Not all adrenal diseases are visible on imaging.
While most adrenal issues involve tumors or growths visible on a CT or MRI scan, some significant diseases can present with normal-looking adrenal glands. In these cases, the glands are anatomically intact but fail to function correctly at a chemical or cellular level.
Micro-Adenomas (Primary Aldosteronism): Some small tumors that overproduce aldosterone (causing high blood pressure) are less than 5mm to 10mm—smaller than a pea. These "micro-adenomas" are often missed by radiologists because they blend into the gland's normal texture.
This is why adrenal pathology and specialized centers like Johns Hopkins are so critical. When imaging is inconclusive, expert microscopic tissue evaluation with specific adrenal function markers is the only way to reach an accurate diagnosis.
Not all adrenal masses contribute to the adrenal hormonal disorders.
The assumed imaging lesion/mass may not be the source of adrenal hormonal disorders. Pathology evaluation with specific functional markers can identify and confirm the source of aberrant hormones and predict clinical outcomes.
In addition, the non-functional masses are pathologically heterogeneous, ranging from non-neoplastic to malignant. Pathological diagnoses are essential.
1. The Prevalence of "Incidentalomas"
The most common scenario for a non-functional mass is an adrenal incidentaloma growth discovered by accident during a scan for an unrelated issue.
Approximately 75% to 80% of all incidentally discovered adrenal masses are non-functional benign adenomas.
These growths are common as people age, appearing in roughly 7% to 10% of individuals over age 70.
2. Common Non-Functional Lesion
Many visible adrenal masses are not made of functional "lesional" tissue (the hormone-secreting cells of the cortex or medulla) at all. Instead, they may be composed of many other non-neoplastic and neoplastic lesions:
Adrenal Myelolipomas ▼
Benign tumors made of fat and bone marrow elements. While they can grow large enough to require surgery, they do not produce any hormones.
Adrenal Cysts ▼
Fluid-filled sacs that appear as distinct masses on imaging. The etiology is broad. Based on the cyst lining, it's generally classified as pseudocyst, endothelial cyst, epithelial cyst, and parasitic cyst. Occasionally, variable tumors can have cystic changes.
Metastatic Lesions ▼
Cancer that has spread to the adrenal gland from elsewhere (like the lung or breast). These masses can be large and invasive but rarely produce adrenal hormones.
Hemorrhage or Hematomas ▼
Internal bleeding within the gland can create a mass-like appearance on a scan that is essentially a collection of blood rather than new tissue growth.
3. Why This Matters for Diagnosis
Adrenal pathology is essential for distinguishing functional from nonfunctional lesions, as imaging alone often cannot determine whether a mass is hormonally active. Although systemic biochemical testing (blood, urine, adrenal vein sampling, etc) is mandatory for every adrenal mass, histopathologic confirmation remains the gold standard. Pathology analysis will identify high-risk and aggressive features and guide correct treatment.
Not all adrenal masses are malignant
While imaging reveals the presence of a mass, adrenal pathology provides the definitive roadmap for treatment by determining the specific nature and aggressiveness of the tissue. In fact, more than 95% of adrenal masses discovered on imaging are benign (noncancerous). These often take the form of "incidentalomas”, benign adenomas found during scans for unrelated conditions, and are especially common in older adults.
Because benign and malignant cells can look strikingly similar on standard imaging, adrenal pathology is critical for an accurate diagnosis. Pathologists provide the definitive "gold standard" for diagnosis by analyzing the tissue at a cellular level.
Pathological evaluation is critical not just for a "yes/no" cancer diagnosis, but for providing the nuanced grading and molecular information required for modern precision medicine, target therapy, and personalized management. Pathologists use standardized scoring/grading systems to determine a tumor’s "grade," which predicts how it will behave in the future and whether adjuvant therapy is needed.
By providing this high-level data, the Johns Hopkins Adrenal Pathology team ensures that patients receive the exact level of care they need—avoiding overtreatment for benign masses while fast-tracking life-saving targeted therapies for aggressive ones.