will also just use "pheo", instead of the full name.
Sunday, April 5, 2009
What to do if pheochromocytoma is diagnosed
This topic is suggested by Dennis.
First of all, making the diagnosis of pheochromocytoma is not a trivial decision. It means more imaging studies and the eventual surgical operation. The patient has to ask two questions: 1) whether the diagnosis is correct, and 2) if the diagnosis is correct, how to proceed with further workups and management.
The experience of the doctor who makes the diagnosis is probably the most critical indicator of whether the diagnosis is correct. The average physicians see few patients with pheochromocytoma in their entire professional life, and they make the diagnosis themselves for even fewer patients. A reasonable question the patient needs to ask the physician is "how many patients with pheochromocytoma have you taken care of?" Most doctors won't be offended by this question. If the doctor has seen fewer than 3 patients, the doctor's experience on pheochromocytoma is too little to make an accurate diagnosis.
The other factor is the doctor's practice environment. Doctors affiliated with an academic center with a large experience on pheochromocytoma have more resources on pheochromocytoma. They know physicians with more experience, they know which radiologists to refer the patients to, and they know which surgeons have the best reputation on pheochromocytoma resecton.
The best doctors on pheochromocytoma are those working in an academic center and doing clinical research on pheochromocytoma. These doctors deal with this disease as part of their career and they have accumulated a large experience on this tumor. They also usually have a program on systemically follow patients after surgical resection.
If the diagnosis is made by an experienced physician, the diagnosis is probably correct. If the diagnosis is made by an inexperienced physician, it may not be necessarily correct, and to have a second opinion from an experienced physician is very prudent. If the patient has the means, it is always a good idea to have a second opinion from another experienced physician even if the diagnosis was already made by an experienced physician, especially when the first physician was not very sure.
To select a surgeon follows the same logic. The best surgeons are those working in an academic center with a large experience on pheochromocytoma and they have operated on more than a few patients with pheochromocytoma. They have seen the tricky perioperative course and work closely with endocrinologists.
As Dennis puts it, a patient should not settle for mere convenience after diagnosed with pheochromocytoma for the first time. Seeking opinions from experienced physicians is very important.
First of all, making the diagnosis of pheochromocytoma is not a trivial decision. It means more imaging studies and the eventual surgical operation. The patient has to ask two questions: 1) whether the diagnosis is correct, and 2) if the diagnosis is correct, how to proceed with further workups and management.
The experience of the doctor who makes the diagnosis is probably the most critical indicator of whether the diagnosis is correct. The average physicians see few patients with pheochromocytoma in their entire professional life, and they make the diagnosis themselves for even fewer patients. A reasonable question the patient needs to ask the physician is "how many patients with pheochromocytoma have you taken care of?" Most doctors won't be offended by this question. If the doctor has seen fewer than 3 patients, the doctor's experience on pheochromocytoma is too little to make an accurate diagnosis.
The other factor is the doctor's practice environment. Doctors affiliated with an academic center with a large experience on pheochromocytoma have more resources on pheochromocytoma. They know physicians with more experience, they know which radiologists to refer the patients to, and they know which surgeons have the best reputation on pheochromocytoma resecton.
The best doctors on pheochromocytoma are those working in an academic center and doing clinical research on pheochromocytoma. These doctors deal with this disease as part of their career and they have accumulated a large experience on this tumor. They also usually have a program on systemically follow patients after surgical resection.
If the diagnosis is made by an experienced physician, the diagnosis is probably correct. If the diagnosis is made by an inexperienced physician, it may not be necessarily correct, and to have a second opinion from an experienced physician is very prudent. If the patient has the means, it is always a good idea to have a second opinion from another experienced physician even if the diagnosis was already made by an experienced physician, especially when the first physician was not very sure.
To select a surgeon follows the same logic. The best surgeons are those working in an academic center with a large experience on pheochromocytoma and they have operated on more than a few patients with pheochromocytoma. They have seen the tricky perioperative course and work closely with endocrinologists.
As Dennis puts it, a patient should not settle for mere convenience after diagnosed with pheochromocytoma for the first time. Seeking opinions from experienced physicians is very important.
Friday, April 3, 2009
Screening for mutations: in whom, and how?
Thank you again, Foxy, for asking an intriguing question on screening for gene mutations that cause pheochromocytoma. As this is a question of general interest, I put it as a new topic.
The chemicals a tumor produces do not tell much about whether the tumor is likely caused by a known mutation. Pheochromocytomas in MENII usually produce epinephrine, while those in VHL usually make norepinephrine. And in general, most pheochromocytomas tend to make norepinephrine, with or without mutations. Extra-adrenal pheochromocytomas (called paragangliomas) in familial paraganglioma (SDH mutations) and in Carney's triad (unknown gene mutations) may not produce catecholamines. Although these patterns of catecholamine secretion exist, they do not help in determining whether a patient should be screened.
