Adrenal Incidentaloma

Improvements in X-ray techniques have led to the discovery of an increasing number of clinically silent adrenal masses called adrenal incidentalomas. An adrenal incidentaloma is an asymptomatic adrenal tumor that is discovered on an imaging test (CAT scan, MRI, etc) which was ordered to evaluate a problem that is unrelated to adrenal disease. This definition does not include patients undergoing imaging procedures as a part of a workup or follow-up for cancer.18 Based on autopsy studies, adrenal masses are among the most common tumors in humans. At autopsy, an adrenal mass is found in at least 3% of people over age 50. By the age of 70, up to 7% of people may have an adrenal incidentaloma. Most adrenal masses cause no health problems. However, a small number of adrenal incidentalomas can cause serious disease.

What kind of tumor can this be?

Adrenal incidentalomas can be functioning (i.e. make too much hormone) or non-functioning. They can be benign or malignant. The majority are non-functioning, benign tumors.

  1. Functioning tumors – aldosterone-producing adenoma, cortisol-producing tumor (i.e. Cushing’s syndrome), virilizing tumor (i.e. androgen-producing tumor), paraganglioma and pheochromocytoma (i.e. adrenaline producing tumor)
  2. Malignant tumors – adrenocortical cancer and metastatic disease
  3. Benign, non-functioning tumors – adenoma, myelolipoma, ganglioneuroma, adrenal cyst, and hematoma

Signs and Symptoms

Adrenal incidentalomas usually are asymptomatic (i.e. there are no symptoms or signs of the disease). Sometimes symptoms of hormone overproduction are discovered on closer questioning after the adrenal tumor is discovered.

Symptoms can include elevated blood pressure, sweating, anxiety, weight loss or gain, hyperglycemia, stretch marks, mood swings, headaches, episodes of passing out, abnormal hair growth or hair loss, changes in libido, etc. However, the majority will have no symptoms at all because they are either nonfunctional or subclinically functional (hypersecreting hormone but not causing any obvious symptoms).

What should be done if I have an incidentaloma?

There are two main questions to answer: 1) is the tumor functional (i.e. making too much hormone) and 2) what is the chance that this is cancer? To answer these questions, a series of tests should be done.

1) Is the tumor functional?

The three main functional tumors to rule out are pheochromocytoma, aldosterone producing adenoma, and cortisol producing tumor (Cushing syndrome). Virilizing tumors (tumors that make too much male hormone) are rare and usually cause signs and symptoms like increased hair growth (i.e. hirsutism), acne, male pattern baldness, and loss of or irregular periods that lead to a work-up. The biochemical (labwork) evaluation of an adrenal incidentaloma includes:

Metanephrine levels – The body breaks down adrenaline into metanephrines and normetanephrines. Levels of epinephrine and norepinephrine and the break down products can be measured by 24 hour urine collection or plasma (blood) levels to aid in diagnosis of an adrenaline secreting tumor (pheochromocytoma). Many physicians feel that the 24 hour urine test is better than the plasma test because it has fewer false positives (i.e. fewer cases of a positive test in someone who does not have a pheochromocytoma). 

24 hour urine study and 1mg low dose Dexamethasone suppression test – After taking 1mg of Dexamethasone at midnight, the cortisol level at 8AM the next morning should be very low (i.e. suppressed) in patients who do NOT have Cushing’s syndrome. (See Cushing’s syndrome: Diagnosis). If the cortisol level after receiving 1 mg of Dexamethasone is not very low, the may have Cushing’s syndrome.
Plasma aldosterone and renin levels – A high aldosterone level with a very low (i.e. suppressed) renin level suggests that the tumor is making too much aldosterone. (See Primary hyperaldosteronism: Diagnosis)

Metabolic panel – measures sodium, potassium, acid/base balance, kidney function and glucose levels. Hormones from the adrenal gland can affect these measurements.

Sex hormones, DHEA-S and other steroid synthesis intermediaries – some adrenal tumors can produce testosterone and other products in the steroid synthesis pathway.

What is the chance that this is cancer?

