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1 All authors: Department of Radiology, University of Michigan Medical Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-9723.
Received February 22, 2000;
accepted after revision April 13, 2000.
Presented at the annual meeting of the American Roentgen Ray Society,
Washington, DC, May 2000.
Abstract
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SUBJECTS AND METHODS. Eighteen proven lipid-poor adenomas, 56 lipid-rich adenomas, and 40 adrenal nonadenomas underwent CT before, immediately after, and 15 min delay after IV contrast injection. Region-of-interest measurements were made of all adrenal lesions at the three time points. The degree of enhancement, enhancement washout, percentage enhancement washout, and relative percentage enhancement washout were calculated for each adrenal mass. Pooled data were analyzed statistically. Optimal threshold values for diagnosing adrenal adenomas were also determined.
RESULTS. The mean CT attenuation of lipid-poor adenomas was significantly higher than that of lipid-rich adenomas at all three phases but not significantly different from that of nonadenomas. The mean percentage enhancement washout on images obtained 15 min after administration of contrast material was similar for lipid-rich and lipid-poor adenomas but was significantly higher than that of nonadenomas. The mean relative percentage enhancement washout was significantly different among all three groups.
CONCLUSION. Lipid-poor adenomas cannot be differentiated from adrenal nonadenomas on the basis of a single mean attenuation value. However, lipid-poor adrenal adenomas show enhancement and enhancement washout features nearly identical to lipid-rich adenomas and can be distinguished from nonadenomas on the basis of a percentage washout threshold value of 60% and a relative percentage washout of 40%.
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Unfortunately, the recent reports about CT contrast enhancement washout curves include only a few lipid-poor adrenal adenomas, and the washout data in these studies combined the results from both lipid-rich and lipid-poor adenomas [3, 4]. The purpose of this study was to compare the specific enhancement washout characteristics of lipid-poor adenomas with those of both lipid-rich adrenal adenomas and adrenal nonadenomas.
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10 H) and lipid-poor (>10 H) groups. Fifty-six lipid-rich
adenomas, 18 lipid-poor adenomas, and 40 nonadenomas were identified.
Forty-five lipid-rich adenomas, seven lipid-poor adenomas, and 24 nonadenomas
were described in a previous report
[4], but comparison of these
three groups was not provided. The patient population with adrenal adenomas (lipid-rich and lipid-poor) consisted of 31 men and 37 women who ranged in age from 23 to 86 years (mean age, 62 years). Six adrenal masses were bilateral. Follow-up consisted of histopathologic proof (11 cases), stability on subsequent CT scans (22 cases), and attenuation measurement of less than 10 H on unenhanced CT scans (41 cases). Of the 74 adrenal adenomas, 18 (24%) measured greater than 10 H on unenhanced CT and were considered lipid-poor. Pathologic proof confirmed the diagnosis in eight of these lipid-poor adenomas (44%). The remaining 10 lipid-poor adrenal adenomas (56%) were found to be stable on a follow-up CT scans.
The 36 patients with nonadenomas consisted of 25 men and 11 women who ranged in age from 35 to 76 years (mean age, 60 years). Four of these adrenal masses were bilateral. The nonadenomas consisted of 33 metastases, two hematomas, two pheochromocytomas, one adrenal cortical carcinoma, one angiosarcoma, and one myelolipoma. The primary malignancy in the 30 patients with adrenal metastases included the following: lung (n = 17), esophageal (n = 3), renal (n = 2), melanoma (n = 2), tongue (n = 1), rectum (n = 1), lymphoma (n = 1), prostate (n = 1), breast (n = 1), and leiomyosarcoma (n = 1). Follow-up of the nonadenomas consisted of histopathologic proof in 14 cases, change in size at follow-up CT in 25 cases, and no change in size in the case of the myelolipoma.
