How Is Adrenal Cancer Diagnosed? Hormone Tests, Scans, and Pathology Explained

Most people reach an adrenal cancer diagnosis by one of two very different roads. The first road starts with hormones. Your body changed in ways that were hard to explain. You gained weight around your face and belly, your blood pressure climbed, your potassium ran low, your periods became irregular, your voice deepened, or you grew hair in new places. You went to appointment after appointment. Someone may have told you it was stress, or aging, or weight, or thyroid. Then one day a doctor ordered a hormone test, and the test was clearly abnormal, and a scan found a mass on one of your adrenal glands. Many adrenal cancer symptoms come from hormones rather than from the tumor pressing on anything, which is exactly why they get mistaken for other conditions for so long. If that was your experience, it was not your imagination, and it was not your fault. The second road starts by accident. You had a CT scan for something completely unrelated, such as belly pain, a kidney stone, a car accident, or a lung question, and the radiologist noticed a mass sitting on top of one of your kidneys. Nobody was looking for it. This is called an adrenal incidentaloma, meaning a mass on the adrenal gland found by chance. Doctors describe this pathway using the term "a disease of modern technology," because better scanners find more of these masses every year. If this is you, please read the section below on masses found by accident before you read anything else, because the great majority of these masses are not cancer.

A workup for a suspected adrenal cancer takes a team.

• An endocrinologist (a doctor who specializes in hormones and the glands that make them) usually leads the hormone testing.

• A radiologist (a doctor who reads scans) decides whether the mass looks reassuring or worrying, and their reading carries real weight.

• An endocrine surgeon or surgical oncologist with adrenal experience plans the operation.

• A Pathologist (a doctor who studies tissue and cells under a microscope) makes the final diagnosis after the tumor is removed.

• A medical oncologist plans any drug treatment, and a genetic counselor helps you decide about genetic testing.

Published reviews of adrenocortical carcinoma care describe exactly this set of consultations as central to getting the diagnosis right, precisely because the disease is rare and the hormone picture is complicated.

Here is the point that matters most about the order of testing. Hormone testing comes before surgery, and before any thought of a biopsy. This is not a formality. The American Cancer Society states plainly that blood and urine tests for adrenal hormones are as important as imaging in diagnosing adrenal cancer, and that doctors often check hormone levels even when there are no obvious symptoms, because hormone changes can be subtle. Hormone results change the operation itself, and they change the anesthesia plan. If a tumor is flooding your body with cortisol, your surgical team needs to know before you go to sleep, because your blood sugar, blood pressure, wound healing, and infection risk are all affected, and because you may need steroid tablets afterward while your other adrenal gland wakes up. And if the tumor turns out to be a pheochromocytoma, which pumps out adrenaline-like hormones, going to surgery unprepared can trigger a dangerous blood pressure crisis on the operating table. That is why the metanephrine test described below is done even when nobody suspects a pheochromocytoma.

The second point surprises almost every patient: a needle biopsy is usually avoided when adrenocortical carcinoma is suspected. That feels backwards, since for most cancers a biopsy is the first step. Two reasons drive it. First, a needle passing through the tumor can drag cancer cells along its track and seed them where they were not before, and published guideline reviews specifically advise against biopsy in a suspected, surgically removable adrenocortical carcinoma because of the risk of spreading the tumor. Second, it usually does not help. The American Cancer Society explains that biopsy samples from benign adrenal adenomas and from adrenal carcinomas can look alike under the microscope, so a biopsy may not answer the question anyway. If the size and features on imaging suggest cancer, the standard approach is to remove the whole tumor and let the pathologist examine all of it.

One more piece of orientation before the tests. This guide is centered on adrenocortical carcinoma, often shortened to ACC, which is cancer of the adrenal cortex (the outer layer of the gland) and is what most people mean by adrenal cancer.

Pheochromocytoma and paraganglioma are different adrenal cancers and work differently. They come from the adrenal medulla (the inner core of the gland) rather than the cortex, and they are diagnosed with different tests, so they are flagged separately below wherever that matters.

Adrenal metastasis is not adrenal cancer at all. That is a cancer that started somewhere else, such as the lung, breast, kidney, or skin, and traveled to the adrenal gland. It is named and treated as the original cancer. And most adrenal masses of any kind are benign. Nothing here is a diagnosis. Talk with your own care team about which tests you need and what your results mean for you.

What Tests Are Used to Diagnose Adrenal Cancer?

There is no single test that says "adrenal cancer." Your doctors work through two questions in parallel.

1. Is this mass making hormones? That is answered by blood, urine, and sometimes saliva tests.

2. Does this mass look worrying? That is answered by scans.

The two answers together usually decide whether the mass is removed, and only the pathology report after removal gives the final diagnosis.

Adrenocortical carcinoma is genuinely rare. The National Cancer Institute reports an annual incidence of about 2 cases per 1 million people, with a median age at diagnosis of 46 years. Published reviews put the worldwide range at 0.5 to 2.0 cases per million per year, with roughly 300 to 400 new cases each year in the United States. Adults with ACC are more often women than men, with reported female-to-male ratios of about 2.5 to 1 or 3 to 1. About 5% to 10% of cases occur in children, most before age 15, so some readers here are parents rather than patients. Roughly 60% of adrenocortical carcinomas produce hormones, and when sensitive laboratory testing is used, up to 80% turn out to be making something.

