Adrenal Cancer

Overview

Adrenal cancer is a rare type of cancer that develops in the small, triangular-shaped glands located just above the kidneys. These glands are vital organs that regulate the body's hormonal balance, and there is one above each kidney. The adrenal glands consist of two different regions: the outer part (cortex) and the inner part (medulla). Cancer can develop in either of these regions, but the most common type is adrenocortical carcinoma, which originates from the outer part.

Adrenal cancer is quite rare and is seen in approximately 1-2 out of every million people each year. Although it can occur at any age, it is most commonly diagnosed in adults between ages 40-50. It tends to occur slightly more in women than in men.

The most important feature of adrenal cancer is that since it develops in a hormone-producing organ, it can secrete excess hormones, leading to various hormonal disorders in the body. Tumors that secrete hormones are called "functional tumors," while those that do not secrete hormones are called "non-functional tumors." Non-hormone-secreting tumors are usually not noticed until they grow and press on surrounding organs, and are often found incidentally during imaging tests done for another reason.

Early diagnosis is very important in this disease. When caught at a small size and completely removable surgically, treatment success is quite high. For this reason, being aware of symptoms and not neglecting regular checkups is vital.

Symptoms

The symptoms seen in adrenal cancer are grouped into two main categories: symptoms related to hormone secretion by the tumor and symptoms related to the tumor growing and pressing on surrounding organs. Non-hormone-secreting tumors generally do not cause symptoms and are noticed incidentally during tests done for another reason.

Adrenal cancer may include the following symptoms:

• Symptoms related to cortisol excess (Cushing syndrome). Cortisol is the body's stress hormone, and when secreted in excess, a typical appearance emerges. Pronounced rounding and redness occurs in the face (moon face). Fat accumulation (buffalo hump) develops in the back and shoulder region. While weight increases in the abdominal area, arms and legs remain thin. The skin becomes thin, bruises easily, and wide purple-colored stretch marks appear in the abdominal area. Muscle weakness is felt, especially in the legs and around the hips. High blood pressure, elevation in blood sugar, or diabetes can develop. Mood changes, irritability, depression, and sleep problems may also accompany.
• Symptoms related to aldosterone excess (Conn syndrome). Aldosterone is the hormone that regulates the body's salt and water balance. In excess, high blood pressure usually emerges that cannot be controlled with medications. Due to low potassium in the blood, muscle weakness, cramps, and fatigue are felt. Frequent urination, especially the need to get up to use the bathroom at night, increases, and accordingly, excessive thirst develops.
• Symptoms related to sex hormone excess. The tumor can produce male hormone (androgen) or female hormone (estrogen). In androgen excess in women, increased hair growth on the face, chest, and abdomen, menstrual irregularities or absence of menstruation, voice deepening, increased acne, and thinning of hair are seen. In estrogen excess in men, breast growth and tenderness, decreased sexual desire, and impotence may occur.
• Symptoms related to tumor growth. As the tumor grows, it begins to press on surrounding organs. Pain, fullness, or discomfort occurs in the abdominal area; this pain can generally radiate to the back. A mass that can be felt by hand in the abdomen may be noticed. Due to pressure on the stomach, early satiety, nausea, and loss of appetite develop. Constipation or change in bowel habits may occur. When the tumor grows backward, back pain is felt.
• Advanced stage symptoms. When cancer spreads to other parts of the body, symptoms related to metastasis appear. In liver metastases, jaundice, abdominal swelling, and abdominal pain are seen. In lung metastases, shortness of breath, cough, and coughing up blood may occur. In bone metastases, severe bone pain and spontaneous fractures can develop. In lymph node metastases, palpable swellings may be noticed. In addition, general deterioration, weakness, fatigue, and involuntary weight loss are also among advanced stage symptoms.

When to See a Doctor

In the following situations, it is recommended that you consult an internal medicine or endocrinology specialist:

• If you have any of the hormonal symptoms described above, especially if you notice sudden onset of facial rounding, uncontrollable high blood pressure, unexplained muscle weakness, or unexpected increase in hair growth in women
• If you feel a palpable mass in the abdominal area or unexplained pain
• If you are experiencing general symptoms such as unexplained weight loss, weakness, or fatigue
• If an incidental mass was detected in the adrenal gland during imaging done for another reason, further evaluation must definitely be done

Causes and Risk Factors

The exact cause of adrenal cancer is not known. However, research shows that genetic factors and some hereditary syndromes play a role in the development of the disease.

Causes may include:

• Genetic factors. Some hereditary syndromes increase the risk of adrenal cancer. Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Multiple Endocrine Neoplasia type 1 (MEN1), and Lynch syndrome can be counted among these. In people with a family history of cancer such as early-onset breast cancer, bone cancer, brain tumor, or sarcoma, the risk may be higher.
• Age and gender. Although the disease can be seen at any age, it is most commonly diagnosed in adults between ages 40-50. It tends to occur slightly more in women than in men.
• Other risk factors. Smoking and exposure to some chemicals are among other factors that may increase risk. However, the relationship between these factors and the disease has not been definitively proven.

