This interesting topic is suggested by a reader. The relationship between corticosteroid and pheo is multifold and involves several fundamental physiological issues.
Firs of all, the close proximity of the adrenal cortex and adrenal medulla is an intriguing phenomenon. The adrenal glands are small organs. An adrenal gland actually is further divided into two organs, the cortex (secreting corticosteroid) and medulla (where pheo is derived from), each with related but different functions. Why is the adrenal medulla wrapped around by the cortex? Why isn't the medulla located inside other organs, say, the spleen or liver, or a free-standing organ like a ganglion? I can only think of two other organs, pituitary and pancreas, which are also further divided into two organs. In the case of pituitary, anterior and posterior; pancreas, exocrine and endocrine. The question is still unsettled. Existing evidence suggests that the corticosteroid secreted by the adrenal cortex is important in maintaining the medulla what it is. If one takes the cells from the medulla and puts them in culture, those cells automatically differentiate into neuronal cells. If one adds high concentrations of corticosteroid into the culture, the medulla cells will remain neuroendocrine cells and do not differentiate into neuronal cells. As the medulla cells are derived from the neurocrest during embryonic development, it is hypothesized that the migrating neurocrest cells encounter adrenal cortex cells (which provide high concentrations of corticosteroid) and really like them and stay with them. Thus the story of adrenal cortex and adrenal medulla.
Second, corticosteroid stimulates catecholamine production and release from cultured adrenal medulla cells. Corticosteroid increases catecholamine production by upregulating the key enzymes for catecholamine production. The mechanisms for which corticosteroid stimulates catecholamine release are not clear and may not be straightforward.
Third, corticosteroid prepares the target tissues of catecholamines to be responsive to catecholamines. That is why patients with adrenal insufficiency often have low blood pressure even when they have high catecholamine levels.
Lastly, there have been a number of case reports on pheo crisis induced by corticosteroid use. The pheo crisis usually starts a few hours after corticosteroid use. There may be hemorrhage within the pheo. In patients with known pheo or an adrenal tumor of unclear nature, corticosteroid should be avoided if possible. When corticosteroid is used, patients should be closely monitored. In my own experience, pheo crisis by corticosteroid is rare and not a predictable event.
On a separate note, I have been very busy recently. To readers who are used to my quick responses, I may appear to become sloppy. I apologize. I am still following this blog closely but not as frequently as before. Please rest assured that I will respond to your questions, just not as timely.
Have a great Thanksgiving!
Dr. Pheo
Tuesday, November 23, 2010
Sunday, October 31, 2010
Report from NANETS meeting
I just returned from the NANETS meeting. Before the meeting, I had hoped that I would get to meet colleagues interested in pheo and see new studies on pheo at the NANETS meeting held in Santa Fe, October 29 and 30. NANETS stands for North American Neuroendocrine Tumor Society. It is a very nice society of doctors who treat neuroendocrine tumors. Pheo is a neuroendocrine tumor. Although the meeting was very informative on carcinoid and pancreatic endocrine tumors, there were literally only one study on pheo and one talk that mentioned pheo in passing.
The one study by a researcher in Dallas essentially showed that the mTOR pathway probably is not particularly important in the transformation from benign to malignant pheo and mTOR inhibitors (such as RAD001) probably won’t work for malignant pheo. The talk on modern gene testing by Dr. Marx at NIH briefly mentions the controversial issue of prenatal diagnosis of MEN2 (I had an earlier post on this topic in this blog) but did not delve further into pheo gene testing.
Dr. Pheo
The one study by a researcher in Dallas essentially showed that the mTOR pathway probably is not particularly important in the transformation from benign to malignant pheo and mTOR inhibitors (such as RAD001) probably won’t work for malignant pheo. The talk on modern gene testing by Dr. Marx at NIH briefly mentions the controversial issue of prenatal diagnosis of MEN2 (I had an earlier post on this topic in this blog) but did not delve further into pheo gene testing.
Dr. Pheo
Saturday, September 11, 2010
Coping with a frustrating disease
In an earlier post, I described my experience on alternative diagnosis for patients who have pheo symptoms but without pheo. Most patients cope with their conditions very well and go on with their lives. A small number of patients would see multiple physicians, get numerous tests and imaging studies, and try all kinds of medications, herbs, or behavioral therapies, just to get a definitive diagnosis and to get back to their "perfect" health. As a pheo specialist, I am often the doctor who tells them not only they don't have pheo but a clear diagnosis cannot be established. I explain that further diagnostic work-up is unlikely to yield a definitive diagnosis. I then discuss the skills of coping with a frustrating disease.
First of all, these patients do have a disease. And the disease is not their fault. They just simply have it and they have not done anything to make the disease afflict on them.
Second, medicine has its limits. In spite of the ever-growing progress in medicine, there are many things we don't know in medicine. Sometimes, a definitive diagnosis cannot be reached no matter how hard one may try. We have to wait for the disease to fully reveal itself over time.
Third, look at the brighter side. Although we don't know the diagnosis, we do know that it is not a bad one. It is not cancer, not heart disease, not a disease that will cost a limb or organ, and not deadly if the symptoms have been going on for many years.
Lastly, the most important issue is coping with the disease. What is the purpose of perfect health? What are the important things in life? Can one pursue the goals in life with the disease? What limits one from doing the desired things? The best approach is to focus on functionality rather than on perfect health. If one can do the things one wants to do, that's not too bad even with the disturbing symptoms mimicking pheo. I like to use a car metaphor. Most of us want to have fancy expensive cars but most of us cannot get those cars. If we keep lamenting on the lack of those cars, we lose the purpose of life. Those of us without fancy cars will get a car we can afford with the functions that we think are the most important. Then we drive the car to do the things we want to do. Simply owning a fancy car won't necessarily drive us somewhere.
