Adrenal Incidentaloma

01Typical Case and Imaging Associations

02Radiologic Anatomy and Pathophysiology

The adrenal glands are paired retroperitoneal organs located superomedial to the upper poles of the kidneys. Each gland has an inverted-Y or -V configuration on axial CT. The cortex (outer layer) is responsible for steroidogenesis (glucocorticoids, mineralocorticoids, androgens), while the medulla (inner layer) produces catecholamines. This dual embryologic origin (cortex from mesoderm, medulla from neural crest) explains the broad histologic spectrum of adrenal incidentalomas, ranging from cortical adenomas and carcinomas to medullary pheochromocytomas and extra-adrenal metastases.

Why adenomas look the way they do on CT: The cornerstone of characterization is intracytoplasmic lipid. Adrenocortical adenomas accumulate cholesterol and other neutral lipids within their cells as part of steroid hormone precursor storage. This intracellular fat lowers the overall bulk attenuation on non-contrast CT. A threshold of $\le \backslash leq$ 10 HU on unenhanced CT identifies "lipid-rich" adenomas with high confidence, approaching 98% specificity for benignity. However, at least 30% of adrenal adenomas contain only small amounts of intracellular fat, resulting in higher unenhanced attenuation. These are termed "lipid-poor" adenomas, and they are the lesions that drive the need for further workup with washout CT or chemical shift MRI.

Why chemical shift MRI works: On gradient-echo sequences, protons in water and protons in fat precess at slightly different Larmor frequencies. At 1.5T, they cycle in and out of phase approximately every 2.2 ms. When water and fat coexist within the same voxel (intracellular lipid in adenomas), the signal on opposed-phase images drops compared to in-phase images because of destructive interference. This signal intensity index (SII) is calculated as:

$$\text{}SII=\frac{S{I}_{\text{in-phase}}-S{I}_{\text{opposed-phase}}}{S{I}_{\text{in-phase}}}\times 100\text{}SII\; =\; \backslash frac\{SI\_\{\backslash text\{in-phase\}\}\; -\; SI\_\{\backslash text\{opposed-phase\}\}\}\{SI\_\{\backslash text\{in-phase\}\}\}\; \backslash times\; 100$$

A threshold of more than 20% MR signal intensity drop yielded a sensitivity of 71% and specificity of 100% for diagnosing adenomas that were indeterminate on CT. Malignant lesions, pheochromocytomas, and metastases generally do not contain enough intracellular lipid to produce this signal drop, which is the basis for their discrimination.

Why washout CT works: Adenomas have a rich capillary network and rapid contrast enhancement, but they also demonstrate rapid de-enhancement (washout) due to their well-organized vascular bed. Malignant lesions and pheochromocytomas tend to retain contrast longer because of their disorganized neovascularity and vascular permeability. An absolute washout greater than 60% is considered to be strongly suggestive of adrenal adenoma, while a relative washout exceeding 40% is similarly indicative.

The MACS paradigm (ESE-ENSAT 2023): The 2023 guidelines propose the term "mild autonomous cortisol secretion" (MACS) for patients without clinical signs of overt Cushing's syndrome but with serum cortisol levels after 1 mg overnight dexamethasone suppression test (DST) exceeding 50 nmol/L (>1.8 mcg/dL). MACS is diagnosed in 20% to 50% of patients with adrenal nodules. This is important because the imaging interpretation must be integrated with the hormonal evaluation. A radiologist should recognize that even a benign-appearing adenoma may carry clinical consequences through autonomous cortisol production.

03Multi-Modality Appearance

CT (Primary Modality)

• Non-contrast CT is the gatekeeper study. A homogeneous adrenal mass with unenhanced CT attenuation of 10 HU or less is highly suggestive of a benign lipid-rich adenoma and requires no further imaging follow-up, regardless of size, per the 2023 ESE-ENSAT guidelines (a change from the 2016 guideline, which also required size <4 cm).

• Lipid-poor adenomas (HU 11-30) require further characterization with washout CT or chemical shift MRI.

