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Adrenal Adenoma Imaging Author: Perry J Horwich, MD; Chief Editor: Eugene C Lin, MD more...

Updated: May 25, 2011

Overview

Adrenal cortical adenoma is a common benign tumor arising from the cortex of the adrenal gland. It commonlyoccurs in adults, but it can be found in persons of any age (see the images below). Adrenal cortical adenomas arenot considered to have the potential for malignant transformation.

Homogeneous, well-defined, 7-HU ovoid mass is seen in the right adrenal gland; this finding is diagnostic of a benign adrenaladenoma.

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Homogeneously enhancing ovoid mass is seen in the left adrenal gland.

Adrenal cortical adenoma can be diagnosed with a high degree of accuracy: the specificity of imaging studies rangesfrom 95-99%, and the sensitivity is greater than 90%. These impressive percentages are a result of the relatively highprevalence of adrenal adenomas in the general population and the extensive radiologic research with imagingmethods, primarily CT and MRI.

The adrenal gland is the fourth most common site of metastasis, and adrenal metastases may be found in as manyas 25% of patients with known primary lesions. Therefore, radiologists frequently face the task of determining

whether an adrenal mass is benign or malignant. The question can directly affect the clinical management of thecase. For instance, the workup for an otherwise resectable lung cancer may reveal the presence of an adrenal massand suggest the possibility of metastatic disease.

The differential diagnosis of adrenal masses includes many primary, metastatic, benign, and malignant entities, mostof which are not discussed at length here. Instead, this article includes practical information that pertains specificallyto adrenal adenomas.

Preferred examination

The modalities of choice in the evaluation of an adrenal mass are computed tomography (CT) scanning, magneticresonance imaging (MRI), and positron emission tomography (PET) scanning. Ultrasonography has a role in theevaluation of a potential adrenal mass in infants, but no appearance is specific for benign adrenal adenoma. [1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11] Note that on CT scans and MRIs, the appearance of intracytoplasmic lipid is different from that of macroscopic fat, as in the case of a myelolipoma .

How should the radiologist proceed in evaluating an incidental small adrenal mass? Two important questions mustbe answered.

First, does the patient have a hormonal or biochemical abnormality that may be caused by an enlarged adrenalgland? If this is the case, the lesion should be surgically removed regardless of the imaging features.

Second, does the patient have a known malignancy? In the absence of a known malignancy, the probability that asmall, well-circumscribed adrenal mass is malignant is nearly zero. The characterization of an adrenal mass is criticalin patients with a known malignancy, in whom the diagnosis of an adrenal metastasis precludes curative surgery.

The authors of a prominent review article suggest that CT without intravenous contrast enhancement should be theinitial study. [1] If the adrenal mass is less than 10 Hounsfield units (HU), a diagnosis of adrenal adenoma can be

made. If the adrenal mass is more than 10 HU, CT with intravenously administered contrast material should follow,and the washout should be calculated; benign lesions typically demonstrate more than 50% washout. In cases inwhich CT findings are equivocal, chemical shift MRI should be performed. When the findings of both modalities areinconclusive, biopsy is advised only when a known extra-adrenal malignancy is present.

Limitations of techniques

Obvious considerations include the availability and cost of CT and MRI. A delay in CT imaging can potentiallydiminish the efficiency of the CT schedule, result in multiple examinations, and expose the patient to ionizingradiation. MRI examination may enable diagnosis without exposing the patient to ionizing radiation; however, MRImay not be as available as CT and can be more expensive.

Radiography

Although plain radiographs can be useful in characterizing old adrenal hemorrhage or commonly calcified adrenalneoplasms, they have no significant role in the diagnosis of adrenal cortical adenoma. [12, 13]

Computed Tomography

CT is, along with MRI, one of the modalities of choice in diagnosing adrenal cortical adenoma.

On CT scans, adrenal cortical adenomas are well-circumscribed mass lesions that are homogeneous in their attenuation and enhancement patterns. The evaluation should be performed by using sections that are 5 mm or thinner to ensure that attenuation measurements are not affected by volume averaging.




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The use of a sufficient milliampere-second (mAs) setting is important so that the measured attenuation values do nothave a significant standard deviation. Heterogeneous enhancement or attenuation can be observed when a lipid-richadenoma and a lipid-poor adenoma coexist. A lesion that is poorly marginated with heterogeneous enhancement isunlikely to be a simple benign adrenal cortical adenoma, and other entities must be considered. [14] (See the imagesbelow.)

Homogeneous, well-defined, 7-HU ovoid mass is seen in the right adrenal gland; this finding is diagnostic of a benign adrenaladenoma.

Contrast-enhanced CT scan demonstrates a homogeneously enhancing ovoid mass in the left adrenal gland. As in this case,attenuation measurements of adrenal masses on contrast-enhanced CT scans are frequently nondiagnostic.

Homogeneously enhancing ovoid mass is seen in the left adrenal gland.