Neither does tumor size or patient sex.
Some other clinical parameters do help. 1) Positive family history certainly suggests familial pheochromocytoma. 2) Age. The younger (<50), the more likely a patient has mutations causing pheochromocytoma. 3) Multifocal pheochromocytomas suggest mutations. 4) Signs of genetic syndromes. For example, a patient may already have meduallary thyroid carcinoma. If a patient has any of these, then genetic testing has higher yield.
Should any patient with pheochromocytoma be screened? At last year's International Symposium on Pheochromocytoma (ISP 2008, Cambridge, UK) which I attended, this topic was lively debated and the arguments were divided at the Atlantic Ocean. The European doctors seem to root for testing everyone as the tests are covered by either insurance or research centers. American doctors are more hesitant. No insurance companies in America I know cover genetic testing of pheochromocytoma in a patient without family history. A few American centers do offer testing in a research setting but the patients have to enter a trial of some sort. It can cost a patient thousands of dollars to do all the commercially available tests.
The other issue is which gene(s) to test first. Six (6) genes are known to cause pheochromocytoma: RET, VHL, NF1, SDHB, SDHD, and SDHC. Clinical history provides some help. Bilateral pheos: RET and VHL first. Extra-adrenal pheos: SDHB, SDHD, and VHL first. The hit rate is not very high even with these clinical history-based strategy. Above all, only 30% of patients without family history really have a mutation known to cause pheochromocytoma.
In my own practice, I highly encourage patients with family history to test for mutations. In those without family history, I explain the above and let them decide. Most patients without family history elect not to do genetic testing. They are followed clinically and by tests and imaging. It is unfortunate that genetic testing even in patients with family history are still not covered by insurance in many instances.
The chemicals a tumor produces do not tell much about whether the tumor is likely caused by a known mutation. Pheochromocytomas in MENII usually produce epinephrine, while those in VHL usually make norepinephrine. And in general, most pheochromocytomas tend to make norepinephrine, with or without mutations. Extra-adrenal pheochromocytomas (called paragangliomas) in familial paraganglioma (SDH mutations) and in Carney's triad (unknown gene mutations) may not produce catecholamines. Although these patterns of catecholamine secretion exist, they do not help in determining whether a patient should be screened.
Neither does tumor size or patient sex.
Some other clinical parameters do help. 1) Positive family history certainly suggests familial pheochromocytoma. 2) Age. The younger (<50), the more likely a patient has mutations causing pheochromocytoma. 3) Multifocal pheochromocytomas suggest mutations. 4) Signs of genetic syndromes. For example, a patient may already have meduallary thyroid carcinoma. If a patient has any of these, then genetic testing has higher yield.
Should any patient with pheochromocytoma be screened? At last year's International Symposium on Pheochromocytoma (ISP 2008, Cambridge, UK) which I attended, this topic was lively debated and the arguments were divided at the Atlantic Ocean. The European doctors seem to root for testing everyone as the tests are covered by either insurance or research centers. American doctors are more hesitant. No insurance companies in America I know cover genetic testing of pheochromocytoma in a patient without family history. A few American centers do offer testing in a research setting but the patients have to enter a trial of some sort. It can cost a patient thousands of dollars to do all the commercially available tests.
The other issue is which gene(s) to test first. Six (6) genes are known to cause pheochromocytoma: RET, VHL, NF1, SDHB, SDHD, and SDHC. Clinical history provides some help. Bilateral pheos: RET and VHL first. Extra-adrenal pheos: SDHB, SDHD, and VHL first. The hit rate is not very high even with these clinical history-based strategy. Above all, only 30% of patients without family history really have a mutation known to cause pheochromocytoma.
In my own practice, I highly encourage patients with family history to test for mutations. In those without family history, I explain the above and let them decide. Most patients without family history elect not to do genetic testing. They are followed clinically and by tests and imaging. It is unfortunate that genetic testing even in patients with family history are still not covered by insurance in many instances.
Thursday, April 2, 2009
Suggestions on posting questions
As readers begin to post comments or questions, I note that it may be hard for me to find questions posted under earlier topics. I would like to ask readers to post specific questions on pheochromocytoma under the most recent topic, whatever it is. For example, if you want to ask about interpretation of a specific chromogranin A test, please post the question under this topic simply because it is the most recent one and the question is easier for me to find.
Please still post comments or editorial questions under the specific topic you like to comment on.
I am not really savvy on the technical aspects of blogging. If there are better ways, please let me know.
Thanks.
Dr. Pheo
Please still post comments or editorial questions under the specific topic you like to comment on.
I am not really savvy on the technical aspects of blogging. If there are better ways, please let me know.
