ELSEVIER
EJR EUROPEAN JOURNAL OF RADIOLOGY
Imaging of adrenal masses
Mark E. Lockhart *, J. Kevin Smith, Philip J. Kenney
Department of Radiology, University of Alabama at Birmingham, 619 South 19th Street, Birmingham, AL 35249-6830, USA Received 8 October 2001; received in revised form 9 October 2001; accepted 10 October 2001
Abstract
Adrenal pathology may be discussed based on hormonal functionality of the adrenals, appearances on imaging modality, or pathological determination. There are three main categories of adrenal function. Hyperfunctional states include Conn’s or Cushing’s syndrome. Lesions with normal function may be detected incidentally. Hypofunctional states may occur from idiopathic Addison’s disease or some bilateral adrenal pathology. The most common modalities for characterization of adrenal pathology are non-enhanced CT, often followed by contrast CT or chemical shift MRI. The common appearance on non-enhanced CT is a well-defined homogeneous lesion with low-density due to the microscopic fat present and adrenal adenomas. When density criteria are not met, many of these may be characterized as adenomas by washed out of contrast or signal decrease using in phase and out-of-phase MRI sequences. Other non-invasive modalities may incidentally discover adrenal lesions, but are not typically used in the work-up. NP-59 is an uncommonly used nuclear medicine technique which is very specific for adenoma when correlated with pathology on other imaging studies. In the rare cases where non-invasive imaging is non-specific, fine needle aspiration or core biopsies may be necessary. However, biopsies have associated risks including infection and hemorrhage. The imaging appearance of an adrenal lesion is often specific such that further imaging is not necessary. These lesions include adrenal adenoma, pheochromocytoma, myelolipoma, adrenal cyst, and some large adrenocortical carcinomas. However, the findings in lesions such as metastasis, smaller primary adrenal carcinomas, lymphoma, granulomatous disease, and many adenomas are not as specific. In the proper clinical situation, follow-up imaging may be necessary, or biopsy may be warranted. @ 2002 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Adrenal gland, diseases; Adrenal gland, CT; Adrenal gland, US; Adrenal gland, MRI; Adrenal gland, neoplasms
1. Introduction
Computed tomography (CT), MRI, and ultrasound enable physicians to peer into the human body and non-invasively diagnose a wide variety of disease pro- cesses. As these technologies improve, reliance on med- ical imaging techniques increases. Imaging of the adrenals especially benefits from the improved resolu- tion and tissue characterization that new techniques allow. The adrenals are very small organs, and adrenal pathology may often be measured in millimeters. As more and more adrenal lesions are diagnosed, a better understanding of the specific characteristics of many adrenal abnormalities is gained. In many cases, the
imaging diagnosis is definitive, requiring no further evaluation. In less-specific lesions, it is important to understand the clinical settings in which an adrenal lesion demands further evaluation and when expectant follow-up is warranted. This review will discuss the typical characteristics of many adrenal lesions and de- scribe the algorithms and dilemmas that occur when such lesions are detected.
An approach to adrenal imaging begins with knowl- edge of the clinical history surrounding the diagnosis. A large irregular adrenal lesion discovered as an inciden- tal finding has different implications than a small adrenal lesion in a patient with paroxysmal hyperten- sion. Many decision pathways use function as a pri- mary branch point. Adrenal lesions are described in the setting of adrenal hyperfunction, hypofunction, or nor- mal function. Indications for evaluation of adrenal hyperfunction include hormonal abnormalities such as Cushing’s (due to hypersecretion of cortisol), Conn’s
* Corresponding author. Tel .: + 1-205-934-7978; fax: + 1-205-975- 7213.
E-mail address: mlockhar@uabmc.edu (M.E. Lockhart).
syndrome (due to hypersecretion of aldosterone), viril- ization, or feminization. Lesions discovered inciden- tally or in the presence of known malignancy may warrant further evaluation. Hypoadrenalism is often idiopathic, but the patient may benefit from the ex- clusion of treatable etiologies. The most commonly encountered situation is an adrenal nodule in a pa- tient with normal adrenal function. In the past, the evaluation of adrenal lesions required invasive proce- dures such as venous sampling or biopsy. Now, how- ever, most lesions are characterized by CT or MRI. The rest require nuclear medicine studies or biopsy.
2. Overview of imaging techniques
CT is generally the preferred primary modality for evaluation of the adrenal glands. CT is fast, readily available, and offers the highest spatial resolution. Helical scanning, using 3-5 mm thick slices to reduce volume averaging, improves the accuracy of density measurement of small adrenal lesions. Contrasted CT and delayed images help characterize enhancement and vessels in the region of the adrenal. Unenhanced CT, however, is often the key series in the evaluation of ‘incidentalomas’ or potential adenomas.
MRI adds an additional means to evaluate adrenal lesions and specifically diagnose adrenal adenoma. MRI has the best contrast resolution for adrenal evaluation. The spatial resolution is adequate for de- tection of lesions as small as 0.5-1.0 cm. MRI adrenal studies should include T1-weighted axial im- ages for anatomic detail and T2 weighted axial im- ages. Fat suppression is used so that heavily T2 weighted images are not degraded by chemical shift artifact from the fat which surrounds the adrenals. Contrast helps, in some studies, to characterize en- hancement patterns. Chemical shift imaging also con- tributes to the characterization of small adrenal masses, with adenomas showing decreased signal in opposed-phase images relative to in-phase images. Multi-planar imaging helps detect extension of adrenal masses into adjacent structures.
Ultrasound is inexpensive, detects adrenal lesions, and discriminates cystic from solid lesions. However, ultrasound has low sensitivity for detection of small masses compared with CT or MRI. Sonographic eval- uation poorly characterizes solid adrenal masses, and poorly detects extension into adjacent structures or to exclude distant metastases.
