Adrenocortical carcinoma is a rare disease in which malignant (cancer) cells form in the outer layer of the adrenal gland.

There are two adrenal glands. The adrenal glands are small and shaped like a triangle. One adrenal gland sits on top of each kidney. Each adrenal gland has two parts. The outer layer of the adrenal gland is the adrenal cortex. The center of the adrenal gland is the adrenal medulla.

The adrenal cortex makes important hormones that:

• Balance the water and salt in the body.
• Help keep blood pressure normal.
• Help manage the body's use of protein, fat, and carbohydrates.
• Cause the body to have masculine or feminine characteristics.

The adrenal medulla makes hormones that help the body react to stress.

Adrenocortical carcinoma is also called cancer of the adrenal cortex. A tumor of the adrenal cortex may be functioning (makes more hormones than normal) or nonfunctioning (does not make hormones). The hormones made by functioning tumors may cause certain signs or symptoms of disease.

Cancer that forms in the adrenal medulla is called pheochromocytoma.

Having certain genetic conditions increases the risk of developing adrenocortical carcinoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for adrenocortical carcinoma include having the following hereditary diseases:

• Li-Fraumeni syndrome
• Beckwith-Wiedemann syndrome
• Carney complex

Possible signs of adrenocortical carcinoma include pain in the abdomen and certain physical changes.

These and other symptoms may be caused by adrenocortical carcinoma:

• A lump in the abdomen.
• Pain the abdomen or back.

A nonfunctioning adrenocortical tumor may not cause symptoms in the early stages.

A functioning adrenocortical tumor makes too much of a certain hormone (cortisol, aldosterone, testosterone, or estrogen).

Too much cortisol may cause:

• Weight gain in the face, neck, and trunk of the body and thin arms and legs
• Growth of fine hair on the face, upper back, or arms
• A round, red, full face
• A lump of fat on the back of the neck
• A deepening of the voice and swelling of the sex organs or breasts in both males and females
• Muscle weakness
• High blood sugar
• High blood pressure

Too much aldosterone may cause:

• High blood pressure
• Muscle weakness or cramps
• Frequent urination
• Feeling thirsty

Too much testosterone (in women) may cause:

• Growth of fine hair on the face, upper back, or arms
• Acne
• Balding
• A deepening of the voice
• No menstrual periods

Men who make too much testosterone do not usually have symptoms.

Too much estrogen (in women) may cause:

• Irregular menstrual periods in women who have not gone through menopause
• Menstrual bleeding in women who have gone through menopause

Too much estrogen (in men) may cause:

• Growth of breast tissue
• Lower sex drive
• Impotence

These and other symptoms may be caused by adrenocortical carcinoma. Other conditions may cause the same symptoms. A doctor should be consulted if any of these problems occur.

Imaging studies and tests that examine the blood and urine are used to detect (find) and diagnose adrenocortical carcinoma.

The tests and procedures used to diagnose adrenocortical carcinoma depend on the patient's symptoms. The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of cortisol or 17-ketosteroids. A higher than normal amount of these in the urine may be a sign of disease in the adrenal cortex.
• Low-dose dexamethasone suppression test: A test in which one or more small doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
• High-dose dexamethasone suppression test: A test in which one or more high doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
• Blood chemistry study: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as potassium or sodium, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Blood tests: Tests to measure the levels of testosterone or estrogen in the blood. A higher than normal amount of these hormones that may be a sign of adrenocortical carcinoma.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). An MRI of the abdomen is done to diagnose adrenocortical carcinoma.
• Adrenal angiography: A procedure to look at the arteries and the flow of blood near the adrenal gland. A contrast dye is injected into the adrenal arteries. As the dye moves through the blood vessel, a series of x-rays are taken to see if any arteries are blocked.
• Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal gland. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the vein, a series of x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormal hormone levels.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

Certain factors affect the prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

• The stage of the cancer (the size of the tumor and whether it is in the adrenal gland only or has spread to other places in the body).
• Whether the tumor can be completely removed in surgery.
• Whether the cancer has been treated in the past.
• The patient's general health.

