In short
Adrenocortical carcinoma is a rare cancer that forms in the outer layer of the adrenal glands. These small, triangle-shaped glands sit on top of the kidneys and make hormones that regulate vital body functions like blood pressure, metabolism, and stress response. When cancer develops here, it can disrupt hormone production and cause widespread changes in the body. Because this cancer is so uncommon—affecting only about 1 or 2 people per million each year—many patients have never heard of it before diagnosis. Understanding how it is found and confirmed is an important step in preparing for treatment and making informed decisions about care.
Key points
- Up to 30% of ACC cases are found by accident during tests for other health issues, highlighting the importance of follow-up on incidental findings.
- No single test can confirm ACC—doctors rely on a combination of physical exams, blood and urine tests, imaging, and sometimes surgery to make a diagnosis.
- Hormone tests are critical because most ACC tumors are functioning, meaning they produce excess cortisol, aldosterone, or sex hormones that cause noticeable symptoms.
- CT, MRI, and PET scans are the main imaging tools used to visualize adrenal tumors and check for cancer spread to the lungs, liver, or bones.
- People with inherited cancer syndromes like Li-Fraumeni or Beckwith-Wiedemann should undergo regular monitoring even without symptoms, as they have a higher risk of developing ACC.
- The Weiss score and Ki67 index are important tools used by pathologists to determine whether an adrenal tumor is benign or malignant.
- Patients interested in clinical trials must undergo additional diagnostic tests, including detailed imaging, hormone panels, and sometimes genetic testing to determine eligibility.
- Five-year survival rates range from 82% for stage 1 disease to just 13% for stage 4 disease, underscoring the importance of early detection.
Introduction: Who Should Undergo Diagnostics
Anyone experiencing symptoms that may point to adrenal gland problems should speak with a healthcare provider about getting tested. These symptoms can vary widely depending on whether the tumor is releasing excess hormones or simply growing large enough to press on nearby organs. Because adrenocortical carcinoma (ACC) is very rare, many people are diagnosed without having any symptoms at all. Studies show that between 20 and 30 percent of ACC cases are discovered by accident during imaging tests ordered for completely unrelated health concerns.
People who should consider diagnostic testing include those with unexplained weight gain in the face, neck, and trunk while their arms and legs remain thin. This pattern is often linked to excess cortisol, a hormone that helps the body use sugar, protein, and fats. Women who notice unusual hair growth on the face, chest, back, or arms—or who develop acne, balding, or a deepening voice—may be producing too much testosterone. Men with breast enlargement or tenderness may have elevated estrogen levels. Both men and women can experience high blood pressure, muscle weakness, frequent urination, or feeling unusually thirsty, which may be signs of too much aldosterone, a hormone that controls water and salt balance in the body.
People who feel a lump in the abdomen, experience pain in the belly or back, or have a sensation of fullness in the stomach should also seek medical attention. These symptoms may occur when a tumor grows large enough to press on nearby organs. In some cases, the tumor does not produce hormones at all, which is called a nonfunctioning tumor. These tumors may not cause symptoms in the early stages, making them harder to detect without imaging tests.
It is also advisable for people with certain inherited conditions to undergo regular monitoring or diagnostic testing, even if they do not have symptoms. These conditions include Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, familial adenomatous polyposis (FAP), Lynch syndrome, multiple endocrine neoplasia (MEN1), neurofibromatosis type 1 (NF1), and Von Hippel-Lindau syndrome. These genetic disorders are linked to a higher risk of developing ACC, and early detection can improve outcomes.
Diagnostic Methods
Once symptoms or risk factors prompt a visit to the doctor, a series of tests are used to determine whether adrenocortical carcinoma is present. No single test can definitively confirm ACC on its own, so healthcare providers rely on a combination of physical exams, imaging studies, blood and urine tests, and sometimes tissue examination to reach a diagnosis. This multi-step approach helps distinguish ACC from benign adrenal growths, which are much more common.
Physical Examination and Medical History
The diagnostic process typically begins with a physical exam and a review of the patient's health history and family medical background. During the exam, the healthcare provider looks for visible signs of hormone excess, such as a rounded face, a fatty hump on the back of the neck, purple stretch marks on the belly, or unusual hair patterns. Blood pressure and weight are also checked. The provider will ask about symptoms like pain, changes in appearance, energy levels, and any family history of cancer or genetic conditions.
