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Review
Adrenal MRI: Techniques and Clinical Applications
Evan S. Siegelman, MD*
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techniques and illustrate the MRI features of thecommonly
encountered lesions of the adrenal gland.
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Author: Evan S. Siegelman, MD
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Hospital of the University of Pennsylvania, Perelman School of
Medicine, University of Pennsylvania, Department of Radiology,
Philadelphia,Pennsylvania, USA.*Address reprint requests to:
E.S.S., Hospital of the University of Pennsylvania, Perelman School
of Medicine, University of Pennsylvania, 1stFloor Silverstein,
Department of Radiology, 34th and Spruce St., Philadelphia, PA
19104-4283. E-mail: [email protected] September
6, 2011; Accepted January 4, 2012.DOI 10.1002/jmri.23601View this
article online at wileyonlinelibrary.com.
JOURNAL OF MAGNETIC RESONANCE IMAGING 36:272285 (2012)
CME
VC 2012 Wiley Periodicals, Inc. 272
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The article reviews current magnetic resonance imaging(MRI)
techniques and illustrates the MRI features of thecommonly
encountered lesions of the adrenal gland. MRmay not always be able
to characterize an adrenal mass.In these instances, reviewing the
patients clinical historyand prior imaging can usually
differentiate benign frommalignant lesions, even if you cannot
establishing anexact tissue diagnosis. The reader is referred to
otherreviews of adrenal imaging that emphasizes the use of CTand
imagingmanagement algorithms that are beyond thepurview of this
focused review (16).
Key Words: adrenal gland; pheochromocytoma; adrenaladenoma;
chemical shift imagingJ. Magn. Reson. Imaging 2012;36:272285.VC
2012 Wiley Periodicals, Inc.
MAGNETIC RESONANCE IMAGING(MRI) TECHNIQUES
In-Phase and Opposed-Phase ChemicalShift Imaging
THE CHEMICAL SHIFT between lipid and water pro-tons is 3.5 ppm.
At 1.5 T the chemical shift is 220Hz, which corresponds to once
every 4.6 msec. Thus,at 1.5 T the ideal dual echo gradient echo
sequencehas echo times of 2.3 and 4.6 msec. On 3 T MR sys-tems the
chemical shift of 440 Hz results in a dualecho sequence with
optimized echo times of 1.15 and2.3 msec (7). Independent of MR
field strength thereare three principles that can be used to
optimize thechemical shift sequence for adrenal and
abdominalimaging.
1. Both the in-phase and opposed images should beobtained in the
same breath-hold (eg, as a dualecho gradient echo sequence).
Simultaneousimage acquisition eliminates slice
misregistrationbetween the opposed-phase and in-phaseimages.
2. The first echo of the dual echo sequence shouldbe the
opposed-phase image. This will ensurethat loss of adrenal gland
signal intensity on theopposed-phase image compared with the
in-phase image is secondary to the presence of lipidand water
protons within the same voxel. If thesecond, longer echo time
corresponded to theopposed-phase image, then signal loss could
beeither from intracellular lipid or from T2* suscep-tibility
effects (8,9).
3. The lowest echo time pair of opposed- and in-phase values
should be chosen in order to maxi-mize signal-to-noise and minimize
T2* suscepti-bility and T2 effects. Thus, at 3 T a dual
echogradient echo sequence with echo times of 1.15and 2.3 msec is
preferred to 3.45 and 4.6 msec.
Many practices now use a dual echo gradient echosequence instead
of a spin echo or fast spin echosequence when performing
T1-weighting imaging ofthe abdomen (10).
Twenty years ago Don Mitchell et al (11) publishedthe seminal
article that showed the utility of chemical
shift MRI in the detection and characterization of
in-tracellular lipid with adrenal masses (Fig. 1a,b).
Otherinvestigators subsequently confirmed the value of
thistechnique (1223).
There are three ways one can establish the presenceof lipid
within an adrenal mass. The first is to qualita-tively compare both
the in-phase and correspondingopposed-phase images side-by-side on
a workstationusing identical window settings. If the adrenal
masshas lower signal intensity on the opposed-phaseimage, it
contains lipid (19). A second more rigorousmethod is to create a
subtraction image (Fig. 1c) (theopposed-phase image is subtracted
from the in-phaseimage) (24). Subtraction images can be generated
bymost MR systems or by any number of secondary ven-dor products.
Any signal present on the subtractedimage indicates the presence of
lipid and water pro-tons within the same voxel (24). If one wanted
to per-form a quantitative measurement of adrenal lesionlipid then
the chemical shift index can be calculated(21). The chemical shift
index is defined as follows:
Chemical shift index [(Signal intensity of adre-nal mass on
in-phase image Signal intensity ofadrenal mass on opposed-phase
image)/Signalintensity of adrenal mass on in-phase image] 100.
A chemical shift index of >15%20% detects
mostlipid-containing adrenal adenomas with high specific-ity
(13,23,25). Rarely, lipid containing adrenal metas-tases can occur
are exceptions to this rule. Both he-patocellular carcinoma (26,27)
and clear cell renal cellcarcinoma (28) contain intracellular
lipid. Patientswith these primary malignancies can develop
adrenalmetastases that also contains intracellular lipidand lose
signal intensity on chemical shift imaging(Fig. 2) (2931).
Fortunately, these patient presenta-tions are rare and the clinical
history of malignancy isknown.
Unenhanced computed tomography (CT) scans canalso establish the
presence of intracellular lipid withinadrenal lesions. An adrenal
mass can be character-ized as an adenoma if the lesion measures
-
gradient echo sequence is ideal for detecting intra-cellular
lipid it can also be used to characterize mac-roscopic fat by
depicting an etching or India-inkartifact at an interface between
intralesional or perile-sional fat and adjacent water containing
tissue (40)
(Fig. 3a,b). I suggest that to unequivocally establishthe
presence of macroscopic fat within an adrenalmyelolipoma, one
should compare an in-phase T1-weighted image with a corresponding
fat-suppressedT1-weighted sequence (4143). These techniques
have
Figure 1.
274 Siegelman
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been used in the female pelvis to establish the pres-ence of fat
within mature cystic teratomas (43,44).Fat-suppressed gradient echo
techniques are pre-ferred over spin echo techniques for two
reasons.First, gradient echo techniques can more readily
beperformed in a breath-hold. Second, when a fat-sup-pressed
gradient echo sequence is performed with anopposed-phase echo time,
it shows greater loss of rel-ative signal intensity when compared
with a corre-sponding fat-suppressed in-phase gradient echo orspin
echo technique (45). CT has similar diagnosticaccuracy in the
detection and characterization of mac-roscopic fat compared with MR
(Fig. 3d).
T2-Weighted Imaging
Studies performed in the late 1980s showed that bothquantitative
and qualitative evaluation of adrenalgland T2 signal intensity had
moderate accuracy indifferentiating between adrenal adenomas and
meta-static disease. Adenomas tend to have signal intensity
comparable to liver or muscle (Fig. 1f), while adrenalmetastases
have T2 signal intensity more similar tospleen (46,47). While these
trends in T2 signal inten-sity still hold true today, chemical
shift imagingremains the most sensitive and specific MR techniqueto
differentiate adenomas from nonadenomas.
Heavily T2-weighted fast spin echo sequences (eg,with echo times
>180 msec) are obtained in many ab-dominal imaging protocols.
Just as these sequencescan be helpful to characterize nonsolid
liver lesionssuch as cysts and hemangiomas, the uncommon ad-renal
cyst or pseudocyst can be characterized withheavily T2-weighted
sequences (41).