Several available radiotracers add specific informa- tion regarding adrenal lesions. Cholesterol analogs such as NP-59 label adrenal cortical cells and can detect functional adenomas as focal areas of increased uptake. When the uptake corresponds to a lesion on CT or MRI, the diagnosis of adenoma is specific [1].
MIBG has high specificity for pheochromocytomas. However, the technique is expensive, time-consuming, not readily available, and has low sensitivity for le- sions smaller than 2 cm [2]. Due to the low spatial resolution and poor anatomic localization of nuclear imaging, CT is still often necessary for surgical plan- ning. There has been recent success in characteriza- tion of adenomas by PET imaging with glucose analogs [1,3].
Radiographs or conventional catheter angiography are occasionally used to evaluate the adrenals. Radio- graphs can detect adrenal calcifications and lead to further imaging, especially in children. Venous sam- pling is very sensitive for aldosteronoma and was once commonly performed for evaluation of func- tional adenomas [4]. However, the technique is inva- sive and expensive, and now rarely performed. In venous mapping, the right adrenal vein may be difficult to access [5]; a 10-30% failure rate has been reported [6]. Complications of the procedure include adrenal infarction, adrenal hemorrhage, hypotension, adrenal insufficiency or thrombosis of the adrenal vein [7].
3. Normal anatomy and embryology
3.1. Normal appearance and location
The normal adrenal (Fig. 1) may vary in shape but typically has the shape of an arrowhead, inverted Y, inverted V, or triangle with medial and lateral crura. In congenital absence of the kidney, the adrenal may have a discoid shape and appear as a linear structure on CT [8]. The normal adrenal is homogeneous and symmetric in appearance on imaging studies. The nor- mal density of the adrenal on non-contrast CT resem- bles the kidney. The normal signal on MRI is isointense or slightly hypointense to the liver [9]. The normal adrenal body measures less than 10-12 mm and the adrenal limbs normally measure less than 5- 6 mm [6]. The right adrenal is located immediately posterior to the IVC and cephalad to the right kid- ney. The left adrenal lies anteromedial to the upper pole of the left kidney. The adrenals are retroperi- toneal structures and are contained within Gerota’s fascia. The renal fascia surrounds the adrenals, but the adrenals have a transverse fibrous lamella which allows separation of adrenal from kidney during nephrectomy [10]. Fat usually surrounds the glands. In newborns, the adrenals may be large due to a thick fetal cortical zone [11].
3.2. Development
The adrenal cortex develops from proliferation of
mesoderm from a groove in the coelom between the mesonephros and gonad. The adrenal medulla arises from the ectoderm due to migration of neural crest cells into the developing adrenal in its upper lumbar location. Sympathetic ganglia and paraganglia simi- larly develop from this migration of neural crest cell [10].
4. Common adrenal abnormalities
4.1. Adenoma
Non-functional adrenal adenoma is the most com- mon adrenal mass [12]. Approximately, 3-8.7% of hu- mans have adrenal adenomas at autopsy [13-16]. The lesions are often small, round or oval, and smooth with
DV 84.0cm
5
ND/P
MF: 1.
NAx 110/5 (co))
IS A
FCM/ 18.0cm
512X51
TANDARD
May =2.0
FL:
ROT:
3
1
0
/ 140
mA 260
BFC)/50.9am
116
(a)
y
6kHz
(b)
well-defined margins (Fig. 2) [17]. Most adrenal nodules < 3 cm are benign [5], although significant overlap with malignant lesions limits the usefulness of size as a criterion [18]. Calcifications, necrosis, and hemorrhage are atypical, although they do occur, especially in larger lesions [5]. High levels of intracellular lipid within ade- nomas allow characterization of adenomas through the use of density readings on CT or phase cancellation by MRI.
Several criteria have been proposed to differentiate adrenal adenomas from metastases. Density measure- ment on CT without contrast enhancement seems to be the most accurate and reliable [7,19]. Diagnosis of adenoma when the density is < 10 HU has a sensitivity of 74% and specificity of 96% [19].
Since many adrenal lesions are incidentally detected on contrasted CT, enhancement patterns of adrenal lesions have been studied to help obviate the need for a
00
15€
(c)
separate non-contrast CT, which would require imaging on a separate visit. Immediate post-contrast density is variable and non-discriminatory. Several authors have reported high sensitivity and specificity for density readings on delayed post-contrast CT, but varying cut- off values (25-37 HU) and delay times have been used (15-60 min). In one study of 78 lesions, all adenomas had CT <37 HU and all non-adenomas had density >41 HU on 30 min delay after contrast [18]. This yielded a specificity and sensitivity for adenoma of 100 and 100%, respectively. Another recent study showed that no malignant lesions had density of less than 25 HU at a 15 min delay [20]. This allows 100% specificity with only minimal interruption of the patient flow in CT. The same study showed 96% sensitivity and 100% specificity for adenoma using a 40% washout after 15 min delay compared to immediate post-contrast images [20].
Most adrenal adenomas contain large amounts of intracellular lipids. This lipid is the basis for chemical shift imaging. Drop in signal on MRI relative to spleen or liver on chemical shift imaging, which compares in- and opposed-phase GRE images (Fig. 3), is the best MRI technique to discriminate adenoma from non-ade- noma [15]. Chemical shift imaging takes advantage of the different speeds of precession of fat and water protons. For in-phase images, the echo time (TE) is selected to align fat and water signals to be additive (the exact TE is field strength dependent). In opposed phase imaging, the TE is selected so the fat and water signal are opposed 180°, resulting in loss of signal in
pixels which contain a mixture of fat and water pro- tons. The signal of the adrenal is compared to the spleen, rather than the liver, so that infiltration of fat within the liver is not confounding [21]. An adrenal-to- spleen ratio can be calculated as the ratio of lesion intensity relative to spleen on in-phase images divided by the signal ratio of lesion to spleen on opposed-phase images. An adrenal-to-spleen ratio < 0.70 indicates adenoma [22,23]. However, the finding is not com- pletely specific since, rarely, malignant adrenal lesions may have similar drop in signal on opposed phase images [24]. Many of the lesions which do not meet criteria for adenomas still represent benign lesions at biopsy [25]. Some malignant lesions, particularly well differentiated adrenal carcinoma, may also have benign imaging features, but this is uncommon [25].
