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KEY FACTS

Imaging
- Well-circumscribed, uniform, low-attenuation, small adrenal mass - Low attenuation due to abundant intracytoplasmic lipid - Imaging features of typical lipid-rich adenomas - NECT: < 10 HU (71% sensitivity, 98% specificity) - MR: Significant decrease in signal on out-of-phase T1WI due to intravoxel lipid and water - May show focal areas of heterogeneous attenuation or absence of signal loss due to degeneration, hemorrhage, and fibrin deposition - Clinical context key to differentiate from collision tumor: Unlikely in absence of extraadrenal malignancy - Lipid-poor adenomas (10-40% cases): Utilize relative or absolute CT contrast washout kinetics for diagnosis
- Accounts for vast majority of adrenal "incidentalomas" - Imaging intensive algorithm suggested for incidental adrenal lesions, though overwhelming majority are benign and hormonally inactive - Primary hyperaldosteronism (Conn syndrome): 80% due to unilateral, typically small (< 2 cm) adenoma - Cushing syndrome: 80-85% due to adrenal hyperplasia
- Typically shows FDG uptake < that of liver on PET/CT
Top Differential Diagnoses
- Adrenal metastases and lymphoma
- Adrenal (macronodular) hyperplasia
- Pheochromocytoma
- Adrenal carcinoma
- Adrenal myelolipoma
- Gastric diverticulum
- Adrenal cyst
Diagnostic Checklist
- Asymptomatic mass: Usually nonfunctioning adenoma, even in patients with known cancer
- NECT and MR are equally accurate for diagnosis of lipid-rich adenoma
- Utilize dedicated CECT adrenal protocol with 15-minute delayed imaging for diagnosis of potential lipid-poor adenomas

TERMINOLOGY

Definitions
- Benign adrenal cortical tumor

IMAGING

General Features
- Best diagnostic clue
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- Imaging strategies target typical adenoma histology: Abundant intracytoplasmic lipid
        - Low attenuation (< 10 HU) on NECT
        - Significant loss of signal on out-of-phase T1WI MR (intravoxel fat and water)
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- Size
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- Cushing syndrome adenoma: 2-5 cm
- Conn syndrome adenoma: Classically < 2 cm (20% < 1 cm)
- Vast majority of incidental, hormonally inactive adrenal adenomas are small (< 2 cm)
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- Morphology
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- Usually round to oval suprarenal mass
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- Key concepts - Most common adrenal cortex tumor (10% bilateral) - Accounts for > 90% of all "incidentalomas" - May occur in up to 9% of general population, diagnosed on 5% of CT exams with various indications - Lipid-rich adrenal adenoma: 60-90% of adenomas - Lipid-poor adrenal adenoma: 10-40% of adenomas - Increased incidence in patients with diabetes and hypertension - NECT (or chemical shift MR): Study of choice to diagnose incidental adrenal masses - Classified into 2 types based on function - Nonhyperfunctioning: Normal hormone levels - Hyperfunctioning: Primary hyperaldosteronism, Cushing syndrome, hyperandrogenism - Cushing syndrome - 15-25% of cases are due to autonomous adrenal adenoma - 80-85% of cases are due toadrenal hyperplasia - Adenomas usually > 2 cm - Primary hyperaldosteronism (Conn syndrome) - 80% of cases are due to****adrenal adenoma - 20% of cases are due to adrenal hyperplasia - Adenomas are often small (< 2 cm)