Dr. Pheo
First of all, these patients do have a disease. And the disease is not their fault. They just simply have it and they have not done anything to make the disease afflict on them.
Second, medicine has its limits. In spite of the ever-growing progress in medicine, there are many things we don't know in medicine. Sometimes, a definitive diagnosis cannot be reached no matter how hard one may try. We have to wait for the disease to fully reveal itself over time.
Third, look at the brighter side. Although we don't know the diagnosis, we do know that it is not a bad one. It is not cancer, not heart disease, not a disease that will cost a limb or organ, and not deadly if the symptoms have been going on for many years.
Lastly, the most important issue is coping with the disease. What is the purpose of perfect health? What are the important things in life? Can one pursue the goals in life with the disease? What limits one from doing the desired things? The best approach is to focus on functionality rather than on perfect health. If one can do the things one wants to do, that's not too bad even with the disturbing symptoms mimicking pheo. I like to use a car metaphor. Most of us want to have fancy expensive cars but most of us cannot get those cars. If we keep lamenting on the lack of those cars, we lose the purpose of life. Those of us without fancy cars will get a car we can afford with the functions that we think are the most important. Then we drive the car to do the things we want to do. Simply owning a fancy car won't necessarily drive us somewhere.
Dr. Pheo
Friday, August 6, 2010
Should you see Dr. Pheo?
A few readers have expressed interest in seeing me for a formal consultation. I appreciate their encouragement. I do often see patients from other parts of the state or country. Seeing an outside expert has some pros and cons.
Pro 1. Definitive answer to specific questions. By the time you feel the need of seeing an outside expert, usually you already have done a lot of tests and imaging and received various opinions. The outside expert has the vantage position of reviewing all of the information and your natural clinical course. Of course the expert is also most experienced on some specific diseases. Whether the answer is yes, no, or further studies needed, you will have an answer.
Pro 2. Getting the best diagnostics and treatments. The outside expert usually works in an academic medical center and works closely with other experts. They can see things that were omitted before and usually do things “right”. Further diagnostic procedures and surgical operations are usually carried out by expert physicians as well.
Con 1. An expert is an expert on certain diseases but not on all diseases. Sometimes my patients are impressed by my knowledge on pheo and other neuroendocrine tumors and they assume that I know everything. I always explain that I do know a lot about pheo and other rare tumors and I am a good general endocrinologist as well, but my knowledge on other medical conditions is limited. Thus an expert can give you definitive answer to your specific question but she/he cannot solve all of your health problems.
Con 2. Follow-up is challenging. Patients and their diseases are ever-changing. For chronic and non-emergent questions, you can easily communicate with the expert by phone or email. For acute issues, it is important to ask a local physician who knows your condition well. Remember that the outside experts usually have responsibilities in research, teaching, and administration, besides clinical care. The expert may go to a scientific conference or vacation. All these make accessibility an issue.
Con 3. Extra cost and insurance coverage issues. These are self-explanatory.
Based on my experience, I believe there are some general rules-of-thumb on whether a patient should see an out-of-town specialist and how the patient can benefit the most from an outside expert. Here are my recommendations:
1. Find a local doctor who you trust and like and who has some basic knowledge on your condition. For pheo-related diseases, an endocrinologist or an internist is a good choice. This doctor has to be open-minded and comfortable at learning new knowledge.
2. Either ask the local doctor to identify an expert or find one yourself. Ask your doctor to contact the expert, explaining why the patient needs to see the expert and what specific questions need to be answered.
3. Before you go, send all doctor’s notes, lab results, CT/MRI and other imaging studies on CDs (not just the reports) to the expert.
4. When you are there, remember the specific questions your doctor and you want to ask the expert. Be realistic about what the expert can do (give definitive answers to specific questions) and cannot do (cure all ills). The expert may already have arranged additional diagnostics and possibly sessions with a surgeon or other experts so that you will have more efficient use of time there.
5. After you return, work closely with your local doctor and make sure that the local doctor and the expert communicate. Carry out the plan laid out by the expert and consult the expert on non-emergent questions. For emergency questions, you have to be lucky to be able to locate the expert all the time. Your local doctor is your best help.
What about seeing Dr. Pheo? All the rules apply. In addition, I will ask you to respect my wish to be anonymous as Dr. Pheo. Of course you will know my real name before you actually see me but please do not divulge Dr. Pheo’s identity publicly. I will post one of my email addresses later.
By the way, I will be on vacation from late August to Early September and may not have internet access during that time.
Dr. Pheo
Pro 1. Definitive answer to specific questions. By the time you feel the need of seeing an outside expert, usually you already have done a lot of tests and imaging and received various opinions. The outside expert has the vantage position of reviewing all of the information and your natural clinical course. Of course the expert is also most experienced on some specific diseases. Whether the answer is yes, no, or further studies needed, you will have an answer.
Pro 2. Getting the best diagnostics and treatments. The outside expert usually works in an academic medical center and works closely with other experts. They can see things that were omitted before and usually do things “right”. Further diagnostic procedures and surgical operations are usually carried out by expert physicians as well.
