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Adrenal imaging
Adrenal Imaging Melvyn Korobkin and Isaac R. Francis CT is the imaging procedure of choice for detecting adrenal masses. In patients with biochemical evidence of an adrenal endocrine syndrome, CT can detect or exclude an adrenal mass in a high percentage of cases. Radionuclide scintigraphy is a useful adjunct in selected cases to characterize an adrenal mass as functional cortical (NP-59} or medullary (MIBG) tissue. In this article, the spectrum of adrenal imaging findings in patients with Cushing's syndrome, Conn's syndrome (primary aldosteronism), and pheochromocytoma is described and illustrated. In patients without an adrenal endocrine syndrome, an adrenal mass is detected on CT as an incidental finding or during a search for metastatic disease. Although pathognomonic findings of adrenal hemorrhage or myelolipoma are occasionally demonstrated, most adrenal masses have nonspecific morphological CT features. Differentiation of common benign adenomas from nonadenomatous adrenal masses, including metastases, remains an important clinical problem. This article reviews the current status, advantages, and limitations of the following methods t o characterize an adrenal mass: (1) percutaneous adrenal biopsy, (2) NP-59 scintigraphy, (3) unenhanced CT densitometry, and (4) opposed-phase chemical shift MRI,
Copyright © 1995 by W.B. Saunders Company
T IS THE IMAGING procedure of choice for evaluation of the adrenal glands. CT is C commonly used to detect or exclude an adrenal mass, although its ability to characterize the nature of such a mass is somewhat limited. In this overview we will summarize the indications for adrenal CT, the CT findings in a variety of adrenal disorders, and the use of radionuclide imaging and MRI to supplement CT findings in selected cases. 1,2 HYPERFUNCTIONING ADRENAL MASSES
CT is often performed when clinical and biochemical studies indicate the presence of abnormal adrenal function. The most common hyperfunctioning adrenal disorders are Cushing's syndrome, primarY aldosteronism (Conn's syndrome) and pheochromocytoma.
Cushing's Syndrome About 70% of patients with Cushing's syndrome have bilateral adrenal hyperplasia, usually caused by a pituitary adenoma. In these patients, CT often shows either normal adrenals (Fig 1) or diffuse thickening of the limbs of both glands (Fig 2). A small percentage of patients have nodules (Fig 3) superimposed on normal or enlarged glands (nodular adrenal hyperplasia). A unilateral cortical adenoma is the cause in about 20% of cases of Cushing's syndrome, and the remaining cases are caused by an adrenal cortical carcinoma. An adenoma typically is smaller than 5 cm and has a nonspecific appearance. Adrenal cortical carcinoma usually is larger than 5 cm and often has central necrosis or evidence of metastatic spread. CT
can detect or exclude a unilateral adrenal mass in virtually 100% of patients with Cushing's syndrome, in part because of the abundant retroperitoneal fat present in this condition. Although CT distinction between adenoma and carcinoma may be impossible for masses between 4 cm and 6 cm in size, this has little practical implication in patients with Cushing's syndrome because surgical resection is performed for either entity in the absence of known metastatic disease.
PrimaryAMosteronism Primary aldosteronism is characterized by moderate to severe hypertension caused by unregulated secretion of excessive amounts of aldosterone. Biochemically, this condition is associated with elevated serum and urinary levels of aldosterone, hypokalemia, and suppression of plasma renin activity. A solitary aldosterone-producing adenoma (APA) is present in about 70% of patients, and surgical adrenalectomy corrects hypertension and hypokalemia in about 75% to 90% of these patients. Most of the other patients have idiopathic hyperaldosteronism (IHA) with bilateral adrenal hyperplasia. Unlike patients with unilateral APA, surgery rarely cures hypertension, and results in permanent adrenal insufficiency. These patients usu-
From the University of Michigan Hospitals, Department of Radiology, Ann Arbor, MI. Address reprintrequests to Melvyn Korobkin, MD, University of Michigan Hospitals, Department of Radiology, 1500 E Medical Center Dr, B1D520, Ann Arbor, MI 48109-0030. Copyright © 1995 by W.B. Saunders Company 0887-2171/95/1604-000655. 00/0
Seminars in Ultrasound, CT, andMRI, Vo116, No 4 (August), 1995: pp 317-330
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Fig 1. CT appearance of normal adrenal glands. (A) The cephalad portion of the right adrenal (arrow) is seen. (B) The three limbs of the left adrenal (arrow) are shown at this level.
ally are treated medically. It is essential, therefore, to differentiate between these two major types of primary aldosteronism. Adrenal CT is less accurate in the evaluation
of primary aldosteronism than it is in the evaluation of Cushing's syndrome and pheochromocytomas (discussed below), because the aldosteronoma is usually a smaller mass (Fig 4). In one
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Fig 2. Cushing's syndrome with bilateral adrenal hyperplasia caused by an ectopic source of ACTH production. CT shows extreme thickening of the limbs of both adrenals (A).
large series, the mean diameter was 18 mm, and 20% were 10 mm or smaller? Using early generation CT scanners, CT sensitivity for detection of APA varied between 50% to 70%. 4 In one series, all aldosteronomas 1.5 cm or larger were detected, whereas only 50% between 10 and 14 mm were identified. 5 More recent studies using current-generation scanners have reported sensitivities of 82% and 88%. 6,7 CT evaluation is hampered because a unilateral aldosteronoma may be associated with n o n aldosterone-secreting nodules in the ipsilateral or contralateral gland, which can result in a false diagnosis of adrenal hyperplasia. 8 In addi-
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tion, bilateral hyperplasia may have a predominant unilateral macronodule and cause an erroneous diagnosis of a unilateral aldosteronoma. Doppman et al 9 recently demonstrated that CT cannot reliably differentiate A P A from I H A whenever bilateral adrenal nodules are shown. In their series, 6 of 21 patients with an A P A were incorrectly diagnosed from CT as having IHA. Non-aldosterone-secreting nodules were detected by CT in addition to aldosteronomas. Sophisticated diagnostic endocrine studies often point to the diagnosis of A P A or I H A and should be used in conjunction with CT findings to make a preliminary diagnosis. Most patients with a unilateral adrenal mass can proceed to unilateral adrenalectomy. Patients with bilateral adrenal nodules, as well as those in whom CT and biochemical evaluations are discordant or equivocal, should probably undergo bilateral selective adrenal vein sampling for aldosterone levels, z°
Pheochromocytoma Adrenal pheochromocytomas usually are large (2 to 5 cm in diameter) and are easily detected with CT (Fig 5A). Intravenous contrast enhancement should not be used in patients suspected of pheochromocytoma, unless alpha-adrenergic blocking drugs have been administered. About 10% of pheochromocytomas are extra-adrenal in location, and these can be difficult to identify. If the adrenals are normal in a patient with
Fig 3. Cushing's syndrome with nodular adrenal hyperplasia. (A) CT shows a nodule (arrow) at the posterior aspect of the right adrenal. (B) A nodule (arrow) is also present in the left adrenal,
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Fig 4. Primary aldosteronism caused by a hyperfunctioning adrenal adenoma. CT shows a 1-cm right adrenal mass (arrow).
compelling biochemical evidence of a pheochromocytoma, the remainder of the abdomen and pelvis should be scanned. Radionuclide scanning with iodine-labelled meta-iodobenzyl guanidine (MIBG) is useful for detecting adrenergic tissue, 1 and this technique is often used to scan the entire body for primary and metastatic pheochromocytoma (Fig 5B). MRI can also be used in selected problem cases; signal intensity of pheochromocytoma tends to be very high on T2-weighted images, especially on medium field strength magnets (Fig 6). Although many extra-adrenal pheochromocy-
tomas in the chest are readily seen as paravertebral masses on standard chest radiographs, we have seen several intracardiac pheochromocytomas that were not seen or clearly localized on chest film. Patients were typically referred to our hospital with unsuccessful localization of a biochemically proven pheochromocytoma. MIBG scintigraphy showed abnormal uptake in the lower thorax (Fig 7A). Bolus-enhanced CT demonstrated the surgically proven tumor in all 13 cases (Fig 7B). Most were localized superior to the left atrium, but one was anterior to the aortic root, and another was lateral to the aortic
Fig 5. Adrenal pheochromocytoma. (A) CT shows a 5-cm left adrenal mass {M). (B) MIBG scintigram shows intense uptake in the same mass (arrow). L, liver.
