Causes and Risk Factors of Adrenocortical Carcinoma

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Experts still don’t quite know exactly what causes adrenal cancers, including adrenocortical carcinoma. This is a cancer of the adrenal cortex, the outer part of the adrenal gland that produces a variety of hormones.

Specific DNA mutations may increase a person’s risk for cancer, including adrenocortical carcinoma. However, having a specific genetic condition doesn’t mean you’ll necessarily develop this type of cancer. Evidence suggests that this cancer is more common in children than adults.

This article will explore the causes and risk factors for adrenocortical carcinoma, including genetics.

Mother and child see medical counsellor

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Common Causes

Unfortunately, experts don’t know what causes adrenocortical carcinoma, a rare form of cancer.


It’s possible that genetics play a part in the development of adrenal cortex tumors. Genetic conditions that may be linked to adrenocortical carcinoma include the following.

Li-Fraumeni Syndrome

Li-Fraumeni syndrome is caused by an inherited mutation that turns off the TP53 gene responsible for tumor suppression. This can lead to adrenocortical carcinoma and other adrenal cancers in children and adults. However, it’s more likely to cause adrenal cancer in children. Nearly eight in 10 cases of childhood adrenal cancer involve this genetic syndrome.

It’s important to note that having this genetic syndrome may increase your risk of developing other types of cancer, as well.

Other Cancers Associated with Li-Fraumeni Syndrome

Other cancers associated with this rare inherited genetic syndrome include:

People with this syndrome have a 50% chance of developing cancer before they turn 40.

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome is a genetic condition that causes people to have large tongues and body sizes. Having it can also increase your risk of developing adrenal cortex cancer, among other cancers.

This condition very rarely causes adrenocortical carcinoma, and when it does, it’s usually in children.

Familial Adenomatous Polyposis (FAP)

Without prompt treatment, people who have familial adenomatous polyposis, a genetically inherited disease, will inevitably develop cancer, including adrenal cancer.

People with FAP are more likely to develop other forms of cancer than they are to develop adrenocortical cancer, though.

Lynch Syndrome 

Lynch syndrome is another hereditary syndrome that increases a person’s risk of developing several cancers, including adrenal cortex cancer. Evidence suggests that this syndrome accounts for only 3% of adult adrenocortical carcinoma cases, however.

Lynch Syndrome Symptoms

Lynch syndrome is also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Symptoms may include:

  • Blood in the stool
  • Diarrhea
  • Prolonged constipation
  • Abdominal cramping
  • Gas, bloating, and a feeling of fullness
  • Unexplained weight loss
  • Vomiting
  • Lethargy

Multiple Endocrine Neoplasia (MEN1)

Multiple endocrine neoplasia is a genetic syndrome in which you’re likely to develop tumors on your pituitary, parathyroid, and pancreas glands. According to the American Cancer Society, approximately 33% of people with MEN1 also develop benign (noncancerous) tumors of the adrenal glands.

This genetic syndrome is rarely a cause for adrenocortical carcinoma, which represents fewer than 2% of all adult cases, according to a 2014 review.

Von Hippel-Lindau Syndrome

Von Hippel-Lindau syndrome (VHL) is an inherited condition. People with VHL are at higher risk for a rare tumor affecting the adrenal glands called pheochromocytoma. This type of tumor can present similarly to adrenocortical carcinoma and can affect the adrenal cortex if it spreads.

More About Pheochromocytoma

This type of adrenal cancer starts in the adrenal medulla. This is the inner part of the adrenal gland. The adrenal cortex, on the other hand, constitutes the outer part of the gland.

In people with VHL, the tumor is rarely malignant and usually is easy to treat. However, even if the tumor isn't malignant, it can cause problems if left untreated.

Carney Complex 

According to the National Cancer Institute, having Carney complex is another risk factor for developing adrenocortical carcinoma. However, there exist few documented cases in which a person with this syndrome has developed adrenal cortex cancer.

Lifestyle Risk Factors

While having diseases or syndromes that cause genetic mutations can increase your risk of developing cancer, gene mutations can also happen on their own for various reasons. 

There’s no direct evidence that certain lifestyle factors can cause adrenocortical carcinoma.  However, some lifestyle habits may increase your risk of developing cancers like adrenocortical carcinoma. 

According to the American Cancer Society, these include:

  • Being overweight
  • Smoking
  • Lack of physical activity
  • Exposure to cancer-causing substances


Adrenocortical carcinoma is a rare cancer that has no common cause. Certain genetic syndromes can increase your risk of developing it, as can some general lifestyle risk factors.

A Word From Verywell

If you have a family history of genetic conditions or syndromes associated with adrenocortical carcinoma, you may wish to undergo genetic testing and counseling.

However, just because you have one of these genetic syndromes, have a family history of adrenocortical carcinoma, or have certain lifestyle habits linked to cancer, doesn’t mean you’ll automatically develop cancer. Ultimately, experts still have a lot to learn about the causes of this rare cancer. 

9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Else T, et al. Adrenocortical carcinoma. Endocr Rev. 2014;35(2): 282-326. doi:10.1210/er.2013-1029

  2. American Cancer Society. What causes adrenal cancer?

  3. American Cancer Society. Adrenal cancer risk factors.

  4. National Organization for Rare Disorders. Li-Fraumeni Syndrome.

  5. Johns Hopkins Medicine. Lynch syndrome.

  6. MedlinePlus. Von Hippel-Lindau syndrome.

  7. National Cancer Institute. von Hippel-Lindau syndrome.

  8. University of Texas Cancer Center. von Hippel Lindau disease.

  9. National Cancer Institute. Adrenocortical carcinoma treatment.

By Steph Coelho
Steph Coelho is a freelance health writer, web producer, and editor based in Montreal. She specializes in covering general wellness and chronic illness.