Adrenal cancer causes and risk factors

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science

This page was reviewed on June 7, 2022.

About 600 people in the United States are diagnosed with adrenal cancer each year, making it a very rare disease. Adrenal tumors are not uncommon, most of which are benign (non-cancerous).

What causes adrenal cancer?

Although genetic syndromes and hereditary traits have been linked to adrenal cancer, most cases occur sporadically, and the causes of adrenal cancer remain largely unknown.

Adrenal cancer risk factors

Risk factors for adrenal cancer are varied. Like many cancer types, the risk for developing adrenal cancer may increase as a result of certain lifestyles and environmental factors, including smoking and exposure to carcinogens. Genetic syndromes have been linked to adrenal cancer.

A rare form of adrenal cancer called pheochromocytoma is largely found in middle-aged adults.

Genetic causes of adrenal cancer

Genetic syndromes considered risk factors for adrenal cancer include those listed below.

Li-Fraumeni syndrome

A mutation in the gene TP53 causes the inherited genetic condition called Li-Fraumeni syndrome. A broken TP53 gene breaks a pathway that typically slows or stops tumor growth in the body, leading to an increased risk of certain cancers. These include adrenal cancer, bone cancer, soft-tissue cancers (sarcomas), leukemias, breast cancer and brain cancer.

Li-Fraumeni syndrome may cause a specific type of adrenal cancer called an adrenal cortex tumor, which develops in the outer layer of the adrenal gland and makes hormones that cause weight gain, fluid retention, early-onset puberty or puberty-like symptoms.

Von Hippel-Lindau syndrome

A rare genetic disorder, von Hippel-Lindau syndrome increases the risk of developing adrenal gland tumors and tumors in the liver, lungs, brain, spinal cord, eyes and inner ears. These tumors are usually noncancerous (benign), but some may be cancerous.

A mutation in the VHL gene causes Von Hippel-Lindau syndrome. This gene regulates how cells grow. A broken VHL gene increases the number of blood vessels, leading to tumor development. Adrenal tumors caused by von Hippel-Lindau syndrome release a hormone called catecholamine, which may lead to high blood pressure, anxiety, panic attacks and excessive sweating.

Multiple endocrine neoplasias

Another set of genetic disorders that may lead to adrenal tumors is multiple endocrine neoplasia (MEN) syndrome. The two types of MEN are: type 1 (MEN1) and type 2 (MEN2). Mutations in the MEN1 gene or the RET gene cause MEN disorders and lead to increased risk for developing certain cancers.

MEN1 patients have a high risk of developing cancers in the pituitary gland, parathyroid gland and pancreas. They also are at an increased risk of developing benign tumors on the adrenal glands, called adrenal adenomas. Patients with MEN2 may develop pheochromocytoma, tumors of the adrenal glands that are typically benign.

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is a disorder diagnosed at birth. Babies with this syndrome are typically large at birth and may have low blood sugar. They may have overly large tongues and internal organs and defects in their abdomen near the belly button. They also have a higher risk of developing certain cancers, including adrenocortical carcinoma, or adrenal cortex cancer.

Lynch syndrome

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is passed down in families like other genetic disorders. Mutations that cause Lynch syndrome are in at least one of several genes that fix mistakes made when cellular processes repair or copy the genome. Mutations in these genes let these mistakes build up, potentially leading to cancer.

People with Lynch syndrome have a much higher risk of developing colon and rectal cancer. They may also develop cancer in the uterine lining, ovaries, stomach, small intestine, pancreas, kidney, brain, ureters (tubes that carry urine from the kidneys to the bladder), bile duct and adrenal gland.

Next topic: What are the symptoms of adrenal cancer?

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