Complications

Adrenal cancer can lead to serious problems if left untreated or in advanced stages.

Hormonal complications. Excess hormones produced by the tumor can cause permanent damage to the body. Cortisol excess leads to diabetes, bone loss, and related fractures. Prolonged bone loss can cause collapses in the spine, shortening of height, and severe back pain. Aldosterone excess leads to uncontrollable high blood pressure, heart enlargement, heart failure, and increased risk of stroke. Long-term high blood pressure can also cause kidney damage.

Complications related to tumor spread. The growing tumor can spread to neighboring organs. The most commonly affected organs are the kidney, liver, pancreas, and spleen. This can lead to loss of function, bleeding, or blockage of the relevant organ. Cancer cells can spread to other parts of the body through blood or lymph. Most commonly it metastasizes to the liver, lungs, bones, and lymph nodes. Liver metastases can cause liver failure, lung metastases can cause respiratory failure, and bone metastases can cause severe pain and spontaneous fractures.

Adrenal crisis. Patients who have had both adrenal glands removed or people whose glands' function is suppressed due to tumor must use hormone medication for life. Not using these medications regularly or not increasing the dose in stressful situations such as febrile illness, accident, or surgery can lead to life-threatening adrenal crisis.

Adrenal crisis symptoms include:

• Extreme weakness and exhaustion
• Low blood pressure and fainting
• Severe nausea, vomiting, and abdominal pain
• Confusion

In these symptoms, emergency medical help should be obtained without delay.

Diagnosis

The diagnosis of adrenal cancer is made by using hormone tests and imaging methods together. During the diagnostic process, answers are sought to three basic questions: whether the mass is benign or malignant, whether it secretes hormones, and how much the disease has spread in the body.

Hormone tests. These tests are done to determine whether the tumor produces excess hormones. Cortisol levels are checked in blood and 24-hour urine. If aldosterone excess is suspected, blood aldosterone and renin levels are measured and compared to each other. For sex hormones, androgen levels are evaluated in women and estrogen levels in men. If the tumor is thought to originate from the inner part, chromogranin A and metanephrine tests are done.

Imaging methods. These methods are used to evaluate the characteristics and spread of the mass. Computed tomography (CT) is an X-ray method that creates cross-sectional images of the body and is the most commonly used test. It provides detailed information about the tumor's size, borders, internal structure, and relationship with surrounding organs.

The main CT findings that increase cancer suspicion are:

• The tumor being larger than 4-5 cm
• Irregular borders and internal structure with different densities
• Areas of necrosis (dead tissue), bleeding, or calcification
• Lymph node enlargement or spread to surrounding organs

Magnetic resonance imaging (MRI) is a method that creates detailed images using powerful magnetic fields and radio waves. It provides superiority over CT especially in evaluating liver metastases and showing the relationship with large vessels.

PET-CT is a special imaging method that shows the high metabolic activity of cancer cells. A slightly radioactive sugary substance given to the patient accumulates in cancer cells and is imaged with a special camera. It is used in detecting metastases, evaluating response to treatment, and in cases of suspected recurrence.

Biopsy. Biopsy (taking a piece with a needle) is not routinely recommended in adrenal gland masses. The main reasons for this are that needle biopsy does not always give definitive results, carries risks such as bleeding and infection, and the possibility of tumor cells being seeded along the needle track. Biopsy is generally done to confirm diagnosis in patients with cancer in another organ and suspected metastasis to the adrenal gland, or in advanced stage patients for whom surgical treatment is not planned.

Staging. After diagnosis is confirmed, staging is done to determine how much the disease has spread. Staging is very important for creating the treatment plan and making predictions about the course of adrenal cancer:

• Stage I: The tumor is 5 cm or smaller, limited only to the adrenal gland, there is no lymph node or distant metastasis.
• Stage II: The tumor is larger than 5 cm, but is still limited only to the adrenal gland, there is no lymph node or distant metastasis.
• Stage III: The tumor is any size, but has spread to surrounding tissues or regional lymph nodes.
• Stage IV: The tumor has made distant metastasis to other organs (such as liver, lung, bone).

Treatment

Treatment of adrenal cancer is planned according to the stage of the tumor, whether it secretes hormones, and the patient's general health condition. Treatment options may include:

Surgical treatment. This is the first and most effective treatment option in localized cancer. The goal is to completely remove the tumor with clean surgical margins. This surgery, called adrenalectomy, can be performed by two different methods:

• Open surgery: Preferred in large tumors (generally larger than 6-8 cm) or when there is suspicion of spread to surrounding tissues. It is done with a larger incision in the abdominal area, allowing better visualization of the tumor and surrounding lymph nodes.
• Laparoscopic (closed) surgery: Applied in smaller tumors (smaller than 6 cm) and when there is no spread to surrounding tissue. It is done with a camera and special surgical instruments entering through several small incisions. Hospital stay is shorter, recovery is faster.

During surgery, surrounding lymph nodes are also removed along with the tumor. If the disease has made a limited number of metastases to a single organ, surgical removal of these metastases may also be considered.

