How is adrenal cancer diagnosed?

Signs and symptoms of adrenal cancers

In about half of people with adrenal cancer, symptoms are caused by the hormones made by the tumor. In the other half, symptoms occur because the tumor has grown so large that it presses on nearby organs. If you or your child has any of the signs or symptoms described in this section, discuss them with your doctor without delay. These symptoms may be caused by an adrenal tumor or by something else. Getting the proper medical tests is the only way to find out. The sooner you get a correct diagnosis, the sooner you can start treatment and the more effective your treatment will be.

Symptoms caused by androgen or estrogen production

In children, the symptoms are most often caused by the androgens (male-type hormones) that the tumor might secrete. The most common symptoms are excessive growth of facial and body hair (such as in the pubic and underarm area). The male hormones may also cause enlargement of the penis in boys or the clitoris in girls. If the tumor secretes estrogens (female-type hormones), it can cause girls to start puberty early. This can cause the breasts to develop and menstrual periods to start. In boys, estrogen-producing tumors may cause breast enlargement.

In adults, the symptoms from high levels of sex hormones are less noticeable because they have already gone through puberty and have breasts and adult patterns of body hair. Women with estrogen-producing tumors and men with androgen-producing tumors usually do not have any symptoms from the hormones, and so may have no symptoms until the tumor is large enough to press on nearby organs.

Symptoms are easier to notice if the tumor is making the hormone usually found in the opposite sex. For example, men with tumors that make estrogen (female hormone) may notice breast enlargement with tenderness. They may also have sexual problems such as erectile dysfunction (impotence) and loss of sex drive. Women with tumors that make androgens (male hormones) may notice excessive facial and body hair growth, receding hairline, irregular menstrual periods, and deepening of their voice.

Symptoms caused by cortisol production

Excessive levels of cortisol causes a problem known as Cushing syndrome. Some people have all of these symptoms, but many people with high cortisol levels have only 1 or 2 symptoms. These signs and symptoms include:

• Weight gain, usually greatest above the collar bone and around the abdomen
• Fat deposits behind the neck and shoulders
• Purple stretch marks on the abdomen
• Excessive hair growth on the face, chest, and back in women
• Menstrual irregularities
• Weakness and loss of muscle mass in the legs
• Easy bruising
• Depression and/or moodiness
• Weakened bones (osteoporosis), which can lead to fractures
• High blood sugar, often leading to diabetes
• High blood pressure

Cushing syndrome may be caused by an adrenal cancer or an adrenal adenoma that produces high levels of cortisol and/or related hormones. Benign pituitary gland tumors can produce high levels of another hormone called adrenocorticotropic hormone (ACTH). This is often called Cushing disease. The high levels of ACTH in turn cause normal adrenal gland tissue to produce more cortisol. This results in the same symptoms as Cushing syndrome. Very rarely ACTH can be produced by other tumors and cause the same symptoms.

Some people with immune system problems or some cancers, such as lymphomas, are treated with drugs chemically related to cortisol. Because there are so many causes of high cortisol levels that can lead to Cushing syndrome, doctors do a number of blood tests, urine tests, and imaging tests to find out whether the patient has an adrenal cortical tumor or some other cause of Cushing syndrome.

Symptoms caused by aldosterone production

The main signs and symptoms caused by aldosterone-producing adrenal tumors are high blood pressure, weakness, muscle cramps, and low blood potassium levels. Adrenal adenomas often produce this hormone, but adrenal cancers rarely do so.

Symptoms caused by a large adrenal cancer pressing on nearby organs

As an adrenal cancer grows, it presses on nearby organs and tissues. This may cause pain near the tumor, a feeling of fullness in the abdomen, or trouble eating because of a feeling of filling up easily.

Medical history and physical exam

The first step is to take your complete medical history to check for any symptoms. Your doctor will want to know if anyone in your family has had adrenal cancer or any other type of cancer. Your doctor will also ask about your menstrual or sexual function and about any other symptoms that you may be having. A physical exam will give other information about signs of adrenal gland cancer and other health problems. Your doctor will thoroughly examine your abdomen for evidence of a tumor (or mass).