Con 1. An expert is an expert on certain diseases but not on all diseases. Sometimes my patients are impressed by my knowledge on pheo and other neuroendocrine tumors and they assume that I know everything. I always explain that I do know a lot about pheo and other rare tumors and I am a good general endocrinologist as well, but my knowledge on other medical conditions is limited. Thus an expert can give you definitive answer to your specific question but she/he cannot solve all of your health problems.
Con 2. Follow-up is challenging. Patients and their diseases are ever-changing. For chronic and non-emergent questions, you can easily communicate with the expert by phone or email. For acute issues, it is important to ask a local physician who knows your condition well. Remember that the outside experts usually have responsibilities in research, teaching, and administration, besides clinical care. The expert may go to a scientific conference or vacation. All these make accessibility an issue.
Con 3. Extra cost and insurance coverage issues. These are self-explanatory.
Based on my experience, I believe there are some general rules-of-thumb on whether a patient should see an out-of-town specialist and how the patient can benefit the most from an outside expert. Here are my recommendations:
1. Find a local doctor who you trust and like and who has some basic knowledge on your condition. For pheo-related diseases, an endocrinologist or an internist is a good choice. This doctor has to be open-minded and comfortable at learning new knowledge.
2. Either ask the local doctor to identify an expert or find one yourself. Ask your doctor to contact the expert, explaining why the patient needs to see the expert and what specific questions need to be answered.
3. Before you go, send all doctor’s notes, lab results, CT/MRI and other imaging studies on CDs (not just the reports) to the expert.
4. When you are there, remember the specific questions your doctor and you want to ask the expert. Be realistic about what the expert can do (give definitive answers to specific questions) and cannot do (cure all ills). The expert may already have arranged additional diagnostics and possibly sessions with a surgeon or other experts so that you will have more efficient use of time there.
5. After you return, work closely with your local doctor and make sure that the local doctor and the expert communicate. Carry out the plan laid out by the expert and consult the expert on non-emergent questions. For emergency questions, you have to be lucky to be able to locate the expert all the time. Your local doctor is your best help.
What about seeing Dr. Pheo? All the rules apply. In addition, I will ask you to respect my wish to be anonymous as Dr. Pheo. Of course you will know my real name before you actually see me but please do not divulge Dr. Pheo’s identity publicly. I will post one of my email addresses later.
By the way, I will be on vacation from late August to Early September and may not have internet access during that time.
Dr. Pheo
Wednesday, July 28, 2010
If not pheo, what do I have?
Pheo is a rare disease. In my practice, I see many patients who are suspected by their doctors of having pheo. After evaluating the patients, I generally find that only about 10% of them really have pheo, but the other 90% do not. The patients' response is usually predictable. Those who are diagnosed by me to have pheo are happy (and apprehensive, of course) after I discuss the nature of the disease and treatment plan. Those who do not have pheo are disappointed and frustrated. From the patients' point of view, they don’t care too much whether they have pheo or not per se, but they do want to feel better. If it is not pheo, what else is wrong?
About half of the patients for whom pheo is ruled out, especially young patients with hypertension, just have “essential hypertension”. Essential hypertension is a vague diagnosis simply meaning that the doctors don’t know why the patients have hypertension. Most patients with essential hypertension have a family history of hypertension. Their hypertension has multiple causes but none of the causes stands out obviously.
About a quarter of patients have obstructive sleep apnea (OSA). Patients with OSA are in a chronic stress mode so that they have catecholamine surges. OSA is pretty common and affects 5-10% of all people. Many people do not know they have OSA. The doctor has to probe whether the patient snores or has daytime somnolence. If the patient has suggestive symptoms, a consultation from a sleep specialist or pulmonologist is very valuable. The effects of CPAP treatment can be dramatic.
Another quarter of patients have anxiety disorder. People tend to have negative emotional reactions toward anxiety disorder. Some would wonder why they have the disease if they are not really anxious about anything. Anxiety disorder is a disease that we don’t know the cause of, just as depression is a disease that we don’t know the cause of. Patients should be evaluated by a psychiatrist to make the anxiety disorder diagnosis and to provide treatment.
There are nearly 30 other diseases that can also mimic pheo. These are generally much rarer and I do not see them often. Finally, I want to emphasize that the above is based on my personal experience; other doctors may have a different view.
Dr. Pheo
About half of the patients for whom pheo is ruled out, especially young patients with hypertension, just have “essential hypertension”. Essential hypertension is a vague diagnosis simply meaning that the doctors don’t know why the patients have hypertension. Most patients with essential hypertension have a family history of hypertension. Their hypertension has multiple causes but none of the causes stands out obviously.
About a quarter of patients have obstructive sleep apnea (OSA). Patients with OSA are in a chronic stress mode so that they have catecholamine surges. OSA is pretty common and affects 5-10% of all people. Many people do not know they have OSA. The doctor has to probe whether the patient snores or has daytime somnolence. If the patient has suggestive symptoms, a consultation from a sleep specialist or pulmonologist is very valuable. The effects of CPAP treatment can be dramatic.
Another quarter of patients have anxiety disorder. People tend to have negative emotional reactions toward anxiety disorder. Some would wonder why they have the disease if they are not really anxious about anything. Anxiety disorder is a disease that we don’t know the cause of, just as depression is a disease that we don’t know the cause of. Patients should be evaluated by a psychiatrist to make the anxiety disorder diagnosis and to provide treatment.
There are nearly 30 other diseases that can also mimic pheo. These are generally much rarer and I do not see them often. Finally, I want to emphasize that the above is based on my personal experience; other doctors may have a different view.