The tests below are described in the order they usually happen. You may not need all of them.

Medical History and Physical Exam

Your first visit is mostly talking. Your doctor will ask when your body started changing and in what order, whether your blood pressure has been creeping up, whether you bruise easily or have purple stretch marks, whether you feel weak going up stairs or getting out of a chair, whether your periods changed, whether you have new acne or hair growth or hair loss, and whether your mood or sleep or memory shifted. Be specific about timing if you can, and bring old photos if your face or body has changed, because the change over time is often more telling than any single moment.

• Family history matters more in adrenal cancer than in most cancers. Published reviews estimate that hereditary cancer syndromes account for roughly 10% to 15% of adrenocortical carcinoma cases. Your doctor will ask about cancers in your parents, siblings, children, aunts, uncles, and grandparents, especially breast cancer, sarcoma, brain tumors, and any cancer diagnosed unusually young, because those patterns point toward Li-Fraumeni syndrome, which is caused by an inherited change in the TP53 gene and is the single most important hereditary cause of ACC. Other syndromes linked to ACC include Beckwith-Wiedemann syndrome, familial adenomatous polyposis, and Carney complex. Our guide to risk factors for adrenal cancer covers these in more detail.

• The exam itself is straightforward and does not hurt. Your blood pressure is measured, often lying down and then standing, because a drop on standing or a very high reading both give clues. Your doctor looks at your face, neck, and abdomen for rounding, the fat pad at the base of the neck, and the stretch marks that come with too much cortisol. They test the strength of your thighs and shoulders, since cortisol excess weakens the large muscles closest to the body first. They press on your abdomen feeling for a mass or an enlarged liver, check your neck and armpits for swollen lymph nodes, look at your legs for swelling that could suggest a clot, and look at your skin. In women, they may look for excess body hair, acne, and thinning scalp hair. In men, they may look for breast tissue growth. None of these findings prove anything by themselves. Together they tell the doctor which hormone tests to prioritize.

Hormone Blood and Urine Tests for Cortisol Excess

Too much cortisol causes Cushing syndrome, and it is the most common hormone problem in adrenocortical carcinoma. Because cortisol normally rises and falls through the day, one random blood draw is close to useless. So the tests are designed to catch cortisol behaving in ways it should not.

• The overnight low-dose dexamethasone suppression test is usually first. You take 1 milligram of dexamethasone, a synthetic steroid tablet, late in the evening, then have blood drawn the next morning after fasting. In a normal body, that tablet tricks the brain into thinking there is plenty of steroid around, so the brain stops signaling and the morning cortisol falls. If a tumor is making cortisol on its own, it ignores the signal and the morning cortisol stays up. It feels like nothing more than swallowing a pill and having one blood draw. Published guideline reviews describe this as the most reliable and easily reproducible screening test, and note that a morning cortisol at or below 1.8 micrograms per deciliter (50 nanomoles per liter) after the tablet essentially rules out autonomous cortisol production. Certain medicines and conditions can interfere, so an abnormal result is often repeated before surgery is planned.

• Late-night salivary cortisol takes advantage of the fact that cortisol should be at its lowest around bedtime. You put a small swab in your mouth at home at a set time, usually near midnight, and mail or bring in the sample. There is no needle and no fasting. A cortisol level that is high when it should be low points to a problem. This test is part of the standard endocrine panel for a suspected ACC.

• The 24-hour urine free cortisol test measures the total amount of cortisol your body dumps into the urine across a full day and night. You collect every drop of urine for 24 hours in a jug the lab provides, usually keeping it cold, and you note the exact start and stop time. It is inconvenient rather than painful, and the main risk is missing a collection, which lowers the result artificially. The National Cancer Institute lists a 24-hour urine test measuring cortisol or 17-ketosteroids as a standard part of the adrenal workup, noting that a higher-than-normal amount can be a sign of disease in the adrenal cortex.

• ACTH is measured with an ordinary blood draw. ACTH is the hormone the pituitary gland in your brain uses to tell the adrenal glands to make cortisol. If cortisol is high and ACTH is low, the cortisol is coming from the adrenal gland itself and not from a brain signal. That distinction matters because a pituitary problem and an adrenal tumor cause the same outward symptoms and need completely different treatment. If cortisol is high but ACTH is not suppressed, your doctor may order a high-dose dexamethasone suppression test or an MRI of the pituitary gland to sort out where the signal is coming from.

Hormone Tests for Aldosterone Excess

Aldosterone controls how much salt and water your body holds onto. Too much of it raises blood pressure and pushes potassium down, a picture sometimes called Conn syndrome. Two tests screen for it, and both are simple blood draws.

