Dr. Elsayes is an Associate Professor, Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX; and Dr. Caoili is a Clinical Associate Professor, Department of Radiology, University of Michigan Health Center, Ann Arbor, MI.
Noninvasive imaging can be useful in overcoming the challenges of
detecting and characterizing adrenal masses. Imaging characteristics
based on morphologic and physiologic features can guide the radiologic
management of adrenal lesions.
Computed tomography (CT)
CT is commonly used to
detect and characterize adrenal masses. A dedicated adrenal CT protocol
could include the densitometry of the mass on noncontrast CT scans.
Measuring the unenhanced attenuation value of adrenal masses is
important for diagnosing lipid-rich adenomas. An unenhanced attenuation
value of less than 10 Hounsfield units (HU) is characteristic of a
benign adrenal mass, and no further imaging evaluation would be
required.1 Use of contrast enhancement washout values would
help to further distinguish adenomas from malignant lesions. Adrenal
masses that have attenuation values >10 HU at unenhanced imaging
should undergo enhanced CT imaging 60 sec after intravenous
administration of contrast material and then
delayed-enhanced CT imaging at 15 min. Enhancement washout percentages
for these masses are calculated. The absolute percentage enhancement
washout can be calculated by measuring the enhanced attenuation, the
delayed enhanced, and the unenhanced values using the following formula:
AEW = EAV-DAV / EAV-UAV
AEW = Absolute enhancement washout
REW = Relative enhancement washout
EAV = Enhanced attenuation value
DAV = Delayed attenuation value
UAV = Unenhanced attenuation value
When noncontrast scans have not been obtained, relative enhancement washout can be calculated as follows:
REW = EAV-DAV / EAV
Absolute threshold values ≥60% and relative washout threshold ≥40%
have been found to be 98% sensitive and 92% specific for diagnosing
Magnetic resonance imaging (MRI)
most important sequence of the adrenal MRI protocol is chemical shift
imaging performed with in-phase and out-of-phase sequences. Loss of
signal intensity of the adrenal mass on out-of-phase images, compared to
the in-phase pulse sequence, is diagnostic of the presence of
intracellular lipid. The accuracy in distinguishing adenomas from
metastatic tumors is 100% if the cutoff value of the signal intensity
index selected is 16.5%.2
However, MRI has been
reported to have limited value in characterizing lipid-poor adenomas.
Haidar has described this limitation in lipid-poor adenomas with
attenuation values >30 HU.3 Similarly, only 62% (8 of a
series of 13 cases) of adrenal adenomas measuring >10 HU on
unenhanced CT were characterized with chemical shift MRI.4
utility of diffusion-weighted MR imaging (DWI) has been studied for the
diagnosis of adrenal tumors. Although pheochromocytomas showed higher
apparent diffusion coefficient (ADC) values in this series, ADC value
has not been found to have significant utility for differentiating
adenomas and metastatic tumors.5
Positron emission tomography (PET)
has been found to be less useful than CT in differentiating adrenal
adenomas from nonadenomas. However, adrenal mass activity, which is
visibly lower than liver activity, is more specific for adenoma, whereas
adrenal mass activity visibly greater than liver activity is more
specific for malignancy.6
Adrenal adenomas are the most
common adrenal lesions, found in 3% of cases at autopsy. An important
characteristic of adrenal adenoma is the presence of intracellular
lipid. CT is the most sensitive and specific imaging modality for
characterization of adrenal masses. As discussed above, an unenhanced
attenuation value <10 HU is characteristic of lipid-rich adenoma
(Figure 1). Threshold values >60% for absolute and >40% for
relative enhancement washout have been found to be 98% sensitive and 92%
specific for diagnosing adrenal adenomas (Figure 2).1
Chemical shift imaging (with in-phase and out-of-phase pulse sequences)
is the most reliable MR technique for diagnosing adrenal adenomas. Most
adrenal adenomas demonstrate a loss of signal intensity on out-of-phase
