Adrenal Adenoma Imaging
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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. The prevalence of adrenal adenoma increases with age; the frequency of unsuspected adenoma is 0.14% in patients aged 20–29 years and 7% in those older than 70 years. [1] Adrenal cortical adenomas are not considered to have the potential for malignant transformation.
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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 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. [2, 3] 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.
Plain radiography and ultrasonography are less sensitive and have been used less frequently since the advent of CT scanning and MRI. Ultrasonography has a role in the evaluation of a potential adrenal incidentaloma (AI) in infants, but no appearance is specific for benign adrenal adenoma.
How should the radiologist proceed in evaluating an incidental small adrenal mass? Two important questions must be answered:
CT without intravenous contrast enhancement should be the initial study. 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. An adenoma can be predicted with an absolute enhancement washout of 60% or more and/or with a relative enhancement washout of 40% or more on contrast-enhanced CT. Adenomas also demonstrate signal loss in opposed-phased MR imaging. If an adrenal adenoma cannot be predicted using these criteria, an evaluation should be done for characteristics that may suggest a pathology such as adrenal cyst or myelolipoma. [4, 5]
18F-fluorodeoxyglucose (18F-FDG) PET/CT has the potential to differentiate between benign and malignant lesions based on the amount of radiopharmaceutical uptake; malignant lesions generally have greater uptake. [6] If a pheochromocytoma is suspected, 18F-dihydroxyphenylalanine (18F-DOPA) or 123I-metaiodobenzylguanidine (123I-MIBG) can be considered in addition to CT and MR. [4]
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.
Some studies have shown that the accuracy of imaging modalities for adenoma may be lower than generally reported because of false positives and negatives. CT sensitivity for large adenoma and cortical carcinoma are influenced by size or location; however, use of larger regions of interest may help minimize decreased CT sensitivity. [7]
Endovascular adrenal vein sampling can be useful in distinguishing bilateral adrenal hyperplasia from a unilateral functional aldosteronoma. [8]
CT is a modality 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. [7, 9, 10, 11]
Although CT does not allow functioning adenomas to be differentiated from nonfunctioning adenomas, the presence of ipsilateral or contralateral adrenocortical atrophy is strongly suggestive of a functioning adenoma that has resulted in Cushing syndrome. [1]
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. [12]
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Histologically, adrenal adenoma contains abundant lipid in the cytoplasm, which appears relatively large and pale in comparison with the nucleus. This intracytoplasmic lipid leads to a decreased CT attenuation value in the adenoma. On unenhanced CT, an increase in the amount of intracytoplasmic lipid is associated with a decrease in the lesion attenuation value. [1]
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. Adenoma-mimicking false-positive lesions that measure 10 HU or less on unenhanced CT have been reported. These lesions include adrenal hyperplasia, adenoma with coexisting non-adenoma, and pheochromocytoma.
Like adenoma, adrenal hyperplasia is composed of abundant lipid-rich adrenocortical cells. This histologic finding may lead to a decreased attenuation value of adrenal hyperplasia on unenhanced CT, making an accurate diagnosis challenging. However, the presence of 3 or more adrenal nodules increases the likelihood of hyperplasia rather than adenoma. [13]
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:
Intravenous contrast agent is administered, and a scan is obtained after an 80-second delay.
A subsequent scan is obtained after a 10-minute delay.
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.
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, [14] 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%.
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. [15, 16] 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. [15]
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. [9]
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 showed that the percentage decrease in signal intensity on chemical shift images is directly proportional to the amount of intracytoplasmic lipid. [17] 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, [18] 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. [19]
Ultrasonography of the adrenal glands may be performed to evaluate abdominal masses in infants and children. [20] 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. [21]
PET has shown promise 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. However, false-positive 18F-FDG PET/CT findings for malignancy have been reported with increased radiopharmaceutical uptake in nonfunctioning adenoma. [22]
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, may decrease the number of adrenal biopsies performed to assess indeterminate lesions.
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. [23]
Park JJ, Park BK, Kim CK. Adrenal imaging for adenoma characterization: imaging features, diagnostic accuracies and differential diagnoses. Br J Radiol. 2016 Jun. 89 (1062):20151018. [Medline]. [Full Text].
