What Is Cushing Syndrome? An Expert Explains

Cushing syndrome (also known as hypercortisolism) is a condition that develops when your body is exposed to too much cortisol over a long period of time. Diagnosing Cushing syndrome can be challenging, and it is not uncommon for patients to go undiagnosed or misdiagnosed for years. Here, Shobana Athimulam, M.D., an endocrinologist at Henry Ford Health, explains this condition and how different specialties work together to diagnose and provide individualized treatment for every patient.

How Excess Cortisol Impacts The Body

Cortisol is a steroid hormone produced by the adrenal glands in response to stress, but also plays a role in many of your bodily functions - such as regulating blood sugar, reducing inflammation and maintaining blood pressure. When you are exposed to abnormally high levels of cortisol over time, it can start to affect your body in many ways.

For people with Cushing syndrome, common signs of hypercortisolism include:

• Rapid weight gain in the face, abdomen, back of neck and shoulders
• Muscle loss in the arms and leg
• Thinning of skin (often coupled with wide purple stretch marks over the abdomen)
• Easily bruised skin
• A round, red face
• Excess facial hair in women
• Menstrual irregularities
• Low libido in men
• Fatigue

Over time, these symptoms can also contribute to increased risk for:

• High blood pressure
• Heart disease
• Osteoporosis and fractures
• Type 2 diabetes or prediabetes
• Infections
• Blood clots in legs and lungs

There are two different classifications of Cushing syndrome - endogenous and exogenous:

Exogenous Cushing Syndrome

This is caused when the body is exposed to too much cortisol from taking glucocorticoids (steroid). Glucocorticoids are commonly prescribed to treat inflammatory conditions such as asthma, lupus, and rheumatoid arthritis. They can also be used to treat joint pain and skin rashes and are prescribed following transplant to prevention rejection of a new organ. They can be taken by mouth, given as a shot, breathed in using an inhaler or rubbed onto the skin (topical).

Endogenous Cushing Syndrome

This is caused when your body makes too much cortisol. The pituitary is a pea-sized gland at the base of the brain that makes a hormone called adrenocorticotropic hormone (ACTH). This hormone communicates with the adrenal glands on how much cortisol the body should make. Endogenous Cushing syndrome can occur from one of the following reasons:

• A tumor in the pituitary gland making too much ACTH results in the adrenal glands making too much cortisol. This is the most common form of endogenous Cushing syndrome (80% of cases) and also known as Cushing disease.
• A tumor on the adrenal gland can also result in too much cortisol. While these tumors are usually benign, in rare cases, a cancerous tumor called adrenocortical carcinoma can form and result in excess cortisol production.
• "In some rare cases, people may develop Cushing syndrome when a tumor in other parts of the body (such as the lungs, pancreas or thyroid) produces ACTH," says Dr. Athimulam. "This is known as Ectopic Cushing Syndrome and these tumors are usually cancerous."

Why It Takes Time To Get A Cushing Syndrome Diagnosis

"Cushing syndrome is rare and many of the symptoms associated are common in other medical conditions. says Dr. Athimulam. "For example, if you come to your provider with concerns about weight gain or fatigue, they may not think of Cushing syndrome right away."

Dr. Athimulam recommends you talk with your primary care provider if you have signs or symptoms associated with Cushing syndrome that are persistent and progressive. Your provider will work to rule out other common health issues based on a physical examination and biochemical testing (blood work). From there, your doctor will likely refer you to an endocrinologist for further testing.

An endocrinologist will use some of the following tests to diagnose Cushing syndrome:

1. A 24-hour urinary cortisol test. This test involves collecting urine over a 24-hour period and measuring the amount of cortisol in it.
2. Late-night salivary cortisol test. Cortisol levels are typically very low at night (when you have a normal sleep-wake cycle). For this test, you will provide a saliva sample between 11p.m. and midnight to measure cortisol levels in the sample. In Cushing syndrome, salivary cortisol will be abnormally high at night.
3. Low-dose dexamethasone suppression test. This test evaluates how the adrenal gland respond to dexamethasone, a low-dose glucocorticoid. You will take this medication by mouth at 11p.m. Then, blood cortisol levels are checked the following day between 8 and 9 a.m. In a person with Cushing syndrome, the cortisol levels will remain high.

If one or more of the above tests are abnormal, your doctor may order additional lab tests (e.g ACTH levels) to confirm the diagnosis. From there, the next step is to determine the cause of Cushing syndrome, either exogenous (due to medication) or endogenous (tumor). If you aren't taking glucocorticoids, your healthcare provider may employ different scans (such as MRI or CT) to locate the tumor responsible for your symptoms.

Treating Cushing Syndrome

Cushing syndrome isn't something that you have to live with forever. Your team of healthcare providers can help you cure Cushing syndrome and improve your symptoms.

If you are taking glucocorticoid medication that is causing exogenous Cushing syndrome, Dr. Athimulam recommends you talk with the prescribing doctor about gradually tapering the dosage over time. This will help control your symptoms and allow your body to recover to a healthy amount of cortisol. Do not try and reduce or stop glucocorticoids on your own.

"When Cushing syndrome is the result of a tumor, surgery is usually the first line of treatment," says Dr. Athimulam. "Surgery to remove a pituitary tumor, adrenal tumor or ectopic tumor is effective and can potentially cure your condition."

If surgery is successful, your body will need time to adjust to a new, lower amount of cortisol. Your endocrinologist will prescribe medication to ensure your body is getting the right amount of cortisol. Over time, your doctor will taper down this medication until you don't need it anymore. This process can take anywhere from 6-18 months. Occasionally, people with endogenous Cushing syndrome, may require lifelong replacement medication after surgery.

If surgery was not successful in removing the whole pituitary tumor, radiation therapy may be utilized following surgery, or as an option for those who are not a surgical candidate.
In patients, who cannot undergo surgery or radiation, medication can be used to reduce or control cortisol levels. This can be used temporarily in patients who are very sick to help improve their symptoms and reduce risks associated with surgery.

"There are many complexities in diagnosis and management of Cushing syndrome," says Dr. Athimulam. "This condition can affect multiple bodily functions at once and require doctors in many fields (including endocrinology, neurosurgery, endocrine surgery, and radiation oncology) to treat completely. That is why it is important be evaluated and treated by a multi-disciplinary team with expertise in managing this condition."

Reviewed by Dr. Shobana Athimulam, an endocrinologist with expertise in adrenal and pituitary disorders, who sees patients at Henry Ford Medical Center - New Center One and Henry Ford Medical Center - Plymouth.