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tected incidentally on abdominal CT scans performed for a variety of disorders. Some adrenal masses have CT features specific for a particular diagnosis, such as hemorrhage or myelolipoma, but most masses are nonspecific on CT and require other noninvasive or invasive imaging studies for more definitive diagnosis. These
Fig 6. Adrenal pheochromocytoma.T2-weighted MRI shows a left adrenal mass with high signal intensity (m).
arch. The tumors ranged in size from 3 to 8 cm, and about half showed central areas of low attenuation. These intracardiac pheochromocytomas were not visible on unenhanced or nonbolus-enhanced CT image s.
Adrenal Insufficiency Adrenal insufficiency, or Addison's disease, is usually idiopathic in origin in this country, and these cases probably are consequences of autoimmune disorders. On imaging studies, the adrenals can be undetected or markedly diminutive in size in patients with adrenal insufficiency (Fig 8). Less often, and frequently undiagnosed or misdiagnosed, adrenal insufficiency results from destruction by bilateral hemorrhage, infection, or metastatic neoplasm. Bilateral adrenal hemorrhage is often first diagnosed by CT, especially when the high attenuation of acute or subacute hematoma is recognized. Bilateral tuberculosis, histoplasmosis, or other granulomatous disease is sometimes associated with adrenal calcification, but the findings are often nonspecific and diagnosis requires biopsy confirmation. NONHYPERFUNCTIONING ADRENAL MASSES
Most adrenal masses detected by CT are found in patients without evidence of known adrenal endocrine dysfunction. They are de-
Fig 7. Cardiac pheochromocytoma (A) MIBG scintigram shows a prominent focus of increased tracer uptake in the thoracic midline (arrow). L, liver. (B) Enhanced CT shows a large inhomogeneous mass (M) in the region of the left atrium.
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Fig 8. Bilateral adrenal atrophy. CT shows markedly thin adrenals (arrows) in this patient with idiopathic adrenal insufficiency.
include radionuclide imaging with iodine-131-6iodomethyl-19-norcholesterol (NP-59), MRI, or percutaneous aspiration biopsy. In the discussion of nonhyperfunctioning adrenal masses, it is useful to distinguish between patients with known primary neoplasms and those in whom an adrenal mass is a strictly incidental finding.
Myelolipoma Adrenal myelolipoma is a benign neoplasm of the cortex composed of mature fat and myeloid tissue found in normal bone marrow. Although uncommon, myelolipoma is not a rare lesion. In a busy abdominal CT practice we see three or four cases every year. Most are asymptomatic and represent incidental findings on CT, although larger lesions may cause pain or may be associated with intratumoral hemorrhage. Sonographic features usually suggest the diagnosis of myelolipoma, because most lesions are highly echogenic, xl For large tumors, propagationspeed artifact producing apparent posterior displacement of the diaphragm is additional evidence favoring a fatty tumor. MRI of myelolipoma shows bright signal intensity on T1weighted images and intermediate signal intensity on T2-weighted images. Although a malignant adrenal lesion can engulf surrounding fat and simulate a myeloli-
poma, in most cases the diagnosis of myelolipoma can be made with confidence when CT measurements confirm the presence of discrete regions of fat attenuation within an adrenal mass. 12 The proportion of CT-detectable fat within an adrenal myelolipoma is variable; in some patients most of the tumor consists of fatty tissue, but in others, thin CT sections of 5 mm or less may be necessary to detect smaller amounts of fat (Fig 9). Thin CT sections may also be
Fig 9. Adrenal myelolipoma. A small amount of fatattenuation tissue (arrow) is seen within this right adrenal mass.
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necessary to resolve questions of a small myelolipoma that can be simulated by partial volume effect of normal extra-adrenal fat on more widely collimated scans. In cases complicated by infarction or hemorrhage, the imaging findings of acute, subacute, or chronic hemorrhage are superimposed on the lesion, potentially complicating the diagnosis. Differential diagnosis includes angiomyolipoma of the upper pole of the kidney, as well as a lipoma or liposarcoma of the adrenal gland or the surrounding retroperitoneal fat. The diagnosis of myelolipoma is usually based on CT alone, although confirmation by percutaneous biopsy has also been reported. Hemorrhage Adrenal hemorrhage can be unilateral or bilateral. When bilateral, it can cause adrenal insufficiency and death if not properly diagnosed and treated. Hypoadrenalism is usually not recognized clinically at the time that CT detects the disorder. 13 Clinical manifestations of adrenal insufficiency in adults often mimic more common conditions such as myocardial infarction, sepsis, or an acute surgical abdomen. Although the clinical diagnosis is sometimes suspected from an abnormally low level of plasma cortisol, the cortisol levels can be normal, and biochemical confirmation in such cases rests on an abnormal response to an adrenocorticotrophic hormone stimulation test. Bilateral adrenal hemorrhage is usually associated with anticoagulant therapy or with the stress caused by surgery, sepsis, or hypotension. Less commonly, it is caused by trauma or hypoxia during delivery. Most anticoagulantassociated adrenal hemorrhage occurs during the first three weeks of treatment. Hemorrhage in such cases is apparently not caused by excessive anticoagulation because prothrombin levels are usually in the therapeutic range, and hemorrhage into the rest of the retroperitoneum or other organs usually does not occur. CT of bilateral adrenal hemorrhage shows both glands to be enlarged, although often in an asymmetric manner. The glands usually having an oval or rounded shape. 13,14The CT density of the glands varies in relation to the time between the hemorrhage and CT examination. An acute or subacute hemorrhage is characterized by high attenuation (50 to 90 HU) within the
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hematoma (Fig 10). Follow-up studies after appropriate treatment show diminution in size of the adrenal masses and a gradual decrease in attenuation value. In the appropriate clinical setting, the detection of bilateral high-attenuation adrenal masses should lead to immediate biochemical studies for adrenal insufficiency, and initiation of prompt therapy with intravenous steroids should be considered. In the older child and adult, unilateral adrenal hemorrhage is usually caused by blunt abdominal trauma. 15 Most unilateral hematomas involve the right adrenal (Fig 11), and associated injuries such as rib fractures or liver injury usually dominate the clinical picture. The CT features are similar to those seen in bilateral hemorrhage except that streaky infiltration of the periadrenal fat is common. Unilateral adrenal hemorrhage has also recently been described in patients undergoing liver transplantation. 16A7 The excision of a segment of the recipient's inferior vena cava typically necessitates ligation and division of the right adrenal vein, sometimes resulting in venous infarction and/or hemorrhage into the right adrenal gland. Sonography and CT have demonstrated right adrenal hemorrhage in about 2% of patients undergoing orthotopic liver transplantation. However, the true incidence of posttransplant adrenal hemorrhage is unknown because imaging procedures are not performed routinely. Postmortem studies in children who died after
Fig 10. Bilateral adrenal hemorrhage. CT shows a high attenuation mass in both adrenals, right (R) larger than left (L), in this patient with adrenal insufficiency after blunt abdominal trauma.