Diffusion-Weighted Imaging
The last decade has seen an greater utilization of
dif-fusion-weighted imaging techniques in the abdomen(4850). The
current literature suggest that neitherdiffusion-weighted imaging
nor evaluation of theapparent diffusion coefficients of adrenal
masses are
Figure 1. MR and CT illustration of a lipid-rich benign right
adrenal adenoma in a 72-year-old man. I clarify below howchemical
shift imaging estimated that the adenoma contains 40% lipid. a:
In-phase T1 weighted gradient echo image (TR 130 msec, TE 4.8 msec,
flip angle 90) shows a 2-cm mass of the right adrenal gland (large
arrow). There is mild promi-nence of the lateral limb of the left
adrenal gland (small arrow). I have modified the signal intensity
values to facilitate the ex-planation of the contrast mechanisms on
the subsequent pulse sequences. The signal intensity of the adrenal
mass is 100,which is the sum of the water and lipid signal
intensities. b: Corresponding opposed-phase T1 weighted image (TE
2.4msec) shows homogeneous moderate loss of signal intensity
indicating the presence of intracellular lipid. The resulting
signalintensity within the lesion is 20. Based on simple
arithmetic, one can then estimate that the adenoma contains 40%
lipid.With an optimally timed opposed-phase image and homogenous
water and fat protons a resultant signal intensity of 20occurs when
40% of signal that is secondary to lipid will opposecancel a
corresponding 40% of water signal, leaving a resid-ual 20%. There
is subtle loss of signal intensity within the lateral limb of the
left adrenal gland (small arrow). The low signalintensity posterior
and lateral to the right adrenal gland represents signal loss
secondary to volume averaging of the upperpole of the right kidney
with the adjacent perirenal fat. c: Postprocessed subtraction
(in-phase/opposed-phase) shows thosevoxels that contain both lipid
and water protons as high in signal intensity. Many radiologists
find this image helpful in orderto establish the presence of
intracellular lipid without having to perform signal intensity
measurements on the in- andopposed-phase images. I have found an
additional advantage of this sequence is that many radiologists
prefer to view highsignal intensity pathology contrasted with a low
signal intensity background. In this image the 80% loss of signal
intensitybetween the in- and opposed-phase image (100 to 20) of the
right adrenal adenoma is depicted as positive signal that meas-ures
80. The highest signal intensity would be expected to be at fat
water interfaces where voxels have roughly equivalent sig-nal from
lipid and water. The interfaces that exhibited an etching artifact
on the opposed-phase image have the highestsignal intensity on this
subtraction image. Signal is present with the mesenteric and
retroperitoneal fat as these tissues arenot composed of hydrogen
protons in a pure lipid environment. Adipocytes have lysosomes and
cell membranes that containprotons that behave like water. Thus, it
is the intracellular water protons within fat containing tissues
that account for themild loss of signal intensity on opposed-phase
imaging and resultant positive signal on this subtraction image. d:
Corre-sponding water-suppressed image (TE 2.4 msec). Many MR
systems have the ability to perform such Dixon techniqueswhere both
fat only and water only images are acquired during the same
sequence that the dual-echo in- and opposed-phase images are
obtained. Such fat only sequences can depict macroscopic fat
containing tissues as high signal intensity.This pulse sequence is
less sensitive than the opposed-phase sequence and the subtraction
image (B,C) for showing high sig-nal intensity within tissues
containing less than 50% lipid. In this instance the signal
intensity of the right adrenal adenomais 40. I find it easier to
characterize adenomas using the dual-echo gradient echo image pair
with or without the subtractionimage than relying on a water
suppressed image. e: Fat-suppressed T1-weighted image (TE 2.4 msec)
shows optimal sup-pression of tissues composed of macroscopic fat.
This is the preferred pulse sequence for showing the loss of fat
signal withinadrenal myelolipomas (Fig. 3). This sequence is less
robust for depicting a change in contrast in those tissues that
containless than 50% lipid. For example, the adrenal adenoma has
signal intensity of 60 (compared with 100 in the
correspondingin-phase image). The opposed-phase image has twice the
signal loss because the lipid in the adenoma cancels an
equivalentamount of water signal at the echo time of 2.4 msec. On
this sequence the fat within the gland is suppressed so it is
notavailable to oppose water proton signal intensity, even though
it is acquired with an opposed-phase echo time. The normalhigh
signal intensity of the liver and pancreas are readily appreciated
on this image. They have the same signal intensity asthe in-phase
image. However, by suppressing the fat, the dynamic range becomes
improved to show the relative difference inT1-signal intensity
among the various abdominal organs. f: T2-weighted fast spin echo
image (TE 104 msec) shows theright adrenal mass has signal
intensity that it hyperintense to liver and paraspinal muscle and
hypointense relative to spleen.Absolute or relative T2 signal
intensity can not reliably differentiate between adrenal adenomas
and nonadenomas. g: Unen-hanced CT shows that the right adrenal
mass if of low attenuation. It had measurements of 7 Hounsfield
units (HU).
Adrenal MRI Techniques, Clinical Applications 275
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useful in differentiating adrenal adenomas from meta-static
disease (5153).
MR Spectroscopy
There is limited experience with use of MR spectros-copy (MRS)
in the characterization of adrenal masses.Studies have shown that
MRS can differentiate adeno-mas from nonadenomas because the former
has alarger lipid peak (54) with a corresponding
greaterlipid/creatine ratio (55). It is unclear whether MRSimproves
distinction between adrenal adenomas ver-sus nonadenomas compared
with an optimized dualecho gradient echo sequence. One potential
nicheapplication of MRS is in the characterization of adre-nal
pheochromocytoma. Kim et al (56) have shownthat three patients with
surgically proven pheochro-mocytoma had a unique spectral peak at
6.8 ppmthat corresponded with the presence of
intralesionalcatecholamines.
Gadolinium-Enhanced Imaging
Multiphase enhanced CT with delayed imaging can of-ten
differentiate adrenal adenomas from nonadeno-mas. The details of
washout CT kinetics is discussedelsewhere (34,5759). In brief,
adenomas tend to losegreater CT attenuation than nonadenomas on
imagingperformed between 1 and 15 minutes after iodine con-trast
administration. If an unenhanced CT showsattenuation values of less
than 10, then enhancedimaging is not required to establish a
diagnosis of ad-enoma. However, lipid-poor adenomas that
haveunenhanced HU of >10 or do not lose signal intensityon
opposed-phase gradient echo images have similarCT washout
enhancement patterns as lipid richadenomas (60,61). Thus, an
enhanced CT withdelayed imaging could be performed in order to
char-acterize a lipid-poor or lipid-absent adrenal mass as abenign
adenoma.
There has been little published experience concern-ing the
utility of gadolinium-enhanced MRI in thecharacterization of
adrenal masses, and what hasbeen published showed conflicting
results. One studythat evaluated the MR enhancement features of
adre-nal masses found that neither absolute enhancementnor
gadolinium washout kinetics were useful in differ-entiating
adenomas from nonadenomas (19). However,two studies from over 20
years ago showed promisingresults (62,63). I currently do not rely
on the enhance-ment features of an adrenal mass to characterize it
asbenign.
PET/MRI
A description of the use of positron emission tomogra-phy (PET)
and PET/CT in the evaluation of the adre-nal gland is beyond the
purview of this review; thereader is referred to a 2011 meta
analysis by Bolandet al (64). As of this writing some of the first
integratedPET-MRI systems have become available. It is tooearly to
determine whether such hybrid systems willoffer significant
advantages in adrenal gland evalua-tion compared with current
imaging techniques (65).