Dr. Pheo
Thursday, June 17, 2010
Is MIBG scan still needed?
MIBG is a chemical that has similar structure to that of catecholamines. Radioiodine-labeled MIBG is taken up by both normal adrenal medulla and pheo. Because pheo is usually much larger than the adrenal medulla, if one exists, it tends to light up with MIBG much more than normal adrenal medulla.
When MIBG scan began to be used clinically in the 1980s, CT and MRI were not yet available in clinical care. Initial clinical studies indeed showed that the MIBG scan was a great test, boasting a sensitivity of 90% (meaning that if there is a pheo, the chance that it will be shown is 90%) and a specificity of 95-100% (meaning that if you don’t have a pheo, the chance that no signal will be shown is 95-100%). The very high specificity was especially appealing to those clinicians who had little experience on pheo. Pheo is a disease nobody wants to miss. So, the reasoning goes, if MIBG scan result is negative, pheo can be ruled out.
Since the 1980s, better biochemical tests have become available and CT and MRI household names. Of course the new tests and CT and MRI have their own problems but every patient suspected to have pheo get those. Should the patient also get an MIBG scan? Will the MIB scan provide new information on whether the patient has pheo in the first place, or if she/he has pheo, how many and where they are?
In this month, two papers with opposite views appear respectively in Journal of Clinical Endocrinology and Metabolism and Endocrine Practice, the former being the world’s leading endocrinology journal, the latter a smaller journal with a readership of mostly American practicing endocrinologists. The first paper is an analysis of 15 clinical studies on MIBG using iodine 123. The conclusion is that MIBG scan has a sensitivity of 94% and specificity of 92%. The authors of this paper believe that their paper “supports the continued utility of I-123 MIBG imaging in the diagnosis and management of patients with pheochromocytoma.”
The second paper is a retrospective clinical study of MIBG scan (both I-131 and I-123) in a large US hospital in the last 14 years. There are quite a few interesting findings in this paper. First, MIBG scan is not really indicated in 76% of patients (in other words, three quarters of modern-day MIBG scans are wasted). Second, the sensitivity and specificity are both only about 70%. Lastly, the most important finding is that the MIBG scan does not provide any new information after biochemical testing and CT or MRI. Even worse, about 35% of the MIBG scans provide misleading information (i.e. showing adrenal uptake but patient does have pheo or no uptake but patient has pheo). The authors of this paper conclude that MIBG scan “is not necessary for most patients in modern practice.”
Why do these two papers have opposite conclusions on the MIBG scan? Like everything else, the devil is in the details. The 15 studies analyzed in the first paper are all well-controlled clinical studies performed by expert clinicians. They use very stringent and clearly defined criteria to call the MIBG scan result positive or negative. As matter of fact, borderline adrenal uptake is considered a negative result. In the second paper, the MIBG scan is ordered by clinicians with various experience on pheo. Borderline adrenal uptake is considered positive result. The authors’ rationale is that most clinicians and patients treat any adrenal uptake as alarming, which I do agree with. If borderline uptake is considered negative, the sensitivity and specificity increase to about 90%. Even that, the MIBG scan still does not provide useful new information. The first paper unfortunately does not address the utility of MIBG scan after biochemical testing and CT or MRI. Besides the second paper, a couple of other papers in the last few years also fail to show that MIBG scan has any clinical utility.
What do I do? My own experience is that MIBG scan seldom helps. I do order it in the following patients who I already diagnose as having pheo: young patients (<50-year-old), patients with family history or mutations, patients with previous pheo, and patients with multiple pheo, patients who have adrenal masses on both sides, and patients in whom CT/MRI does not find the pheo. Those patients are rare, though.
Dr. Pheo
When MIBG scan began to be used clinically in the 1980s, CT and MRI were not yet available in clinical care. Initial clinical studies indeed showed that the MIBG scan was a great test, boasting a sensitivity of 90% (meaning that if there is a pheo, the chance that it will be shown is 90%) and a specificity of 95-100% (meaning that if you don’t have a pheo, the chance that no signal will be shown is 95-100%). The very high specificity was especially appealing to those clinicians who had little experience on pheo. Pheo is a disease nobody wants to miss. So, the reasoning goes, if MIBG scan result is negative, pheo can be ruled out.
Since the 1980s, better biochemical tests have become available and CT and MRI household names. Of course the new tests and CT and MRI have their own problems but every patient suspected to have pheo get those. Should the patient also get an MIBG scan? Will the MIB scan provide new information on whether the patient has pheo in the first place, or if she/he has pheo, how many and where they are?
In this month, two papers with opposite views appear respectively in Journal of Clinical Endocrinology and Metabolism and Endocrine Practice, the former being the world’s leading endocrinology journal, the latter a smaller journal with a readership of mostly American practicing endocrinologists. The first paper is an analysis of 15 clinical studies on MIBG using iodine 123. The conclusion is that MIBG scan has a sensitivity of 94% and specificity of 92%. The authors of this paper believe that their paper “supports the continued utility of I-123 MIBG imaging in the diagnosis and management of patients with pheochromocytoma.”
The second paper is a retrospective clinical study of MIBG scan (both I-131 and I-123) in a large US hospital in the last 14 years. There are quite a few interesting findings in this paper. First, MIBG scan is not really indicated in 76% of patients (in other words, three quarters of modern-day MIBG scans are wasted). Second, the sensitivity and specificity are both only about 70%. Lastly, the most important finding is that the MIBG scan does not provide any new information after biochemical testing and CT or MRI. Even worse, about 35% of the MIBG scans provide misleading information (i.e. showing adrenal uptake but patient does have pheo or no uptake but patient has pheo). The authors of this paper conclude that MIBG scan “is not necessary for most patients in modern practice.”
