PET/CT for Adrenal Assessment

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1 Residents Section Structured Review rticle lake et al. PET/CT of the drenal Glands Residents Section Structured Review rticle Michael. lake 1 Priyanka Prakash Carmel G. Cronin lake M, Prakash P, Cronin CG Keywords: adrenal glands, adrenal incidentalomas, adrenal masses, PET/CT DOI: /JR Received October 18, 2009; accepted after revision November 27, ll authors: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., oston, M ddress correspondence to M.. lake (mblake2@partners.org). WE This is a Web exclusive article. CME This article is available for CME credit. See for more information. JR 2010; 195:W91 W X/10/1952 W91 merican Roentgen Ray Society PET/CT for drenal ssessment drenal incidentalomas are found in approximately 5% of all CT examinations in the general population. In healthy individuals, 80% of incidentally found adrenal masses are benign nonfunctioning adenomas [1]. Even in those with a known primary malignancy, approximately 40 57% of adrenal incidentalomas are benign [2]. ccurate characterization of adrenal nodules is critical for appropriate staging and optimal management of patients both those with and those without known malignancy. We discuss the clinical utility and imaging features of PET/ CT in the evaluation of adrenal lesions. Imaging Technique PET/CT protocols vary among institutions. In our institution patients fast for a minimum of 4 hours before imaging. fter receiving an IV injection of FDG, patients consume 1,350 ml of low-attenuating oral contrast material over 45 minutes. While waiting the 60 minutes between FDG administration and subsequent imaging, patients are encouraged to rest and activities including talking, chewing, and walking are restricted. Thereafter, low-radiation-dose unenhanced CT is performed first primarily for attenuation correction. Then, the PET data are acquired and are followed immediately by a fully diagnostic standard-dose IV contrast-enhanced CT examination with the previously administered water-attenuation oral contrast material outlining the gastrointestinal tract. If a patient has a known indeterminate adrenal lesion before imaging, the PET/CT protocol may be adapted to include diagnosticquality unenhanced CT images and delayed CT images of the adrenal area at minutes after contrast administration to further characterize the adrenal lesion [3]. Imaging Features Normal drenal Gland The normal adrenal gland is larger than the spatial resolution of PET; however, it is usually barely visible on FDG PET. Combined PET/ CT can show normal mild FDG uptake in the location of the glands visible on the coregistered CT (Figs. 1 and 2). The average mean and maximum standardized uptake values (SUVs) are 0.90 ± 0.15 (SD) and 0.83 ± 0.17, respectively, for the right adrenal and 1.10 ± 0.15 and ± 0.15 for the left adrenal. The maximum SUVs of normal adrenal glands range from 0.95 to 2.46 [4]. n adrenal is usually considered malignant if its intensity is higher than that of the liver; however, because the average mean SUV of the liver is , physiologic adrenal uptake may, in some cases, be in the range of malignant lesions. enign Lesions Versus Malignant Lesions (denomas Versus Metastases) Metastases to the adrenal glands are common and may be difficult to distinguish from benign adenomas. The most common primary sites are the lung (Figs. 3 and 4), breast (Fig. 5), skin (melanoma) (Fig. 6), kidney, thyroid gland, and colon. drenal metastases are usually clinically silent. Up to 50% of adrenal masses in patients with known malignancy may be benign; thus, noninvasive characterization is key to preventing unnecessary biopsy [5]. Characterization of adrenal adenoma on unenhanced CT is dependent on the mass having a high lipid content, with an attenuation value of less than 10 HU (Fig. 1). ecause up to 30% of adrenal adenomas are lipid poor and more than 10 HU [6] (Fig. 2), further imaging traditionally, an adrenal protocol contrast-enhanced CT is required for differentiation of adenoma from metastasis. To date, FDG PET and PET/CT are imperfect imaging techniques because benign JR:195, ugust 2010 W91