• The aldosterone-to-renin ratio compares the amount of aldosterone in your blood to the amount of renin, a kidney hormone that normally drives aldosterone production. If aldosterone is high while renin is pushed down, the aldosterone is being made without permission. Endocrine Society guidance is that everyone with an adrenal mass and high blood pressure should be screened this way, regardless of what their potassium is doing, and testing is also advised for anyone with low potassium even without high blood pressure. Reviews note that an aldosterone level under 9 nanograms per deciliter makes primary aldosteronism unlikely, while a level above 15 is suggestive. Timing and preparation matter here more than for most blood tests. You may be asked to eat normal amounts of salt, to have low potassium corrected first, and to pause certain blood pressure medicines for a while, sometimes switching to a different type in the meantime. Do not stop any medicine on your own. Your doctor will tell you what to change and when.

• Potassium is measured on the same kind of basic blood panel your doctor already orders. Low potassium in someone with high blood pressure and an adrenal mass is a meaningful clue. Very low potassium along with severe muscle weakness can also be a sign of an aggressive cortisol-producing tumor. Normal potassium does not rule out aldosterone excess, which is why the ratio is measured too.

Hormone Tests for Androgens and Estrogens

Sex hormone testing is where adrenocortical carcinoma often reveals itself. Guideline reviews note that measuring sex hormones is not routine for every small adrenal mass, but that it becomes genuinely useful when imaging looks indeterminate or worrying, because elevated levels point toward a tumor arising from the adrenal cortex rather than a cancer that spread there from elsewhere. More than half of people with adrenocortical carcinoma have at least one of these hormones elevated.

All of these are ordinary blood draws, usually taken together.

• DHEAS (dehydroepiandrosterone sulfate) is an adrenal androgen and is one of the most useful markers of an adrenocortical tumor.

• Testosterone is measured in women, where a high level can explain deepening voice, new facial or body hair, acne, scalp hair loss, and irregular or absent periods.

• Androstenedione and 17-hydroxyprogesterone are steroid building blocks that pile up when the adrenal cortex is overproducing, and a raised 17-hydroxyprogesterone can also point toward congenital adrenal hyperplasia, a noncancerous condition, especially when both adrenal glands are enlarged.

• Estradiol is measured in men and in women past menopause, where a raised level can explain breast tissue growth, reduced sex drive, and other feminizing changes.

These changes are not cosmetic footnotes. They affect how you see yourself in the mirror, how strangers treat you, your relationships, and your sense of your own body. Many people carry them for years while being told the cause was something else. Bringing them up at appointments is medically useful, not vanity, and a good endocrinology team will treat them as real findings.

Plasma Free Metanephrines and 24 Hour Urine Metanephrines

Pheochromocytoma is a different adrenal cancer and works differently. It arises from the adrenal medulla, the inner core of the gland, and it makes catecholamines, the adrenaline-like hormones behind the body's stress response. A paraganglioma is the same kind of tumor arising outside the adrenal gland. Because these tumors are handled so differently from adrenocortical carcinoma, they get their own guide sections throughout this series.

This test still belongs in every adrenal workup, including yours, even if nobody thinks you have a pheochromocytoma. Here is why. Metanephrines are the breakdown products of catecholamines, and measuring them is how a pheochromocytoma is found.

• Plasma free metanephrines, drawn from a vein while you lie down

• 24-hour urine fractionated metanephrines, collected the same way as the urine cortisol test, as the recommended screening tests, with a reported sensitivity of 99% and specificity of 97% when modern laboratory methods are used.

The National Cancer Institute's clinician summary reports sensitivity of 97% to 99% for plasma free metanephrines with a specificity around 85%, and notes that plasma testing is a reasonable first step with 24-hour urine testing used for confirmation.

The reason this is treated as mandatory rather than optional is safety, not curiosity. Surgery, anesthesia, and even needle biopsy can provoke a pheochromocytoma into releasing a surge of catecholamines, and guideline reviews state directly that pheochromocytoma should always be excluded biochemically before any adrenal mass is sampled with a needle, to avoid a potentially lethal blood pressure crisis. Pheochromocytomas are also not rare in this setting and are easy to miss on symptoms alone. Roughly 5% of adrenal masses found by accident turn out to be pheochromocytomas, more than 30% of pheochromocytomas are discovered as incidental findings, and in one large multicenter study about half of the people whose pheochromocytoma was found incidentally had normal blood pressure. Some are described as "silent," causing no symptoms at all. A ten-minute blood draw removes a serious surgical risk. That is why it is not skipped.

Steroid Metabolite Profiling in Urine

At some specialized centers, you may be offered urine steroid metabolomics, sometimes called steroid metabolite profiling. Instead of measuring a handful of hormones one at a time, this test uses mass spectrometry to measure dozens of steroid breakdown products in a single urine collection and looks at the overall pattern. Adrenocortical carcinomas tend to make steroids inefficiently and leave behind a distinctive fingerprint of immature steroid precursors that a benign adenoma does not.

For you, the test is just another urine collection. What it adds is discrimination in the hardest cases. Published guideline reviews report that, as a stand-alone test, urine steroid profiling detected adrenocortical cancer with a sensitivity of about 80%, but that when it was combined with imaging features, specifically a density above 20 Hounsfield units and a size above 4 centimeters, the combination had a negative predictive value of 99.7%. In plain terms, a reassuring combined result is very reassuring. Availability is still limited, and advanced steroid profiling can also pick up subtle hormone production in tumors that were previously labeled nonfunctioning. If it is not offered where you are, that is not a gap in your care, and it is a reasonable thing to ask about if a second opinion at a high-volume center is on the table.