MANAGEMENT OF ADRENAL MASSES
The management of an adrenal mass detected by MRIis influenced
by the clinical history. The following dis-cussions are based on
the two most commonlyencountered clinical settings. The first is
the inciden-tal adrenal lesion. This is defined by the
AmericanCollege of Radiology and others as an adrenal mass(>1
cm) discovered incidentally on cross-sectionalimaging examination
performed for other reasons (6).The second clinical situation is
when one detects anadrenal lesion in a patient with a known
primarymalignancy.
There have been many reviews on the imaging fea-tures,
pathology, and/or management of adrenalincidentalomas by
radiologists (5,6,66,67) endocri-nologists/internists (6870)
surgeons (71,72), andmultidisciplinary panels (73). The management
of thepatient depends on the clinical context in which theadrenal
mass is detected.
Patients With No Known Primary Malignancy
If a patient does not have a known malignancy thenan adrenal
mass discovered at cross-sectional imag-ing will rarely represent
occult metastatic disease. Ina CT study from Rhode Island Hospital
not a singleadrenal malignancy was found among 973 consecu-tive
non-oncologic patients with 1049 adrenal masses.Even among the 14
patients who developed a subse-quent cancer on follow-up imaging,
the initial adrenalmass remained stable (74). In a subpopulation
ofthese patients, 321 adrenal lesions with HU of >10were present
in 290 patients. None of these lesionsthat could not be
characterized as a benign adenomaby CT HU measurement showed growth
or wereshown to be malignant at follow-up imaging.
Thus,radiologists may be justified in stating that there is lit-tle
or no chance of malignancy when encountering anisolated adrenal
mass in a patient without cancer.
The consensus is that tissue sampling or surgicalexcision should
be performed for an adrenal inciden-taloma that measures >4 cm
in order to excludemalignancy (68,69,75). Others suggest excision
onlyfor those lesions >6 cm and either surgery or closefollow-up
in those masses that measure between 4and 6 cm (73). The reason for
having such a lowthreshold for tissue sampling is that the risk of
malig-nancy in adrenal incidentalomas >6 cm is 25%(5,72,73,75).
As the technique of laparoscopic adre-nalectomy has matured,
surgeons have a lowerthreshold for excising suspect adrenal masses
(76). Inone center adrenocortical carcinomas measuring upto 10 cm
were successfully removed with a laparo-scopic approach (77).
Obviously, biopsy or surgerycan be avoided if imaging can
characterize the largeradrenal mass as a benign lesion such as
myelolio-poma (Fig. 3) or cyst (70).
There is still no clear consensus how often patientswith
- Dr. Cawood et al (78) that such recommendationswould result in
potential unnecessary radiation to thepatient along with increased
financial and emotionalcosts. The Italian Association of Clinical
Endocrinolo-gists (AME) (70) posit that there is insufficient data
toprovide confident recommendations of the frequencyof imaging
follow-up but do state that there is littleutility in performing
imaging following a
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adenomas, aldosterone-producing adrenal adenomas,and
pheochromocytoma.
Pheochromocytoma
Pheochromocytomas are catecholamine-secretingneoplasms. 90% of
pheochromocytomas originatewithin the adrenal medulla and 90% of
adrenal pheo-chromocytomas are benign (79,80). The classic signsand
symptoms of pheochromocytoma are hyperten-sion, along with the
triad of episodic headaches,sweating, and palpitations (81,82).
One-quarter ofpatients with pheochromocytomas will present with
anadrenal incidentaloma and between 1% and 15% of ad-renal
incidentalomas will be secondary to pheochromo-cytoma
(70,79,80,83,84). The clinical findings of pheo-chromocytoma are
nonspecific and sporadic. Manypatients with pheochromocytoma, like
President Eisen-hower, are only found to have the tumor at
autopsy(81,85). In one autopsy series of 54 patients with
pheo-chromocytoma, the diagnosis was unexpected in 75%yet felt to
contribute to patient mortality in over half(86). Because
pheochromocytoma has been called thegreat masquerader (86) and the
great mimic (82)endocrinologists suggest that all patients who
are
found to have an adrenal mass should be screenedwith 24-hour
urine metanephrines in order to excludethe presence of excess
catecholamine production(68,70).
Patients with specific heritable syndromes are athigher risk of
developing pheochromocytoma. Thesesyndromes include von Hippel
Landau (VHL), type 1neurofibromatosis, multiple endocrine neoplasia
type2 (MEN2), and subtypes of the paraganglioma syn-dromes (87). Up
to 25% of patients with sporadic phe-ochromocytoma contain germline
mutations at genetictesting (88). The genetics and clinical
manifestationsof these conditions are beyond the purview of this
ar-ticle but are referenced for those with interest (87,89).
As adrenal pheochromocytoma is derived from theadrenal medulla
and not the cholesterol-rich adrenalcortex, pheochromocytomas do
not lose signal inten-sity on chemical shift imaging and almost all
have HUof >10 (20,84,90) (Fig. 4ad). Pheochromocytomasthat
contains lipid are rare and reportable (91). Thus,while it may be
difficult or impossible for radiologiststo distinguish between
hyperfunctioning and nonhy-perfunctioning adrenal adenoma, I think
it is reasona-ble to state that a pheochromocytoma can beexcluded
with high confidence when an unenhanced
Figure 3. MR illustration on an asymptomatic left adrenal
myeloliopoma in a 71-year-old woman. a: In-phase T1-weighted
gra-dient echo image (TR 159 msec, TE 4.6 msec) shows a
heterogeneous left abdominal mass that has components that
aremostly hyperintense relative to liver. b: Corresponding
opposed-phase T1 weighted image (TE 2.3 msec) shows internal loss
ofsignal intensity (arrows) within some of the intratumoral foci
where adipocytes and nonadipocytes are within the same
voxel.Etching artifact (double arrows) around an oval component
within the anterior portion of the mass indicates a fatwater
inter-face. As the surrounding tissue follows the signal intensity
of mesenteric and subcutaneous fat, one could conclude that this
isalso composed of fat. c: Fat-suppressed T1-weighted gradient echo
image obtained as a 3D technique (TR 4.0, TE 1.8 msec,flip angle
10) shows signal loss both within the anterior and posterior
portions of the mass. This confirms the presence ofmacroscopic fat.
Other pulse sequences confirmed that this mass was originating from
the adrenal gland. An exophytic leftupper pole angiomyolipoma or
left retroperitoneal well-differentiated liposarcoma could have a
similar appearance (123125). d:Corresponding unenhanced CT scan
also shows the presence of macroscopic fat within the mass.
278 Siegelman
-
CT or chemical shift MR establishes the presence oflipid within
an adrenal lesion.
Other MRI features of pheochromocytomas are highT2 signal
intensity relative to skeletal muscle andoccasional T2 signal
intensity approaching that of cer-ebral spinal fluid (CSF) (Fig.
4e) (90). One wouldexpect true isointensity to CSF to occur focally
withinthe less common cystic pheochromocytoma (92) orthose larger
lesions that have cystic necrosis (93). Ondynamic enhanced MR and
CT, pheochromocytomastypically hyperenhance compared with
adenomas(90,93). CT washout kinetics should not be used toexclude a
pheochromocytoma as there can be overlapwith adenomas (94).