Thanks.
Dr. Pheo
Doctor-patient interaction: in response to Foxy's question
Thank you, Foxy, for your comments and question. You have just touched upon an important but overlooked issue in physician-patient relationship. You astutely observe that some doctors can be nervous and defensive when they are seeing patients with rare diseases (including PHEOCHROMOCYTOMA) that they know little about. There is no simple solution to the problem but I can provide some background here so that we can think of creative ways to solve the problem.
Physicians are used to be viewed as knowledgeable experts. They are supposed to help patients, to guide, and to cure. Many physicians also have a large ego as well and enjoy the role of a healer and its associated prestige. When they see a patient who suffers from a disease they know almost nothing, all the pretext of their psyche suddenly does not exist any more. A good number of physicians take this as an opportunity to learn with the patient and acknowledge their ignorance and willingness to learn, while some others will act out and use defensiveness to hide their embarrassment.
Although I don't think patients are to blamed for the problem, patients are indeed also part of the issue. Patients sometimes unknowingly encourage bad physician behaviors. For example, some patients may take arrogance as confidence of a physician. Some patients like black-and-white decisions and take discussion of nuances as indecisiveness of a physician.
At the end of the day, I guess the physician-patient relationship is like any other relationships--you relate with the one you like, and you separate from the one you dislike, and face the consequences.
Finding a good physician should aim at different goals at different disease stages. For definitive diagnosis, you need an expert on pheochromocytoma even though the expert may not be a perfect lady/gentleman. For surgical resection, you need an expert surgeon who has many cases before yours. For follow up, the character of the doctor is more important than knowledge and above all, you may not have a local expert in the first place.
As many of my own patients are from out-of-town, they often ask me how to pick a local doctor to coordinate the care for pheochromocytoma. The advice I give to my own patients is the follows: 1) you trust and like the doctor, 2) the doctor has an open mind on diseases she/he is not familiar with. The specialty of the doctor is not so important.
Let's not even start mentioning the hurdles on choosing physicians placed by HMO, the insurances, and other societal beings.
Dr. Pheo
Physicians are used to be viewed as knowledgeable experts. They are supposed to help patients, to guide, and to cure. Many physicians also have a large ego as well and enjoy the role of a healer and its associated prestige. When they see a patient who suffers from a disease they know almost nothing, all the pretext of their psyche suddenly does not exist any more. A good number of physicians take this as an opportunity to learn with the patient and acknowledge their ignorance and willingness to learn, while some others will act out and use defensiveness to hide their embarrassment.
Although I don't think patients are to blamed for the problem, patients are indeed also part of the issue. Patients sometimes unknowingly encourage bad physician behaviors. For example, some patients may take arrogance as confidence of a physician. Some patients like black-and-white decisions and take discussion of nuances as indecisiveness of a physician.
At the end of the day, I guess the physician-patient relationship is like any other relationships--you relate with the one you like, and you separate from the one you dislike, and face the consequences.
Finding a good physician should aim at different goals at different disease stages. For definitive diagnosis, you need an expert on pheochromocytoma even though the expert may not be a perfect lady/gentleman. For surgical resection, you need an expert surgeon who has many cases before yours. For follow up, the character of the doctor is more important than knowledge and above all, you may not have a local expert in the first place.
As many of my own patients are from out-of-town, they often ask me how to pick a local doctor to coordinate the care for pheochromocytoma. The advice I give to my own patients is the follows: 1) you trust and like the doctor, 2) the doctor has an open mind on diseases she/he is not familiar with. The specialty of the doctor is not so important.
Let's not even start mentioning the hurdles on choosing physicians placed by HMO, the insurances, and other societal beings.
Dr. Pheo
My credential
One reader suggests that I add my credential. Here is a bit about my credential:
I have an MD degree and a PhD degree (in one of the biological sciences). I am board-certified in Internal Medicine and Endocrinology. I practice as a specialist in pheochromocytoma and other neuroendocrine tumors in a large US hospital. I do clinical research in pheochromocytoma.
I never copy and paste any sentences to my blog. In other words, I type every letter in my blog.
The initial blogs are common situations in pheochromocytoma and I say the same words many times to my patients. Therefore I write them down here so that any one interested can read them. I anticipate I will answer more questions than write on general topics in the near future.
The real testament of my credential will be and should be whether my answers to specific questions make sense, help patients and colleagues, and are later confirmed to be correct.
I have an MD degree and a PhD degree (in one of the biological sciences). I am board-certified in Internal Medicine and Endocrinology. I practice as a specialist in pheochromocytoma and other neuroendocrine tumors in a large US hospital. I do clinical research in pheochromocytoma.
I never copy and paste any sentences to my blog. In other words, I type every letter in my blog.