• Washout CT protocol: Non-contrast, 60-second post-contrast (portal venous), and 15-minute delayed phases. Formulas:

$$\text{}APW=\frac{H{U}_{\text{enhanced}}-H{U}_{\text{delayed}}}{H{U}_{\text{enhanced}}-H{U}_{\text{unenhanced}}}\times 100\text{}APW\; =\; \backslash frac\{HU\_\{\backslash text\{enhanced\}\}\; -\; HU\_\{\backslash text\{delayed\}\}\}\{HU\_\{\backslash text\{enhanced\}\}\; -\; HU\_\{\backslash text\{unenhanced\}\}\}\; \backslash times\; 100$$

$$\text{}RPW=\frac{H{U}_{\text{enhanced}}-H{U}_{\text{delayed}}}{H{U}_{\text{enhanced}}}\times 100\text{}RPW\; =\; \backslash frac\{HU\_\{\backslash text\{enhanced\}\}\; -\; HU\_\{\backslash text\{delayed\}\}\}\{HU\_\{\backslash text\{enhanced\}\}\}\; \backslash times\; 100$$

• APW $\ge \backslash geq$ 60% or RPW $\ge \backslash geq$ 40% favors adenoma.

• Recent data suggest that washout CT with the established thresholds for APW and RPW may be insufficient to reliably differentiate all adrenal masses, particularly in lipid-poor adenomas and hypervascular metastases (renal cell carcinoma, hepatocellular carcinoma).

• Myelolipoma: The typical adrenal myelolipoma appears as an adrenal lesion with fat-containing components; CT shows fat density of -30 HU to -100 HU in the adrenal tumor. When the lesion contains $\ge \backslash geq$ 50% macroscopic fat, the diagnosis can be made with confidence.

• Pheochromocytoma: Typically >20-30 HU on unenhanced CT, vivid arterial enhancement, heterogeneous with cystic or necrotic components.

• ACC: Large (usually >4-6 cm), heterogeneous, irregular margins, calcifications, necrosis, local invasion, inferior vena cava thrombus.

• Adrenal hemorrhage: Acute phase is hyperdense (50-90 HU); chronic phase shows progressive decrease in density and decrease in size.

• Adrenal cyst: Near-water density, thin wall, no enhancement. Types include endothelial, epithelial, parasitic, and pseudocysts.

MRI (Second-Line for Indeterminate Lesions)

• Chemical shift imaging (CSI): Signal drop on opposed-phase relative to in-phase images confirms intracellular lipid and supports adenoma. CSI was able to distinguish adenomas (decreased signal intensity on opposed-phase images relative to in-phase images) from other benign and malignant lesions (no signal change). The adrenal-to-spleen chemical shift ratio (ASR) and the SII are the most commonly used quantitative measures.

• T1W: Adenomas are isointense to liver. Hemorrhage may be T1 hyperintense (methemoglobin). Myelolipoma is T1 hyperintense due to macroscopic fat, with signal drop on fat-suppressed sequences.

• T2W: Adenomas are isointense to slightly hyperintense relative to liver. Pheochromocytoma demonstrates the classic T2 "light bulb sign" (very hyperintense), although this finding is seen in only about 35% of cases and its absence does not exclude the diagnosis. ACC is heterogeneous on T2W.

• DWI/ADC: Restricted diffusion (low ADC) suggests malignancy (metastasis, ACC) or cellular lesions. However, there is overlap, and DWI alone is not sufficient for characterization.

• Dynamic contrast-enhanced MRI: Most adenomas exhibited homogeneous enhancement patterns with rapid washout. ACC and metastases show heterogeneous, persistent enhancement.

Ultrasound

• Limited role in adrenal imaging. Useful in neonates (adrenal hemorrhage, neuroblastoma) and as an initial modality when masses are large enough to be detected incidentally during abdominal sonography.

• Adenomas are small, homogeneous, and hypoechoic. Myelolipomas are echogenic (fat). Pheochromocytomas are solid, variable echogenicity.

• Color Doppler may show hypervascularity in pheochromocytoma and ACC.

