Adrenocortical Carcinoma Causes, Symptoms, Diagnosis, Treatment, Prevention

Adrenocortical Carcinoma Causes, Symptoms, Diagnosis, Treatment

What Is Adrenocortical Carcinoma?

Adrenocortical carcinomais a cancer of the adrenal gland. The condition is also called cancer of the adrenal cortex, adrenal cortical cancer, or adrenocortical cancer. This cancer is very rare.

The adrenal gland is a small organ above the kidney. It makes important hormones. There are two adrenal glands in the body. One sits on top of each kidney. Adrenal glands are part of the endocrine system. Your endocrine system helps regulate body activities.

Adrenocortical carcinoma develops in the outer layer of the adrenal gland. This layer is called the cortex. It produces hormones that

  • help control blood pressure
  • balance water and salt in the body
  • help manage the body's use of protein, fat, and carbohydrates
  • cause a person to have male or female characteristics.
Adrenocortical cancer can spread to other parts of the body including the lungs, liver, or bones.

Small lumps on the adrenal gland are not uncommon. They are usually benign (noncancerous) growths called adrenal adenomas. In some cases, doctors may have trouble distinguishing an adenoma from a cancer, so you may need special testing or repeat examinations.

Another type of adrenal gland tumor, called a pheochromocytoma, can develop in the inner part of the gland, or adrenal medulla. However, this article will only discuss cancers that arise in the adrenal cortex.

What Causes Adrenocortical Carcinoma? 

The answer is unknown. There is no known association with smoking, alcohol consumption, or other occupational or environmental exposures. There is a small minority of patients with a hereditary component that may be related to genetic syndromes, such as those with p53 gene abnormalities (the p53 gene codes for a protein which has been demonstrated to be a tumor suppressor protein; ie. when abnormal, the cell may acquire an ability to become cancer).

Risk Factors of Adrenocortical Carcinoma

There are few known risk factors for cancers of the adrenal cortex. However, the following factors may contribute:

  • Sex: female
  • Children under 5 years old
  • Adults between 40 and 50 years old
  • A genetic defect may cause adrenocortical cancer in some children, but the majority of cases are nonhereditary

Having certain genetic conditions increases the risk of developing adrenocortical carcinoma

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for adrenocortical carcinoma include having the following hereditary diseases:

  • Li-Fraumeni syndrome
  • Beckwith-Wiedemann syndrome
  • Carney complex

Symptoms of Adrenocortical Carcinoma

Tumors of the adrenal gland are classified as either functioning or nonfunctioning:

  • A functioning adrenocortical tumor overproduces certain hormones. It may trigger symptoms.
  • A nonfunctioning adrenocortical tumor doesn't secrete hormones. It may not cause symptoms early on.
The symptoms associated with functioning adrenocortical tumors vary. They depend on which hormones are overproduced and on the patient's age.

Cortisol helps the body use sugar, protein, and fats. Having too much of this hormone may cause

  • weight gain in the abdomen, face, neck, and chest
  • excessive hair growth on the face, chest, back, or arms
  • purple or pink stretch marks on the belly
  • a lump of fat behind the neck and shoulders
  • deepening of the voice
  • swelling of the sex organs or breasts (in men and women)
  • irregular menstrual periods (in women)
  • severe fatigue and muscle weakness
  • easy bruising
  • bone fractures
  • moodiness and/or depression
  • high blood sugar
  • high blood pressure.
Some of these symptoms are also characteristic of Cushing syndrome. This noncancerous condition affects the pituitary gland in the brain.

Aldosterone helps control the balance of water and salts in the kidney. Having too much of this hormone may lead to

  • high blood pressure
  • muscle weakness or cramps
  • frequent urination
  • feeling thirsty
  • fluid build-up in the body's tissues
Androgens and estrogen are hormones that help develop and maintain sex characteristics that distinguish males and females.The major androgen is testosterone. Women with too much testosterone may have

  • hair growth on the face and body
  • acne
  • balding
  • a deepening of the voice
  • menstrual changes.
Women who have too much estrogen may experience

  • irregular menstrual periods
  • menstrual bleeding (if they have stopped having periods).
Men with too much estrogen may have

  • breast growth and tenderness
  • lower sex drive
  • inability to get or maintain an erection.
In children, the symptoms are different. An adrenal tumor that produces male sex hormones can cause

  • excessive facial, pubic, and underarm hair
  • an enlarged penis (in boys)
  • an enlarged clitoris (in girls).
A tumor that secretes female sex hormones in children can set off

  • early puberty (in girls)
  • breast enlargement (in boys).
Some patients experience symptoms when the tumor grows and presses on nearby organs and tissues. This may be felt as a lump or pain near the tumor, fullness in the belly, or trouble with eating or weight loss.

