CUSHING’S SYNDROME: When Too Much Is Too Much

By Ahmet Bahadir Ergin, MD

Have you ever heard of Cushing’s syndrome? As a physician, I hear from people that their dog got it somehow. But this disease can happen in humans. Which leads to the question: what is Cushing’s Syndrome?

Significant weight gain in a short time, round face, excessive body hair, pink or purplish stretch marks, maybe a fat pad between the shoulders, easy bruising, or weakness in your thighs or arms. These are some symptoms of Cushing’s syndrome. Frightening isn’t it? In addition, flushing of the skin, excessive hair growth, and weight gain with abdominal distension (bloating) often occur. What about high blood pressure, elevated blood glucose or osteoporosis that developed relatively fast when you were otherwise healthy? These are also conditions that accompany Cushing’s. Additional features of Cushing’s syndrome can occur, such as irregular periods in women, decreased sex drive in men, acne, slow healing of cuts or wounds, frequent or unusual infections, depression, psychosis, headaches and visual disturbances.

Cushing’s syndrome is the result of elevated hormone levels in the body, specifically a hormone called cortisol. Cortisol is a very important steroid hormone produced in our adrenal [u-dree-nal] glands, which is a gland that sits on top of each of the kidneys. It helps us regulate our blood pressure, blood glucose (sugar), immune system and strength. But too much of a good thing is not so good, as excessive cortisol can lead to serious health consequences such as hypertension, diabetes and osteoporosis. Most of the time the detrimental effects of cortisol are gradual and patients may have some or all of the features of this syndrome.

The most common reason for this syndrome is the use of cortisol or cortisol-like drugs, commonly known as steroids. These drugs are mostly used in the treatment of diseases such as arthritis or asthma. They are also used after organ transplants and with chemotherapy. Prednisone [predne-son] is the most commonly prescribed steroid.

The second reason for Cushing’s syndrome is excessive production of cortisol by the body due to a tumor in the adrenal glands. Adrenal glands are responsible for normal daily cortisol production. Any tumor inside the adrenal gland that results in overproduction of cortisol can cause Cushing’s syndrome.

A third cause of Cushing’s syndrome is overproduction of adrenocorticotropic [a-dre-no-kor-ti-ko-tro-pik] hormone (ACTH) by the pituitary gland, a part of the brain that is located at eye level in the head. The pituitary gland controls secretion of many hormones, including cortisol. A tumor in the pituitary that secretes excessive amounts of a hormone that stimulates the adrenal (ACTH) will cause the gland to secrete too much cortisol. This results in Cushing’s syndrome, more specifically called Cushing’s disease. This is the most common disease state causing Cushing’s syndrome.

A fourth cause of Cushing’s syndrome is a tumor outside the pituitary that oversecretes ACTH and stimulates the adrenal to oversecrete cortisol. This is referred to as ectopic [ek-top-ik] Cushing’s and is the rarest form of Cushing’s syndrome.

Although the severity of signs and symptoms may be much less remarkable, obesity can partly mimic some features of this syndrome. Obesity is becoming an epidemic in our country, given that 30 percent of the U.S. population is obese and 60 percent is overweight. On the other hand, Cushing’s syndrome due to a tumor inside the body is quite rare.

Diagnosis of Cushing’s syndrome can be a challenge for clinicians. Because of the difficulty making a diagnosis, if Cushing’s syndrome is suspected, your physician will usually refer you to a specialist, an endocrinologist, for evaluation.

The endocrinologist will order screening tests for suspected Cushing’s syndrome. If the tests are positive, then confirmatory tests and even further tests are obtained to determine where the cause of the Cushing’s is located. These tests may take days to complete. It is very important that patients follow instructions provided by clinicians to ensure the correct interpretation of these tests. And it is not unusual to be asked to repeat testing when the result is borderline or unclear. So be prepared to be patient!

Imaging is the final step in confirming the location of disease after biochemical tests are completed. Sometimes even imaging may not totally localize the disease. Then, in some cases, trying to find the source of the problem might require specialized testing of your internal veins to measure where the excess cortisol might be coming from.

If Cushing’s syndrome is caused by steroid drugs, then simply stopping the use of steroids may reverse signs of Cushing’s syndrome. If the disease is located in the adrenal gland, surgical removal of the adrenal tumor is indicated and may be done with laparoscopic surgery or with a more traditional surgical approach.

If the patient has an ACTH-producing tumor in the pituitary, a surgical procedure to remove the tumor through an incision through the nose is performed. The size and degree of tumor invasiveness and surgeon’s experience play a role in the success of surgery.

The cure rate is high if a single tumor is located in one of the adrenal glands, provided that the whole adrenal gland on that side is totally removed by the surgeon. When the tumor is in the pituitary gland, chance of cure is between 60 to 90 percent. The disease may recur even after many years of surgery. Thus, lifetime follow-up is necessary. When recurrence or relapse happens in pituitary tumors, alternative treatments can include repeating the surgery, radiation therapy, medical therapy or a combination of these treatments. Radiation therapy takes months or even years to work, and you may need medication treatment in the meantime. Medications used to treat Cushing’s syndrome include cabergoline [ca-BER-goe-leen], pasireotide [pasi-REE-oh-tide], ketoconazole [KEE-toe-KON-a-zole] and metyrapone [me-TIR-a-pone]. Some of these medications, however, have limitations and restrictions by the FDA in their use. What might or might not be of benefit to you should be discussed with your endocrinologist. When surgery is not possible, even initially, then radiation or medical treatment might be recommended.

Some treatment side effects that are acceptable to one patient may not even be an option for another patient. The decision is generally based on your medical team composed of surgeons, endocrinologists and radiologists and you as to best approach and with regard to your input and comfort level. The bottom line, Cushing’s syndrome is treatable and often curable. No one should go untreated due to the grave consequences of excessive cortisol for the body.

On the other end of the spectrum, those who become Cushingoid [kush-ing-oyd] during their medical treatment due to steroid drugs may experience adrenal insufficiency at the same time or shortly after stopping the treatment. During times of stress, such as when undergoing surgery or experiencing infection, if you have used steroid drugs for a long time, you may need extra cortisol.

Most of the symptoms or signs of the disease will go away after successful treatment of Cushing’s syndrome. Of course, the earlier that you are diagnosed and treated, the better the chances are for complete recovery. In the early stages of recovery, be prepared to feel aches and pains because of relative cortisol deficiency after a long period of excessive cortisol exposure. Your endocrinologist will help you balance your cortisol level for a smooth recovery. During recovery, start exercising slowly and eat sensibly to help lose the cortisol weight gain and to improve your bone density. Your endocrinologist might recommend a bone density test called a DEXA to look at whether the cortisol has had an effect on your bones. Support groups also may be helpful during the treatment and recovery process. Be sure to ask your endocrinologist about resources that are available in your community.

Dr. Ahmet Bahadir Ergin is a last year Fellow in Endocrinology at Cleveland Clinic. He graduated from Marmara University School of Medicine, Istanbul, Turkey. He completed his post-graduate training in Internal Medicine at Cleveland Clinic-Fairview Hospital. Dr. Ergin’s clinical interests include pituitary/adrenal disorders as well as thyroid diseases, including thyroid cancer. He has worked on multiple research studies related to thyroid cancer and diabetes mellitus. His studies have been published in peer-reviewed medical journals. He is also currently authoring a book about dynamic endocrine testing in endocrinology. Dr. Ergin will be joining Jackson Clinic in Montgomery, Alabama this summer.