Your blood and urine will be tested to look for high levels of the hormones produced by some adrenal adenomas and carcinomas. If an adrenal tumor or cancer is suspected, imaging tests will be done to look for a tumor. These tests can also help see if it has spread.

If a mass is seen on an imaging test and it is likely to be an adrenal cancer, doctors will recommend surgery to remove the cancer. Generally, doctors do not recommend removing a sample of the tumor to look at under the microscope to see if it is cancer (a biopsy) before surgery to remove the tumor. That is because doing a biopsy can increase the risk that an adrenal cancer will spread outside of the adrenal gland.

Imaging tests

Chest x-ray

This can show if the cancer has spread to the lungs. It may also be useful to determine if there are any serious lung or heart diseases.

Ultrasound

Ultrasound tests use sound waves to take pictures of parts of the body. A device called a transducer produces the sound waves, which are reflected by tissues of nearby organs. The pattern of sound wave echoes is detected by the transducer and analyzed by a computer to create an image of these tissues and organs. This test can show if there is a tumor mass in the adrenal gland. It can also diagnose tumor masses in the liver if the cancer has spread there. In general, it is not used to look for adrenal tumors unless a CT scan isn’t able to be done.

Computed tomography (CT)

The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a conventional x-ray, a CT scanner takes many pictures as the camera rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine will take pictures of many slices of the part of your body that is being studied.

CT scans show the adrenal glands fairly clearly and often can confirm the location of the cancer. It can also help show whether your cancer has spread into your liver or other organs nearby. CT scans can also show lymph nodes and distant organs where metastatic cancer might be present. The CT scan can help determine if surgery is a good treatment option.

Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body.

The injection can cause some flushing (redness and warm feeling that may last hours to days). A few people are allergic to the dye and get hives. Rarely, more serious reactions like trouble breathing and low blood pressure can occur. Medicine can be given to prevent and treat allergic reactions. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans can also be used to precisely guide a biopsy needle into a suspected metastasis. For this procedure, called a CT-guided needle biopsy, the patient remains on the CT scanning table, while a radiologist moves a biopsy needle toward the location of the mass. CT scans are repeated until the doctors are sure that the needle is within the mass. A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about ½ inch long and less than 1/8 inch in diameter) is removed and examined under a microscope.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table slides in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

Positron emission tomography (PET)

In this test, radioactive glucose (sugar) is injected into the patient’s vein. Because cancer cells use sugar much faster than normal tissues, radioactivity will tend to concentrate in the cancer. A scanner can spot the radioactive deposits. This test can be helpful for spotting small collections of cancer cells and may be used to find cancer that has spread. It also may help in deciding if an adrenal tumor is likely to be benign or malignant (cancer).

A special type of PET scan is currently used in research settings. It uses a radioactive form of a substance called metomidate. This substance seems to concentrate in adrenal cortical tissue, particularly adenomas and carcinomas. PET scanning with metomidate may in the future be helpful in distinguishing tumors that start in the adrenal cortex from cancers that started in other organs and then spread to the adrenals. It may also be helpful in finding adrenal cancer that has spread outside the adrenals.

Magnetic resonance imaging (MRI)

MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross sectional slices of the body like a CT scanner, it can also produce slices that are parallel with the length of your body. For some MRI scans, a contrast material called gadolinium is injected into a vein (IV). MRI may sometimes provide more information than CT scans because it can better distinguish adrenal cancers from benign tumors.

MRI scans are particularly helpful in examining the brain and spinal cord. In people with suspected adrenal tumors, an MRI of the brain may be done to examine the pituitary gland. Tumors of the pituitary gland, which lies underneath the front of the brain, can cause symptoms and signs similar to adrenal tumors.

MRI scans are a little more uncomfortable than CT scans. First, they often take up to an hour. You have to be placed inside a tube, which is confining and can upset people who become anxious in tight spaces (claustrophobia). If you have problems with tight spaces, tell your doctor before your MRI. Medicine may be given before the scan to help with anxiety. If that doesn't work, the exam may be scheduled at an open MRI scanner. These machines are not so enclosing and so are easier for some patients, although the drawback is that the pictures may not be as good. The machine also makes a thumping noise that you may find disturbing. Some places will provide headphones with music to block this sound out.

