Overview
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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
Most (99%) 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 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., breast, lung) may spread (metastasize) to the adrenal
glands.
Incidence and Prevalence
Worldwide, about 1 out of 1 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
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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. LiFraumeni 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:
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Gardner syndrome
Carney triad
Cowden syndrome
Familial polyposis
Turcot syndrome
Signs and Symptoms
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Adrenal cancer does not always produce symptoms. Both nonfunctioning
adrenocortical carcinomas and large functioning tumors may cause the following:
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Fever
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.
Complications
A functioning adrenocortical tumor that produces excess cortisol may result in
Cushing's syndrome. Approximately 30–40% of patients with Cushing's syndrome
and an adrenal mass are diagnosed with adrenal cancer.
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Symptoms of Cushing's syndrome include the following:
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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:
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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
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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.
Imaging Tests
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.
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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
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. 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
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.
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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.
Surgery
Surgical removal of the adrenal gland (called adrenalectomy) is the only 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, kidneys)
often requires extensive surgery. Adrenal tumors that have not spread are
sometimes removed using laparoscopic adrenalectomy, which is performed through a
smaller incision.
Chemotherapy
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 (Lysodren®) 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, diarrhea) and neurological
disturbances (e.g., depression, lethargy, sleepiness).
When mitotane therapy fails, cisplatin (Platinol®) may be tried, alone or combined
with other agents. Drug combinations used include the following:
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Cyclophosphamide (Cytoxin®, Neosar®), doxorubicin (Adriamycin®),
cisplatin
Fluorouracil (Adrucil®, Efudex®), doxorubicin, cisplatin
Cisplatin with VP-16
Neuroblastoma may be treated with chemotherapy in addition to surgery (adjuvant
therapy) using carboplatin (Paraplatin®), cyclophosphamide, doxorubicin, and
etoposide (Vepesid®).
Side effects of chemotherapy are often severe and include gastrointestinal
disturbances, low blood count (anemia), skin disorders, and neurological disorders.
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Radiation Therapy
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 (Nizoral®) 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 (Aldactone®). 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 (Arimidex®) and anti-androgens such as
bicalutamide (Casodex®) may be used to treat excessive androgen production.
Prognosis
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.
Prevention
Adrenal cancer cannot be prevented.