Pituitary-dependent Cushing's syndrome

What is pituitary-dependent Cushing's syndrome?

Pituitary-dependent Cushing's syndrome, also called Cushing's disease (a condition specifically caused by a tumor in the pituitary gland), is a form of Cushing's syndrome. It develops when the body has too much of a hormone called cortisol (a hormone that helps the body respond to stress and regulates many body functions) over a long period of time.12

Cushing's disease, hypercortisolism

The condition gets its name from Harvey Cushing, an American neurosurgeon who first described patients with this condition in 1912.3 While Cushing's syndrome can have various causes, pituitary-dependent Cushing's syndrome specifically refers to cases where a pituitary tumor is responsible for the excess cortisol production.2

This is a progressive condition, meaning it gets worse over time when left untreated.2 The pituitary tumor that causes this disease is usually very small and in most cases is noncancerous. These tumors are sometimes called pituitary adenomas (benign growths in the pituitary gland).2

• Pituitary gland
• Adrenal glands
• Hypothalamus
• Brain
• Kidneys

Understanding cortisol and its role in the body

Cortisol is sometimes called the "stress hormone" because your body releases extra cortisol during times of stress.4 The adrenal glands, two small glands located on top of your kidneys, make cortisol.5 Under normal circumstances, cortisol is released in response to stress, exercise, and waking up in the morning.2

Cortisol is essential for many important body functions. It helps maintain blood pressure, regulate blood sugar levels, reduce inflammation, and turn the food you eat into energy.5 The hormone also helps balance the effect of insulin to keep blood sugar normal and helps the body respond to stress.3

When cortisol levels are too high over a period of time, things like blood pressure and weight start to become unregulated. Food may not be processed correctly, and diabetes can develop. You can feel stressed and have a hard time sleeping. Your moods may even be affected, and you may become frustrated or irritated.6

What causes this condition?

Pituitary-dependent Cushing's syndrome occurs when a tumor develops in the pituitary gland, a small gland about the size of a pea located at the base of the brain.23 This tumor forces the pituitary gland to create an abnormally large amount of a hormone called ACTH (adrenocorticotropic hormone, which signals the adrenal glands to produce cortisol).2

This oversupply of ACTH travels through the bloodstream to the adrenal glands and signals them to make too much cortisol.3 The result is that too much cortisol circulates in the body, causing the symptoms of the disease.

The most common cause of spontaneous Cushing's syndrome is a small benign tumor of the pituitary gland, which accounts for around 70% of all cases.34 It is important to note that there are no known environmental triggers, and the condition is not hereditary.3

Signs and symptoms

The symptoms of pituitary-dependent Cushing's syndrome can vary from person to person and usually develop gradually, which means the diagnosis may not be clear for some time.3 Rapid or excessive weight gain, particularly around the stomach area, is often the first sign.2

Common physical changes include a rounded, red face (sometimes called "moon face"), a fatty hump between the shoulders (called a "buffalo hump"), and weight gain in the trunk while the arms and legs may look thin.14 The skin may become thin and fragile, bruising easily, and purple or pink stretch marks may appear on the stomach, hips, thighs, breasts, and underarms.1

Other symptoms include muscle weakness, particularly at the top of the arms and legs, slow wound healing, and acne or skin darkening.12 People may experience increased thirst and urination, increased appetite, and excessive hair growth on the face and body.7

The condition also affects mental and emotional health. People may experience depression, anxiety, fatigue, problems with memory and attention, mood changes, and irritability.27 Sleep problems are common, with disrupted sleep patterns and insomnia.6

Hormonal changes can also occur. People who menstruate may notice their periods becoming irregular or stopping completely, while those with a penis may experience erectile dysfunction.2

Who is affected?

Pituitary-dependent Cushing's syndrome is a rare condition. The number of people with endogenous Cushing's syndrome (meaning the excess cortisol comes from inside the body) ranges from about 40 to 70 people out of every million.54 However, these numbers may not reflect the true number of people with this illness, as it is not uncommon for people to go undiagnosed.7

The condition most often affects adults, usually between the ages of 30 to 50, though it can also occur in children.53 It affects about three times as many women as men.54 Although it is rare in children, some as young as six have been diagnosed.3

The condition may be more likely to be found in people who have type 2 diabetes with blood glucose levels that stay too high over time, along with high blood pressure.5

How is it diagnosed?

Diagnosing pituitary-dependent Cushing's syndrome can be a long and complex process because other illnesses have similar symptoms.8 If your doctor suspects you might have this condition, you will likely be referred to a specialist called an endocrinologist (a doctor who specializes in hormone-related diseases).4

The endocrinologist will perform a physical exam and look for signs such as a round face, a hump on the back of the neck, and thin, bruised skin with stretch marks.8 Your doctor will be able to confirm the diagnosis by measuring the levels of ACTH and cortisol in your body.2

Several tests may be used to diagnose the condition. Urine and blood tests measure hormone levels and show if the body is making too much cortisol. For urine tests, you may be asked to collect your urine over a 24-hour period.8 A saliva test can check cortisol levels from a small sample of saliva collected at night, as cortisol normally drops in the evening in people without the syndrome.8

Imaging tests such as CT or MRI scans can take pictures of the pituitary gland to see if there is a tumor.8 The symptoms of the condition can be very wide ranging, which means the diagnosis may not be immediately considered, and this can cause a delay in diagnosis.3

Treatment options

The first-line treatment for pituitary-dependent Cushing's syndrome is pituitary surgery to remove the tumor.9 This surgery is followed by disease remission in around 78% of patients, though relapse occurs in around 13% of patients during the 10-year period after surgery.9 In this case, there is a good chance that an operation on the pituitary gland to remove the tumor will solve the problem.3

When surgery fails or is not possible, several other treatment options are available. Medical therapy can be used before surgery, after unsuccessful surgery, or as primary therapy when surgery is not an option.9

Medications work in different ways to control cortisol levels. Some medications reduce the amount of cortisol the adrenal glands produce. Others block the effects of cortisol in the body. The medications used most commonly include drugs that target the adrenal glands to reduce cortisol production, and drugs that target the pituitary gland itself.9

Radiation therapy can be used to reduce the size of the pituitary tumor, particularly if an individual is experiencing neurological signs because of the tumor's size and pressure on other parts of the brain.10 This treatment is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hormone deficiency affecting other pituitary hormones.9

In some circumstances, it may be necessary to remove one or both adrenal glands. This surgery provides a rapid and definitive control of cortisol excess in nearly all patients, but it results in the need for lifelong hormone replacement therapy.9

Possible complications

Without treatment, pituitary-dependent Cushing's syndrome can cause serious health problems and can possibly be fatal.4 The condition is associated with increased illness and death.9

Complications can include high blood pressure, high blood sugar or type 2 diabetes, weak and brittle bones (osteoporosis), infections, and blood clots, especially in the lungs and legs.47 Heart attack, depression, weight gain, memory problems or difficulty concentrating, and high cholesterol are also possible.4

The sooner treatment starts, the better the chances for recovery.1 With treatment, patients can lead active lives with fewer symptoms.7