The initial blogs are common situations in pheochromocytoma and I say the same words many times to my patients. Therefore I write them down here so that any one interested can read them. I anticipate I will answer more questions than write on general topics in the near future.
The real testament of my credential will be and should be whether my answers to specific questions make sense, help patients and colleagues, and are later confirmed to be correct.
Wednesday, April 1, 2009
Surgical resection of pheochromocytoma
There are 3 surgical approaches to remove a pheochromocytoma: 1) open adrenalectomy, 2) laparoscopic adrenalectomy, and 3) cortex-preserving partial adrenalectomy.
The open adrenalectomy used to be the only approach but is now usually reserved for large (>10 cm) tumors. The whole adrenal gland along with the tumor is removed.
Laparoscopic adrenalectomy is the main procedure nowadays and is performed for most patients with pheochromocytoma. Again, the whole adrenal gland along with the tumor is removed.
Cortex-preserving partial adrenalectomy only removes the tumor but preserves the adrenal cortex (at least in theory). It is possible only in some patients. It is appealing to young patients with familial pheochromocytoma. These patients will have multiple pheochromocytomas on both adrenal glands and have to take medications for many many years if they have both adrenal glands removed at a young age.
The most important factors for a successful operation are experienced surgeon and anesthesiologist, and of course, careful preoperative preparation. The specific approach a surgeon adopts is less a factor. The surgeon has to be proficient in the specific approach she/he uses.
The open adrenalectomy used to be the only approach but is now usually reserved for large (>10 cm) tumors. The whole adrenal gland along with the tumor is removed.
Laparoscopic adrenalectomy is the main procedure nowadays and is performed for most patients with pheochromocytoma. Again, the whole adrenal gland along with the tumor is removed.
Cortex-preserving partial adrenalectomy only removes the tumor but preserves the adrenal cortex (at least in theory). It is possible only in some patients. It is appealing to young patients with familial pheochromocytoma. These patients will have multiple pheochromocytomas on both adrenal glands and have to take medications for many many years if they have both adrenal glands removed at a young age.
The most important factors for a successful operation are experienced surgeon and anesthesiologist, and of course, careful preoperative preparation. The specific approach a surgeon adopts is less a factor. The surgeon has to be proficient in the specific approach she/he uses.
Tuesday, March 31, 2009
Preoperative preparation for pheochromocytoma
Once a patient is diagnosed with pheochromocytoma, the patient needs to start medical treatment until she/he is ready for surgical resection. The preoperative medical preparation is often not optimal in clinical practice. Preoperative preparation, however, is critical for an uneventful operation and postoperative recovery.
First of all, pheochromocytoma is not an indication for urgent operation. There is time to prepare the patient for surgical resection of the tumor. For the uninitiated doctors and patients, the diagnosis of pheochromocytoma could elicit a sense of excitement and urgency. They would intuitively imagine that it makes sense to remove the tumor as soon as possible. While pheochromocytoma should be removed as soon as possible, the patient has to be prepared meticulously for the surgery.
The technical part of surgical resection of a pheochromocytoma is not complicated by itself. The tricky part is the patient's "hemodynamic status" during and after operation. "Hemodynamic status" means the patient's hear rate, blood pressure, and quality of the microcirculation inside organs. Pheochromocytoma differs from most other tumors because it produces catecholamines which increase blood pressure and heart rate to dangerous levels. Anesthesia and manipulation of the tumor often release large bouts of catecholamines that dramatically change the patient's "hemodynamic status". Preoperative preparation help prevent these complications and that's why it should be given to all patients.
The preoperative preparation needs to achieve 3 goals: 1) normalization of blood pressure, 2) replenishment of the patient's body fluid, and 3) recovery of heart function. All 3 goals are critically important and all should be met before the operation. Clinically inapparent abnormal heart functions are rather common in patients with pheochromocytoma and these should be reversed as much as possible before the operation.
There are 3 components in the preoperative preparation: 1) blood pressure medications, 2) salty food or intravenous infusion of fluids, and 3) a sufficient duration of the preparation for at least 2 weeks.
Depending on the patient's individual conditions, the doctors may make some adjustment on the regimen of preoperative preparation.
In my own experience, pheochromocytoma resection nowadays is remarkably safe if the patient is carefully prepared before the operation. The same operation can become disastrous if the patient is not carefully prepared. And most importantly, there is no reason why a patient is not carefully prepared. No excuse. Period.
Dr. Pheo
First of all, pheochromocytoma is not an indication for urgent operation. There is time to prepare the patient for surgical resection of the tumor. For the uninitiated doctors and patients, the diagnosis of pheochromocytoma could elicit a sense of excitement and urgency. They would intuitively imagine that it makes sense to remove the tumor as soon as possible. While pheochromocytoma should be removed as soon as possible, the patient has to be prepared meticulously for the surgery.