CT Scan of the Abdomen

A CT scan (computed tomography) is the main imaging test for an adrenal mass. You lie on a table that slides through a ring-shaped scanner. Contrast dye is usually given through a vein, which often causes a warm flush and a metallic taste for a moment. The scan itself takes minutes and is painless. The adrenal glands show up well on CT, and the National Cancer Institute lists CT of the abdomen and chest as the core staging study.

Two pieces of CT vocabulary are worth learning, because they will appear in your report. Hounsfield units, written HU, are simply a measure of density, of how much a tissue blocks the X-ray beam. Water is set at 0 HU and fat runs roughly from minus 40 to minus 100 HU. Benign adrenal adenomas are typically full of fat, so they are less dense and read low. The widely accepted threshold is that a homogeneous mass measuring 10 HU or less on a scan taken without contrast is a benign, fat-rich adenoma. Guideline reviews describe this as highly reliable in one direction: across six studies, a density above 10 HU picked up 100% of malignant masses, meaning a mass at or below 10 HU is virtually never cancer. The catch is the other direction. Pooled specificity was only about 56% to 59%, because 30% to 40% of perfectly benign adenomas are low in fat and read above 10 HU. So a low number is strongly reassuring, while a higher number is a reason to look further, not a diagnosis.

Washout is the second term. It describes how quickly contrast dye drains out of a mass. The radiologist measures density before contrast, about a minute after contrast, and again 10 to 15 minutes later, then calculates how much of the dye has cleared. Benign adenomas soak up dye quickly and let it go quickly. Cancers and other worrying masses tend to hold onto it. Traditional thresholds are an absolute washout above 60% or a relative washout above 40% for an adenoma, and adrenocortical carcinomas typically show a relative washout below 40%. Newer data have tempered enthusiasm for these cutoffs, since roughly 8% to 22% of malignant tumors are misclassified by them, and to catch every malignant tumor the relative washout threshold would have to move so far that specificity collapses to about 15%. Washout is a helpful clue, not a verdict.

Putting it together, radiologists weigh several features.

• Size matters: the American Cancer Society notes that tumors larger than 4 centimeters, about 1.5 inches, suggest adrenal cancer. A meta-analysis found adrenocortical carcinoma in about 2% of masses 4 centimeters or smaller, about 6% of those 4.1 to 6 centimeters, and about 25% of those larger than 6 centimeters.

• Shape and texture matter: irregular borders, uneven internal appearance from areas of dead tissue or bleeding, and growth into nearby structures all raise concern, while benign adenomas are usually small, smooth, and uniform.

• Density and washout matter as described above.

• Growth over time matters, though less than people assume, since up to a quarter of benign adenomas enlarge slightly. One caution worth knowing: the scan that first found your mass was probably not optimized for adrenal glands, so your team may repeat a dedicated adrenal CT with thin slices and a proper washout protocol rather than rely on the original images.

Source: Endotext, NCBI Bookshelf, National Library of Medicine

MRI and Chemical Shift Imaging

An MRI (magnetic resonance imaging) uses a strong magnet and radio waves instead of X-rays. You lie inside a tube for 30 to 45 minutes while the machine makes loud knocking and buzzing sounds, and you will be given ear protection. Contrast called gadolinium is sometimes injected. If enclosed spaces are hard for you, say so beforehand, because there are options.

The American Cancer Society explains that CT is the most common imaging test for adrenal tumors, with MRI used in particular situations: to avoid radiation, which matters especially for children and during pregnancy, to gather more information when CT is unclear, and to look at the pituitary gland in the brain when high cortisol might be coming from an ACTH-producing tumor there rather than from the adrenal gland. MRI is also good at showing whether a tumor has grown into the large veins, including the vena cava, which changes how an operation is planned. The National Cancer Institute notes that MRI can add specificity to CT in evaluating an adrenal mass and can show tumor extension beyond the gland's capsule.

Chemical shift imaging is the MRI equivalent of measuring fat on CT, and it is worth understanding because it appears in reports. Water molecules and fat molecules resonate at slightly different frequencies inside a magnetic field. By taking one set of images where their signals add together (in phase) and another where they cancel each other out (out of phase), the scanner can reveal how much fat is inside a mass. Benign adenomas, which are full of fat, lose signal noticeably on the out-of-phase images. Adrenocortical carcinomas and pheochromocytomas generally do not. Reviews report that this technique identifies adenomas with a sensitivity of 84% to 100% and a specificity of 92% to 100%. Typical MRI features of adrenocortical carcinoma are intermediate to high signal on both T1 and T2 sequences, an uneven internal appearance from bleeding or dead tissue, and no significant signal loss on chemical shift images. As with everything else here, there is overlap, so MRI supports the picture rather than settling it.

FDG PET/CT

An FDG PET/CT scan measures how hungry tissue is for sugar. You fast beforehand, then a small amount of radioactive glucose called FDG is injected into a vein. You rest quietly for about an hour while it circulates, then the scanner takes pictures of where the sugar is being used. Cancer cells are usually more metabolically active than normal cells, so they light up brighter. Most machines take a CT at the same time, so the bright spots can be located precisely. The scan is painless, and the radiation dose is comparable to other diagnostic scans.

