Differentiation of Adrenal Adenomas from Non-Adenomatous Lesions: Diagnostic Value of Unenhanced Spectral CT

1. Introduction

According to the Society of Abdominal Radiology, an adrenal incidentaloma is defined as an incidentally detected adrenal nodule or mass unrelated to the clinical indication for the imaging examination performed [1]. More recently, a refined definition has been proposed, restricting adrenal incidentalomas to lesions measuring ≥1 cm and excluding patients with current or prior extra-adrenal malignancy [2].

Adrenal incidentalomas are relatively common, with a reported prevalence of approximately 3–7% in the adult population, and the majority represent benign, non-functioning adenomas. Accurate characterization of adrenal lesions as benign or malignant is therefore crucial, as imaging findings directly influence patient management and follow-up strategies [3,4,5].

Historically, CT characterization of adrenal lesions has relied on two main principles. First, an unenhanced attenuation value of ≤10 Hounsfield units (HU) has been considered diagnostic of lipid-rich adenomas, obviating the need for further imaging. Second, lesions with attenuation values >10 HU have traditionally been evaluated using contrast-enhanced washout techniques to differentiate lipid-poor adenomas from non-adenomatous lesions, with commonly accepted thresholds of ≥60% for absolute washout and ≥40% for relative washout [5,6,22].

More recently, an unhenanced attenuation threshold of >20 HU was proposed, in order to increase sensitivity in detecting benign lesions [2]. In parallel, dual-energy CT (DECT) has emerged as a promising technique for tissue characterization beyond conventional HU measurements, exploiting the energy-dependent attenuation properties of different materials [7,8,9,10].

In particular, unenhanced dual-energy CT allows spectral attenuation analysis using virtual monoenergetic images (VMIs). The presence of intracellular lipid within adrenal adenomas results in characteristic decrease in attenuation at lower energy levels, potentially providing incremental diagnostic information, even in lesions with attenuation values above 10 HU [11,12,13,14,15,16].

Based on previous evidence [17], we hypothesized that the attenuation difference between low- and high-energy VMIs (40–140 keV) could serve as a reliable discriminative parameter for differentiating adrenal adenomas from non-adenomatous lesions.

The aim of this study was to evaluate the diagnostic performance of unenhanced spectral CT for diagnosis of adrenal adenomas, in comparison with conventional unhenanced <10 HU and <20 HU cut-offs.

2. Materials and Methods

2.1. Study Population

Adult patients with adrenal nodular lesions who underwent unenhanced abdominal dual-energy Spectral CT between September 2021 and December 2025 were retrospectively identified from the institutional database of our University hospital. CT examinations were performed for various clinical indications, including both incidentally detected and clinically suspected adrenal lesions.

Inclusion and exclusion criteria are summarized in Figure 1.

The reference standard for all adrenal lesions was based on histopathologic examination, and/or interval imaging follow-up. Lesions showing no change in size for at least 12 months were considered as benign adenomas, whereas lesions demonstrating a size increase greater than 20% in maximum diameter were considered as non-adenomatous.

2.2. Spectral CT Image Acquisition

All images were acquired using dual-layer spectral-detector CT (IQon, Philips Healthcare), which provides both conventional (120 kVp) and spectral-based images.

Technical parameters are reported in Table 1.

Axial, unenhanced conventional 120-kVp and VMIs at 40 keV and 140 keV were reconstructed with contiguous 2-mm-thick sections.

Conventional images were reconstructed using an iterative reconstruction algorithm (iDose 4, level 3; Philips Healthcare), and VMIs were reconstructed using a dedicated spectral image reconstruction algorithm (Spectral, level 3; Philips Healthcare).

2.3. Image Analysis

All image data were postprocessed using the proprietary workstation (IntelliSpace Portal, version 9.0; Philips Healthcare).

Image analysis was conducted by two board-certified radiologists in consensus, both blinded to clinical information and final diagnosis.

To measure mean unenhanced attenuation on conventional images and VMIs, a circular region of interest (ROI) was placed manually within the center of each adrenal lesion, avoiding surrounding fat or normal adrenal parenchyma.

For each lesion, measurements from three separate ROIs were averaged to ensure data consistency. The spectral attenuation difference (Δ40–140 keV) was calculated as the difference between attenuation values measured on 40-keV and 140-keV VMIs using an identical ROI.

The spectral attenuation curve was also reconstructed from the VMIs at different energy levels.

2.4. Statistical Analysis

Statistical analyses were performed by using Med Calc software (MedCalc Statistical Software version 23.0.8 (MedCalc Software Ltd., Ostend, Belgium) and Matlab (Matlab, MathWorks v. R2024b, Natick, MA, USA)). Group comparisons were performed using the Mann–Whitney U test. Receiver operating characteristic analysis was conducted to assess diagnostic performance and determine optimal thresholds using the Youden index.