The technical part of surgical resection of a pheochromocytoma is not complicated by itself. The tricky part is the patient's "hemodynamic status" during and after operation. "Hemodynamic status" means the patient's hear rate, blood pressure, and quality of the microcirculation inside organs. Pheochromocytoma differs from most other tumors because it produces catecholamines which increase blood pressure and heart rate to dangerous levels. Anesthesia and manipulation of the tumor often release large bouts of catecholamines that dramatically change the patient's "hemodynamic status". Preoperative preparation help prevent these complications and that's why it should be given to all patients.
The preoperative preparation needs to achieve 3 goals: 1) normalization of blood pressure, 2) replenishment of the patient's body fluid, and 3) recovery of heart function. All 3 goals are critically important and all should be met before the operation. Clinically inapparent abnormal heart functions are rather common in patients with pheochromocytoma and these should be reversed as much as possible before the operation.
There are 3 components in the preoperative preparation: 1) blood pressure medications, 2) salty food or intravenous infusion of fluids, and 3) a sufficient duration of the preparation for at least 2 weeks.
Depending on the patient's individual conditions, the doctors may make some adjustment on the regimen of preoperative preparation.
In my own experience, pheochromocytoma resection nowadays is remarkably safe if the patient is carefully prepared before the operation. The same operation can become disastrous if the patient is not carefully prepared. And most importantly, there is no reason why a patient is not carefully prepared. No excuse. Period.
Dr. Pheo
Monday, March 30, 2009
The final diagnosis of pheochromocytoma
The final diagnosis of pheochromocytoma is based on three critical pieces of evidence: 1) elevated biochemical markers for pheochromocytoma, 2) an adrenal tumor, and 3) agreement between the extent of marker elevation and the imaging characteristics of the tumor. I have discussed 1) and 2) in previous posts, I will focus on 3) in this one.
What I mean for "agreement" is that the tumor size and the levels of markers should be roughly matching because larger tumors tend to have higher marker levels. For example, if a patient has plasma normetanephrine levels 20 fold elevated and has a 2-cm left adrenal tumor, the small adrenal tumor is not the pheochromocytoma that produces such high levels of plasma normetanephrine. There should be another tumor somewhere in the body. Another example. If a patient has plasma normetanephrine levels 1.5 fold elevated but has a left adrenal tumor measuring 5.5 cm, this left adrenal tumor is probably not a pheochromocytoma. I cannot give a very quantitative rule about marker levels and tumor size because there are no such rules. A doctor's experience is key here. The good news is that most tumors do have agreement between marker levels and tumor size on the first imaging study.
Dr. Pheo
What I mean for "agreement" is that the tumor size and the levels of markers should be roughly matching because larger tumors tend to have higher marker levels. For example, if a patient has plasma normetanephrine levels 20 fold elevated and has a 2-cm left adrenal tumor, the small adrenal tumor is not the pheochromocytoma that produces such high levels of plasma normetanephrine. There should be another tumor somewhere in the body. Another example. If a patient has plasma normetanephrine levels 1.5 fold elevated but has a left adrenal tumor measuring 5.5 cm, this left adrenal tumor is probably not a pheochromocytoma. I cannot give a very quantitative rule about marker levels and tumor size because there are no such rules. A doctor's experience is key here. The good news is that most tumors do have agreement between marker levels and tumor size on the first imaging study.
Dr. Pheo
The first follower of this blog
Today I noticed that this blog has its first follower. I thank you, my friend, to follow this blog. I promise all of you that you will find this blog providing much-needed information on pheochromocytoma diagnosis and treatment. I want to take this opportunity to remind you of asking me questions about pheochromocytoma or commenting on the contents of my blog.
I believe that my blog has a unique niche among all websites on pheochromocytoma. The most important feature of this blog is that it is interactive. It will be just like a doctor friend who has in-depth knowledge in pheochromocytoma. Either you are not sure whether you have pheochromocytoma, or you do have it but are not sure what the best treatment is, or you want to know how you should be followed after tumor resection, you can ask Dr. Pheo. In the future, after many questions are asked and answered, you probably will find your questions already answered by reading past articles. As pheochromocytoma and neuroendocrine tumors are so intriguing, I am sure that I will always have something to write about, and you will always have something to ask about.
Dr. Pheo
I believe that my blog has a unique niche among all websites on pheochromocytoma. The most important feature of this blog is that it is interactive. It will be just like a doctor friend who has in-depth knowledge in pheochromocytoma. Either you are not sure whether you have pheochromocytoma, or you do have it but are not sure what the best treatment is, or you want to know how you should be followed after tumor resection, you can ask Dr. Pheo. In the future, after many questions are asked and answered, you probably will find your questions already answered by reading past articles. As pheochromocytoma and neuroendocrine tumors are so intriguing, I am sure that I will always have something to write about, and you will always have something to ask about.
