Diagnostic Approach for Incidental Adrenal Mass

Initial Evaluation

• The American College of Radiology recommends obtaining a non-contrast CT of the adrenal mass to measure Hounsfield Units (HU) as the essential first step in determining if the mass is benign or requires further investigation 1, 2, 3
• If the mass measures <10 HU and is homogeneous and well-circumscribed, it is definitively a benign lipid-rich adenoma requiring no further imaging workup 1, 2, 3
• If the mass measures >10 HU, proceed to second-line imaging with either washout CT or chemical shift MRI to further characterize the lesion 1, 4, 5

Hormonal Evaluation

• The American College of Endocrinology recommends screening for pheochromocytoma with plasma or 24-hour urinary metanephrines, especially if the mass has >10 HU on non-contrast CT or if the patient has any symptoms of catecholamine excess (headaches, palpitations, sweating, anxiety attacks) 1, 2, 5, 3
• Check aldosterone-to-renin ratio only if the patient has hypertension and/or hypokalemia 1, 2, 5, 3
• Measure serum androgens (DHEA-S, testosterone, androstenedione) if there are clinical signs of virilization or if adrenocortical carcinoma is suspected based on imaging 1, 2

Size-Based Management

• For masses <3 cm, most are benign and extensive workup is not justified in patients without cancer history 6, 7, 3
• For masses 3-5 cm, consider follow-up CT, additional imaging characterization, or surgical consultation depending on imaging characteristics and hormonal function 6, 7
• For masses >5 cm, should be removed due to higher risk of malignancy (up to 6.3% when HU >20) 6, 4, 7

Multidisciplinary Consultation

• Maintain a low threshold for multidisciplinary review involving endocrinology, surgery, and radiology when imaging is not consistent with a benign lesion, evidence of hormone hypersecretion is found, or the tumor grows significantly during follow-up (>5 mm/year) 1, 2, 4, 5, 8

Critical Pitfalls to Avoid

• Do not perform adrenal mass biopsy routinely—it is rarely indicated and carries unnecessary risks including tumor seeding and potential hypertensive crisis if pheochromocytoma is present 1, 2, 7, 5, 3
• Avoid unnecessary repeated imaging for small masses with confirmed benign characteristics (<10 HU, <4 cm, non-functional), as this increases radiation exposure, patient anxiety, and healthcare costs without clinical benefit 1, 5, 3, 8

Imaging Evaluation of a 2 cm Adrenal Incidentaloma

Initial Non‑Contrast CT Assessment

• The American College of Radiology (ACR) recommends that the first step in evaluating an adrenal incidentaloma is a non‑contrast CT to measure attenuation in Hounsfield units (HU); a lesion with HU ≤ 10 is classified as a benign lipid‑rich adenoma and requires no further imaging 9.
• When the non‑contrast CT shows HU > 10, the lesion is considered indeterminate and second‑line imaging is required 9.

Second‑Line Imaging Options

Delayed Contrast‑Enhanced CT (Washout Study)

• Perform dynamic contrast‑enhanced CT followed by delayed images at approximately 10–15 minutes; calculate relative percentage washout = [1 – (delayed HU / dynamic HU)] × 100 % 9.
• A relative washout > 50 % indicates a benign adenoma, whereas washout < 50 % suggests malignancy 9.
• This washout protocol achieves ≈ 98 % accuracy for characterizing adrenal masses 9.

Chemical‑Shift MRI

• Out‑of‑phase MRI showing signal loss compared with in‑phase images identifies a benign adenoma 10.
• Chemical‑shift MRI correctly characterizes ≈ 89 % of lesions whose non‑contrast CT attenuation lies between 10–30 HU, offering higher sensitivity and specificity than CT alone 9.
• MRI is preferred when radiation exposure is a concern 9.

Size‑Based Risk Stratification

• According to ACR guidance, adrenal masses < 3 cm are most often benign and extensive work‑up is generally not justified in patients without a known extra‑adrenal malignancy 11.
• Lesions > 5 cm carry a substantially higher risk of malignancy and should be surgically resected 11.

Biopsy Considerations

• Routine adrenal biopsy is discouraged because it carries risks of tumor seeding and hypertensive crisis if an undiagnosed pheochromocytoma is present 12.
• Biopsy may be contemplated only when non‑invasive imaging remains indeterminate and the patient has a known extra‑adrenal malignancy [9][12].
• Prior to any biopsy, biochemical exclusion of pheochromocytoma is mandatory [12][11].

