Cushing’s syndrome, sometimes called "hypercortisolism,” is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Cortisol is critical to health and is normally secreted from the cells of the adrenal glands in response to stimulation by another hormone called ACTH (adrenal corticotropic hormone). Abnormally high levels of cortisol can lead to many health problems, including fatigue, high blood pressure, diabetes mellitus, obesity, osteoporosis, muscle weakness, changes in mood and thinking, and other disorders.

There are two types of Cushing’s syndrome:

Endogenous Cushing’s syndrome
Endogenous Cushing’s syndrome occurs when tumors in the body produce high levels of cortisol or its precursor, ACTH. Approximately 20,000 people in the U.S. have been diagnosed with Cushing's syndrome and approximately another 3,000 people are diagnosed each year. The syndrome afflicts all racial and ethnic groups equally, although women are disproportionately affected.

Exogenous Cushing’s Syndrome
Exogenous Cushing’s syndrome occurs when steroid medications such as prednisone are given at high doses for prolonged periods of time for the treatment of another disease, such as asthma or rheumatoid arthritis. Exogenous Cushing’s syndrome was not studied by Corcept.

Cause of Cushing’s Syndrome

Endogenous Cushing’s syndrome is caused by tumors that produce excessive cortisol or its precursor hormone, ACTH (“adrenocorticotrophic hormone”), which simulates production of excess cortisol. These tumors are typically classified based on their location:

• Pituitary tumor: These are known as pituitary adenomas. Most pituitary tumors are benign but they can secrete large amounts of adrenocorticotropic hormone (ACTH), which in turn stimulates the production of excess cortisol by the adrenal glands. Cushing’s disease is the name used when Cushing’s syndrome is produced by a pituitary tumor.
• Adrenal tumor: These can be either benign or malignant. They release cortisol.
• Ectopic tumor: These can be either benign or malignant, can occur anywhere in the body (often, for example, in the lungs) and can also be very small and difficult to locate and remove. They produce ACTH, which in turn stimulates cortisol production.

Even though the tumors that cause Cushing’s syndrome are usually benign, exposure to excess cortisol can have significant health consequences and dramatically reduce the patient's quality of life.

The preferred treatment for Cushing’s syndrome is to remove surgically the tumor that is causing the disease, although surgery is effective in only about one-half of the cases.

Symptoms of Cushing's Syndrome

According to the National Institutes of Health, the primary symptoms experienced by Cushing's syndrome patients include:

• Upper body obesity, collection of fat between the shoulders (“buffalo hump”), thin arms and legs and a round, red, full face (“moon face”)
• Glucose intolerance (which can lead to diabetes)
• High blood pressure
• Weak muscles
• Persistent backache, bone pain, and thinning bones (which can lead to rib and spinal fractures)
• Depression, anxiety, changes in behavior, fatigue and headache
• Thin skin with easy bruising
• Acne or skin infections and purple marks at least 1/2“ wide on abdomen, thighs, and breasts
• Slow growth rate in children
• Increased thirst and urination
• In some women, excess hair growth on the face, neck, chest, abdomen, and thighs, and irregular or no menstruation
• In some men, decreased fertility or impotence