Adrenocortical carcinoma is a rare and aggressive cancer that develops in the outer layer of the adrenal glands, small organs sitting on top of the kidneys that control vital functions like blood pressure, metabolism, and stress response. Though uncommon, affecting only about one in a million people each year, this disease can significantly impact hormone levels and spread quickly to other parts of the body if not detected early.

How Common is Adrenocortical Carcinoma?

Adrenocortical carcinoma is extremely rare, making it challenging both to diagnose and to study. The annual incidence is estimated at between 0.7 and 2 cases per million people worldwide^[1][5][13]. Despite being rare, it represents the most common type of cancer originating in the adrenal glands^[1].

This cancer can strike at any age, but it shows two distinct peaks in occurrence. The first peak appears in children younger than five years old, and the second occurs in adults between their 40s and 50s^[5][8][9]. Some sources note that the median age at diagnosis is around 55 years^[12]. Women appear to be affected slightly more often than men, representing about 55 to 60 percent of all cases^[13].

What Causes Adrenocortical Carcinoma?

The exact cause of adrenocortical carcinoma remains unknown to researchers. While they cannot pinpoint a single reason why this cancer develops, they have identified certain genetic factors that appear to play a role. Some people inherit conditions that make them more vulnerable to developing this disease, while others may develop genetic changes over time that trigger abnormal cell growth^[1].

Scientists have discovered that specific genetic mutations, or changes in genes, seem to drive the development of adrenocortical carcinoma. Two genes in particular, called TP53 and IGF2, are frequently altered in people with this cancer. These genes normally act as tumor suppressors, meaning they help control how cells grow and divide. When these protective genes mutate, cells can multiply uncontrollably and form cancerous tumors^[1][9].

Risk Factors and Inherited Conditions

Certain inherited conditions significantly increase a person’s risk of developing adrenocortical carcinoma. While most cases occur sporadically without any family history, some people carry genetic syndromes that make them more susceptible. Understanding these risk factors can help both patients and doctors remain vigilant for early signs of the disease^[1][4].

People with the following hereditary conditions have an elevated risk of adrenocortical carcinoma:

• Li-Fraumeni syndrome, caused by inherited mutations in the TP53 gene
• Beckwith-Wiedemann syndrome, a childhood growth disorder
• Carney complex, which causes tumors in various endocrine glands
• Familial adenomatous polyposis (FAP), characterized by numerous polyps in the colon
• Lynch syndrome, which increases the risk of several types of cancer
• Multiple endocrine neoplasia type 1 (MEN1), affecting hormone-producing glands
• Neurofibromatosis Type 1 (NF1), causing tumors along nerves
• Von Hippel-Lindau (VHL) syndrome, leading to tumor growth in various organs

Childhood cases of adrenocortical carcinoma are most often related to Li-Fraumeni syndrome, while adult cases are less likely to have a genetic cause^[12]. However, anyone with a family history of these syndromes should discuss screening options with their healthcare provider.

Recognizing the Symptoms

The symptoms of adrenocortical carcinoma vary widely depending on whether the tumor produces excess hormones and how large it has grown. Many people with this cancer do not experience any symptoms early on, especially if the tumor is not producing hormones. This is one reason why the disease is often discovered accidentally during medical scans for other reasons^[1][4].

There are two main types of adrenocortical tumors: functioning and non-functioning. Functioning tumors produce excessive amounts of hormones, which leads to noticeable symptoms throughout the body. Most adrenocortical carcinomas are functioning tumors. Non-functioning tumors do not affect hormone production but may grow large enough to press on nearby organs and tissues, causing discomfort or other problems^[1][4].

Common symptoms that may occur regardless of hormone production include abdominal or back pain, a noticeable lump in the abdomen, and a feeling of fullness in the belly. These symptoms typically result from the tumor’s physical presence and its effect on surrounding organs^[2][4].

