Results from the Pheo Survey

By Joyce Graff and Sue Buckley

In the summer of 2011 we conducted an online and telephone survey of 367 people with pheochromo­cytoma and/or paraganglioma. For the sake of simplicity, we will refer to both in this paper as “pheos”. Most of the respondents were people who had contacted one of three organizations, seeking help with their symptoms. When they first reached out, many did not know what was causing their symptoms, but they recognized from the websites and discussions that their symptoms were not unique. Figure 1 shows the DNA diagnosis known when people first reported symptoms, and the DNA diagnosis now known.

People were asked to respond to an online survey at SurveyMonkey.com prepared by Joyce Graff and Sue Buckley. Inspiration for this survey was provided by ten people that Joyce and Sue had been in touch with by telephone for up to 14 months, working to help them get a diagnosis of their symptoms. The barriers they were running into seemed ridiculously impossible. Even with a family history of pheos and a genetic diagnosis of VHL, some of these people had experienced doctors who refused to run the tests for pheo, ran them incorrectly, or failed to interpret the results. More than one had been told multiple times that “it can’t be a pheo, it’s too rare.”

The survey was launched in order to determine how widespread these issues might be, and to report to the International Symposium on Pheochromocytoma and Paraganglioma, being held in September in Paris, asking the doctors there to help fill some of the knowledge gaps in the field. The attendees of this conference include the world’s top experts on pheochromocytoma. The gap between their expert knowledge and the knowledge about pheos of the average doctor in the field is a serious problem for patients. While expert care exists, getting the patient from the street into the office of a doctor who can really help is a major hurdle.

We asked patients to describe their experience getting a diagnosis of their first pheo/para, or their most difficult experience if it was not the first. A number of major themes emerged.

Symptoms lead and mislead

The most commonly known symptoms of pheo are known as the “classic triad”: headaches, heavy sweating, and high blood pressure and/or palpitations. It is not necessary to have all three. 187 respondents had two or more of the “classic triad” symptoms; 12 had all three.

102 respondents had a genetic diagnosis in hand. Another 20 had a family history of pheos. Yet only 7 pheos were found through routine screening.

It took an average of 3.5 years for people to get a diagnosis of pheo, with some people going 10-28 years before they received a diagnosis.

5% of people with pheos had none of these symptoms at all even when they had a visible lump in the area of the head and neck. This is actually not unusual for people with paragangliomas. One person commented: “I saw a GP for several years, then age 19 an ENT took out my tonsils but I still had lumps, so I went to a cardiologist who sent me to a plastic surgeon for a ‘snip-snip’ surgery of what they thought was a gland but it turned out to be a tumor of the carotid body.”

Regular screening saves lives and reduces long-term damage

People who knew they had a familial risk factor and were going through regular screening did the best. Many experienced few if any symptoms. The pheo was found on a regular scan or through regular blood or urine testing, and treatment was performed in a timely manner. They also reported the best outcomes—all symptoms resolved completely, and they went on with their lives.

Delayed diagnosis hurts

During the time people were waiting for their diagnosis, people reported many serious issues. First, of course, their symptoms worsened, making it difficult to concentrate, undermining their energy and stamina. As the tumors grew, serious emotional fragility developed, sometimes resulting in explosive temper which caused problems at work and in relationships. Even worse, the fact that their doctors did not believe they were sick, or accused them of using drugs, or of hypochondria or other psychiatric disorders had a severe impact on their feelings of self-worth and frequently led to feelings of helplessness and hopelessness. Many said they felt they had lost control of their lives. People with such advanced tumors often had some of the symptoms even after the tumor was removed.

Children do get pheos

Some of the reports in the medical literature claim that young children do not get pheos, with some physicians declaring that it is not necessary to test children under 5 years old for pheo. In this survey, 25% of respondents had their first symptoms before age 15, 5% of them before age 6. While the average age of onset of symptoms was 28.3 years, the range was 0–82, and 13 respondents had their first symptoms before the age of 6, with one diagnosed and removed before the first birthday.

