Editor’s Note: What follows is a transcription of selected questions and answers from well over 2 hours of panel discussions at National Cushing’s Patient Education Day, March 1, 2014. The panels included Dr. Adriana Ioachimescu (endocrinologist, Emory University, Atlanta, GA), Dr. Nelson Oyesiku (neurosurgeon, Emory University), Dr. Mary Lee Vance (endocrinologist, University of Virginia, Charlottesville, VA), Dr. Edward Oldfield (neurosurgeon, University of Virginia) and Dr. Jared DeFife (clinical psychologist, Emory University), Louise Pace, President of the CSRF, Karen Campbell and Ellen Whitton, both CSRF directors.
Is stress related to Cushing’s?
Dr. Vance – If the question is, does stress cause Cushing’s, the answer is no. What I tell my medical patients about stress, is that stress is what gets us up in morning. My goal is get a 24hr urine sample on all of the NFL football players before the Super Bowl game. Their levels will be above the ceiling. I don’t mean to downplay the importance of stress, but many people who have never had Cushing’s have elevated cortisol in stressful situations. Cushing’s is defined as the consistent elevation of cortisol.
Dr. Ioachimescu – I have had numerous patients tell me they experienced Cushing’s symptoms after a stressful situation, but I cannot connect the dots based on the literature published on this topic. My personal opinion is that stress might be a contributory factor to worse symptoms, but it doesn’t appear to a significant player. This is unlike autoimmune disorders where the temporal relationship with stress has been better described.
How do you tell when you got Cushing’s? Cushing’s was first mentioned to me because of my appearance during my 20’s, but I wasn’t diagnosed until my 40’s. Is it possible to have it that long?
Dr. Ioachimescu – Usually patients don’t get all the symptoms that one can find in a text book . Also, each patient is different, so presentation can vary in timing and severity. However, 20 years between someone thinking about this diagnosis and actually getting a diagnosis, seems a bit long to me. Twenty years of untreated Cushing’s will likely lead to very serious medical problems such as muscle weakness, broken bones, kidney stones, diabetes mellitus and other complications. Cushing’s syndrome speaks up and makes its presence known in a few months or years.
Dr. Vance – Based on appearance, I can’t tell when a patient walks into my office, whether she has Polycystic Ovarian Syndrome (PCOS) or Cushing’s. I can speculate, but I don’t know before I do the testing. There is so much overlap in what they look like. There are some text book cases where a patient has the big round red face, big supraclavicular fat pads on the neck, big dark purple stretch marks, losing their muscle strength, etc. where Cushing’s can be more obvious, but in most cases, you can’t tell by appearance. PCOS is more common, affecting about 8% of women of reproductive age. Patients can sometimes look back and pinpoint when certain symptoms started. I agree that 20 years is a long time.
Could you address the subject of cyclical Cushing’s? I have a daughter who has a pituitary tumor and a number of Cushing’s symptoms, but her tests always come back normal.
Dr. Ioachimescu – I can tell you what the term cyclical Cushing’s means to me: biochemical tests for Cushing’s are abnormal at times and normal at other times. Usually there is a window of a few weeks or a few months where cortisol is found elevated. Usually the patients themselves also recognize when they are entering one of these phases. I usually tell them to call me and have a night time salivary cortisol checked at home. This is my understanding of this very controversial and ambiguous term. One should have some biochemical test to show Cushing’s during a time when they are not feeling well. If the testing is always normal, I have a problem calling it cyclical Cushing’s.
Dr. Vance – First, let’s go back to what we know about these tumors. We know that not all pituitary tumors actively produce anything. Pituitary tumors that secrete hormones are what we call autonomous; they work on their own and are not usually subject to normal regulation. The most important term here is “the consistent overproduction of cortisol”. That is the definition of Cushing’s. Even in a patient who has Cushing’s due to an ACTH secreting tumor, there is variability in the amount of ACTH produced in any given 24hr period. So if you get five 24hr urinary cortisol measurements, maybe only 3 are elevated. That’s not cyclic Cushing’s, but rather normal variation. I think the term cyclical Cushing’s has been way overused and I have argued this with many endocrine colleagues. I think the term is often used by patients who have normal tests, but really want to have Cushing’s. Consistent overproduction of cortisol as demonstrated by 24 hr urine, over-night dexamethasone, or salivary tests is how you define Cushing’s. I know that may sound harsh, but patients can have a very strong belief that they have Cushing’s, they come to us, tell us they think they have Cushing’s and we evaluate them. The problem is that there are many things that look like Cushing’s, but aren’t. So to me, the diagnosis is consistent overproduction of cortisol.