Symptoms from Excess Cortisol

When a tumor produces too much cortisol, a hormone that helps the body respond to stress and manage metabolism, it can cause a group of symptoms known as Cushing syndrome. People with this condition often notice weight gain concentrated in the face, neck, and trunk of the body, while their arms and legs may appear thin. The face becomes round and flushed, sometimes described as a “moon face.” A fatty hump may develop on the upper back, just below the neck, often called a “buffalo hump”^[2][4].

Other signs of excess cortisol include fine hair growth on the face, upper back, or arms, muscle weakness, high blood sugar levels, high blood pressure, easy bruising, and changes in mood. Women may experience irregular menstrual periods, while men might notice deepening of the voice or swelling of the sex organs or breasts^[2][4].

Symptoms from Excess Aldosterone

Tumors that produce too much aldosterone, a hormone that helps control blood pressure and the balance of water and salt in the body, can cause different symptoms. People may develop high blood pressure, muscle weakness or cramps, frequent urination, and excessive thirst. These symptoms occur because aldosterone affects how the kidneys handle fluids and minerals^[2][4].

Symptoms from Excess Sex Hormones

When adrenocortical tumors produce too much testosterone or other male sex hormones called androgens, women may notice unwanted hair growth on the face and body, acne, balding, deepening of the voice, and absence of menstrual periods. This collection of masculine characteristics developing in women is called virilization. Men who produce excess testosterone typically do not show obvious symptoms^[2][4][9].

Excess estrogen, a female sex hormone, can cause irregular menstrual periods in women. In men, too much estrogen may lead to breast enlargement and tenderness, reduced sex drive, and difficulty achieving or maintaining an erection. This development of feminine characteristics is called feminization^[2][4].

In children, excess sex hormones can cause premature development of adult sexual characteristics, a condition known as precocious puberty. This may include excessive facial, pubic, and underarm hair, as well as changes in the genitals^[9].

Prevention and Screening

Unfortunately, there are no known ways to prevent adrenocortical carcinoma in people without inherited risk factors. Since researchers do not fully understand what causes the disease in most cases, specific prevention strategies have not been developed. However, people with known genetic syndromes that increase their risk should work closely with their healthcare team to establish appropriate monitoring plans^[1].

For individuals with inherited conditions like Li-Fraumeni syndrome or Beckwith-Wiedemann syndrome, genetic counseling can provide valuable information about personal risk and the potential for passing these conditions to children. Some families may benefit from regular screening, though there is no standard screening protocol for adrenocortical carcinoma in the general population^[4].

Because many cases are discovered incidentally during imaging tests for other health issues, maintaining regular medical care and following up on any unexpected findings during scans can lead to earlier detection. Early diagnosis generally offers better treatment outcomes^[1].

How the Disease Affects the Body

To understand how adrenocortical carcinoma impacts health, it helps to know what the adrenal glands normally do. These small, triangle-shaped glands sit on top of each kidney. The outer layer, called the adrenal cortex, produces several essential hormones. These hormones help balance water and salt in the body, maintain normal blood pressure, control how the body uses proteins, fats, and carbohydrates, and influence sexual characteristics^[4][7].

When cancer develops in the adrenal cortex, it disrupts this delicate hormonal balance. The cancerous cells often produce excessive amounts of one or more hormones, flooding the body with levels far beyond what is normal. This hormonal excess creates the various symptoms described earlier, from weight gain and high blood pressure to changes in physical appearance^[1].

Adrenocortical carcinoma is considered very aggressive because the tumors can grow rapidly and spread to other parts of the body. The disease can metastasize, meaning cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system to establish new tumors in distant organs. Common sites of spread include the lungs, liver, and bones^[1][9].

The changes in gene function that drive adrenocortical carcinoma affect how cells grow and divide. Normally, tumor suppressor genes act as brakes on cell growth, preventing cells from multiplying too quickly. When these genes mutate and stop working properly, cells can grow out of control, forming tumors. The cancer cells may also produce abnormal amounts of hormones or hormone precursors, further disrupting normal body functions^[1][5].