compared to in-phase images (Figure 3).7-9 A decrease in signal intensity of >16.5% is considered diagnostic of adenomas.2 Uniform enhancement on immediate contrast-enhanced images is also typical of adenomas.10
Small, rounded foci of altered signal intensity may be seen within
adenomas, owing to cystic changes, hemorrhage, or variations in
Foci of macroscopic fat have rarely
been reported in adrenocortical adenomas, which were preoperatively
interpreted as myelolipomas on the basis of radiologic findings. The
lipomatous tissue may represent degenerative phenomena within an
adrenocortical adenoma or may be an additional neoplastic component of a
tumor. Regardless of their origin, extensive (myelo) lipomatous changes
in adrenocortical tumors can lead to misinterpretation in the
preoperative work-up of patients with adrenal masses.12
Mimics of adrenal adenomas
uncommon, various adrenal masses can mimic adrenal adenomas, mainly due
to low attenuation on CT or the signal loss on out-of-phase MR pulse
sequences compared to in-phase sequences. Simple cysts can mimic adrenal
lipid-rich adenomas on unenhanced CT, as it could demonstrate
attenuation value <10 HU. However, simple cysts do not enhance on
postcontrast series, and they also exhibit high-signal intensity on
T2-weighted MR images (Figure 4). Metastatic deposits containing
intracellular lipid could develop secondary to primary malignancies
containing intracellular lipid such as hepatocellular carcinoma or renal
cell carcinoma (clear cell subtype).13,14 The presence of
intracellular lipid in these masses results in signal loss in
out-of-phase pulse sequences compared to in-phase pulse sequences,
making them difficult to differentiate from the more common adrenal
adenomas. Adrenal cortical carcinoma (ACC) has also been reported to
contain intracellular lipid.15 However, adrenal cortical
carcinomas are usually large at presentation, and the distribution of
intracellular lipid in ACC would be rather inhomogeneous.
are the most common malignant lesions involving the adrenal gland.
Adrenal metastases are found in up to 27% of patients with malignant
epithelial tumors at autopsy.16 Common primary tumors that metastasize to the adrenal glands include carcinomas of the lung, bowel, breast, and pancreas.17
Metastases are usually bilateral (Figure 5), but they may also be
unilateral. On CT, metastases typically have attenuation values >10
HU on unenhanced CT. They also demonstrate absolute enhancement washout
of <60%, and a relative enhancement of <40%.1
MRI, metastases usually exhibit low-signal intensity on T1-weighted
images and high-signal intensity on T2-weighted images, with
heterogeneous enhancement after administration of contrast. The most
important diagnostic feature is the lack of signal loss on out-of-phase
images (in contradistinction to that seen with adrenal adenoma).7-9
tumors are uncommon and represent the coexistence of two adjacent but
histologically distinct tumors without histological admixture. If a
collision tumor is not recognized, however, biopsy only of the benign
component of the tumor can result in potential misdiagnosis.18 MR imaging can improve characterization of the separate components of collision tumors.18
Adrenal masses containing macroscopic fat
most common adrenal mass containing macroscopic fat is myelolipoma.
Myelolipoma is an uncommon benign tumor composed of mature adipose
tissue and hematopoietic tissue. Most of these lesions are discovered
incidentally. The fatty component of this tumor can be diagnosed by the
presence of areas of negative attenuation value on CT. On MRI,
macroscopic fat is hyperintense on nonfat-suppressed T1-weighted images.
The use of fat suppression can help confirm the diagnosis by
demonstrating a loss of signal intensity within the fatty component
(Figure 6).19 Myelolipomas can be large and symptomatic
secondary to spontaneous hemorrhage. Rarely, large myelolipomas can be
confused with other retroperitoneal lipomatous tumors such as
Congenital adrenal hyperplasia can have
a characteristic appearance of multiple bilateral adrenal masses
containing extensive macroscopic fat that could result from prolonged
stimulation of the adrenal cortex by elevated ACT levels (Figure 7).