Patient – I was diagnosed with cyclical Cushing’s due to an adrenal tumor. I did notice that my symptoms came and went. The best thing I did was keep a journal of my symptoms so that when I saw my doctor, we could discuss it. A doctor at NIH is looking at cyclical Cushing’s using hair samples and I was part of that protocol. (See Clinical Trials and Research pages – included in protocols 97-CH-0076 and 00-CH-0160)
I’ve heard that once you have Cushing’s you always have Cushing’s, is that true?
Dr. Vance – I disagree with statement. Once you have Cushing’s, you may still have some of the long term effects due to Cushing’s, but that’s not Cushing’s. It’s a consequence of having had Cushing’s that was treated successfully. I don’t want people to label themselves as still having Cushing’s when they don’t. I think that is a disservice to those patients.
Dr. Oyesiku – I agree completely. If you are in remission you don’t have Cushing’s. Of course you do need to be followed just in case there is a recurrence.
Are there any guidelines for tapering replacement medications?
Dr. Ioachimescu – As far as tapering, there are 2 components to this process. The first is seeing your endocrinologist to discuss how you are feeling and keeping track of the physical parameters which should be improving. The second component consists of blood tests done some time after the last dose of hydrocortisone to determine how much cortisol is being made by the body. Following surgery, some patients are discharged on higher than physiologic doses for a while, then we calculate the approximate physiological replacement dose based on their body surface area. However, the most important part of the taper is how the patient is feeling. Often patients come back and say they have lost a lot of weight, they are very tired, dizzy when they stand up and have blood pressure readings in the 80’s and 90’s with no blood pressure medications on board. If the replacement dose is lower than physiologic and cortisol is still undetectable, then the taper is too quick. So, what we do is increase it for a while. There is not a reason to rush. On the other hand, there are patients who say, “I’m not losing weight and the stretch marks and easy bruising are not getting better”. If this is a tiny person taking 20mg in the morning and 10 mg in the afternoon, they are probably being over-replaced. In this situation, we will taper the dose and the patient usually feels better. It’s a matter of a patient communicating with the doctor to determine what dose is appropriate for that point in time. There is no algorithm that works for everyone.
Dr. Vance – We don’t have an algorithm, but we do have a policy. When a patient has surgery and the cortisol goes to less than one, we are ecstatic. In the old days, when I was more naive, I used to send people home on 20mg in the AM and 10mg in the PM, which was the standard at that time. Of course patients were calling me back 5 times a day telling me how terrible they felt. Then a light bulb went on and I realized that you cannot take someone from a very high cortisol level down to a normal level, immediately, because they are going to get steroid withdrawal and feel worse. So generally, we send them home on a higher dose for at least 4 weeks, then we go down to maybe 20 mg in the AM and 10 in the PM. When they come back for an appointment 8 weeks after surgery, we reassess them off of hydrocortisone replacement for 2 days. Two days off of replacement does not cause adrenal insufficiency because your body still produces aldosterone, which is an adrenal hormone that regulates blood pressure, sodium and potassium. It is not dependent on ACTH. While the replacement medication is being withheld, you may feel weak and not well, but this does not result in adrenal insufficiency. A taper should be gradual decline. There is not one regimen that fits everybody.
Do pituitary Cushing’s patients have pituitary surgery or brain surgery?
Dr. Oyesiku – So, technically it is brain surgery. If you look at the boundaries of the brain; the bone, the dura, etc., the pituitary is attached to the brain by the stalk and it sits in the cranial vault, which is where the brain sits. Yes, part of the pituitary tissue arises from the gut during development, but the pituitary has 2 parts to it, the anterior and posterior. The anterior part arises from the gut, but the back part has nerve connections that come from the brain. So, I don’t know what else you would call it. You wouldn’t call it ENT surgery and neurosurgeons do pituitary surgery. So technically it is brain surgery, but it’s not brain surgery in the sense that you need to go through the brain or into the brain.
Dr. Vance – I agree 100%, but I prefer the term pituitary surgery. I don’t like to use the term brain surgery because people get the wrong idea. When you think of brain surgery, or a brain tumor, the biggest concern is of brain cancer. So, I use the term pituitary surgery. Of course we do know that the pituitary gland hangs off the brain tissue, but it’s not the same as a brain tumor cancer. So I prefer to call it a pituitary surgery, but it is done by a neurosurgeon.