Dr. Pheo
Sunday, March 29, 2009
Imaging studies for diagnosing pheochromocytoma
If a doctor feels that the biochemical tests show a reasonable chance for pheochromocytoma, the doctor will order abdominal CT or MRI to see if there is an adrenal tumor. Abdominal ultrasound is not good enough for characterizing an adrenal tumor. On CT, most pheochromocytomas appear as a high-density mass, and on MRI, several protocols will determine if an adrenal mass is more likely to be a benign adenoma or "atypical" or "consistent with" pheochromocytoma.
A contrast material will be given intravenously. The contrast material is given because it will tell if a given organ or tumor has a lot fo blood supply or not. Pheochromocytoma has many blood vessels in it, thus it shows "enhancement" (just means it appears much brighter after contrast material is given.)
Sometimes, the biochemical tests suggest pheochromocytoma but CT or MRI does not find any adrenal masses. Now two things are possible: either the patient has pheochromocytoma but the tumor is somewhere else, or the patient does not actually have pheochromocytoma. The doctor should pause and weigh the evidence and decide which way to go.
If the biochemical tests strongly suggest that a patient has pheochromocytoma, regardless of imaging results, a functional scan called "MIBG" is done afterwards. Pheochromocytoma is very savvy in taking up MIBG. The value of MIBG scan is questionable for most patients but is considered an extra layer of caution. The MIBG scan can be falsely positive for some patients.
A contrast material will be given intravenously. The contrast material is given because it will tell if a given organ or tumor has a lot fo blood supply or not. Pheochromocytoma has many blood vessels in it, thus it shows "enhancement" (just means it appears much brighter after contrast material is given.)
Sometimes, the biochemical tests suggest pheochromocytoma but CT or MRI does not find any adrenal masses. Now two things are possible: either the patient has pheochromocytoma but the tumor is somewhere else, or the patient does not actually have pheochromocytoma. The doctor should pause and weigh the evidence and decide which way to go.
If the biochemical tests strongly suggest that a patient has pheochromocytoma, regardless of imaging results, a functional scan called "MIBG" is done afterwards. Pheochromocytoma is very savvy in taking up MIBG. The value of MIBG scan is questionable for most patients but is considered an extra layer of caution. The MIBG scan can be falsely positive for some patients.
Thursday, March 26, 2009
How is pheochromocytoma diagnosed?
Once pheochromocytoma is suspected in a given patient, biochemical tests need to be done first. A common mistake is doing an abdominal imaging test before biochemical tests are done. Imaging tests should only be done after biochemical tests highly suggest pheochromocytoma.
There are actually a few issues with biochemical tests that can make the test selection and test result interpretation rather complicated. There are 5 biochemical tests for pheochromocytoma: 2 measure chemicals in the blood, 3 measure chemicals in the urine. The 2 blood tests are called "plasma catecholamines" and "plasma fractionated metanephrines". The 3 urine tests are called "24-hour urine catecholamines", "24-hour urine metanephrines", and "24-hour Vanillylmandelic acid (VMA)". Another blood test called "chromogranin A (CGA)" may be occasionally used but this test is secondary to the other 5 tests.
So which test or tests to use? There are no clear or definitive answers to this question. A doctor has to take several issues into consideration. Usually only specialists like Dr. Pheo myself knows most of the nuts and bolts of all those tests but even specialists sometimes do not know what the best test is. In an ideal situation, "plasma fractionated metenephrines" are the test Dr. Pheo prefers for a variety of reasons. For a certain patient in certain situation, any one of the 5 tests can be the best test.
Now the results are back. What do they mean? Test results should not be simply labeled as "normal" or "abnormal". The extent of elevation of the results compared with normal reference range is very important. Test results are also open to interference by medications, diseases, and human errors. So if you have a test result that is only 20% above the normal range, don't panic. Chances are you don't have pheochromocytoma. On the other hand, a 20% increase may indicate pheochromocytoma in other people. Really tricky, isn't it? Although Dr. Pheo myself is very comfortable in interpreting test results for most patients, Dr. Pheo at times has to ponder on some results for days before making a call.
There are actually a few issues with biochemical tests that can make the test selection and test result interpretation rather complicated. There are 5 biochemical tests for pheochromocytoma: 2 measure chemicals in the blood, 3 measure chemicals in the urine. The 2 blood tests are called "plasma catecholamines" and "plasma fractionated metanephrines". The 3 urine tests are called "24-hour urine catecholamines", "24-hour urine metanephrines", and "24-hour Vanillylmandelic acid (VMA)". Another blood test called "chromogranin A (CGA)" may be occasionally used but this test is secondary to the other 5 tests.