Why do these two papers have opposite conclusions on the MIBG scan? Like everything else, the devil is in the details. The 15 studies analyzed in the first paper are all well-controlled clinical studies performed by expert clinicians. They use very stringent and clearly defined criteria to call the MIBG scan result positive or negative. As matter of fact, borderline adrenal uptake is considered a negative result. In the second paper, the MIBG scan is ordered by clinicians with various experience on pheo. Borderline adrenal uptake is considered positive result. The authors’ rationale is that most clinicians and patients treat any adrenal uptake as alarming, which I do agree with. If borderline uptake is considered negative, the sensitivity and specificity increase to about 90%. Even that, the MIBG scan still does not provide useful new information. The first paper unfortunately does not address the utility of MIBG scan after biochemical testing and CT or MRI. Besides the second paper, a couple of other papers in the last few years also fail to show that MIBG scan has any clinical utility.
What do I do? My own experience is that MIBG scan seldom helps. I do order it in the following patients who I already diagnose as having pheo: young patients (<50-year-old), patients with family history or mutations, patients with previous pheo, and patients with multiple pheo, patients who have adrenal masses on both sides, and patients in whom CT/MRI does not find the pheo. Those patients are rare, though.
Dr. Pheo
Sunday, May 23, 2010
Prenatal diagnosis of pheo-causing mutations
For people carrying mutations that cause pheo, the risk of having children with the same mutation is 50%. The decision on whether to have children is ultimately a personal decision, and is largely influenced by people's own experience with the mutations. Most people with pheo-causing mutations do decide to have children and are happy with their decisions. Some of my patients choose not to have children because they feel the burden on the children and themselves would be too big.
Some patients wonder if these mutations can be diagnosed before implantation or in early pregnancy. This is a complicated ethical issue. The technology is certainly available. Since the mutations are already known in most cases, finding the mutation is present or not is straightforward. If the mutation is found, to discard a fertilized egg or terminate an early pregnancy means very differently to different people, and extreme views exist. All the genetic syndromes that have pheo as a component are usually not very bad, and people with these syndromes can have very productive life, making the prenatal diagnosis controversial.
Currently these prenatal diagnostics are not offered to most people. If you have a very negative experience with a genetic pheo syndrome and desire to have children without it, you may want to talk with your doctor to see if it is possible to do a prenatal diagnosis.
Dr. Pheo
Some patients wonder if these mutations can be diagnosed before implantation or in early pregnancy. This is a complicated ethical issue. The technology is certainly available. Since the mutations are already known in most cases, finding the mutation is present or not is straightforward. If the mutation is found, to discard a fertilized egg or terminate an early pregnancy means very differently to different people, and extreme views exist. All the genetic syndromes that have pheo as a component are usually not very bad, and people with these syndromes can have very productive life, making the prenatal diagnosis controversial.
Currently these prenatal diagnostics are not offered to most people. If you have a very negative experience with a genetic pheo syndrome and desire to have children without it, you may want to talk with your doctor to see if it is possible to do a prenatal diagnosis.
Dr. Pheo
Tuesday, April 6, 2010
Clonidine suppression test
In the last two months, I have explained why the glucagon stimulation test and adrenal venous sampling should not be used any more for the purpose of pheo diagnosis. In this piece, I will go over a good test that has some value in pheo diagnosis; this is the clonidine suppression test.
First of all, why do we need this test? As I have described in previous postings, the results of pheo markers are not black and white. Most people with normal results do not have pheo. The risk of pheo is substantial if the results are 2-3-fold higher than normal. Those are the easier ones to interpret. The results are harder to digest if they are slightly elevated (higher than normal, but less than 2-3-fold elevated). Clonidine suppression test is intended to clarify the meaning of slightly elevated pheo markers.
Clonidine is a medication used for treating hypertension. It works on the brain to decrease the “sympathetic tone”, that is, the intensity of nerve signals to the adrenal medulla. Clonidine suppresses the release of catecholamines and metanephrines from normal adrenal medulla. Pheo is a tumor of the adrenal medulla and it essentially does things on its own. Catecholamines and metanephrines released from a pheo are less suppressed by clonidine than the normal adrenal medulla. Clonidine is thus used to differentiate pheo from normal.
The test is not really standardized and every center has its own protocol and interpretation criteria. The patient has to be off diuretics, tricyclics, and beta blockers for 1-5 days and off all medications for 12 hours. After an overnight fast, the patient goes to the clinic in the morning, and catecholamines and metanephrines are measured at baseline and 3 hours after taking clonidine. The passing results (no pheo) are 50% decrease and/or back to normal.
The major adverse effect of the test is hypotension, which can be severe.
There are a few caveats about the clonidine suppression test. 1) It should never be considered as a “gold standard” for pheo diagnosis. It is just one of the tests that help diagnosing pheo. 2) The results of the clonidine suppression test can be confusing too. Catecholamines and metanephrines may be trending toward different directions. Some markers may be even higher after clonidine. 3) The test is not needed for most patients. Even in the patient who should benefit most from it, I always find that it confirms my clinical suspicion rather than adds new information. 4) It is contra-indicated if the patients can not be off the medications.