Are there tests for cognitive function and exercises that could lead to improved function?
Dr. DeFife – For those types of questions, you would want to find a neuropsychologist. Neuoropsychology is a specialty that uses specific tests to determine cognitive function, such as memory, attention, something called executive function and performance. They can help you develop a picture of what particular areas are affected. They can evaluate your performance as some of your function may fall in normal ranges, but there may be focal areas that were affected. They can also help you develop strategies to deal with those areas.
Dr. Vance – At UVA, we work with our neurospychologists all the time. Just be prepared that the testing takes about an entire day. It’s a big deal; not just 36 questions.
Dr. DeFife – Also, it is designed to be frustrating. It is designed to take you to the limits of your performance. So, during that whole day of testing, you will be tested at and past your limits. It can be frustrating that you are at your performance limit, yet they are pushing you to do more, but this is how they determine your limits. These tests do a good job of measuring your performance.
Patient: I looked at some Alzheimer’s books and found that games can be useful. So, I play games with my son. It’s probably a lot cheaper.
Karen: Along that line, a number of years ago, there was an article in the CSRF newsletter by Dr. Fava from Italy, who answered a question about concentration. (http://csrf.net/doctors-articles/recovery/answers-from-a-psychiatrist/) He pointed out that for a number of years those with military jobs have had a physical job that didn’t include studying and reading. When their service time was over, they tried to return to school, but experienced concentration difficulties because they were out of practice. While Cushing’s is distinctly different, we also haven’t been using our brains much, and practice can be useful. Dr. Fava suggested “reading, doing puzzles such as picture puzzles, crosswords, and math puzzles, or memorizing some of your favorite quotations, or other things that you find interesting.”
Do you work with psychiatrists? I seem to have difficulty getting my psychiatrist and endocrinologist to communicate.
Dr. Vance – I work with psychiatrists all the time. There are psychiatrists that are very interested and work with my patients, but it’s more than just giving someone an antidepressant. Insurance companies do not like to pay for psychotherapy, which can be very beneficial.
Dr. DeFife – Coming from the psychology side of things, while psychiatry can play a role, I think it is most useful to have a psychologist on board. If you look at the American Psychological Association reports, psychotherapy is effective for a variety of conditions. There is a thought out there that you can give someone an antidepressant and they will get better, but that doesn’t happen with this disorder. Psychotherapy is important and underutilized. There isn’t really an advocacy group for psychotherapy the same way there is with the pharmaceutical companies and antidepressants. The evidence is there that psychotherapy can be as affective and longer lasting than psychiatric medications. Another thing with communication is that our medical system isn’t set up with teams of doctors. Our system grew up around fee for service models where doctors developed specialties. Health care is now moving towards a team care approach where you would bring doctors from different disciplines together to work together on specific issues, but this is slow to happen.
My recovery is taking a long time. Is this normal or should I fuss at my endocrinologist?
Dr. Vance – There is not magic bullet. There is such a spectrum of recovery. Most of our patients say it takes at least a year.
Dr. Oldfied – But that is not everyone. Some patients take 2 years or even longer.
Dr. Ioachimescu – Everyone is different. But, you need to identify the problem should there be one. Fatigue is a very vague term with a variety of causes. You should talk to your endocrinologist because I think endocrinologists usually go beyond what the lab results say. You aren’t the only patient who says ,“My labs are perfect, but I don’t feel well”. You should ask your endocrinologist to communicate with your primary care physician to make sure everything else is OK. If everything else is OK, perhaps it’s time to move towards neuropsychological testing or psychotherapy. This way, you often find out something about yourself that you don’t know and that can help you cope better with the situation.
Could you comment on gastric bypass surgery for Cushing’s patients in remission who have not been able to lose weight?
Dr. Vance – This is not something to be taken lightly. We and other centers have seen patients with Cushing’s who had gastric bypass surgery before they were diagnosed. Needless to say, it wasn’t very successful. Basically if you go to Midus, you get a muffler, if you go to a bariatric surgeon, you can get gastric bypass surgery. There is nothing wrong with that. However, it is a lot safer to do it with a program, such as Weight Watchers, and exercise. Gastric bypass surgery is not a walk in the park and there are significant risks of complications.