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lateral metastases, or less common combinations of adrenal lesions (eg, adenoma or metastasis) are included in the differential diagnosis. Adenoma Versus Carcinoma
Fig 11. Unilateral adrenal hemorrhage. CT shows a high attenuation right adrenal hematoma (H). Note the streaky soft-tissue attenuation in the periadrenal fat posterior to the adrenal hematoma, a feature commonly associated with traumatic adrenal hemorrhage.
liver transplantation showed a large right adrenal hemorrhage in 10% of cases. Cyst Although we list cysts in the group with characteristic CT findings, there is a remarkable paucity of reports on the CT appearance of adrenal cysts. Either gland can be involved, and there is a 3:1 female predilection. Pathologically, four types of adrenal cysts are recognized: endothelial, epithelial, parasitic, and pseudocysts. 18 Adrenal pseudocysts, probably caused by prior hemorrhage into a normal or abnormal gland, are most commonly detected radiologically. Adrenal cysts, especially pseudocysts, can have a thickened wall, nodularity, septation, or soft tissue components making it difficult to exclude a neoplasm 19 (Fig 12).
Nonhyperfunctioning adrenal adenomas are common neoplasms, as indicated by an incidence of 2.8% for adenomas larger than 3 mm in one autopsy study. 21 Adenomas larger than 1 cm are seen in about 1% of patients undergoing abdominal CT. These "incidentalomas" must be differentiated from adrenal cortical carcinoma (as well as metastases, discussed below). Unlike adenomas, adrenal cortical carcinomas are rare and often present with abdominal pain or a palpable mass. About half of patients with adrenal carcinoma will show manifestations of excess hormone production (usually Cushing's syndrome). CT features typical of benign adenomas include (1) smooth contour, (2) sharp margination, and (3) size smaller than 5 cm (Fig 13). When these features are present and biochemical studies are normal, surveillance with CT at 6 and 12 months is often recommended to confirm lack of growth. Lesions larger than 5 cm, or those with irregular margins, should be removed because they are atypical of benign adenoma. Features typical of carcinoma are (1) size larger than 5 cm, (2) central areas of low attenuation caused by tumor necrosis, (3) tumor calcification, and (4) evidence of hepatic, nodal, or venous spread 22,23 (Fig 14). On MRI, an adrenal carcinoma typically shows high signal
Granulomatous Disease Tuberculosis, histoplasmosis, or other granulomatous infection usually involves both adrenal glands, but often in an asymmetric pattern. The CT features are nonspecific and include soft tissue masses, cystic changes, and calcification reflecting the age of the process and degree of necrosis. 2° Percutaneous biopsy is often required to confirm the diagnosis of granulomatous disease and to identify the organism. The absence of high attenuation within the lesions usually helps exclude bilateral hemorrhage. Bi-
Fig 12. Adrenal pseudocyst. CT shows a thick-walled right adrenal cyst caused by an old traumatic hemorrhage.
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Adrenal metastases are not nearly as common as nonhyperfunctioning adrenal cortical adenomas, but they occur with sufficient frequency to cause significant problems with differential diagnosis. This problem has been a topic of continuing investigation for several years. When an adrenal mass is the only finding suspicious of metastatic disease in an oncologic patient, confirmation of its nature may be crucial in determining whether curative therapy of
the primary neoplasm is warranted. This issue occurs most commonly in patients with carcinoma of the lung, because confirmation of an isolated adrenal metastasis will preclude a thoracotomy or curative radiotherapy program. Even in patients with lung cancer, an adrenal mass is more likely to be an adenoma than a metastasis. 24 Although some CT features are more commonly found in metastases than in adenomas, no single feature or combination of features can reliably distinguish a metastasis from an adenoma. Metastases tend to be larger and less well defined than adenomas. Metastases also tend to have inhomogeneous attenuation and a thick irregular enhancing rim (Fig 15). Adenomas tend to be smaller and homogeneous in density. Because CT imaging features alone do not usually permit unequivocal differentiation of adrenal adenomas and metastases, percutaneous biopsy is often used to establish the correct diagnosis. Extensive investigation has been undertaken recently on potential noninvasive approaches to making this critical differential diagnosis. The focus of this effort has been on three different methodologies: NP-59 scintigraphy, CT densitometry, and MRI. NP-59 scintigraphy. Francis et a125 reported on the use of NP-59 scintigraphy in evaluation of 28 oncologic patients with unilateral adrenal mass. Adenomas larger than 2 cm accumulate NP-59, whereas metastases do not. Thus, functioning adrenal tissue is suggested if the NP-59 scintigram is "hot" on the side of the CTdepicted adrenal mass (Fig 16). Each of the 14
Fig 14. Adrenal carcinoma. CT shows a large (>5 cm) inhomogeneous right adrenal mass, highly suggestive of a primary carcinoma in this patien t without a known extraadrenal neoplasm.
Fig 15. Bilateral adrenal metastases. CT shows large bilateral adrenal masses in a patient with carcinoma of the lung. There is slight " w a l l " thickening in both lesions.
Fig 13. Adrenal adenoma. Unenhanced CT shows a small, sharply marginated, homogeneous right adrenal mass (M). Visible low attenuation on this unenhanced scan measured close to O HU, highly suggestive of a benign lesion.
intensity on T2-weighted images. On radionuclide imaging, NP-59 accumulates in adenomas and is typically absent in cortical carcinoma.
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Fig 16, Adrenal adenoma. NP-59 scintigram shows increased uptake in the adrenal gland (arrow), confirming that the adrenal mass detected on a prior CT represents an adenoma, L, liver.
patients in this study with concordant uptake had a proven adrenal adenoma. In the 11 patients with decreased uptake on the side of a CT-detected adrenal mass (discordant uptake), none proved to have an adenoma; nine had metastases and two had cysts. Although the absence of NP-59 labelling cannot distinguish between a metastasis and most other forms of adrenal masses, it does seem to exclude an adenoma. Despite these encouraging results, the lack of routine commercial availability of NP-59 has limited its applicability to the adenoma versus metastasis problem. Even in our own institution where NP-59 was developed and is readily available, it has not yet significantly reduced the use of percutaneous biopsy of an adrenal mass in oncologic patients when significant therapeutic decisions depend on the confirmation or exclusion of adrenal metastasis. CTdensitometry. Several recent studies suggest that adenomas can be differentiated from nonadenomatous adrenal masses based on their unenhanced CT attenuation values. In one series the mean attenuation value for 38 benign adrenal masses (presumably mostly adenomas) was -2.2 HU + 10.6 (SD), which was significantly less than a mean of 28.9 HU +- 10.6 for 28 malignant masses. 26 More importantly, none of the malignant lesions had an unenhanced attenuation value less than 0 HU. The sensitivity of CT
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for the diagnosis of benign adrenal mass was 47% and the specificity was 100%. Even at a threshold level of 10 HU, the sensitivity to specificity ratio was 79%:96%. In our own recent series of 51 proved adrenal masses, 27 the mean unenhanced attenuation value was 12 HU - 8.8 for 34 adenomas, which was significantly less than 31 HU --- 6.3 for 17 nonadenomas (Fig 13). More importantly, none of the n0nadenomas had an attenuation value less than 18 HU, whereas 88% of the adenomas did. Based on a threshold value of 10 HU, the sensitivity: specificity ratio for the diagnosis of adrenal adenoma in our study was 75%:96%. Two other recently reported series evaluating unenhanced CT values of adrenal masses have shown similar results. 2s,29 It is now clear that adrenal adenomas can be differentiated from metastases and other nonaden0matous adrenal masses based on their unenhanced CT attenuation values with very high specificity and acceptable sensitivity. MR/. There has been extensive investigation of the MRI features of benign and malignant adrenal lesions. Initial studies using low field strength magnets (0.35 to 0.5 T) suggested that adrenal adenomas had a lower signal intensity on T2-weighted images than did nonadenomas, including metastatic lesions. 3°-32 This was reflected in a lower ratio of the intensity of the adrenal tumor to the adjacent liver or fat. Subsequent studies showed that the separation between the two groups was not so complete, with an overlap between approximately 20% to 30%. The overlap is even more extensive on higher field magnets; at 1.5 T the calculated T2 relaxation time of the tumor is the most useful criterion, but even here some overlap between metastasis and adenoma is observed. 33,34 More recent MRI investigations have evaluated a number of different sequences and techniques, including gradient echo sequences and gadolinium-enhanced patterns. Although some investigations have suggested that the pattern of gadolinium enhancement differs significantly between adrenal adenomas and nonadenomas, 35 other studies have not confirmed these initial observations. 36,37The most promising new approach is chemical shift imaging. This technique takes advantage Of the different resonant frequency peaks that exist for hydrogen atoms
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Fig 17. Bilateral adrenal adenomas. (A) Tl-weighted, in-phase gradient echo MRI shows adrenal masses that are nearly isointense compared to the liver. (B) Opposed-phase image shows that the adrenal masses are now hypointense compared with liver, indicating that they contain lipid as well as water elements.