So which test or tests to use? There are no clear or definitive answers to this question. A doctor has to take several issues into consideration. Usually only specialists like Dr. Pheo myself knows most of the nuts and bolts of all those tests but even specialists sometimes do not know what the best test is. In an ideal situation, "plasma fractionated metenephrines" are the test Dr. Pheo prefers for a variety of reasons. For a certain patient in certain situation, any one of the 5 tests can be the best test.
Now the results are back. What do they mean? Test results should not be simply labeled as "normal" or "abnormal". The extent of elevation of the results compared with normal reference range is very important. Test results are also open to interference by medications, diseases, and human errors. So if you have a test result that is only 20% above the normal range, don't panic. Chances are you don't have pheochromocytoma. On the other hand, a 20% increase may indicate pheochromocytoma in other people. Really tricky, isn't it? Although Dr. Pheo myself is very comfortable in interpreting test results for most patients, Dr. Pheo at times has to ponder on some results for days before making a call.
Tuesday, March 24, 2009
How pheochromocytoma is suspected?
In the present times and for the majority of patients, pheochromocytoma becomes a concern in 3 situations: symptoms, adrenal tumor, and familial syndromes.
The symptoms of pheochromocytoma are very diverse thus pheochromocytoma has earned the name as a "master mimicker" of other diseases. The symptoms can be as simple as mild hypertension but can also be as dramatic as strokes. The unique symptoms of pheochromocytoma "spells" are not as common nowadays as described in the classic literature. The spells may be elicited by emotional stress, exertion, pressure to the abdomen, or other stimuli the patients themselves often can figure out and avoid. The spells start with a sudden sense of doom or extreme fear, accompanied with headache, heart pounding, sweating, eye sensitivity to light, and other symptoms. A spell can last a few minutes to much longer. Blood pressure is invariably increased initially during a spell but blood pressure may drop to hypotension range due to reflexes of the body. Unusual hypertension and one or more components of the spell may make the doctor suspect pheochromocytoma. Only 0.2%-2% people with these symptoms actually have pheochromocytoma while symptoms are caused by other diseases in the majority of patients.
A mass in the adrenal glands is another reason for the doctor to suspect pheochromocytoma. Up to 5% of adrenal masses are pheochromocytoma. Therefore, tests for pheochromocytoma should be performed whenever a patient is found to have an adrenal mass. Pheochromocytoma found this way can be "silent" and the patient may be even free of symptoms.
The third situation is monitoring people who are carriers for mutations that cause familial tumor syndromes. Multiple endocrine neoplasia type II (MENII), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and familial paraganglioma syndrome are the most common syndromes. Carriers of the mutations related to these syndromes need to be screened periodically by blood tests and imaging.
Of course a combination of any of the 3 situations can occur.
The symptoms of pheochromocytoma are very diverse thus pheochromocytoma has earned the name as a "master mimicker" of other diseases. The symptoms can be as simple as mild hypertension but can also be as dramatic as strokes. The unique symptoms of pheochromocytoma "spells" are not as common nowadays as described in the classic literature. The spells may be elicited by emotional stress, exertion, pressure to the abdomen, or other stimuli the patients themselves often can figure out and avoid. The spells start with a sudden sense of doom or extreme fear, accompanied with headache, heart pounding, sweating, eye sensitivity to light, and other symptoms. A spell can last a few minutes to much longer. Blood pressure is invariably increased initially during a spell but blood pressure may drop to hypotension range due to reflexes of the body. Unusual hypertension and one or more components of the spell may make the doctor suspect pheochromocytoma. Only 0.2%-2% people with these symptoms actually have pheochromocytoma while symptoms are caused by other diseases in the majority of patients.
A mass in the adrenal glands is another reason for the doctor to suspect pheochromocytoma. Up to 5% of adrenal masses are pheochromocytoma. Therefore, tests for pheochromocytoma should be performed whenever a patient is found to have an adrenal mass. Pheochromocytoma found this way can be "silent" and the patient may be even free of symptoms.
The third situation is monitoring people who are carriers for mutations that cause familial tumor syndromes. Multiple endocrine neoplasia type II (MENII), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and familial paraganglioma syndrome are the most common syndromes. Carriers of the mutations related to these syndromes need to be screened periodically by blood tests and imaging.
Of course a combination of any of the 3 situations can occur.
Friday, March 20, 2009
What is pheochromocytoma?
Pheochromocytoma is a tumor from the inner part of the adrenal gland. Each person has two adrenal glands, one on each side of the body. The adrenal gland is located on top of the kidney (thus the name ad-renal). The adrenal gland has an outer layer and an inner core. The outer layer is called cortex while the inner core called medulla. Pheochromocytoma is a tumor from the adrenal medulla. There are other cells in the body that are very similar to the cells in adrenal medulla and they can also produce pheochromocytoma as well. In that case, the pheochromocytoma is called paraganglioma.
