Cushing’s syndrome is a disorder that develops due to long-term exposure to high levels of the hormone cortisol. When cortisol levels remain too high over a long period of time, it can lead to symptoms such as weight gain, a rounded or “moon” face, a fatty hump at the back of the neck, muscle weakness, and changes in mood or memory, among others. Women may also experience excess hair growth and irregular menstrual periods.

There are two types of Cushing’s syndrome. The most common type, exogenous Cushing’s syndrome, results from something outside the body—such as medicine prescribed for another health condition—which causes cortisol levels to remain high. In rare cases, Cushing’s syndrome can also result from the body’s own overproduction of cortisol. This is called endogenous Cushing’s syndrome.

Cushing’s syndrome can be serious if not recognized and treated. With accurate diagnosis and appropriate management, many people can recover or experience significant improvement in their symptoms and quality of life.

Cushing’s syndrome is a condition that occurs after prolonged exposure to excessive cortisol. Cortisol helps regulate many important functions, including blood pressure, blood sugar, metabolism, the body’s response to stress, and inflammation. The adrenal glands produce cortisol in response to signals from the pituitary gland, which releases a hormone called adrenocorticotropic hormone (ACTH) to control how much cortisol is made.

When cortisol levels remain high, it can affect many parts of the body, including the skin, muscles, bones, heart, blood vessels, and brain. Sometimes a tumor can cause the body to make too much cortisol. Excess cortisol can also come from medications called glucocorticoids, a type of corticosteroid that acts like cortisol in the body.

The two main types of Cushing’s syndrome are:

• Exogenous Cushing’s syndrome develops from the use of some types of corticosteroid medications.
• Endogenous Cushing’s syndrome results from the body’s own overproduction of cortisol, often due to tumors or abnormal growths that affect hormone regulation.

Cushing’s syndrome can affect people of any age, including children, but it is most often diagnosed in adults between the ages of 30 and 50. It is more common in women than in men. Because the symptoms can develop slowly and may resemble those of other health problems, diagnosis is sometimes delayed.

Cushing’s syndrome develops when the body is exposed to high levels of cortisol for a long time. The causes fall into two main categories: exogenous (from outside the body) and endogenous (from within the body).

The most common cause is exogenous, which means the condition results from taking medications that act like cortisol. These medications, such as glucocorticoids (a class of corticosteroids), are often prescribed to treat conditions such as asthma, rheumatoid arthritis, lupus, or to prevent organ rejection after a transplant. When used in high doses for a long time, these drugs can lead to Cushing’s syndrome.

Endogenous Cushing’s syndrome occurs when the body itself produces too much cortisol. This can happen for several reasons:

• Pituitary tumors: Noncancerous tumors in the pituitary gland can produce too much ACTH, which signals the adrenal glands to make more cortisol. This is the most common endogenous cause of Cushing’s syndrome. When caused by pituitary tumors, Cushing’s syndrome is called Cushing’s disease.
• Ectopic ACTH-producing tumors: These tumors occur outside the pituitary gland and make ACTH, resulting in higher-than-normal cortisol levels. They may occur in the lungs, pancreas, thyroid, or thymus.
• Adrenal tumors: Tumors on the adrenal glands can make too much cortisol. These tumors are usually benign but can sometimes be cancerous.

Risk factors for Cushing’s syndrome include:

• Long-term use of glucocorticoids
• Being between the ages of 30 and 50
• Female sex
• Having type 2 diabetes and prolonged periods of high blood sugar in combination with high blood pressure
• Presence of tumors in the pituitary gland, adrenal glands, or other organs such as the lungs, pancreas, thyroid, or thymus
• History of organ transplant requiring immune-suppressing medications
• Certain genetic syndromes or family history of endocrine tumors

Symptoms of Cushing’s syndrome may include:

• Weight gain, especially in the face, upper back, and abdomen
• Rounded, full face (“moon face”)
• Increased fat at the back of the neck and between the shoulders
• Loss of fat on arms and legs
• Wide purple stretch marks (called striae) on the abdomen, thighs, breasts, or under the arms
• Thin skin or easy bruising
• Muscle weakness, especially in the hips and shoulders
• Bone loss or fractures
• High blood pressure
• High blood sugar or diabetes
• Tiredness
• Depression, anxiety, or mood changes
• Difficulty thinking clearly or memory problems
• Slow growth or obesity in children
• Excess hair growth on the face, neck, chest, abdomen, or thighs (in women)
• Irregular or absent menstrual periods (in women)
• Decreased interest in sex and erectile dysfunction (in men)
• Increased risk of infections
• Headache
• Increased thirst and urination

To diagnose Cushing’s syndrome, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests.