Patel J, Davenport MS, Cohan RH, Caoili EM. Can Established CT Attenuation and Washout Criteria for Adrenal Adenoma Accurately Exclude Pheochromocytoma?. AJR Am J Roentgenol. 2013 Jul. 201(1):122-7. [Medline].
Korivi BR, Elsayes KM. Cross-sectional imaging work-up of adrenal masses. World J Radiol. 2013 Mar 28. 5(3):88-97. [Medline]. [Full Text].
Wale DJ, Wong KK, Viglianti BL, Rubello D, Gross MD. Contemporary imaging of incidentally discovered adrenal masses. Biomed Pharmacother. 2017 Mar. 87:256-262. [Medline].
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Kim SJ, Lee SW, Pak K, Kim IJ, Kim K. Diagnostic accuracy of 18F-FDG PET or PET/CT for the characterization of adrenal masses: a systematic review and meta-analysis. Br J Radiol. 2018 Jun. 91 (1086):20170520. [Medline].
Park SY, Park BK, Park JJ, Kim CK. CT sensitivity for adrenal adenoma according to lesion size. Abdom Imaging. 2015 Oct. 40 (8):3152-60. [Medline].
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Seo JM, Park BK, Park SY, Kim CK. Characterization of lipid-poor adrenal adenoma: chemical-shift MRI and washout CT. AJR Am J Roentgenol. 2014 May. 202 (5):1043-50. [Medline].
Shi JW, Dai HZ, Shen L, Xu DF. Dual-energy CT: clinical application in differentiating an adrenal adenoma from a metastasis. Acta Radiol. 2014 May. 55 (4):505-12. [Medline].
Yasaka K, Gonoi W, Akai H, Katsura M, Akahane M, Kiryu S, et al. Differentiation of adrenal tumors in patients with hepatocellular carcinoma: adrenal adenoma versus metastasis. Eur J Radiol. 2013 Aug. 82 (8):1213-8. [Medline].
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Pena CS, Boland GW, Hahn PF, et al. Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT. Radiology. 2000 Dec. 217(3):798-802. [Medline].
Ho LM, Paulson EK, Brady MJ, Wong TZ, Schindera ST. Lipid-poor adenomas on unenhanced CT: does histogram analysis increase sensitivity compared with a mean attenuation threshold?. AJR Am J Roentgenol. 2008 Jul. 191(1):234-8. [Medline].
Halefoglu AM, Bas N, Yasar A, Basak M. Differentiation of adrenal adenomas from nonadenomas using CT histogram analysis method: A prospective study. Eur J Radiol. 2009 Jan 21. [Medline].
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Boland GW, Dwamena BA, Jagtiani Sangwaiya M, Goehler AG, Blake MA, Hahn PF, et al. Characterization of Adrenal Masses by Using FDG PET: A Systematic Review and Meta-Analysis of Diagnostic Test Performance. Radiology. 2011 Apr. 259(1):117-26. [Medline].
Perry J Horwich, MD Staff Physician, Instructor of Radiology, Department of Radiology, Beth Israel – Deaconess Medical Center
Perry J Horwich, MD is a member of the following medical societies: American College of Radiology, Radiological Society of North America, International Society for Magnetic Resonance in Medicine
Disclosure: Nothing to disclose.
Stephen A Okon, MD
Stephen A Okon, MD is a member of the following medical societies: American Medical Association, American Roentgen Ray Society
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
Arnold C Friedman, MD, FACR Professor, Department of Radiology, University of Florida Health Science Center; Chief, Department of Radiology, Shands-Jacksonville Hospital
Arnold C Friedman, MD, FACR is a member of the following medical societies: American College of Radiology, American Institute of Ultrasound in Medicine, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America
Disclosure: Nothing to disclose.
Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, 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, Society of Nuclear Medicine and Molecular Imaging
Disclosure: Nothing to disclose.
Glenn Krinsky, MD
Glenn Krinsky, MD is a member of the following medical societies: Alpha Omega Alpha, Radiological Society of North America
Disclosure: Nothing to disclose.
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