Adrenal Adenoma Imaging 

Adrenal cortical adenoma is a common benign tumor arising from the cortex of the adrenal gland. It commonly occurs in adults, but it can be found in persons of any age (see the images below). Adrenal cortical adenomas are not considered to have the potential for malignant transformation.

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

The adrenal gland is the fourth most common site of metastasis, and adrenal metastases may be found in as many as 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 the case. For instance, the workup for an otherwise resectable lung cancer may reveal the presence of an adrenal mass and suggest the possibility of metastatic disease.

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

Preferred examination

The modalities of choice in the evaluation of an adrenal mass are computed tomography (CT) scanning, magnetic resonance imaging (MRI), and positron emission tomography (PET) scanning. Ultrasonography has a role in the evaluation 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 must be answered.

First, does the patient have a hormonal or biochemical abnormality that may be caused by an enlarged adrenal gland? 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 a small, well-circumscribed adrenal mass is malignant is nearly zero. The characterization of an adrenal mass is critical in 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 the initial 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 in which CT findings are equivocal, chemical shift MRI should be performed. When the findings of both modalities are inconclusive, 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 potentially diminish the efficiency of the CT schedule, result in multiple examinations, and expose the patient to ionizing radiation. MRI examination may enable diagnosis without exposing the patient to ionizing radiation; however, MRI may not be as available as CT and can be more expensive.

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

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.

The use of a sufficient milliampere-second (mAs) setting is important so that the measured attenuation values do not have a significant standard deviation. Heterogeneous enhancement or attenuation can be observed when a lipid-rich adenoma and a lipid-poor adenoma coexist. A lesion that is poorly marginated with heterogeneous enhancement is unlikely to be a simple benign adrenal cortical adenoma, and other entities must be considered.^[14] (See the images below.)

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% sensitivity and 100% specificity. The decision about how to measure attenuation should be made carefully. The selected region of 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 attenuation measurement (obtained 10 minutes after the injection) of 30 HU or less is diagnostic of benign adenoma, but only a small 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 delayed enhancement. 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 a washout 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 well understood. 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 had values of less than 30 HU on delayed images and were correctly diagnosed as benign adrenal cortical adenomas without use of the washout criteria. If the 2 lesions are excluded from the series, the accuracy for this method is 100%.

Additional larger series are needed to confirm these striking findings. It is important to remember that benign lesions such 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 nodules have 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]

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 intensity and enhancement patterns. For small lesions (< 1.5 cm), thin 5-mm sections should be used to ensure that signal intensity measurements are not affected by volume averaging.

T1-weighted and T2-weighted signal intensity characteristics of benign adrenal adenomas and adrenal metastases are 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 signal intensity from the spleen can be used as a reference, and ensuring identical preimaging values with both sequences is important. A decrease of 20% in the signal intensity on out-of-phase images relative to that on in-phase images is diagnostic. The signal intensity from liver should not be used as a reference because it may contain lipid. (See the images below.)

Results of 2 series show that the percentage decrease in signal intensity on chemical shift images is directly proportional to the amount of intracytoplasmic lipid.^[16] Therefore, MRI findings are unlikely to be diagnostic if an adrenal 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 used for 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 described washout with MRI,^[4] the calculations are much more cumbersome to perform than with CT washout in the diagnosis of 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 adrenal hemorrhage that mimicked a collision tumor.^[5]

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 than neuroblastomas but slightly more common than pheochromocytomas in children. As a rule, functional adenomas appear earlier than nonfunctional adenomas, and compared with benign adrenal cortical adenoma, adrenal adenocarcinoma is more likely to be functional.^[18]

Preliminary studies have shown the promise of PET in differentiating adenomas from malignant processes in the adrenal gland. Malignant neoplasms tend to have an increased uptake of fluorine-18-fluorodeoxyglucose relative to benign masses. In a meta-analysis of 1391 adrenal lesions, fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) had a sensitivity of 97% and specificity of 91% for differentiating benign disease from malignant disease.^[19] Because this test does not depend on the presence of lipid, it can potentially be used to characterize 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 cortical tissue. A Japanese study found that the norcholesterol uptake rate was more sensitive than the CT attenuation value and MR suppression index (96%, 79%, and 67%, respectively) for functioning adrenal adenomas of greater than or equal to 2.0 cm.^[6]

No angiographic findings specific for adrenal adenoma have been identified.

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