The authors have described a rare entity presumed to represent lipomatous metaplasia.20
Adrenal lipomatous metaplasia is a known pathological entity
characterized by small oval foci of macroscopic lipid occupying an
otherwise unremarkable adrenal cortex. Because all the cases reported
previously have been in the pathology literature, it is not surprising
that they have been in patients with hypersecretory adrenal lesions such
as hyperplasia, adenoma, and carcinoma that required surgical
resection. In our cases, there was no clinical evidence of
hypersecretory or structural adrenal abnormalities.20
Adrenal cortical carcinoma has rarely been reported to contain foci of macroscopic fat.21
cysts are the most common pathologic subtype of adrenal cyst,
accounting for approximately 40% of adrenal cysts. Simple cysts
demonstrate fluid attenuation (<20 HU) on noncontrast series; thus
they could mimic lipid rich adenoma. Simple cysts, however, exhibit no
significant enhancement on postcontrast series. On MRI, simple cysts are
typically hypointense on T1-weighted images and hyperintense on
T2-weighted images, with no soft-tissue component and no internal
enhancement.22 Pseudocysts are the second most common cystic
lesions of the adrenal gland, accounting for approximately 39% of
adrenal cysts. They are more likely than simple adrenal cysts to be
symptomatic. Pseudocysts typically arise after an episode of adrenal
hemorrhage and do not have an epithelial lining. Peripheral curvilinear
calcification may be present, which represents a characteristic pattern
of a complicated cyst that is well depicted by CT
(Figure 8), but difficult to appreciate on MR images.23,24
Adrenal pseudocysts may have a complicated appearance on MR images,
manifesting septations, blood products, soft-tissue components secondary
to hemorrhage or hyalinized thrombus.23,25
Adrenal cortical hyperplasia
cortical hyperplasia is often seen in patients with Cushing syndrome
(the result of hyperproduction of cortisol) and less commonly in Conn’s
disease. The hyperplasia may be diffuse or nodular and typically is
bilateral. On CT and MRI, the attenuation and signal intensity of
hyperplastic adrenal glands are usually similar to that of the normal
adrenal gland, although noncontrast attenuation could be lower in some
cases. Similarly, signal intensity may also decrease on out-of-phase
pulse sequences compared to in-phase pulse sequences, especially in
patients with adenomatous cortical nodules. Bilateral cortical
hyperplasia is seen in 45% of patients with Cushing syndrome, whereas
nodular cortical hyperplasia is seen in only 3% of these patients.26
hemorrhage can occur in the settings of postoperative states, trauma,
stress, hypotension, and various bleeding diatheses as well as eclampsia
of pregnancy and sepsis. On CT, adrenal hemorrhage can be seen as high
density on unenhanced images (Figure 9). Its appearance overlaps with
that of other lesions following contrast enhancement.
Adrenal insufficiency (Addison’s disease) can be a secondary effect of bilateral adrenal hemorrhage.27
MR imaging is the most sensitive and specific modality for diagnosing
adrenal hemorrhage. MR imaging features vary according to the age of the
hematoma. The appearance of blood products at MR imaging varies with
their stage of evolution. Acute blood in the form of deoxyhemoglobin is
isointense relative to muscle on T1-weighted images and has low
intensity on T2-weighted images. Subacute blood in the form of
methemoglobin is hyperintense on T1-weighted images. Initially,
methemoglobin is intracellular and has low signal intensity on
T2-weighted images. Subsequently, as the red cells lyse and the
methemoglobin becomes extracellular, it has high signal intensity on
T2-weighted images. Old hemorrhage has low signal intensity on both T1-
and T2-weighted images because of the presence of hemosiderin.
T1-weighted fat-saturated images are quite sensitive in the detection of
methemoglobin. GRE images can magnify the susceptibility effects of
decreased signal intensity seen with hemosiderin and deoxyhemoglobin,
thereby increasing their conspicuity. Similarly, a lesion that loses a
substantial amount of signal intensity on in-phase images compared with
out-of-phase images obtained with a shorter echo time may contain blood
are uncommon tumors arising from the adrenal medulla and the sympathetic
paraganglia. Sympathetic ganglia are found predominantly in the
para-axial region of the trunk along the prevertebral and paravertebral
sympathetic chains and in the connective tissue in or near the walls of
pelvic organs. Pheochromocytoma has been called the “10% tumor” because
approximately 10% are bilateral, 10% are malignant, 10% occur in
children, and 10% are extra-adrenal. It is difficult to differentiate
benign pheochromocytomas from malignant, histologically. Therefore,
malignancy is usually established by local invasion or metastases.