in water and triglyceride (lipid) molecules. The result of this difference is a decrease in the signal intensity of tissue containing both lipid and water, as compared with tissue containing no lipid. Because many adrenal adenomas contain large amounts of cytoplasmic lipid, they should be ideally suited for detection by the lipid-sensitive chemical shift MRI techniques. Using opposed-phase, breath-hold, gradient echo sequences, a specific type of chemical shift technique, several investigators have now shown good results for differentiating adrenal adenomas from metastases and other nonadenomatous masses. 36-4° In a retrospective study using qualitative simple visual analysis, Mitchell et a138 showed a relative loss of signal intensity of adrenal masses compared with upper abdomi-
nal tissues in 95% of adenomas and in none of their nonadenomas. In a prospective study using a more elaborate qualitative analysis, we also showed37 that only adrenal adenomas showed a decrease in relative signal intensity on opposed phase images (Figs 17 and 18). The sensitivity of this finding was approximately 80% when the adrenal mass was compared with liver or muscle. Other recent studies have emphasized the use of a quantitative threshold value that appears to separate adenomas from nonadenomas.36,4° One of these studies4° (the only one reported at 0.5 T rather than the more common 1.5 T) described a signal intensity ratio comparing the adrenal masses with spleen that resulted in no overlap between the two groups (sensitivity and specificity both equal to 100%).
Fig 18. Left adrenal metastasis. (A} Tl-weighted, in.phase gradient echo MRI shows a small left adrenal mass (M) that is hypointense compared with liver and isointense compared with the paraspinal muscles. (B) Opposed-phase image shows that the adrenal mass {M) has retained its relative signal intensity in comparison with the liver and paraspinal muscles, indicating that it does not contain a significant amount of lipid.
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our own experience and seven publications (total of 666 percutaneous adrenal biopsies), the complication rate for percutaneous adrenal biopsy ranges from 1% to 12%, with an overall rate of 5.3%. 44 A recent study of 97 patients reported an overall complication rate of 9%, 4z whereas another study of 277 patients found a major complication rate of 2.8%. 45 These rates are comparable with our own recent study of 83 biopsies, which showed a major complication rate of 3.6% and a total complication rate of 8.4%. 44
Fig 19. Percutaneous CT-guided fine-needle aspiration biopsy of a small left adrenal mass performed with the patient in
the prone position, complicated by pneumothorax. (Reprinted with permission from J Comput Assist Tomogr. 44)
Although it is now clear that opposed-phase chemical shift imaging can characterize an adrenal mass as an adenoma with a high degree of specificity and an acceptable sensitivity, it is currently uncertain whether quantitative methods using calculated signal intensity ratios or qualitative assessment using simple visual analysis will be adopted by the radiological community. Percutaneous biopsy. Although we are rapidly approaching the time when unenhanced CT values and/or opposed-phase chemical shift MRI will be used to characterize many adrenal masses as adenomas, avoiding the necessity of percutaneous adrenal biopsy, we currently perform biopsies in many oncology patients. The reported accuracy of percutaneous biopsy varies from 80% to 1 0 0 % . 41 As in other sites, a positive result almost always accurately indicates a malignant lesion, whereas a negative result may indicate a benign adenoma, an inadequate specimen, or a sampling error. 42 The most commonly reported complications of adrenal biopsy are hemorrhage (Fig 19) and pneumothorax (Fig 20), with isolated reports of acute pancreatitis, 43 adrenal abscess, bacteremia, and needle tract metastasis. 44It is difficult to assess a true complication rate for percutaneous adrenal biopsy, because many of the reported series involve a small number of patients. In addition, some papers report all complications, while others tabulate only "major" complications (those requiring treatment or hospitalization). Based on the compilation of
Fig 20. Right adrenal mass biopsy performed using the transhepatic approach, with the patient in the left decubitus pQsition, complicated by subcapsular and intrahepatic hemorrhage. (A) 22-gauge needle traversing the liver. (B) Large subcapsular hematoma (arrowheads) and intrahepatic hematoma (arrow). (Reprinted with permission from J Comput Assist Tomogr. 44)
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1, Francis IR, Gross MD, Shapiro B, et al: Integrated imaging of adrenal disease. Radiology 184:1-13, 1992 2. Dunnick NR: Adrenal imaging: Current status. AJR Am J Roentgenol 154:927-936, 1990 3. Young WF Jr, Hogan M J, Klee GG, et al: Primary aldosteronism: Diagnosis and treatment. Mayo Clin Proc 65:96-110, 1990 4. White EA, Schambelan M, Rost CR, et al: Use of computed tomography in diagnosing the cause of primary aldosteronism. N Engl J Med 303:1503-1507, 1980 5. Geisinger MA, Zelch MG, Bravo EL, et al: Primary hyperaldosteronism: Comparison of CT, adrenal venography and venous sampling. AJR Am J Roentgenol 141:299302, 1983 6. Ikeda DM, Francis 1R, Glazer GM, et al: The detection of adrenal tumors and hyperplasia in patients with primary aldosteronism: Comparison of scintigraphy, CT and MR imaging. AJR Am J Roentgenol 153:301-306, 1989 7. Dunnick NR, Leight GS, Roubidoux MA, et al: CT in the diagnosis of primary aldosteronism: sensitivity in 29 patients. AJR Am J Roentgenol 160:321-324, 1993 8. Hollack CEM, Prummel MF, Tiel-Van Buul MMC: Bilateral adrenal tumors in primary aldosteronism: Localization of a unilateral aldosteronoma by dexamethasone suppression scan. J Intern Med 119:545-548, 1991 9. Doppman JL, Gill JR, Miller DL, et al: Distinction between hyperaldosteronism due to bilateral hyperplasia and unilateral aldosteronoma: Reliability of CT. Radiology 184:677-682, 1992 10. Blevins LS, Wand GS: Primary aldosteronism: An endocrine perspective. Radiology 184:599-600, 1992 11. Musante F, Derchi LE, Zappasodi F, et al: Myelolipoma of the adrenal gland: Sonographic and CT features. AJR Am J Roentgenol 151:961-964, 1988 12, Palmer WE, Gerard-McFarland EL, Chew FS: Adrenal myelolipoma. AJR Am J Roentgenol 156:724, 1991 13. Wolverson MK, Kannegiesser H: CT of bilateral adrenal hemorrhage with acute adrenal insufficiency in the adult. AJR Am J Roentgenol 142:311-314, 1984 14. Ling D, Korobkin M, Silverman PM, et al: CT demonstration of bilateral adrenal hemorrhage. A JR Am J Roentgenol 141:307-308, 1983 15. Murphy BJ, Casillas J, Yrizarry JM: Traumatic adrenal hemorrhage: Radiologic findings. Radiology 169:701703, 1988 16. Bowen A, Keslar PJ, Newman B, et al: Adrenal hemorrhage after liver transplantation. Radiology 176:8588, 1990 17. Solomon N, Sumkin J: Right adrenal gland hemorrhage as a complication of liver transplantation: CT appearance. J Comput Assist Tomogr 12:95-97, 1988 18. Cheema P, Cartegena R, Staubitz W: Adrenal cysts: Diagnosis and treatment. J Urol 126:396-399, 1981 19. Johnson CD, Baker ME, Dunnick NR: CT demonstration of an adrenal pseudocyst. J Comput Assist Tomogr 9:817-819, 1985 20. Wilson DA, Muchmore HG, Tisdal RG, et al: Histoplasmosis of the adrenal glands studied by CT. Radiology 150:779-783, 1984