Parents who knew the genetic risk factors knew to refuse a doctor’s declaration that the child was making it up or trying to get out of school. Those who immediately sought another opinion from someone with experience in pheos or in the known genetic condition were able to get timely help for their child. Children who struggled for years with these symptoms reported feeling depressed, being labeled by teachers as “a bad kid,” sometimes labeled as having ADD or autism, being angry, and/or losing friends.

No one believed I was sick

As people read our checklist of symptoms that might occur, several were surprised to realize they could be indicative of a pheo. Some said they were embarrassed to discuss some of these symptoms with their doctor, not thinking they were related: heavy sweating, constipation or chronic diarrhea, nervous tremors or tics, anxiety or feelings of doom. Dizziness, fatigue, and headaches were usually reported.

Symptoms can lead doctors astray

In his book “How Doctors Think,” Dr. Jerome Groopman reports that there is a phenomenon in medicine today which he calls the “zebra retreat” to describe a doctor’s shying away from a rare diagnosis. “Powerful forces in modern medicine discourage hunting for them. Often the laboratory tests and procedures needed to pin down an arcane diagnosis are hard to perform, highly specialized, and expensive. In an era of cost containment, when insurers and managed care plans scrutinize how much physicians spend on any one patient, doctors have a strong disincentive to pursue ideas that are ‘out there.’” Instead, the tendency is to look first to the most common conditions—the kinds of things this doctor sees every day. It takes time, attention, and courage for a physician to look beyond the obvious and arrive at a diagnosis of any rare disease.

In the case of pheos, the symptoms legitimately reported seem to have a tendency to route many doctors’ thinking toward one of heart disease or psychological issues. Here is why.

Heart disease

The chemicals generated by the pheo may cause the heart to race, the blood pressure to become erratic, nervous tics, and/or moderate to severe headaches, all of which might raise concerns of a heart attack or stroke (Figure 2). In fact, the pheo overworks the cardiovascular system and can in some cases lead to heart disease or stroke. However, once medications to slow the heart or handle angina are in the system, the best diagnostic tests for pheo may not work—there may be a “false negative” report—the test will say there is no pheo, but in fact the results are false. This makes it much more difficult to diagnose a pheo.

Psychological issues

When patients report anxiety, panic attacks, feelings of doom, fatigue, sometimes alternating with spurts of boundless energy, and mood swings for no good reason, it is logical to think this person is under stress at home, work or school, or has some more serious psychological issue going on (Figure 3). Many people were referred for psychiatric counseling and/or prescribed drugs. In two cases the psychiatrist identified that there was an underlying physical cause and sent the patient for testing that did identify the pheo. But more often the mood-altering or anti-psychotic drugs cause a false-negative test for a pheo.

Ideally the tests for a pheo should be run BEFORE prescribing medications for anxiety. More often, the thought to run the pheo testing occurs after these psych meds are already in the bloodstream.

Pregnancy is a particularly dangerous time to have a pheo

Five women in our study reported having pheos during pregnancy. The initial diagnosis was pre-eclampsia or toxemia, but fortunately most of the obstetricians consulted by these patients recognized that there was more going on, and/or sent the woman to a high-risk obstetrician who recognized the problem. In two cases the baby died. Women with one of these risk factors who becomes pregnant or is considering becoming pregnant should get tested for a pheo as soon as possible. It is possible to remove a pheo during the early stages of pregnancy without harm to the baby. However the longer the baby lives with the hormones generated by the pheo, the greater the potential harm to mother and child. Childbirth with a pheo in place is potentially life-threatening both to mother and child.

Time is the enemy

As noted earlier, when pheos are diagnosed at early stages, before or at the beginning of the onset of symptoms, proper treatment usually results in full recovery.