Hyperfunctioning Adrenal Cortical Neoplasms
Cortisol-Producing Adrenal Neoplasms
Cortisol-producing adrenal adenoma. Two-thirds ofpatients with
Cushing syndrome are secondary to
ACTH producing pituitary adenomas (Cushing dis-ease) (9597). In
patients with Cushing disease theadrenal glands typically are
enlarged bilaterally andmaintain their adreniform shape. Twenty
percent ofcases of Cushing syndrome are secondary to
cortisolproduction by the adrenal glands (96). Most of theseadrenal
lesions are cortisol-producing adenomas andfewer will be from
adrenal cortical carcinoma. In onereview of three case series 12%
of adrenal incidentalo-mas were found to be cortisol-producing
adenomas(70), while the group from Rhode Island Hospital foundonly
one cortisol-producing adenoma among 1049 con-secutive adrenal
incidentalomas (74). The size andamount of lipid within an adrenal
adenoma does notdifferentiate hyperfunctioning from
nonhyperfunction-ing lesions (98). However, a specific imaging
feature isrelative atrophy of the remainder of the ipsilateral
ad-renal and contralateral adrenal glands (95,99).
The various endocrine tests to evaluate for Cushingsyndrome is
beyond the scope of this review but is
Figure 4. CT and MRI fea-tures of a pheochromocy-toma in a
61-year-oldwoman with hypertension.a: Unenhanced CT examshows a
left adrenal massthat measured 20 Houns-field units. Thus the
lesioncan not be characterized asan adenoma. bd: In-phase(b),
opposed-phase (c), andcorresponding subtractionimage (d) shows a
low sig-nal intensity adrenal lesionon in-phase imaging thatdoes
not show signal losson opposed-phased imagingand no corresponding
sig-nal on the subtractionimage. e: Fat-suppressedrespiratory
triggered T2-weighted image shows thatthe adrenal mass has
het-erogeneous signal intensityand is hyperintense relativeto
spleen. These are sug-gestive but not diagnosticimaging features of
pheo-chromocytoma. The patienthad a confirmatory 24-hoururine
metanephrine test.
Adrenal MRI Techniques, Clinical Applications 279
-
detailed elsewhere (96). Common signs and symptomsof Cushing
syndrome include central obesity, hyper-tension, diabetes, and
depression (69). Cushing syn-drome and metabolic syndrome share
several clinicalfeatures (100). In one case series, patients with
bothmetabolic syndrome and an adrenal incidentalomabenefited from
adrenalectomy (101). It is hypothesizedthat these patients had
subclinical Cushing syn-drome. One should suggest a diagnosis of
subclinicalCushing syndrome in patients with an adrenal ade-noma
who have coexistent obesity, hypertension,and hepatic steatosis.
The latter is readily depictedon chemical shift imaging and is
associated withboth Cushing syndrome and metabolic
syndrome(102,103).
Cortisol-producing adrenal cortical carcinoma. Adrenalcortical
carcinomas are rare, with an annual inci-dence of 12 per million
(104,105). In a series of4027 adrenal cortical carcinomas in 3982
patientsthe median size was 13 cm, with an interquartilerange of 8
to 29 cm (105). In another series of 725 ad-renal cortical
carcinomas less than 5% of tumors wereless than 6 cm in size.
Adrenal cortical carcinomascan be either hyperfunctioning (60%) or
nonhyper-functioning (40%). Nonhyperfunctioning tumors tendto
present when they are of a larger size, similar toretroperitoneal
sarcomas. Signs and symptoms arerelated to local mass effect.
Hyperfunctioning tumorsmay present with signs and symptoms of
Cushingsyndrome or virilization due to androgen secretion(106).
The MRI features of adrenal cortical carcinomashave been
reported in small series. Cross-sectional
imaging features include large size, ill-define margins,and
internal heterogeneity (107). As these carcinomasare derived from
the adrenal cortex, chemical shiftMR can reveal intracellular lipid
within portions ofthese tumors (Fig. 5) (108,109) The presence of
tumorthrombus in the inferior vena cava through spreadfrom the
adrenal veins can help to differentiate adre-nal cortical
carcinomas from metastatic disease(41,110). Clinically, when one
encounters an adrenalmass that has heterogeneous loss of signal
intensityon opposed-phase imaging, the most likely diagnosisis a
benign adrenal cortical adenoma composed ofboth lipid-rich and
lipid-poor adrenal cortical cells(14). However, if the size is
>4 cm, the outer marginsare ill defined, or if there is thrombus
present in theadjacent adrenal vein, renal vein or IVC, the
massshould be considered an adrenal cortical carcinoma
Aldosterone-producing adrenal adenoma
Primary aldosteronism (PA) is a form of secondaryhypertension
that is secondary to increased aldoste-rone production independent
of the renin-angiotensinaxis (111). In the older literature it was
postulatedthat 1% of patients with hypertension may have
PA.However, with the implementation of a more sensitivescreening
test (plasma aldosterone / plasma renin ac-tivity [PRA] ratio
[abbreviated ARR]) and the realiza-tion that only a minority of
patients with PA have hy-pokalemia, it is now estimated that up to
12% ofpatients with hypertension may be secondary to
PA(111,112).
There are two forms of PA: single aldosterone-pro-ducing
adenomas and bilateral adrenal hyperplasia.
Figure 5. MR illustration ofan adrenal cortical carci-noma in an
87-year-oldwoman. a: Coronal fast spinecho T2-weighted imageshows a
large left retroperi-toneal mass. bd: In-phase(b), opposed-phase
(c), andsubtraction image (d) showsheterogeneous signal inten-sity
mass on in-phase imag-ing that shows subtle signalloss on
opposed-phasedimaging that is confirmedas positive signal
(arrows)on the corresponding sub-traction image. The patienthad
pathology-proven meta-static adrenal cortical carci-noma. As this
malignancy isderived from the adrenalcortex, it can show
thepresence of lipid on chemi-cal shift imaging.
280 Siegelman
-
Patients with a single hypersecreting aldosterone-pro-ducing
adenoma benefit from adrenalectomy, whilepatients with bilateral
hyperplasia are treated medi-cally. Similar to cortisol-producing
adenomas, theMRI features of aldosterone-producing adenomas arenot
specific in terms of size or lipid content. Atrophyof the
contralateral adrenal gland can suggest thepresence of adenoma
hypersecretion. Conversely,thickening of the limbs of the bilateral
adrenal glandscan suggest a diagnosis of hyperplasia (113).
As Drs. Cicala and Mantero discuss (111), oneshould not hesitate
to perform a laparoscopic adre-nalectomy in a young woman with
hypertension, hy-pokalemia, and an abnormal elevated ARR.
However,with the prevalence of adenomas on cross-sectioningimaging
being as high as 3% in individuals in their5th decade and 10% in
their 8th decade (73,83), olderhypertensive patients should have a
confirmatory hor-monal test prior to adrenalectomy. One
procedurethat radiologists can perform to confirm a hyperfunc-
tioning lesion is adrenal vein sampling; increased se-rum
aldosterone should lateralize to the side that hasthe adenoma
(114).
In one study of 11 hypertensive patients with
primaryaldosteronism and single adenomas, the adrenal
veinaldosterone hypersecretion was ipsilateral to the ade-noma in
eight, contralateral in two, and symmetricin one. All 10 patients
who underwent adrenalectomy(the ipsilateral adrenal in eight and
the contralateral ad-renal gland in two) improved clinically (115).
In a muchlarger series of 950 patients with primary
aldosteronism,15% would have had unnecessary adrenalectomy, 4%would
have had the wrong adrenal gland removed, and19% of patients would
have been deprived of adrenalec-tomy if the decision to perform or
not perform adrenalec-tomy was based on the CT and MR findings
without con-firmatory adrenal vein sampling. One review
suggestslimiting the use of cross-sectioning imaging to exclude
ahyperfunctioning adrenal cortical carcinoma as the etio-logy of
the hypertension (111).
