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Cushing disease

Pituitary Cushing disease; ACTH-secreting adenoma

Cushing disease is a condition in which the pituitary gland releases too much adrenocorticotropic hormone (ACTH). The pituitary gland is an organ of the endocrine system.

Cushing disease is a form of Cushing syndrome. Other forms of Cushing syndrome include exogenous Cushing syndrome, Cushing syndrome caused by adrenal tumor, and ectopic Cushing syndrome.

Causes

Cushing disease is caused by a tumor or excess growth (hyperplasia) of the pituitary gland. The pituitary gland is located just below the base of the brain. A type of pituitary tumor called an adenoma is the most common cause. An adenoma is a benign tumor (not a cancer).

With Cushing disease, the pituitary gland releases too much ACTH. ACTH stimulates production and release of cortisol, a stress hormone. Too much ACTH causes the adrenal glands to make too much cortisol.

Cortisol is normally released during stressful situations. It controls the body's use of carbohydrates, fats, and proteins. It also reduces the immune system's response to swelling (inflammation).

Symptoms

Symptoms of Cushing disease include:

  • Upper body obesity (above the waist) and thin arms and legs
  • Round, red, full face (moon face)
  • Slow growth rate in children

Skin changes that are often seen include:

  • Acne or skin infections
  • Purple stretch marks (1/2 inch or 1 centimeter or more wide), called striae, on the skin of the abdomen, thighs, upper arms, and breasts
  • Thin skin with easy bruising, most commonly on the arms and hands

Muscle and bone changes include:

  • Backache, which occurs with routine activities
  • Bone pain or tenderness
  • Collection of fat between the shoulders (buffalo hump)
  • Weakening of the bones, which leads to rib and spine fractures
  • Weak muscles

Women may have:

  • Excess hair growth on the face, neck, chest, abdomen, and thighs
  • Menstrual cycle that becomes irregular or stops

Men may have:

  • Decreased or no desire for sex (low libido)
  • Erection problems

Other symptoms or problems may include:

  • Mental changes, such as depression, anxiety, or changes in behavior
  • Fatigue
  • Frequent infections
  • Headache
  • Increased thirst and urination
  • High blood pressure
  • Diabetes

Exams and Tests

The health care provider will perform a physical examination and ask about your symptoms.

Tests are done to confirm there is too much cortisol in the body, and then to determine the cause.

These tests confirm too much cortisol:

These tests determine the cause:

  • Blood ACTH level
  • Brain MRI
  • Corticotropin-releasing hormone test, which acts on the pituitary gland to cause the release of ACTH
  • Dexamethasone suppression test (high dose)
  • Inferior petrosal sinus sampling (IPSS) -- measures ACTH levels in the veins that drain the pituitary gland compared to the veins in the chest

Other tests that may be done include any of the following:

Treatment

Treatment involves surgery to remove the pituitary tumor, if possible. After surgery, the pituitary gland may slowly start to work again and return to normal.

During the recovery process from surgery, you may need cortisol replacement treatments because the pituitary needs time to start making ACTH again.

Radiation treatment of the pituitary gland may also be used if the tumor is not completely removed.

If the tumor does not respond to surgery or radiation, you may need medicines to stop your body from making cortisol.

If these treatments are not successful, the adrenal glands may need to be removed to stop the high levels of cortisol from being produced. Removal of the adrenal glands can cause the pituitary tumor to get much bigger (Nelson syndrome).

Outlook (Prognosis)

Untreated, Cushing disease can cause severe illness, even death. Removal of the tumor may lead to full recovery, but the tumor can grow back.

Possible Complications

Health problems that may result from Cushing disease include:

When to Contact a Medical Professional

Call your provider if you develop symptoms of Cushing disease.

If you have had a pituitary tumor removed, call your provider if you have signs of complications, including signs that the tumor has returned.

References

Molitch ME. Anterior pituitary. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 224.

Stewart PM, Newell-Price JDC. The adrenal cortex. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016:chap 15.

    • Endocrine glands

      Endocrine glands - illustration

      Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary to secrete hormones which determine the rate of metabolism in the body (the more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity).

      Endocrine glands

      illustration

    • Striae in the popliteal fossa

      Striae in the popliteal fossa - illustration

      Striae in the popliteal fossa: Striae or stretch marks result from stretching of the skin, or other influences such as Cushing syndrome. Most pregnant women experience striae at some point during their pregnancy. This picture shows striae in the popliteal fossa (the area on the back side of the leg at the knee joint). When the striae first appear they have a violaceous (red-purple) color, but over time they take-on a dull white appearance.

      Striae in the popliteal fossa

      illustration

    • Striae on the leg

      Striae on the leg - illustration

      Stretch marks (striae) result from rapid stretching of the skin which may occur with obesity, pubertal growth spurts, pregnancy, or from other influences such as Cushing syndrome.

      Striae on the leg

      illustration

      • Endocrine glands

        Endocrine glands - illustration

        Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary to secrete hormones which determine the rate of metabolism in the body (the more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity).

        Endocrine glands

        illustration

      • Striae in the popliteal fossa

        Striae in the popliteal fossa - illustration

        Striae in the popliteal fossa: Striae or stretch marks result from stretching of the skin, or other influences such as Cushing syndrome. Most pregnant women experience striae at some point during their pregnancy. This picture shows striae in the popliteal fossa (the area on the back side of the leg at the knee joint). When the striae first appear they have a violaceous (red-purple) color, but over time they take-on a dull white appearance.

        Striae in the popliteal fossa

        illustration

      • Striae on the leg

        Striae on the leg - illustration

        Stretch marks (striae) result from rapid stretching of the skin which may occur with obesity, pubertal growth spurts, pregnancy, or from other influences such as Cushing syndrome.

        Striae on the leg

        illustration

      Review Date: 5/7/2017

      Reviewed By: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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