21. Commons RR, Callaway CP: Adenomas of the adrenal cortex. Arch Intern Med 81:37-41, 1984 22. Dunnick NR, Heaston D, Halvorsen R, et al: CT appearance of adrenal cortical carcinoma. J Comput Assist Tomogr 6:978-982, 1982 23. Fishman EK, Deutch BM, Hartman DS, et al: Primary adrenoeortical carcinoma: CT evaluation with clinical correlation. A JR Am J Roentgenol 148:531-535, 1987 24. Oliver TW Jr, Bernardino ME, Miller JL, et al: Isolated adrenal masses in non-small cell bronchogenic carcinoma. Radiology 153:217-218, 1984 25. Francis IR, Staid A, Gross MD, et al: Adrenal masses in oncologic patients: Functional and morphologic evaluation. Radiology 166:353-356, 1988 26. Lee M J, Hahn PF, Papanicolaou N, et al: Benign and malignant adrenal masses: CT distinction with attenuation coefficients, size, and observer analysis. Radiology 179:415518, 1991 27. Brodeur FJ, KorobkJn M, Yutzy GG, et al: Differentiation of adrenal adenomas from nonadenomas using CT attenuation numbers. Radiology 193(P):195, 1994 28. van Erkel AR, van Gils APG, Lequin M, et al: CT and MR distinction of adenomas and nonadenomas of the adrenal gland. J Comput Assist Tomogr 18:432-438, 1994 29. Singer AA, Obuchowski NA, Einstein DM, et al: Metastasis or adenoma? Computed tomographic evaluation of the adrenal mass. Cleve Clin J Med 61:200-205, 1994 30. Reinig JW, Doppman JL, Dwyer AJ, et al: MRI of indeterminate adrenal masses. AJR Am J Roentgenol 147:493-496, 1986 31. Glazer GM, Woolsey EJ, Borrello J, et al: Adrenal tissue characterization using MR imaging. Radiology 158:7379, 1986 32. Chang A, Glazer HS, Lee JKT, et al: Adrenal gland: MR imaging. Radiology 163:123-128, 1987 33. Baker ME, Blinder R, Spritzer C, et al: MR evaluation of adrenal masses at 1.5 T. AJR Am J Roentgenol 153:307-312, 1989 34. Kier R, McCarthy S: MR characterization of adrenal masses: Field strength and pulse sequence considerations. Radiology 171:671-674, 1989 35. Krestin GP, Steinbrich W, Friedmann G: Adrenal masses: Evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies. Radiology 171:675680, 1989 36. Reinig JW, Stutley JE, Leonhardt CM, et al: Differentiation of adrenal masses with MR imaging: Comparison of techniques. Radiology 192:41-46, 1994 37. Korobkin M, Lombardi TJ, Aisen AM, et al: Characterization of adrenal masses using chemical shift and gadolinium enhanced MR imaging. Radiology 1995 (in press) 38. Mitchell DG, Crovello M, Matteucci T, et al: Benign adrenocortical masses: Diagnosis with chemical shift MR imaging. Radiology 185:345-35l, 1992 39. Tsushima Y, Ishizaka H, Matsumoto: Adrenal masses: Differentiation with chemical shift, fast low-angle shot MR imaging. Radiology 186:705-709, 1993 40. Bilbey JH, McLoughlin RF, Kurkjian PS: MR of adrenal masses: Value of chemical-shift imaging to distin-
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guish adenomas from other tumors. AJR Am J Roentgenol 1995 (in press) 41. Bernardino ME, Walther MM, Phillips VM, et al: CT-guided adrenal biopsy: Accuracy, safety, and indications. AJR Am J Roentgenol 144:67-69, 1985 42. Silverman SG, Mueller PR, Pinkney LP, et al: Predictive value of image-guided adrenal biopsy: Analysis of results of 101 biopsies. Radiology 187:715-718, 1993 43. Kane NM, Korobkin M, Francis IR, et al: Percutane-
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ous biopsy of left adrenal masses: Prevalence of pancreatitis after anterior approach. AJR Am J Roentgenol 157:777780, 1991 44. Mody MK, Kazerooni EA, Korobkin M: Percutaneous biopsy of adrenal masses: Immediate and delayed complications. J Comput Assist Tomogr 1995 (in press) 45. Welch TJ, Sheedy PF II, Johnson CM, et al: Percutaneous adrenal biopsy: Review of 10-year experience. Radiology 193:341-344, 1994
Copyright © 1995 by W.B. Saunders Company
T IS THE IMAGING procedure of choice for evaluation of the adrenal glands. CT is C commonly used to detect or exclude an adrenal mass, although its ability to characterize the nature of such a mass is somewhat limited. In this overview we will summarize the indications for adrenal CT, the CT findings in a variety of adrenal disorders, and the use of radionuclide imaging and MRI to supplement CT findings in selected cases. 1,2 HYPERFUNCTIONING ADRENAL MASSES
CT is often performed when clinical and biochemical studies indicate the presence of abnormal adrenal function. The most common hyperfunctioning adrenal disorders are Cushing's syndrome, primarY aldosteronism (Conn's syndrome) and pheochromocytoma.
Cushing's Syndrome About 70% of patients with Cushing's syndrome have bilateral adrenal hyperplasia, usually caused by a pituitary adenoma. In these patients, CT often shows either normal adrenals (Fig 1) or diffuse thickening of the limbs of both glands (Fig 2). A small percentage of patients have nodules (Fig 3) superimposed on normal or enlarged glands (nodular adrenal hyperplasia). A unilateral cortical adenoma is the cause in about 20% of cases of Cushing's syndrome, and the remaining cases are caused by an adrenal cortical carcinoma. An adenoma typically is smaller than 5 cm and has a nonspecific appearance. Adrenal cortical carcinoma usually is larger than 5 cm and often has central necrosis or evidence of metastatic spread. CT
can detect or exclude a unilateral adrenal mass in virtually 100% of patients with Cushing's syndrome, in part because of the abundant retroperitoneal fat present in this condition. Although CT distinction between adenoma and carcinoma may be impossible for masses between 4 cm and 6 cm in size, this has little practical implication in patients with Cushing's syndrome because surgical resection is performed for either entity in the absence of known metastatic disease.
PrimaryAMosteronism Primary aldosteronism is characterized by moderate to severe hypertension caused by unregulated secretion of excessive amounts of aldosterone. Biochemically, this condition is associated with elevated serum and urinary levels of aldosterone, hypokalemia, and suppression of plasma renin activity. A solitary aldosterone-producing adenoma (APA) is present in about 70% of patients, and surgical adrenalectomy corrects hypertension and hypokalemia in about 75% to 90% of these patients. Most of the other patients have idiopathic hyperaldosteronism (IHA) with bilateral adrenal hyperplasia. Unlike patients with unilateral APA, surgery rarely cures hypertension, and results in permanent adrenal insufficiency. These patients usu-
From the University of Michigan Hospitals, Department of Radiology, Ann Arbor, MI. Address reprintrequests to Melvyn Korobkin, MD, University of Michigan Hospitals, Department of Radiology, 1500 E Medical Center Dr, B1D520, Ann Arbor, MI 48109-0030. Copyright © 1995 by W.B. Saunders Company 0887-2171/95/1604-000655. 00/0
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Fig 1. CT appearance of normal adrenal glands. (A) The cephalad portion of the right adrenal (arrow) is seen. (B) The three limbs of the left adrenal (arrow) are shown at this level.
ally are treated medically. It is essential, therefore, to differentiate between these two major types of primary aldosteronism. Adrenal CT is less accurate in the evaluation
of primary aldosteronism than it is in the evaluation of Cushing's syndrome and pheochromocytomas (discussed below), because the aldosteronoma is usually a smaller mass (Fig 4). In one
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Fig 2. Cushing's syndrome with bilateral adrenal hyperplasia caused by an ectopic source of ACTH production. CT shows extreme thickening of the limbs of both adrenals (A).