3. Results

3.1. Patient Demographics

A total of 258 patients were initially identified. After application of exclusion criteria, 60 patients were included in the final analysis, thirty-one males and twenty-nine females, mean age of 66 years. Forty-nine lesions were adenomas and eleven were non-adenomatous lesions: metastases (8), pheochromocytomas (2) and adrenal carcinoma (1).

3.2. Diagnostic Performance Figures, Tables and Schemes

ROC curve analysis demonstrated that optimal threshold to discriminate adenomas from non-adenomas, using Δ40–140 keV, was -17 HU, with values below this cutoff are indicative of benign lesions.

The diagnostic performance of all three parameters was high: HU ≤10 (AUC = 0.81), HU ≤20 (AUC = 0.88), and Δ ≤ –17 (AUC = 0.90). These values indicate good discriminative ability between benign and malignant lesions.

The diagnostic performance of the spectral attenuation difference was superior to that of conventional attenuation thresholds, with the highest area under the curve (Figure 2).

Significant differences were observed between benign and malignant lesions across all evaluated parameters (p < 0.0001). Adenomas exhibited lower unenhanced attenuation values and more negative spectral attenuation differences compared with non-adenomatous lesions (Figure 3 and Figure 4).

The results of the quantitative analysis are shown in Figure 5.

Diagnostic performance metrics are summarized in the bar plot (Figure 6), clearly showing that the spectral attenuation difference (Δ40–140 keV) provides the most balanced combination of sensitivity, specificity, and predictive values compared to the other evaluated rules.

4. Discussion

According to the 2023 European Society of Endocrinology (ESE) guidelines, unenhanced CT is considered the first imaging modality in the characterization of adrenal incidentalomas. [18]

Our results support the role of conventional attenuation thresholds as reliable and well-established criteria for the characterization of adrenal lesions.

The 10 HU threshold is highly specific but less sensitive for the diagnosis of adrenal adenoma, while the 20 HU threshold improves sensitivity to the detriment of specificity. [19].

Despite the very low prevalence of malignancy among homogeneous adrenal nodules <4 cm with attenuation between 10 and 20 HU, especially in patients without history of extra-adrenal malignancy, additional imaging or a 12-months follow-up are required.

The diagnostic accuracy of contrast-enhanced CT with a delayed washout (absolute and relative) is very low because up to one-third of pheochromocytomas and malignant tumors may show rapid washout similar to adenomas, while a notable fraction of benign adenomas do not meet the rapid washout criteria. [19,20,21,23,24,25,26]

Finally, despite FDG-PET/CT represents the most reliable imaging method in the assessment of adrenal masses indeterminate at unenhanced CT, few malignant lesions are FDG-negative, especially renal cancer, and a subset of benign adenomas, especially if endocrine active, are FDG-positive.

Dl-DECT has emerged as a useful tool for the characterization of incidental adrenal masses, because the ability to analyse lesion attenuation across a spectrum of energy levels provides crucial information on tissue composition. [15].

Spectral analysis allows detection of fat within adenomas, similarly to MRI with chemical shift imaging, even when mean attenuation exceeds 10 HU, overcoming the main limitation of conventional CT.

Our data demonstrate that the attenuation difference between 40 keV and 140 keV VMIs offers superior diagnostic performance compared with conventional unenhanced attenuation thresholds.

The diagnostic rule based on a conventional unenhanced attenuation value ≤ 10 HU, traditionally used to identify lipid-rich adenomas, demonstrated a good discriminative ability, with an AUC of 0.82. Increasing the attenuation threshold to ≤ 20 HU resulted in an improvement in sensitivity for benign lesions, yielding an AUC of 0.88. However, this gain in sensitivity was accompanied by a higher false-positive rate.

The diagnostic rule based on the spectral attenuation difference between 40 keV and 140 keV VMIs (Δ40–140 keV ≤ −17 HU) exhibited the highest diagnostic accuracy, with an AUC of 0.90.

Our results are consistent with prior literature. Nagayama et al., using ΔHU between 140 and 40 keV and 19 HU as the optimal threshold, demonstrated sensitivity and specificity of 76% and 97% respectively, in a group of adrenal lesions with attenuation of 10–30 HU, potentially eliminating the need for additional diagnostic work-ups, in this set of lesions [17].

Our study has several limitations. First, it is a retrospective single-center study, which may limit the generalizability of the findings. Additionally, the overall sample size is relatively small, especially regarding patients with non-adenomatous lesions. The limited number of such cases may affect the statistical power and the strength of the conclusions drawn.

Larger multicenter studies are warranted to validate these findings.

5. Conclusions

Unenhanced Spectral CT using the attenuation difference between 40 keV and 140 keV VMIs demonstrates higher diagnostic accuracy for differentiating adrenal adenomas from non-adenomatous lesions.

Integration of spectral parameters into diagnostic algorithms may reduce the number of indeterminate incidental adrenal lesions, avoiding the need for additional imaging in lesions with attenuation values between 10 HU and 20 HU.