Dr. Ioachimescu – After successful treatment of Cushing’s has been documented, I always recommend life style changes to improve weight. I highly recommend some type of a supervised program because it keeps the patient motivated. Without supervision, most people don’t have the discipline to stay the course. You could choose to work with a nutritionist, a personal trainer, or even just an app on your phone that keeps you aware of what you are doing. I do not prescribe any of the weight loss medications that are on the market today. I do not think they are worth the risks and I think they do very little. Gastric bypass is something to consider if supervised diet and exercise have not worked, but there are no studies on outcomes of gastric bypass surgery in cured Cushing’s patients.
Patient – This is just very frustrating. I feel like someone took my car and wrecked it and I’m the one who has to fix it. I’m trying, but I feel like I have to work twice as hard to lose weight and that’s what makes me angry. I know it will take hard work but it’s an emotional thing as well as a physical one.
Is there a good way to talk to your doctor so that you are heard?
Dr. DeFife – I’m so glad you asked that question. I go through that too whenever I go to a doctor’s office. How do you get them to take you seriously? I have a couple of thoughts. One, have a family member with you at the appointment because you get looked at differently. I have seen this. I think physicians are well intentioned, but we all know there is a difference. Second, track your symptoms. If you have a list of symptoms that you track, you can say that during this period of time, this was fine for me. Now, during this period of time, this is how I’m feeling. (Editor’s note: there is a symptom tracker for Cushing’s on this website.) If you are concerned about quality of life issues there is a questionnaire on-line called the Schwartz Outcome Scale or SOS 10, that you can use to track quality of life. (Editor’s note: SOS 10 description, SOS 10 questionnaire) With the symptoms and the time frame in front of them, not only do they not have to ask you the questions, but I think with something like that, you are more likely to be taken seriously, particularly with a condition like Cushing’s. Another thing is know your doctor when you are doing well. Then they will get to know that you are not just a person who always comes in with complaints. Otherwise, they see a patient with complaints that they do not have a relationship with. If you have an established relationship, then they can tell that changes are taking place because that trusting relationship is already in place.
Coming in to a physician’s office prepared and dressed professionally can make a difference. That goes with having a list of questions, having someone with you, handling the appointment in a professional manner and being kind and warm. The onus shouldn’t be on the patient, but it can help.
I feel like my Cushing’s is back, but I’m getting push back from my doctor, who doesn’t seem to want to order any tests. What should I do?
Dr. Vance – I am a physician who tells my patients that if Cushing’s comes back, they will probably know it before I can prove it with tests. I always test whenever a patient tells me that they think it is back. There is no reason not to. No physician wants to miss something. Perhaps you are seeing the wrong doctor.
Dr. Ioachimescu – Same with me. I don’t think you should be getting the push back. We as endocrinologists ask patients to come back even if they are feeling well and especially when they aren’t. I always tell my patients that if something comes up between appointments, let me know. With all the electronic ways that I can communicate with patients, if I get a “worry” message from one of my Cushing’s patients, they could come to see me next week.
Dr. Oyesiku – If you get push back on your care, just remember you have a choice. You pay for your health insurance, it’s yours and you should be able to use it. If you get push back from your insurance company about getting a second opinion, jump up and down and stamp your feet at them. Don’t settle for less. One thing I’ve learned is that sometimes physicians don’t want to say they don’t know. We’ve been taught all this stuff and sometimes we think we know everything, but we don’t. If you get push back after having had Cushing’s, it’s probably time to seek a second opinion. The other thing is that if I notice that I am not listening or communicating with a patient, it’s time for me to put myself in that patient’s shoes, because at that point you start seeing things in a slightly different light.
Do you have suggestions for patients who do not live close to a major endocrine or neuroendocrine center?
Dr. Ioachimescu – Start with your primary care physician and see if there is a local endocrinologist. Then have that endocrinologist contact a major center and see where that takes you. You might make plans to travel just once in a while, perhaps not for all your endocrine care. The key is communication between your local endocrinologist and the endocrinologist at the major center. These days, electronic communication make things a lot easier. We owe it to you to communicate with you and your local doctors.
Dr. Vance – I agree completely. We see so many patients that I can’t provide day to day care for all of them. So I do work with the patient’s local endocrinologist or their primary care doctor if they don’t have an endocrinologist. One thing I do recommend is to see your consulting endocrinologist at least once a year. I have patients that were operated on 10 years ago, but they still come back every year just so I can keep my eye on them. If they are on special treatments, I usually see them twice a year. Both UVA and Emory are tertiary referral centers and we are there to support other physicians.