Your doctor may ask about your symptoms, how long you have had them, and whether you have taken glucocorticoid medications or have other risk factors for Cushing’s syndrome. During the physical exam, your doctor will look for signs such as weight gain in specific areas, a rounded face, thin skin, easy bruising, purple stretch marks, muscle weakness, and high blood pressure.

Additional tests are necessary to make a diagnosis. They may include the following:

• 24-hour urinary free cortisol test: measures the amount of cortisol in your urine collected over a full day. High levels suggest Cushing’s syndrome.
• Late-night salivary cortisol test: checks cortisol levels in a saliva sample collected late at night, when levels should normally be low. Elevated levels may indicate Cushing’s syndrome.
• Low-dose dexamethasone suppression test: involves taking a small dose of dexamethasone (a steroid) at night, followed by a blood test for cortisol the next morning. In healthy people, dexamethasone lowers cortisol levels, but in Cushing’s syndrome, cortisol remains high.
• Blood tests for adrenocorticotropic hormone (ACTH): help determine whether the cause is related to the pituitary gland, adrenal glands, or another source.
• Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans: used to look for tumors in the pituitary gland or adrenal glands.
• Inferior petrosal sinus sampling: involves blood samples taken from veins near the pituitary gland. This test can help distinguish between pituitary and other causes of excess ACTH.

Because symptoms of Cushing’s syndrome can overlap with other conditions, your doctor may need to repeat some tests or use a combination of tests to confirm the diagnosis and identify the underlying cause.

The choice of treatment for Cushing’s syndrome depends on the cause of the condition. The main goal is to lower the level of cortisol in the body. Main treatments include:

• Gradual reduction of glucocorticoid medications: If Cushing’s syndrome is caused by taking glucocorticoid medicines, the doctor will slowly decrease the dose to the lowest possible amount or switch to a different medication, if appropriate. Stopping these medicines suddenly can be dangerous, so it must be done under medical supervision.
• Surgical removal of tumors: If a tumor is causing the body to make too much cortisol, surgery to remove the tumor is often the first choice. This may involve removing a tumor from the pituitary gland, adrenal gland, or another part of the body.
• Radiation therapy: If surgery is not possible or does not fully remove the tumor, radiation may be used to destroy remaining tumor cells. Radiation can take time to work, and additional treatments may be needed while waiting for its effects.
• Medications to control cortisol: If surgery is not possible, while waiting for radiation to work, or if cortisol remains high, medicines can lower cortisol production or block its effects. Some medicines target pituitary tumors.
• Bilateral adrenalectomy: In rare cases, both adrenal glands may be removed to stop cortisol production. People who have this surgery will need to take hormone replacement medicines for life.

Treatment is tailored to each person’s situation, and ongoing follow-up is important to monitor and manage any long-term effects.

People with Cushing’s syndrome are at increased risk for certain complications. These include:

• Heart disease and stroke due to high blood pressure
• Type 2 diabetes, which may require medication or insulin
• Bone density loss (osteoporosis) and weakened bones that are more likely to fracture
• Muscle weakness, especially in the hips and shoulders
• Increased infections due to a weakened immune system
• Increased risk of clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
• Higher levels of “bad” (LDL) cholesterol and lower levels of “good” (HDL) cholesterol, which can add to the risk of heart disease or stroke
• Kidney stones
• Depression and mood changes
• Memory loss or trouble concentrating
• Cuts and injuries that take longer to heal
• Irregular menstrual periods or infertility
• Erectile dysfunction and reduced sex drive

The outlook for people with Cushing’s syndrome varies depending on the underlying cause, when the condition is diagnosed, the person’s age, overall health, and how well the condition responds to treatment. Many people experience significant improvement or even a cure when the cause of excess cortisol is identified and treated, especially if treatment begins early. However, some people may continue to have health problems related to Cushing’s syndrome that require additional treatment.

Some complications, such as high blood pressure, diabetes, bone loss, or mood changes, may improve after cortisol levels return to normal, but others can persist and require ongoing care. People with Cushing’s syndrome have a higher risk of serious health problems, including heart disease and infections, even after treatment. Lifelong follow-up to monitor for recurrence and manage any lasting effects helps ensure the best possible outcomes and quality of life for people with Cushing’s syndrome.