8/11/2017 The Radiology Assistant : Adrenals

Adrenals
Differentiating benign from malignant
Theo Falke and Robin Smithuis
Radiology Department of the Groene hart hospital in Gouda and the Rijnland hospital in Leiderdorp,
the Netherlands

Publicationdate September 26, 2005

Update: 19-5-06
Adrenal masses are seen in 1% of CT-
examinations.
Most of these masses are benign.
Even in patients with a known malignancy these
masses are usually non-functioning adenomas.
The issue is how to differentiate these benign
adenomas from malignant adrenal masses.

Adrenal masses: benign versus malignant

The most common tumor in the adrenal gland is

the adenoma.
Adenomas are reported to occur in from 1.4% to
8.7% of postmortem examinations.
Adenomas large enough to be recognized at
abdominal CT examination are found in 1% of
patients.

Right adrenal gland with a lipid-rich adenoma

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CT-examination

Adrenal adenomas have two properties that

differentiate them from non-adenomas. (1)
1. 70% of adenomas contain high intracellular fat
(lipid-rich adenomas) and will be of low
attenuation on unenhanced CT.
2. Adenomas rapidly wash out contrast.

Unenhanced CT. Using a safe threshold value of

10HU on a native CT scan results in a sensitivity
of 70% and a high specificity of 98% for the
ROI at least 1/2 size of mass. Do not include adjacent diagnosis of an adenoma.
periadrenal fat.
A density equal to or below 10 HU is considered
diagnostic of adenoma.
30% of adrenal adenomas do not contain enough
intracellular lipid to have a density of less than
10 HU and cannot be differentiated from
malignant masses on an unenhanced CT.
These adenomas are called lipid-poor (3).

Enhanced and Delayed scan.

Although on the initial enhanced CT (at 60 sec)
most adenomas show mild enhancement, while
malignant tumors and pheochromocytomas show
strong enhancement, there is too much overlap
in attenuation values to allow differentiation
between malignant and benign.
A number of these adenomas however can be
differentiated from malignant masses on the
basis of their fast wash-out of contrast.
The wash-out can be calculated by comparing the
Absolute enhancement wash out > 60% = attenuation value at 60 sec with the attenuation
adenomaRelative enhancement wash out > 40% =
adenoma
value on a delayed scan at 15 minutes.

The most commonly used formula is the

'enhancement wash out' formula presented on
the left (sometimes called absolute wash out).
Attenuation values are measured on unenhanced,
initial enhanced (at 60 sec) and delayed CT (at
15 min) .

Click here to go to the Adrenal Characterization

Calculator.

A calculator for the enhancement washout

formula aswell as another formula for the
'relative wash out' (only based on the enhanced
and delayed scan) is given in reference 1.
You only need to fill in the attenuation values and
an answer is given whether the mass is probably
an adenoma or not. (1)

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CT-Algorithm benign versus

malignant

Mostly an adrenal mass will be found on an

enhanced CT that is performed in patients with
abdominal complaints or patients that are
referred for lungcarcinoma staging.
As differentiation between benign and malignant
is usually not possible on the initial enhanced CT
(at 60sec), ordering the patient back for a
dedicated adrenal-CT is the best strategy (
although some prefer MRI).
Algorithm for differentiating adenomas from non- If on the unenhanced-CT the density is equal to
adenomas. or below 10 HU the lesion is considered to be an
adenoma and no further workup is neccessary
If the density is more than 10 HU the wash out
should be calculated.
If the washout is not compatible with an
adenoma, a biopsy can be performed if a
definitive diagnosis is crucial to the patients
management.

On the left an adrenal mass identified during

staging for lungcarcinoma.
On an enhanced CT at 60 sec the attenuation
value was 22HU.
The next day patient was ordered back for
dedicated adrenal CT.
On the unenhanced CT the attenuation value was
-19HU indicating the presence of a lipid-rich
Adenoma in patient with lungcarcinoma. LEFT: initial
enhanced CT (22HU). RIGHT: unenhanced CT (-19HU).
adenoma.
No further work up was needed.

