Download Overview Adrenal cancer is a rare disease that originates in the

Overview
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
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:
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:
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.
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
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.
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.
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, 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
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, and 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:
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.
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.