Nuclear Medicine / PET-CT

• FDG PET-CT: Low FDG uptake strongly favors benign adenoma. FDG PET/CT SUVmax was associated with malignancy in adrenal tumors. An adrenal-to-liver SUV ratio >1.5-2.0 raises concern for malignancy. False-positive findings occur in approximately 5% of adrenal lesions identified as positive at PET, including adrenal adenomas, endothelial cysts, and inflammatory or infectious lesions.

• I-123 or I-131 MIBG: Positive uptake in pheochromocytoma and paraganglioma. MIBG scintigraphy has a sensitivity of about 85-90% for pheochromocytoma and is used for localization and staging, not primary characterization.

• Ga-68 DOTATATE PET-CT: Dual tracer PET-CT using FDG and Ga-68 DOTANOC could be informative in preoperative characterization of large indeterminate adrenal masses; pheochromocytomas showed preferential uptake of Ga-68 over FDG.

• NP-59 (I-131 6-beta-iodomethyl-norcholesterol): Adrenocortical scintigraphy. Functioning adenomas show concordant uptake; nonfunctioning adenomas and ACC show discordant or absent uptake.

04Reporting Pearls and Next Best Step

When reporting an adrenal incidentaloma, the radiologist must address two parallel tracks: (A) Is this mass benign or malignant? and (B) Is this mass hormonally active? The imaging report drives both pathways.

Pertinent positives and negatives to include in the report:

• Lesion size (maximum axial dimension).

• Unenhanced attenuation in HU (with a region-of-interest placed centrally, avoiding the edges to reduce partial volume averaging with periadrenal fat).

• Homogeneity versus heterogeneity (necrosis, hemorrhage, calcification).

• Margins: smooth, well-defined (benign) versus irregular, infiltrative (malignant).

• Washout percentages (APW and RPW) if a dedicated washout study was performed.

• Presence of macroscopic fat (myelolipoma) or microscopic fat (chemical shift signal drop).

• Comparison with prior imaging if available: stability over 12 or more months strongly favors benignity.

• Bilateral involvement (raises concern for metastases, bilateral adenomas, congenital adrenal hyperplasia, lymphoma, infiltrative disease, or bilateral pheochromocytoma in hereditary syndromes).

• Pertinent negative: "No evidence of local invasion, IVC thrombus, or retroperitoneal lymphadenopathy."

Next Best Step algorithm (synthesized from the 2023 ESE-ENSAT guideline, ACR IFC, and ACR Appropriateness Criteria):

1. If unenhanced HU $\le \backslash leq$ 10 and homogeneous: Benign lipid-rich adenoma. No further imaging follow-up is recommended, regardless of size. The 2023 ESE guideline also does not recommend measuring plasma free or urinary fractionated metanephrines in patients with adrenal incidentaloma showing 10 HU or less on unenhanced imaging. Recommend hormonal workup with 1 mg overnight DST.

2. If unenhanced HU 11-20, homogeneous, <4 cm: Options include immediate additional imaging with another modality (washout CT or chemical shift MRI) or interval imaging in 12 months.

3. If unenhanced HU >20, or heterogeneous, or $\ge \backslash geq$ 4 cm: Recommend dedicated adrenal imaging with washout CT or chemical shift MRI and multidisciplinary team discussion. For masses $\ge \backslash geq$ 4 cm that are heterogeneous with HU >20, consider surgical resection, especially in children, adolescents, pregnant women, and adults under 40 years of age.

4. If washout CT confirms adenoma (APW $\ge \backslash geq$ 60% or RPW $\ge \backslash geq$ 40%): Benign. Recommend hormonal workup. No further imaging if hormonal workup is unremarkable.

5. If indeterminate after CT and MRI: Consider PET-CT or image-guided biopsy (only after pheochromocytoma has been excluded biochemically). Adrenal mass biopsy should not be performed routinely for the workup of an adrenal incidentaloma. Biopsy is reserved for suspected metastasis in patients with known extra-adrenal malignancy when histologic confirmation will change management.

6. All patients: Recommend 1 mg overnight DST (serum cortisol cutoff $\le \backslash leq$ 50 nmol/L or $\le \backslash leq$ 1.8 mcg/dL). Screen for pheochromocytoma with plasma or urinary fractionated metanephrines (except when HU $\le \backslash leq$ 10 per 2023 ESE). Measure aldosterone-renin ratio if hypertensive or hypokalemic.

