Cushing's Syndrome and Disease: Disorder that Many Times Goes Undiagnosed

MD Anderson Cancer Center
Date: 02/28/2011


Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from the University of Texas M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, our subject is Cushing's disease and also Cushing's syndrome, which are endocrine disorders that are treated here at M. D. Anderson and one of our premier surgeons in endocrinology is Dr. Nancy Perrier, she is our guest today. She is a Professor of Surgical Oncology here at M. D. Anderson and also in the section of Surgical Endocrinology. Welcome Dr. Perrier.

Dr. Perrier: Thank you Lisa, pleased to be here.

Lisa Garvin: Let's talk about Cushing's disease first. It's a disease of the adrenal gland, correct?

Dr. Perrier: Well, Cushing actually was a neurosurgeon who practiced in the early 1930's, Lisa, and he was, named Harvey Cushing and the disease is named after him. Cushing's disease is literally defined as a tumor of the pituitary gland that causes excess ACTH production, adrenocorticotropin hormone, which stimulates the adrenal glands to make excess cortisol. We refer to the disease as Cushing's disease when the tumor is in the pituitary gland as described by the neurosurgeon Harvey Cushing. Cushing's syndrome is manifestation of the disease when there is no primary tumor in the pituitary with excess ACTH production. So there is either a primary tumor in the adrenal gland itself in the cortical matter making excess cortisol or ACTH production elsewhere. So as a surgical endocrinologist who operates on adrenal glands, we treat the manifestations of the pituitary disease when it becomes incurable by pituitary resection or when the disease results from a tumor in the adrenal gland.

Lisa Garvin: What are the symptoms? Are the symptoms the same between the disease and the syndrome? And what are the symptoms?

Dr. Perrier: They are the same. The disease and the syndrome are both the result of excess cortisol. The definitions merely relate the source of the adrenocorticotropin hormone production. The symptoms of Cushing's syndrome or disease is cortisol excess, which is manifest as central obesity and by that I mean individuals who have increased body fat in their central truncal region, it's the stigmata of having striae on the abdominal wall, having weakness of the extremities, having classically patients end up with a fat pad at the posterior portion of the neck, and those are all the result of cortisol excess. Patients bruise quite easily, frequently they have hypertension, which is high blood pressure, but all manifestations of excess cortisol production.

Lisa Garvin: I do know that cortisol, you know, these glycemic diets tend to focus on cortisol. I wonder how many people out there are undiagnosed, because these symptoms are kind of generalized, I mean I have some of those symptoms, but I don't know that I have Cushing's. Is it, does it go undiagnosed?

Dr. Perrier: Yes, it can go undiagnosed. And so it requires an index of suspicion for the primary care physician to actually identify the physical findings aside from the clinical manifestations Lisa, the biochemical diagnosis can be rendered with hormonal testing, which is done through blood work.

Lisa Garvin: Now, why is this treated in a cancer setting?

Dr. Perrier: Well, the Cushing's syndrome results from a tumor of the adrenal gland. Frequently, these tumors are benign, but they require resection and often it's difficult to define whether the tumor is benign or malignant until it is resected, number one. Number two, there is an adrenocortical carcinoma which is primary tumor of the adrenal gland, which can make excess cortisol and the patient presents with symptoms of hypercortisolism, which is excess cortisol and those tumors have a grave prognosis and they can lead to significant morbidity and mortality, so the workup should be precise, it should be efficient, and it should treat the disorder both a benign and malignant in the same manifestation because we don't frequently know preoperatively the diagnosis. As a clinician, there are our index of suspicion may be elevated by patients based on the size of the adrenal lesion, based on the rapidity of the onset of symptoms, and based on the radiographic findings.

Lisa Garvin: Now let's talk about a little bit of anatomy. The pituitary gland is pretty much in the center part of your skull or head, correct?

Dr. Perrier: Correct. The pituitary gland sits in the sella, which is in the, at the base of the skull, correct, and if a tumor is present in the pituitary gland that makes excess hormone, that stimulates the adrenal glands, that results in adrenocortical hyperplasia or hyperfunction and cortisol excess and that is Cushing's disease and that tumor can be surgically corrected by a neurosurgeon resecting that tumor from the pituitary. If that surgery is unsuccessful or if the tumor recurs and cannot be resected, then we address the primary either with medical therapy or with primary resection of the adrenal glands where the cortisol is actively being produced. If the patient Lisa has Cushing's syndrome, then the tumor is actually in the adrenal glands and...

Lisa Garvin: Which sit on top of the kidneys?

Dr. Perrier: Yes. The adrenal glands are in the retroperitoneum, which is defined as that portion of the body that is behind the abdominal cavity and these glands do sit superior and on the superior posterior aspect of the kidneys.

Lisa Garvin: What are the surgical challenges of operating on the pituitary?