2 lake et al. functioning adrenal adenomas may show increased FDG PET uptake; however, uptake is usually only mild to moderate in intensity at most (Fig. 2). In a study by Metser et al. Fig. 1 xial images of 70-year-old man with history of lung cancer. and, CT scan () and PET image () show benign left adrenal adenoma (straight arrows) (noncontrast attenuation = 8 HU). No significant FDG uptake within this adenoma was seen at PET or at PET/CT (not shown). Mild FDG uptake (curved arrow, ) in location of normal right adrenal gland on coregistered CT is not clearly identified on PET image (). Fig. 2 xial images of 79-year-old woman with lung cancer., Contrast-enhanced CT scan shows solid indeterminate left adrenal nodule (arrow) (noncontrast attenuation = 39 HU)., drenal nodule (arrow) does not show significant FDG uptake on PET image. Nodule was confirmed to be lipid-poor adenoma at biopsy. [7], PET/CT had a sensitivity and specificity of 98.5% and 92%, respectively, for the differentiation of lipid-poor adenomas and 98.5% and 93% for all adenomas from malignant lesions. More recently, oland et al. [8] found that PET/CT had sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 99%, 100%, 100%, 93%, and 99% for the detection of benign lesions and 100%, 99%, 93% and 100%, respectively, for the detection of malignancy. Metser et al. also found that when 3.1 was used as a cutoff for the maximum SUV, PET/CT had a sensitivity and specificity of 98.5% and 92% of the differentiation of malignant lesions from benign lesions. Evaluation of PET/CT images before biopsy is paramount because areas of necrosis or normal-appearing adrenal tissue may show less or no significant FDG uptake and should not be targeted given that they may yield an erroneous negative or nondiagnostic biopsy (Fig. 5). In rare instances, the adrenal gland may appear normal or minimally thickened despite the presence of an FDGavid metastasis, thus making PET/CT useful in detecting otherwise occult disease. PET/ CT has also been shown to be of use in guiding biopsy in the rare occurrence of adrenal collision tumors [9]. Conversely, interpretation should not be based solely on quantitative and qualitative PET characteristics because lesions measuring less than 1 cm may be less than the resolution of PET. Posttreatment PET/CT may be valuable in showing residual hypermetabolic tumor when anatomic findings alone are equivocal [7]. Primary Lymphoma Primary lymphoma of the adrenals is rare, and secondary adrenal lymphomatous involvement has been reported in 1 4% of affected patients (Fig. 7). PET/CT has been found to be valuable in distinguishing nonfunctioning adrenal neoplasm or hyperplasia from lym- Fig year-old man with adenocarcinoma of lung. and, xial unenhanced CT scan () and axial (left, ) and coronal (right, ) PET images show solid indeterminate right adrenal mass (arrows) (36 HU). This lesion shows moderate FDG uptake at PET. It was confirmed to be adrenal lung adenocarcinoma metastasis at biopsy. W92 JR:195, ugust 2010

3 PET/CT of the drenal Glands Fig year-old woman with adenocarcinoma of lung. Coronal fused PET/CT (top) and PET (bottom) images show left hilar lymphadenopathy (curved white arrows) and bilateral adrenal masses (straight white arrows). drenal masses (black arrows) showed high FDG uptake and were confirmed to be adrenal lung adenocarcinoma metastases at biopsy. phomatous involvement. The degree of FDG avidity in adrenal lymphoma tends to parallel that in other involved areas so that the resolution of adrenal gland uptake after treatment often follows that of uptake in other regions [7]. Pheochromocytoma Pheochromocytoma is a rare tumor that may be asymptomatic, is bilateral in 10% of patients, is malignant in 10% of cases, and may occur in certain familial syndromes most commonly, in multiple endocrine neoplasia syndromes. Differentiating an adrenal adenoma from a pheochromocytoma