Figure 6. MR and CT imaging of growth of an adrenal metastases
in a 58-year-old woman with bronchogenic carcinoma. a:Coronal fast
spin echo T2-weighted image shows a left apical bronchogenic
carcinoma and a heterogeneous left adrenal mass(arrow). b,c: In-
and opposed-phase images show no loss of signal intensity within
the left adrenal mass. d: Unenhanced CTexamination performed 4
months later shows marked interval growth. The mass had HU of
30.
Adrenal MRI Techniques, Clinical Applications 281
-
Patients With Known Primary Malignancy
In patients with known primary cancers, differentiat-ing between
an adrenal adenoma and metastatic dis-ease has implications in
terms of treatment, staging,and prognosis. The decision to perform
therapeuticadrenalectomy for known metastatic disease is
con-troversial. The literature suggests that patients whomay
benefit from adrenal metastatectomy should haveisolated metastatic
disease to the adrenal gland fromrenal cell or colon primary tumors
(116,117). Whenpatients with colorectal cancer have prior resection
ofliver metastases, no survival benefit was shown whena subsequent
adrenal metatasis was also removed.
When imaging patients with primary malignanciesand metastatic
disease to the adrenal gland, addi-tional sites of metastatic
disease are often depictedconcurrently (Fig. 2). Metastatic disease
to the adrenalgland differs from adenomas in many respects.
First,most adrenal adenomas lose signal intensity on chemi-cal
shift imaging, where it is only the rare metastaticlipid-containing
hepatocellular carcinoma or metastaticclear cell renal cell
carcinoma that contains lipid. Sec-ond, metastatic lesions of the
adrenal gland grow fasterthan adrenal adenomas (Fig. 6). Most
adenomas willstay the same size when followed by imaging and 20%may
grow by 12 cm over a 3-year period (70,118).There is less data on
the growth rate of adrenal metas-tases in part because patients die
before mid- andlong-term follow-up imaging is performed. However,
itcan be assumed that most metastatic foci will showsignificant
growth at 6 months follow-up, while almostall adenomas will show
minimal or no growth (5,119).Third, patients with metastatic
disease often have theprimary malignancy (Fig. 6) and other sites
of meta-static disease (Fig. 2) depicted on imaging. In a studyfrom
MD Anderson of 1639 patients who presentedwith metastatic disease
of unknown primary, only four(0.2%) presented with isolated
metastatic disease tothe adrenal gland. The metastases were
bilateral inthree and each of the four patients had an adrenalmass
that was larger than 6 cm. The characterizationof these adrenal
lesions should not create a diagnosticdilemma. Finally, size does
matter. On average, meta-static adrenal lesions are larger than
adenomas. In twostudies that compared the imaging features of
61adenomas with 42 adrenal metastases the latter hadan average size
range of 4.55.0 cm, while the formerbenign adenomas had an average
size range of 1.92.4cm (53,120). Some oncologic patients may still
haveindeterminate adrenal masses that cannot be catego-rized based
on current and/or prior imaging. If clinicalmanagement requires
adrenal mass categorization, onecould perform an image-guided
biopsy to establish thepresence of metastatic disease
(121,122).
CONCLUSION
I leave you with three take-home messages concerningMRI of the
adrenal gland.
1. If an adrenal lesion losses signal intensity on
anopposed-phase image when compared with an
in-phase image, the lesion contains intracellularlipid and is
likely an adrenal adenoma. Chemicalshift imaging cannot establish
whether an adre-nal mass is hyperfunctioning or not.
Radiologistsshould familiarize themselves with the signs,symptoms,
and evaluation of hyperfunctioningadrenal lesions so we can
eliminate the wordsclinical correlation is suggested from our
imag-ing reports.
2. In patients with no known primary malignancy,an incidental
adrenal lesion that does notcontain lipid on chemical shift imaging
is notoccult metastatic disease. Those adrenal lesionsthat do not
lose signal intensity are mostlikely to represent lipid-poor
adenomas or apheochromocytoma.
3. Adrenal metastases are not uncommon inpatients with primary
malignancies. Intervalgrowth of adrenal metastases, larger size,
andfindings of other sites of metastatic disease areoften present.
Aggressively searching for anyprior cross-sectional imaging to
establish growthis always preferable to suggesting a
follow-upimaging exam or tissue sampling in order to es-tablish a
diagnosis. The former strategy is cost-effective, minimizes
uncertainty for the patient,the patients family and healthcare
providers,and should be considered an obligation for thoseof us
involved in the performance and interpreta-tion of diagnostic
imaging.
REFERENCES
1. Blake MA, Cronin CG, Boland GW. Adrenal imaging. AJR Am
JRoentgenol 2010;194:14501460.
2. Boland GW. Adrenal imaging: why, when, what, and how? Part1.
Why and when to image? AJR Am J Roentgenol 2010;195:W377381.
3. Boland GW. Adrenal imaging: why, when, what, and how? Part3.
The algorithmic approach to definitive characterization of
theadrenal incidentaloma. AJR Am J Roentgenol 2011;196:W109111.
4. Boland GW. Adrenal imaging: why, when, what, and how? Part2.
What technique? AJR Am J Roentgenol 2011;196:W15.
5. Boland GW, Blake MA, Hahn PF, Mayo-Smith WW.
Incidentaladrenal lesions: principles, techniques, and algorithms
for imag-ing characterization. Radiology 2008;249:756775.
6. Berland LL, Silverman SG, Gore RM, et al. Managing
incidentalfindings on abdominal CT: white paper of the ACR
incidentalfindings committee. J Am Coll Radiol 2010;7:754773.
7. Merkle EM, Schindera ST. MR imaging of the adrenal
glands:1.5T versus 3T. Magn Reson Imaging Clin N Am 2007;15:365372,
vii.
8. Schindera ST, Soher BJ, Delong DM, Dale BM, Merkle EM.Effect
of echo time pair selection on quantitative analysis for ad-renal
tumor characterization with in-phase and opposed-phaseMR imaging:
initial experience. Radiology 2008;248:140147.
9. Tsushima Y, Dean PB. Characterization of adrenal masses
withchemical shift MR imaging: how to select echo times.
Radiology1995;195:285286.
10. Yamashita Y, Yamamoto H, Namimoto T, Abe Y, Takahashi
M.Phased array breath-hold versus non-breath-hold MR imagingof
focal liver lesions: a prospective comparative study. J MagnReson
Imaging 1997;7:292297.
11. Mitchell DG, Crovello M, Matteucci T, Petersen RO,
MiettinenMM. Benign adrenocortical masses: diagnosis with
chemicalshift MR imaging. Radiology 1992;185:345351.
12. Bilbey JH, McLoughlin RF, Kurkjian PS, et al. MR imaging
ofadrenal masses: value of chemical-shift imaging for
282 Siegelman
-
distinguishing adenomas from other tumors. AJR Am J Roent-genol
1995;164:637642.
13. Fujiyoshi F, Nakajo M, Fukukura Y, Tsuchimochi S.
Characteri-zation of adrenal tumors by chemical shift fast
low-angle shotMR imaging: comparison of four methods of
quantitative evalua-tion. AJR Am J Roentgenol
2003;180:16491657.
14. Gabriel H, Pizzitola V, McComb EN, Wiley E, Miller FH.
Adrenallesions with heterogeneous suppression on chemical shift
imag-ing: clinical implications. J Magn Reson Imaging
2004;19:308316.
15. Haider MA, Ghai S, Jhaveri K, Lockwood G. Chemical shift
MRimaging of hyperattenuating (>10 HU) adrenal masses: does
itstill have a role? Radiology 2004;231:711716.