NP-59, or 1-6B-iodomethyl-19-norcholesterol, scans are extremely accurate for characterizing a lesion as an adrenal cortical adenoma. However, they cannot differ- entiate metastases from other non-adenoma lesions [15].
4.2. Metastasis
Adrenal metastases are found in up to 27% of pa- tients with malignant epithelial tumors at autopsy [26]. Adrenal metastases commonly arise from lung, breast, lymphoma, or melanoma primaries [27]. Metastases (Fig. 4) are typically larger and more heterogeneous than adenomas. The lesion margins may be ill-defined or have a thick enhancing rim on contrasted study [28]. However, small metastases may be homogeneous and
well-defined. When the lesions are small, pre-contrast CT attenuations are <10 HU. When large, central necrotic areas may be less than 10 HU, but thick or nodular periphery is usually present distinguishing these from adenomas. The presence of extra-adrenal metas- tases makes the specific diagnosis of adrenal metastasis less critical. In the setting of extra-adrenal primary malignancy, diagnosis of a solitary metastasis in the adrenal may change the treatment from surgical resec- tion to systemic therapy.
On MRI adrenal metastases have non-specific low T1/high T2 signal characteristics. Unlike adrenal ade- nomas, adrenal metastases do not drop signal on op- posed phase MRI [14]. Hemorrhage is uncommon, but may occur, especially in lung carcinoma or malignant melanoma metastases. Calcifications due to metastases are rare [1].
4.3. Lymphoma
Adrenal involvement occurs in nearly 25% of patients with non-Hodgkin’s lymphoma at autopsy [7], but only approximately 4% of antemortem CT’s in similar pa- tients demonstrate adrenal lesions [29]. In non- Hodgkin’s lymphoma (NHL), adrenal involvement is usually associated with diffuse forms of the disease [29]. On CT, adrenal lymphoma (Fig. 5) appears as single or bilateral homogeneous solid involvement without cal- cifications [7]. The shape of the adrenals may be main- tained [13]. Usually only mild enhancement of the lesions occurs with intravenous contrast. Primary adrenal NHL tends to be cystic and heterogeneous [30]. When primary adrenal NHL is bilateral (50-68% of
cases) [13,30], adrenal insufficiency results in two-thirds of cases [30]. It is the most common cause of adrenal insufficiency due to malignant invasion [31]. The diag- nosis is suggested by the presence of adenopathy else- where in the body [13]; however, other lymph- adenopathy does not need to be present [32,33]. Char- acteristics on MRI are non-specific and may be similar to metastases [34]. There is typically low T1 signal and heterogeneous high T2 signal [33]. An advantage of MRI is the ability to image in multiple planes to determine IVC patency, which may be difficult to confirm, even on an optimized CT [33].
4.4. Pheochromocytoma
Pheochromocytoma is a rare lesion most commonly found in the adrenal medulla [35], but it may arise in the retroperitoneal ganglia, organ of Zuckerkandl, or urinary bladder [9]. Cases may occur in the chest, skull base, vagina, anus, or spermatic cord [35,36]. Clinical symptamotology, such as uncontrolled hypertension, may direct a search for the lesion. Most pheochromocy- tomas are sporadic. However, approximately 10% are associated with syndromes including Von Hippel-Lin- dau, multiple endocrine neoplasia, neurofibromatosis, and tuberous sclerosis [36-38]. Pheochromocytomas in the setting of multiple endocrine neoplasia tend to be smaller than in sporadic cases. Multiplicity is more commonly associated with syndromic lesions [36].
Small pheochromocytomas are often homogeneous, solid masses that typically measure above 10 HU on non-contrast CT. More commonly, they are large [36], with central necrosis [39]. On CT, pheochromocytomas
typically enhance very intensely (Fig. 6). Calcifications occur in approximately 12% of pheochromocytoma [39]. A common anecdotal concern has been the release of catecholamines associated with intravenous contrast injection. Previous studies have shown acute release of catecholamines after ionic contrast [40]. However, there is no association of acute catecholamine elevation with low osmolar contrast agents [41]. On the other hand, biopsy of a pheochromocytoma may result in death from hypertensive crisis.
On MRI, there is characteristic bright T2 signal and bright enhancement of the lesion [7,12]. Enhancement is usually rapid and intense with intravenous contrast [42]. The lesions typically have low or isointense signal relative to the liver on T1 weighted sequences [43]. Central necrosis may be present. MRI and CT are equivalent for detection of primary adrenal pheocho- mocytoma, but MRI is significantly more accurate than CT for extra-adrenal disease [43]. In one study, MRI was 100% sensitive, including detection of an intracar- diac lesion [44]. This compared favorably with other imaging modalities [44]. The specificity was less than MIBG imaging in this series.
Whole body meta-iodobenzylguanidine (MIBG) compounds labeled with radio-iodine, can detect func- tional lesions, and are superior to other studies in the detection of extra-adrenal lesions [43,45]. MIBG can be particularly useful in evaluation of metastases in pa- tients with malignant pheochromocytoma or rare tu- mors in the chest. For patients with suspected pheochromocytoma and negative MIBG, F-18 FDG PET may be useful [5].