On the left a dedicated adrenal protocol in a

patient with an adrenal mass.
On the unenhanced CT there is a small
homogeneous mass that is well defined. The
density is 9 HU, which is characteristic of a lipid-
rich adenoma.
Dedicated adrenal protocol in a patient with an adrenal Although the protocol should have stopped at
mass
that moment, i.v. contrast was given to
determine the washout.
The enhancement washout = (43 - 22) : (43 - 9)
= 62% indicating a fast washout characteristic of
an adenoma.
The lower the density on the unenhanced CT and
the faster the washout the more confident you
can be in making the diagnosis of an adenoma..

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Adenoma on the right is homogeneously of low
density. Metastasis on the left is inhomogeneous and
centrally of low attenuation due to necrosis.
Bilateral adrenal masses with signal drop on opposed
phase MRI diagnostic of lipid containing adenomas.
In patients with a known extra-adrenal malignancy a
total score > 7 points was highly accurate for the
diagnosis metastasis.
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The discriminating parameters on CT based on
attenuation values only apply to homogenous
lesions.
Metastases may have a relative low HU due to
central necrosis.
MRI
Although chemical shift MRI is commonly
performed, it is believed by some not to provide
additional information beyond that which is
already available on unenhanced CT (4).
The characterization of a lesion as an adenoma
relies on the ratio of a decreased relative signal
intensity from in phase to opposed phase images
and the ratio of adrenal mass and various organs
on T2-weighted and chemical shift images.
There are no reported studies yet that compare
unenhanced CT, delayed enhanced CT, and
chemical shift for the discrimination between
adenomas and nonadenomas.
Morphologic features
Adenomas are generally small, homogeneous and
well-defined lesions with clear margins. Although
the presence of these features are non-specific
the absence strongly suggests a nonadenoma.
In a retrospective study Gufler et al (5) combined
morphologic criteria with the density
measurements on unenhanced CT and found a
high accuracy in differentiating adrenal
adenomas from metastases in patients with a
known malignancy. They proposed a scoring
system based on density (10% of HU), contour
(plus 2 if blurred), homogeneity (plus 1 if
inhomogeneous) and size (in cm).
By setting a threshold at 7 points all but one
lesion in 56 patients were classified correctly.
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Fine-needle aspiration in an adrenal mass shows a cell
with droplets of fat typical for a adrenocortical cell. As
this sample was taken from an adrenal mass this
finding was characteristic of an adenoma.
CT guided FNA of the left adrenal gland via a posterior
approach. The black dot at the end of the needle
(green arrow) indicates that the tip of the needle is
seen in this image.
Non-specific adrenal mass in a patient with lung
cancer, who was a possible candidate for curative
surgery. Transhepatic CT-guided FNA proved the
presence of metastatic disease.
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Percutaneous biopsy
With the new imaging algorithms there is a
decreasing need to perform percutaneous Fine
needle aspiration (FNA) for definitive
characterization. Because a benign cytological
diagnosis does not exclude malignancy, FNA
cannot be recommended as a standard procedure
in the diagnostic work-up.
Major complications (2.8-3.6%) include
pneumothorax that requires treatment,
hemorrhage, abscess, pancreatitis, and seeding
along the track.
Prior to FNA a clinical and laboratory assessment
should be done to exclude the possibility of a
pheochromocytoma as FNA may precipitate a
hypertensive crisis.
Adrenal biopsies can be performed via a posterior
approach with the patient in the prone position.
The risk of a pneumothorax can be reduced by
caudal angulation of the gantry.
The lateral decubitus approach is also safe and
well tolerated. The patient is placed 'downside'
for whichever adrenal gland that is being
biopsied. This position elevates the diaphragm on
the lesion side and decreases the volume of the
lung, thereby reducing the risk of the needle
traversing the lung en route to the adrenal gland.
The reported accuracy of FNA is 90-96%.
Findings from FNA are most likely to be
conclusive if the mass is a metastatic tumor.
FNA should only be performed when the
diagnosis is crucial to patient management
(figure).
Specific Adrenal tumors
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Primary Adrenocortical carcinoma