The CT protocol consisted of images obtained during three distinct phases: before administration of contrast material (unenhanced), at a 50- to 80-sec delay after administration of contrast material (enhanced), and at a 15-min delay after administration of contrast material (delayed contrast-enhanced). All phases were performed on the same scanner. The CT scans were obtained with either a nonhelical unit (HiSpeed Advantage; General Electric Medical Systems, Milwaukee, WI) or a helical unit (HiLite Advantage or LightSpeed CT/i; General Electric Medical Systems). Imaging parameters for the nonhelical unenhanced and delayed contrast-enhanced examinations were as follows: contiguous 3- or 5-mm sections, 120 kVp, and 280 mA. The enhanced examination had a similar technique except for section thickness, which varied from contiguous 5- or 10-mm sections. Parameters for the unenhanced and delayed contrast-enhanced examinations for the helical unit were as follows: 3- or 5-mm collimation, 1:1 pitch, 120 kVp, and 200-280 mA. Enhanced imaging used a collimation of 5, 7, or 10 mm and a 1:1 pitch. Imaging parameters for the LightSpeed CT/i unit were similar for all three phases and consisted of the following: 5-mm collimation, 1:1 pitch, 120 kVp, and 200-280 mA. Enhanced scans were obtained after IV injection of 150 mL of diatrizoate sodium 50 (Hypaque; Nycomed, New York, NY) or iohexol 300 (Omnipaque; Nycomed). IV contrast material was administered with a power injector at a rate of 2.0-3.0 mL/sec.
The maximal diameter and location of the adrenal masses were recorded. CT attenuation values were measured on images obtained during each of the three phases with a circular region of interest for all adrenal masses. The region of interest covered one half to two thirds of the mass. Edges were avoided to prevent potential partial volume artifacts, and cystic, calcified, or necrotic regions were excluded. At least two measurements were obtained for each mass during each phase of imaging. The mean attenuation value was recorded. Enhancement was defined as the difference between the enhanced attenuation value and the unenhanced attenuation value. Enhancement washout was defined as the difference between the enhanced attenuation value and the delayed contrast-enhanced attenuation value. Washout percentages were calculated using the following equation: percentage enhancement washout = (enhancement washout / enhancement) x 100. The relative percentage enhancement washout was also calculated for all adrenal masses using the following equation: relative percentage enhancement washout = (enhancement washout / enhanced attenuation value) x 100 (Fig. 1A,1B,1C). The mean attenuation values, the percentage enhancement washouts, and the relative percentage enhancement washouts for all adrenal masses were analyzed and compared using the unpaired Student's t test. A p value of less than 0.01 was considered statistically significant. The optimal threshold values for absolute and relative percentage washout were determined by comparing their various sensitivities and specificities for diagnosing adrenal adenomas.
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The mean attenuation values of the adrenal masses on unenhanced, enhanced, and delayed contrast-enhanced CT are shown in Table 1 and Figure 2. The mean unenhanced value of the lipid-poor adenomas was significantly higher than that of the lipid-rich adenomas (p < 0.001) but was not significantly different from the value of the nonadenomas (p = 0.24). The mean enhanced attenuation value of the lipid-poor adenomas was significantly higher than that of the lipid-rich adenomas (p < 0.01) but was not significantly different from that of the nonadenomas (p = 0.03). The mean delayed contrast-enhanced attenuation value of the lipid-poor adenomas was significantly higher than that of the lipid-rich adenomas (p < 0.001) but was not significantly different than that of the nonadenomas (p = 0.03).
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Results of the comparisons of the enhancement, enhancement washout, and percentage enhancement washout of the adrenal masses are shown in Table 2 and Figure 3. No significant difference was seen in enhancement (p = 0.40), enhancement washout (p = 0.73), or percentage enhancement washout (p = 0.11) between the lipid-poor and the lipid-rich adenomas. In contrast, the mean enhancement, enhancement washout, and percentage enhancement washout were all significantly lower (p < 0.001) for the nonadenomas than for the adenomas.