Dr. Perrier: The surgical challenges at the pituitary are the fact that it is a tight space and that the tumors are frequently small and the gland itself is small. The approach by our neurosurgery colleagues can be transsphenoidal, which is through the mouth, which is the most common approach to removing the primary tumor in the pituitary. When we are removing the adrenal gland tumor, and as an endocrine surgeon I operate on abdominal tumors, we can remove these glands through a laparoscopic approach, and that can be either through the abdomen or through the back. If, however, we think that the tumor is a malignancy by preoperative suggestion based on as we previously said rapid exacerbation of symptoms or criteria based on radiographic or x-ray findings, we would approach that tumor through an open abdominal anterior operation.

Lisa Garvin: Is robotics appropriate? A robot surgery for either of these?

Dr. Perrier: Lisa, we are excited about the advancements of what the robotic procedure has offered us. It is, we are capable of doing this operation with the robot and here at M. D. Anderson our practice is that we address these tumors when they are not obviously malignant through the back, through the, what we call the retroperitoneal approach. For the last three years, we have been performing these laparoscopically, and over the last 12 months, we have advanced that procedure to perform these with the robot. It is technically a superior modality in that it offers 3 and 4D magnification of the tumor. It allows significant 360 degree articulation of the instruments that we were not able to achieve with a pure laparoscopic approach. When we operate on these tumors in these cavities, we are operating with a small space and around very important life threatening structures and so precision and excellent visualization are key to successful intervention.

Lisa Garvin: And both of these are primarily surgical diseases, I mean, do they ever get follow up with chemotherapy or radiotherapy?

Dr. Perrier: If the tumor that's causing the cortisol excess, Lisa, is a malignancy in the adrenal gland, then postoperative chemotherapy, and in some cases, preoperative chemotherapy by our medical oncology neuroendocrine colleagues is certainly in order. On occasion, if we are not able to provide a complete resection of the tumor, then radiation therapy is an option, although it is less common.

Lisa Garvin: What is life like for people with Cushing's disease or syndrome if it's benign? What is life like for them after treatment? Do they have to get hormonal replacement?

Dr. Perrier: Excellent question Lisa. There are two adrenal glands that function in the body, and if the tumor is isolated on one side, which it frequently is, if it's primarily in the adrenal gland, we resect the adrenal gland and the other adrenal gland is able to suffice and to be hormonally active enough to render those patients into a hormonal status that does not require any postoperative management. On occasion, patients may need a temporary steroid taper, but long-term effects are excellent and the other adrenal is capable of being perfectly efficient.

Lisa Garvin: What about research? Are you conducting any research on to these, you know, the disease and the syndrome, any new surgical approaches or anything?

Dr. Perrier: Sure. We are promoting and advancing the safe implementation of using the robotic procedure to perform these operations, and so prospectively, we are looking at outcomes of patients who have had robotic adrenalectomy. Our medical oncology group has a longstanding history in treating adrenocortical tumors that make excess cortisol and the outcomes of medical chemotherapy in the preoperative and postoperative arena is a longstanding tradition of M. D. Anderson. Lisa, it's interesting one of our prior division heads here in the early days in the 1970's at Anderson when it was in one of its earlier stages of being a large institution, was a gentleman named Dr. Bob Hickey and he was the President of the American Association of Endocrine Surgeries in 1992 and 93 and his research was based on, and his legacy was based on his ability and his work in doing adrenal gland resection and rendering those patients with biochemical cure without recurrence. So there is a tradition here at Anderson, and it's interesting of course, as a surgeon he was one of our prior division heads and one of our leaders. And in fact, one of our large auditoriums here at the Institution is called the Hickey Auditorium named in his honor. So we do have a legacy of providing outgoing, outcomes based research and looking at surgical techniques and medical therapy of this disease.

Lisa Garvin: Now the take away message for people who may think they have this, I mean, like I said, I could probably tick off a couple of those symptoms myself including the fat pad on the back of my neck, but is there a tipping point? I mean should you have like three or more of these symptoms before you seek medical attention?

Dr. Perrier: Sure. Of course, of course, hypertension and obesity are frequent in the American population and those are the central, but the obesity that occurs with Cushing's is different than, than generalized obesity. It is a central constellation of increased girth and patients usually have thin extremities. There is a weakness associated with, which is muscle weakness of the proximal muscles. I often ask patients the question of do their arms get tired when they blow dry their hair or can they clean the ceiling fans or clean the top shelves of the kitchen cabinets, and if they have difficulty with that proximal muscle weakness, that is a sign perhaps of looking further, the addition of hypertension, of having abdominal striae, which are different and clearly substantially differentiated from the striae that may come with generalized childbirth.

Lisa Garvin: Like stretch marks.

Dr. Perrier: Yes, like stretch marks. These patients tend to bruise easily, they have thin skin, and so if multiple constellation of symptoms occur, again, the disease is not common, but I would, I would offer the advice of at least posing the question to the primary care physician.

Lisa Garvin: Great! Thank you very much.

Dr. Perrier: Thank you Lisa.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact Ask M. D. Anderson at 1877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.

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