Cushing's Syndrome

Taking glucocorticoid medications is the most common cause of Cushing syndrome. Your doctor can review all your medications — pills, injections, creams and inhalers — to determine if you're taking medications that can cause the disorder. If you are, you probably won't need other tests.

Cushing syndrome from endogenous cortisol production can be difficult to diagnose because other conditions have similar signs and symptoms. Diagnosing Cushing syndrome can be a long and extensive process. You'll likely need to see a doctor who specializes in hormonal disorders (endocrinologist).

Your doctor will conduct a physical exam and look for indications of Cushing syndrome, such as rounding of the face, a pad of fatty tissue between the shoulders and neck, and thin skin with bruises and stretch marks.

If you haven't been using a corticosteroid medication, these diagnostic tests may help pinpoint the cause:

Urine and blood tests. These tests measure hormone levels and show whether your body is producing excessive cortisol. For the urine test, you may be asked to collect your urine over a 24-hour period. Urine and blood samples will be sent to a laboratory to be analyzed.

Your doctor might also recommend other specialized tests that involve measuring cortisol levels before and after using hormone medications to stimulate or suppress cortisol.

Saliva test. Cortisol levels normally rise and fall throughout the day. In people without Cushing syndrome, levels of cortisol drop significantly in the evening. By analyzing cortisol levels from a small sample of saliva collected late at night, doctors can see if cortisol levels are too high.

Imaging tests. CT or MRI scans can provide images of your pituitary and adrenal glands to detect abnormalities, such as tumors.

Petrosal sinus sampling. This test can help determine whether the cause of Cushing syndrome is rooted in the pituitary or somewhere else. For the test, blood samples are taken from the veins that drain the pituitary gland (petrosal sinuses).

A thin tube is inserted into your upper thigh or groin area while you're sedated and is threaded to the petrosal sinuses. Levels of ACTH are measured from the petrosal sinuses and from a blood sample taken from the forearm.

If the ACTH level is higher in the sinus sample, the problem stems from the pituitary. If the ACTH levels are similar between the sinuses and forearm, the root of the problem lies outside of the pituitary gland.

These tests help your doctor diagnose Cushing syndrome, and they may help rule out other medical conditions, such as polycystic ovary syndrome — a hormone disorder in women with enlarged ovaries. Depression, eating disorders and alcoholism also can partially mimic Cushing syndrome.

Treatments for Cushing syndrome are designed to lower the high level of cortisol in your body. The best treatment for you depends on the cause of the syndrome. Options include:

Reducing corticosteroid use

If the cause of Cushing syndrome is long-term use of corticosteroid medications, your doctor may be able to keep your Cushing syndrome signs and symptoms under control by reducing the dosage of the drug over a period of time, while still managing the condition for which you take it. Don't reduce the dose of corticosteroid drugs or stop taking them on your own. Do so only under your doctor's supervision.

Abruptly discontinuing these medications could lead to deficient cortisol levels. Slowly tapering off corticosteroid drugs allows your body to resume normal cortisol production.

Surgery

If the cause of Cushing syndrome is a tumor, your doctor may recommend complete surgical removal. Pituitary tumors are typically removed by a neurosurgeon, who may perform the procedure through your nose. For a tumor in the adrenal glands, lungs or pancreas, the surgeon can remove it through a standard operation or by using minimally invasive surgical techniques, with smaller incisions.

After the operation, you'll need to take cortisol replacement medications to provide your body with the correct amount of cortisol. In most cases, you'll eventually return to normal adrenal hormone production, and your doctor can taper off the replacement drugs. Your endocrinologist will use blood tests to help determine if you need cortisol replacement and when it may be stopped.

However, this process can take up to a year or longer. In some instances, people with Cushing syndrome never return to normal adrenal function. They then need lifelong replacement therapy.

Radiation therapy

If the surgeon can't totally remove a pituitary tumor, he or she will usually prescribe radiation therapy as well as surgery. Additionally, radiation may be used for people who aren't suitable candidates for surgery.

Radiation can be given in small doses over a six-week period, or with a technique called stereotactic radiosurgery. In the latter procedure, a large, one-time dose of radiation is delivered to the tumor, and the radiation exposure to surrounding tissues is minimized.

Medications

Medications can be used to control cortisol production when surgery and radiation don't work. Medications might also be used before surgery in people who have become very sick with Cushing syndrome to improve signs and symptoms and minimize surgical risk. Medical therapy may not completely improve all of the symptoms of excess cortisol.

Medications to control excessive production of cortisol at the adrenal gland include ketoconazole, mitotane (Lysodren) and metyrapone (Metopirone).

Mifepristone (Korlym, Mifeprex) is approved for people with Cushing syndrome who have type 2 diabetes or glucose intolerance. Mifepristone does not decrease cortisol production, but it blocks the effect of cortisol on your tissues.

Side effects from these medications may include fatigue, nausea, vomiting, headaches, muscle aches, high blood pressure, low potassium and swelling. Some have more-serious side effects, such as neurological side effects and liver toxicity.

Newer medications for Cushing syndrome include pasireotide (Signifor), given as a twice-daily injection, and osilodrostat (Isturisa), a pill. Other medications are being developed.

In some cases, the tumor or its treatment will cause the pituitary or adrenal gland to produce not enough of other hormones, and your doctor will recommend hormone replacement medications.

If none of these treatment options is appropriate or effective, your doctor may recommend surgical removal of your adrenal glands (bilateral adrenalectomy). This procedure will cure excess production of cortisol but will require lifelong replacement medications.