4.5. Neuroblastoma
The most common adrenal mass in a young child [5], neuroblastoma usually presents with a palpable abdom- inal mass. Approximately, 66-80% of neuroblastomas are located in the adrenal glands [7,46]. They com- monly contain calcifications, necrosis, or hemorrhage. Calcifications may be visible on conventional radio- graphs, but more are seen by CT (up to 85% of cases) [46]. Evaluation for local tumor extension as well as distant metastasis may be performed by CT or MRI [11]. On MRI there is a typical mixed low T1/high T2 signal appearance with marked heterogeneity within the lesion. For staging of tumor, MRI is considered by some to be superior to CT [47].
Ultrasound is the preferred initial imaging modality due its availability and lack of ionizing radiation to the child. The mass is usually visible, and typically has calcifications and heterogeneity [48]. MIBG is sensitive to neuroblastoma as well as pheochromocytoma.
4.6. Adrenocortical carcinoma
Primary adrenal carcinoma is a rare lesion. It is hyperfunctional in 40-50% of cases [9,15]. Approxi- mately, 57% of functional lesions are associated with Cushing’s syndrome [49]. Virilization or feminization also occur, but hyperaldosteronism rarely occurs.
Approximately, 76% are large (> 6 cm) at presenta- tion (Fig. 7) [49]. Small lesions may be homogeneous on non-enhanced CT, but usually display heteroge- neous peripheral enhancement with contrast CT [49].
Large tumors commonly demonstrate necrosis or hem- orrhage pathologically or on CT [27,49]. Approxi- mately, 30% have calcifications detected by CT [27]. A thin capsular rim may be present which is different than either enhancing tumor or surrounding tissues [49]. The tumor spreads by local extension, lymphatic extension, renal vein extension, or to the liver, lung or bone [7].
MRI allows multi-planar evaluation, and it is best for defining extension of tumor into the IVC [7]. Het- erogeneous T1 and heterogeneous T2 signal on MRI
are due to the presence of hemorrhage and necrosis within the lesion. There is usually peripheral nodular enhancement and central hypoperfusion on contrasted MRI [9]. These lesions may contain focal areas of well differentiated cortical tissue which can contain signifi- cant intracellular lipid, as in benign adenomas, so lim- ited areas of signal drop-out in a large heterogeneous adrenal mass should not prevent biopsy or resection [9].
It should be noted that biologically aggressive adrenal carcinomas can vary in their histologic appear-
(a)
(b)
¥ 36.0cm
NDARD
20
(a)
ance, so that the pathologist may not be able to accu- rately distinguish cortical adenoma from cortical ade- nocarcinoma on a histologic basis alone. This appears more problematic with needle biopsy specimens.
4.7. Hematoma
Adrenal hematomas generally result from trauma, sepsis, hypotension, or anti-coagulation therapy. In newborns, hypoxia, septicemia, birth trauma, and coag- ulopathy are common etiologies [14]. Left sided hemor- rhage may result from left renal vein thrombosis [11]. Patients with coagulopathies are prone to bilateral hemorrhages [50]. When bilateral, adrenal hemorrhage in adults may rarely result in sudden adrenal insuffi- ciency [51].
Adrenal hematomas are often associated with severe trauma, but in some cases it may be the only abdominal finding [52]. Burks et al. report a 2% occurrence of adrenal hemorrhage (Fig. 8) in trauma patients [53]. We have noted adrenal hemorrhage in approximately 0.8% of approximately 6000 trauma patients imaged by CT (Kenney and co-workers, unpublished data). Adrenal hematomas in trauma are usually right sided or bilat- eral [54]. The acute density is 50-90 HU [5], and decreases on follow-up within days to weeks. Acute adrenal hemorrhage is hyperechoic relative to the liver on ultrasound evaluation. The adrenal shape may be preserved despite enlargement of the gland [11]. Se-
quential sonograms can be used to document decrease in size and liquefaction of hematoma if the diagnosis is uncertain. The gland may return to normal appearance or it may calcify within 8-12 weeks [3,55].
The appearance on MRI varies with the age of the blood products. Acute hemorrhage will have intermedi- ate or high T1 signal. Chronic hematoma has non-spe- cific low T1/high T2 appearance or low signal on T1 and T2.
4.8. Myelolipoma
Myelolipomas are usually non-functional unilateral benign lesions with variable mixture of fat and myeloid components [12]. The lesions are usually asymptomatic or present with pain if they hemorrhage [56]. The presence of gross fat on CT (density < - 30 HU) (Fig. 9) is diagnostic [17,56]. Presence of fat on all MRI sequences is also characteristic of myelolipoma [15,57]. The high T1 signal and moderate T2 signal should resemble other fat within the abdomen [58]. Fat-satura- tion techniques may occasionally be helpful. There have been case reports of malignant tumors, including ter- atoma or liposarcoma [57], containing gross fat, but they are rare [9]. Although, there is almost always some region of definite fat on CT or MRI, a myelolipoma may occasionally have predominantly myeloid components.
Myelolipomas may demonstrate flow on Doppler ultrasound, or enhancement on CT or MRI as the myeloid portion is vascular. Focal calcifications may be present in the myelolipomas in up to 24% of cases [5,56]. A pseudocapsule can often be identified between the mass and the adjacent retroperitoneal fat, which represents a thin rim of residual adrenal cortex around the lesion [56]. Hemorrhage occurs more often in males and may occur in large myelolipomas [56]. In cases of myelolipoma complicated by hemorrhage, CT is the most accurate imaging for diagnosis [59]. Rarely extra-
adrenal myelolipomas have been described in the pelvis or retroperitoneal fat [56]. These lesions resemble adrenal myelolipomas, but may be indistinguishable from liposarcoma [59].
