Adrenal Cancer (Adrenocortical Carcinoma)

What adrenal cancer is

Each adrenal gland has two parts. The outer cortex makes cortisol (stress hormone), aldosterone (salt and blood pressure hormone) and small amounts of sex hormones (androgens). The inner medulla makes adrenaline. Adrenocortical carcinoma starts in the cortex. Tumors of the medulla, such as pheochromocytoma and neuroblastoma, are different diseases.

Most adrenal masses are not cancer. Small, benign adrenal adenomas are found in a few percent of adults who have CT scans. Cancer is more likely when a mass is large (especially over 4 to 6 cm), growing, irregular, or has particular features on CT or MRI. The adrenal glands are also a common site for cancer to spread from elsewhere, such as the lung, which is called adrenal metastasis.

Symptoms

Hormone-related symptoms

About half to two-thirds of adrenocortical carcinomas make excess hormones.

Too much cortisol (Cushing's syndrome): the most common pattern.

• weight gain around the belly and face, with thin arms and legs
• a round face and fat pad between the shoulders
• wide purple stretch marks, thin skin and easy bruising
• muscle weakness, especially getting up from a chair
• high blood pressure, high blood sugar and diabetes
• mood changes, depression and poor sleep

Too many androgens (male hormones):

• in women: excess facial and body hair, acne, deepening voice, male-pattern hair loss and irregular or absent periods
• in children: early puberty, rapid growth and acne

Too much estrogen: rare. Breast enlargement and reduced sex drive in men.

Too much aldosterone (Conn syndrome): high blood pressure and low potassium, causing cramps, weakness and thirst. This is usually from a benign adenoma rather than cancer.

Rapid onset of combined cortisol and androgen excess over a few months is a classic warning sign of adrenal cancer.

Symptoms from tumor size

Tumors that do not make hormones are often large when found and may cause:

• pain or fullness in the belly, side or back
• a feeling of fullness after eating little
• weight loss, fever, fatigue

Causes and risk factors

Most adrenal cancers occur without a known cause. Inherited conditions raise the risk, especially in children:

• Li-Fraumeni syndrome (TP53 gene changes), the most important, particularly in childhood cases
• Beckwith-Wiedemann syndrome
• Lynch syndrome
• multiple endocrine neoplasia type 1 (MEN1)
• familial adenomatous polyposis

Genetic counseling and testing are recommended for everyone diagnosed with adrenocortical carcinoma, especially children.

Diagnosis

Hormone tests

Every adrenal mass is checked for hormone production:

• cortisol: overnight dexamethasone suppression test, 24-hour urine cortisol, late-night saliva cortisol
• androgens and their precursors, such as DHEA-S and testosterone
• aldosterone and renin, with potassium, in people with high blood pressure
• metanephrines in blood or urine to rule out pheochromocytoma before any biopsy or surgery

Imaging

• CT scan: measures size and density. Benign adenomas are usually small and fat-rich (low density). Cancers are usually larger, irregular and high density.
• MRI and sometimes PET-CT help characterize the mass and look for spread to the liver, lungs, lymph nodes and bones.

Needle biopsy is generally avoided for a suspected primary adrenal cancer, because it can spread cancer cells and often does not give a clear answer. The diagnosis is usually confirmed by examining the whole tumor after surgery.

Stages

Treatment

Treatment is best done at a center experienced in adrenal cancer.

• Surgery (adrenalectomy): complete removal of the tumor and gland, with nearby lymph nodes and any involved tissue, without breaking the tumor capsule. Open surgery is usually preferred for suspected cancer. This is the only potentially curative treatment.
• Mitotane: an oral medicine that destroys adrenal cortex cells. It is often given after surgery to reduce the risk of the cancer coming back, and for advanced disease. It requires blood level monitoring and causes adrenal insufficiency, so steroid replacement is needed.
• Chemotherapy: a combination of etoposide, doxorubicin and cisplatin with mitotane is the standard for advanced disease.
• Radiation therapy: to the tumor bed in some people after surgery, and to relieve symptoms from metastases.
• Controlling hormone excess: medicines that block cortisol production or action, and treatment of high blood pressure, diabetes and low potassium.
• Clinical trials: immunotherapy and targeted drugs are being studied.

After removal of a cortisol-producing tumor, the other adrenal gland may be temporarily suppressed, so steroid replacement is often needed for months.

Outlook

Outlook depends mainly on the stage and whether surgery removes all the tumor. Small tumors that are completely removed have the best prognosis. Adrenal cancer often recurs, so regular CT scans and hormone tests are needed for years after treatment. Advanced disease is harder to treat, but treatment can control the cancer and its hormone effects for a period. Children with adrenal cancer often do better than adults.

Frequently asked questions

What are the first signs of adrenal cancer?

Often the first signs come from excess hormones: rapid weight gain in the face and belly, purple stretch marks, muscle weakness and high blood pressure from cortisol, or excess hair, acne and deepening voice in women from androgens. Others notice belly or back pain, or the tumor is found by chance on a scan.

Are most adrenal tumors cancerous?

No. Most adrenal masses are small, benign adenomas, often found incidentally on scans done for other reasons. Adrenal cancer is rare. Features that raise concern include large size, rapid growth, irregular shape and specific CT findings.

Is adrenal cancer curable?

It can be, especially when found early and removed completely by an experienced surgeon. Mitotane after surgery lowers the chance of recurrence in some people. Advanced adrenal cancer is harder to cure, but treatment can control it and its symptoms.

How is adrenal cancer different from pheochromocytoma?

Adrenal cancer (adrenocortical carcinoma) arises in the outer cortex and often makes cortisol or androgens. Pheochromocytoma arises in the inner medulla, makes adrenaline-like hormones, and causes episodes of pounding headache, sweating and racing heart. Most pheochromocytomas are benign.