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. 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:
|
|
Fever
|
|
|
Palpable
(able to be felt with the fingers) abdominal mass
|
|
|
Persistent
abdominal pain |
|
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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) |
|
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High blood
pressure (hypertension) |
|
|
Increased
blood sugar, diabetes (hyperglycemia)
|
|
|
Increased
body fat (adiposity) in the face, neck, and abdomen
|
|
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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)
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 is staged.
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,
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:
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.
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