My own experience is that the best use of the clonidine suppression test is for comforting patients who are very anxious about their borderline pheo markers and want all possible reassurance that they do not have pheo.
Dr. Pheo
First of all, why do we need this test? As I have described in previous postings, the results of pheo markers are not black and white. Most people with normal results do not have pheo. The risk of pheo is substantial if the results are 2-3-fold higher than normal. Those are the easier ones to interpret. The results are harder to digest if they are slightly elevated (higher than normal, but less than 2-3-fold elevated). Clonidine suppression test is intended to clarify the meaning of slightly elevated pheo markers.
Clonidine is a medication used for treating hypertension. It works on the brain to decrease the “sympathetic tone”, that is, the intensity of nerve signals to the adrenal medulla. Clonidine suppresses the release of catecholamines and metanephrines from normal adrenal medulla. Pheo is a tumor of the adrenal medulla and it essentially does things on its own. Catecholamines and metanephrines released from a pheo are less suppressed by clonidine than the normal adrenal medulla. Clonidine is thus used to differentiate pheo from normal.
The test is not really standardized and every center has its own protocol and interpretation criteria. The patient has to be off diuretics, tricyclics, and beta blockers for 1-5 days and off all medications for 12 hours. After an overnight fast, the patient goes to the clinic in the morning, and catecholamines and metanephrines are measured at baseline and 3 hours after taking clonidine. The passing results (no pheo) are 50% decrease and/or back to normal.
The major adverse effect of the test is hypotension, which can be severe.
There are a few caveats about the clonidine suppression test. 1) It should never be considered as a “gold standard” for pheo diagnosis. It is just one of the tests that help diagnosing pheo. 2) The results of the clonidine suppression test can be confusing too. Catecholamines and metanephrines may be trending toward different directions. Some markers may be even higher after clonidine. 3) The test is not needed for most patients. Even in the patient who should benefit most from it, I always find that it confirms my clinical suspicion rather than adds new information. 4) It is contra-indicated if the patients can not be off the medications.
My own experience is that the best use of the clonidine suppression test is for comforting patients who are very anxious about their borderline pheo markers and want all possible reassurance that they do not have pheo.
Dr. Pheo
Wednesday, March 17, 2010
Adrenal venous sampling, another outdated test
I started this blog a year ago. I am very happy to see that it has been well received by the readers and I hope it will continue to be helpful to people with suspected or diagnosed pheo and to colleagues.
The clinical research on pheo is growing at an amazing speed. Almost every month, interesting reports appear in reputable journals. In this month's Journal of Clinical Endocrinology and Metabolism, a paper written by Dr. Young at Mayo Clinic (he is on Dr. Pheo's pheo doctor list) and associates provide pretty definitive evidence that another old test for pheo diagnosis, adrenal venous sampling (AVS), should not be used any more. It remains a great test for some other adrenal disorders.
AVS had been invented way before the modern tests and imaging methods were used; it probably has seen its best times. Most younger endocrinologists are not even aware of this test, for a good reason, as it is seldom used for diagnosing pheo in the last 20 years. AVS is invasive and requires significant experience to do it right. A radiologist would insert a cannula into each of the main veins in the patient's groin and advance it into the adrenal veins. Catecholamines are then measured in the adrenal veins and in a peripheral vein. If one side shows much higher levels of catecholamines than the other side, it is then concluded that this side may have a pheo, at least so believed by the proponents of this test.
I missed the heydays of AVS. I never ordered it myself because I never felt it was needed in my own practice. I have taken care of patients who had this test done to them. It is invariably ordered by an endocrinologist who completed training many years ago, and the indications are not clear. The situation is usually like this: a patient would have some pheo symptoms and pheo markers are elevated but CT/MRI and MIBG scan do not clearly show any adrenal tumors. Someone would then suggest AVS. In my limited experience, AVS does not help in any tangible ways. On the other hand, it often reinforces a misconception that the patient has a pheo. In spite of my strong belief, it is not easy to convince my colleagues not to use it because there have not been studies to show the fallacy of AVS, until this paper appears.
This paper is not a typical study of diagnostic test. It does not address sensitivity or specificity. Rather, it shows the results of AVS in patients without pheo. The major observations are: 1) catecholamine levels are much higher in the adrenal veins than in peripheral veins (no surprise as they are supposed to be); 2) the catecholamine levels vary tremendously between individuals (300-fold difference); 3) catecholamines in the right adrenal veins tend to be higher than in the left one (can be as high as 83-fold). All the above are considered by some as evidence of pheo but remember all those patients do NOT have pheo. The data from this paper thus cast a large doubt on the value of AVS.
Regardless of what criteria are used for interpreting AVS results, the most important fact on AVS is that it has no clear indications in modern medicine and should not be ordered in the first place for diagnosing pheo. I cannot think of a clinical situation where AVS will aid in the diagnosis or localization of pheo.
I’d like to hear your experience on AVS.
Dr. Pheo
The clinical research on pheo is growing at an amazing speed. Almost every month, interesting reports appear in reputable journals. In this month's Journal of Clinical Endocrinology and Metabolism, a paper written by Dr. Young at Mayo Clinic (he is on Dr. Pheo's pheo doctor list) and associates provide pretty definitive evidence that another old test for pheo diagnosis, adrenal venous sampling (AVS), should not be used any more. It remains a great test for some other adrenal disorders.
