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Neurosciences and Behavioral Health Center

Cushing's Disease

Cushing's disease (also called ACTH-producing pituitary tumor) is a pituitary tumor that secretes adrenocorticotrophin hormone (ACTH), which causes overproduction of cortisol by the adrenal glands.

Symptoms of Cushing's Disease

Excessive cortisol production causes:

  • Weight gain (particularly in the abdomen and neck)
  • Loss of muscle (thinning and weakness of the legs and arms)
  • Depression
  • Sleep disturbance
  • Memory loss
  • Difficulty concentrating
  • Loss of sexual function
  • Infertility
  • Loss of menstrual periods
  • Thin skin, easy bruising and red stretch marks (usually on the abdomen)
  • High blood pressure
  • Diabetes mellitus
  • Osteoporosis and bone fractures
  • Abnormal lipids (cholesterol)
  • Heart disease
  • Kidney stones


Cushing's disease is the most difficult diagnosis of all pituitary disorders to diagnose. Weight gain, obesity, depression, diabetes and high blood pressure are common problems, but Cushing's disease is rare.

The diagnosis requires in two separate stages:

  • The first stage establishes if the patient is producing cortisol
  • The second stage determines the precise cause of this excess cortisol production

A multidisciplinary approach involving endocrinologists and neurosurgeons is essential for the correct diagnosis and appropriate management of patients with Cushing’s disease.

Screening for Excess Cortisol Production

There are three screening tests used to detect excess and abnormal cortisol production:

  • 24-hour urine-free cortisol levels
  • Late-night salivary cortisol levels
  • Blood cortisol response to 1 mg of dexamethasone at 11 p.m. combined with a blood cortisol at 8 a.m. the next day (overnight low dose dexamethasone test).

These tests are equally reliable as screening tests (about 95 percent accurate).

Since they aren't 100 percent accurate, several tests are often needed to make the diagnosis of Cushing's syndrome (i.e., excess cortisol production) and include:

  • Measurement of serum ACTH levels
  • Blood cortisol response to 8 mg of dexamethasone at 11 p.m. (overnight low dose dexamethasone test) combined with a blood cortisol at 8 a.m. the next day
  • CRH stimulation test
  • Inferior petrosal sinus sampling (requires hospitalization and a procedure by a specialist)
  • Special imaging of the pituitary (MRI), and the chest and abdomen (CT or MRI)

These tests are almost always used in combination, so that the diagnosis can be established with certainty.



The best treatment patients with a pituitary tumor causing Cushing’s syndrome is removal of the tumor by an experienced neurosurgeon, one who performs pituitary surgery frequently.

Because the tumors that cause Cushing’s disease are often very small, the condition requires surgeons with skills that are different from the skills used to remove large pituitary tumors. Although most neurosurgeons have some experience with pituitary tumor surgery, only a few have a large amount of experience with Cushing’s disease and have a demonstrated record of success in treating it.


Medication is used to control adrenal gland cortisol overproduction, but does not treat the source of the problem (the pituitary tumor).

Ketoconazole is most often used in patients who have persistent Cushing's despite surgery and/or radiation, while waiting for the radiation to become effective. Careful monitoring is necessary to establish the optimal dose and to determine if the dose is effective and to make sure there are no unwanted effects on the liver.

Radiation Therapy

If surgery does not cure Cushing’s disease, we can use irradiation to return cortisol production to normal and control tumor growth, which works in 50-60 percent of patients.

Another option, Gamma Knife radiosurgery, a precisely targeted, single dose of radiation, has the advantage of being delivered in a single treatment, compared to conventional irradiation therapy, which takes 5 weeks of daily treatment on weekdays.


Call 434.924.1825.


Content was created using EBSCO’s Health Library. Edits to original content made by Rector and Visitors of the University of Virginia. This information is not a substitute for professional medical advice.


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