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Dynamic and delayed contrast-enhanced CT scans demonstrate a homogeneously enhancing mass in the right adrenal gland.The degree to which enhancement diminishes over time is referred to as washout, which can be calculated by using the followingformula: [1 - (attenuation at 10 minutes/attenuation at 80 seconds)] X 100, where the attenuations are in Hounsfield units. In thiscase, the washout equals [1 (36/99)] X 100, or 64%. Findings from a recent publication in a major journal suggests that anywashout greater than 50% is diagnostic of a benign adrenal adenoma. Further studies are needed to confirm these promisingresults.

CT examination without intravenously administered contrast material

Findings from multiple studies confirm that an attenuation of 10 HU or less is diagnostic of adrenal cortical adenoma,with 79% sensitivity and 96% specificity. With a threshold of 0 HU, the diagnosis may be made with 47% sensitivityand 100% specificity. The decision about how to measure attenuation should be made carefully. The selected regionof interest should be as large as possible without including adjacent tissues, particularly periadrenal fat.

CT examination with intravenously administered contrast material

The initial enhancement patterns of adrenal cortical adenomas and adrenal metastases overlap substantially;therefore, simple attenuation measurements are not useful in distinguishing between the two. A delayed attenuationmeasurement (obtained 10 minutes after the injection) of 30 HU or less is diagnostic of benign adenoma, but only asmall percentage of adrenal adenomas have this finding.

A calculation termed contrast-agent washout can be used to reliably determine if an adrenal mass is benign or malignant. Washout is calculated as follows:

1. Intravenous contrast agent is administered, and a scan is obtained after an 80-second delay.2. A subsequent scan is obtained after a 10-minute delay.3. A region of interest is drawn over the adrenal mass, and the attenuation is measured in Hounsfield units at 80

seconds and at 10 minutes.4. The percentage of contrast agent washout is equal to [1 (attenuation at 10 minutes/attenuation at 80

seconds)] X 100, where the attenuations are in Hounsfield units.

Washout is a measurement of the percentage decrease between the initial enhancement and the delayedenhancement. A large decrease is a high-percentage washout, and a small decrease is a low-percentage washout. If delayed enhancement is exactly half of the initial enhancement, the washout is exactly 50%.

In a series of 101 adrenal masses, [15] a washout of greater than 50% was specific for benign adrenal adenoma, and awashout of less than 50% was specific for metastasis. Interestingly, these findings are not correlated with the

percentage of intracytoplasmic lipid, and the physiologic mechanism resulting in this distinction is not wellunderstood. With a threshold of 50%, use of the washout value yields 98% sensitivity and 100% specificity.

In this series, the 2 missed lesions were benign adenomas that had washouts of 0% and 40%. Both lesions hadvalues of less than 30 HU on delayed images and were correctly diagnosed as benign adrenal cortical adenomaswithout use of the washout criteria. If the 2 lesions are excluded from the series, the accuracy for this method is100%.

Additional larger series are needed to confirm these striking findings. It is important to remember that benign lesionssuch as adrenal hematomas or pseudocysts do not enhance with the intravenous administration of contrast material;therefore, these lesions do not have a washout value.

Studies comparing CT histogram analysis with mean CT attenuation analysis for the evaluation of adrenal noduleshave found that histogram analysis has greater sensitivity for diagnosis of adenoma. [2, 3] In a study of lipid-poor

adenomas on unenhanced CT, Ho et al found that although both methods have 100% specificity, using a threshold of more than 10% negative pixels yielded a sensitivity of 84%, compared with 68% for a mean attenuation threshold of less than 10 H. [2]

Magnetic Resonance Imaging

CT and MRI are the modalities of choice in diagnosing adrenal cortical adenoma.

On MRIs, adrenal cortical adenomas are well-circumscribed mass lesions that have homogeneous signal intensityand enhancement patterns. For small lesions (< 1.5 cm), thin 5-mm sections should be used to ensure that signalintensity measurements are not affected by volume averaging.




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T1-weighted and T2-weighted signal intensity characteristics of benign adrenal adenomas and adrenal metastasesare not specific and overlap significantly. However, in-phase and out-of-phase imaging (eg, chemical shift imaging)can be used to diagnose adrenal cortical adenomas with 81-100% sensitivity and 94-100% specificity.

Out-of-phase chemical shift images of lipid-rich adrenal adenomas show a decrease in signal intensity. The signalintensity from the spleen can be used as a reference, and ensuring identical preimaging values with both sequencesis important. A decrease of 20% in the signal intensity on out-of-phase images relative to that on in-phase images isdiagnostic. The signal intensity from liver should not be used as a reference because it may contain lipid. (See theimages below.)

MRIs obtained with in-phase (left) and out-of-phase (right) imaging after CT imaging. Note how the signal intensity in the leftadrenal mass (white arrow) decreases (ie, the mass is darker) relative to that of the spleen on the out-of-phase images. As in thiscase, a signal intensity decrease of 20% or greater is diagnostic of a benign adrenal adenoma.

An adrenal adenoma (arrows) is diagnosed with follow-up MRI when decreased signal intensity is seen on the out-of-phaseimage.

