Adrenal cancer is a rare cancer that forms in the adrenal glands, two small triangular-shaped glands that sit on top of each kidney. The most common form, called adrenocortical carcinoma (ACC), starts in the outer layer of the gland, known as the cortex. This outer layer produces hormones that regulate blood pressure, stress response, water balance, and sex characteristics. Because these glands are so deeply involved in hormone production, adrenal cancer often causes noticeable hormonal changes throughout the body, sometimes long before the tumor itself is detected.
Types of Adrenal Tumors
The adrenal gland has two distinct parts, and cancer can arise in either one. The outer cortex produces hormones like cortisol, aldosterone, testosterone, and estrogen. Cancers starting here are called adrenocortical carcinomas. The inner core, called the medulla, produces adrenaline and related hormones. Tumors in the medulla are called pheochromocytomas and are a separate disease with different treatment approaches. When people refer to “adrenal cancer,” they almost always mean adrenocortical carcinoma.
ACC tumors are further classified as functioning or non-functioning. A functioning tumor overproduces hormones, which often triggers recognizable symptoms. A non-functioning tumor has no effect on hormone levels, which means it can grow for longer before being noticed. Roughly half or more of ACCs are functioning, and they most commonly overproduce cortisol.
Symptoms From Excess Hormones
The symptoms of adrenal cancer depend heavily on which hormone the tumor is overproducing, if any. Excess cortisol causes a collection of changes known as Cushing syndrome: weight gain concentrated in the face and midsection, thinning skin that bruises easily, muscle weakness, high blood sugar, and high blood pressure. These changes can develop gradually, making them easy to dismiss at first.
Tumors that overproduce aldosterone raise blood pressure and lower potassium levels, which can cause muscle cramps, weakness, and frequent urination. Androgen-producing tumors cause masculinizing effects, including excess facial and body hair, a deeper voice, and irregular periods in women. Estrogen-producing tumors in men can cause breast tenderness and growth. Non-functioning tumors, by contrast, tend to cause symptoms only once they grow large enough to press on surrounding organs, producing abdominal pain, a feeling of fullness, or a mass you can feel in the abdomen.
Who Is at Risk
Most cases of adrenal cancer occur without a known genetic cause, but several inherited conditions significantly raise the risk. Li-Fraumeni syndrome, caused by mutations in the TP53 gene, is the most strongly associated. About 13% of people with Li-Fraumeni syndrome develop an adrenal tumor, and in children with ACC, roughly half carry a TP53 mutation regardless of whether they have a family history of cancer. The median age of onset for adrenal tumors in Li-Fraumeni syndrome is just 3 years old.
Lynch syndrome, familial adenomatous polyposis, and Beckwith-Wiedemann syndrome also carry an increased risk, though the percentages are much smaller. Beckwith-Wiedemann syndrome is notable for its extremely early onset, with a median age of just 10 months at diagnosis. Other hereditary syndromes linked to adrenal tumors include multiple endocrine neoplasia types 1 and 2, and von Hippel-Lindau disease, though these more commonly involve the adrenal medulla rather than the cortex.
How Adrenal Cancer Is Diagnosed
Diagnosis involves both hormone testing and imaging, and the blood and urine work is considered just as important as the scans. For cortisol-producing tumors, you may be asked to collect all your urine over a 24-hour period to measure cortisol output. Another common test involves taking a small dose of a synthetic steroid the night before a morning blood draw. In a healthy person, this suppresses cortisol production. In someone with a cortisol-producing tumor, cortisol levels stay high because the tumor operates independently.
If aldosterone overproduction is suspected, blood tests will show elevated aldosterone alongside low potassium and low renin, a kidney hormone that normally helps regulate blood pressure. Androgen-producing tumors show elevated DHEAS or testosterone, while estrogen-producing tumors show high estrogen levels. CT scans and MRI are used to measure the tumor’s size, determine whether it has spread, and help distinguish cancer from the much more common benign adrenal tumors that show up incidentally on scans done for other reasons.
Stages and What They Mean
Adrenal cancer is staged using the ENSAT system, which is the internationally accepted standard because it closely correlates with outcomes. The stages are straightforward:
- Stage I: Tumor smaller than 5 cm, confined to the adrenal gland, no spread.
- Stage II: Tumor larger than 5 cm, still confined to the gland, no spread.
- Stage III: Tumor has invaded nearby tissues or reached regional lymph nodes.
- Stage IV: Cancer has spread to distant parts of the body.
A recent modification to the system reclassifies lymph node involvement from stage III to stage IV, because survival data showed that patients with positive lymph nodes have outcomes more similar to those with distant spread.
Survival Rates by Stage
Based on data from patients diagnosed between 2015 and 2021, the five-year relative survival rates for adrenal cancer are 80% for localized disease (confined to the gland), 62% for regional disease (spread to nearby structures), and 39% for distant disease (spread to other organs). These numbers reflect all patients in each category and don’t account for individual factors like age, overall health, or how well the tumor responds to treatment. Earlier-stage tumors have meaningfully better outcomes, which is one reason functioning tumors, despite their disruptive symptoms, sometimes carry a silver lining: the hormonal changes can lead to earlier detection.
Surgery as the Primary Treatment
Complete surgical removal of the tumor is the most important treatment for adrenal cancer and the only approach that offers a chance of cure. The goal is what surgeons call an R0 resection: removing the entire tumor with clean margins and no disruption of the tumor capsule. For suspected ACC, guidelines recommend treatment at high-volume centers with multidisciplinary teams, because the complexity of achieving a complete resection directly affects outcomes. Some cases require removing the tumor along with surrounding tissue and even parts of adjacent organs in a single piece to ensure no cancer cells are left behind.
For smaller, clearly benign-appearing tumors, minimally invasive surgery is preferred because it results in less pain, shorter hospital stays, and fewer complications. But when cancer is suspected or confirmed, open surgery is often necessary to safely remove the tumor intact and inspect surrounding tissues.
Treatment for Advanced Disease
A medication called mitotane is central to the treatment of adrenal cancer, both after surgery to reduce recurrence risk and as a primary therapy for advanced disease. Mitotane is unique in cancer treatment because it specifically targets adrenal cells. It disrupts the machinery those cells use to process cholesterol, which is the raw material for hormone production. Free cholesterol builds up inside the cells and becomes toxic, killing them. The drug needs to reach a specific concentration in the blood to be effective, and achieving that level can take weeks. It also suppresses normal adrenal function, so patients on mitotane need hormone replacement therapy.
For metastatic disease, mitotane is combined with a multi-drug chemotherapy regimen. Treatment is typically started after mitotane has had at least a week to build up in the body. Side effects from mitotane can include nausea, fatigue, dizziness, and neurological symptoms at higher blood levels, which is why regular blood monitoring is necessary to keep concentrations within a narrow therapeutic range.