Cushing's syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at March 15, 2016
StartCushing's syndrome

Cushing’s syndrome is a condition that is caused by the body being exposed to abnormally high levels of cortisol. Treatments can help decrease blood cortisol levels and ameliorate the symptoms associated with Cushing’s syndrome.


Definition & Facts

Approximately 10 to 15 out of every one million Americans are affected by Cushing’s syndrome. The condition is most frequently diagnosed in adults between the ages of 20 and 50.

Cortisol is one of several hormones manufactured by the two adrenal glands, which are small endocrine glands located on top of each kidney. The amount of cortisol that is released into the bloodstream at any given time is monitored by a complex set of endocrinological checks and balances that include substances secreted by the hypothalamus and the pituitary gland. Cortisol helps maintain blood pressure and cardiovascular functions, and it also helps to promote healthy blood glucose levels by balancing insulin production.

In response to stress or fear, the brain signals the adrenals to release excess cortisol into the bloodstream, thereby initiating the fight-or-flight response. Cortisol acts to shunt blood away from body systems such as the digestive system, reproductive system, and immune system that might not be essential in a life-or-death situation.

Symptoms & Complaints

To some extent, Cushing’s syndrome may be seen as an exaggeration of cortisol’s beneficial short-term effects. Patients with Cushing’s syndrome exhibit a variety of symptoms, which can make this condition difficult to diagnose. Some of the most common symptoms include:

  • Elevated blood pressure: excess cortisol levels raise blood pressure and heart rate.
  • High cholesterol: Cholesterol and triglyceride levels often rise with cortisol levels, and these can form arterial plaque, which often leads to cardiovascular dysfunction. Insulin production may also be affected, leading to a predisposition toward diabetes.
  • Weight gain: Abnormal cortisol levels signal the brain falsely for the need for more carbohydrates, which often leads to the buildup of fat deposits. Fat deposits typically occur in the face, neck, trunk, and abdomen, leading to the “moon face” and “buffalo hump” that are found in many Cushing’s patients.
  • Thin limbs: Cushing’s syndrome can promote wasting of the skeletal muscles that are found in the arms and legs.
  • Skin changes: Skin thins and bruises far more easily. Due to the suppression of the immune system, acne is not uncommon, and wounds may be slow to heal.
  • Sexual changes: Women with Cushing’s syndrome may experience excess hair growth and menstrual irregularities, while men may experience erectile dysfunction. Both sexes may experience a decrease in libido.
  • Susceptibility to infection: Since cortisol suppresses the immune response, people with Cushing’s syndrome typically are more prone to infections.
  • Psychological changes: Patients with Cushing’s syndrome are prone to depression and may have more difficulty controlling angry outbursts.


The most common cause of Cushing’s syndrome today is the prolonged use of corticosteroid medications, which are prescribed to treat a variety of conditions ranging from lupus to chronic back pain. The short-term use of corticosteroids for the treatment of conditions like asthma or eczema are not generally linked with this syndrome except in cases of dramatic overuse. Endogenous causes of Cushing’s syndrome include:

  • Pituitary gland tumors: The pituitary gland releases adrenocorticotropic hormone, (ACTH) in response to a signal from the hypothalamus. ACTH signals the adrenal glands to release cortisol. Pituitary tumors can cause excess ACTH production. In these cases, the condition is often referred to as Cushing’s disease rather than Cushing’s syndrome.
  • Adrenal gland tumors: A tumor can force the adrenal gland into overdrive so that it produces excessive amounts of cortisol. The most common of these tumors is adrenal adenoma, which is a nonmalignant tumor. Adrenal hypertrophy is also associated with the onset of this condition.
  • Ectopic ACTH-Secreting tumors: In rare instances, tumors outside the brain can secrete ACTH. Such tumors are typically found in the lungs or pancreas, or the thyroid or thymus glands.
  • Familial: There may be a genetic factor toward the types of tumors that lead to excess ACTH and/or cortisol production.

Diagnosis & Tests

It can be difficult to diagnose Cushing’s syndrome as the condition mimics symptoms from many other diseases. Dramatic changes in a patient’s physical appearance is often one of the key clues, and physicians frequently ask to look at before-and-after photographs. A thorough physical examination will be performed, and if the primary physician suspects Cushing’s syndrome, he or she will arrange to bring in an endocrine specialist.

The first step in confirming the diagnosis may be blood tests and urine tests to determine whether excess levels of cortisol are present in the body. Saliva testing is often utilized as well since individuals who do not have Cushing’s syndrome show characteristic fluctuations in cortisol levels throughout the day.

Once physicians have confirmed the existence of excess cortisol levels, they will begin to search for the reason why those cortisol levels are elevated. Such tests may include Petrosal sinus sampling and various imaging studies such as CT scans and MRIs. It’s also important to distinguish the condition from Pseudo-Cushing’s syndrome that is sometimes found in individuals affected by alcoholism or abnormally high estrogen levels.

Treatment & Therapy

Optimal treatments for Cushing’s syndrome depend upon the specific cause of the condition in any given individual. If the long-term use of corticosteroids is implicated in the condition, physicians may try alternative methods of managing the disease that called for the use of corticosteroids. No individual should ever discontinue the use of corticosteroids without medical supervision, however.

Surgery may be required when the underlying cause of a patient’s Cushing’s syndrome is a tumor. If the tumor involves the pituitary gland, it will need to be performed by a trained neurosurgeon. If the tumor involves the adrenal glands, the patient may need replacement cortisol therapy until the adrenal glands begin producing adequate levels of cortisol again. If Cushing’s syndrome is caused by a pituitary tumor that can’t be removed for whatever reason, radiation therapy may be indicated to try and shrink the tumor.

Medications like ketoconazole (Nizoral®), mitotane (Lysodren®) and metyrapone (Metopirone®) may also be prescribed, which either decrease the body’s cortisol production or block the effects of cortisol upon body tissues.

Prevention & Prophylaxis

Cushing’s syndrome that is linked to tumors affecting endocrine glands cannot be prevented, but the excessive use of corticosteroid medications can be mitigated to some degree.

It’s important for physicians and patients to understand the risks associated with the use of corticosteroid medications and to keep their use to within safe limits whenever possible.