Adrenocortical carcinoma may be cured if treated at an early stage.

Stages of Adrenocortical Carcinoma

After adrenocortical carcinoma has been diagnosed, tests are done to find out if cancer cells have spread within the adrenal gland or to other parts of the body.

The process used to find out if cancer has spread within the adrenal gland or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen or chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium may be injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Adrenal angiography: A procedure to look at the arteries and the flow of blood near the adrenal gland. A contrast dye is injected into the adrenal arteries. As the dye moves through the blood vessel, a series of x-rays are taken to see if any arteries are blocked.
• Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal gland. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the vein, x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormal hormone levels.
• Cavagram: A procedure to look at the inferior vena cava and the flow of blood through the inferior vena cava. A contrast dye is injected into a blood vessel. As the contrast dye moves through the blood vessel to the inferior vena cava, a series of x-rays are taken to see if there are any changes to the inferior vena cava and the flow of blood through the inferior vena cava.
• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs, such as the vena cava, and make echoes. The echoes form a picture of body tissues called a sonogram.
• Adrenalectomy: A procedure to remove the entire adrenal gland. A tissue sample is viewed under a microscope by a pathologist to check for signs of cancer.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

• Through tissue. Cancer invades the surrounding normal tissue.
• Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
• Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for adrenocortical carcinoma:

Stage I

In stage I, the tumor is 5 centimeters or smaller and is found only in the adrenal gland.

Stage II

In stage II, the tumor is larger than 5 centimeters and is found only in the adrenal gland.

Stage III

In stage III, the tumor can be any size and may have spread to fat or lymph nodes near the adrenal gland.

Stage IV

In stage IV, the tumor can be any size and has spread:

• to fat or organs and to lymph nodes near the adrenal gland; or
• to other parts of the body. Adrenocortical carcinoma commonly spreads to the lung, liver, bones, and peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen).

Recurrent Adrenocortical Carcinoma

Recurrent adrenocortical carcinoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the adrenal cortex or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with adrenocortical carcinoma.

Different types of treatments are available for patients with adrenocortical carcinoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Three types of standard treatment are used:

Surgery

Surgery to remove the adrenal gland (adrenalectomy) is often used to treat adrenocortical carcinoma. Sometimes the nearby lymph nodes are also removed.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Mitotane may be used to treat adrenocortical carcinoma. Mitotane stops the adrenal cortex from making hormones and relieves symptoms caused by the hormones.

New types of treatment are being tested in clinical trials.

Below describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Stage I Adrenocortical Carcinoma

Treatment of stage I adrenocortical carcinoma is usually surgery (adrenalectomy). Lymph nodes may be removed if they are larger than normal.

Stage II Adrenocortical Carcinoma

Treatment of stage II adrenocortical carcinoma is usually surgery (adrenalectomy). Lymph nodes may be removed if they are larger than normal.

Stage III Adrenocortical Carcinoma

Treatment of stage III adrenocortical carcinoma may include the following:

• Surgery (adrenalectomy with or without removal of lymph nodes).
• A clinical trial of radiation therapy for tumors that cannot be removed by surgery.
• A clinical trial of mitotane for tumors that cannot be completely removed by surgery.

Stage IV Adrenocortical Carcinoma

Treatment of stage IV adrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:

• Mitotane therapy.
• Radiation therapy to bones where cancer has spread.
• Chemotherapy followed by surgery to remove the tumor.
• Surgery to remove the tumor.
• Surgery to remove cancer from places where it has spread.
• A clinical trial of chemotherapy or biologic therapy.

Treatment Options for Recurrent Adrenocortical Carcinoma

Treatment of recurrent adrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:

• Surgery to remove the tumor.
• Surgery to remove the cancer from places where it has spread.
• A clinical trial of chemotherapy or biologic therapy.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.