CT Findings

NECT

- Smooth, well defined, round or oval in shape
- Homogeneous soft tissue mass of 0-20 HU
- **Lipid-rich adrenal adenoma** (60-90% of cases)
        - Uniform low attenuation
                  - Metaanalysis of < 10 HU threshold: 71% sensitivity, 98% specificity
                  - Sensitivity may increase to almost 90% with histogram analysis (identify negative pixels), though variable results and scanner dependent
- **Lipid-poor adrenal adenoma** (10-40% of cases)
        - Attenuation varies from 10-30 HU
        - Difficult to differentiate from metastases on NECT
- Cushing syndrome due to adrenal adenoma
        - Remainder of ipsilateral gland and contralateral adrenal gland may be atrophic due to ↓ ACTH levels
        - ↑ cortisol: Feedback inhibition on pituitary ACTH
- ACTH-independent macronodular hyperplasia: Multiple, bilateral, functioning adrenal adenomas
- Conn syndrome due to adrenal adenoma
        - Remainder of ipsilateral gland and contralateral adrenal gland appear normal
- Large adenomas
        - More heterogeneous than small adenomas
        - ± hemorrhage, cystic degeneration, calcification
                  - Growth should raise suspicion for malignancy

CECT

- Enhancing adrenal mass that deenhances rapidly
        - Dedicated adrenal CT exam incorporates initial dynamic enhanced phase (~ 70-second delay) and 15-minute delay
        - Relative percentage washout = dynamic enhanced (HU) - delayed (HU) / dynamic enhanced HU
                  - Relative percentage washout > 40%: 96% sensitivity, 100% specificity
        - Absolute percentage washout (if NECT available) = dynamic enhanced (HU) - delayed (HU) / dynamic enhanced (HU) - unenhanced (HU)
                  - Absolute percentage washout > 60%: 86-88% sensitivity, 92-96% specificity
        - 10-minute delay utilized by some centers, but shorter delay may decrease sensitivity
        - Adrenal washout calculators readily available online
        - Utilize technique for indeterminate, potentially lipid-poor adenomas
        - Clinical context critical: Rapid washout can be seen with pheochromocytomas, renal cell, hepatocellular carcinoma, and hypervascular metastases
- Dual-energy CT and iodine subtraction techniques can generate virtual noncontrast (VNC) images
        - May identify lipid-rich adenomas and obviate need for additional imaging
        - Iodine:VNC ratio ≥ 6.7 has sensitivity and specificity of 95% for adenoma (higher ratios in adenoma compared to metastasis)

MR Findings
- T1WI and T2WI - Low to intermediate signal
- Chemical shift (in- and out-of-phase) imaging - Mainstay of MR diagnosis - Sensitivity and specificity equivalent to NECT - Signal loss on out-of-phase T1WI due to intravoxel water and fat protons - Inverse relationship between percentage of lipid-rich cells and relative ↓ signal on out-of-phase imaging - May not identify lipid-poor adenomas - Visual inspection of signal in phase (SIP) and out of phase (SOP), though quantitative analysis may be helpful - Adrenal to spleen chemical shift imaging (CSI) ratio: Lesion:spleen SOP/adrenal/spleen SIP - < .71 = adenoma - Adrenal signal intensity index: 100 x (SIP - SOP) / SIP - > 16.5% = adenoma - Beware technical pitfalls - Sampling of 1st echo pair at 3T is challenging - India ink artifact mimics signal loss, particularly in small adrenal lesions - Other primary or secondary adrenal lesions may contain lipid - Adenomas and metastases may coexist in same gland (collision tumor)
- T1 C+ MR - Rapid, uniform enhancement and deenhancement
- Ancillary MR techniques - Diffusion MR: Not specific (ADC overlap between adenomas and metastases) - MR spectroscopy: Choline:creatinine and choline:lipid ratio discriminatory threshold ratios may aid in adrenal lesion characterization, though larger studies needed

Ultrasonographic Findings

Grayscale ultrasound

- Nonspecific, solid suprarenal mass
        - Right suprarenal mass seen more clearly left due to acoustic window provided by liver

