Applied Radiology

Radiologic evaluation of adrenal masses plays a primary role in patients with adrenal masses of unknown etiology. Benign adrenal masses of no particular significance, such as small cysts and most adenomas, are common, incidentally discovered lesions. These masses must be distinguished from those masses that may require a specific histologic diagnosis, such as adrenal metastasis, adrenal cortical carcinomas, and pheochromocytomas.

Fortunately, the majority of adrenal adenomas can be distinguished from these entities. This distinction relies on the fact that most adrenal adenomas contain abundant intracellular lipid. This lipid can be detected specifically by using so-called MR chemical-shift techniques or by measurement of attenuation on unenhanced CT scans. Masses that do not demonstrate such lipid may require histologic diagnosis, except in those cases where the clinical situation or endocrinologic findings provide a specific diagnosis.

This review will concentrate on the differentiation of lipid-containing adrenal adenomas from other adrenal masses, usually metastasis in oncologic patients. Helpful diagnostic signs of other primary adrenal neoplasms on MRI will be discussed.

Adenomas vs metastases

A distinction is made pathologically between true adrenal adenomas and the much more common adrenal cortical nodules.1,2 Adrenal adenomas are grossly distinct masses in the adrenal gland that are well-demarcated from the surrounding adrenal gland. In these cases, the surrounding adrenal cortex is either normal or atrophic due to the suppression by feedback mechanisms from the overproduction of steroid hormones.1,2

Adrenal adenomas most commonly are hyperfunctioning, producing either aldosterone or cortisol. Adrenal cortical nodules are much more common as incidental findings. Most commonly, they are not hyperfunctioning and not associated with any detectable hormonal disturbance. Grossly, they are not as discrete as the adrenal adenomas and are poorly demarcated from the remainder of the gland. The rest of the adrenal is mildly hyperplastic or has small nodules scattered within it. Adrenal cortical nodules are common findings in older patients, especially those with atherosclerotic disease.2 Both adrenal adenomas and adrenal cortical nodules almost always contain large amounts of intracellular steroid hormone production.

A variety of MR imaging techniques have been used to evaluate adrenal masses. On average, many adrenal adenomas will demonstrate lower signal intensity on T2-weighted images than adrenal metastases or other solid adrenal masses.3,4 Dynamic gadolinium-enhanced images also have been used to differentiate adrenal adenomas from other masses. Many adrenal masses, including most metastases and pheochromocytomas, will demonstrate fairly rapid enhancement during a dynamic gadolinium study.5 Most adrenal adenomas, however, will demonstrate mild enhancement or peripheral enhancement. T2-weighted images and dynamic studies have some specificity for distinguishing benign from malignant adrenal masses; however, there is considerable overlap in appearance between adenomas and metastases (figure 1), and these studies should not be relied on for diagnosis.6-8

Chemical-shift imaging techniques are most useful for the evaluation of possible adrenal adenoma. These techniques are designed to detect the presence of lipid within adrenal adenomas. Intracellular lipid is abundant in nearly all adrenal adenomas, both functioning and nonfunctioning. This lipid is used in the production of steroid hormones produced by the adrenal gland. If such lipid is detected by MR techniques in an adrenal mass, the mass is overwhelmingly likely to be a benign adrenal adenoma.9-11

Chemical-shift imaging refers to specific MR imaging techniques where additional diagnostic information is obtained by taking advantage of the chemical shift or frequency difference between nuclei. The term "chemical shift" is derived from nuclear magnetic resonance spectroscopy, where it is used to define a frequency difference from an internal standard. In MR imaging, it is used loosely to describe imaging in which the frequency difference between fat and water is taken advantage of.

In a constant magnetic field, fat and water process at slightly different frequencies. This difference is 220 Hz at 1.5 Tesla, 160 Hz at 1.0 Tesla, and 80 Hz at 0.5 Tesla. Opposed-phase images are achieved via T1-weighted gradient recalled echo sequences (e.g., 2D FLASH) by selecting the TE such that the transverse magnetization of water and fat are opposed (e.g., TE = 2.1 or 6.3 msec at 1.5 Tesla).12 In these sequences, the signal represents the difference between the individual fat and water contributions.

Practically, the TE need not be an exact multiple of 2.1 to 2.3 to achieve the opposed-phase effect; imaging constraints sometimes require a slightly different TE (figure 1). Evidence of adequate opposed-phase effect can be seen at fat-water interfaces, where a black-line artifact may be seen, or in bone marrow, where there is intermixed fatty and hematopoetic marrow. The opposed-phase image should be compared to an in-phase image, where individual fat and water contributions are additive (e.g., TE = 4.2 msec at 1.5 Tesla). In order to produce T1 contrast on gradient-recalled echo pulse sequences, a TR greater than 100 msec and a flip angle of 75° to 90° typically are selected.

A large number of studies have established that opposed-phase techniques are helpful for diagnosing a subset of adrenal adenomas.8,9,13-19 Both quantitative and qualitative assessments of the opposed-phase images have been performed. In quantitative image analysis, the signal intensity of the adrenal mass and the signal intensity of the spleen are measured on the in-phase and opposed-phase image. Ideally, the sequence parameters (TR, field of view, acquisition matrix, slice thickness, etc.) are identical between the two sequences, except for the TE. A chemical-shift ratio is computed and is defined as the signal intensity of the adrenal mass on the opposed-phase image divided by the signal intensity of the spleen on the opposed-phase image divided by the signal intensity of the lesion on the in-phase image divided by the signal intensity of the spleen on the in-phase image. A cutoff value of 0.70 to 0.80 yields high specificity for the diagnosis of adenoma.8,13,17,18,20