The lack of identification of Cushing’s patients by medical professionals astonishes me. What’s being done to increase awareness of Cushing’s among primary care physicians and internists?
Dr. Ioachimescu – One of ways Emory is trying to increase awareness is through Continuing Medical Education (CME) programs. Doctors are mandated to take a certain number of CME hours per year to keep their licenses up to date. We have put the focus on the pituitary and we invite our colleagues back periodically. Then, there is something called the Internal Medicine Board Review course. Internists and all physicians are required to re-certify in their specialties.
They usually take recertification courses before the exam. I am one of those who talk about the pituitary and adrenal glands during the recertification courses where they also hear about the heart, lungs, etc. Also, my Internal Medicine Grand Rounds topic was about the pituitary gland, which exposed my university colleagues to the issue. I’m not sure that the problem is completely about awareness. Cushing’s is a rare disorder and I think the medical community is still at the point where they see diabetes, which is very prevalent and have only heard of Cushing’s, which they rarely see. They need to think outside the box and generate a referral to a specialized center when needed. One of the things that we are trying to teach the internists, is that they don’t need to go all the way through the testing and understand all the subtleties. What they need to do is to communicate with an endocrinologist. And you are correct, I’ve found Internists and family practitioners a little less prepared to do that compared to gynecologists (OBGYN), who seem a little more in tune with endocrine issues and will refer patients to us.
Dr. Vance – Those of us on this panel are in academic medical centers and our job is to teach. We start with medical students, interns, residents, fellows and we do our best. I agree that general physicians really don’t know what to look for unless they come to one of our centers for some type of program. In my experience, the OBGYN community diagnoses PCOS and they don’t necessarily pick up Cushing’s very often. To increase awareness, we give conferences. So, it’s not lack of awareness, I think it’s a lack of sensitivity to the issue. Because again, when you are seeing 30 patients a day and two thirds of them are overweight, another third are depressed, and 25% have diabetes, it’s hard to put Cushing’s together.
Louise – Patients are still waiting years for a diagnosis. I think the key is increasing public awareness. We need to be out there on 60 Minutes, on Dateline, etc. Any article that makes it into a major newspaper, greatly increases the number of phone calls and emails we get.
Dr. Ioachimescu – We have tested our referral patterns and we have had a lot of warranted self-referrals in patients with Cushing’s. Increasing awareness in the public domain is very useful, but sometimes your insurance company will not let you see a specialist if you are self-referred.
Patient – My story was in the CSRF newsletter and now that I have my story all printed out, every time I see a medical professional, chiropractor, dentist, etc., they get a copy of it. This is my way of trying to make them more aware.
What do you think about internet information?
Ellen – In my mind, internet information for rare diseases is a blessing and a curse because there are websites that will give you really good, reliable information, which is what the CSRF aspires to do. But, there are a lot of websites out there that do not accurate information. I also think that Cushing’s patients who are very sick, very frustrated, can’t sleep and are on the internet all night searching for a solution, are particularly vulnerable to misinformation. You want that magic diet, that magic supplement, that magic thing that is going to solve the problem. But, remember what your Mom probably said, “if it sounds too good to be true, it probably is”. If you are taking any kind of supplement or making any radical diet changes, be sure your doctor is aware of it, as some of these things can have bad interactions with your prescription medications. We do get correspondence from patients who are doing some strange things that have no medical basis in an effort to cure themselves. Keep in contact with your doctor. If you find things that you want to ask, go ahead and ask but there are people who are very willing to empty your wallet for you. So, be careful.
Dr. Vance – I want to tell you a true story. There was a TV commercial that advertised a supplement that could get rid of abdominal fat and they make it look like Cushing’s. So I looked at the ingredients in it and it was magnolia bark, from magnolia trees. I now have a retirement plan; I have a huge, huge magnolia tree in my backyard and I’m going to get my residents and fellows to come and scrape the bark. What is in magnolia bark that will make you lose weight? Absolutely nothing!
Dr. DeFife – If you are doing a google search, you are going through some emotions. You are bored, frustrated, or you feel disconnected. That time would be much better spent away from Goggle by tracking your symptoms or reconnecting with your life. You may be really scared, but the time is better spent by acknowledging your feelings and getting some support from someone.