AVS had been invented way before the modern tests and imaging methods were used; it probably has seen its best times. Most younger endocrinologists are not even aware of this test, for a good reason, as it is seldom used for diagnosing pheo in the last 20 years. AVS is invasive and requires significant experience to do it right. A radiologist would insert a cannula into each of the main veins in the patient's groin and advance it into the adrenal veins. Catecholamines are then measured in the adrenal veins and in a peripheral vein. If one side shows much higher levels of catecholamines than the other side, it is then concluded that this side may have a pheo, at least so believed by the proponents of this test.
I missed the heydays of AVS. I never ordered it myself because I never felt it was needed in my own practice. I have taken care of patients who had this test done to them. It is invariably ordered by an endocrinologist who completed training many years ago, and the indications are not clear. The situation is usually like this: a patient would have some pheo symptoms and pheo markers are elevated but CT/MRI and MIBG scan do not clearly show any adrenal tumors. Someone would then suggest AVS. In my limited experience, AVS does not help in any tangible ways. On the other hand, it often reinforces a misconception that the patient has a pheo. In spite of my strong belief, it is not easy to convince my colleagues not to use it because there have not been studies to show the fallacy of AVS, until this paper appears.
This paper is not a typical study of diagnostic test. It does not address sensitivity or specificity. Rather, it shows the results of AVS in patients without pheo. The major observations are: 1) catecholamine levels are much higher in the adrenal veins than in peripheral veins (no surprise as they are supposed to be); 2) the catecholamine levels vary tremendously between individuals (300-fold difference); 3) catecholamines in the right adrenal veins tend to be higher than in the left one (can be as high as 83-fold). All the above are considered by some as evidence of pheo but remember all those patients do NOT have pheo. The data from this paper thus cast a large doubt on the value of AVS.
Regardless of what criteria are used for interpreting AVS results, the most important fact on AVS is that it has no clear indications in modern medicine and should not be ordered in the first place for diagnosing pheo. I cannot think of a clinical situation where AVS will aid in the diagnosis or localization of pheo.
I’d like to hear your experience on AVS.
Dr. Pheo
Monday, February 1, 2010
Adieu, Glucagon Stimulation Test
In the olden days, there were a few dynamic tests to diagnose pheo. In those days, none of the biochemical tests and imaging methods that we take for granted today was available. If you and I feel frustrated now over diagnosing a pheo, imagine how people felt then!
The glucagon stimulation test was one of the dynamic tests invented in those days. Glucagon is a hormone produced by the alpha cells in the pancreatic islets (insulin is by the beta cells in the same islets). Glucagon has many functions. The main one is to increase blood glucose levels (that’s why it is used to treat hypoglycemia). It also stimulates the heart and increases blood pressure. At the beginning, increase of blood pressure after glucagon was used to diagnose pheo; later, the test changed to increase of norepinephrine after glucagon.
The glucagon stimulation test began to fade away after better tests for pheo were discovered. It is seldom used in the last 20 years. Whether it has any unique value in modern-day medicine, however, is never satisfactorily answered. I have been asked by my own patients about the glucagon stimulation test and some patients wonder if the test can uncover a hidden pheo. A recent study systemically examined the body’s response to glucagon and largely settled the question.
This study shows that norepinephrine increases dramatically after glucagon in only about ¼ to ½ of pheo patients. In the other ½ to ¾ of pheo patients, the increase in norepinephrine levels is too small to have any diagnostic value. In other words, it is not sensitive enough. In the subgroup of patients who have borderline metanephrine results and need further testing, the performance of glucagon stimulation test is similar.
The glucagon stimulation test is not without risks. A few patients had hypertensive crisis. One patient developed visual problems that eventually recovered in a few months.
This study, along with a few others, clearly demonstrates that the glucagon stimulation test has no place in diagnosing pheo in modern medicine. We should not use it any more for the purpose of diagnosing pheo.
Dr. Pheo
The glucagon stimulation test was one of the dynamic tests invented in those days. Glucagon is a hormone produced by the alpha cells in the pancreatic islets (insulin is by the beta cells in the same islets). Glucagon has many functions. The main one is to increase blood glucose levels (that’s why it is used to treat hypoglycemia). It also stimulates the heart and increases blood pressure. At the beginning, increase of blood pressure after glucagon was used to diagnose pheo; later, the test changed to increase of norepinephrine after glucagon.
The glucagon stimulation test began to fade away after better tests for pheo were discovered. It is seldom used in the last 20 years. Whether it has any unique value in modern-day medicine, however, is never satisfactorily answered. I have been asked by my own patients about the glucagon stimulation test and some patients wonder if the test can uncover a hidden pheo. A recent study systemically examined the body’s response to glucagon and largely settled the question.
This study shows that norepinephrine increases dramatically after glucagon in only about ¼ to ½ of pheo patients. In the other ½ to ¾ of pheo patients, the increase in norepinephrine levels is too small to have any diagnostic value. In other words, it is not sensitive enough. In the subgroup of patients who have borderline metanephrine results and need further testing, the performance of glucagon stimulation test is similar.
The glucagon stimulation test is not without risks. A few patients had hypertensive crisis. One patient developed visual problems that eventually recovered in a few months.
This study, along with a few others, clearly demonstrates that the glucagon stimulation test has no place in diagnosing pheo in modern medicine. We should not use it any more for the purpose of diagnosing pheo.