16. Israel GM, Korobkin M, Wang C, Hecht EN, Krinsky GA.
Com-parison of unenhanced CT and chemical shift MRI in
evaluatinglipid-rich adrenal adenomas. AJR Am J Roentgenol
2004;183:215219.
17. Jhaveri KS, Wong F, Ghai S, Haider MA. Comparison of CT
his-togram analysis and chemical shift MRI in the
characterizationof indeterminate adrenal nodules. AJR Am J
Roentgenol 2006;187:13031308.
18. Korobkin M, Giordano TJ, Brodeur FJ, et al. Adrenal
adenomas:relationship between histologic lipid and CT and MR
findings.Radiology 1996;200:743747.
19. Korobkin M, Lombardi TJ, Aisen AM, et al. Characterization
ofadrenal masses with chemical shift and gadolinium-enhancedMR
imaging. Radiology 1995;197:411418.
20. Namimoto T, Yamashita Y, Mitsuzaki K, et al. Adrenal
masses:quantification of fat content with double-echo chemical
shift in-phase and opposed-phase FLASH MR images for
differentiationof adrenal adenomas. Radiology 2001;218:642646.
21. Outwater EK, Siegelman ES, Huang AB, Birnbaum BA.
Adrenalmasses: correlation between CT attenuation value and
chemicalshift ratio at MR imaging with in-phase and
opposed-phasesequences. Radiology 1996;200:749752.
22. Outwater EK, Siegelman ES, Radecki PD, Piccoli CW,
MitchellDG. Distinction between benign and malignant adrenal
masses:value of T1-weighted chemical-shift MR imaging. AJR Am
JRoentgenol 1995;165:579583.
23. Rescinito G, Zandrino F, Cittadini G Jr, Santacroce E,
GiasottoV, Neumaier CE. Characterization of adrenal adenomas and
me-tastases: correlation between unenhanced computed tomogra-phy
and chemical shift magnetic resonance imaging. ActaRadiol
2006;47:7176.
24. Savci G, Yazici Z, Sahin N, Akgoz S, Tuncel E. Value of
chemicalshift subtraction MRI in characterization of adrenal
masses.AJR Am J Roentgenol 2006;186:130135.
25. Halefoglu AM, Yasar A, Bas N, Ozel A, Erturk SM, Basak
M.Comparison of computed tomography histogram analysis
andchemical-shift magnetic resonance imaging for adrenal
masscharacterization. Acta Radiol 2009;50:10711079.
26. Basaran C, Karcaaltincaba M, Akata D, et al.
Fat-containinglesions of the liver: cross-sectional imaging
findings withemphasis on MRI. AJR Am J Roentgenol
2005;184:11031110.
27. Martin J, Sentis M, Zidan A, et al. Fatty metamorphosis of
hepa-tocellular carcinoma: detection with chemical shift
gradient-echo MR imaging. Radiology 1995;195:125130.
28. Outwater EK, Bhatia M, Siegelman ES, Burke MA, Mitchell
DG.Lipid in renal clear cell carcinoma: detection on
opposed-phasegradient-echo MR images. Radiology
1997;205:103107.
29. Sydow BD, Rosen MA, Siegelman ES. Intracellular lipidwithin
metastatic hepatocellular carcinoma of the adrenalgland: a
potential diagnostic pitfall of chemical shift imagingof the
adrenal gland. AJR Am J Roentgenol 2006;187:W550551.
30. Kreft B, Zhou H, Albers P. [Adrenal gland metastasis of
clear-cell renal cell carcinoma: a diagnostic problem in
chemical-shiftMRT imaging.] Rofo 2003;175:12751277.
31. Shinozaki K, Yoshimitsu K, Honda H, et al. Metastatic
adrenaltumor from clear-cell renal cell carcinoma: a pitfall of
chemicalshift MR imaging. Abdom Imaging 2001;26:439442.
32. Ho LM, Paulson EK, Brady MJ, Wong TZ, Schindera ST.
Lipid-poor adenomas on unenhanced CT: does histogram
analysisincrease sensitivity compared with a mean attenuation
thresh-old? AJR Am J Roentgenol 2008;191:234238.
33. Johnson PT, Horton KM, Fishman EK. Adrenal imaging
withmultidetector CT: evidence-based protocol optimization and
in-terpretative practice. Radiographics 2009;29:13191331.
34. Kamiyama T, Fukukura Y, Yoneyama T, Takumi K, Nakajo
M.Distinguishing adrenal adenomas from nonadenomas: combineduse of
diagnostic parameters of unenhanced and short 5-minutedynamic
enhanced CT protocol. Radiology 2009;250:474481.
35. Perri M, Erba P, Volterrani D, et al. Adrenal masses in
patientswith cancer: PET/CT characterization with combined CT
histo-gram and standardized uptake value PET analysis. AJR Am
JRoentgenol 2011;197:209216.
36. Cyran KM, Kenney PJ, Memel DS, Yacoub I. Adrenal
myeloli-poma. AJR Am J Roentgenol 1996;166:395400.
37. Kenney PJ, Wagner BJ, Rao P, Heffess CS. Myelolipoma: CT
andpathologic features. Radiology 1998;208:8795.
38. Pereira JM, Sirlin CB, Pinto PS, Casola G. CT and MR imaging
ofextrahepatic fatty masses of the abdomen and pelvis:
techniques,diagnosis, differential diagnosis, and pitfalls.
Radiographics2005;25:6985.
39. Rao P, Kenney PJ,Wagner BJ, Davidson AJ. Imaging and
pathologicfeatures of myelolipoma. Radiographics
1997;17:13731385.
40. Hood MN, Ho VB, Smirniotopoulos JG, Szumowski J.
Chemicalshift: the artifact and clinical tool revisited.
Radiographics 1999;19:357371.
41. Elsayes KM, Mukundan G, Narra VR, et al. Adrenal masses:
MRimaging features with pathologic correlation.
Radiographics2004;24(Suppl)1:S7386.
42. Krebs TL, Wagner BJ. MR imaging of the adrenal
gland:radiologic-pathologic correlation. Radiographics
1998;18:14251440.
43. Bazot M, Boudghene F, Billieres P, Antoine J, Uzan S, Bigot
J.Value of fat-suppression gradient-echo MR imaging in the
diag-nosis of ovarian cystic teratomas. Clin Imaging
2000;24:146153.
44. Outwater EK, Blasbalg R, Siegelman ES, Vala M. Detection
oflipid in abdominal tissues with opposed-phase gradient-echoimages
at 1.5 T: techniques and diagnostic importance. Radio-graphics
1998;18:14651480.
45. Siegelman ES, Outwater EK, Vinitski S, Mitchell DG. Fat
sup-pression by saturation/opposed-phase hybrid technique: spinecho
versus gradient echo imaging. Magn Reson Imaging
1995;13:545548.
46. Baker ME, Blinder R, Spritzer C, Leight GS, Herfkens RJ,
Dun-nick NR. MR evaluation of adrenal masses at 1.5 T. AJR Am
JRoentgenol 1989;153:307312.
47. Kier R, McCarthy S. MR characterization of adrenal
masses:field strength and pulse sequence considerations.
Radiology1989;171:671674.
48. Bittencourt LK, Matos C, Coutinho AC Jr.
Diffusion-weightedmagnetic resonance imaging in the upper abdomen:
technicalissues and clinical applications. Magn Reson Imaging Clin
N Am2011;19:111131.