Angiographic Findings
- Conventional - Adrenal arteriography - Catheterization of renal or inferior adrenal arteries shows vascular supply of adrenal tumors - Adenomas are usually hypo- to moderately vascular - No arterial encasement or venous laking or puddling, which are malignant vascular features - Adrenal venography - Most commonly to obtain adrenal vein samples - Advocated for patients with primary hyperaldosteronism triaged to adrenalectomy - Technically difficult study but may confirm laterality of small, aldosterone-secreting adenoma - Technical approach and criteria for positive study varies; ACTH stimulation may increase accuracy - Adrenal adenoma is seen as filling defect within adrenal gland displacing adjacent vessels - Circumferential vein frequently seen around adrenal adenoma
Nuclear Medicine Findings
- PET/CT - Utilized as part of malignancy staging - Markedly increased F-18 FDG uptake characteristic of metastases - Adenomas may also accumulate F-18 FDG, typically less intense than liver - Potential false-negatives: Metastases from primary carcinomas that are non-FDG avid (e.g., neuroendocrine tumors) - SUV thresholds published but adenomas typically less intense than liver
- Adrenocortical scintigraphy by using NP-59 - NP-59 is cholesterol analog that binds to low-density lipoprotein receptors of adrenal cortex - NP-59 used and dexamethasone: Accentuate uptake in non-ACTH-dependent adrenal tissues (adenoma) - Normal NP-59: When both adrenal glands are seen 5 days after injection or thereafter - Adrenal adenoma: Unilateral early adrenal visualization before day 5 after NP-59 injection - Adrenal hyperplasia: Bilateral early adrenal visualization before day 5 after NP-59 injection
Imaging Recommendations
- NECT is initial study of choice to confirm diagnosis of lipid-rich adrenal adenoma - ROI should encompass lesion: Attenuation < 10 HU is diagnostic
- In- and out-of-phase MR equivalent to NECT for lipid-rich lesions - Signal dropout on out-of-phase T1WI MR: Qualitative assessment typically suffices
- CECT, including 15-minute delayed phase, used for potential lipid-poor adenomas: Calculate either relative or absolute washout

DIFFERENTIAL DIAGNOSIS

Adrenal Metastases and Lymphoma
- Adrenal metastases - Unilateral or bilateral masses ± central necrosis, hemorrhage - Usually known to have malignancy elsewhere - NECT: Metastases mimic lipid-poor adenoma - CECT: Hypo- or hypervascular and prolonged washout pattern
- Adrenal lymphoma - Usually spread to adrenal gland from retroperitoneal tumor - Unilateral or bilateral masses - Unilateral primary lymphoma (non-Hodgkin) can mimic adenoma - Hypovascular; moderate enhancement with contrast
Adrenal Myelolipoma
- Small or large, asymptomatic adrenal mass
- Intramural macroscopic fatty elements on imaging
Adrenal Hyperplasia
- Adrenal glands are often symmetrically enlarged
- Width of adrenal gland limbs > 10 mm (diagnostic)
- No discrete mass or nodule seen as rule
- Dominant macronodule of macronodular hyperplasia mimics small adrenal adenomas - Cortisol-secreting adenoma: Remainder of ipsilateral and contralateral glands, atrophic (↓ ACTH) - Macronodular hyperplasia: Both glands are enlarged (due to elevated ACTH levels)
- No obvious enhancement and washout pattern seen
Pheochromocytoma
- Tumor > 3 cm in most cases; classically T2 hyperintense
- Highly vascular tumor prone to hemorrhage, necrosis
- Bilateral adrenal tumors in multiple endocrine neoplasia (MEN) syndromes
Unilateral Adrenal Hemorrhage
- Chronic hematoma: Well-defined, round, low-density, mass-like lesion simulating adenoma
Adrenal Carcinoma
- Rare, unilateral, invasive and enhancing mass
- 6 cm when initially diagnosed
Gastric Diverticulum
- Abnormal, rounded soft tissue lesion in left suprarenal area; mimics adrenal mass
- Diverticular contents do not enhance, whereas adenomas do
- Distend stomach with gas and fluid; scan in prone position to distend diverticulum
Ganglioneuroma
- Younger patients; mean age: 27 years
- Larger mass; average tumor size: 8 cm
Adrenal Cyst
- Attenuation similar to lipid-rich adenoma
- Lack of enhancement, rim calcification may suggest diagnosis