can be associated with multiple endocrine neoplasias (MEN2), Von
Hippel-Lindau Disease (VHL) (Figure 10), Von Recklinghausen
neurofibromatosis (NF1) and nonsyndromic familial pheochromocytoma.28 Elevated levels of urinary metanephrine or resting plasma catecholamines can suggest the diagnosis of pheochromocytoma.
appearances of pheochromocytomas are non-specific by CT and frequently
overlap with other adrenal masses. MRI is increasingly used because of
its multiplanar capability, high sensitivity for contrast enhancement,
and lack of ionizing radiation. In our series of 18 surgically proven
pheochromocytomas, the MRI appearances were variable. Most cases
demonstrate high intensity on T2-weighted images. However, markedly
increased T2 signal intensity is not as common as thought in the past.
Pheochromocytomas do not contain intracellular lipids leading to lack of
signal dropout on chemical shift pulse sequences. Variable postcontrast
appearances can be also seen in these tumors with a characteristic
persistent enhancement on delayed phase.29
Adrenal cortical carcinomas
cortical carcinomas are rare tumors, affecting approximately 2 patients
per million, with a peak incidence in patients 30 to 70 years of age.30
Adrenocortical carcinoma is typically an aggressive malignancy with a
poor prognosis, although less virulent forms do occur. The tumors can
present either due to hormone production causing Cushing syndrome or
Conn syndrome, or due to mass effect from the primary or metastatic
lesions. Other manifestations include an abdominal mass and abdominal
Typically, adrenal cortical carcinoma is large at
presentation, usually measuring more than 6 cm. Heterogeneous texture on
CT and MRI is usually noted, owing to the presence of internal
hemorrhage, necrosis, and calcification (Figure 11).31
Adrenocortical carcinoma can contain foci of intracytoplasmic lipid,
which results in a loss of signal intensity on out-of-phase images.31,32 Large adrenal carcinomas tend to invade the adrenal vein and inferior vena cava.
adenoma is the most common adrenal mass, and metastases is the most
common malignant adrenal mass. Most imaging techniques were developed to
differentiate adenoma from metastatases, with CT washout technique as
the most sensitive and specific imaging technique. Using CT, <10 HU
on noncontrast series indicates a lipid-rich adenoma, and >10 HU on
noncontrast series is indeterminate, and one should proceed with the
washout technique. Washout >60% indicates diagnostic for lipid poor
MRI is helpful in the setting of heterogeneous mass as
well as in contrast issues, such as allergy, or renal insufficiency.
In-phase/out-of-phase MRI is very useful for diagnosing lipid-rich and
most lipid-poor adenomas, but is limited in characterizing few cases of
lipid poor adenomas. 16.5% signal dropout is diagnostic of adenoma.
Metastatic deposits of primary malignancies containing intracellular lipid (such as HCC and RCC) could mimic adenoma.
cysts may also mimic adenoma on noncontrast CT. Rarely, adrenal
cortical carcinoma contains intracellular lipid and very rarely contains
macroscopic fat. The presence of macroscopic fat is consistent with
myelolipoma, until proven otherwise. Pseudocyst can have a large
heterogeneous pattern, thus mimicking carcinoma.
are better characterized by MRI. Although variable, a constellation of
features, including lack of intracellular lipid, high signal intensity
on T2-weighted images, and contrast enhancement, is suggestive of
pheochromocytoma. Elevated plasma metanephrine levels are also
Adrenal cortical carcinoma is typically large and
heterogeneous at presentation. The tumor can present due either to
hormone production causing Cushing syndrome or Conn syndrome or to mass
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- Israel GM, Korobkin M, Wang C, et al. Comparison of unenhanced CT
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- Tsushima Y, Takahashi-Taketomi A, Endo K. Diagnostic utility of
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- Caoili EM, Korobkin M, Brown RK, et al. Differentiating adrenal
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- Korobkin M, Lombardi TJ, Aisen AM, et al. Characterization of
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- Namimoto T, Yamashita Y, Mitsuzaki K, et al. Adrenal masses:
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- Shinozaki K, Yoshimitsu K, Honda H, et al. Metastatic adrenal tumor
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