large series, the mean diameter was 18 mm, and 20% were 10 mm or smaller? Using early generation CT scanners, CT sensitivity for detection of APA varied between 50% to 70%. 4 In one series, all aldosteronomas 1.5 cm or larger were detected, whereas only 50% between 10 and 14 mm were identified. 5 More recent studies using current-generation scanners have reported sensitivities of 82% and 88%. 6,7 CT evaluation is hampered because a unilateral aldosteronoma may be associated with n o n aldosterone-secreting nodules in the ipsilateral or contralateral gland, which can result in a false diagnosis of adrenal hyperplasia. 8 In addi-
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tion, bilateral hyperplasia may have a predominant unilateral macronodule and cause an erroneous diagnosis of a unilateral aldosteronoma. Doppman et al 9 recently demonstrated that CT cannot reliably differentiate A P A from I H A whenever bilateral adrenal nodules are shown. In their series, 6 of 21 patients with an A P A were incorrectly diagnosed from CT as having IHA. Non-aldosterone-secreting nodules were detected by CT in addition to aldosteronomas. Sophisticated diagnostic endocrine studies often point to the diagnosis of A P A or I H A and should be used in conjunction with CT findings to make a preliminary diagnosis. Most patients with a unilateral adrenal mass can proceed to unilateral adrenalectomy. Patients with bilateral adrenal nodules, as well as those in whom CT and biochemical evaluations are discordant or equivocal, should probably undergo bilateral selective adrenal vein sampling for aldosterone levels, z°
Pheochromocytoma Adrenal pheochromocytomas usually are large (2 to 5 cm in diameter) and are easily detected with CT (Fig 5A). Intravenous contrast enhancement should not be used in patients suspected of pheochromocytoma, unless alpha-adrenergic blocking drugs have been administered. About 10% of pheochromocytomas are extra-adrenal in location, and these can be difficult to identify. If the adrenals are normal in a patient with
Fig 3. Cushing's syndrome with nodular adrenal hyperplasia. (A) CT shows a nodule (arrow) at the posterior aspect of the right adrenal. (B) A nodule (arrow) is also present in the left adrenal,
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Fig 4. Primary aldosteronism caused by a hyperfunctioning adrenal adenoma. CT shows a 1-cm right adrenal mass (arrow).
compelling biochemical evidence of a pheochromocytoma, the remainder of the abdomen and pelvis should be scanned. Radionuclide scanning with iodine-labelled meta-iodobenzyl guanidine (MIBG) is useful for detecting adrenergic tissue, 1 and this technique is often used to scan the entire body for primary and metastatic pheochromocytoma (Fig 5B). MRI can also be used in selected problem cases; signal intensity of pheochromocytoma tends to be very high on T2-weighted images, especially on medium field strength magnets (Fig 6). Although many extra-adrenal pheochromocy-
tomas in the chest are readily seen as paravertebral masses on standard chest radiographs, we have seen several intracardiac pheochromocytomas that were not seen or clearly localized on chest film. Patients were typically referred to our hospital with unsuccessful localization of a biochemically proven pheochromocytoma. MIBG scintigraphy showed abnormal uptake in the lower thorax (Fig 7A). Bolus-enhanced CT demonstrated the surgically proven tumor in all 13 cases (Fig 7B). Most were localized superior to the left atrium, but one was anterior to the aortic root, and another was lateral to the aortic
Fig 5. Adrenal pheochromocytoma. (A) CT shows a 5-cm left adrenal mass {M). (B) MIBG scintigram shows intense uptake in the same mass (arrow). L, liver.
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tected incidentally on abdominal CT scans performed for a variety of disorders. Some adrenal masses have CT features specific for a particular diagnosis, such as hemorrhage or myelolipoma, but most masses are nonspecific on CT and require other noninvasive or invasive imaging studies for more definitive diagnosis. These
Fig 6. Adrenal pheochromocytoma.T2-weighted MRI shows a left adrenal mass with high signal intensity (m).
arch. The tumors ranged in size from 3 to 8 cm, and about half showed central areas of low attenuation. These intracardiac pheochromocytomas were not visible on unenhanced or nonbolus-enhanced CT image s.
Adrenal Insufficiency Adrenal insufficiency, or Addison's disease, is usually idiopathic in origin in this country, and these cases probably are consequences of autoimmune disorders. On imaging studies, the adrenals can be undetected or markedly diminutive in size in patients with adrenal insufficiency (Fig 8). Less often, and frequently undiagnosed or misdiagnosed, adrenal insufficiency results from destruction by bilateral hemorrhage, infection, or metastatic neoplasm. Bilateral adrenal hemorrhage is often first diagnosed by CT, especially when the high attenuation of acute or subacute hematoma is recognized. Bilateral tuberculosis, histoplasmosis, or other granulomatous disease is sometimes associated with adrenal calcification, but the findings are often nonspecific and diagnosis requires biopsy confirmation. NONHYPERFUNCTIONING ADRENAL MASSES
Most adrenal masses detected by CT are found in patients without evidence of known adrenal endocrine dysfunction. They are de-
Fig 7. Cardiac pheochromocytoma (A) MIBG scintigram shows a prominent focus of increased tracer uptake in the thoracic midline (arrow). L, liver. (B) Enhanced CT shows a large inhomogeneous mass (M) in the region of the left atrium.
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Fig 8. Bilateral adrenal atrophy. CT shows markedly thin adrenals (arrows) in this patient with idiopathic adrenal insufficiency.
include radionuclide imaging with iodine-131-6iodomethyl-19-norcholesterol (NP-59), MRI, or percutaneous aspiration biopsy. In the discussion of nonhyperfunctioning adrenal masses, it is useful to distinguish between patients with known primary neoplasms and those in whom an adrenal mass is a strictly incidental finding.
Myelolipoma Adrenal myelolipoma is a benign neoplasm of the cortex composed of mature fat and myeloid tissue found in normal bone marrow. Although uncommon, myelolipoma is not a rare lesion. In a busy abdominal CT practice we see three or four cases every year. Most are asymptomatic and represent incidental findings on CT, although larger lesions may cause pain or may be associated with intratumoral hemorrhage. Sonographic features usually suggest the diagnosis of myelolipoma, because most lesions are highly echogenic, xl For large tumors, propagationspeed artifact producing apparent posterior displacement of the diaphragm is additional evidence favoring a fatty tumor. MRI of myelolipoma shows bright signal intensity on T1weighted images and intermediate signal intensity on T2-weighted images. Although a malignant adrenal lesion can engulf surrounding fat and simulate a myeloli-
poma, in most cases the diagnosis of myelolipoma can be made with confidence when CT measurements confirm the presence of discrete regions of fat attenuation within an adrenal mass. 12 The proportion of CT-detectable fat within an adrenal myelolipoma is variable; in some patients most of the tumor consists of fatty tissue, but in others, thin CT sections of 5 mm or less may be necessary to detect smaller amounts of fat (Fig 9). Thin CT sections may also be
Fig 9. Adrenal myelolipoma. A small amount of fatattenuation tissue (arrow) is seen within this right adrenal mass.
