The non-functional adenomas are the most common in adrenal incidentalomas, accounting for 70%-80%.22,23 It is usually homogeneous and relative smaller. The occurrence rate of incidental pheochromocytomas increased, ranging from 5% to 58% in studies.7,24,25 Homogeneous pheochromocytomas without necro-cystic changes and hemorrhage may be mistaken as lipid-poor adenomas, especially those without lipid on unenhanced CT. While classic clinical symptom and biochemical test is of great value to differentiate adenomas from pheochromocytomas, these are not fully reliable. Only 11% adenomas are functional.19 Likewise, negative results of biochemical test can not exclude pheochromocytomas, up to 40% patients with pheochromocytomas were asymptomatic in a study.11 Hence, preoperative image examination plays a vital role in diagnosis.
Chemical shift MR is sensitive to detect intracellular lipid, image analysis of signal loss in in-phase and opposed-phase characterize lipid-rich adenomas.26 However, for hyperattenuating adrenal masses greater than 10 HU, CT is superior to chemical shift MRI.27 Thus, adrenal CT protocol has been recommended for assessment of adrenal lesions.6 It not only demonstrates imaging features of size, morphology, lipid content of the lesion, but also provides attenuation values on different phases and washout characteristic.
Our study showed that tumor size of two groups did not differ significantly. Several studies indicated that pheochromocytomas were usually larger than adenomas,11,21 in discordance with our study. Only pheochromocytomas without necro-cystic changes and hemorrhage were included in our study. Generally, incidence rate of heterogeneity increases when tumors get larger. The discrepancy of inclusion criteria contributes to different result.
There were few studies on enhancement pattern of adenomas and pheochromocytomas on dual-phase enhanced CT. In a study that evaluated the time density curve (TIC) of adenomas and non-adenomas at dynamic contrast-enhanced CT, 84% adenomas showed rapidly wash-in in early phase (≤ 1 minute) followed washout feature,28 but the TIC of pheochromocytomas included in non-adenomas group was not present alone. Northcutt et al.19 found there was difference on enhancement pattern between the two entities. 85% adenomas demonstrated a higher enhancement level on venous phase. No adenomas enhanced greatly on arterial phase, while 25% pheochromocytomas did. In our study, enhancement pattern was similar in two groups, persistent enhancement pattern was the most common (52.9% in both tumors). 26.5% adenomas enhanced higher on arterial phase, in discordance of study by Northcutt et al.19 It was dubious whether the enhancement pattern of lipid-rich adenomas, lipid-poor adenomas and adenomas without lipid differed.
Adenoma without lipid showed precontrast values of 36.5 HU (range, 25-48 HU), higher than that of lipid-poor adenoma in a retrospective study consisting of 145 cases (mean, 22.0 HU).29 Still, precontrast CT values in pheochromocytomas were significantly higher than that of adenomas without lipid (41.4 HU vs 36.5 HU, p=0.006) . A cutoff value of 40.7 HU yielded a sensitivity of 70.6% and specificity of 76.5% for pheochromocytomas, but there was not definitely reliable differentiating adenomas without lipid from pheochromocytomas.
Recently, some researches suggested that arterial and venous enhancement level was significantly higher in pheochromocytomas than in adenomas, and it can avoid misdiagnosis combined with washout features.19-21 In a study by Northutt et al.,19 attenuation on arterial and venous phase in 22 pheochromocytomas was significantly higher than that in 41 adenomas (104 HU vs 37 HU, 119 HU vs 60 HU respectively). No adenomas exceeded 85 HU in the arterial phase, and 58% pheochromocytomas were higher than 110 HU in the arterial phase. Subsequently, Northcutt et al.20 drew the similar conclusion by increasing the sample size with 26 pheochromocytomas and 200 adenomas, the mean venous enhancement values of pheochromocytomas and lipid-poor adenomas were 111 HU and 76 HU respectively. A threshold of 130 HU on venous phase was 38% sensitive and 100% specific for pheochromocytomas. Mohammed et al.21 found venous enhancement level greater than 85 HU showed good diagnostic performance for pheochromocytomas, with sensitivity of 88.2%, specificity of 83.7%. There were some differences on findings of ours and theirs. Significant differences were not found between the two groups, although the mean arterial and venous enhancement level of pheochromocytomas was higher than that of adenomas without lipid (100 HU vs 85 HU, p=0.223; 103 HU vs 96 HU, p=0.905). In our research, 14.7% (5/34) adenomas without lipid and only 35.3% (6/17) pheochromocytomas were greater than 110 HU on the arterial phase. 64.7% (22/34) adenomas without lipid and 52.9% (9/17) pheochromocytomas enhanced greater than 85 HU on venous phase. The main distinction between ours and theirs was inclusion criteria for adenomas and pheochromocytomas. On one hand, the size of homogeneous pheochromocytomas in our study was relatively smaller, however, a study by Kim et al.30 revealed the enhancement level on 1 minute did not differ significantly between small and large pheochromocytomas (the size thresold: 3 cm) . On the other hand, all lipid-poor adenomas in our study showed no lipid on precontrast CT, which was different from almost all of studies. The unenhanced CT values of adenomas without lipid were higher than that of lipid-rich and lipid-poor adenomas, which may indicated the decreased ratio of lipid-rich cell.31 Researches revealed the attenuation on arterial and venous phase of lipid-poor adenomas was significantly higher compared to lipid-rich adenomas.19,20 We noted the enhancement level of adenomas without lipid in our study was greater than that of lipid-poor adenomas in Northcutt's study (arterial phase, 85 HU vs 57 HU; venous phase, 96 HU vs 86 HU).19 As no study investigated the correlation between enhancement level on arterial and venous phase and precontrast values of adenomas, inclusion criteria for adenomas without lipid in our study may contribute to the discrepancy of studies. Nevertheless, no adenoma without lipid showed enhancement level greater than 130 HU on venous phase in our study, in line with study by Northcutt et al.,20 but only 4 pheochromocytomas met the level (4/17, 23.5%).
The PPE could reflect the blood supply characteristic of tumors in some degree. Our study demonstrated that distribution of the PPE of adenomas without lipid and pheochromocytomas was discriminative. The distribution of PPE of adenomas without lipid was agminated while that of pheochromocytomas was discrete. This feature may be related to variable imaging appearance of pheochromocytomas, from hypovascular to highly vascular lesion.10,12 A range of 100%-240% of PPE yielded sensitivity of 88.2%, specificity of 47.1% for diagnosing adenomas without lipid. Compared to APW and RPW obtained from a relatively long delayed phase, the chief advantage of PPE is that it can be obtained conveniently from biphasic enhanced CT in clinical practice. Additional delayed scan may be avoided for patient if indeterminate adrenal incidentaloma was found with homogeneous density. However, further studies are needed to explore the potential value of PPE due to its low specificity.
There were several limitations of our study. First, the sample size of both tumors was small owing to the strict inclusion criteria. The occurrence rate of pheochromocytomas was low, much less of homogeneous lesions without necro-cystic changes and hemorrhage. Similarly, lipid-poor adenomas without lipid on unenhanced CT were not common. Second, we did not perform delayed scan and washout characteristic was not calculated in the study. Further study are needed to investigate its value in the differentiation of homogeneous pheochromocytomas and adenomas without lipid. Third, the restrospective nature of our study result in some inherent limitations, particularly, contrast volume and infusion rate, which may affect enhancement level.