Adrenocortical Carcinoma

Adrenocortical carcinoma is a rare but aggressive cancer that develops in the outer layer of the adrenal glands, small organs that sit on top of your kidneys and produce vital hormones. Though it affects only about 1 or 2 people per million each year, this cancer can cause serious health problems by releasing excessive amounts of hormones or growing large enough to press on nearby organs.

Table of contents

• What is adrenocortical carcinoma?
• Location and anatomy
• Types of tumors
• How common is this condition?
• Signs and symptoms
• Causes and risk factors
• How is it diagnosed?
• Treatment options
• Outlook and prognosis

What is adrenocortical carcinoma?

Adrenocortical carcinoma is a cancer that develops in the adrenal cortex, which is the outer layer of the adrenal glands^[1]. The adrenal glands are small, triangle-shaped organs that sit on top of each kidney. Although they are small, these glands control many important functions in your body^[3]. This type of cancer is also called adrenal cortical cancer or cancer of the adrenal cortex^[4].

adrenal cortical cancer, cancer of the adrenal cortex, ACC, adrenocortical cancer

Location and anatomy

There are two adrenal glands in the human body. One adrenal gland sits on top of each kidney^[2]. Each adrenal gland has two parts: the outer layer called the adrenal cortex, and the center called the adrenal medulla^[4].

• Adrenal glands
• Adrenal cortex
• Kidneys

The adrenal cortex makes important hormones that help your body in several ways. These hormones balance water and salt in the body, help keep blood pressure normal, help control how your body uses protein, fat, and carbohydrates, and cause the body to have masculine or feminine characteristics^[2].

Types of tumors

A tumor of the adrenal cortex may be functioning or nonfunctioning^[4]. A functioning tumor makes more hormones than normal, while a nonfunctioning tumor does not make more hormones than normal. Most adrenocortical carcinomas are functioning tumors^[2]. The hormones made by functioning tumors may cause certain signs or symptoms of disease.

Functioning tumors release excessive amounts of hormones, including aldosterone, cortisol, estrogen, and testosterone. Symptoms vary depending on the type of hormone^[1]. Non-functioning tumors don’t affect hormone production, but they can grow so large that they press on nearby organs and tissues^[1].

How common is this condition?

Adrenocortical carcinoma is a very rare disease with an incidence of about 0.7 to 2.0 cases per million people per year^[13]. Even though it is extremely rare, it is the most common type of adrenal cancer. Each year, about 1 in 1 million people receive a diagnosis of adrenocortical carcinoma^[1].

This cancer can occur at any age, but it has two peak periods of incidence. The first peak occurs in children, particularly those younger than 5 years old. The second peak occurs in adults, typically between the ages of 40 and 50 years^[13]. Women are affected slightly more frequently than men, representing about 55% to 60% of cases^[13].

Signs and symptoms

Many people with adrenocortical carcinoma may not have symptoms in the early stages, especially if the tumor is nonfunctioning. Studies show that 20% to 30% of adrenocortical carcinoma diagnoses happen after healthcare providers do imaging tests for unrelated health issues^[1].

When symptoms do develop, they may be related to the tumor’s size or to hormone production. Common symptoms related to tumor size include abdominal or back pain, a lump in the abdomen, and a feeling of fullness in the abdomen^[4].

Symptoms from too much cortisol

When a functioning tumor makes too much cortisol (a hormone that helps the body use sugar, protein, and fats), patients may experience weight gain in the face, neck, and trunk of the body with thin arms and legs, growth of fine hair on the face, upper back, or arms, a round, red, full face (sometimes called “moon face”), a lump of fat on the back of the neck (called “buffalo hump”), deepening of the voice, swelling of the sex organs or breasts in both males and females, muscle weakness, high blood sugar, and high blood pressure^[4].

Symptoms from too much aldosterone

Too much aldosterone (a hormone that helps control the balance of water and salts in the kidney) may cause high blood pressure, muscle weakness or cramps, frequent urination, and feeling thirsty^[2].

Symptoms from too much testosterone or estrogen

Women who make too much testosterone may have growth of fine hair on the face, upper back, or arms, acne, balding, deepening of the voice, and no menstrual periods^[2]. Men who make too much testosterone do not usually have signs or symptoms. Women with too much estrogen may experience irregular menstrual periods. Men with too much estrogen may have breast growth and tenderness, lower sex drive, and inability to get or maintain an erection^[2].

Causes and risk factors

Researchers don’t know the exact cause of adrenocortical carcinoma^[1]. However, certain factors increase the risk of developing this condition.

