Adrenocortical Tumor

What is Adrenocortical Tumor?

Adrenocortical tumor (ACT) is a rare tumor of the adrenal gland. These tumors can range from benign tumors to aggressive, malignant cancers. Other names for ACT are adrenocortical cancer, cancer of the adrenal cortex, adrenocortical adenoma, and adrenocortical carcinoma.

The adrenal glands are located on top of each kidney. The outer layer of the adrenal gland is called the adrenal cortex. The job of the adrenal glands is to produce hormones such as cortisol and aldosterone. These hormones have a variety of important functions that include:

Controlling how the body uses carbohydrates, fats, and proteins for energy
Helping the body cope with stress
Controlling blood pressure
Regulating water, potassium and salt in the body

The adrenal glands are located on top of each kidney and produce hormones the control important bodily processes.

The adrenal cortex also produces small amounts of male and female sex hormones, called androgens and estrogens. These hormones influence the development of male and female characteristics.

Adrenocortical cancer is very rare in children. It makes up only 0.2% of childhood cancers. In the United States, there are about 25 new cases every year.

In adults, adrenocortical tumors are classified as adrenocortical carcinoma (malignant) or adrenocortical adenoma (benign). However, in children, it can be hard to determine the type of adrenocortical tumor, and aggressiveness can be harder to predict. Therefore, the treatment plan for ACT in children relies on recognizing a potential spectrum of aggressiveness in such tumors, and considering tumor biology as well as clinical course, rather than strictly relying on whether a tumor is initially classified as a “carcinoma” or “adenoma.”

Treatment for adrenocortical tumor usually includes surgery to remove the tumor and adrenal gland. There is a very good chance of cure with complete resection of the tumor by surgery. If the cancer spreads outside the adrenal gland, then treatment will include chemotherapy.

Risk Factors and Causes of Adrenocorticol Tumors

Adrenocortical tumors are more common in girls than boys. This cancer occurs most often in younger children, usually between 1 and 4 years old.

Certain hereditary factors may increase risk, and the tendency to develop ACT may be passed down in families.

Genetic Predisposition and ACT

Hereditary syndromes that increase risk for adrenocortical tumor include Li-Fraumeni Syndrome (TP53 gene) and Beckwith-Wiedemann Syndrome. Children with these conditions will undergo regular screening including abdominal ultrasound to watch for adrenocortical tumor.

Signs and Symptoms of Adrenocortical Tumors

Most children with adrenocortical tumor have signs and symptoms due to excess hormones. If the cancer causes more hormones to be made than normal, it is called functioning ACT. In children, most (90%) of adrenocortical tumors are “functioning.” In teens, about half of adrenocortical tumors are “functioning.”

Androgens - In pediatric adrenocortical tumor, most tumors release higher than normal amounts of male sex hormones (androgens). In boys, this may cause early puberty including increased facial and body hair, early growth of pubic or underarm hair, body odor, acne and deepening voice. Extra androgens in females can cause growth of facial and body hair and deepening voice. Older girls may also lose their menstrual cycle.
Estrogens - If female hormones (estrogens) are overproduced, girls can show early signs of puberty including breast development and menstrual periods (rare). Extra estrogen in boys may cause the growth of breast tissue.
Cortisol - Cortisol is a hormone produced by the cortex of the adrenal gland. This hormone acts to help regulate the body’s stress response. Adrenocortical tumors can result in an overproduction of cortisol, a condition known as Cushing syndrome. Signs of too much cortisol include a rounded face, weight gain, development of a hump on the upper back caused by an abnormal deposit of fat (“buffalo hump”), stretch marks, high blood sugar, and high blood pressure.
Aldoesterone - Aldosterone is a hormone important for kidney function. It helps to balance water, salt, and potassium in the body. Adrenocortical tumors can produce excess aldosterone which can result in high blood pressure, thirst, weakness, and muscle cramps.

Other general signs and symptoms of adrenocortical tumor include:

Lump or swelling in the abdomen (belly).
Pain in the abdomen or back.
A feeling of fullness due to the tumor pressing on the stomach.