Louise – The thing is, if you have Cushing’s and don’t know about it, you are desperate and awake all night, so you have time on your hands. I can really see why patients spend hours searching on the computer.
Dr. Ioachimescu – When you search things on Google, there are pages that come up and there are several ways to make sure that someone is on the first page of results. One often used tactic is to pay to be listed first.
Louise – There are number of Cushing’s chats on-line where people who are or aren’t diagnosed offer their suggestions on medical issues. I want to caution everyone. Don’t take advice from other patients; you need to speak with your physician.
Ellen – Another word of caution about websites where patients post. It is often the sickest patients who post the most. So you may read about one very drastic scenario, and immediately think, this is what is going to happen to me. In reality, that is one individual’s, perhaps very unusual story, but it can be frightening and discouraging. The people who have one surgery and get better, are less likely to be out there posting continuously. Everything on the internet was put there by someone, so ask yourselves, “Where did this come from?”
Have you seen an alteration of personality in patients who have had surgery?
Dr. Vance – First you need to define personality versus personal responses. Personalities are not different, but emotional aspects and mood changes are part of the recovery process.
Is Cushing’s hereditary?
Dr. Ioachimescu – yes, Cushing’s can be hereditary, but this is EXTREMELY rare.
Dr. Vance – That said, I treated one of my patients and his daughter, both for pituitary Cushing’s. That kind of transmission is EXTREMELY rare. In growth hormone producing tumors, there are specific genetic defects that run in families. When we talk about hereditary pituitary tumors, it’s mostly thought to be multiple endocrine neoplasia type 1. That means pituitary, parathyroid and pancreatic tumors. But in a large study by the Mayo Clinic, only about 3% of patients with any type of pituitary tumor had MEN 1. But, we may be finding out more in the future, like we now know about the genetic defects in growth hormone tumors.
Attention Deficit Disorder (ADD) runs in my family. How can I tell if my inability to focus is ADD or related to Cushing’s?
Dr. Ioachimescu – You need to work with a team of professionals with the endocrinologist, psychologist and neuropsychologist all doing their part.
Dr. DeFife – With ADD, if you walk into someone’s office and they diagnose you with ADD and give you a stimulant without doing any testing, walk out, especially if it’s your child. Go to a neuropsychologist who can do specific testing for ADD. Attention and concentration difficulties have a variety of causes, but there is specific testing for ADD involving computerized tests that measure attention.
Could you comment on DHEA supplements for cured Cushing’s patients?
Dr. Vance – DHEA is an adrenal hormone that is a weak male hormone (androgen). It’s been studied in women to increase libido or sex drive. The problem is that DHEA is not a drug. It is a food supplement not subject to FDA regulation. So, you go to a health food store and you buy a bottle of DHEA that says it contains 50 mg, but you have no idea what you are actually getting. They only way you know, particularly if you are a women and you are getting too much of it, is that you will get a beard and acne. There have been some nice studies, particularly in women for libido, but here in the US, you don’t really know what you are getting.
Are there any best practices for managing the transition of going back to work and dealing with mood changes, cortisol replacement and fatigue?
Dr. Vance – The most important thing is taking your medication as prescribed. I preach that if you are on hydrocortisone replacement, you should take it first thing in the morning on awakening and not wait until breakfast. Also, you should not take it past 6 PM or you won’t sleep. Even though those instructions are written on my prescriptions, patients don’t always follow my directions. Number one is making sure that you are on the right medications and getting a good night’s sleep. There is no magic formula; it’s patience. You are steps ahead of others because you are aware of your symptoms and what they might mean, which I think helps people cope with the recovery process.
Can I take my replacement hydrocortisone and my thyroid medication at the same time in the morning?
Dr. Vance – Yes, you can take them together, but not with calcium.
Are there triggers for Cushing’s?
Dr. Oyesiku – No, we don’t know of any.
Dr. Vance – No, I don’t think we know of any. In diabetes, the triggers can be genetics and obesity.
If my performance drops when I return to work, what can I do to protect myself?
Dr. Vance – If my patients let me know that they need to go back to work part time rather than full time, I will write a letter explaining their limitations. There is a recovery period, which takes an unknown period of time, but, with successfully treated Cushing’s, I don’t put them on permanent disability.
I have diabetes insipidus and have had a bilateral adrenalectomy. Sometimes it’s hard to tell if my sodium is low or my cortisol is low. Have you heard anything the taste in your mouth being different?