PET/CT does two jobs in adrenal cancer. It helps judge whether an adrenal mass is likely malignant, and it looks for spread everywhere in the body at once. Published reviews report a sensitivity of about 97% and a specificity of about 91% for separating malignant from benign adrenal lesions, with other reviews reporting ranges of 93% to 100% and 80% to 100%. The most useful measurement is a comparison: the ratio of uptake in the adrenal mass to uptake in the liver. A ratio below roughly 1.45 to 1.6 strongly predicts a benign lesion, which is why PET/CT is especially valuable for avoiding an unnecessary operation on a mass with equivocal CT features and low sugar uptake.

Two limitations are honest and worth knowing. FDG PET/CT cannot tell adrenocortical carcinoma apart from an adrenal metastasis, a lymphoma, or a pheochromocytoma, because all of them are metabolically active. And it can mislead in both directions: false negatives happen with very small tumors or tumors full of dead tissue, and false positives happen with inflammatory conditions such as sarcoidosis or tuberculosis and with some benign adenomas. Some specialized centers offer a different PET tracer, metomidate, which binds specifically to adrenal cortex enzymes and can confirm that a mass truly arose from the cortex when that is in doubt.

MIBG and DOTATATE Scans for Pheochromocytoma and Paraganglioma

This subsection is about pheochromocytoma and paraganglioma, not about adrenocortical carcinoma. These scans are not part of a routine ACC workup, but you may hear them mentioned while your team is ruling other things out, so here is what they are.

• An MIBG scan uses a tracer that behaves chemically like the building blocks of adrenaline, so cells of the adrenal medulla and related nerve tissue absorb it. It is injected into a vein, and images are taken over one to three days, sometimes with an iodine solution given first to protect the thyroid. The National Cancer Institute lists the MIBG scan among tests used to find pheochromocytoma and paraganglioma and to determine whether they have spread, and it also lists MIBG as a way to tell the difference between adrenocortical carcinoma and pheochromocytoma. Guideline reviews describe MIBG scanning as the preferred method for pinpointing a pheochromocytoma when the clinical, laboratory, and CT findings do not agree, or when several tumors need to be excluded.

• A DOTATATE scan is a PET scan that uses a tracer that locks onto somatostatin receptors, which are plentiful on many of these tumors. The National Cancer Institute lists an octreotide scan, an older version of the same idea, among staging tests for pheochromocytoma and paraganglioma, and its clinician summary describes DOTATATE PET/CT alongside MIBG as imaging used to watch for recurrence after these tumors are removed. In practice, DOTATATE PET has become the more sensitive of the two for finding small or widely scattered deposits, especially in paraganglioma.

If a pheochromocytoma or paraganglioma is confirmed, the rest of your care diverges from the ACC pathway in symptoms, diagnosis, genetics, staging, treatment, and outlook. Our guides on adrenal cancer stages and adrenal cancer treatment address these tumors separately.

Chest Imaging and Bone Imaging for Staging

Once adrenocortical carcinoma is suspected or confirmed, your team needs to know whether it has traveled. CT of the chest is mandatory, not optional. The National Cancer Institute's clinician summary states that a chest CT is necessary to assess possible lung spread, and published reviews report that lung deposits are present in 40% to 80% of cases that have spread. The chest CT is quick and often done in the same appointment as the abdominal CT.

The abdominal CT already covers the liver and the abdominal lining, which, along with the lungs, are the most common places adrenocortical carcinoma goes. Bones and the large veins are less commonly involved but are checked when there is a reason. Guideline reviews recommend imaging of the chest, abdomen, and pelvis with dedicated attention to the inferior vena cava and renal veins, plus assessment of nearby lymph nodes. If you have bone pain, an unexplained fracture, or a blood test suggesting bone involvement, a bone scan may be added, or the FDG PET/CT may serve that purpose since it images the whole body at once. Guidance is to consider bone imaging when it is clinically indicated rather than reflexively for everyone. Ultrasound is sometimes used to look specifically at whether the tumour has grown into the vena cava.

For an adrenal mass found by accident that looks worrying enough to remove, guideline reviews advise staging with a chest CT and sometimes an FDG PET/CT before the operation, so that spread is not discovered afterward.

Why a Biopsy Is Usually Avoided, and When It Is Used

This is worth repeating carefully, because it runs against everything patients expect about cancer diagnosis. If your imaging and hormone tests suggest adrenocortical carcinoma, your doctors will most likely recommend removing the whole tumor rather than sampling it with a needle first. The American Cancer Society states that generally doctors would not recommend an initial biopsy, and that if a tumor looks suspicious on imaging, it will be removed if possible.

• There are three reasons.

• First, the risk of spreading the tumor. A needle passing in and out can carry cancer cells along its path, and published guideline reviews specifically advise against biopsy of a suspected, surgically removable adrenocortical carcinoma because of the risk of tumor dissemination.