4.9. Adrenal hyperplasia
Adrenal cortical hyperplasia may be primary, or secondary to a pituitary or hypothalamic lesion, or ectopic ACTH production. Hyperplasia, which is visi- ble on CT, is most often associated with Cushing’s
(b)
6kH
~
(c)
disease, but may be seen in Conn’s syndrome or adrenogenital syndrome [12]. In patients with hyperal- dosteronism, differentiation of hyperplasia and ade- noma determines whether medical or surgical intervention is indicated [4]. In hyperplasia, the adrenals are enlarged bilaterally but maintain an adreniform shape, usually with smooth surface [11] (Fig. 10). Less often, they may have a normal appear- ance or nodular enlargement [12]. Bilateral nodular adrenals are not specific for hyperplasia. In one series, 25% (5/24) of patients with this appearance had subse-
quent diagnosis of adrenal adenoma [4]. The greatest enlargement of the adrenals in hyperplasia is associated with ectopic ACTH production due to various tumors, such as bronchial carcinoid [60].
5. Uncommon findings
5.1. Adrenal cysts
Adrenal cysts are rare, but imaging findings are often
diagnostic. Approximately, 84% represent either en- dothelial cysts or pseudocysts [13,15]. True cysts (Fig. 11) are characterized by thin non-enhancing walls and fluid attenuation on CT [12,15,61]. They have fluid density, and peripheral calcifications may be seen in 15% [62]. Pseudocysts are usually low density, but they may have thick walls, internal septations, and calcifications [12]. On
CT approximately 54% (20/37) of benign adrenal cysts had calcifications, usually in the cyst wall [61]. Higher density within the cyst may occur due to hemorrhage. A lack of enhancement helps to differentiate adrenal cysts from other adrenal lesions such as adenomas [61].
Simple cysts have the characteristic homogeneous low T1/high T2 signal on MRI that is seen in cysts of
cm D/P
M
V
other organs. An atypical signal may result from protenacious material or blood in the cyst. Pseudo- cysts can be large and complex in appearance on MRI [63], possibly due to hemorrhage. Variable sig- nal intensity on T1- or T2-weighted images may oc- cur with differing stages of heme within the cyst. A complex cyst may be difficult to differentiate from metastasis or other necrotic tumor or abscess [5]. When very large, cysts may be difficult to localize to the adrenal [15]. The multi-planar capability of MRI or ultrasound is beneficial for localizing a large mass to the adrenal [62].
5.2. Granulomatous disease
Granulomatous disease is the second most common cause of chronic adrenal insufficiency in the U.S., af- ter idiopathic Addison’s disease [12]. Granulomatous infections are usually due to tuberculosis or histoplas- mosis. In adrenal tuberculosis, the adrenals are often bilaterally, but asymmetrically, involved [15,17]. When bilateral, adrenal insufficiency may result [15]. The di- agnosis is usually made by biopsy.
In the sub-acute phase, adrenal enlargement with peripheral enhancement is present [64]. Cystic low- density or necrotic changes may be present. Calcifica- tions are usually present later in the disease process [12], occurring in up to 50% of cases secondary to tuberculosis [65]. In diffuse involvement with histo- plasmosis (Fig. 12), the adrenals are also enlarged with peripheral enhancement and central low-density.
The adrenal enlargement may be more symmetric than in tuberculous involvement. Calcifications may be present [64].
5.3. Hemangioma
Hemangioma of the adrenal is a rare, benign lesion which may resemble hemangioma in the liver. Find- ings on CT include peripheral nodular enhancement after contrast, central low attenuation, with or with- out ‘filling-in’ on delayed images (Fig. 13) [9]. Adrenal hemangiomas may be large, measuring up to 15 cm in one case series. Conventional radiographs may demonstrate calcifications in up to 64% (7/11) of adrenal hemangiomas. The calcifications may have a speckled appearance on CT [66]. On MRI, low T1 signal and moderate or high T2 signal are typical. Areas of hemorrhage or necrosis may be visible on T1-weighted images with areas of high signal [67]. There is characteristic peripheral enhancement which may persist on delayed post-contrast images.
5.4. Ganglioneuroma
Ganglioneuroma is a benign neoplasm which arises from the sympathetic ganglia. Only approximately 10% occur in children. Imaging characteristics resem- ble neuroblastoma within the adrenal [12]. The lesions are well-defined homogeneously hypodense adrenal masses which may contain calcifications. Some hetero- geneous enhancement may be present [64].
6. Diagnostic pitfalls
There are several normal structures which may sim- ulate an adrenal mass on CT. Many of these are less common with the recent generations of CT and better techniques, but still may be encountered. In the evaluation of adrenal lesions, oral contrast is impor- tant to prevent misinterpretation of the gastric fundus [68] or a gastric diverticulum as an adrenal lesion. With large masses it may be difficult to differentiate a renal lesion such as cyst or tumor from an adrenal
lesion [68]. Splenic lobulation or tortuous splenic ves- sels may be mistaken for adrenal lesions [68], espe- cially in non-enhanced studies. Contrasted CT can usually address any uncertainty in these cases. Pan- creatic masses occur in the retroperitoneal space and may also simulate adrenal pathology [68,69]. As the imaging technology improves and better spatial reso- lution is obtained, multi-planar reconstruction of im- ages of the adrenals may further reduce potential misinterpretation of normal structures for adrenal pathology.
167.0 (ci)
12:05
36.0cm
DARD N
A
512
Mag
7
F
A
(a)
7. Discussion
At our institution CT is the cornerstone of adrenal imaging since it is readily available, rapidly performed, has good sensitivity for detecting adrenal lesions, and has excellent ability to depict normal adrenal glands. For lesions indeterminate on CT, MRI is performed. Ultrasound and angiography are not commonly used on a known lesion, but they may occasionally detect an unexpected adrenal lesion, initiating further evaluation.