Blood and Urine Tests
Laboratory tests of blood and urine are essential for detecting abnormal hormone levels. Because the adrenal cortex produces several hormones—including cortisol, aldosterone, and sex hormones like testosterone and estrogen—these substances are measured to see if they are outside a healthy range. Elevated levels of any of these hormones can suggest that a tumor is functioning and secreting hormones into the bloodstream.
For example, if cortisol levels are too high, the patient may have symptoms of Cushing syndrome, which include weight gain in the upper body, a round face, and muscle weakness. If aldosterone is elevated, the patient may have high blood pressure and low potassium levels, causing muscle cramps and frequent urination. Blood tests can also reveal whether male or female sex hormones are abnormally high, which can lead to changes in physical appearance and reproductive function.
Imaging Studies
Imaging tests are critical for visualizing the adrenal glands and identifying tumors. The most commonly used imaging methods include computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans. These tests create detailed pictures of the inside of the body and help doctors see the size, location, and characteristics of a tumor. They can also reveal whether the cancer has spread to other areas such as the lungs, liver, or bones.
CT scans use X-rays to produce cross-sectional images of the body. MRI scans use magnets and radio waves to create detailed images of soft tissues. PET scans involve injecting a small amount of radioactive material into the body, which is absorbed by rapidly dividing cancer cells, allowing them to show up on the scan. These imaging tests help healthcare providers examine the adrenal glands and surrounding structures without surgery.
Surgery and Tissue Examination
In some situations, the only way to make a definitive diagnosis of ACC is to remove the adrenal gland through surgery and examine the tissue in a laboratory. A doctor who specializes in studying body tissues, called a pathologist, analyzes the removed gland to determine whether cancer cells are present. This approach is especially common when imaging and hormone tests suggest cancer but do not provide absolute confirmation.
The pathologist uses several criteria to distinguish between a benign adrenal adenoma and adrenocortical carcinoma. One of the most widely used tools is the Weiss score, which evaluates features such as the structure of the cells, how they are dividing, and whether they have invaded nearby tissues. A higher Weiss score increases the likelihood that the tumor is malignant. The proliferation rate of cells, including the mitotic count and the Ki67 index, also provides important information about how aggressively the tumor is growing.
Distinguishing ACC from Other Conditions
One of the main challenges in diagnosing ACC is telling it apart from benign adrenal adenomas, which are common and usually harmless. Adenomas may also produce hormones or appear as lumps on imaging tests, making them difficult to distinguish from cancerous tumors without careful evaluation. Doctors look at the size of the tumor, the speed at which it is growing, the presence of hormone overproduction, and the results of imaging tests to make this distinction. Tumors larger than 4 to 6 centimeters are more likely to be cancerous, although smaller tumors can also be malignant.
Another condition that must be ruled out is pheochromocytoma, a tumor that forms in the inner part of the adrenal gland, called the adrenal medulla. Pheochromocytomas produce different hormones than ACC and cause different symptoms, such as episodes of high blood pressure, rapid heartbeat, sweating, and headaches. Blood and urine tests measuring catecholamines help differentiate this tumor from ACC.
Diagnostics for Clinical Trial Qualification
Patients who are considering enrolling in clinical trials for adrenocortical carcinoma must undergo specific diagnostic tests and evaluations to determine whether they meet the study's criteria. Clinical trials are research studies that test new treatments, drugs, or combinations of therapies to improve outcomes for patients with ACC. Because ACC is rare, participation in clinical trials can provide access to cutting-edge therapies that are not yet widely available.
Enrollment criteria for clinical trials often include detailed imaging studies to confirm the stage of the disease. Staging describes how far the cancer has spread and helps researchers select patients who are most likely to benefit from the experimental treatment being tested. The European Network for the Study of Adrenal Tumors (ENSAT) staging system is commonly used in ACC clinical trials. This system divides the disease into four stages based on tumor size, lymph node involvement, and whether the cancer has spread to distant organs.
Blood and urine tests measuring hormone levels are also standard requirements for clinical trial entry. These tests help classify the tumor as functioning or nonfunctioning and provide baseline information about the patient's overall health. Liver function tests, kidney function tests, and complete blood counts are often required to ensure that the patient can safely tolerate the experimental treatment.
