Decoding Your Diagnosis: Testing, Pathology, and Genetics

The journey to a diagnosis for an adrenal mass involves a careful sequence of imaging, hormone testing, and often genetic evaluation. Because some adrenal tumors produce powerful hormones that can cause a medical crisis if disturbed, the order of these tests is critical for your safety.

The First Rule: No Biopsy Before Hormone Testing

If you have an adrenal mass, your doctors must first determine if it is a Pheochromocytoma (PPGL)—a tumor that produces adrenaline-like hormones ^[1].

• The Risk: Performing a biopsy or surgery on an unrecognized PPGL can trigger a life-threatening “hypertensive crisis” (a sudden, extreme spike in blood pressure) ^[2].
• The Test: Doctors measure metanephrines in your blood or urine ^[1]. For the most accurate blood test, you should be lying flat on your back (supine) for at least 20 minutes before the blood is drawn ^[3].
• Other Hormone Checks: You will also likely have a dexamethasone suppression test to see if the tumor is making too much cortisol ^[4]. Depending on your symptoms, your doctor may also check aldosterone, renin, or male/female sex hormones ^[2].

Note: A biopsy is generally not a routine part of diagnosing a resectable adrenal tumor. Even after PPGL is ruled out, biopsies are mostly reserved for situations where doctors suspect the tumor might be a metastasis from another cancer or lymphoma.

Reading Your Imaging: The CT Scan

Imaging, specifically a Computed Tomography (CT) scan, provides clues about whether a tumor is benign (harmless) or malignant (cancerous). Radiologists use Hounsfield Units (HU) to measure the density of the tumor ^[5].

• < 10 HU: Tumors with low density (lots of intracellular lipid/fat) on an unenhanced CT are strongly suggestive of a benign adenoma ^[5].
• 10 to 20 HU: This is an indeterminate range.
• > 20 HU: Tumors with higher density are more concerning for Adrenocortical Carcinoma (ACC), PPGL, or a metastasis, but are not definitively cancer ^[6].
• Other Red Flags: Doctors also look for tumors larger than 4 cm, irregular shapes, contrast “washout” rates, or evidence that the tumor is invading nearby organs or blood vessels ^[7][5]. Size alone does not diagnose cancer.

Understanding the Pathology Report

If the tumor is removed, a pathologist examines the tissue under a microscope. Their report will include several key “scores” that help predict how the cancer might behave.

The Weiss Score

The Weiss score is a standard tool used to evaluate conventional adrenocortical tumors ^[8]. It looks at nine different features, such as how the cells look and whether the tumor is invading blood vessels.

• Score of 0–2: Suggests the tumor is likely benign (an adenoma), though borderline cases require expert review ^[8].
• Score of 3 or higher: Generally indicates Adrenocortical Carcinoma (ACC) ^[8].
• Note: Some rare variants, like oncocytic tumors, use different scoring systems (such as the Lin-Weiss-Bisceglia system) because they look different under the microscope ^[9][10].

The Ki-67 Index

The Ki-67 index measures how fast the cancer cells are dividing ^[11]. It is expressed as a percentage. A higher percentage means the tumor is more “aggressive” and may be more likely to return after surgery ^[11][12]. This number is a prognostic marker that your multidisciplinary team integrates with your stage, margins, and overall health to determine your follow-up plan ^[13].

The Role of Genetics

Hereditary risk is a major factor in adrenal tumors, though it varies significantly by the type of tumor.

• PPGL: Up to 35% or more of people with PPGL have an underlying germline genetic mutation (such as SDHx, VHL, or RET). Current medical guidelines recommend universal germline testing for almost everyone diagnosed with PPGL ^[14][15][16].
• ACC: Hereditary links in adult ACC are less common but do exist, such as Li-Fraumeni Syndrome (TP53 gene) or Lynch Syndrome ^[14][17]. Recommendations for testing depend heavily on your age (more common in childhood ACC), family history, and specific tumor features.

Finding a genetic link can help your doctors tailor your treatment and alert your family members through cascade testing. Genetic counseling is highly recommended before testing to help you understand the limits of a negative test, the possibility of uncertain results, and what the results mean for you and your family’s screening needs ^[18][19].