There has been great interest in the evaluation of the increasing number of adrenal lesions that are detected on imaging studies for indications unrelated to the adrenals. These have been described as incidentalomas. Incidentalomas have been noted on 0.35-4.4% of CT studies [70]. In a large institution where we perform over 12,000 abdominal CT’s every year, these numbers would predict that as many as 500 incidental adrenal lesions would be discovered. A large number of these lesions will require additional resources for follow-up or immediate characterization. Imaging diagnosis of the incidental adrenal mass without laboratory abnor- mality is based on several criteria including size, mor- phologic appearance, density, and MR signal characteristics. Approximately, 78-87% of lesions smaller than 3 cm are benign, at least 90% of lesions >3 cm are malignant [71]. Unfortunately, there is an unacceptable overlap of benign and malignant lesions based on size alone. Still, most adrenal algorithms
recommend a lesion >5 cm should be biopsied or resected, unless the imaging appearance is clearly that of a benign lesion such as a large myelolipoma or cyst. A smaller lesion will undergo CT or MRI evaluation to look for the criteria for adenoma which are men- tioned previously in this article. Small indeterminate lesions may be followed closely to confirm stability by CT or MRI, especially in patients with no prior history of malignancy.
Not all adrenal abnormalities can be resolved by non-invasive imaging. Percutaneous biopsy can be very useful in several specific situations. An adrenal lesion may be the most accessible of multiple lesions in a patient with undiagnosed malignancy to characterize for therapy. In a patient with known malignancy, a solitary adrenal metastasis greatly affects therapy so biopsy is warranted. In patients with known non- adrenal malignancy, an adrenal lesion will still repre- sent a benign lesion in approximately half of cases [72]. If the lesion is malignant then systemic therapy may be the best option, whereas a benign adrenal lesion may allow curative surgery if no other metastatic lesions are present.
For adrenal biopsy, use of FNA versus core biopsy may depend on the level of confidence of pathologists at an individual institution to interpret aspiration sam- ples. The accuracy of biopsy is 85-96% with almost no false positive results [73,74]. Serious complications from adrenal biopsy occur in approximately 3-5%
[15,73,74]. These may include pneumothorax, hemor- rhage, pancreatitis, abscess, bactremia or metastatic seeding of the needle tract [5,15]. However, the fine needle technique is usually not adequate to differentiate adenoma from adrenocortical carcinoma [5].
Staging and evaluation of extent of adrenal malig- nancies is usually possible with CT, but for very large tumors is best done by MRI with multiple planes. Nuclear medicine techniques image the entire body but provide poor spatial detail.
8. Conclusion
At present most adrenal disorders can be correctly diagnosed and managed with the use of non-invasive cross sectional imaging methods, primarily CT and occasionally MRI or nuclear medicine. However, the radiologist must be aware of the various pathologic processes and their imaging patterns. Invasive proce- dures such as biopsy can often be avoided. Neverthe- less, some lesions have atypical or non-specific
147.0 (01)
12:1
36.0cm
5
ARD
Ma
(b)
147.0 (001)
36.0cm
12.13
DARD
51
Mag
A
(c)
appearances such that non-invasive diagnosis is not possible in every case.
References
[1] Dunnick NR, Korobkin M, Francis I. Adrenal radiology: distin- guishing benigh from malignant adrenal masses. Am J Roentgenol 1996;167:861-7.
[2] Shady KL, Brown JJ. MR imaging of the adrenal glands. Magn Reson Imaging Clin N Am 1995;3:73-85.
[3] Boland GW, Lee MJ. Magnetic resonance imaging of the adrenal gland. Crit Rev Diagn Imaging 1995;36:115-74.
[4] Doppman JL, Gill JR, Miller DL, Chang R, Gupta R, Friedman TC, Choyke PL, Feuerstein IM, Dwyer AJ, Jicha DL, Walther MM, Norton JA, Linehan WM. Distinction between hyperaldos- teronism due to bilateral hyperplasia and unilateral aldos- teronoma: reliability of CT. Radiology 1992;184:677-82.
[5] Udelsman R, Fishman EK. Radiology of the adrenal. En- docrinol Metab Clin North Am 2000;29:27-42 viii.
[6] Vincent JM, Morrison ID, Armstrong P, Reznek RH. Computed tomography of diffuse, non-metastatic enlargement of the adrenal glands in patients with malignant disease. Clin Radiol 1994;49:456-60.
[7] Sohaib SA, Reznek RH. Adrenal imaging. BJU Int 2000;86(Suppl. 1):95-110.
[8] Kenney PJ, Robbins GL, Ellis DA, Spirt BA. Adrenal glands in patients with congenital renal anomalies: CT appearance. Radi- ology 1985;155(1):181-2.
[9] Krebs TL, Wagner BJ. The adrenal gland: radiologic-pathologic correlation. Magn Reson Imaging Clin N Am 1997;5:127-46.
[10] Avisse C, Marcus C, Patey M, Ladam-Marcus V, Delattre JF, Flament JB. Surgical anatomy and embryology of the adrenal glands. Surg Clin North Am 2000;80:403-15.
[11] Westra SJ, Zaninovic AC, Hall TR, Kangarloo H, Boechat MI. Imaging of the adrenal gland in children. Radiographics 1994;14:1323-40.
[12] Cirillo RL, Bennett WF, Vitellas KM, Poulos AG, Bova JO. Pathology of the adrenal gland: imaging features. Am J Roentgenol 1998;170:429-35.
[13] Dunnick NR. Adrenal imaging: current status. Am J Roentgenol 1990;154:927-36.
[14] Korobkin M, Dunnick NR. Characterization of adrenal masses. Am J Roentgenol 1995;164:643-4.
[15] Francis IR, Korobkin M. Incidentally discovered adrenal masses. Magn Reson Imaging Clin N Am 1997;5:147-64.