The two types of cancer to rule out are 1) metastases (i.e. cancer from somewhere else that spreads to the adrenal gland) and 2) adrenocortical cancer (i.e. primary adrenal cancer). Some cancers such as melanoma, breast, and lung cancer may send metastases to the adrenal gland. In order to determine if the adrenal incidentaloma is a metastasis, patients should have age-appropriate health screening. This includes routine mammograms, chest X-ray, and colonoscopy as directed by their primary care doctor. Occasionally, a PET scan (a special X-ray that looks for cancer elsewhere in the body) may be necessary if there is a history or a high suspicion of other types of cancers.  In order to determine if the adrenal incidentaloma is an adrenocortical cancer, the imaging tests should be reviewed carefully. The size and appearance of an adrenal mass on either CAT scan or MRI can help determine the chance of adrenocortical cancer. Tumors smaller than 4 cm are rarely cancer (only about 2 to 3%), while tumors greater than 6 cm have about a 25% chance of being cancer. Tumors between 4 and 6 cm have approximately a 7% risk of being an adrenocortical cancer. In addition, on CAT scan, the Hounsfield units (HU) can help to determine the risk of cancer. A tumor with a smooth border that is less than 10 HU on a CAT scan without contrast strongly suggests that the tumor is benign (i.e. an adrenal adenoma). A tumor with irregular borders, signs that it is growing into surrounding structures (i.e. invasion), or with high HUi may be suspicious for an adrenocortical cancer. Biopsy of adrenocortical carcinoma is not recommended if it is surgically resectable. However, in cases where there is concern that this represents a metastasis from another cancer site, a CT-guided biopsy may be helpful in directing care, especially in patients with a history of lung, breast, or kidney cancer. Before a biopsy of the adrenal gland, it is crucial to rule out a pheochromocytoma in order to avoid the potential for life-threatening increases in blood pressure known as a “pheo-crisis.” It is very important to understand that a benign biopsy result is not 100% accurate and there is still a chance that it could be cancer. 

Do I need a biopsy?

One common mistake is to perform a biopsy when an adrenal “incidentaloma” is discovered. This can be dangerous if the tumor is a pheochromocytoma as a needle entering an adrenaline secreting tumor can precipitate a hyperensive crisis. Adrenal masses should never be biopsied unless a pheochromocytoma has been ruled out with biochemical tests. Even then, a biopsy is rarely helpful or necessary. The main reason to biopsy an adrenal mass is to make a diagnosis of an adrenal metastasis in someone with another type of cancer for whom the physician is deciding between systemic therapy and an operation. An example of this is someone with lung cancer and an adrenal tumor. If the adrenal tumor is a metastatic lung cancer, the patient will likely get chemotherapy and not an operation to remove the lung cancer metastasis. If an adrenocortical cancer is biopsied, cells may escape the tumor and line the needle tract with tumor cells that can grow over time.

Treatment of adrenal incidentalomas

Patients with a functional adrenal tumor (i.e. making too much hormone) are usually offered an operation to remove the adrenal gland which includes the tumor. For patients with non-functional tumors, the size of the tumor and imaging characteristics will determine if an operation is indicated. If the tumor has suspicious characteristics on imaging (i.e. irregular borders, evidence of invasion, etc), then it should be removed. In 2002, the National Institutes of Health released a consensus statement with the following guidelines for who should have an adrnealectomy based on the size of the tumor:

Size of Tumor    Risk of Cancer          Recommendation
Less than 4 cm         2 to 3%          Observation
4 to 6 cm            7%          Adrenalectomy 
Greater than 6 cm           25%          Adrenalectomy

For tumors between 4 and 6 cm in size, the general recommendation is to remove it, but the patient’s age, other health problems, and imaging characteristics of the tumor should be taken into consideration. If there are reasons the patient may not tolerate an operation, then observation is the best treatment. Since CAT scan and MRI underestimate the size of adrenal tumors (i.e. the adrenal tumors are often bigger in the operating room than on CAT scan), many physicians use slightly different size criteria and recommend observing tumors less than 3 cm, removing any tumor greater than 5 cm, and removing tumors between 3 and 5 cm if the patient is healthy enough. 

Follow-up of adrenal incidentalomas

If the tumor is not removed, it is important to have close follow-up to see if the tumor becomes functional or if it grows. Studies have shown that most adrenal incidentalomas that are observed will not grow or become hyperactive. Only 5 to 25% grow, while 3 to 4% shrink. While up to 20% of tumors will become functional, it is unlikely to happen in tumors smaller than 3 cm. The risk that a tumor will become hyperactive is greatest in the first 3 to 4 years and Cushing syndrome is the most likely problem to develop.

For patients with an adrenal incidentaloma who have not undergone surgery, recommendations for follow-up may include:

  1. Repeat CAT scan 6 to 12 months after diagnosis
  2. Repeat lab testing every 12 months for 5 years 

If the tumor does not grow after the first year, repeat imaging may not be necessary. Your doctor will help you decide the frequency and type of follow-up testing.