Hormone-Related Signs and Symptoms of Pediatric Adrenocortical Tumor (ACT)
Androgen	Estrogen	Cortisol	Aldosterone
Excess androgens or estrogens can produce early signs of puberty or changes not usually seen in children of that gender
Male characteristics such as facial and body hair, acne, deepening voice, increased growth	Female characteristics such as breast development	Rounded “moon” face, weight gain, fatty hump on upper back, stunted height, high blood sugar, high blood pressure	High blood pressure, thirst, muscle cramps or weakness

Diagnosis of Adrenocortical Tumors

Doctors look for adrenocortical tumors in several ways. These include:

A health history and physical exam helps doctors learn about signs and symptoms of excessive production of adrenal cortex hormones, general health, past illness, and risk factors. Family history of cancer is important because cancers in close relatives may suggest the presence of an inherited risk. When a child is diagnosed with ACT, genetic testing and counseling is recommended for the child and family. Doctors will test for certain gene changes (mutations) that increase risk for cancer such as the TP53 gene.
Lab studies are used to look at substances in the blood and urine. Doctors will check levels of glucose in the blood and electrolytes such as potassium and sodium. Measuring blood and urine levels of adrenal hormones is often the first step in diagnosing adrenal gland dysfunction.
Imaging tests help identify the tumor, see how big the tumor is, and find out if it has spread to other places such as the liver, lungs, lymph nodes, or bones.
- Ultrasound uses sound waves to create an image of the organs and tissues within the body. An abdominal ultrasound is often one of the first tests doctors use to see if there is a tumor in the adrenal gland in children. It also shows if the tumor has invaded the vascular system.
- Magnetic resonance imaging (MRI) uses radio waves and magnets to make detailed pictures of the body. The images made by MRI can give more information about the type of tumor and the potential spread of disease. MRI of the abdomen allows doctors to see the adrenal gland and tumor.
- Computed tomography (CT scan) uses x-rays to create cross-sectional images of the organs and tissues inside the body. The machine takes many pictures to make a very detailed image. The images are taken as a series of “slices” of the body and are saved to a computer. These slices or sections can allow very small tumors to be seen. A chest CT scan can help doctors to see if it has spread to the lungs.
- Positron emission tomography (PET scan) uses radioactive glucose (sugar) given through a vein to make computerized images of the body. The glucose travels through the body and is taken up by cells which use sugar for energy. This allows the different tissues and organs to appear as colored pictures on a computer screen. Cancer cells often grow and divide faster than other cells, and they take up more glucose. This can allow the tumor to be seen more clearly on a PET scan. PET can sometimes detect cancer in areas of the body that do not appear on a CT scan or MRI.
- A bone scan uses a special scanner to take pictures of the body. In this test, the patient receives an injection with small amount of radioactive material that travels throughout the body in the blood. This substance collects in the bones and can highlight areas where cancer has spread. This test is not typically used in children with ACT, particularly where PET scans are readily available.
Tissue from the tumor will be examined to check for signs of cancer in the cells and learn more about the histology. A pathologist looks at the tissue samples using a microscope to see if there are cancer cells. The way cells look under a microscope is important to make a diagnosis. This information is also used to evaluate how aggressive the tumor is likely to be. Usually, a biopsy is not performed before surgery. Instead, the tissue is examined after surgery to remove the adrenal gland (adrenalectomy).

Adenoma vs Carcinoma

The tumor will be examined and classified according to the histology, mainly as adenoma or carcinoma. However, in children, adrenocortical tumors can have a range of behavior. Not all carcinomas are similarly aggressive, and some tumors initially described as adenomas may have features that are more invasive or need more follow-up than expected.

Staging of Adrenocortical Tumor

The stage, or extent of disease, of adrenocortical tumor depends on several factors:

Tumor size
If the tumor can be completely removed with surgery
Whether the tumor has spread

More than half of patients with adrenocortical tumor have metastatic disease at the time of diagnosis. The most common places for the disease to spread are the liver and lungs. ACT may also spread to lymph nodes, bones, and other places in the abdomen.

Prognosis for Adrenocortical Tumor

Recovery from ACT depends on whether surgery completely removes the tumor. Chance of survival is higher with complete resection, or full removal of cancer by surgery. If caught early and with successful surgery, the five-year overall survival for adrenocortical tumor is 85%. For more advanced cancer, survival rate is less than 40%. All patients require long-term monitoring and care by a multidisciplinary team.