[16] Hedeland H, Ostberg G, Hokfelt B. On the prevalence of adrenocortical adenomas in an autopsy material in relation to hypertension and diabetes. Acta Med Scand 1968;184:211-4.
[17] Korobkin M, Francis IR. Imaging of adrenal masses. Urol Clin North Am 1997;24:603-22.
[18] Szolar DH, Kammerhuber F. Quantitative CT evaluation of adrenal gland masses: a step forward in the differentiation between adenomas and nonadenomas. Radiology 1997;202:517- 21.
[19] Korobkin M, Brodeau FJ, Yutzy GG, Francis IR, Quint LE, Dunnick NR, Kazerooni EA. Differentiation of adrenal ade- nomas from nonadenomas using CT attenuation values. Am J Roentgenol 1996;166:531-6.
[20] Korobkin M, Brodeur FJ, Francis IR, Quint LE, Dunnick NR, Londy F. CT time-attentuation washout curves of adrenal adenomas and nonadenomas. Am J Roentgenol 1998;170:747- 52.
[21] Bilbey JH, McLoughlin RE, Kurkjian PS, Wilkins GE, Chan NH, Schmidt N, Singer J. MR imaging of adrenal masses: value of chemical-shift imaging for distinguishing adenomas from other tumors. Am J Roentgenol 1995;164:637-42.
[22] Outwater EK, Siegelman ES, Huang AB, Bimbaum BA. Adrenal masses: correlation between CT attenuation value and chemical shift ratio at MR imaging with in-phase and opposed-phase sequences. Radiology 1996;200:749-52.
[23] McNicholas MMJ, Lee MJ, Mayo-Smith WW, Hahn PF, Boland GW, Mueller PR. An imaging algorithm for the differen- tial diagnosis of adrenal adenomas and metastases. Am J Roentgenol 1995;165:1453-9.
[24] Reinig JW, Stutley JE, Leonhardt CM, Spicer KM, Margolis M, Caldwell CB. Differentiation of adrenal masses with MR imag- ing: comparison of techniques. Radiology 1994;192:41-6.
[25] Cook DM. Adrenal mass. Endocrinol Metab Clin North Am 1997;26:829-52.
[26] Abrams HL, Spiro R, Goldstein N. Metasteses in carcinoma: analysis of 1000 autopsied cases. Cancer 1950;3:74-85.
[27] Dunnick NR, Heaston D, Halvorsen R, Moore AV, Korobkin M. CT appearance of adrenal cortical carcinoma. J Comput Assist Tomogr 1982;6:978-82.
[28] Gillams A, Roberts CM, Shaw P, Spiro SG, Goldstraw P. The value of CT scanning and percutaneous fine needle aspiration of adrenal masses in biopsy-proven lung cancer. Clin Radiol 1992;46:18-22.
[29] Paling MR, Williamson BR. Adrenal involvement in non- Hodgkin lymphoma. Am J Roentgenol 1983;141:303-5.
[30] Kato H, Itami J, Shiina T, Uno T, Arimizu N, Fujimoto H, Mikata A, Tamaru J, Araki A. MR imaging of primary adrenal lymphoma. Clin Imaging 1996;20:126-8.
[31] Falchook FS, Allard JC. CT of primary adrenal lymphoma. J Comput Assist Tomogr 1991;15:1048-50.
[32] Pagliuca A, Gillett DS, Salisbury JR, Basu RN, Mufti GJ. Bilateral adrenal lymphoma presenting as Addison’s disease. Postgrad Med J 1989;65:684-6.
[33] Lee FT, Thornbury JR, Grist TM, Kelcz F. MR imaging of adrenal lymphoma. Abdom Imaging 1993;18:95-6.
[34] Glazer GM. MR imaging of the liver, kidneys, and adrenal glands. Radiology 1988;166:303-12.
[35] Radin DR, Ralls PW, Boswell WD Jr., Colletti PM, Lapin SA, Halls JM. Pheochromocytoma: detection by unenhanced CT. Am J Roentgenol 1986;146:741-4.
[36] Manger WM, Gifford RW Jr., Hoffman BB. Pheochromocy- toma: a clinical and experimental overview, vol. 9. Year Book Medical Publishers, 1985:1-89.
[37] Moulton JS, Moulton JS. CT of the adrenal glands. Semin Roentgenol 1988;23:288-303.
[38] Daneman A. Adrenal neoplasms in children. Semin Roentgenol 1988;23:205-15.
[39] Welch TJ, Sheedy PF II, van Heerden JA, Sheps SG, Hattery RR, Stephens DH. Pheochromocytoma: value of computed to- mography. Radiology 1983;148:501-3.
[40] Raisanen J, Shapiro B, Glazer GM, Desai S, Sisson JC. Plasma catecholamines in pheochromocytoma: effect of urographic con- trast media. Am J Roentgenol 1984;143:43-6.
[41] Mukherjee JJ, Peppercorn PD, Reznek RH, Patel V, Kaltsas G, Besser M, Grossman AB. Pheochromocytoma: effect of nonionic contrast medium in CT on circulating catecholamine levels. Radiology 1997;202:227-31.
[42] Kier R, McCarthy S. MR characterization of adrenal masses: field strength and pulse sequence considerations. Radiology 1989;171:671-4.
[43] Quint LE, Glazer GM, Francis IR, Shapiro B, Chenevert TL. Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and 1-131 MIBG scintigraphy. Radiology 1987;165:89-93.
[44] Lucon AM, Pereira MA, Mendonca BB, Halpern A, Wajchen- beg BL, Arap S. Pheochromocytoma: study of 50 cases. J Urol 1997;157:1208-12.
