Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 22, 2016

Hypercortisolism, also known as cortisol excess or Cushing syndrome, is a disorder caused by abnormally high amounts of the hormone, cortisol in the patient’s body. It has multiple causes and there are several different treatments for the condition.


Definition & Facts

Hypercortisolism is a condition caused by prolonged exposure to abnormally high levels of the hormone cortisol. Taking too much corticosteroid medication is the most common cause. In other cases, the patient’s body simply makes too much cortisol.

Cushing's disease is a variant caused by a tumor of the pituitary gland (pituitary adenoma). Untreated Cushing's disease can eventually kill. While removing the tumor can result in full recovery, the tumor does sometimes grow back.

Cushing syndrome is most common in people between the ages of 20 and 50, and it is much more common in women than in men.

Symptoms & Complaints

Common symptoms of hypercortisolism include the following:

The weight gain caused by Cushing syndrome will follow a characteristic pattern. The patient will typically have fatty deposits in the face (moon face), between the shoulders (buffalo hump), and around their middle.

Women with Cushing's syndrome may also develop irregular or absent periods and hirsutism, with the latter being abnormally thick and visible body hair and facial hair. Men with the disorder can develop erectile dysfunction and decreased fertility and decreased sex drive. Cushing syndrome can stunt a child’s growth.

Other symptoms associated with hypercortisolism can include cognitive difficulties, impulsivity, severe fatigue, depression, anxiety, high blood pressure (hypertension), bone loss that eventually causes bone fractures, headache, and weakened muscles. Hypercortisolism can also eventually cause diabetes mellitus type 2.

A patient should see their doctor if they develop any of the above symptoms, especially if they are taking any type of corticosteroid medication.


Hypercortisolism is caused by excess amounts of cortisol. The condition can be caused either by an imbalance within the body or by taking excessive amounts of corticosteroid medications. If Cushing syndrome is caused by a medication, it is sometimes described as exogenous Cushing syndrome. Medications that contain cortisol, like corticosteroids, are used to treat conditions like asthma, inflammatory bowel disease, or arthritis. They are also used to treat pain and prevent the body from rejecting transplanted organs.

The adrenal glands produce cortisol. The body uses cortisol to regulate the body’s metabolism of proteins, fats and carbohydrates. Cortisol also helps keep the cardiovascular system functioning properly and regulates blood pressure. In endogenous Cushing syndrome, the adrenal glands make more cortisol than the body needs. Endogenous Cushing syndrome has multiple causes including:

  • A tumor of the pituitary gland. A tumor of the pituitary gland or pituitary adenoma can produce too much of a hormone called ACTH. That hormone then causes the adrenal glands to make cortisol.
  • A disease or tumor that directly involves the adrenal glands
  • An ectopic tumor that secretes ACTH. In rare cases, a tumor will develop on an organ that normally does not make ACTH; such a tumor is described as ectopic. 
  • Familial Cushing syndrome

Diagnosis & Tests

Hypercortisolism can be very difficult to diagnose, since many of the symptoms resemble those of other conditions. The doctor will begin by conducting a physical examination, during which they will look for such recognizable traits as a moon face or buffalo hump. 

The doctor will have to conduct tests to rule out diseases with similar symptoms and to determine the cause of the disease if the patient has not been taking corticosteroid medications. For example, the doctor will take samples of the patient’s blood, saliva and/or urine and measure their cortisol levels. The doctor may also ask the patient to collect their own urine for a 24-hour period. 

The doctor can order imaging tests like magnetic resonance imaging (MRI)s or computed tomography (CT) scans that will enable them to take a look at the patient’s pituitary and adrenal glands. Such tests will let them find tumors or other abnormalities.

In petrosal sinus sampling, the doctor draws blood from the petrosal sinuses, which are veins connected to the pituitary gland. The blood test can tell the doctor if the patient’s endogenous Cushing syndrome is caused by an abnormality affecting the pituitary gland.

Treatment & Therapy

There are several different treatments for hypercortisolism. In cases of exogenous Cushing syndrome, the doctor will reduce the amount of corticosteroid medication the patient is taking. This has to be done carefully, since the patient is taking the medication to treat another condition. The doctor will gradually substitute the corticosteroid with another medication.

If the hypercortisolism is caused by a disease affecting the adrenal glands and/or the pituitary gland, the doctor will treat the condition. The cause of endogenous Cushing syndrome will typically be a tumor. In some cases, the surgeon will be able to remove the tumor completely. The doctor will then prescribe cortisol replacement medications, for it will take time for the body to heal and start producing a normal amount of cortisol.

If the doctor can’t remove the whole tumor, or if the patient is too ill to safely undergo surgery, the doctor will recommend radiation therapy. They may administer the radiation in small doses over six weeks, or they may administer a single large dose in a procedure called stereotactic radiosurgery or gamma knife surgery.

If the surgery and radiation prove ineffective, or the patient has severe symptoms, the doctor may prescribe various medications. For example, a new medication, pasireotide is given to patients who either can’t undergo pituitary gland surgery or who underwent an unsuccessful procedure.

Mifepristone is given to people who have glucose intolerance or Type 2 diabetes as well as Cushing syndrome. Other medications include metyrapone, mitotane, and ketoconazole.

Finally, if all else fails, the surgeon may remove the patient’s adrenal glands. In this case, the patient will have to take cortisol replacement medication for the rest of their life.

Prevention & Prophylaxis

People who take corticosteroids should know the signs and symptoms of Cushing syndrome, so they can spot them early and get treatment. It is best to avoid such drugs when possible.

There are, unfortunately, no specific ways to prevent the endogenous forms of Cushing syndrome. People should have regular check-ups, especially if they believe they might be susceptible, so their doctor can examine them and spot any changes that might indicate Cushing syndrome.