What is Adrenal Cancer?
Adrenal cancer is a rare disease that originates in the adrenal glands. The adrenal glands are located on top of the kidneys and consist of two parts that function separately: the outer layer (cortex) and the inner area (medulla).
The cortex produces three major hormones: cortisol (a glucocorticoid), aldosterone (a mineralocorticoid), and dehydroepiandrosterone (DHEA; an androgen). The medulla produces epinephrine (adrenaline), norepinephrine, and dopamine.
Adrenal tumors can increase hormone production (called functioning tumors). Adrenal tumors that do not produce hormones are called nonfunctioning. Symptoms of adrenal cancer and treatment for the condition depend on whether the tumor is functioning or nonfunctioning, and on which hormone is being overproduced.
Types of Adrenal Tumors
Most adrenal tumors are noncancerous (i.e., benign) adrenal cortical adenomas and do not require treatment. These tumors usually do not cause symptoms, are small, and are found incidentally during diagnostic imaging.
The most common type of adrenal cancer develops in the adrenal cortex and is called adrenocortical carcinoma. Functioning adrenocortical carcinomas may produce symptoms related to increased hormone production.
Nonfunctioning tumors may cause pain from pressure on abdominal organs and rarely a mass in the abdomen that is able to be felt with the fingers (palpable).
Cancers that develop in the adrenal medulla include neuroblastoma (originates in undeveloped nerve cells) and pheochromocytoma (originates in cells that produce epinephrine and norephinephrine). Neuroblastoma usually occurs in infants and children and pheochromocytoma more commonly occurs in people who are in their 30s and 40s.
Other types of cancer (e.g.,lung, breast) may spread (metastasize) to the adrenal glands.
Incidence and Prevalence
Worldwide, about one out of one million people develop adrenal cancer each year. Prevalence of the condition is slightly higher in men in their 40s and 50s and in children younger than 5 years old.
Causes and Risk Factors
The cause of adrenal cancer is unknown and most cases do not have identifiable risk factors. In some cases, heredity plays a role in the development of the disease. Li-Fraumeni syndrome and type 1 multiple endocrine neoplasia (MEN1) are genetic mutations in tumor suppressor genes that increase the risk for several types of cancer, including adrenal cancer.
Genetic testing may be recommended in families with a high incidence of suspected tumor suppressor gene mutation. Other familial syndromes associated with adrenal cancer include:
- Gardner syndrome
- Carney triad
- Cowden syndrome
- Familial polyposis
- Turcot syndrome
Signs and Symptoms
Adrenal cancer does not always produce symptoms. Both nonfunctioning adrenocortical carcinomas and large functioning tumors may cause the following:
- Palpable (able to be felt with the fingers) abdominal mass
- Persistent abdominal pain
- Sensation of abdominal “fullness”
- Weight loss
Additional symptoms of functioning adrenocortical carcinoma depend on which hormones are overproduced. Overproduction of androgens (e.g., dehydroepiandrosterone, estrogen) usually does not produce symptoms in men because the testicles produce testosterone, which is a more potent androgen. Rarely, abnormal breast enlargement (gynecomastia) occurs in men. Excess androgens may cause early puberty in children and masculinization (i.e., abnormal facial and body hair, deepening voice) in women and children.
A functioning adrenocortical tumor that produces excess cortisol may result in Cushing’s syndrome. Approximately 30 to 40% of patients with Cushing’s syndrome and an adrenal mass are diagnosed with adrenal cancer. Symptoms of Cushing’s syndrome include the following:
- Absence of menstruation (amenorrhea)
- Bruising easily
- Excessive growth of facial and body hair in women (hirsutism)
- Flushing (reddish complexion)
- High blood pressure (hypertension)
- Increased blood sugar, diabetes (hyperglycemia)
- Increased body fat (adiposity) in the face, neck, and abdomen
- Loss of bone mass (osteoporosis); may cause spinal curvature
- Severe acne
- Slowed growth rate in children
- Stretch marks (abdominal striae)
- Weakness and muscle wasting
Conn’s syndrome is caused by increased aldosterone production and may result from a functioning tumor in the adrenal cortex. Symptoms of Conn’s syndrome include the following:
- Chronic excessive thirst (polydipsia)
- Excessive urination (polyuria)
- High blood pressure (hypertension)
- Low level of potassium in the blood (hypokalemia)
The hallmark of pheochromocytoma is sudden or sustained high blood pressure that is often resistant to treatment. Other symptoms include severe headaches, sweating, heart palpitations (rapid pulse), and nausea. Symptoms of neuroblastoma include abdominal pain and bone pain resulting from metastatic disease.
Diagnosis of adrenal cancer involves taking a medical history and performing a physical examination, blood and urine tests, imaging tests, and a biopsy. Medical history includes family history of adrenal cancer, menstrual (in women) and sexual history, and the patient’s history of symptoms. Physical examination includes palpating (feeling with the fingers) the abdomen for evidence of an adrenal mass.
