Cushing Syndrome

Cushing syndrome occurs as a result of excessive exposure to the hormone cortisol. Cortisol is the main hormone involved in reactions to stress. Elevated cortisol levels are caused by either medications or a tumor in the pituitary gland. The latter is called Cushing disease.

The syndrome was first described in 1932 by the surgeon Dr. Harvey Cushing (1869-1939). The syndrome is most often caused by medications called steroids. Some common symptoms include weight gain, skin problems, and anxiety. Many symptoms are reversible when cortisol levels return to normal. However, long-term exposure to elevated cortisol could result in complications such as heart disease and osteoporosis.

3-D Structure of cortisol. Source: Wikimedia Commons

Other Names

Cushing syndrome is also called hypercortisolism or hyperadrenocorticism.

Signs and Symptoms

Below are some common symptoms of Cushing syndrome:

• Upper body obesity, round face and neck, and thinning arms and legs
• Slow growth rates in children
• Skin problems, such as acne or reddish-blue streaks in the skin (called striae)
• High blood pressure
• Muscle and bone weakness
• Moodiness, irritability, or depression
• High blood sugar
• Excessive sweating
• Frequent urination
• Constipation

Women with the syndrome may also have increased growth of hair on their face and body and experience menstrual irregularities. Men may become less fertile and have a reduced or absent sex drive.

Because cortisol is involved in the response to stress, Cushing syndrome often causes anxiety.

Causes

Cushing syndrome has two causes:

1. Medication either causes the body to make too much cortisol, or the medication itself contains extra cortisol and taking it pushes the level above normal.
2. A person’s body makes more cortisol than it needs.

Normally, the hypothalamus in the brain triggers a chain of events that causes the adrenal glands to release cortisol into the bloodstream. When everything is working correctly, the body is balanced, releasing the right amount of cortisol for daily needs. But problems with the adrenal glands, pituitary gland, or hypothalamus can cause the glands to make too much cortisol. Conditions that might cause the body to make too much cortisol include the following:

• Pituitary tumors
• Ectopic ACTH syndrome
• Adrenal tumors
• Familial (genetic) Cushing syndrome

Diagnosis

When symptoms of Cushing syndrome appear in individuals taking high doses of medications that elevate cortisol levels, a diagnosis can be made based on a physical exam.

Two tests are available to detect excessive cortisol production and secretion by the adrenal medulla. In the dexamethasone suppression test, the drug dexamethasone is given and the amount of cortisol and adrenocorticotropin hormone (ACTH) excreted in the urine is measured. Dexamethasone administration normally reduces cortisol secretion, but in Cushing syndrome cortisol is continually secreted. Another test measures the amount of cortisol in either the urine or saliva.

Medical imaging is performed if Cushing disease (a pituitary tumor) or abnormal adrenal function is suspected. Tumors in the adrenal gland can be seen on computerized tomography (CT) scans, and pituitary tumors can be visualized using magnetic resonance imaging (MRI).

Sometimes an adrenal scintigraphy is performed, although this is not common in the United States. In this procedure, radioactive iodocholesterol is injected into a vein. The compound collects in the adrenal glands and is detected by a gamma counter.

Treatment

Treatment for Cushing syndrome depends on the cause. If it is caused by the use of medicine to treat another disorder, a health care provider can reduce the dose or change the medicine. If the body is making too much cortisol, treatments may include oral medication, surgery, radiation, or a combination of these treatments.

Chances of Developing Cushing Syndrome

The risk of developing Cushing syndrome is higher with high dose, long-term steroid treatment.

Related Problems

Persistent or untreated Cushing syndrome that lasts for a year or more can cause complications. Some complications are reversible when cortisol levels return to normal.

Complications

Elevated cortisol levels increase insulin sensitivity and blood sugar levels. In some people, this can lead to diabetes. The high blood pressure and other cardiovascular effects of cortisol can lead to heart disease. Often the high blood pressure is reversible when cortisol levels return to normal, but heart damage can be permanent. Some individuals with the syndrome have low levels of calcium in the blood because cortisol hinders calcium absorption. Persistently low calcium can cause bones to weaken and osteoporosis. Ultimately, people with Cushing syndrome have an increased risk of premature death.

Cortisol suppresses the immune system. In fact, the drug prednisone used for the treatment of many autoimmune diseases, such as arthritis, is a precursor of cortisol. Excessive cortisol can therefore increase the risk of infection, increase bleeding, and impair wound healing.

Expected Outcome

In most cases Cushing syndrome can be cured. Discontinuation of any medications that are causing the syndrome will return cortisol levels to normal, but complications may still exist.

Epidemiology

The incidence of Cushing syndrome not caused by medications is approximately 13 in one million individuals.^[1]

References

1. ↑ Adler GK. eMedicine. Cushing Syndrome