PATHOLOGY

General Features

Etiology
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- Unknown
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Associated abnormalities

- MEN syndromes
- Most adrenals with adenoma have normal function
        - Occasionally adenoma causes adrenal hyperfunction
- Normal adrenocortical secretory hormones
        - Cortisol, aldosterone, androgens

Gross Pathologic & Surgical Features
- Well-delineated, tan-yellow, ovoid mass
- 3 microscopic patterns - Pure (fasciculata- or reticularis-type cells), mixed, or hybrid
- May have focal areas of degeneration, hemorrhage, and fibrin deposition
Microscopic Features
- 70% of adenomas: High % of intracytoplasmic lipid
- 30% of adenomas: Low % of intracytoplasmic lipid

CLINICAL ISSUES

Presentation

Most common signs/symptoms

- Asymptomatic incidental CT finding
- Conn syndrome: Hypertension and weakness
- Cushing syndrome: Moon facies, truncal obesity, purple striae, and buffalo hump
- Virilization in women
- Lab data: ↑ aldosterone, cortisol, &/or androgens
- Diagnosis: Clinical, biochemical, imaging, histology

Demographics

Age

- Prevalence of adenoma increases with age
        - Peak at 60-69 years, decreasing thereafter

Epidemiology

- Most common adrenal tumor of all incidentalomas
- ↑ incidence in patients with diabetes or hypertension
- Occurs in up to 9% of population (postmortem data)

Natural History & Prognosis
- Prognosis: Excellent when incidental and nonhyperfunctioning
Treatment
- No treatment when asymptomatic incidental finding
- Laparoscopic removal of gland if hyperfunctioning

DIAGNOSTIC CHECKLIST

Consider
- Asymptomatic mass: Usually nonhyperfunctioning adenoma, even in patient with known cancer
Image Interpretation Pearls
- Well-defined, low-density (< 10 HU) suprarenal mass
- Enhances with washout pattern > 50% within 15 minutes
- Out-of-phase T1WI MR: Signal dropout, lipid-rich mass

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References

Selected References

Tables

Washout Criteria/Enhancement Kinetics of Adrenal Adenoma

Absolute Washout	Relative Washout	Exceptions
[(Post HU - delayed HU) / (post HU - pre HU)] x 100	[(Post HU - delayed HU) / post HU] x 100	Significant minority of pheochromocytomas meet washout criteria for adenoma (25-33%) but rarely contain intracytoplasmic lipid
≥ 60% highly suggestive of adenoma	≥ 40% highly suggestive of adenoma	Noncontrast attenuation (HU) ≥ 43 in adrenal mass without hemorrhage or calcification should raise suspicion for malignancy

Images

Selected Images

Axial in-phase T1 MR in a 77-year-old man with urothelial cancer shows a relatively homogeneous, 4.2-cm right adrenal mass .

Axial out-of-phase T1 MR in the same patient shows marked signal loss in the adrenal mass , indicating intracytoplasmic lipid and consistent with adrenal adenoma.

Axial CECT in the same patient shows heterogeneous enhancement of the right adrenal mass (75 HU), indeterminate on single-phase CT.

Axial PET/CT in the same patient shows mild uptake in the right adrenal mass , less than that of the adjacent hepatic parenchyma , further supporting the diagnosis of adenoma made on MR.

Axial in-phase T1 MR shows a mildly heterogeneous right adrenal mass in a 62-year-old woman with hirsutism.

Axial out-of-phase T1 MR shows signal dropout at the periphery of the mass and in the liver , indicating intracellular lipid. The mass was resected based on indeterminate imaging features and shown to be an adenoma with central degeneration, which can be seen with adenomas and can be confused with a collision tumor.