[45] Sisson JC, Frager MS, Valk TW, Gross MD, Swanson DP, Wieland DM, Tobes MC, Beierwaltes WH, Thompson NW. Scintigraphic localization of pheochromocytoma. N Engl J Med 1981;305:12-7.
[46] Bousvaros A, Kirks DR, Grossman H. Imaging of neuroblas- toma: an overview. Pediatr Radiol 1986;16:89-106.
[47] Bilal MM, Brown JJ. MR imaging of renal and adrenal masses in children. Magn Reson Imaging Clin N Am 1997;5:179-97.
[48] Sohaib SA, Peppercorn PD, Allan C, Monson JP, Grossman AB, Besser GM, Reznek RH. Primary hyperaldosteronism (Conn syndrome): MR imaging findings. Radiology 2000;214:527-31.
[49] Fishman EK, Deutch BM, Hartman DS, Goldman SM, Zer- houni EA, Siegelman SS. Primary adrenocortical carcinoma: CT evaluation with clinical correlation. Am J Roentgenol 1987;148:531-5.
[50] Ames DE, Asherson RA, Ayres B, Cassar J, Hughes RV. Bilateral adrenal infarction, hypoadrenalism and splinter haem- orrhages in the ‘primary’ antiphospholipid syndrome. Br J Rheumatol 1992;31:117-20.
[51] Wolverson MK, Kannegiesser H. CT of bilateral adrenal hemor- rhage with acute adrenal insufficiency in the adult. Am J Roentgenol 1984;142:311-4.
[52] Murphy BJ, Casillas J, Yrizarry JM. Traumatic adrenal hemor- rhage: radiologic findings. Radiology 1988;169:701-3.
[53] Burks DW, Mirvis SE, Shanmuganathan K. Acute adrenal injury after blunt abdominal trauma: CT findings. Am J Roentgenol 1992;158:503-7.
[54] Sivit CJ, Ingram JD, Taylor GA, Bulas DI, Kushner DC, Eichelberger MR. Posttraumatic adrenal hemorrhage in children: CT findings in 34 patients. Am J Roentgenol 1992;158:1299- 302.
[55] Kenney PJ, Stanley RJ. Calcified adrenal masses. Urol Radiol 1987;9:9-15.
[56] Kenney PJ, Wagner BJ, Rao P, Heffess CS. Myelolipoma: CT and pathologic features. Radiology 1998;208:87-95.
[57] Cyran KM, Kenney PJ, Memel DS, Yacoub I. Adrenal myelolipoma. Am J Roentgenol 1996;166:395-400.
[58] Musante F, Derchi LE, Bazzocchi M, Avataneo T, Gandini G, Mucelli RS. MR imaging of adrenal myelolipomas. J Comput Assist Tomogr 1991;15:111-4.
[59] Rao P, Kenney PJ, Wagner BJ, Davidson AJ. Imaging and pathologic features of myelolipoma. Radiographics 1997;17: 1373-85.
[60] Sohaib SA, Hanson JA, Newell-Price JD, Trainer PJ, Monson JP, Grossman AB, Besser GM, Reznek RH. CT appearance of the adrenal glands in adrenocorticotrophic hormone-dependent Cushing’s syndrome. Am J Roentgenol 1999;172:997-1002.
[61] Rozenbit A, Morehouse HT, Amis ES Jr. Cystic adrenal lesions: CT features. Radiology 1996;201:541-8.
[62] Tung GA, Pfister RC, Papanicolaou N, Yoder IC. Adrenal cysts: imaging and percutaneous aspiration. Radiology 1989;173:107- 10.
[63] Aisen AM, Ohl DA, Chenevert TL, Perkins P, Mikesell W. MR of an adrenal pseudocyst. Magn Reson Imaging 1992;10:997- 1000.
[64] Kawashima A, Sandler CM, Fishman EK, Charnsangavej C, Yasumori K, Honda H, Ernst RD, Takahashi N, Raval BK, Masuda K, Goldman SM. Spectrum of CT findings in nonmalig- nant disease of the adrenal gland. Radiographics 1998;18:393- 412.
[65] Sawczuk IS, Reitelman C, Libby C, Grant D, Vita J, White RD. CT findings in Addison’s disease caused by tuberculosis. Urol Radiol 1986;8:44-5.
[66] Sabanegh E Jr., Harris MJ, Grider D. Cavernous adrenal he- mangioma. Urology 1993;42(3):327-30.
[67] Honig SC, Klavans MS, Hyde C, Siroky MB. Adrenal heman- gioma: an unusual adrenal mass delineated with magnetic reso- nance imaging. J Urol 1991;146:400-2.
[68] Berliner L, Bosniak MA, Megibow A. Adrenal pseudotumors on computed tomography. J Comput Assist Tomogr 1982;6(2):281- 5.
[69] McLoughlin RF, Bilbey JH. Tumors of the adrenal gland: findings on CT and MR imaging. Am J Roentgenol 1994;163:1413-8.
[70] Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev 1995;16:460-84.
[71] Caudel AG, Gattuso P, Reyes CV, Prinz RA, Castelli MJ. Fine-needle aspiration biopsy of adrenal masses in patients with extraadrenal malignancy. Surgery 1993;114:1132-7.
[72] Oliver TW Jr., Bernardino ME, Miller JI, Mansour K, Greene D, Davis WA. Isolated adrenal masses in nonsmall-cell broncho- genic carcinoma. Radiology 1984;153:217-8.
[73] Silverman SG, Mueller PR, Pinkney LP, Koenker RM, Seltzer SE. Predictive value of image-guided adrenal biopsy: analysis of results of 101 biopsies. Radiology 1993;187:715-8.
[74] Welch TJ, Sheedy PF II, Stephens DH, Johnson CM, Swensen SJ. Percutaneous adrenal biopsy: review of a 10-year experience. Radiology 1994;193:341-4.