MRI images demonstrate a homogeneous ovoid mass in the right adrenal gland (arrows). A concomitant loss of signal intensity,relative to that of the spleen, with out-of-phase imaging is diagnostic of benign adrenal adenoma.

Results of 2 series show that the percentage decrease in signal intensity on chemical shift images is directlyproportional to the amount of intracytoplasmic lipid. [16] Therefore, MRI findings are unlikely to be diagnostic if anadrenal mass has values greater than 30 HU on nonenhanced CT scans.

The visual inspection of signal intensity loss on out-of-phase images is as effective as signal intensity measurements.One important technical point is that the echo time used for out-of-phase imaging should be shorter than that usedfor in-phase imaging, so that signal intensity loss reflects the presence of lipid and not T2 decay.

MRI cannot be used to definitively characterize lipid-poor adenomas. Although Krestin et al previously describedwashout with MRI, [4] the calculations are much more cumbersome to perform than with CT washout in the diagnosisof a lipid-poor adenoma.

A metastatic adrenal lesion located in or adjacent to an adrenal adenoma has been referred to as a collision tumor.One case report documents the MRI features of a benign adrenal cortical adenoma with concomitant adrenalhemorrhage that mimicked a collision tumor. [5]

Ultrasonography

Ultrasonography of the adrenal glands may be performed to evaluate abdominal masses in infants and children. [17]

No ultrasonographic finding is specific for adrenal adenoma. Note that adrenal adenomas are rare in children,accounting for less than 1% of all neoplasms in this population. Adrenal adenomas are much less common thanneuroblastomas but slightly more common than pheochromocytomas in children. As a rule, functional adenomas




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appear earlier than nonfunctional adenomas, and compared with benign adrenal cortical adenoma, adrenaladenocarcinoma is more likely to be functional. [18]

Nuclear Imaging

Preliminary studies have shown the promise of PET in differentiating adenomas from malignant processes in theadrenal gland. Malignant neoplasms tend to have an increased uptake of fluorine-18-fluorodeoxyglucose relative tobenign masses. In a meta-analysis of 1391 adrenal lesions, fluorine-18-fluorodeoxyglucose positron emissiontomography (FDG-PET) had a sensitivity of 97% and specificity of 91% for differentiating benign disease frommalignant disease. [19] Because this test does not depend on the presence of lipid, it can potentially be used tocharacterize both lipid-rich and lipid-poor adenomas. The use of whole-body PET, especially in staging lung cancer,will probably decrease the number of adrenal biopsies performed to assess indeterminate lesions.

Iodomethyl-19-norcholesterol (NP-59) is an investigational radiopharmaceutical that is taken up by adrenal corticaltissue. A Japanese study found that the norcholesterol uptake rate was more sensitive than the CT attenuation valueand MR suppression index (96%, 79%, and 67%, respectively) for functioning adrenal adenomas of greater than or equal to 2.0 cm. [6]

Angiography

No angiographic findings specific for adrenal adenoma have been identified.

Endovascular adrenal vein sampling can be useful in distinguishing bilateral adrenal hyperplasia from a unilateralfunctional aldosteronoma. [20]

Contributor Information and Disclosures Author Perry J Horwich, MD Staff Physician, Instructor of Radiology, Department of Radiology, Beth Israel - DeaconessMedical Center

Perry J Horwich, MD is a member of the following medical societies: American College of Radiology , InternationalSociety for Magnetic Resonance in Medicine , and Radiological Society of North America

Disclosure: Nothing to disclose.

Coauthor(s)Stephen A Okon, MD Consulting Staff, Assistant Professor of Radiology, Department of Radiology, Beth IsraelMedical Center

Stephen A Okon, MD is a member of the following medical societies: American Medical Association and AmericanRoentgen Ray Society


Specialty Editor BoardGlenn Krinsky, MD Chief of Abdominal Imaging Section, Associate Professor, Department of Radiology, NewYork University School of Medicine

Glenn Krinsky, MD is a member of the following medical societies: Alpha Omega Alpha and Radiological Societyof North America


Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, HuttValley District Health Board, New Zealand


Arnold C Friedman, MD FACR, Professor, Department of Radiology, Arizona Health Science Center at theUniversity of Arizona.




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Arnold C Friedman, MD is a member of the following medical societies: American College of Radiology , AmericanInstitute of Ultrasound in Medicine , American Roentgen Ray Society , Association of University Radiologists , andRadiological Society of North America


Robert M Krasny, MD Resolution Imaging Medical Corporation

Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society andRadiological Society of North America


Chief Editor Eugene C Lin, MD Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine , American College of Radiology , Radiological Society of North America , and Society of Nuclear Medicine


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2. Ho LM, Paulson EK, Brady MJ, Wong TZ, Schindera ST. Lipid-poor adenomas on unenhanced CT: doeshistogram analysis increase sensitivity compared with a mean attenuation threshold?. AJR Am J Roentgenol . Jul 2008;191(1):234-8. [Medline] .

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