can be difficult with CT alone because both neoplasms can have similar CT appearances. The imaging technique of choice in localizing pheochromocytoma is metaiodobenzylguanidine (MIG) scintigraphy, which has a high sensitivity (95 100%) and specificity (100%) [10]. Fig. 5 xial (left), coronal (middle), and sagittal (right) fused contrast-enhanced PET/CT and PET images of 58-year-old woman with history of breast cancer and large necrotic right adrenal mass (white arrows). Mass shows high FDG uptake at periphery of lesion and little uptake in central necrotic part (black arrows). iopsy confirmed it to be breast cancer metastasis. Shulkin et al. [10] compared FDG PET with MIG scintigraphy for the detection of benign pheochromocytomas; they found that MIG scintigraphy had a sensitivity of 83%, whereas FDG PET had a sensitivity of 58%. For malignant pheochromocytomas, MIG scintigraphy had a sensitivity of 88% and FDG PET had a sensitivity of 82%. lthough MIG scintigraphy had a better sensitivity than FDG PET, all of the MIG-negative lesions showed avid FDG uptake. These authors concluded that most pheochromocytomas accumulate FDG, that FDG uptake is found in a greater percentage of malignant than benign pheochromocytomas, and that FDG PET is especially useful in defining the distribution of pheochromocytomas that fail to concentrate MIG. There are recent reports in small patient cohorts that newer PET-specific tracers for the sympathetic system, 11 C-hydroxyephedrine and 18 F-dihydroxyphenylalanine [11], have shown promising results; however, the results for 18 F-fluorodopamine have been less impressive. drenocortical Carcinoma drenocortical carcinoma is a rare primary malignant neoplasm of unknown cause with an estimated annual incidence of 1 2 per million in the United States. Patients usually present with advanced-stage disease and have a poor prognosis; radical surgery, when feasible, constitutes the only effective treatment Fig. 6 Coronal PET image of 59-year-old man with nasal melanoma (black arrow) shows FDG-avid adrenal mass (white arrow). Mass was confirmed to be adrenal melanoma metastasis at biopsy. JR:195, ugust 2010 W93

4 lake et al. Fig year-old woman with history of lymphoma. and, xial contrast-enhanced CT scan shows elongated, indeterminate right adrenal mass (arrow) that is somewhat maintaining adreniform configuration., On axial (left), coronal (middle), and sagittal (right) fused PET/CT and PET images, mass (arrows) shows significant FDG uptake. Mass was confirmed to be -cell lymphoma at biopsy. of both local and distant disease. echerer et al. [12] evaluated FDG PET in patients with known adrenocortical carcinoma (n = 10) and reported that FDG PET showed a sensitivity and specificity of 100% and 95%, respectively. dditional lesions that had not been detected at anatomic imaging alone were identified with the addition of PET in 30% of patients, and the addition of PET modified the management protocol in 20%. In a later study, Leboulleux et al. [13] found sensitivities for the detection of distinct lesions and the diagnosis of metastatic organs were 90% and 93%, respectively. However, PET/CT cannot offer tissue characterization and cannot differentiate among malignant lesion types. More recently, PET was performed using 11 C-metomidate (METO), a marker of 11β-hydroxylase, for adrenocortical imaging with variable success [14, 15]. Hennings et al. [16] found that METO PET had sensitivity and specificity of 89% and 96% for the identification of tumors of adrenocortical origin (n = 73). METO can differentiate adrenal metastases and pheochromocytomas from adrenocortical tumors (adenomas and adrenocortical carcinomas); however, METO cannot distinguish between adenomas and adrenocortical carcinomas. nother marker for 11β-hydroxylase is (R)-1-(1-phenylethyl)- 1 H-imidazole-5-carboxylic acid 2-18 F-fluoroethylester (FETO); FETO has a longer half-life than METO, allows longer imaging protocols than METO, and is currently under investigation. FDG PET/CT remains the study of choice