Mitotane treatment. Mitotane is a medication specific to adrenal cancer. It selectively destroys adrenal gland cells and suppresses hormone production.

It is used in two ways:

• Adjuvant treatment: Given preventively in patients with high risk of recurrence after surgery.
• Metastatic disease: First-line treatment in widespread disease.

During mitotane treatment, drug levels are monitored with regular blood tests. It needs to reach a certain level in the blood to be effective, but above this level the risk of side effects increases.

Chemotherapy. Used in patients who do not respond to mitotane or whose disease is progressing. Chemotherapy drugs target rapidly dividing cancer cells. It is usually given together with mitotane. Side effects of chemotherapy include nausea, vomiting, temporary hair loss, fatigue, and susceptibility to infections.

Radiotherapy. Radiotherapy is a treatment method that aims to destroy cancer cells using high-energy rays. It is a painless procedure and is usually done in short sessions applied every weekday.

It is used for two purposes:

• Applied to regions with high local recurrence risk after surgery to destroy remaining microscopic tumor cells.
• Used palliatively to relieve symptoms such as pain related to metastases.

Treatment of hormone excess. In hormone-secreting tumors, additional treatments are applied to control the effects of excess hormones. Appropriate medications are started for high blood pressure, blood sugar is regulated, potassium balance is maintained. In cortisol excess, medications that suppress steroid synthesis such as ketoconazole can be used. In aldosterone excess, aldosterone antagonists such as spironolactone are preferred.

Living with Adrenal Cancer

Regular follow-up is essential. Adrenal cancer is a disease that can recur. For this reason, regular doctor checkups after treatment are very important.

The follow-up program usually includes:

• Physical examination and imaging (CT or MRI) every 3-6 months for the first 2-3 years
• Annual checkups thereafter
• Regular blood and urine tests according to the hormones secreted by the tumor
• Regular blood drug level monitoring in patients using mitotane

Use your hormone medications regularly. Patients who have had both adrenal glands removed must use hormone medication for life.

These medications are:

• Instead of cortisol: Prednisolone or hydrocortisone, two-three times a day
• Instead of aldosterone: Fludrocortisone, once a day

Take your medications regularly as your doctor recommends. Remember that the medication dose may need to be increased in stressful situations such as febrile illness, accident, or surgery.

Learn adrenal crisis symptoms. Symptoms such as extreme weakness, low blood pressure, fainting, nausea, vomiting, and abdominal pain may be harbingers of adrenal crisis. Get emergency medical help without delay in these symptoms. Carrying a card or medical alert bracelet that says "Adrenal Insufficiency – Requires Steroid Treatment in Emergency" can be life-saving for emergency intervention.

Adopt healthy lifestyle habits. If you are using corticosteroids, pay attention to salt and sugar consumption. To prevent bone loss risk, eat foods rich in calcium and vitamin D; consume milk, yogurt, cheese, and green leafy vegetables. If you are using mitotane, avoid fatty and processed foods to not strain the liver. Do not neglect drinking plenty of water.

Exercise regularly. Regular physical activity preserves muscle strength, reduces fatigue, and supports bone health. Low-impact exercises such as walking, swimming, and cycling are ideal. Consult your doctor before starting an exercise program.

Protect yourself from infections. Medications used can increase infection risk. Wash your hands frequently, avoid crowded environments. Get your flu and pneumonia vaccines. Consult your doctor if you have infection symptoms such as fever or cough.

Get support. Do not hesitate to ask for support from your family and friends during the disease process. Communicating with people who have experienced similar situations is very valuable for information sharing and moral support. Do not hesitate to get psychological support when needed.

Preparing for Your Appointment

Preparing before going to your doctor's appointment makes the visit more productive.

What you can do:

• Note the symptoms you are experiencing, when they started, how often they occur, and what triggers the symptoms.
• If you are tracking blood pressure, record your measurements.
• List all medications, vitamins, and supplements you are using.
• Find out if there is a history of cancer, adrenal gland disease, or hereditary syndrome in your family.
• Bring previous imaging tests and blood tests if available.
• Write down your questions in advance.

Questions you can ask your doctor:

• What is the likelihood of the mass being benign or malignant?
• Is the tumor secreting hormones?
• What stage is my disease?
• Which treatment options are appropriate for me?
• Will surgery be needed? Which method will be applied?
• What are the risks of surgery? How will the recovery process be?
• Will I need additional treatment after surgery?
• Will I need to use hormone medication?
• How often should I have checkups?
• What should I do in case of adrenal crisis?
• What should I pay attention to in my daily life?

Your doctor may ask you:

• What symptoms are you experiencing? When did symptoms start?
• Do you have a blood pressure problem? Are you using blood pressure medication?
• Do you have diabetes?
• If you are female, how is your menstrual cycle?
• Have you recently gained or lost weight?
• Have you noticed bruising, stretch marks, or darkening on your skin?
• Is there a history of cancer in your family?
• Do you smoke?
• Have you had cancer treatment before?