Cushings Disease



Editors
James W. Findling, MD
William F. Young, Jr., MD



Additional Resources
Mayo Clinic
Pituitary Society

What Is Cushing disease?

Cortisol is a hormone in the body that is directly connected to the stress response. In a healthy individual, the pituitary gland releases adrenocorticotropic hormone (ACTH), a hormone that stimulates the production and release of cortisol. When an individual faces a stressful situation, the body releases additional cortisol. Sometimes the body is not able to properly regulate the production of this hormone, leading to an overproduction of it. Cushing syndrome and Cushing disease are both conditions that occur when the body produces too much cortisol. Cushing disease and Cushing syndrome are not the same condition, but they are often confused with one another. Cushing syndrome occurs when the body produces too much cortisol. While this can happen for many reasons, it often occurs when the patient uses corticosteroid medication. Cushing disease occurs when a tumor on the pituitary gland causes the gland to produce too much ACTH, the hormone responsible for cortisol production. Too much ACTH in the system makes the adrenal glands produce cortisol in high levels.

Cushing disease can also occur with excess growth of the pituitary gland. The excessive growth, known as hyperplasia, also causes the release of too much ACTH, which then leads to over-production of cortisol. Both Cushing syndrome and Cushing disease cause the same symptoms, including red lines on the abdomen, abdominal weight gain, and roundness to the face.

What causes Cushing disease?

Cushing disease is a relatively rare condition, only affecting 10 to 15 people per million every year. It is more common in women and occurs most often in people between the ages of 20 and 50. Adenoma is the most common cause of Cushing disease. Adenoma is a pituitary tumor that is almost always benign. The tumors can be hard to diagnose, because they are quite small, so many people who have Cushing disease have a delayed diagnosis. Having an endocrinologist help with the diagnostic process can improve the chances of a prompt, successful diagnosis for patients who have symptoms of Cushing syndrome and Cushing disease.

What are the signs and symptoms of Cushing disease?

Changes in appearance:

  • Wide, purple stretch marks on the skin (chest, armpits, abdomen, flanks)
  • Rapid and unexplained weight gain with a rounder face and abdomen
  • Increased fat in the neck and above the collarbone and upper back
  • Skin changes (bruising without injury, acne, hair growth) and red cheeks

Mood and thinking:

  • Memory loss or not being able to think clearly
  • Depression
  • Mood and behavior disorders

Other symptoms:

  • Fatigue
  • Muscle weakness
  • Menstrual cycle disorders
  • Osteoporosis
  • High blood glucose (diabetes)
  • High blood pressure
  • Blood clots in leg veins
  • Heart attack
  • Stroke
  • Fracture

How is Cushing disease diagnosed?

Diagnosing Cushing disease can be difficult because symptoms develop slowly, and because elevated cortisol levels can happen in cycles. As a result, cortisol levels may not be elevated at the time of testing.

Testing begins with hormone blood tests to determine if blood cortisol levels are too high. This may require more than one test to establish a state of excessive blood cortisol. If the patient is not taking cortisol medications, the doctor will schedule an MRI to pinpoint the location of any tumors.

If you are struggling with symptoms of elevated cortisol levels, schedule an appointment with your endocrinologist to rule out Cushing disease.

How is Cushing disease treated?

The first line therapy is surgical removal of the tumor. Cure rates with an experienced pituitary surgeon are about 90% in people with small tumors. A patient will typically have transsphenoidal microsurgery through the nasal sinuses.

People who are not cured usually have repeat surgery. When surgery does not work, radiation therapy may treat any remaining tumor mass. Several medications to block the adrenal glands (such as ketoconazole, metyrapone or mitotane) are often used while waiting for radiation to have an effect. In some cases, a type of drug called a dopamine agonist can reduce ACTH levels and cortisol production. Pasireotide (given by injection under the skin) can also reduce ACTH levels and cortisol production. Mifepristone is another medication that stops cortisol from working on the body. The adrenal glands are rarely removed.