49. Qayyum A. Diffusion-weighted imaging in the abdomen and
pel-vis: concepts and applications. Radiographics
2009;29:17971810.
50. Koh DM, Collins DJ. Diffusion-weighted MRI in the body:
appli-cations and challenges in oncology. AJR Am J Roentgenol
2007;188:16221635.
51. Miller FH, Wang Y, McCarthy RJ, et al. Utility of
diffusion-weighted MRI in characterization of adrenal lesions. AJR
Am JRoentgenol 2010;194:W179185.
52. Tsushima Y, Takahashi-Taketomi A, Endo K. Diagnostic
utilityof diffusion-weighted MR imaging and apparent diffusion
coeffi-cient value for the diagnosis of adrenal tumors. J Magn
ResonImaging 2009;29:112117.
53. Sandrasegaran K, Patel AA, Ramaswamy R, et al.
Characteriza-tion of adrenal masses with diffusion-weighted
imaging. AJRAm J Roentgenol 2011;197:132138.
54. Leroy-Willig A, Roucayrol JC, Luton JP, Courtieu J,
NiesenbaumN, Louvel A. In vitro adrenal cortex lesions
characterization byNMR spectroscopy. Magn Reson Imaging
1987;5:339344.
55. Faria JF, Goldman SM, Szejnfeld J, et al. Adrenal masses:
char-acterization with in vivo proton MR spectroscopyinitial
experi-ence. Radiology 2007;245:788797.
56. Kim S, Salibi N, Hardie AD, et al. Characterization of
adrenalpheochromocytoma using respiratory-triggered proton MR
Adrenal MRI Techniques, Clinical Applications 283
-
spectroscopy: initial experience. AJR Am J Roentgenol
2009;192:450454.
57. Sangwaiya MJ, Boland GW, Cronin CG, Blake MA, Halpern
EF,Hahn PF. Incidental adrenal lesions: accuracy of
characteriza-tion with contrast-enhanced washout multidetector
CT10-mi-nute delayed imaging protocol revisited in a large
patientcohort. Radiology 2010;256:504510.
58. Caoili EM, Korobkin M, Francis IR, et al. Adrenal masses:
char-acterization with combined unenhanced and delayed enhancedCT.
Radiology 2002;222:629633.
59. Foti G, Faccioli N, Manfredi R, Mantovani W, Mucelli RP.
Evalu-ation of relative wash-in ratio of adrenal lesions at early
bipha-sic CT. AJR Am J Roentgenol 2010;194:14841491.
60. Pena CS, Boland GW, Hahn PF, Lee MJ, Mueller PR.
Characteri-zation of indeterminate (lipid-poor) adrenal masses: use
ofwashout characteristics at contrast-enhanced CT.
Radiology2000;217:798802.
61. Park BK, Kim CK, Kim B, Lee JH. Comparison of
delayedenhanced CT and chemical shift MR for evaluating
hyperattenu-ating incidental adrenal masses. Radiology
2007;243:760765.
62. Krestin GP, Freidmann G, Fishbach R, Neufang KF, Allolio
B.Evaluation of adrenal masses in oncologic patients:
dynamiccontrast-enhanced MR vs CT. J Comput Assist Tomogr
1991;15:104110.
63. Krestin GP, Steinbrich W, Friedmann G. Adrenal masses:
evalu-ation with fast gradient-echo MR imaging and Gd-DTPA-enhanced
dynamic studies. Radiology 1989;171:675680.
64. Boland GW, Dwamena BA, Jagtiani Sangwaiya M, et al.
Charac-terization of adrenal masses by using FDG PET: a
systematicreview and meta-analysis of diagnostic test performance.
Radi-ology 2011;259:117126.
65. Wehrl HF, Sauter AW, Judenhofer MS, Pichler BJ.
CombinedPET/MR imagingtechnology and applications. Technol
CancerRes Treat 2010;9:520.
66. Dunnick NR, Korobkin M. Imaging of adrenal
incidentalomas:current status. AJR Am J Roentgenol
2002;179:559568.
67. Siegelman ES. MR imaging of the adrenal neoplasms. MagnReson
Imaging Clin N Am 2000;8:769786.
68. Terzolo M, Bovio S, Pia A, Reimondo G, Angeli A.
Managementof adrenal incidentaloma. Best Pract Res Clin Endocrinol
Metab2009;23:233243.
69. Young WF Jr. Clinical practice. The incidentally discovered
adre-nal mass. N Engl J Med 2007;356:601610.
70. Terzolo M, Stigliano A, Chiodini I, et al. AME position
statementon adrenal incidentaloma. Eur J Endocrinol
2011;164:851870.
71. Shen WT, Sturgeon C, Duh QY. From incidentaloma to
adreno-cortical carcinoma: the surgical management of adrenal
tumors.J Surg Oncol 2005;89:186192.
72. ONeill CJ, Spence A, Logan B, et al. Adrenal
incidentalomas:risk of adrenocortical carcinoma and clinical
outcomes. J SurgOncol 2010;102:450453.
73. Grumbach MM, Biller BM, Braunstein GD, et al. Management
ofthe clinically inapparent adrenal mass (incidentaloma). AnnIntern
Med 2003;138:424429.
74. Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adre-nal
mass on CT: prevalence of adrenal disease in 1,049 consec-utive
adrenal masses in patients with no known malignancy.AJR Am J
Roentgenol 2008;190:11631168.
75. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal
inci-dentaloma in Italy. Study Group on Adrenal Tumors of the
Ital-ian Society of Endocrinology. J Clin Endocrinol Metab
2000;85:637644.
76. Mazzaglia PJ, Vezeridis MP. Laparoscopic adrenalectomy:
bal-ancing the operative indications with the technical advances.
JSurg Oncol 2010;101:739744.
77. Brix D, Allolio B, Fenske W, et al. Laparoscopic versus open
ad-renalectomy for adrenocortical carcinoma: surgical and
onco-logic outcome in 152 patients. Eur Urol 2010;58:609615.
78. Cawood TJ, Hunt PJ, OShea D, Cole D, Soule S.
Recommendedevaluation of adrenal incidentalomas is costly, has high
false-positive rates and confers a risk of fatal cancer that is
similar tothe risk of the adrenal lesion becoming malignant; time
for arethink? Eur J Endocrinol 2009;161:513527.
79. Lenders JW, Eisenhofer G, Mannelli M, Pacak K.
Phaeochromo-cytoma. Lancet 2005;366:665675.
80. Plouin PF, Amar L, Lepoutre C. Phaeochromocytomas and
func-tional paragangliomas: clinical management. Best Pract ResClin
Endocrinol Metab 2010;24:933941.
81. Manger WM. An overview of pheochromocytoma: history,
cur-rent concepts, vagaries, and diagnostic challenges. Ann N YAcad
Sci 2006;1073:120.
82. Cohen DL, Fraker D, Townsend RR. Lack of symptoms inpatients
with histologic evidence of pheochromocytoma: a diag-nostic
challenge. Ann N Y Acad Sci 2006;1073:4751.
83. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y,
BornsteinSR. The clinically inapparent adrenal mass: update in
diagnosisand management. Endocr Rev 2004;25:309340.
84. Kasperlik-Zaluska AA, Roslonowska E, Slowinska-Srzednicka
J,et al. 1,111 patients with adrenal incidentalomas observed at
asingle endocrinological center: incidence of chromaffin tumors.Ann
N Y Acad Sci 2006;1073:3846.
85. Messerli FH, Loughlin KR, Messerli AW, Welch WR. The
presi-dent and the pheochromocytoma. Am J Cardiol
2007;99:13251329.