Advanced Imaging Pitfalls

• FDG‑PET is not recommended for initial characterization of adrenal incidentalomas; it is reserved for lesions that remain indeterminate after CT and MRI [9][11].
• Plain radiography and abdominal ultrasound have very limited diagnostic value for adrenal lesions and should be avoided [12][11].

Imaging and Management of Incidentally Discovered Adrenal Adenomas

Initial Imaging – Non‑Contrast CT

• Non‑contrast CT attenuation measurement is the mandatory first test to classify adrenal incidentalomas. The American College of Radiology recommends measuring Hounsfield Units (HU) to decide whether further work‑up is needed. 13, 14
• Lesions with ≤10 HU are definitively benign lipid‑rich adenomas (≈100 % specificity) and require no additional imaging. Sensitivity of this threshold is modest (48‑56 %). 13, 14, 15, 16
• Lesions with >10 HU are indeterminate and must proceed to second‑line imaging (washout CT or chemical‑shift MRI). 13, 14

Second‑Line Imaging for Indeterminate Masses (HU > 10)

Contrast‑Enhanced Washout CT

• Dynamic contrast‑enhanced CT with delayed images at 10–15 min is used to calculate washout. 13, 14
• Absolute percentage washout > 60 % indicates a benign adenoma. 13
• Relative percentage washout > 40 % also indicates a benign adenoma. 13
• Limitation: Approximately one‑third of benign adenomas fail to meet washout criteria, and some malignant lesions (including adrenocortical carcinoma and hypervascular metastases) can show washout values in the adenoma range. 13

Chemical‑Shift MRI

• Out‑of‑phase MRI demonstrating signal loss compared with in‑phase images identifies microscopic fat, a hallmark of benign adenomas. The American College of Radiology endorses this technique for indeterminate lesions. 13, 14
• Chemical‑shift MRI correctly characterizes ≈89 % of lesions with non‑contrast CT attenuation between 10–30 HU. 14
• MRI provides higher sensitivity and specificity than CT alone for indeterminate masses and avoids additional radiation exposure. 14
• A homogeneous signal‑intensity drop is diagnostic of a lipid‑rich adenoma; heterogeneous drop may be seen in pheochromocytoma or adrenocortical carcinoma and should be interpreted cautiously. 13

Size‑Based Risk Stratification

• Masses <3 cm are most often benign; extensive work‑up is generally unnecessary in patients without known extra‑adrenal malignancy. 17, 14, 15
• Masses 3–5 cm warrant either follow‑up imaging or additional characterization, depending on imaging features. 17, 14
• Masses >5 cm should be surgically resected because of a substantially higher risk of malignancy. 17, 14, 15

Advanced Imaging – Limited Role

• FDG‑PET is not recommended for initial characterization of adrenal incidentalomas. It should be reserved for lesions that remain indeterminate after both CT and MRI have been performed. 17, 14
• Some malignancies (e.g., renal‑cell carcinoma metastases) may be PET‑avid, but others can be PET‑negative, limiting the sensitivity of FDG‑PET. 14
• Plain radiography and abdominal ultrasound have very limited diagnostic value for adrenal lesions and should be avoided. 17, 14

Role of Biopsy – Rarely Indicated

• Routine adrenal biopsy is discouraged because of risks such as tumor seeding, hemorrhage, and hypertensive crisis. The American College of Radiology advises against its routine use. 13, 17
• Biopsy may be considered only when non‑invasive imaging remains indeterminate and the patient has a known extra‑adrenal malignancy where confirming metastatic disease would alter management. 13, 17
• Prior to any biopsy, pheochromocytoma must be biochemically excluded (plasma or 24‑hour urinary metanephrines) to prevent a life‑threatening hypertensive crisis. 13, 17
• Suspected adrenocortical carcinoma should not be biopsied because of the risk of needle‑tract seeding. 13

Critical Pitfalls to Avoid

• Do not rely solely on washout CT, as about one‑third of pheochromocytomas demonstrate washout in the adenoma range and one‑third of adenomas fail to wash out appropriately. Comprehensive assessment with MRI or additional criteria is required. 13
• Never perform a biopsy before confirming the absence of pheochromocytoma biochemically, since undiagnosed pheochromocytoma can cause fatal hypertensive crises during the procedure. 13, 17