If you or your child has these symptoms, discuss them with your doctor right away.

How Is Adrenocortical Carcinoma Diagnosed?

Your doctor will ask about your symptoms, and medical and family history. A physical exam will be done.

Your bodily fluids may be tested. This can be done with:

  • Blood tests
  • Urine tests
Your doctor may need detailed pictures of the body. These can be made with:

  • CT scan
  • MRI scan
  • Positron emission tomography (PET)/CT scan
  • Adrenal angiography and/or venography
  • X-ray
After cancer of the adrenal cortex is confirmed, you will be referred to an oncologist. This type of doctor focuses on cancer.

Additional testing will be done to determine what stage the cancer has reached. The stage of a tumor is determined by its size and how far it has spread from its point of origin.

How Can Adrenocortical Carcinoma Be Treated?

Early stage disease is highly curable through surgical resection of the tumor by specially trained surgical oncologists, such as endocrine surgeons, who specialize in treating this disease. The problem is that many, if not most, ACCs are found at advanced stages.

While there is no curative treatment available for metastatic and recurrent ACC, patients may still benefit from various modalities of therapy.

If the tumor can be fully removed, surgical resection is the primary recommended route. If possible, complete surgical resection is preferred over incomplete resection (higher reported survival rates support this). After surgery, mitotane treatment (a drug therapy) may be utilized to potentially improve cure rates and increase survival. While this is an attractive idea, supportive clinical literature has been quite inconsistent. Some studies showed improved benefit with therapy whereas other studies did not. Probably one of the best studies to date was published by Terzolo et al. (2007). In this study, patients who received postoperative mitotane therapy had higher rates of recurrence-free survival compared with those who did not receive mitotane.

If the tumor is not resected, the patient has the potential to develop distant metastases or advanced adrenocortical carcinoma. Mitotane is also utilized in patients with unresectable tumors of any stage. Potential gastrointestinal and neurological side effects include vomiting, nausea, and anorexia; these can also be attributed to lack of cortisol. Occasionally, the side effects may limit the use of this medicine.

There is a variety of chemotherapies, such as cisplatin, etoposide, doxorubicin, streptozotocin, vinca alkaloids, that can be used to treat ACC. Newer therapies, such as gemcitabine, taxanes, capecitabine, and bevacizumab, maybe utilized, although supportive data are scant. Supportive care may be important, especially for those who have had complete surgical resection of their adrenal gland(s), in the form of hormone-replacement therapy. After a tumor is surgically removed, often hormone deficiency ensues if hormones are not administered to the body. Various hormones and dosages can be given as directed and monitored by an endocrinologist.

For advanced disease, other local modalities of therapies may be pursued in terms of palliating (improving) symptoms. These modalities, including radiation therapy, radiofrequency ablation (RFA), cryotherapy, and nerve ablative techniques, may be important to manage tumor complications of growth. Sometimes RFA or radiation therapy may be administered in the primary management of adrenocortical carcinoma in a particular clinical situation.

The rarity of adrenocortical carcinoma means that the potential opportunities to perform adequate clinical study are limited, which is the obvious reason that there is a paucity of clinical data on this rare disease. Researchers and clinicians caring for patients with this disease are committed to continue studying and working on finding new ways to diagnose, manage, and monitor this disease. An example of a team of physicians dedicated to this challenge is the UCLA endocrine surgery team. Any patient with this rare disease should be encouraged to seek, at minimum, evaluation at a center like UCLA's, which is dedicated to treatment of these rare tumors.

Prevention for Adrenocortical Carcinoma

There are no known preventive measures. Healthy lifestyle choices may reduce your risk for cancers of all types.