Adrenocortical carcinomas are rare and often

diagnosed at an advanced stage. They tend to be
large at diagnosis. Patients present with
abdominal pain, palpable mass or Cushing's
syndrome (50%). The combination of Cushing's
syndrome and virilization is frequently found. CT
demonstrates a large inhomogeneous mass with
heterogeneous enhancement. An adrenal
carcinoma is not likely to be less than 5 cm in
diameter. Central necrosis is common.
Calcification is seen in 20-30% of cases.

Most tumours spread by both the haematogenous

(lung, liver and bone) and the lymphogenous
route. Metastases to the contralateral adrenal, or
simultaneous bilateral involvement may
occasionally be found.

Large inhomogeneous mass with central calcification

typical of an adrenal carcinoma.

As in renal cell carcinoma tumour tends to spread

early by direct invasion of surrounding
structures. Extension of the tumour into the renal
vein or inferior vena cava is not unusual. MR can
be helpful in defining the cephalic extent of the
tumour . This is important to the surgeon to gain
vascular control.

LEFT: Same case as above. Tumor thrombus extents

into right atrium and causes tricuspid valve
insufficiency. RIGHT: Tumor emboli in the lung
following surgery..

On the left a patient with a small right adrenal

carcinoma on CT with high SI on T2-weighted
MRI, indistinguishable from lipid-poor adenoma
except for invasion into the inferior vena cava.

Venous extention of the tumor into the inferior vena

cava.

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LEFT: Diffuse enlargement and irregular enhancement
of the adrenal glands due to metastatic
disease.RIGHT: Pathologic specimen. Notice extension
of tumor into the peripelvine fat.
T1-weighted MRI demonstrates left adrenal metastasis
in a patient with previous resection of the right liver
lobe for metastasis.
LEFT: adrenal mass containing islands of fat specific
for the diagnosis myelolipoma.RIGHT: different case
with high SI on T1WI indicating fat in myelolipoma.
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Metastases
Adrenal metastases are found in 27% of
postmortem studies in patients with malignant
neoplasms. Lung and breastcarcinoma and
melanoma are the most common primary
tumors.
A diagnosis of adrenal metastasis is important in
examining patients with cancer because the
metastasis indicates inoperable stage IV disease
(except in ipsilateral renal cancer).
Adrenal metastases have no specific imaging
features. Statistically most non-adenomas are
metastases.
On the left a patient with partial liver resection
for metastasis of a colon carcinoma. Left adrenal
metastasis in follow up with no specific imaging
findings. The lesion is indistinguishable from a
true lipid poor adenoma or non-adenoma such as
a neuroendocrine tumour, primary adrenocortical
carcinoma, sarcoma or lymphoma and infection.
Adenoma
As mentioned above adenomas can be divided
into lipid-rich adenomas ( 10HU on unenhanced
CT). Lipid-poor adenomas do contain intracellular
lipid but not enough to be of an attenuation value
The NIH state-of-the-science conference has
proposed a minimal standard evaluation for
adenomas to rule out endocrine function (4).
Myelolipoma
Myelolipomas are benign tumors composed of
bone marrow elements. Usually they are easy to
recognize on CT or MR because they contain
areas of fat. Calcifications are seen in 20% of
cases.
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Myelolipoma mainly composed of fat.
Phaeochromocytoma (adrenal paraganglioma) on CT
and MRI. There is strong enhancement on enhanced
CT and very high signal intensity on T2-weighten MRI.
Extra-adrenal paraganglioma on the left side of the
aorta in Zuckerkandle's organ. Notice the very high
signal on the T2-weighted MRI.
LEFT: chronic adrenal hemorrhage demonstrates a
mass-like aspect of the left adrenal gland that is
hyperintense in T1 and T2 MRI with an hypo-intense
halo representing hemosiderin.RIGHT: Neonatal
hemorrhage demonstrates a mass-like aspect of the
right adrenal gland that is hyperintense in T1 and T2
with an hypointense ring which represents
hemosiderin.
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On the left another adrenal mass mainly
composed of fat. Diagnosis myelolipoma.
Pheochromocytoma
Pheochromocytomas are paragangliomas arising
from the adrenal medulla. They are hormonally
active in 90% of cases. Morphologic findings on
CT and MRI include large variation in size,
homogeneity, and margination of the tumours
and significant enhancement in most cases. On
MRI tumours have a low SI on T1-weighted
images and a very high SI on T2-weighted
images.
Pheochromocytomas are sometimes called the
10% tumor because they are associated with a
10% risk of malignancy, 10% of the tumors are
bilateral, 10% are hormonally inactive and 10%
are extra-adrenal (figure).
Usually, tumors are larger than 3 cm when seen.
They are highly vascular, and larger tumors are
prone to hemorrhage and necrosis, even when
they are benign.
Hemorrhage
Extensive adrenal hemorrhage may occur at any
age and under various circumstances such as
severe stress as in surgery, sepsis, burns,
hypotension, trauma, hemorrhagic diathesis and
underlying conditions such as adenoma, cyst and
tumour.
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Cyst