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necessary to resolve questions of a small myelolipoma that can be simulated by partial volume effect of normal extra-adrenal fat on more widely collimated scans. In cases complicated by infarction or hemorrhage, the imaging findings of acute, subacute, or chronic hemorrhage are superimposed on the lesion, potentially complicating the diagnosis. Differential diagnosis includes angiomyolipoma of the upper pole of the kidney, as well as a lipoma or liposarcoma of the adrenal gland or the surrounding retroperitoneal fat. The diagnosis of myelolipoma is usually based on CT alone, although confirmation by percutaneous biopsy has also been reported. Hemorrhage Adrenal hemorrhage can be unilateral or bilateral. When bilateral, it can cause adrenal insufficiency and death if not properly diagnosed and treated. Hypoadrenalism is usually not recognized clinically at the time that CT detects the disorder. 13 Clinical manifestations of adrenal insufficiency in adults often mimic more common conditions such as myocardial infarction, sepsis, or an acute surgical abdomen. Although the clinical diagnosis is sometimes suspected from an abnormally low level of plasma cortisol, the cortisol levels can be normal, and biochemical confirmation in such cases rests on an abnormal response to an adrenocorticotrophic hormone stimulation test. Bilateral adrenal hemorrhage is usually associated with anticoagulant therapy or with the stress caused by surgery, sepsis, or hypotension. Less commonly, it is caused by trauma or hypoxia during delivery. Most anticoagulantassociated adrenal hemorrhage occurs during the first three weeks of treatment. Hemorrhage in such cases is apparently not caused by excessive anticoagulation because prothrombin levels are usually in the therapeutic range, and hemorrhage into the rest of the retroperitoneum or other organs usually does not occur. CT of bilateral adrenal hemorrhage shows both glands to be enlarged, although often in an asymmetric manner. The glands usually having an oval or rounded shape. 13,14The CT density of the glands varies in relation to the time between the hemorrhage and CT examination. An acute or subacute hemorrhage is characterized by high attenuation (50 to 90 HU) within the
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hematoma (Fig 10). Follow-up studies after appropriate treatment show diminution in size of the adrenal masses and a gradual decrease in attenuation value. In the appropriate clinical setting, the detection of bilateral high-attenuation adrenal masses should lead to immediate biochemical studies for adrenal insufficiency, and initiation of prompt therapy with intravenous steroids should be considered. In the older child and adult, unilateral adrenal hemorrhage is usually caused by blunt abdominal trauma. 15 Most unilateral hematomas involve the right adrenal (Fig 11), and associated injuries such as rib fractures or liver injury usually dominate the clinical picture. The CT features are similar to those seen in bilateral hemorrhage except that streaky infiltration of the periadrenal fat is common. Unilateral adrenal hemorrhage has also recently been described in patients undergoing liver transplantation. 16A7 The excision of a segment of the recipient's inferior vena cava typically necessitates ligation and division of the right adrenal vein, sometimes resulting in venous infarction and/or hemorrhage into the right adrenal gland. Sonography and CT have demonstrated right adrenal hemorrhage in about 2% of patients undergoing orthotopic liver transplantation. However, the true incidence of posttransplant adrenal hemorrhage is unknown because imaging procedures are not performed routinely. Postmortem studies in children who died after
Fig 10. Bilateral adrenal hemorrhage. CT shows a high attenuation mass in both adrenals, right (R) larger than left (L), in this patient with adrenal insufficiency after blunt abdominal trauma.
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lateral metastases, or less common combinations of adrenal lesions (eg, adenoma or metastasis) are included in the differential diagnosis. Adenoma Versus Carcinoma
Fig 11. Unilateral adrenal hemorrhage. CT shows a high attenuation right adrenal hematoma (H). Note the streaky soft-tissue attenuation in the periadrenal fat posterior to the adrenal hematoma, a feature commonly associated with traumatic adrenal hemorrhage.
liver transplantation showed a large right adrenal hemorrhage in 10% of cases. Cyst Although we list cysts in the group with characteristic CT findings, there is a remarkable paucity of reports on the CT appearance of adrenal cysts. Either gland can be involved, and there is a 3:1 female predilection. Pathologically, four types of adrenal cysts are recognized: endothelial, epithelial, parasitic, and pseudocysts. 18 Adrenal pseudocysts, probably caused by prior hemorrhage into a normal or abnormal gland, are most commonly detected radiologically. Adrenal cysts, especially pseudocysts, can have a thickened wall, nodularity, septation, or soft tissue components making it difficult to exclude a neoplasm 19 (Fig 12).
Nonhyperfunctioning adrenal adenomas are common neoplasms, as indicated by an incidence of 2.8% for adenomas larger than 3 mm in one autopsy study. 21 Adenomas larger than 1 cm are seen in about 1% of patients undergoing abdominal CT. These "incidentalomas" must be differentiated from adrenal cortical carcinoma (as well as metastases, discussed below). Unlike adenomas, adrenal cortical carcinomas are rare and often present with abdominal pain or a palpable mass. About half of patients with adrenal carcinoma will show manifestations of excess hormone production (usually Cushing's syndrome). CT features typical of benign adenomas include (1) smooth contour, (2) sharp margination, and (3) size smaller than 5 cm (Fig 13). When these features are present and biochemical studies are normal, surveillance with CT at 6 and 12 months is often recommended to confirm lack of growth. Lesions larger than 5 cm, or those with irregular margins, should be removed because they are atypical of benign adenoma. Features typical of carcinoma are (1) size larger than 5 cm, (2) central areas of low attenuation caused by tumor necrosis, (3) tumor calcification, and (4) evidence of hepatic, nodal, or venous spread 22,23 (Fig 14). On MRI, an adrenal carcinoma typically shows high signal
Granulomatous Disease Tuberculosis, histoplasmosis, or other granulomatous infection usually involves both adrenal glands, but often in an asymmetric pattern. The CT features are nonspecific and include soft tissue masses, cystic changes, and calcification reflecting the age of the process and degree of necrosis. 2° Percutaneous biopsy is often required to confirm the diagnosis of granulomatous disease and to identify the organism. The absence of high attenuation within the lesions usually helps exclude bilateral hemorrhage. Bi-
Fig 12. Adrenal pseudocyst. CT shows a thick-walled right adrenal cyst caused by an old traumatic hemorrhage.
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Adrenal metastases are not nearly as common as nonhyperfunctioning adrenal cortical adenomas, but they occur with sufficient frequency to cause significant problems with differential diagnosis. This problem has been a topic of continuing investigation for several years. When an adrenal mass is the only finding suspicious of metastatic disease in an oncologic patient, confirmation of its nature may be crucial in determining whether curative therapy of
the primary neoplasm is warranted. This issue occurs most commonly in patients with carcinoma of the lung, because confirmation of an isolated adrenal metastasis will preclude a thoracotomy or curative radiotherapy program. Even in patients with lung cancer, an adrenal mass is more likely to be an adenoma than a metastasis. 24 Although some CT features are more commonly found in metastases than in adenomas, no single feature or combination of features can reliably distinguish a metastasis from an adenoma. Metastases tend to be larger and less well defined than adenomas. Metastases also tend to have inhomogeneous attenuation and a thick irregular enhancing rim (Fig 15). Adenomas tend to be smaller and homogeneous in density. Because CT imaging features alone do not usually permit unequivocal differentiation of adrenal adenomas and metastases, percutaneous biopsy is often used to establish the correct diagnosis. Extensive investigation has been undertaken recently on potential noninvasive approaches to making this critical differential diagnosis. The focus of this effort has been on three different methodologies: NP-59 scintigraphy, CT densitometry, and MRI. NP-59 scintigraphy. Francis et a125 reported on the use of NP-59 scintigraphy in evaluation of 28 oncologic patients with unilateral adrenal mass. Adenomas larger than 2 cm accumulate NP-59, whereas metastases do not. Thus, functioning adrenal tissue is suggested if the NP-59 scintigram is "hot" on the side of the CTdepicted adrenal mass (Fig 16). Each of the 14
Fig 14. Adrenal carcinoma. CT shows a large (>5 cm) inhomogeneous right adrenal mass, highly suggestive of a primary carcinoma in this patien t without a known extraadrenal neoplasm.
Fig 15. Bilateral adrenal metastases. CT shows large bilateral adrenal masses in a patient with carcinoma of the lung. There is slight " w a l l " thickening in both lesions.