Blood and Urine Tests
Blood and urine tests are used to detect elevated levels of hormones (e.g., cortisol, aldosterone) and other substances (e.g., potassium). The patient’s symptoms determine which tests are performed.
Computed tomography (CT scan) and magnetic resonance imaging (MRI scan) are the imaging studies of choice used to produce images of the adrenal gland and identify abnormal enlargement or tumors.
CT scan uses x-rays to produce detailed images of the adrenal glands, other abdominal organs, and lymph nodes. In some cases, a contrast agent (dye) is used to detect metastasis.
MRI uses magnetic fields to produce a cross-sectional image that detects abnormal enlargement of the adrenal gland. This test may be used to help determine if adrenal tumors are benign or cancerous (malignant).
Biopsy is the surgical removal of cells or tissue for microscopic evaluation. This procedure may be used to evaluate an adrenal mass for cancer cells however the pathologic accuracy is often in question. During biopsy, ultrasound or CT scan is used to guide a needle into the tumor to remove cells (called a fine needle aspirate) or a larger amount of tissue (called core tissue biopsy). The cells are then examined under a microscope and if cancerous cells are found, the cancer
Treatment for adrenal cancer depends on the stage of the disease at diagnosis. Options include surgery, chemotherapy, and radiation. Treatment for patients with functioning tumors usually involves using medications to manage symptoms.
Pheochromocytomas require treatment before surgery (neoadjuvant treatment) for high blood pressure, which often includes alpha-blockers (e.g., phenoxybenzamine, prazosin) followed by beta-blockers (e.g., propranolol), and metyrosine.
Surgical removal of the adrenal gland (called adrenalectomy) is the only established cure for adrenal cancer. It is important to determine if the cancer has spread before surgery, because metastases to lymph nodes or other organs (e.g., liver, lungs, and kidneys) often require extensive surgery. Adrenal tumors that have not spread are sometimes removed using laparoscopic adrenalectomy, which is performed through a smaller incision.
Chemotherapy is a treatment that travels throughout the body via the bloodstream (called a systemic treatment) that often uses a combination of drugs to destroy cancer cells. It is used as a palliative treatment for metastatic adrenal cancer and may also be used in addition to surgery (adjuvant therapy). Drugs may be administered orally or through a vein (intravenously).
Mitotane (LysodrenÆ) suppresses adrenal gland function and is the drug of choice to treat inoperable adrenal cancer. Approximately 20% of adrenal cancer patients respond to treatment with mitotane. Side effects include gastrointestinal disturbances (e.g., loss of appetite, nausea, vomiting, and diarrhea) and neurological disturbances (e.g., depression, lethargy, sleepiness).
When mitotane therapy fails, cisplatin (PlatinolÆ) may be tried, alone or combined with other agents. Drug combinations used include the following:
- Cyclophosphamide (CytoxinÆ, NeosarÆ), doxorubicin (AdriamycinÆ), cisplatin
- Fluorouracil (AdrucilÆ, EfudexÆ), doxorubicin, cisplatin
- Cisplatin with VP-16
Neuroblastoma may be treated with chemotherapy in addition to surgery (adjuvant therapy) using carboplatin (ParaplatinÆ), cyclophosphamide, doxorubicin, and etoposide (VepesidÆ).
Side effects of chemotherapy are often severe and include gastrointestinal disturbances, low blood count (anemia), skin disorders, and neurological disorders.
Radiation therapy uses high energy x-rays to destroy cancer cells. Radiation is not used as a primary treatment for adrenal cancer. It is sometimes used as a pain relieving (palliative) treatment for metastatic adrenal cancer.
Medical Management of Functioning Tumors
Treatment for patients with functioning tumors includes managing symptoms caused by increased hormone production. Increased cortisol production (Cushing’s syndrome) is often treated with aminoglutethimide or ketoconazole (NizoralÆ) to inhibit cortisol build-up (synthesis). They may be used alone, or in combination with chemotherapy. Side effects include nausea, vomiting, and abdominal pain.
Excess aldosterone production ( Conn’s syndrome) is usually treated using spironolactone (AldactoneÆ). Spironolactone is an aldosterone antagonist (i.e., counteracts the action of aldosterone). Side effects include ulcers, abnormal breast enlargement in men (gynecomastia), fever, and headache.
Aromatase inhibitors such as anastrozole (ArimidexÆ) and anti-androgens such as bicalutamide (CasodexÆ) may be used to treat excessive androgen production.
The prognosis for adrenal cancer depends on the stage of the disease. Metastatic tumors have a poor prognosis. The 5-year survival rate when surgical removal of the cancer is achieved is approximately 40%. About 80% of cases recur within 10 years after treatment.
Adrenal cancer cannot be prevented.