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Comparisons of the percentage enhancement washout and the relative percentage enhancement washout of the adrenal masses are depicted in Table 3 and Figure 4. Unlike the true percentage enhancement washout, the relative percentage enhancement washout of the lipid-poor adenomas was significantly lower than that of the lipid-rich adenomas (p < 0.001). Nevertheless, the relative percentage enhancement washout was still significantly higher for lipid-poor adenomas than that of the nonadenomas (p < 0.001).
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The optimal threshold value of percentage enhancement washout for both lipid-poor and lipid-rich adenomas was 60%, with a corresponding sensitivity and specificity of 89% and 95% for lipid-poor adenomas and of 79% and 95% for the lipid-rich adenomas. For the relative percentage enhancement washout, the optimal threshold value was 50% for the lipid-rich adenomas, with a corresponding sensitivity of 93% and a specificity of 98%. For lipid-poor adenomas, the optimal threshold was 40%, with a corresponding sensitivity of 83% and specificity of 93%.
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In one study, the mean percentage of enhancement washout for adenomas was 70% 15 min after IV contrast administration compared with 20% for nonadenomas [4]. It is not surprising that most of the adenomas included in that study were lipid-rich adenomas with an unenhanced CT attenuation of 10 H or less, because 60-90% of adrenal adenomas fall in this category. Although lipid-poor adenomas (unenhanced CT attenuation value of > 10 H) represent only a minority of adenomas, these adenomas are especially important because they typically cannot be characterized as adenomas on the basis of unenhanced CT attenuation values. To our knowledge, contrast enhancement features of lipid-poor adrenal adenomas in comparison with those of lipid-rich adenomas and with adrenal nonadenomas have not yet been systematically assessed.
Korobkin et al. [4] described the CT time-attenuation washout curves of 52 adrenal adenomas, seven of which were lipid-poor. Although the curves were not analyzed separately for the lipid-rich and the lipid-poor groups, all seven lipid-poor adenomas evaluated 15 min after enhancement met the threshold criteria for absolute percentage washout calculated for the entire group of adenomas, and six of the seven met the threshold criteria for the relative percentage washout. Szolar and Kammerhuber [3] reported on the accuracy of delayed contrast-enhanced CT for the diagnosis of adenomas; these researchers examined 24 adenomas at 10 min and 37 adenomas at 30 min after IV contrast enhancement. A more recent study concluded that the optimal relative percentage enhancement washout was 50% or greater to diagnose adrenal adenoma [13]. Unfortunately, neither of these reports considered lipid-rich and lipid-poor adenomas separately.
Our results indicate that lipid-poor adenomas—although similar to nonadenomas in CT attenuation value on unenhanced, enhanced, and 15-min delayed contrast-enhanced scans—respond to contrast enhancement in a manner significantly different from nonadenomas and nearly identical to lipid-rich adenomas (Table 2 and Fig. 3). Our findings suggest that the pharmacokinetics of IV contrast enhancement of lipid-poor adrenal adenomas appears to be identical to that of lipid-rich adenomas and significantly different from that of adrenal nonadenomas. Compared with adrenal nonadenomas, the lipid-poor adenomas had a higher mean attenuation value on enhanced CT and a lower mean attenuation value on delayed enhanced CT, although these differences did not acquire statistical significance (p = 0.03 for both comparisons). These differences in attenuation values resulted, however, in a highly significant difference between the two groups (p < 0.001) for the mean contrast enhancement, enhancement washout, and percentage enhancement washout.
Our results confirm those of a previous report [3], which noted that adrenal adenomas show significantly more initial contrast enhancement than nonadenomas. Lipid-poor adenomas showed enhancement nearly identical to that of lipid-rich adenomas and significantly greater than that of nonadenomas. Lipid-poor adenomas also showed an enhancement washout nearly identical to that of lipid-rich adenomas and significantly greater than that of nonadenomas. The mean percentage enhancement washout of the lipid-poor adenomas was also statistically identical to that of the lipid-rich adenomas and was significantly greater than that of the nonadenomas.