Fig 13. Adrenal adenoma. Unenhanced CT shows a small, sharply marginated, homogeneous right adrenal mass (M). Visible low attenuation on this unenhanced scan measured close to O HU, highly suggestive of a benign lesion.
intensity on T2-weighted images. On radionuclide imaging, NP-59 accumulates in adenomas and is typically absent in cortical carcinoma.
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Fig 16, Adrenal adenoma. NP-59 scintigram shows increased uptake in the adrenal gland (arrow), confirming that the adrenal mass detected on a prior CT represents an adenoma, L, liver.
patients in this study with concordant uptake had a proven adrenal adenoma. In the 11 patients with decreased uptake on the side of a CT-detected adrenal mass (discordant uptake), none proved to have an adenoma; nine had metastases and two had cysts. Although the absence of NP-59 labelling cannot distinguish between a metastasis and most other forms of adrenal masses, it does seem to exclude an adenoma. Despite these encouraging results, the lack of routine commercial availability of NP-59 has limited its applicability to the adenoma versus metastasis problem. Even in our own institution where NP-59 was developed and is readily available, it has not yet significantly reduced the use of percutaneous biopsy of an adrenal mass in oncologic patients when significant therapeutic decisions depend on the confirmation or exclusion of adrenal metastasis. CTdensitometry. Several recent studies suggest that adenomas can be differentiated from nonadenomatous adrenal masses based on their unenhanced CT attenuation values. In one series the mean attenuation value for 38 benign adrenal masses (presumably mostly adenomas) was -2.2 HU + 10.6 (SD), which was significantly less than a mean of 28.9 HU +- 10.6 for 28 malignant masses. 26 More importantly, none of the malignant lesions had an unenhanced attenuation value less than 0 HU. The sensitivity of CT
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for the diagnosis of benign adrenal mass was 47% and the specificity was 100%. Even at a threshold level of 10 HU, the sensitivity to specificity ratio was 79%:96%. In our own recent series of 51 proved adrenal masses, 27 the mean unenhanced attenuation value was 12 HU - 8.8 for 34 adenomas, which was significantly less than 31 HU --- 6.3 for 17 nonadenomas (Fig 13). More importantly, none of the n0nadenomas had an attenuation value less than 18 HU, whereas 88% of the adenomas did. Based on a threshold value of 10 HU, the sensitivity: specificity ratio for the diagnosis of adrenal adenoma in our study was 75%:96%. Two other recently reported series evaluating unenhanced CT values of adrenal masses have shown similar results. 2s,29 It is now clear that adrenal adenomas can be differentiated from metastases and other nonaden0matous adrenal masses based on their unenhanced CT attenuation values with very high specificity and acceptable sensitivity. MR/. There has been extensive investigation of the MRI features of benign and malignant adrenal lesions. Initial studies using low field strength magnets (0.35 to 0.5 T) suggested that adrenal adenomas had a lower signal intensity on T2-weighted images than did nonadenomas, including metastatic lesions. 3°-32 This was reflected in a lower ratio of the intensity of the adrenal tumor to the adjacent liver or fat. Subsequent studies showed that the separation between the two groups was not so complete, with an overlap between approximately 20% to 30%. The overlap is even more extensive on higher field magnets; at 1.5 T the calculated T2 relaxation time of the tumor is the most useful criterion, but even here some overlap between metastasis and adenoma is observed. 33,34 More recent MRI investigations have evaluated a number of different sequences and techniques, including gradient echo sequences and gadolinium-enhanced patterns. Although some investigations have suggested that the pattern of gadolinium enhancement differs significantly between adrenal adenomas and nonadenomas, 35 other studies have not confirmed these initial observations. 36,37The most promising new approach is chemical shift imaging. This technique takes advantage Of the different resonant frequency peaks that exist for hydrogen atoms
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Fig 17. Bilateral adrenal adenomas. (A) Tl-weighted, in-phase gradient echo MRI shows adrenal masses that are nearly isointense compared to the liver. (B) Opposed-phase image shows that the adrenal masses are now hypointense compared with liver, indicating that they contain lipid as well as water elements.
in water and triglyceride (lipid) molecules. The result of this difference is a decrease in the signal intensity of tissue containing both lipid and water, as compared with tissue containing no lipid. Because many adrenal adenomas contain large amounts of cytoplasmic lipid, they should be ideally suited for detection by the lipid-sensitive chemical shift MRI techniques. Using opposed-phase, breath-hold, gradient echo sequences, a specific type of chemical shift technique, several investigators have now shown good results for differentiating adrenal adenomas from metastases and other nonadenomatous masses. 36-4° In a retrospective study using qualitative simple visual analysis, Mitchell et a138 showed a relative loss of signal intensity of adrenal masses compared with upper abdomi-
nal tissues in 95% of adenomas and in none of their nonadenomas. In a prospective study using a more elaborate qualitative analysis, we also showed37 that only adrenal adenomas showed a decrease in relative signal intensity on opposed phase images (Figs 17 and 18). The sensitivity of this finding was approximately 80% when the adrenal mass was compared with liver or muscle. Other recent studies have emphasized the use of a quantitative threshold value that appears to separate adenomas from nonadenomas.36,4° One of these studies4° (the only one reported at 0.5 T rather than the more common 1.5 T) described a signal intensity ratio comparing the adrenal masses with spleen that resulted in no overlap between the two groups (sensitivity and specificity both equal to 100%).
Fig 18. Left adrenal metastasis. (A} Tl-weighted, in.phase gradient echo MRI shows a small left adrenal mass (M) that is hypointense compared with liver and isointense compared with the paraspinal muscles. (B) Opposed-phase image shows that the adrenal mass {M) has retained its relative signal intensity in comparison with the liver and paraspinal muscles, indicating that it does not contain a significant amount of lipid.
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our own experience and seven publications (total of 666 percutaneous adrenal biopsies), the complication rate for percutaneous adrenal biopsy ranges from 1% to 12%, with an overall rate of 5.3%. 44 A recent study of 97 patients reported an overall complication rate of 9%, 4z whereas another study of 277 patients found a major complication rate of 2.8%. 45 These rates are comparable with our own recent study of 83 biopsies, which showed a major complication rate of 3.6% and a total complication rate of 8.4%. 44
Fig 19. Percutaneous CT-guided fine-needle aspiration biopsy of a small left adrenal mass performed with the patient in
the prone position, complicated by pneumothorax. (Reprinted with permission from J Comput Assist Tomogr. 44)
Although it is now clear that opposed-phase chemical shift imaging can characterize an adrenal mass as an adenoma with a high degree of specificity and an acceptable sensitivity, it is currently uncertain whether quantitative methods using calculated signal intensity ratios or qualitative assessment using simple visual analysis will be adopted by the radiological community. Percutaneous biopsy. Although we are rapidly approaching the time when unenhanced CT values and/or opposed-phase chemical shift MRI will be used to characterize many adrenal masses as adenomas, avoiding the necessity of percutaneous adrenal biopsy, we currently perform biopsies in many oncology patients. The reported accuracy of percutaneous biopsy varies from 80% to 1 0 0 % . 41 As in other sites, a positive result almost always accurately indicates a malignant lesion, whereas a negative result may indicate a benign adenoma, an inadequate specimen, or a sampling error. 42 The most commonly reported complications of adrenal biopsy are hemorrhage (Fig 19) and pneumothorax (Fig 20), with isolated reports of acute pancreatitis, 43 adrenal abscess, bacteremia, and needle tract metastasis. 44It is difficult to assess a true complication rate for percutaneous adrenal biopsy, because many of the reported series involve a small number of patients. In addition, some papers report all complications, while others tabulate only "major" complications (those requiring treatment or hospitalization). Based on the compilation of
Fig 20. Right adrenal mass biopsy performed using the transhepatic approach, with the patient in the left decubitus pQsition, complicated by subcapsular and intrahepatic hemorrhage. (A) 22-gauge needle traversing the liver. (B) Large subcapsular hematoma (arrowheads) and intrahepatic hematoma (arrow). (Reprinted with permission from J Comput Assist Tomogr. 44)
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