Dr. Vance – First, you do have a challenging situation. With diabetes insipidus, you need to take medication to keep your urinary output and keep your sodium normal and with no adrenal glands, you have to take 2 hormones, one to keep your blood pressure and sodium and potassium normal, and your cortisol replacement. After pituitary surgery, about 10% of patients develop low sodium, but it’s very temporary. Their symptoms are the same as those patients with low cortisol. Usually its fatigue, headache, nausea, and sometimes vomiting, but we can’t tell the difference as physicians until we have sodium and cortisol test results. But, patients may have some subtle way to distinguish between the two.
Dr. Ioachimescu – You should have a set of labs including how concentrated the urine is so there should be a way to distinguish pretty rapidly. Notice your urine output and caffeine intake, or really anything that is high is water content, like watermelon.
Dr. Oyesiku – I think it was earlier this week, where there was an article in the Wall Street Journal that said about 20-25% of symptoms that patients have are unexplained. So it may be that what you taste is unexplained, comes and goes and is related to something, but we don’t know what. A medical professional may say I’ve never heard that, but it is real to you. Maybe it’s something we just don’t know yet.
Does Cushing’s cause white spots in the brain?
Dr. Oyesiku – So white spots in the brain, they are called UBO’s or unidentified bright objects, which is really the neuroradiological term. As we all get older, we are all entitled to a certain number of UBO’s. It reflects aging of the small blood vessels in the brain. So the radiologist may have looked at your MRI and compared it to one that was several years ago and found more UBO’s.
Is the diabetes associated with Cushing’s type I or II?
Dr. Vance – Usually the diabetes associated with Cushing’s is Type 2. What it means is that you are making insulin, but not enough. So you will need medication to control your sugar. With Type 1, your pancreas doesn’t make insulin. After cure of Cushing’s the diabetes can go away, or at least get much easier to control and be treated with fewer medications.
I’ve heard that Cushing’s also occurs in horses and dogs. Is this true?
Dr. Vance – Yes, Cushing’s is more common in horses and dogs than in humans. With horses, their tumors are actually in what is called the intermediate lobe of the pituitary. Humans don’t have much of an intermediate lobe at all. And, they respond to medications, such as cabergoline. Why they get it, I don’t think anyone knows. There is a drug, called retinoic acid, that has been studied in dogs. It cured all the dogs in the study. It has also been tested in Italy in humans, and about half of the patients got better. It’s supposed to turn off the switch that controls ACTH, but we do not have access to it here in the US. It’s also known that cats get pituitary tumors that secrete growth hormone.
After pituitary surgery, my cortisol levels didn’t come down for about 2 months. I don’t have any pituitary gland left, but my cortisol is normal. How can that be?
Dr. Vance – You could have had some residual tumor that self-destructed. We call that infarcted, meaning it self-destructed. If you are being followed and everything is normal, then that’s great! I tell my patients that I can’t do better than normal.
Does it make sense that even after being cured from Cushing’s, that I still have diabetes and high blood pressure?
Dr. Ioachimescu – Both high blood pressure and diabetes can run in families. But if you have secondary hypertension, which is what we call it if it is caused by something else, like Cushing’s, the vessels can get a little stiff if blood pressure has been high for a period of time. Once the vessels get stiff, it’s hard to undo the damage. It’s a fairly common situation that the hypertension persists, but it usually gets better and easier to control. It’s the same with diabetes. If the pancreas is worn out from making so much insulin over a long period of time, it’s hard to completely reverse that, but again, it usually gets better and easier to control.
I had both adrenal glands removed, so do I now have Addison’s disease?
Dr. Vance – Addison’s goes back to Thomas Addison who described adrenal failure in the 1800’s. In the 1800’s, you couldn’t order a blood test, but he described people who were very ill and were dying because their adrenal glands weren’t working. Then, this was primarily due to tuberculosis destroying the adrenal glands. There is also another use of that term which is called autoimmune adrenal failure. That means that the body destroys its own adrenals. If someone has their adrenals removed, the correct term to use is adrenal insufficiency, not Addison’s.
Dr. Ioachimescu – President Kennedy had the autoimmune version of Addison’s.
What is Nelson’s syndrome?
Dr. Vance – Years ago we didn’t have tools like MRI’s to visualize the pituitary gland. Thus, the solution was to remove the adrenals. The pituitary tumor was there, but there wasn’t a way to see it. Remember that pituitary tumors can be very small. But, if you take out the adrenal glands, the tumor can grow big. That is called Nelson’s. People with Nelson’s have a very deep tan.