Report language matters. Standardized macros that make explicit recommendations for hormonal evaluation and endocrinology referral in patients with adrenal incidentalomas lead to improved adherence to clinical guidelines.

05Differential Diagnosis

06Board Traps

Trap 1: The lipid-poor adenoma masquerading as a malignant lesion. About 30% of adenomas have unenhanced CT attenuation >10 HU and will not be characterized on non-contrast CT alone. A trainee who stops at the non-contrast scan and calls this "indeterminate, cannot exclude malignancy" without recommending washout CT or chemical shift MRI has failed to complete the algorithm. The board expects you to know the full characterization pathway.

Trap 2: The partial volume artifact. Small adrenal nodules (<1.5 cm) are vulnerable to partial volume averaging with periadrenal fat. This can falsely lower the measured HU, making a non-adenoma appear to be a lipid-rich adenoma. Always place the ROI carefully within the center of the nodule, and be cautious when the nodule is barely above the 1 cm threshold.

Trap 3: Assuming all T2-bright adrenal lesions are pheochromocytomas. The T2 "light bulb sign" is not pathognomonic. Cysts, hemorrhage, and some metastases (melanoma, renal cell carcinoma) can also be T2 hyperintense. The light bulb sign has a sensitivity of only about 35% for pheochromocytoma. The board tests your understanding that clinical correlation (elevated metanephrines) is mandatory before labeling a T2-bright lesion as pheochromocytoma.

Trap 4: Performing biopsy before excluding pheochromocytoma. This is a life-threatening mistake. Fine-needle aspiration of a pheochromocytoma can trigger a hypertensive crisis. Always confirm normal metanephrines before any percutaneous adrenal biopsy.

Trap 5: The India ink artifact pitfall at 3T. Chemical shift imaging has similar diagnostic efficacy for differentiating adrenal adenomas and nonadenomas at 1.5T and 3T, but quantitative thresholds may differ slightly. At 3T, the first opposed-phase echo occurs at approximately 1.1 ms, and the signal-to-noise ratio characteristics change. A trainee unfamiliar with the TE values at 3T may misinterpret the chemical shift sequences. The fundamental principle remains the same: fat-water destructive interference at opposed-phase echo times.

Trap 6: Hypervascular metastases mimicking adenoma washout. Metastases from renal cell carcinoma, hepatocellular carcinoma, and thyroid carcinoma are hypervascular and can show pseudo-washout, meeting the APW $\ge \backslash geq$ 60% threshold. Pheochromocytomas and hypervascular metastases may also wash out but should have a different clinical presentation; they also may have a higher absolute attenuation on the contrast phase. Board-tested concept: always correlate washout values with the absolute enhancement values and clinical context.

Trap 7: The size criterion update in ESE-ENSAT 2023. The authors removed the size criterion of <4 cm from the criteria for benign adrenal adenoma that does not require further imaging. If the mass is homogeneous and $\le \backslash leq$ 10 HU on unenhanced CT, no further imaging is needed regardless of size. A trainee applying the older 2016 criteria (which required both $\le \backslash leq$ 10 HU and <4 cm) may inappropriately recommend follow-up imaging for a clearly benign lipid-rich adenoma.

Trap 8: The MACS clinical integration. The 2023 ESE-ENSAT guidelines recommend the 1 mg overnight DST with a cutoff of serum cortisol at 50 nmol/L (1.8 mcg/dL) to identify MACS. Even if imaging confirms a benign adenoma, the hormonal workup may reveal MACS, which carries increased cardiovascular morbidity and mortality. The radiologist's role is to prompt the referring clinician toward biochemical evaluation in the report, not simply to characterize the mass as benign and close the loop.

Core competency being tested: The ability to construct a systematic, algorithm-driven approach to an adrenal incidentaloma, integrating non-contrast CT density, washout kinetics, chemical shift MRI physics, clinical correlation, and hormonal workup into a coherent management pathway. The board expects you to move efficiently from "Is it benign?" to "Is it functional?" to "What is the next step?" without ordering unnecessary tests or missing the diagnosis.