A frequent question to this publication is “Why did it take doctors so long to recognize that I had Cushing’s syndrome?” Cushing’s syndrome is considered to be one of the most difficult disorders to diagnose. The signs and symptoms develop slowly and may often be overlooked both by patients and their health care providers. At the time of diagnosis, most patients are thought to have had active disease for at least five years. It is not unusual for patients themselves to raise the question of whether they have Cushing’s syndrome. Often this follows reading a description of the disorder in popular magazines or in a publication such as this. When patients begin to question whether they may have the disorder, they may be faced with skepticism on the part of their provider. Why is the diagnosis so difficult?

The signs and symptoms of Cushing’s syndrome are very nonspecific. Weight gain, abdominal obesity, insulin resistance or diabetes, hypertension, and depression are among the most common reasons that people see a doctor. Cushing’s syndrome affects only about 10 to 15 people per million per year. Since 60% of the population is overweight, 3% have diabetes and 5% have hypertension, the vast majority of patients with a combination of these abnormalities will not have Cushing’s syndrome. When a doctor sees dozens of patients with a combination of these signs in any given week, it is not surprising that the diagnosis may be missed.

In my Endocrinology practice, most patients in whom I diagnose Cushing’s syndrome are referred for some other problem. Patients have been sent in for obesity, diabetes, infertility, and irregular menses, only to be found to have Cushing’s syndrome. Of course, as an endocrinologist, my index of suspicion is higher. Often the diagnosis is missed just because of its rarity. No one has thought of it. Still, most of the time, when the possibility of the patient having Cushing’s syndrome enters my mind, the patient turns out to not have it. The reality is that most overweight patients with diabetes and hypertension do not have Cushing’s syndrome. I would estimate that for every 300 patients I have screened, I have found the disorder in one. But, I would rather test 300 patients to find one case, than to not test 300 patients and miss one case. It is (unfortunately) understandable that if a physician has just tested 299 patients and all had normal cortisol levels, he may be reluctant to continue the pursuit.

As a result, it is often the patient who raises the question of whether Cushing’s syndrome exists. While many doctors will appropriately welcome the input from the patient, some will dismiss the possibility out of hand, and others will feel threatened that the patient has thought of a diagnosis before they have. What are patients to do if they think they might have it? How can they be sure that adequate testing has been performed?

In today’s health care environment, most patients will need to start with their primary care provider. Unlike an endocrinologist, the average internist or family physician is likely to see only one or two cases of Cushing’s syndrome in his lifetime. Thus, the primary care provider may not be well versed in the latest developments in testing. There are a bewildering number of tests available to help in the diagnosis: Morning and afternoon cortisol levels, 24 hour urine tests, testing the ability to suppress cortisol production, and testing the capacity to stimulate cortisol production have been augmented by midnight cortisol levels, salivary cortisol testing, CRH testing and petrosal sinus sampling. Most primary care providers can not be expected to be up on the latest developments and tests. However, the basic principle remains unchanged: Diagnosis of Cushing’s syndrome requires demonstration of excessive production of cortisol along with disordered regulation of cortisol production. As such, the best screening test remains measurement of 24 hour cortisol production. No matter how low, a random blood cortisol level is not sufficient to exclude the diagnosis. A sufficiently low blood cortisol level in the morning after taking a single dose of dexamethasone at night is also considered an appropriate test to exclude the diagnosis. In addition, since the overproduction of cortisol can be episodic, a single normal study should be repeated if the clinical index of suspicion is high.

So, if you suspect you might have Cushing’s syndrome, how should you bring it up with your primary care provider? To get the most from any doctor’s visit, be sure that the doctor’s agenda and yours match. This is particularly true when first approaching your primary care physician about Cushing’s. If the doctor’s schedule lists you for a ten minute visit to address your diabetic control, and your agenda is to discuss whether you might have Cushing’s syndrome, it will not be a productive visit. When you are scheduling the visit, be sure that the office staff is aware that there is a specific issue you wish to discuss, and ask that the purpose of the visit be listed on the doctor’s schedule. Never raise the question as a last minute thought as you are about to leave the office. If you have read an article (such as this) that you would like to share with the doctor, send it in ahead of time. Handing the doctor an article to read at the time of your visit will either result in wasting valuable time during the visit, or increase the likelihood that the article will be “filed” rather than read. In addition, avoid springing hot new information regarding the latest trends in testing. The latest medical specialty journal article or web listing may be thought provoking, but is unlikely to be adequately tested and accepted. For example, midnight cortisol testing (blood or saliva) may become the test of choice in the future, but it is not currently accepted as a substitute for 24 hour urine testing as the best screening test. You may wish to bring along a few old photographs that illustrate changes in your appearance that have occurred over time to help illustrate why you suspect the diagnosis.

Your primary care provider may send you to an Endocrinologist if the screening test is abnormal. Due to the limitation of the number of patients I can see, I usually will guide the primary care doctor through the initial screening process, and only see the patient once the screening tests are completed. The choice of a specialty provider is frequently mandated by your insurance, but in general, be sure that an endocrinologist is Board Certified in Endocrinology and Metabolism by the American Board of Internal Medicine. The Endocrinologist being a Fellow of the American College of Endocrinology is further assurance that they have proven their competency in the field. If you have a choice of several endocrinologists, you might ask your primary care physician to contact them and ask each endocrinologist if they have seen other Cushing’s patients and are comfortable handling your case.

The same principle regarding agenda holds with the specialist. If your visit was scheduled to evaluate your diabetes, be sure that the specialist knows of your concerns of Cushing’s syndrome before the visit. Be sure that all relevant data such as lab studies and prior consultations arrive before you do.

If your initial tests indicate Cushing’s, your endocrinologist may need to do further testing to locate the source of the problem, which is usually a pituitary or an adrenal tumor. These tumors are usually treated surgically. Surgery for Cushing’s disease, a pituitary tumor, is best done by a surgeon with extensive experience in pituitary surgery. Adrenal surgery can now be done laproscopically by experienced surgeons.

Occasionally a patient will have all the signs and symptoms of Cushing’s syndrome but all tests return normal. While there are unusual cases of “periodic hormonogenesis”, most of the time multiple normal test results indicate that Cushing’s syndrome is not the cause of the problem. However, if the testing is borderline, or the suspicion remains, the diagnostic process should be revisited in the future.

Author: Dr. Robert Levine, MD (Summer, ’00)

Editor’s Note: Dr. Levine is an endocrinologist with a private practice in Nashua, New Hampshire. He has been in practice for 15 years and has seen numerous Cushing’s patients during the course of his practice. Part 2 of this article on follow up visits after treatment appears in the Doctor’s Articles, Recovery section of this website.