Adrenal Carcinoma

Adrenal Carcinoma

Adrenal carcinoma (ACC) is a rare endocrine malignancy. According to the National Cancer Institute survey and the SEER (Surveillance, Epidemiology and End Results) database it affects only 0.7–2.0 persons per one million people. That translates into about 300 cases per year in the USA. At diagnosis, most individuals are between 30 and 50 years of age or are younger than 5 years of age.

ACC is deadly with a very poor prognosis because of late clinical presentation and limited effectiveness of chemotherapy.  Five-year survival rates vary from 65% in patient’s whose disease is found early to less than 10% in those with advanced cancer.

The Adrenal Glands

The adrenal glands are a pair of small and triangle shaped endocrine glands on top of each kidney. Each adrenal gland consists of two regions: the outer cortex and the inner medulla. The gland is the source of many important hormones in the body, which performs vital functions including the response to stress. When there is an adrenal carcinoma, too many hormones be made.


Epidemiology

Although rare, ACC is one of the most aggressive endocrine malignancies. The incidence of ACC is more frequent in women than in men. The prognosis of ACC is generally poor because most patients are diagnosed at an advanced stage when the tumor has grown significantly. ACC is more prevalent in children and in adults between 40 and 50.

Types of ACC

ACC can be classified as follows:

  • Differentiated: Most functioning tumors are differentiated.
  • Anaplastic: anaplastic tumors rarely produce hormones.
  • Hormonal: Approximately 60% of adrenocortical carcinomas produce high levels of hormones.

Symptoms

In almost half of the cases of ACC, abnormal hormone secretion cannot be detected and therefore patients do not show symptoms related to the hypersecretion of hormones. In most occasions, ACC is discovered when there is an abdominal pain. A lump in the abdomen or pain in the back may arise due to ACC.

Other signs or symptoms are related to too much secretion of hormones from the affected adrenal gland.

Hypersecretion of cortisol results in symptoms including:

  • Increase in weight in the upper region of body and face
  • Growth of fine hair mainly on the shoulders, arms and face
  • Reddish face
  • Soft fatty lump behind the neck
  • Deepening of the voice
  • Sex organs become swollen
  • Muscle strength becomes less
  • Increase in blood sugar
  • Hypertension

Hypersecretion of aldosterone may cause:

  • Hypertension
  • Muscle cramps
  • Urination is more often than usual
  • Dry throat (thirst)

Hypersecretion of testosterone in women may cause:

  • Deepening of the voice
  • Growth of fine hair mainly on the shoulders, arms and face
  • Acne
  • Balding
  • Menstrual periods to stop
  • Hypersecretion of testosterone in men lacks symptoms

Hypersecretion of estrogen in women may cause:

  • Menstrual irregularities (before menopause)
  • Menstrual bleeding (after menopause)

Hypersecretion of estrogen (in men) may cause:

  • Impotence
  • Enlargement of breast tissue
  • Low libido

In children, symptoms of early puberty can occur.

Risk factors

In most cases, the cause of ACC is unknown. However, people with certain hereditary conditions—such as Li-Fraumeni syndrome, Von Hippel-Lindau syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia (MEN-1), familial adenomatous polyposis (FAP) and Carney Complex—have a higher risk of developing an adrenal gland tumor.

Smoking has been associated with ACC.

Pathophysiology of ACC

The pathogenesis of ACC is not well understood.

The hereditary component of ACC demonstrates that there can be specific genes associated with this cancer in some cases. These genes are being studied.

An example of an involved gene is one which leads to expression of IGF-II (insulin-like growth factor II). This is linked to development of ACC. IGF-II is strongly over-expressed in 90 % cases of ACC. The insulin like growth factors play an important role in the development of the adrenal cortex and its role has been largely documented in adrenocortical tumors.

Research continues to explore the genetic component of ACC.

Diagnosis

Physical exam and history: Abdominal lumps can be detected by physical examinations. A patient’s symptoms are taken into consideration before performing other tests.

Urine examination: The quantity of cortisol secreted with the urine all throughout the day is measured. This gives an idea regarding the functioning of adrenal cortex.

Dexamethasone suppression test: In this test the hormone dexamethasone can be given, and urine samples are tested for the level cortisol for three days. The test can be used to detect if there is a tumor secreting cortisol than is not under normal control.

Blood test: The amounts of potassium or sodium ions and hormones like testosterone or estrogen (that may be released from the abnormal adrenal gland) in the blood are tested.

Ultrasound tests use sound waves to get pictures of possible masses.

CT scan (CAT scan): It is an imaging procedure of the internal organs of the body with the help of X ray machine attached to a computer.

MRI: The imaging technique is based on the use of a strong magnetic field and radio waves. The images can be viewed on a computer screen and ACC can be detected.

Adrenal angiography and venography: This procedure gives a series of X-ray images of the flow of blood through the arteries and veins near the adrenal gland.

PET scan: The PET scanner is an imaging technique, which helps to find out the spread of the disease.

For most people, their symptoms, blood tests and imaging tests can give a good idea if there is an ACC present. A biopsy must be used to make a definite diagnosis. This can be done before surgery using ultrasound to guide the biopsy. It can be done at the time of surgery.

Treatment

Surgery: Surgery is the main treatment for ACC at stage I and II i.e. if detected at an early stage. Small cancers can sometimes be removed by laparascopy, with a small camera and small incisions. Primary tumor and metastatic lesions can be removed by surgery. Surgery in combination with chemotherapy and radiation therapy can be an option for stage III and stage IV ACC.

Adjuvant radiation or chemotherapy with mitotane has not been proven to be of value in improving survival. Mitotane can reduce the symptoms of excess hormones.

Radiation therapy Radiation therapy can used to prevent reoccurrence or to help shrink tumors that have spread. It can be used in combination with chemotherapy to treat patients who have been detected late (Stage III or Stage IV).

Chemotherapy: There are a number of drugs being studied and used to treat ACC. Mitotane may be used to treat to reduce symptoms of adrenocortical carcinoma in Stages III and IV. Mitotane prevents hormone synthesis in the adrenal cortex. Mitotane is also used in combination with some of the other chemotherapy agents. Clinical trials are conducted to improve the types of treatment available at present.

Biologic therapy Biologic therapy is tries to use the immune system of an affected person to fight cancer. Clinical trials are being carried out to establish this form of treatment.

Prognosis

The treatment of ACC is planned after the stage in which the disease is diagnosed.

  • Stages I and II: These stages indicate localized cancers that have not spread. Tumors in Stage I tumors are around 5 cm across while stage II tumors are larger.
  • Stage III: The cancer has grown beyond the gland or has spread to nearby lymph nodes.
  • Stage IV: This represents cancers, which have spread to other organs extensively and are therefore not operable.

Many factors influence prognosis including stage of cancer, extent of spread, possibility of surgery and the health conditions of patient when diagnosed. If the tumor is diagnosed early, when the cancer has not yet spread, there is a chance of cure. Recurrence after surgery can lead to more serious prognosis. Currently, only 10 % people who diagnosed after metastasis remain alive after 5 years.

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  9. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.