Other tests

Laparoscopy

This procedure uses a laparoscope, a thin, flexible tube with a tiny video camera on the end. It is inserted through a small surgical opening in the patient's side to allow the surgeon to see where the cancer is growing. It can spot distant spread as well as enlarged lymph nodes. Sometimes it is combined with ultrasound to give a better picture of the cancer. Laparoscopy may be done to help predict whether it will be possible to completely remove the cancer by surgery. In addition to viewing adrenal tumors through the laparoscope, surgeons can sometimes remove small benign adrenal tumors through this instrument. This method is described in the section, “Surgery for adrenal cancer.”

Biopsy

Imaging tests may find tumors, but often the only way to know for sure that a tumor is cancer is to remove a sample of tumor tissue to look at under the microscope. This is called a biopsy. If a thin needle that only removes tiny bits of tissue is used, it is called a fine needle aspiration, or FNA for short. When a larger needle that removes a thin cylindrical core of tissue is used, it is called a core needle biopsy. In either case, the biopsy is often done using a CT scan or ultrasound to guide the tip of the needle into the tumor.

Since adrenal adenomas and cancers can look alike under the microscope, a biopsy may not be able to tell whether or not an adrenal tumor is cancerous. Also, a needle biopsy of an adrenal cancer can actually spread tumor cells. For these reasons, a biopsy is generally not done before surgery if an adrenal tumor's size and certain features seen on imaging tests suggest it is cancer. Work-up with blood tests for hormone production and imaging studies are more useful than biopsies in the diagnosis of adrenal cancer.

If the cancer appears to have metastasized (spread) to another part of the body such as the liver, then a needle biopsy of the metastasis may be done. If a patient is known to have an adrenal tumor and a liver biopsy shows adrenal cells are present in the liver, then the tumor is cancer.

In general, a biopsy is only obtained in a patient with adrenal cancer when there are tumors outside the adrenals and the doctor needs to know if these are spread (metastases) from an adrenal cancer or are caused by some other cancer or disease. Adrenal tumors are sometimes biopsied when the patient is known to have a different type of cancer (like lung cancer) and knowing that there is spread to the adrenal glands would alter treatment.

Tests for adrenal hormones

Blood and urine tests to measure levels of adrenal hormones are important in deciding whether a patient with signs and symptoms of adrenal cancer has the disease. For urine tests, you may be asked to collect all of your urine for 24 hours. Blood and urine tests are as important as imaging studies in the diagnostic work-up of adrenal cancer. Doctors choose which tests to do based on the patient's symptoms. Doctors know which symptoms are associated with high levels of certain hormones, so they can focus on ways to look for the hormones most likely to be affected. Often doctors will check hormone levels even when symptoms of high hormone levels are not present. This is because symptoms of abnormal hormone levels can be very subtle and blood tests may even be able to detect changes in hormone levels before symptoms occur.

Tests for high cortisol levels

The tests used in this case include measuring levels of cortisol in the blood and in the urine. If an adrenal tumor is making cortisol, these levels will be abnormally high. These tests may be done after giving the patient a dose of dexamethasone. Dexamethasone is a drug that acts like cortisol. If given to someone who does not have an adrenal tumor, it will decrease production of cortisol and similar hormones. In someone with an adrenal cortex tumor, these hormone levels will remain high after they receive dexamethasone. Blood levels of ACTH will also be measured to help distinguish adrenal tumors from other diseases that can cause high cortisol levels.

Tests for high aldosterone levels

The level of aldosterone will be measured and will be high if the tumor is making aldosterone. Also, high aldosterone leads to low levels of potassium and renin (a hormone produced by the kidneys) in their blood.

Tests for high androgen or estrogen levels

Patients with androgen-producing tumors will have high levels of dehydroepiandrosterone sulfate (DHEAS) or testosterone and patients with estrogen-producing tumors will have high levels of estrogen in their blood.