As the tumor grows and injects larger and larger amounts of hormones into the bloodstream, symptoms worsen and often affect the individual’s energy, mood, temper, and thus their interactions with other people. People who waited years for a diagnosis reported problems in school, in the workplace, and in relationships. This in turn sometimes results in divorce or loss of work, which might also mean loss of health insurance and serious financial problems. Loss of health insurance results in greater difficulty in accessing the medical attention needed to diagnose a pheo. It also results in loss of self-esteem and can lead to self-destructive behaviors. Here are some quotes from people who waited 3+ years to get a diagnosis:

• Out of work since January 2011 with symptoms they now think are a pheo. I work for a huge hospital, but 6 months after you go out on disability they terminate you and make you pay COBRA insurance at exorbitant prices.

• Severe emotional trauma within the family unit by constant disregard by health professionals and being made to feel like idiots when clearly something serious was occurring.

• The first pheo took 3 years to find. I thought I had major psychiatric issues during that time.

• If the doctors tell you often enough that you’re crazy, you begin to believe it. Certainly my wife believed them and left with the kids.

• I found it difficult to control my anger when my adrenaline spiked (recognized it after diagnosis)

• Anxiety so bad that at one time I was suicidal and even self-medicated with alcohol and felt better when I did this. As soon as I got sober, the issues came back.

Preparing for the surgery

We know that “blocking” is important before surgery, administering drugs to block the negative effects of the pheo and keep the heart rate at a manageable level for the surgeon and anesthesiologist, so that you will come safely through the surgery. Four times patients were sent quickly into surgery. Twice the family knew to refuse and require proper blocking before the surgery.

What also is not routinely discussed is how the body will readjust to its “new normal” after the pheo is removed. Depending how long the pheo has been pumping drugs into your system, your body may need some weeks or months to readjust. You may feel strange and need to make a special effort to calm yourself. Just know that this is par for the course, you will get through this, and your body will achieve its new normal in the course of things.

How to protect yourself:

As families, we can educate ourselves, and make sure that when we experience this kind of symptom or see a family member going through this kind of downward spiral, we take action immediately, advocate for ourselves and our loved ones, seek expert help, and get to a timely diagnosis.

However, at the same time, we need help from the experts in educating the medical community. Respondents to this survey contacted an average of 5.5 different kinds of doctors each before getting a diagnosis—often several doctors in each specialty area. The top kinds of physicians consulted were: general practitioners or internists, endocrinologists, and Emergency Room physicians. Pediatricians and obstetricians/gynecologists are also on the front lines of care for children and pregnant women. The knowledge and experience of these specialists with pheos and the genetic conditions that can cause them tends to be sparse on the ground. Never hesitate to seek a second—or third—opinion, and to ask or check the resumes of physicians to see what they know about pheos.

Because of the possible misdirection that our symptoms may present, it is important that cardiologists and psychiatrists also know to think of a possible pheo. In some cases, the patient’s short fuse sometimes caused less than polite behaviors in the doctor’s office. Instead of being offended, it would be good if the doctor considered the possibility that this is a symptom. Certainly within the family we need to acknowledge when behavior changes, and see it as a possible symptom that something is wrong medically and needs to be checked out. While the doctor sees what occurs during that 12-minute appointment, family and friends who have known this person for years can notice the changes much more readily. We know when behavior is not normal for this person.

Educating yourself is your best defense for yourself and your family members. Twenty percent of people with VHL may get a pheo, and in some families the risk is higher (or lower). People with SDH mutations are likely to get even more pheos and paragangliomas. With knowledge and early diagnosis, we can avoid the worst consequences of these conditions and live normal and happy lives.

To see the patient survey report, go to: www.vhl.org/pheo/pheo-survey.pdf. The doctor survey report for the pheo survey is at: www.vhl.org/pheo/pheo-med-report.pdf.

As printed in the VHL Family Forum 19:3, September 2011. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.