Cushing syndrome involves persistently high levels of a hormone called cortisol.
Exogenous Cushing syndrome is caused by use of drugs that increase blood cortisol levels. The most common cause of exogenous Cushing syndrome is oral steroids, which are often prescribed for conditions such as asthma, lupus, or rheumatoid arthritis.
Endogenous Cushing syndrome results from excessive production of cortisol within the body. Approximately 60% to 70% of patients with this syndrome have a benign tumor in a specific part of the brain (the pituitary gland) that causes excess production of cortisol. This form is known as Cushing disease. Cushing syndrome can be less commonly caused by tumors in the lungs, pancreas, thyroid gland, or adrenal gland.
Although the exact number of people with Cushing syndrome is unknown, it is diagnosed in approximately 2 to 8 per 1 million people annually, typically between ages 30 and 49 years.
Common Signs and Symptoms of Cushing Syndrome
Patients with Cushing syndrome commonly develop a round face, muscle weakness, easy bruising, purple stretch marks, and fat pads on the upper back.
Other common signs and symptoms of Cushing syndrome include recent weight gain, menstrual irregularities, depression, high blood pressure, high blood sugar, excessive hair growth, and sleep disorders.
How Is Cushing Syndrome Diagnosed?
After confirming that exogenous steroids have not been used, clinicians diagnose Cushing syndrome by measuring cortisol in the urine or saliva or by checking morning cortisol levels after patients take a nighttime synthetic steroid pill. Patients typically need to undergo more than 1 of these tests to confirm the diagnosis of Cushing syndrome. Additional blood sampling techniques and magnetic resonance imaging (MRI) of the pituitary or adrenal gland can help determine the source of excess cortisol.
It is important to make the diagnosis because patients with Cushing syndrome are at increased risk of heart attack, stroke, diabetes, high cholesterol, depression, anxiety, bone fractures, blood clots, and infections and have a higher overall mortality than individuals without Cushing syndrome.
How Is Cushing Syndrome Treated?
Surgery is the first-line treatment for tumors causing Cushing syndrome. Although pituitary surgery is the most commonly performed operation, surgical techniques vary depending on the type, size, and location of the tumor.
If surgery is not feasible or effective, patients with Cushing syndrome are often treated with medication, such as osilodrostat, levoketoconazole, or mifepristone, which the US Food and Drug Administration (FDA) has approved for this condition. Other commonly used drugs are ketoconazole, metyrapone, and etomidate.
Patients who are not fully cured after surgery may also be treated with radiation therapy, which has a 92% success rate among those with pituitary gland tumors.
Typical Outcomes After Treatment of Cushing Syndrome