Factors that influence chance of cure include:

Tumor size
Whether the initial surgery completely removes the cancer
Patient’s age (Prognosis is better in children younger than 3 years old.)
Histological features
Whether the cancer has spread to other parts of the body (liver, lungs, bones, lymph nodes)
Alteration in certain genes in the tumor
If cancer has come back (recurrent)

Treatment of Adrenocorticol Tumors

Surgery to remove the adrenal gland (adrenalectomy) is the main treatment for adrenocortical tumors. When possible, the goal of treatment is complete removal (resection) of the tumor. This type of tumor requires special care during surgery. The adrenal gland is delicate (friable) and can break apart easily during surgery. If parts of the tumor break off (tumor spill), then the chance for spread of the cancer is high. For this reason, a biopsy is not usually used to diagnose ACT before surgery.

Management and pre-operative planning by expert surgeons familiar with pediatric adrenocortical tumors is highly recommended for children with suspected ACT. A multidisciplinary team, including oncologists, endocrinologists and anesthesia specialists, is also important for peri-operative care to help manage blood pressure and changes in electrolytes, body fluids and hormones that may be affected by a large or hormone-producing adrenal mass.

A pathologist will examine the tumor after it is removed with surgery. A multidisciplinary team can then review the findings and conduct additional tests as needed to complete the staging and tailor the care plan for the patient.

If the tumor is completely removed, there is a good chance for cure. For patients with small tumors, surgery alone may be an effective treatment.
For patients with large tumors or advanced disease, systemic chemotherapy is used in addition to surgery. Medicines used for ACT include mitotane as well as other chemotherapy agents such as cisplatin.
Radiation therapy may be considered for adrenocortical tumor, especially if the cancer has spread. Before starting radiation therapy, patients should be tested for the TP53 gene mutation.

Patients with advanced cancer who do not respond to other treatments might consider participating in a clinical trial.

Hormone monitoring and therapy can help patients who have abnormal levels of hormones due to the tumor or treatment. Medicines can be given to help relieve some of the problems of hormone imbalance due to a functioning tumor (extra hormones) or to restore hormone levels that have been affected by the tumor or other treatments.

Patients may need hormone replacement therapy after removal of the adrenal gland and/or treatment with mitotane or other chemotherapy which can affect hormone production. Low adrenal hormones can cause a variety of problems including problems regulating blood pressure and blood sugar.

ACT is a complex disease, and a multidisciplinary care team is important including pediatric oncology, diagnostic imaging, surgery, pathology, radiation oncology, endocrinology, nutrition, and genetic counseling.

All ACT patients ages 21 and younger are invited to participate in an observational study registry of this rare cancer:

International Pediatric Adrenocortical Tumors Registry (IPACTR)

Life After Adrenocortical Tumor

Adrenocortical tumor is a very rare cancer in children. Children with this cancer need ongoing care to monitor hormone levels and watch for cancer recurrence.

Endocrine function monitoring

Monitoring of endocrine function in patients with ACT is important. Patients with functioning tumors need medicines to treat symptoms of overproduction. People who have lower adrenal gland function need hormones to help regulate the body’s normal functions, including the response to stress.

Genetic testing and counseling

Children with adrenocortical tumor should be tested for the TP53 gene. People with a germline mutation in this gene have a condition called Li-Fraumeni Syndrome. Family members of patients with an identified mutation should also be tested. The TP53 gene is located in cells throughout the body. Its job is to tell cells to make a tumor suppressor protein that keeps bad or damaged cells from dividing. A change in TP53 puts people at higher risk for certain cancers because the signal to stop “bad” cells does not work correctly. People with a mutation in this gene should avoid exposure to radiation whenever possible. Lifelong monitoring is important because of high cancer risk.

Late Effects of Adrenocorticol Tumor Therapy

For general health and disease prevention, all cancer survivors should adopt healthy lifestyle and eating habits, as well as continue to have regular physical checkups and screenings by a primary physician. Childhood cancer survivors treated with systemic chemotherapy should be monitored for acute and late effects of therapy.

Survivors treated with systemic chemotherapy or radiation should be monitored for acute and late effects of therapy. Serious chronic health conditions are present 25 years after diagnosis in approximately 25% of survivors, according to the Childhood Cancer Survivor Study. These conditions include second cancers (increased risk following exposure to radiation), congestive heart failure (exposure to doxorubicin), infertility or complications during pregnancy, and end-stage renal disease or renal failure.

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Reviewed: June 2018