because it can show additional sites of metastatic disease in addition to adrenal metastases. dvantages of PET/CT PET/CT has a high sensitivity and specificity for the differentiation of benign adrenal lesions from malignant adrenal lesions. Pitfalls and Limitations of PET/CT 5% false-positive rate for PET/CT has been reported secondary to a variety of causes including significant FDG uptake in some adrenal adenomas, adrenal endothelial cysts, and inflammatory and infectious lesions [17]. Furthermore, false-negative findings may be seen in adrenal metastatic lesions with hemorrhage or necrosis, small (< 10 mm) metastatic nodules, and metastases from pulmonary bronchoalveolar carcinoma or carcinoid tumors [17]. Furthermore, PET/CT cannot offer tissue characterization or differentiate among malignant lesion types. Conclusion PET/CT is a powerful adrenal imaging tool, with PET/CT offering high sensitivity and specificity for the differentiation of benign adrenal lesions from malignant adrenal lesions and the capacity to incorporate a diagnostic CT adrenal protocol to aid in adrenal lesion characterization if required. References 1. Paulsen SD, Nghiem HV, Korobkin M, Caoili EM, Higgins EJ. Changing role of imaging-guided percutaneous biopsy of adrenal masses: evaluation of 50 adrenal biopsies. JR 2004; 182: Dunnick NR, Korobkin M. Imaging of adrenal incidentalomas: current status. JR 2002; 179: lake M, Slattery JM, Kalra MK, et al. drenal lesions: characterization with fused PET/CT image in patients with proved or suspected malignancy initial experience. Radiology 2006; 238: agheri, Maurer H, Cone L, Doss M, dler L. Characterization of the normal adrenal gland with 18 F FDG PET/CT. J Nucl Med 2004; 45: Elaini, Shetty SK, Chapman VM, et al. Improved detection and characterization of adrenal disease with PET-CT. RadioGraphics 2007; 27: oland GW, Lee MJ, Gazelle GS, Halpern EF, McNicholas MM, Mueller PR. Characterization of adrenal masses using unenhanced CT: an analysis of the CT literature. JR 1998; 171: Metser U, Miller E, Lerman H, Lievshitz G, vital S, Even-Sapir E. 18 F-FDG PET/CT in the evaluation of adrenal masses. J Nucl Med 2006; 47: oland GW, lake M, Holalkere NS, Hahn PF. PET/CT for the characterization of adrenal masses in patients with cancer: qualitative versus quantitative accuracy in 150 consecutive patients. JR 2009; 192: lake M, Sweeney T, Kalra MK, Maher MM. Collision adrenal tumors on PET/CT. JR 2004; 183: Shulkin L, Thompson NW, Shapiro, Francis IR, Sisson JC. Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET. Radiology 1999; 212: Fiebrich H, rouwers H, Kerstens MN, et al. W94 JR:195, ugust 2010

5 PET/CT of the drenal Glands 18 F-DOP PET is superior to conventional imaging with 123 I-metaiodobenzylguanidine scintigraphy, CT, and MRI in localizing tumors causing catecholamine excess. J Clin Endocrinol Metab 2009; 94: echerer, Vierhapper H, Pötzi C, et al. FDG- PET in adrenocortical carcinoma. Cancer iother Radiopharm 2001; 16: Leboulleux S, Dromain C, onniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adreno- FOR YOUR INFORMTION cortical carcinoma: a prospective comparison with computed tomography. J Clin Endocrinol Metab 2006; 91: Zettinig G, Mitterhauser M, Wadsak W, et al. Positron emission tomography imaging of adrenal masses: (18)F-fluorodeoxyglucose and the 11betahydroxylase tracer (11)C-metomidate. Eur J Nucl Med Mol Imaging 2004; 31: Gross MD, vram, Fig LM, Fanti S, l-nahhas, Rubello D. PET in the diagnostic evaluation of adrenal tumors. Q J Nucl Med Mol Imaging 2007; 51: This article is available for CME credit. See for more information. 16. Hennings J, Lindhe O, ergstrom, Sundin, Hellman P. [11C]Metomidate positron emission tomography of adenocortical tumors in correlation with histopathological findings. J Clin Endocrin Metab 2006; 91: Chong S, Lee KS, Kim HY, et al. Integrated PET- CT for the characterization of adrenal gland lesions in cancer patients: diagnostic efficacy and interpretation pitfalls. RadioGraphics 2006; 26: JR:195, ugust 2010 W95