Coronal T1 MR in a 34-year-old woman with hypertension and hypokalemia shows an intermediate-signal left adrenal lesion . Note the incidental high-signal right renal cyst .

Coronal out-of-phase T1 MR shows marked signal suppression of the left adrenal lesion, confirming a clinically functional, imaging apparent, lipid-rich adenoma . Signal suppression is due to intravoxel cytoplasmic lipid and water. Aldosterone-secreting adenomas are typically small (< 2 cm).

Axial NECT in the same patient shows a 1.5-cm, low-attenuation (5 HU), lipid-rich left adrenal adenoma .

Adrenal vein sampling was subsequently performed, which confirmed an aldosterone-secreting left adrenal lesion. Gross photo of the laparoscopically resected left adrenal gland shows an exophytic, well-circumscribed adrenocortical adenoma .

Coronal T1 MR of the lumbar spine in a 67-year-old woman shows an incidental, low-signal left adrenal mass .

Coronal NECT in the same patient shows low attenuation of the left adrenal mass (HU -7). Noncontrast attenuation of HU < 10 is consistent with adrenal adenoma.

Coronal portal venous-phase CT in the same patient shows mild enhancement of the left adrenal mass (HU 73).

Coronal 15-minute delayed-phase CECT shows washout of the left adrenal mass (HU 36) with relative washout of 51%, highly suggestive of an adrenal adenoma . Biochemical work-up, including metanephrines, performed due to the size of the mass was normal.

Axial in-phase T1 MR in a 68-year-old woman with colon cancer shows a mildly heterogeneous left adrenal mass .

Axial out-of-phase T1 MR in the same patient shows diffuse signal loss in the left adrenal mass , consistent with intracytoplasmic lipid in an adrenal adenoma. The mass remained stable over 4 years since incidental detection on initial surveillance imaging.

Additional Images

Axial CECT in a 68-year-old woman with colon cancer shows an indeterminate-signal, heterogeneous left adrenal mass (HU 65) with relatively low central attenuation.

Axial T2 FS MR in the same patient shows low signal at the periphery of the mass and increased signal centrally. Central degeneration, hemorrhage, and fibrosis are known features of some adrenal adenomas. The mass demonstrated diffuse signal loss on out-of-phase MR, consistent with intracellular lipid and adenoma.

Axial NECT in a 34-year-old woman with elevated 24-hour urine cortisol and Cushing syndrome shows a low-attenuation (HU -6) right adrenal mass , confirmed to be an adrenal adenoma at surgical pathology.

Axial in-phase T1 MR shows small, bilateral adrenal masses .

Axial opposed-phase T1 MR shows a loss of signal in both adenomas, confirming the presence of lipid.

Axial NECT shows a homogeneous, low-density right adrenal adenoma and a normal left adrenal gland.

Axial NECT shows a homogeneous, low-density adenoma that is larger than typical, which had grown slowly over 10 years.

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KEY FACTS

Imaging

Top Differential Diagnoses

Diagnostic Checklist

TERMINOLOGY

Definitions

IMAGING

General Features

Best diagnostic clue

Size

Morphology

CT Findings

NECT

CECT

MR Findings

Ultrasonographic Findings

Grayscale ultrasound

Angiographic Findings

Nuclear Medicine Findings

Imaging Recommendations

DIFFERENTIAL DIAGNOSIS

Adrenal Cyst

PATHOLOGY

General Features

Etiology

Associated abnormalities

Gross Pathologic & Surgical Features

Microscopic Features

CLINICAL ISSUES

Presentation

Most common signs/symptoms

Demographics

Age

Epidemiology

Natural History & Prognosis

Treatment

DIAGNOSTIC CHECKLIST

Consider

Image Interpretation Pearls

References

Selected References

Tables

Washout Criteria/Enhancement Kinetics of Adrenal Adenoma

Images

Selected Images

Additional Images

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