How concerned should I be about a pituitary tumor returning?
Dr. Oldfield – One of the reasons I like using the technique of the tissue envelope is that I can be pretty confident that all of the tumor is entirely out. If I work around the edges, I can see if there is invasion of the surface of the pituitary gland and the lining of the sella. Most patients don’t have a recurrence of Cushing’s Disease, however only time will tell. To a certain extent the percentages change depending on how low your cortisol went after the surgery. If it went to really low levels, that’s a pretty good sign.
When do you use medical treatments for Cushing’s?
Dr. Vance – In our center, we use medical treatments in patients with failed pituitary surgery, but we usually combine that with focused radiation treatment, knowing that no form of radiation is effective immediately. So, we use medications to control Cushing’s while waiting for the radiation to become effective. The time that it takes for radiation to be effective is highly variable. We stop the medication periodically to assess cortisol production.
Dr. Ioachimescu – We do same thing.
How do you distinguish between PCOS and Cushing’s?
Dr. Vance – Again, you can’t tell by a physical exam as there are so many similarities, not identical, but similar. Of the 3 screening tests for Cushing’s, (24 hr urine, overnight dex, and salivary cortisol), they are about equally reliable at 92-94%. One is not better than the other, they all have limitations which is why as pointed out earlier, you may need to have several tests done. For PCOS, there are some subtle parameters about the pituitary hormones FSH/LH that we measure. We often measure the male hormone testosterone, but that can be elevated in people with Cushing’s as well. PCOS is much more common in women of reproductive age, not in a 60 year old, than Cushing’s. So we like to rule out Cushing’s based on the urine test and the salivary test or dex test. If those come back normal, then we pursue treatment for PCOS because that is a large source of infertility and a lot of these young women are trying to become pregnant.
Does high job stress after having had Cushing’s, bring on more symptoms?
Dr. Ioachimescu – A very high stress job is never a good thing whether you have had Cushing’s or not. Keep in mind that cortisol and adrenalin are stress hormones that you need to battle stress. If you need to fight that battle over and over again, for days or months in the workplace, things are not going to be good. For a while, you can take it, but over time it becomes detrimental regardless of whether you have had Cushing’s or not. If you notice new symptoms or symptoms similar to what you experienced when you had Cushing’s, you should see your endocrinologist. Don’t immediately blame it on job stress.
Dr. DeFife – From the psychologists perspective, we look at Cushing’s as a medical problem that effects your mood and your functioning from day to day, but cortisol and adrenalin can also increase in interpersonal interactions at work or at home. And, we know that interpersonal stress can affect our bodies. So, it’s a medical condition that needs to be taken seriously, however, you also need to take your life seriously. What’s the difference between stress that increases performance and what is detrimental? We all need a little stress to increase performance, like today on this panel, we are probably all a little nervous. And that kind of stress is helpful to performance. But, there is a point where that effect tapers off and too much stress and anxiety begins to negatively influence performance. Then we get what is called work burnout, which is a syndrome that looks like you are emotionally exhausted. From day to day you feel fatigued, it’s hard to get anything done, you feel just worn out, overwhelmed, and experience a general feeling of lack of personal accomplishment. You go to your job every day, but you don’t feel there is meaning there or that you are contributing or being productive. There’s also a sense of isolation and distance from people. That’s when you know that it’s time to see your doctor and also to figure out what you can do to better your situation, increase your meaning and your sense of connection with others. It may mean saying no to things, which is difficult for most of us to do.
Why is gamma knife or radiation not considered as a treatment option before surgery?
Dr. Vance – While it is less invasive, radiation does not provide a cure immediately. We have looked at our series of Cushing’s patients and 70% of those treated with gamma knife achieved a cure, meaning normal 24hr urinary cortisol, but the average time for that to happen was 13 months. Some were cured earlier, but some much later. In addition to that, 15% of those who went into remission had a relapse. So we never use radiation as a first line treatment.
Drs. Oyesiku and Oldfield – No, we have not used radiation as a first line treatment.
Dr. Ioachimescu – In the hands of an experienced pituitary surgeon we should have an immediate cure in somewhere around 85 to 90% of patients. Granted there are some risks with anesthesia and complications, but the best data we have with radiation is somewhere around 70%. So, a greater number of patients are cured by surgery and it is immediate, rather than taking a year or more to achieve normal levels.