Inherited genetic conditions

Having certain genetic conditions increases the risk of adrenocortical carcinoma. Risk factors include having the following hereditary diseases: Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, familial adenomatous polyposis, Lynch syndrome, multiple endocrine neoplasia type 1, neurofibromatosis type 1, and Von Hippel-Lindau syndrome^[1][4].

Genetic mutations

In other cases, certain genetic mutations (changes in genes) appear to increase risk. For example, research shows changes in the tumor suppressor genes TP53 and IGF2 appear to drive adrenocortical carcinoma^[1]. Tumor suppressor genes manage cell growth. When these genes change, your cells may multiply uncontrollably and become cancerous tumors.

How aggressive is the cancer?

Adrenocortical carcinoma is very aggressive because the tumors can grow very quickly and spread (metastasize) from your adrenal gland to other areas of your body, including your lungs or bones^[1]. Cancer that spreads from your adrenal gland to other parts of your body is more difficult to treat^[1].

How is it diagnosed?

To diagnose adrenocortical carcinoma, a healthcare professional might start with a physical exam and review of your health history and family medical history^[16]. Diagnosis also involves blood and urine tests and imaging tests.

Blood and urine tests

Lab tests of blood and urine may show levels of hormones made by the adrenal glands that are outside a healthy range. Those hormones include cortisol, aldosterone, and androgens^[16]. These tests help identify whether a tumor is functioning (producing excess hormones) or nonfunctioning.

Imaging tests

Imaging tests used to diagnose adrenal cancer include CT scans, MRI, and positron emission tomography scans (PET scans)^[16]. Healthcare professionals use the images to examine growths on the adrenal glands. Imaging tests also can look for signs that the cancer has spread to other areas of the body.

Surgery and biopsy

In some situations, to make a diagnosis of adrenal cancer, the adrenal gland that might have cancer is removed with surgery. Then, the gland is examined in a lab by a doctor who studies body tissues, called a pathologist^[16]. Testing can show whether the gland has cancer.

Treatment options

Treatment for adrenocortical carcinoma often includes surgery to remove the adrenal gland. Other treatments also might be used in some situations, including radiation therapy and medicines such as chemotherapy and immunotherapy^[16].

Surgery

Surgery for adrenal cancer typically involves removing the entire adrenal gland. This procedure is called an adrenalectomy^[16]. Surgery is the main treatment for cancer that can be completely removed. When the cancer is limited to the adrenal gland, complete removal of the tumor offers the best chance for a cure^[3].

If the cancer has spread to nearby tissues or lymph nodes, more extensive surgery may be needed. An en bloc resection removes the tumor and surrounding tissues as a single piece^[15]. In some cases where the tumor cannot be completely removed, debulking surgery may be performed to remove as much of the cancer as possible. This helps reduce symptoms caused by high hormone levels and tumor growth^[15].

Medication therapy

Mitotane is the only approved medication specifically for adrenocortical carcinoma and has been used since 1960^[12]. Mitotane is a drug that suppresses adrenal function. It may be given after surgery to help prevent the cancer from coming back, or it may be used to treat cancer that has spread^[15].

Other medications may be given to control symptoms caused by excess hormones. These include ketoconazole (a drug that decreases production of cortisol) and spironolactone (a drug that blocks the effects of aldosterone)^[15].

Chemotherapy

For advanced or metastatic disease, chemotherapy may be used. The most common chemotherapy regimen combines etoposide, doxorubicin, and cisplatin (EDP) with mitotane. This combination has been shown to have a response rate of about 23%^[12].

Radiation therapy

Radiation therapy may be used after surgery to reduce the risk of cancer recurrence, especially for patients with a high risk of the cancer coming back^[12].

Clinical trials

Clinical trials are an important part of cancer treatment and research. Trials are available to adrenocortical carcinoma patients and may offer access to new treatments being studied^[17].

Outlook and prognosis

The outlook for adrenocortical carcinoma depends on several factors, including the stage of the cancer at diagnosis and whether it can be completely removed with surgery. When adrenal cancer is found early, a cure may be possible. When the cancer has spread beyond the adrenal glands, a cure becomes less likely^[3].

Survival rates vary significantly by stage. Survival at 5 years ranges from 82% for stage 1 disease to 13% for stage 4 disease defined by distant metastases^[12]. About 70% of patients present with stage 3 or 4 disease at diagnosis^[12].

A major challenge with adrenocortical carcinoma is that it often comes back (recurs) even after successful treatment. The condition is very aggressive, and healthcare providers can treat it with surgery and medication, but recurrence is common^[1]. Local recurrence and metastatic disease are common complications^[13].

Treatment outcomes are generally better when patients receive care at specialized centers where a multidisciplinary team of endocrinologists, oncologists, surgeons, radiologists, and radiotherapists work together^[24].