Cushings Disease – Pathophysiology
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.
Cushing disease is caused by a tumor or excess growth (hyperplasia) of the pituitary gland. The pituitary gland is located at the base of the brain. A type of pituitary tumor called an adenoma is the most common cause. An adenoma is almost always benign (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 and also helps reduce the immune system’s response to swelling (inflammation).
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 marks (1/2 inch or more wide), called striae, on the skin of the abdomen, thighs, 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)
- Thinning of the bones, which leads to rib and spine fractures
- Weak muscles
Women often 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
Other symptoms may include:
- Mental changes, such as depression, anxiety, or changes in behavior
- Increased thirst and urination
Exams and Diagnostic Tests
Tests are done to confirm there is too much cortisol in the body, then to determine the cause.
These tests confirm too much cortisol:
- 24-hour urine cortisol
- Dexamethasone suppression test (low dose)
- Salivary cortisol levels (early morning and late at night)
These tests determine 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:
- Fasting blood glucose and hemoglobin A1c to test for diabetes
- Lipid and cholesterol testing
- Bone mineral density scan to check for osteoporosis
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, you may need cortisol replacement treatments. 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.
Untreated, Cushing disease can cause severe illness, even death. Removal of the tumor may lead to full recovery, but the tumor can grow back.
- Compression fractures
- High blood pressure
- Kidney stones
- Mental illness
McGee S. Cushing syndrome. In: Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, Pa: Elsevier Saunders. 2012:chap 13.
Molitch M. Anterior pituitary. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia, Pa: Elsevier Saunders; 2011:chap 231.
Stewart PM, Krone NP. The adrenal cortex. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds.Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa: Elsevier Saunders; 2011: chap 15.