• Second, it usually cannot answer the question. Benign adenoma cells and adrenocortical carcinoma cells look similar under a microscope, and the features that identify a cancer, such as invasion into the capsule or into veins, can only be judged by looking at the whole tumor and its edges. Needle aspiration is specifically described as not accurate for separating benign from malignant primary adrenal tumors.

• Third, it carries real risk of its own, with reported complication rates of up to 14% in some series, including collapsed lung, bleeding, infection, and pancreatitis.

There are narrow situations where a biopsy is the right call, and they share one feature: the question is not "is this an adrenal cancer?" but "what kind of tissue is this?"

• Suspected lymphoma: Lymphoma involving the adrenal glands is treated with drug therapy, not surgery, so tissue is needed to make the diagnosis. It often involves both glands and makes no hormones.

• Suspected metastasis from another cancer: If you already have a known cancer elsewhere and an adrenal mass appears, sampling it can confirm whether that cancer has spread, which may change your treatment. The American Cancer Society gives exactly this example.

• Confirming spread of a known adrenal cancer: If there is a mass in the liver or elsewhere and it is unclear whether it came from your adrenal tumor or from something unrelated, a needle biopsy of that distant spot, not of the adrenal gland, can settle it.

• A tumor that cannot be removed: When surgery is not possible, tissue may be needed to guide drug treatment.

• Suspected infection or an infiltrative condition: Needle sampling is useful for diagnosing infections and conditions such as sarcoidosis in the adrenal gland.

In every one of these situations, one rule holds. Pheochromocytoma must be ruled out with metanephrine testing before a needle goes anywhere near an adrenal mass.

Pathology After Surgery: Weiss Score, Ki-67, Mitotic Rate, and Margins

The pathology report from your surgery is the document that turns a suspicion into a diagnosis, and it is also the document that shapes what happens next. It usually takes several days to a couple of weeks. Four things in it matter most.

The Weiss score is how pathologists decide whether an adrenal cortex tumor is benign or malignant. It is a checklist of nine features, and the tumor scores one point for each one it has. Adopted into the World Health Organization classification, it is described as the reference standard for making this call under the microscope, and a score of 3 or higher indicates malignancy with high specificity, while a score of 2 is considered suggestive. In plain language, the nine items are:

• High nuclear grade: The control centers of the cells look large, dark, and irregular rather than uniform.

• High mitotic rate: More than 5 cells caught in the act of dividing per 50 high-powered microscope fields, meaning the tumor is multiplying fast.

• Atypical mitoses: Cells dividing in visibly disordered, abnormal ways.

• Few clear cells: A quarter or less of the tumor is made of the pale, fat-filled cells that dominate a normal adrenal cortex.

• Diffuse architecture: The tumor has lost the orderly cords and nests of normal adrenal tissue and grows as a solid sheet.

• Necrosis: Areas of dead tissue inside the tumor, which happens when a mass outgrows its blood supply.

• Venous invasion: Tumor cells found growing inside veins.

• Sinusoidal invasion: Tumor cells found growing inside the small blood channels that thread through the adrenal gland.

• Capsular invasion: Tumor cells pushing through the outer covering of the tumor.

One important caveat: for the rare oncocytic variant of adrenocortical carcinoma, the standard Weiss criteria overcall malignancy, so pathologists use a modified system called Lin-Weiss-Bisceglia instead.

The Ki-67 proliferation index is a stain that marks cells actively preparing to divide, reported as a percentage. Adrenocortical carcinomas typically show a Ki-67 above 10%, while benign adenomas generally fall below that. The ranges overlap, so Ki-67 is interpreted alongside the rest of the picture rather than on its own. It also carries prognostic weight: an index above 20% is associated with worse outcomes, and Ki-67 below 10% is one of the criteria used to define lower-risk disease in the ongoing ADIUVO trial of mitotane after surgery. Your Ki-67 number is one of the things that will be discussed when deciding whether you need treatment after your operation.

Resection margin status describes whether any cancer was left behind.

• R0 means the tumor was removed completely with clean edges.

• R1 means microscopic cancer remained at an edge.

• R2 means visible cancer was left.

This single item is the most powerful thing in the report. Published reviews state that complete resection with negative margins is the most important prognostic factor in adrenocortical carcinoma, and that people who achieve R0 do significantly better than those with R1 or R2 margins. The National Cancer Institute similarly lists completeness of resection among the three key prognostic factors, along with stage and pathological grade, and describes radical open surgical removal as the only method for achieving long-term disease-free survival. Reoperation is recommended for an R2 resection when it is technically feasible.

Together, these findings drive what comes after surgery. They determine your stage, they determine whether mitotane or radiation is discussed, they determine whether a clinical trial is a good fit, and they set your follow-up schedule, which typically means checks every 3 months for the first 2 years, every 6 months until year 5, and yearly after that. Our guide to adrenal cancer treatment walks through those decisions.

Genetic Counseling and Germline Genetic Testing

Genetics carries more weight in adrenal cancer than in most cancers, and genetic counseling here is a real recommendation rather than a footnote.

• Germline testing looks at the genes you were born with, in every cell of your body, which is different from tumor testing that looks only at changes inside the cancer. It is usually done on a blood or saliva sample. A genetic counselor explains what a result would and would not mean, including for your children, siblings, and parents, before anything is drawn. For adrenocortical carcinoma, hereditary syndromes account for an estimated 10% to 15% of cases.