Qualitative assessment of image contrast is highly accurate as well. For qualitative signal intensity analysis, the relative tissue contrast between the adrenal lesion is compared to spleen on the in-phase image and compared to the spleen on the opposed-phase image to judge whether there is any relative loss of signal intensity on the opposed-phase image.18,20

The efficacy of opposed-phase MR imaging for distinguishing adrenal adenomas from other masses is now well established.11,17,18,20 Intracellular lipid usually is abundant in adenomas and cortical nodules, but metastases and pheochromocytomas lack such lipid (figure 2).9-11

Typical adrenal adenomas exhibit a signal intensity that is similar or greater with respect to spleen or liver on in-phase T1-weighted images.21 On opposed-phase images performed with similar parameters, adrenal adenomas show a reversal of tissue contrast with respect to spleen, demonstrating the presence of lipid.11,13,14,17,18,20,22-24 The presence of MR-observable lipid is highly predictive of a benign lesion, but it also is reported in adrenal carcinomas.25,26

Adrenal metastases to the adrenal gland contain no such deposits of intracellular lipid and, therefore, show no relative loss of signal intensity on opposed-phase images compared to in-phase images (figure 2). Theoretically, some types of metastases, such as those from clear cell carcinomas of the kidney, may have some intracellular lipid that is observable histologically. These types of metastases, however, have not been reported to show loss of signal intensity on opposed-phase images.

MRI vs CT

Many studies of noncontrast-enhanced CT support the use of CT attenuation coefficients (Hounsfield units [HU]) for the diagnosis of most adrenal adenomas.6,16,27-29 Controversy exists as to what attenuation coefficient is the most accurate for discriminating adrenal adenomas from metastasis, but the larger studies suggest a cutoff value of 18 HU.27 More recent studies suggest that delayed contrast-enhanced CT may prove equally efficacious in discriminating adrenal adenomas from metastasis, although other cutoff criteria must be used.30

Because CT and MRI both depend upon the presence of lipid in the adrenal adenoma for a specific diagnosis, it is unclear whether CT or MRI is more accurate for discriminating adrenal adenomas from metastasis. Indeed, studies suggest that measurements of loss of signal on an opposed-phase image and attenuation coefficients on CT are highly correlated and are likely to misclassify the same subset of lesions.31 That is, an adrenal adenoma that contains very little or no lipid is likely to be misclassified as a possible malignant lesion on both types of examinations.

For these reasons, no specific recommendations can be given as to whether MRI or CT is more accurate for classification of adrenal masses as benign or malignant.

Certain subsets of adrenal masses may give discrepant findings on CT and MRI.31 For example, an adrenal cyst will show no evidence of lipid on chemical-shift imaging; therefore, based on these sequences alone, it may be misclassified as a possible malignant lesion. In this situation, T2-weighted images are helpful for correct classification of an adrenal cyst. CT will show low attenuation to the cyst and correctly classify it as a benign adrenal mass. On the other hand, hemorrhagic lesions may give higher attenuation coefficients on CT but be classified correctly on the basis of MR findings, by virtue of high signal intensity on T1-weighted images.

Pheochromocytoma

There are no specific MRI findings for pheochromocytoma. The clinical situation, however, often is helpful in that a patient with biochemical evidence of a pheochromocytoma and an adrenal mass is highly likely to have a pheochromocytoma. They do not demonstrate chemical shift evidence of lipid.

Suggestive MRI findings are very high signal intensity on T2-weighted sequences (figure 3), a pseudocapsule around the adrenal mass, and, frequently, the presence of internal hemorrhage.15,32-36 Because of the high signal intensity on T2, these lesions frequently are seen easily on MRI, and MRI may be the procedure of choice for identifying them in the abdomen.32-38

Adrenal cortical carcinoma

Adrenal cortical carcinoma may be seen at any age. The clinical situation usually suggests that a large mass might be an adrenal cortical carcinoma. They rarely are detected at a small size. On MRI, these masses have a characteristic appearance, with a high signal intensity on T1-weighted images representing hemorrhage and a very heterogeneous appearance on T2-weighted sequences due to necrosis and hemorrhage (figure 4).26,39-41

MRI is particularly useful for evaluation of these masses because it accurately can locate the epicenter of the mass in the adrenal gland with coronal or sagittal images, establishing that the mass does not arise from the pancreas, the liver, or the upper pole of the kidney. Furthermore, MRI may detect the presence of renal vein or IVC invasion. Adrenal cortical carcinoma may contain areas of lipid that are observable on chemical-shift techniques.25,26

Because of the large size of these masses with necrosis, they rarely are confused with adenomas. The clinical significance of MR-observable lipid in adrenal cortical carcinoma is unclear, although undoubtedly it is related to the intracellular lipid needed for adrenocortical steroid hormone production.

Conclusion

The primary function of MRI or CT in evaluating the incidental adrenal mass is to diagnose correctly those adrenal cortical nodules and adenomas that contain lipid. Adrenal masses that do not have CT or MRI evidence of lipid may require biopsy for diagnosis if the clinical context does not make the diagnosis clear. Reasonable MRI and CT criteria to use in the evaluation of incidental adrenal masses are a chemical-shift ratio of 0.70 to 0.80 or computed tomography Hounsfield units of less than 18 for a diagnosis of adenomas.

As a group, adrenal adenomas may be distinguished from metastasis by their T2-weighted signal intensity characteristics and their dynamic gadolinium enhancement pattern. There are less data to support using these measures in individual patients, however, and they should not be relied on for diagnosis of a benign mass.

Other adrenal masses, such as pheochromocytomas and adrenal cortical carcinomas, have suggestive diagnostic signs on MR imaging. There is no specific MRI appearance for these tumors, however, and histologic confirmation is necessary. AR

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