Dr. Pheo
Friday, January 1, 2010
“Adrenal medulla hyperplasia”
Recently I saw an elderly patient with episodic hypertension. The pheo markers were mildly elevated at times but normal at others. Before I saw the patient, abdominal and pelvic CT had already been done and some thickening of left adrenal gland was noted. No tumors were identified. MIBG scan had also been done, and there was a slight uptake in the left adrenal area. A few of those involved in the patient’s care believed that she/he had pheo. The patient also firmly accepted the pheo diagnosis after reading about pheo. Once again, I was the pain-in-the-neck doctor and told the patient that it was very unlikely that she/he had pheo. Then someone brought up the issue of “adrenal medulla hyperplasia” and wondered if it was not pheo, it might be “adrenal medulla hyperplasia”. I have followed the literature on this alleged condition for a while and would like to share my thoughts here with you.
Adrenal medulla, the inner part of adrenal gland where pheo is derived from, is part of the sympathetic nervous system (the “fight-and-flight” system). The exact role of adrenal medulla in blood pressure control is still not so clear. For example, most patients with bilateral adrenalectomy do not have low blood pressure. In the earlier part of last century, adrenalectomy was used to treat hypertension with mixed results. The adrenal medulla has a very small mass of less than 1 gram. The adrenal medulla of some patients indeed becomes bigger with more cells (“hyperplasia”). In patients with multiple endocrine neoplasia type 2 (MEN2), adrenal medulla hyperplasia occurs before pheo develops. In patients with long-standing hypertension, the adrenal gland tends to be bigger and both cortex and medulla are bigger.
In the literature, there are a handful of reports claiming adrenal medulla hyperplasia can cause symptoms very similar to that of pheo. In these reports, usually the patients have labile hypertension and pheo is suspected. The pheo markers are either normal or mildly elevated. The adrenal glands are either normal or mildly enlarged but clearly without a tumor on CT or MRI. MIBG scan typically is borderline positive. These reports then claim the patients immediately get better after unilateral or bilateral adrenalectomy. The pathology exam of course shows adrenal medulla hyperplasia.
Based on my own experience, my discussion with other experts on pheo, and review of literature, I simply think there are no adequate evidence and no need to consider the so-called adrenal medulla hyperplasia as a disease in clinical practice. My reasoning is as follows:
1. Adrenal medulla hyperplasia is either a pre-tumor lesion or a secondary change caused by hypertension rather than causing hypertension.
2. Nowadays most patients with labile hypertension can be satisfactorily controlled by medications.
3. There are no universal criteria accepted by pathologists to diagnose adrenal medulla hyperplasia.
4. Most patients with “adrenal medulla hyperplasia” do not have labile hypertension.
5. The diagnosis of “adrenal medulla hyperplasia” is often a hindsight after pheo is not found in the adrenal.
6. Most patients continue to experience the same symptoms after adrenalectomy.
As medicine is ever-developing, I can imagine that adrenal medulla hyperplasia may indeed cause symptoms in a small number of patients. The problem is that many patients will undergo unnecessary and ineffective adrenalectomy if we allow “adrenal medulla hyperplasia” to be in the differential diagnosis of hypertension. The proponents of “adrenal medulla hyperplasia” need to establish a clear set of diagnostic criteria to identify the few patients who might benefit from adrenalectomy.
Dr. Pheo
Adrenal medulla, the inner part of adrenal gland where pheo is derived from, is part of the sympathetic nervous system (the “fight-and-flight” system). The exact role of adrenal medulla in blood pressure control is still not so clear. For example, most patients with bilateral adrenalectomy do not have low blood pressure. In the earlier part of last century, adrenalectomy was used to treat hypertension with mixed results. The adrenal medulla has a very small mass of less than 1 gram. The adrenal medulla of some patients indeed becomes bigger with more cells (“hyperplasia”). In patients with multiple endocrine neoplasia type 2 (MEN2), adrenal medulla hyperplasia occurs before pheo develops. In patients with long-standing hypertension, the adrenal gland tends to be bigger and both cortex and medulla are bigger.
In the literature, there are a handful of reports claiming adrenal medulla hyperplasia can cause symptoms very similar to that of pheo. In these reports, usually the patients have labile hypertension and pheo is suspected. The pheo markers are either normal or mildly elevated. The adrenal glands are either normal or mildly enlarged but clearly without a tumor on CT or MRI. MIBG scan typically is borderline positive. These reports then claim the patients immediately get better after unilateral or bilateral adrenalectomy. The pathology exam of course shows adrenal medulla hyperplasia.
Based on my own experience, my discussion with other experts on pheo, and review of literature, I simply think there are no adequate evidence and no need to consider the so-called adrenal medulla hyperplasia as a disease in clinical practice. My reasoning is as follows:
1. Adrenal medulla hyperplasia is either a pre-tumor lesion or a secondary change caused by hypertension rather than causing hypertension.
2. Nowadays most patients with labile hypertension can be satisfactorily controlled by medications.
3. There are no universal criteria accepted by pathologists to diagnose adrenal medulla hyperplasia.
4. Most patients with “adrenal medulla hyperplasia” do not have labile hypertension.
5. The diagnosis of “adrenal medulla hyperplasia” is often a hindsight after pheo is not found in the adrenal.
6. Most patients continue to experience the same symptoms after adrenalectomy.
As medicine is ever-developing, I can imagine that adrenal medulla hyperplasia may indeed cause symptoms in a small number of patients. The problem is that many patients will undergo unnecessary and ineffective adrenalectomy if we allow “adrenal medulla hyperplasia” to be in the differential diagnosis of hypertension. The proponents of “adrenal medulla hyperplasia” need to establish a clear set of diagnostic criteria to identify the few patients who might benefit from adrenalectomy.
Dr. Pheo
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