• Li-Fraumeni syndrome, caused by an inherited change in the TP53 gene, is the most significant. A particular TP53 variant called p.R337H is common in southern Brazil, where childhood adrenocortical carcinoma occurs at 10 to 15 times the worldwide rate.

• Beckwith-Wiedemann syndrome, caused by a disturbance in a region of chromosome 11, carries an estimated 7.5% risk of adrenocortical tumor development in affected children.

• Familial adenomatous polyposis and Carney complex are also linked. Genetics specialists are listed among the standard consultations for anyone with suspected hereditary disease.

• Every child diagnosed with adrenocortical carcinoma should be evaluated for a hereditary syndrome. The National Cancer Institute lists a TP53 mutation, Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and hemihyperplasia as the recognized risk factors for childhood adrenocortical carcinoma, and pediatric ACC is so tightly linked to germline TP53 that a diagnosis in a child is itself a reason to test. If you are the parent of a child with ACC, ask for a referral to genetics early, because the result affects surveillance for your child, and potentially for you and your other children.

• For pheochromocytoma and paraganglioma, the recommendation is even broader, and this is a genuine difference from ACC. The National Cancer Institute states that all patients diagnosed with pheochromocytoma or paraganglioma should have genetic counseling to learn their risk of an inherited syndrome and related cancers. Testing is often recommended when there is a personal or family history of a related syndrome, when there are tumors in both adrenal glands, when there is more than one tumor in a single gland, when there are signs of excess catecholamine release or a malignant paraganglioma, or when the diagnosis is made before age 40. Testing is sometimes recommended for people aged 40 to 50 with a single adrenal tumor and no family history, and is generally not recommended above age 50. When a gene change is found, testing is then offered to at-risk relatives who have no symptoms.

A positive germline result is not only bad news. It can explain years of unanswered questions; it opens the door to surveillance that catches problems early, and it gives your relatives information they can act on. Our guides on adrenal cancer screening and adrenal cancer prevention explain what surveillance for hereditary syndromes actually involves, since there is no population screening for adrenal cancer.

What About an Adrenal Mass Found by Accident?

If you are reading this because a scan for something else turned up a mass on your adrenal gland, start here. An adrenal incidentaloma is defined as an adrenal mass found by chance during imaging done for reasons unrelated to the adrenal glands, and by convention it needs to be at least 1 centimeter across to trigger a workup.

These are common. In autopsy studies, the prevalence is about 2.3%, with a range from 1% to 8.7%. Older CT studies found them in well under 1% of scans, but two studies using modern high-resolution CT reported rates of 4.4% and 5%, much closer to the autopsy figures. Age matters a great deal: adrenal masses are found in about 0.2% of people under 30, about 3% of people around age 50, and up to 10% of people over 70. They are found in both adrenal glands in about 10% to 15% of cases. They are very rare in childhood, accounting for only 0.3% to 0.4% of tumors in children and adolescents. Radiology series report them slightly more often in women, most likely because women have more abdominal imaging.

The overwhelming majority are benign. Guideline reviews state that 80% to 90% of adrenal incidentalomas are benign adrenal adenomas. The most careful analysis, restricted to nine studies that best matched the real-world situation of someone referred for assessment of a mass found by accident, reported the following breakdown: 88.1% nonfunctioning benign adenomas, 6% adenomas with mild autonomous cortisol secretion, 1.2% aldosterone-producing adenomas, 3% pheochromocytomas, 1.4% adrenocortical carcinomas, and 0.2% metastases from another cancer. If you have no history of cancer, the chance that an incidentally found adrenal mass is a metastasis has been estimated as low as 0.4%.

The workup answers exactly two questions, and it is designed to be finished quickly rather than dragged out.

1. Is it making hormones? Guideline reviews call for screening everyone with an incidentaloma for cortisol excess with the 1-milligram overnight dexamethasone suppression test, and for pheochromocytoma with plasma free or urinary metanephrines, plus testing for aldosterone excess in anyone with high blood pressure or low potassium. Sex hormones are measured when the imaging looks indeterminate or worrying. If both adrenal glands are involved, your doctor will also consider whether the glands are underproducing rather than overproducing.

2. Does it look worrying on imaging? That is answered by a CT without contrast, reviewed by an experienced radiologist, looking at size, density in Hounsfield units, and whether the mass is uniform or patchy.

How those two answers combine is fairly systematic.

• A homogeneous mass measuring 10 HU or less can be confirmed as a benign adenoma with no further imaging and no imaging follow-up at all, and recent evidence extends that reassurance even to masses larger than 4 centimeters if they are clearly uniform and low in density.

• For a uniform mass under 4 centimeters with a density of 11 to 20 HU, the chance of malignancy is under 10%, and the usual approach is one additional imaging study, chosen from FDG PET/CT, MRI with chemical shift imaging, or a CT with a washout protocol, or alternatively a single repeat scan at 12 months to confirm nothing has changed.

• Masses that are 4 centimeters or larger and either denser than 20 HU or patchy in appearance carry the greatest concern and are discussed by a multidisciplinary team, with immediate surgical removal the most likely recommendation and chest CT or FDG PET/CT done first to check for spread.