Cysts may be of any size and in most instances

are unilateral. Large cysts may be complicated by
hemorrhage and consequent onset of acute
symptoms. Pathological substrates include
epithelial , endothelial, parasitic, and
pseudocysts. Most importantly lesions show a
thin wall and no enhancement after intravenous
Patient with a left adrenal cyst on T2-weighted TSE contast material.
(left) and fat-suppressed T1W-image after i.v. injection
of Gadolineum (right).

1. Chest x-ray: wash out measurement

This site provides a calculator to measure the wash-out of adrenal masses for differentiation of benign
masses (usually adenomas) from malignant lesions (usually metastases).
2. Imaging of Adrenal Incidentalomas: Current Status
N. Reed Dunnick and Melvyn Korobkin
Am. J. Roentgenol., Sep 2002; 179: 559 - 568.
3. Adrenal Masses: Characterization with Combined Unenhanced and Delayed Enhanced CT
Elaine M. Caoili et al.
Radiology 2002;222:629-633.
4. Management of the clinically inapparent Adrenal Mass 'Incidentaloma' NIH State-of-the-Science
Conference Feb 4-6, 2002.
State of the Science Statement (html and pdf) and 3 day video conference
5. Differentiation of adrenal adenomas from metastases with unenhanced computed tomography.
Gufler H, Eichner G, Grossmann A, Krentz H, Schulze CG, Sauer S, Grau G.
J Comput Assist Tomogr. 2004 Nov-Dec;28(6):818-22.
6. eMedicine - Pheochromocytoma : Article by Anant Krishnan, MD
7. Adrenal Masses in the Cancer Patient: Surveillance or Excision
Ian C. Mitchell, Fiemu E. Nwariaku
The Oncologist, Vol. 12, No. 2, 168-174
8. Evaluation of adrenal masses in patients with bronchogenic carcinoma using 18F-fluorodeoxyglucose
positron emission tomography
JJ Erasmus, EF Patz Jr, HP McAdams, JG Murray, J Herndon, RE Coleman and PC Goodman
American Journal of Roentgenology, Vol 168, 1357-1360
9. Integrated PET-CT for the Characterization of Adrenal Gland Lesions in Cancer Patients: Diagnostic
Efficacy and Interpretation Pitfalls
Semin Chong et al
RadioGraphics 2006;26:1811-1824
10. Pearls and Pitfalls in Interpretation of Abdominal and Pelvic PET-CT
Michael A. Blake et al
RadioGraphics 2006;26:1335-1353
11. The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management
Georg Mansmann, Joseph Lau, Ethan Balk, Michael Rothberg, Yukitaka Miyachi and Stefan R. Bornstein
Endocrine Reviews 25 (2): 309-340

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