Pathology reports from a previous biopsy or surgery are critical documents for trial enrollment. These reports confirm the diagnosis of ACC and provide information about the tumor's characteristics, such as the Weiss score, Ki67 index, and resection status (whether the tumor was completely removed or not). Researchers use this information to group patients and determine who is eligible for specific arms of a trial.
Some clinical trials also require genetic testing or molecular profiling of the tumor. Advances in understanding the genetic changes that drive ACC have led to the development of targeted therapies aimed at specific mutations. For example, changes in genes like TP53, CTNNB1, or alterations in the insulin-like growth factor pathway may make a patient eligible for trials testing drugs that target these abnormalities.
Imaging tests such as CT, MRI, or PET scans are repeated at regular intervals during clinical trials to monitor how well the treatment is working. These scans measure changes in tumor size and detect any new areas where the cancer may have spread. Patients must be willing to undergo these tests as part of the trial protocol.
In addition to medical tests, clinical trials often assess a patient's overall health status using a performance scale. This scale measures how well a person can carry out daily activities and helps researchers determine if the patient is strong enough to participate in the study. Patients who are very weak or unable to care for themselves may not qualify for certain trials because the treatment could be too difficult for them to tolerate.
Participation in a clinical trial requires informed consent, meaning the patient must fully understand the purpose of the study, the potential risks and benefits, and the tests and procedures involved. Diagnostic testing for trial qualification is more extensive than standard diagnostic testing, but it provides valuable information that can guide personalized treatment decisions even outside the trial setting.
Prognosis and Survival Rate
Prognosis
The prognosis for adrenocortical carcinoma depends on several factors, including the stage at which the cancer is diagnosed, whether it can be completely removed with surgery, and how well it responds to treatment. When ACC is found early and the tumor is confined to the adrenal gland, the chances of long-term control or cure are significantly better. However, ACC is often discovered at an advanced stage because early-stage tumors may not cause noticeable symptoms. The disease is very aggressive, meaning it can grow quickly and spread to other parts of the body such as the lungs, liver, or bones.
Complete surgical removal of the tumor offers the best chance for a favorable outcome. If the tumor has not spread to nearby tissues or distant organs, surgery can sometimes result in long-term remission. However, even after successful surgery, ACC often comes back, which is called recurrence. This happens because cancer cells may remain in the body even when they cannot be seen on imaging tests. The likelihood of recurrence is higher in patients with larger tumors, incomplete removal of the tumor, or cancers that have already spread to lymph nodes.
Factors that affect prognosis include the tumor's size, whether it has invaded nearby tissues, the presence of cancer in lymph nodes, and the proliferation rate of cancer cells as measured by the Ki67 index and mitotic count. Patients with functioning tumors that produce excess hormones may experience symptoms that affect their quality of life, but the hormonal activity itself does not necessarily predict a worse outcome. Advanced ACC that has spread to distant organs is much more difficult to treat, and outcomes are generally poorer in these cases.
Survival Rate
Survival rates for adrenocortical carcinoma vary widely depending on the stage of the disease at diagnosis. Patients with stage 1 ACC, where the tumor is smaller than 5 centimeters and confined to the adrenal gland, have a five-year survival rate of approximately 82 percent. Stage 2 ACC, with tumors larger than 5 centimeters but still localized, has a somewhat lower survival rate. When the disease progresses to stage 3, meaning it has spread to nearby tissues or lymph nodes, the outlook becomes more challenging. Stage 4 ACC, defined by the presence of distant metastases, has a five-year survival rate of around 13 percent.
About 70 percent of patients with ACC are diagnosed with stage 3 or stage 4 disease, which means the majority of patients face a more difficult prognosis. For patients with metastatic ACC, the cancer has often spread to the lungs, liver, or bones by the time it is detected. In these cases, treatment focuses on controlling the disease, managing symptoms, and improving quality of life rather than achieving a cure. Tumors that have spread usually lead to death within 1 to 3 years, although some patients live longer with aggressive treatment.
It is important to remember that survival statistics are averages based on large groups of patients and cannot predict what will happen to any individual person. Some patients with advanced ACC respond well to treatment and live longer than expected, while others may experience a more aggressive course of disease. Advances in treatment, including surgery, chemotherapy, targeted therapies, and supportive care, continue to improve outcomes for some patients with ACC.
