Adrenal Tumor Diagnosis

Adrenal cancer, also known as adrenocortical carcinoma (ACC), begins in the outer layer of the adrenal gland, which produces hormones that regulate the body’s metabolism, blood pressure, sexual development and stress response. ACC develops when cells in the adrenal cortex undergo harmful DNA changes that promote uncontrolled cell growth. Some cases are linked to an inherited cancer predisposition syndrome, such as Li-Fraumeni, Beckwith-Wiedemann or multiple endocrine neoplasia type 1 (MEN1), but many have no clear cause.

The symptoms of adrenal cancer can vary based on whether the tumor produces hormones. A functioning adrenal tumor may elevate hormone levels, which can lead to unexplained weight gain, high blood pressure, muscle weakness, easy bruising, new or worsening diabetes, excess hair growth, menstrual changes or voice deepening. Although a nonfunctioning adrenal tumor will not affect hormone levels, it may cause back or abdominal pain or a sensation of fullness as it grows.

ACC treatment typically centers on surgical removal when feasible. Surgery may be combined with radiation therapy, chemotherapy (mitotane) or other systemic therapies based on the stage and hormone activity of the tumor.

Although adrenal cancer is rare—often cited in 1 to 2 cases per million people per year—adrenal “incidentalomas” are relatively common. These benign adrenal masses are often found on imaging scans performed for an unrelated reason.

How are adrenal tumors detected?

Adrenal tumors are most often identified in one of two ways:

• During an evaluation for hormone-related symptoms, such as high blood pressure that is difficult to control, unexplained weight changes, new-onset diabetes or signs of androgen or cortisol excess
• Incidentally on an imaging scan performed for another reason

A complete diagnostic workup may include:

• Imaging to characterize the tumor and check for cancer spread
• Hormone testing to determine whether the mass is functioning or nonfunctioning
• Selective procedures, such as biopsy (only if the results could change the treatment plan)

Imaging tests used for diagnosing adrenal tumors

Imaging can help the physician determine whether an adrenal mass looks benign or suspicious, estimate its size, evaluate any local invasion and check for spread. Common imaging tests include:

Computed tomography (CT) scan

Often the first-line imaging test for adrenal tumors, a CT scan can help the physician:

• Characterize the adrenal mass in terms of its size, borders and density
• Differentiate a common benign incidentaloma from a more suspicious lesion
• Evaluate nearby structures and possible metastases

In many cases, a specialized adrenal CT scan will be performed to see how the mass looks before and after contrast dye is given. The healthcare team will evaluate how quickly the mass absorbs and then releases the dye—sometimes referred to as its “washout” pattern— which can help determine whether the tumor is more likely to be benign or cancerous.

Magnetic resonance imaging (MRI) scan

MRI may be useful for evaluating an adrenal mass if:

• CT results are inconclusive
• More soft-tissue detail is needed
• Radiation avoidance is preferred

Additionally, the healthcare team may use an MRI scan to check for vascular involvement or evaluate tissue composition.

Ultrasound

Ultrasound is not usually the primary imaging test for diagnosing adrenal tumors in adults, mainly because their adrenal glands can be difficult to visualize. However, ultrasound imaging may be used:

• In children
• During pregnancy
• For an initial look at the abdomen, with follow-up CT/MRI for characterization

Nuclear medicine/functional imaging

Rather than using a single test for every patient, functional imaging can vary based on the suspected tumor type. Options may include:

• Metaiodobenzylguanidine (MIBG) scan – This nuclear medicine imaging test uses a small amount of radioactive tracer to identify certain adrenal and nerve-related tumors. It is most commonly used when pheochromocytoma or paraganglioma is suspected or confirmed (and in select neuroendocrine tumor settings) to help clinicians detect and pinpoint the location of the disease.
• FDG-PET/CT – Often used in oncology, this noninvasive imaging test combines positron emission tomography (PET) and CT to help detect cancer by highlighting areas of increased metabolic activity. FDG-PET/CT uses fluorodeoxyglucose (FDG), a radioactive tracer that accumulates in cells that use large amounts of sugar—such as many cancer cells—allowing physicians to pinpoint and evaluate suspicious areas.

Laboratory tests used for diagnosing adrenal tumors

Lab work for diagnosing adrenal tumors focuses on identifying excess hormone production and guiding next steps. Common tests include:

• Cortisol excess evaluation (Cushing syndrome screening) – This diagnostic evaluation may include an overnight dexamethasone suppression test, a late-night salivary cortisol test and/or a 24-hour urine-free cortisol test. Blood ACTH may be added to help determine whether cortisol excess is adrenal in origin.
• Pheochromocytoma evaluation – This laboratory analysis typically includes measurement of plasma-free metanephrines or 24-hour urine fractionated metanephrines and catecholamines. These tests are important to perform before biopsy or surgery if pheochromocytoma is suspected. Pheochromocytomas produce excess catecholamines, such as adrenaline and noradrenaline, and physically manipulating the tumor can trigger a sudden, massive hormone release, potentially leading to a hypertensive crisis.
• Aldosterone excess evaluation – Often used when high blood pressure and/or low potassium are present, this laboratory evaluation determines the aldosterone-to-renin ratio (ARR), usually with confirmatory testing if positive.
• Androgen/sex steroid excess evaluation – This diagnostic workup may be useful if ACC is suspected or if virilization, menstrual changes or certain other signs are present. Depending on the clinical picture, tests may include DHEA-S, testosterone, estradiol and/or steroid precursors.
• Basic bloodwork – The physician may order testing for electrolytes (especially potassium), glucose/A1c and other labs as clinically indicated.

Additionally, a 24-hour urine collection may be used to measure:

• Urine-free cortisol (cortisol excess)
• Fractionated metanephrines/catecholamines (pheochromocytoma)

This test can be particularly helpful when hormone levels fluctuate or if confirmatory testing is needed.

Cortisol can be assessed through blood, urine or saliva. Because cortisol levels vary naturally throughout the day, many clinicians rely on standardized screening tests, such as the overnight dexamethasone suppression test or the late-night salivary cortisol test, rather than a single random blood cortisol level.

Adrenal vein sampling (AVS) is not a routine test for most adrenal masses. It is primarily used in select patients with suspected primary aldosteronism to determine whether one adrenal gland is overproducing aldosterone. This can help the physician decide whether to recommend surgery or medication-based treatment.

Procedures used for diagnosing adrenal tumors

Biopsy is often the standard procedure for confirming a cancer diagnosis because it allows a pathologist to examine a tissue sample under a microscope to identify cancerous cells. However, biopsy is not routinely performed on adrenal masses—especially if adrenocortical carcinoma is suspected—because the procedure often cannot reliably distinguish benign adrenal cortex tumors from ACC and may carry risks. Therefore, biopsy is considered selectively, most commonly when:

• There is a history of another cancer and the physician suspects the adrenal lesion could be a metastasis.
• The result would clearly change the treatment plan.

Importantly, clinicians typically rule out pheochromocytoma before any biopsy is considered. If a pheochromocytoma is disturbed by a biopsy or another invasive procedure, a sudden, severe spike in blood pressure may occur.

Benefit from world-class care at Moffitt Cancer Center

If you would like to learn more about the diagnostic process for adrenal tumors, you can request an appointment with a specialist in the Endocrine Oncology Program at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.