Previous reports have suggested that knowledge of the relative percentage enhancement washout can be useful because the unenhanced CT attenuation value of an adrenal mass may not be known if the delayed contrast-enhanced scan is obtained immediately after initial detection during a standard enhanced CT examination. The relative percentage enhancement washout is an approximation to the absolute enhancement washout and is calculated by deleting the unenhanced value from the formula for percentage enhancement washout. This approximation to the absolute enhancement washout percentage becomes equal to the true percentage enhancement washout only for adenomas with an unenhanced attenuation value of 0 H, which is close to the mean attenuation of lipid-rich adenomas. It is not surprising, therefore, that lipid-poor adenomas have a significantly lower relative percentage enhancement washout than lipid-rich adenomas, because not including their higher unenhanced attenuation value (mean, 26 ± 7.0 H) lowers the calculated percentage. Despite the lower relative percentage enhancement washout of lipid-poor adenomas, it is still significantly higher than that of the adrenal nonadenomas. It can therefore be helpful in distinguishing lipid-poor adenomas and non-adenomas when the unenhanced attenuation value is not known.
The optimal threshold percentage enhancement washout and relative percentage enhancement washout for the diagnosis of adrenal adenoma and their associated sensitivity and specificity on scans obtained 15 min after IV contrast administration are similar to those previously reported [4]. The optimal threshold percentage enhancement washout was 60% in both studies. At this threshold the specificity of 95% for both lipid-poor and lipid-rich adenomas in our study is nearly identical to the 96% specificity for the combined group in the prior study [4]. The sensitivities of 89% and 79% for the lipid-poor and lipid-rich adenomas, respectively, are also similar to the sensitivity of 88% from the previous combined group [4]. For the relative percentage enhancement washout, our determination of the optimal threshold of 40% for our lipid-poor adenomas is identical to that for the previous combined group, but the sensitivity (83% versus 96%) and specificity (93% versus 100%) are lower. For the lipid-rich adenomas, a relative percentage enhancement washout threshold of 50% was associated with a more optimal sensitivity (93%) and specificity (98%), similar to the results of the combined group (96% and 100%, respectively) described in the previous report [4].
There are several limitations to our study. First, a number of the lipid-rich adenomas were not verified histologically and did not have long-term imaging follow-up. The diagnosis of adenoma was made solely on its unenhanced CT attenuation measurement of 10 H or less. However, the validity of this criterion as evidence of adenoma has been corroborated by a number of large series [2, 4,5,6, 8]. Second, although our un-enhanced and delayed contrast-enhanced images were obtained with 3- or 5-mm slice collimation, the 5-, 7-, or 10-mm collimation used for the initial enhanced images could have resulted in falsely low attenuation values if partial volume errors were made because of the inclusion of smaller masses. Third, our patient population does not reflect a consecutive group of patients with an adrenal mass seen on CT. This is because some patients, not included in our series, with an adrenal mass measuring less than 10 H on unenhanced CT did not receive contrast enhancement and were therefore not included in our study. Similarly, some patients with a known malignancy and widespread metastases at the time an adrenal mass was first detected did not undergo unenhanced or delayed contrast-enhanced CT. Bias in our study group or our calculations may have been introduced by the selective nature of our population. Lastly, although CT attenuation measurements were made only in homogenous portions of an adrenal mass, the unlikely possibility of an inhomogeneous metastasis or other mass coexisting with an adenoma (collision tumor) was not addressed in our study.
In summary, lipid-poor adrenal adenomas show contrast enhancement washout nearly identical to that of the more common lipid-rich adenomas and significantly greater than that of nonadenomas. Although lipid-poor adenomas cannot be differentiated from nonadenomas on the basis of their CT attenuation value alone before or after contrast enhancement, they can be differentiated by their percentage enhancement washout and relative percentage enhancement washout with an acceptable sensitivity and high specificity.
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