Our adrenal glands, triangular in shape, sit above our kidneys. Each of the two adrenal glands has an inner portion known as the adrenal medulla, and an outer portion called the adrenal cortex. Adrenocortical carcinoma is a form of cancer that develops within the adrenal cortex.

Adrenocortical carcinoma is very rare. It accounts for about 1% of all cancer diagnoses among children, and between 0.02 and 0.2% of all cancer diagnoses among adults. It occurs more frequently in females than in males.

Treatments are not always as effective for adrenocortical carcinoma as they are for other types of cancer, so early diagnosis and treatment are especially important in helping to improve outcomes.

“Because adrenocortical carcinoma is such a rare cancer, reported survival rates may be underestimated,” says Smilow Cancer Hospital endocrine surgeon Courtney Gibson, MD. “Also, recent advances in treatment may lead to improved survival outcomes.”

Adrenocortical carcinoma is a rare type of cancer that affects the adrenal glands, specifically the adrenal cortex. Only about 1 person out of 1 million is diagnosed with the condition. Though it affects both children and adults, the average age of onset is 46.

In healthy people, the adrenal cortex produces a variety of hormones, including cortisol and aldosterone. These hormones help regulate blood pressure levels and metabolism, among other important functions.

When someone has adrenocortical carcinoma, a mutation causes the adrenal cortical cells to multiply uncontrollably, leading to the formation of a tumor. Adrenocortical tumors may produce too many adrenal hormones, which can lead to abnormal blood pressure or additional problems.

Doctors don’t know why people develop adrenocortical carcinoma, but it’s more common among people who have certain inherited conditions, including mutations to the TP53 gene or IGF2 gene. Half of people with this type of cancer have a family history of the condition.

People who have adrenocortical carcinoma may experience the following symptoms:

• Abdominal pain or fullness
• A lump or mass within the abdomen
• Back pain or discomfort
• Menstrual abnormalities
• High blood pressure
• Deepening voice
• Growth of body hair
• Development of acne
• Breast development in males
• Changes in weight
• Fat developing disproportionately around the midsection
• Development of a rounded or moon-shaped face
• Fatigue, depression, and/or anxiety
• Bruising easily
• Diabetes
• Muscle weakness

People who have these health conditions may be at increased risk of adrenocortical carcinoma:

• Li-Fraumeni syndrome
• Beckwith-Wiedemann syndrome
• Carney complex
• Hemihyperplasia
• Lynch syndrome
• Familial adenomatous polyposis
• Neurofibromatosis type 1
• Multiple endocrine neoplasia type 1
• Werner syndrome

Smoking may increase the risk of adrenocortical carcinoma, particularly among men.

If doctors suspect adrenocortical carcinoma, they obtain a medical history, perform a physical exam, and order diagnostic tests, such as lab tests to check hormone levels and imaging studies to look for an adrenal mass, to confirm the presence of the cancer.

When learning about a patient’s medical history, doctors will ask about symptoms and any other existing medical conditions, including diabetes or inherited conditions like Li-Fraumeni syndrome or Lynch syndrome. Doctors will also ask about a family history of inherited conditions or adrenocortical carcinoma.

During a physical exam, doctors may feel the abdomen for the presence of a mass. They may look for unexplained bruises, a moon-shaped face, enlarged breasts in men, facial hair in women, or other symptoms of the disease.

To confirm the presence of adrenocortical carcinoma, doctors will typically request blood tests that may show whether the blood contains abnormal levels of sodium or potassium, or if there are higher-than-normal levels of certain hormones—an indication of adrenocortical carcinoma. Some doctors also order a urine test to check for the presence of hormones, such as cortisol; high levels may be an indication that the adrenal gland is producing too many hormones. It is important to note that in up to one-third of cases, there is no excess hormone being secreted by the tumor, which often leads to a delay in diagnosis, because patients are typically asymptomatic when the tumor is not secreting any hormones.

The following imaging studies may also show the presence of a mass on the adrenal gland:

• CT scan
• MRI
• Ultrasound
• PET scan
• X-ray

In addition, doctors may order genetic tests to check for mutations to the TP53, IGF2, or other genes.

Adrenocortical carcinoma is best treated by endocrinologists, endocrine oncology specialists, endocrine surgeons, and others who are familiar with this rare disease. Because it’s difficult to treat, seeing a coordinated group of specialists with specific expertise in this area may lead to better outcomes.  

• Surgery is the recommended treatment for adrenocortical carcinoma. Surgeons strive to remove the affected adrenal gland with a clear margin of healthy tissue, to ensure that no cancer is left behind. If the cancer is caught early, before it has spread, surgically removing the affected adrenal gland may be curative. There is often invasion into surrounding organs, such as the kidney, liver, or inferior vena cava (IVC); in such cases, portions of these organs will also need to be removed at the time of surgery.

• Chemotherapy. Some people with adrenocortical carcinoma receive chemotherapy after surgery. The chemotherapy drug mitotane may help to reduce the production of cortisol, which may help to improve symptoms or slow the progression of advanced disease. However, mitotane usage must be closely monitored, since it may have serious side effects. 

Patients with adrenocortical carcinoma, a rare malignant lesion, have a poor prognosis. Two determinants of long-term survival are the tumor stage at presentation and curative resection by an experienced surgeon. Surgical resection can improve disease-free survival in a very select group of patients with no metastatic disease and a good performance status. Unfortunately, most patients with metastatic disease have a poor overall prognosis. However, overall 5-year survival rates can be as high as 45%.

“We institute a multidisciplinary approach to the management of patients with adrenocortical carcinoma,” says Dr. Gibson, of the Yale Endocrine Cancers Program. “A coordinated expert team of endocrine surgical oncologists, endocrinologists, medical oncologists, and radiation oncologists work closely together, to ensure that our patients receive the most effective, cutting-edge treatment for this rare, aggressive malignancy.”