Pheochromocytoma makes substances called catecholamines. These substances constrict blood vessels, increase blood pressure, deplete the body of fluids, and hurt the heart. Catecholamines are also normally produced by the adrenal medulla. Only in excess amounts, catecholamines cause harm to the body.
Pheochromocytoma is indeed very rare. Because a common symptom of pheochromocytoma is hypertension, pheochromocytoma is often considered in patients with unusual hypertension. Another reason that pheochromocytoma is often an issue is adrenal mass identified through the wide use of abdominal imaging.
Pheochromocytoma is a tricky disease. It can be deadly if not diagnosed or treated properly. On the other hand, if diagnosed and treated properly, patients with pheochromocytoma can be completely cured. Although the most common presentation of pheochromocytoma is hypertension, pheochromocytoma can mimics many other diseases such as anxiety, palpitation, or heart attack. In a recent study, it is shown that more than 20% of patients who undergo surgical removal of a presumable pheochromocytoma end up not having pheochromocytoma. Similarly more than 20% of patients who indeed have pheochromocytoma are diagnosed as a dangerous surprise.
I welcome patients and colleagues to post comments or questions to this blog and we can go over all aspects of pheochromocytoma on a case-by-case basis. Please keep any personal information confidential. For example, even if you yourselves may have hypertension and a concern for pheochromocytoma, just say "a friend of mine (or my cousin Johnny), 45-year-old man, has hypertension for a year and his doctor tells him that he may have pheochromocytoma."
Pheochromocytoma makes substances called catecholamines. These substances constrict blood vessels, increase blood pressure, deplete the body of fluids, and hurt the heart. Catecholamines are also normally produced by the adrenal medulla. Only in excess amounts, catecholamines cause harm to the body.
Pheochromocytoma is indeed very rare. Because a common symptom of pheochromocytoma is hypertension, pheochromocytoma is often considered in patients with unusual hypertension. Another reason that pheochromocytoma is often an issue is adrenal mass identified through the wide use of abdominal imaging.
Pheochromocytoma is a tricky disease. It can be deadly if not diagnosed or treated properly. On the other hand, if diagnosed and treated properly, patients with pheochromocytoma can be completely cured. Although the most common presentation of pheochromocytoma is hypertension, pheochromocytoma can mimics many other diseases such as anxiety, palpitation, or heart attack. In a recent study, it is shown that more than 20% of patients who undergo surgical removal of a presumable pheochromocytoma end up not having pheochromocytoma. Similarly more than 20% of patients who indeed have pheochromocytoma are diagnosed as a dangerous surprise.
I welcome patients and colleagues to post comments or questions to this blog and we can go over all aspects of pheochromocytoma on a case-by-case basis. Please keep any personal information confidential. For example, even if you yourselves may have hypertension and a concern for pheochromocytoma, just say "a friend of mine (or my cousin Johnny), 45-year-old man, has hypertension for a year and his doctor tells him that he may have pheochromocytoma."
Thursday, March 19, 2009
Introduction by Dr. Pheo
Hi,
I am a medical specialist in pheochromocytoma and other neuroendocrine tumors. These tumors are rare and a general doctor may not have enough experience in them. Diagnosis and treatment of these tumors are therefore often sub-optimal. I would like to share my experience with patients and colleagues through this blog and hope all of us will benefit.
I will initially keep my identity anonymous. Please keep in mind that I do NOT establish a physician-patient relationship between me and another person through communicating with this blog. I can NOT offer specific medical opinions on this blog. I am happy to provide general information regarding your question. You are solely responsible for the consequences of using the information I provide here. If you have a question, please keep your personal information confidential and use general precautions as you would in any communications over the internet.
I can not promise that I will check the blog frequently. For questions you consider urgent, please direct them to your own physicians.
Best regards,
Dr. Pheo
I am a medical specialist in pheochromocytoma and other neuroendocrine tumors. These tumors are rare and a general doctor may not have enough experience in them. Diagnosis and treatment of these tumors are therefore often sub-optimal. I would like to share my experience with patients and colleagues through this blog and hope all of us will benefit.
I will initially keep my identity anonymous. Please keep in mind that I do NOT establish a physician-patient relationship between me and another person through communicating with this blog. I can NOT offer specific medical opinions on this blog. I am happy to provide general information regarding your question. You are solely responsible for the consequences of using the information I provide here. If you have a question, please keep your personal information confidential and use general precautions as you would in any communications over the internet.
I can not promise that I will check the blog frequently. For questions you consider urgent, please direct them to your own physicians.
Best regards,
Dr. Pheo
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