86. Sutton MG, Sheps SG, Lie JT. Prevalence of clinically
unsus-pected pheochromocytoma. Review of a 50-year autopsy
series.Mayo Clin Proc 1981;56:354360.
87. Opocher G, Schiavi F. Genetics of pheochromocytomas and
par-agangliomas. Best Pract Res Clin Endocrinol Metab
2010;24:943956.
88. Neumann HP, Bausch B, McWhinney SR, et al. Germ-line
muta-tions in nonsyndromic pheochromocytoma. N Engl J Med
2002;346:14591466.
89. Barontini M, Dahia PL. VHL disease. Best Pract Res Clin
Endo-crinol Metab 2010;24:401413.
90. Elsayes KM, Menias CO, Siegel CL, Narra VR, Kanaan Y,
Hus-sain HK. Magnetic resonance characterization of
pheochromocy-tomas in the abdomen and pelvis: imaging findings in
18surgically proven cases. J Comput Assist Tomogr
2010;34:548553.
91. Blake MA, Krishnamoorthy SK, Boland GW, et al.
Low-densitypheochromocytoma on CT: a mimicker of adrenal
adenoma.AJR Am J Roentgenol 2003;181:16631668.
92. Lee TH, Slywotzky CM, Lavelle MT, Garcia RA. Cystic
pheochro-mocytoma. Radiographics 2002;22:935940.
93. Blake MA, Kalra MK, Maher MM, et al. Pheochromocytoma:an
imaging chameleon. Radiographics 2004;24(Suppl 1):S8799.
94. Park BK, Kim CK, Kwon GY, Kim JH. Re-evaluation of
pheo-chromocytomas on delayed contrast-enhanced CT:
washoutenhancement and other imaging features. Eur Radiol
2007;17:28042809.
95. Choyke PL, Doppman JL. Case 18: adrenocorticotropic
hormone-dependent Cushing syndrome. Radiology 2000;214:195198.
96. Newell-Price J. Diagnosis/differential diagnosis of
Cushingssyndrome: a review of best practice. Best Pract Res Clin
Endo-crinol Metab 2009;23(Suppl 1):S514.
97. Orth DN. Cushings syndrome. N Engl J Med 1995;332:791803.98.
Ichiyanagi O, Sasagawa I, Izumi T, et al. Relationship between
clear cell/compact cell ratio and computed tomographic
attenu-ation number in adrenocortical adenoma. Int Urol
Nephrol1999;31:585590.
99. Choyke PL. Commentary on Computed tomography in the
diag-nosis of adrenal disease and Nonfunctioning adrenal
masses:incidental discovery on computed tomography. AJR Am
JRoentgenol 2009;192:568570.
100. Krikorian A, Khan M. Is metabolic syndrome a mild form of
Cush-ings syndrome? Rev Endocr Metab Disord 2010;11:141145.
101. Chiodini I, Morelli V, Salcuni AS, et al. Beneficial
metaboliceffects of prompt surgical treatment in patients with an
adrenalincidentaloma causing biochemical hypercortisolism. J
ClinEndocrinol Metab 2010;95:27362745.
102. Law K, Brunt EM. Nonalcoholic fatty liver disease. Clin
Liver Dis2010;14:591604.
103. Rockall AG, Sohaib SA, Evans D, et al. Hepatic steatosis
inCushings syndrome: a radiological assessment using
computedtomography. Eur J Endocrinol 2003;149:543548.
104. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent
ofdisease at presentation and outcome for adrenocortical
carci-noma: have we made progress? World J Surg 2006;30:872878.
284 Siegelman
-
105. Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical
carci-noma in the United States: treatment utilization and
prognosticfactors. Cancer 2008;113:31303136.
106. Fassnacht M, Allolio B. Clinical management of
adrenocortical car-cinoma. Best Pract Res Clin Endocrinol Metab
2009;23:273289.
107. Bharwani N, Rockall AG, Sahdev A, et al. Adrenocortical
carci-noma: the range of appearances on CT and MRI. AJR Am
JRoentgenol 2011;196:W706714.
108. Schlund JF, Kenney PJ, Brown ED, Ascher SM, Brown
JJ,Semelka RC. Adrenocortical carcinoma: MR imaging appearancewith
current techniques. J Magn Reson Imaging 1995;5:171174.
109. Mackay B, el-Naggar A, Ordonez NG. Ultrastructure of
adrenalcortical carcinoma. Ultrastruct Pathol 1994;18:181190.
110. Chiche L, Dousset B, Kieffer E, Chapuis Y. Adrenocortical
carci-noma extending into the inferior vena cava: presentation of
a15-patient series and review of the literature. Surgery
2006;139:1527.
111. Cicala MV, Mantero F. Primary aldosteronism: what
consensusfor the diagnosis. Best Pract Res Clin Endocrinol Metab
2010;24:915921.
112. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis
ofprimary aldosteronism, including surgically correctable forms,in
centers from five continents. J Clin Endocrinol Metab
2004;89:10451050.
113. Lingam RK, Sohaib SA, Vlahos I, et al. CT of primary
hyperal-dosteronism (Conns syndrome): the value of measuring the
ad-renal gland. AJR Am J Roentgenol 2003;181:843849.
114. Kahn SL, Angle JF. Adrenal vein sampling. Tech Vasc
IntervRadiol 2010;13:110125.
115. Schwab CW, 2nd, Vingan H, Fabrizio MD. Usefulness of
adrenalvein sampling in the evaluation of aldosteronism. J
Endourol2008;22:12471250.
116. Muth A, Persson F, Jansson S, Johanson V, Ahlman H,
Wang-berg B. Prognostic factors for survival after surgery for
adrenalmetastasis. Eur J Surg Oncol 2010;36:699704.
117. Mourra N, Hoeffel C, Duvillard P, Guettier C, Flejou JF,
Tiret E.Adrenalectomy for clinically isolated metastasis from
colorectalcarcinoma: report of eight cases. Dis Colon Rectum
2008;51:18461849.
118. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence
andnatural history of adrenal incidentalomas. Eur J
Endocrinol2003;149:273285.
119. Pantalone KM, Gopan T, Remer EM, et al. Change in
adrenalmass size as a predictor of a malignant tumor. Endocr
Pract2010;16:577587.
120. Gufler H, Eichner G, Grossmann A, et al. Differentiation of
adre-nal adenomas from metastases with unenhanced computed
to-mography. J Comput Assist Tomogr 2004;28:818822.
121. Paulsen SD, Nghiem HV, Korobkin M, Caoili EM, Higgins
EJ.Changing role of imaging-guided percutaneous biopsy of
adrenalmasses: evaluation of 50 adrenal biopsies. AJR Am J
Roent-genol 2004;182:10331037.
122. Mazzaglia PJ, Monchik JM. Limited value of adrenal biopsy
inthe evaluation of adrenal neoplasm: a decade of experience.Arch
Surg 2009;144:465470.
123. Craig WD, Fanburg-Smith JC, Henry LR, Guerrero R, BartonJH.
Fat-containing lesions of the retroperitoneum:
radiologic-pathologic correlation. Radiographics
2009;29:261290.
124. Ellingson JJ, Coakley FV, Joe BN, Qayyum A, Westphalen
AC,Yeh BM. Computed tomographic distinction of perirenal
liposar-coma from exophytic angiomyolipoma: a feature analysis
study.J Comput Assist Tomogr 2008;32:548552.
125. Israel GM, Bosniak MA, Slywotzky CM, Rosen RJ. CT
differen-tiation of large exophytic renal angiomyolipomas and
perirenalliposarcomas. AJR Am J Roentgenol 2002;179:769773.
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