• Everything in between, such as a large mass with intermediate density or a small patchy mass, goes to the team for discussion with extra imaging, and if it stays unclear the choice is between surgery and a repeat scan in 6 to 12 months.

Two numbers are worth holding onto if you end up on the surveillance path.

• The risk that a mass which looked clearly benign at diagnosis later turns out to be malignant has been estimated at less than 1 in 1,000. And a meta-analysis of 32 studies found that only 2.5% of these masses grew by 10 millimeters or more over an average of nearly three and a half years, that malignant transformation was never observed, and that the risk of developing an obvious hormone excess syndrome during follow-up was under 0.1%.

• Adrenocortical carcinomas that start as incidental findings behave very differently, growing rapidly within months, generally faster than 0.8 centimeters per year. That difference in behavior is exactly what interval imaging is looking for. If your team recommends watching rather than operating, that is a decision grounded in good evidence, not a way of putting you off.

Source: National Cancer Institute - Credit Terese Winslow

What Happens After Your Test Results Come Back?

Once adrenocortical carcinoma is confirmed, the next step is staging, which means establishing how far the cancer has gone so that treatment can be planned. Two closely related systems are used: the AJCC system and the ENSAT system developed by the European Network for the Study of Adrenal Tumors, and they are essentially the same except that ENSAT reserves stage IV strictly for cancer that has spread to distant sites. In the National Cancer Institute's summary:

• Stage I is a tumor 5 centimeters or smaller confined to the adrenal gland

• Stage II is a tumor larger than 5 centimeters still confined to the gland

• Stage III has spread to nearby lymph nodes or grown into neighboring tissue, organs, or large blood vessels

• Stage IV has spread to distant parts of the body such as the lung, bone, or the lining of the abdomen.

Stage strongly predicts outcome. Our guide to adrenal cancer stages covers this in detail, and our guide to adrenal cancer survival rates puts the numbers in context.

Your case should then be discussed by a multidisciplinary team, meaning the endocrinologist, surgeon, radiologist, pathologist, and oncologist looking at your scans, laboratory results, and pathology together in the same room rather than passing you between clinics. Guideline reviews specifically call for team discussion of any adrenal mass with meaningful risk of malignancy, and published reviews list treatment at a specialized center among the factors that influence prognosis in adrenocortical carcinoma.

This is the part you can most directly influence, so it deserves emphasis. Complete surgical removal with clean margins is described in the literature as the most important prognostic factor in adrenocortical carcinoma, and the National Cancer Institute states that radical open surgical excision remains the only method for achieving long-term disease-free survival. Getting a complete removal is a matter of surgical skill and experience. Published reviews note that expected mortality after this operation is under 5% but that it varies significantly with surgical expertise, and that the operation demands familiarity with complex anatomy behind the abdominal cavity, with tumor involvement of major veins, and when to abandon a minimally invasive approach and open the abdomen to avoid spilling tumor. The core surgical requirements are removal of the gland in one piece, cancer-free margins, no tumor spillage, and removal of enlarged lymph nodes. Adrenal cancer is rare enough that many excellent general surgeons will see only a handful of cases in a career.

Adrenocortical carcinoma is genuinely difficult to diagnose under the microscope. Benign adenomas and carcinomas can look alike; the Weiss score requires judgment about nine separate features; Ki-67 ranges overlap between benign and malignant tumors, and the oncocytic variant needs a different scoring system entirely to avoid being overcalled as cancer. Having slides reviewed by a pathologist who sees adrenal tumors regularly can confirm the diagnosis, refine the grade, or occasionally change it. Asking for this is not doubting your team. It is standard practice in rare cancers.

Two conversations can be important before treatment starts rather than after, because timing limits your options.

• The first is fertility. Surgery, radiation, and drug treatment can all affect the ability to have children; hormone excess itself can disrupt menstrual cycles and cause infertility, and mitotane treatment comes with a recommendation to use contraception. If having children in the future matters to you, or might matter, raise it at your first or second appointment and ask for a referral to a fertility specialist before treatment begins.

• The second is hormone replacement. If your tumor has been making cortisol, your other adrenal gland has been idle and will not switch back on immediately, so you may need steroid tablets for a period after surgery. If you are treated with mitotane, glucocorticoid replacement is described as mandatory in order to prevent adrenal insufficiency.

Make sure you leave the hospital knowing whether you are on replacement steroids, how to increase the dose if you get sick, and who to call.

Write your questions down before appointments, and bring someone with you if you can. Our guide to questions to ask about adrenal cancer has a list you can print, and our guide to adrenal cancer support can help you find other people who have been through this. For background on the disease itself, start with our adrenal cancer facts guide. And remember that every decision described here belongs to you and your own care team, who know your full situation in a way no article can.

Sources:

• Adrenocortical Carcinoma Diagnosis & Prognosis, National Cancer Institute

• Childhood Adrenocortical Carcinoma, National Cancer Institute

• Tests for Adrenal Cancer, American Cancer Society

• Adrenocortical Carcinoma, StatPearls, NCBI Bookshelf

• Imaging Incidental Adrenal Lesions, PubMed Central