Echogenicity of benign adrenal focal lesions on imaging with new ultrasound techniques - report with pictorial presentation.

AIM: The aim of the research was to assess the echogenicity of benign adrenal focal lesions using new ultrasound techniques. MATERIAL AND
METHOD: 34 benign adrenal masses in 29 patients were analyzed retrospectively. The examinations were conducted using Aplio XG (Toshiba, Japan) ultrasound scanner with a convex probe 1-6 MHz in the B-mode presentation with the combined use of new ultrasound techniques: harmonic imaging and spatial compound sonography. The size of the adrenal tumors, their echogenicity and homogeneity were analyzed. Statistical analysis was conducted using the STATISTICA 10 software.
RESULTS: The following adrenal masses were assessed: 12 adenomas, 10 nodular hyperplasias of adrenal cortex, 7 myelolipomas, 3 pheochromocytomas, a hemangioma with hemorrhage and a cyst. The mean diameter of nodular hyperplasia of adrenal cortex was not statistically different from that of adenomas (p = 0.075). The possibility of differentiating between nodular hyperplasia and adenoma using the parameter of hypoechogenicity or homogeneity of the lesion was demonstrated with the sensitivity and specificity of 100% and 41.7%, respectively. The larger the benign adrenal tumor was, the more frequently did it turn out to have a mixed and inhomogenous echogenicity (p < 0.05; ROC areas under the curve: 0.832 and 0.805, respectively).
CONCLUSIONS: A variety of echogenicity patterns of benign adrenal focal lesions was demonstrated. The image of an adrenal tumor correlates with its size. The ultrasound examination, apart from its indisputable usefulness in detecting and monitoring adrenal tumors, may also allow for the differentiation between benign lesions. However, for lesions found incidentally an algorithm for the assessment of adrenal incidentalomas is applicable, which includes computed tomography and magnetic resonance imaging.

Introduction

Based on the data from the literature it is estimated that normal adrenal glands can be visualized in a large proportion (69–99%) of ultrasound scans in adult individuals(. However, it is not that easy in practice due to the similar echogenicity of adrenal glands to that of the retroperitoneal adipose tissue as well as a number of other factors such as the acoustic window, the quality of the ultrasound device and the experience of the examiner. Despite the fact that sonography is not a method of choice in the diagnostic assessment of the adrenal glands in adults, it represents an important technique for the evaluation of patients with disorders of these glands. Due to the easy access and noninvasive nature of the abdominal ultrasound scan, it is used as the first imaging examination, which often reveals pathologies in the adrenal area. Ultrasound scans are conducted in individuals with neoplastic diseases, hypertension, endocrinological disorders and for the monitoring of patients with already diagnosed small, hormonally inactive benign adrenal masses.

Sometimes abdominal ultrasound examinations performed due to causes which are unrelated to any adrenal pathology reveal adrenal masses by coincidence (incidentaloma). These are found in 1–10% of abdominal scans. Adrenal incidentalomas should not be ignored and require further diagnostic investigation, since nearly 25% of these lesions are surgically treated due to oncological or endocrinological disorders(.

The ultrasound examination represents an important method for the detection of adrenal focal lesions. Its’ advantages and disadvantages have been presented in Tab. 1.

Tab. 1

Advantages and disadvantages of adrenal sonography

Advantages	Disadvantages
Inexpensive, easily accessible, non-invasive, multiplanar Used for the diagnosis of diseases of the abdominal cavity, in patients with hypertension, oncological and endocrinological disorders Imaging of adrenal masses of > 10 mm (right side) and 15–20 mm (left side) in diameter Recommended for the monitoring of incidentalomas Possibility of ultrasound-guided biopsy	Dependent on the examining physician Does not always visualize nor-mal adrenal glands Usually does not differenti-ate between different adrenal masses

Aim of the research

The aim of the research is to establish the echostructure and its possible trends in benign adrenal masses using new ultrasound techniques in combination such as harmonic imaging and spatial compound sonography, which are often found in contemporary ultrasound scanners.

Material and method

The study was approved by the competent bioethics committee. The patients gave their informed consent to take part in the study. Ultrasound scan images of confirmed adrenal focal lesions obtained in the years 2010–2013 from 37 patients with the use of new ultrasound techniques were retrospectively analyzed. 34 adrenal masses in 29 patients were benign in nature. The final diagnosis was made based on the results of computed tomography, magnetic resonance imaging, blood chemistry tests, at least one year follow-up examinations or a histopathological examination after surgery (for 11 adrenal masses).

The examinations were conducted using the Aplio XG ultrasound sanner (Toshiba, Japan), a convex probe 1–6 MHz in the B-mode presentation with the combined use of new ultrasound techniques: harmonic imaging and spatial compound sonography. The size of the adrenal tumors, their echogenicity and homogeneity were analyzed. The mean diameter of an adrenal tumor was calculated on the basis of three maximum perpendicular dimensions measured on axial images and in the frontal plane.

Statistical analysis was conducted using the STATISTICA 10 software (StatSoft Inc.). The distribution of quantitative characteristics was assessed using the Shapiro–Wilk W test. Independent quantitative characteristics were assessed using the Mann–Whitney U test. The evaluation of echogenicity of the lesions was conducted using the Fisher's test. The p value of < 0.05 was considered statistically significant. The relationship between echogenicity and diameter of adrenal mass was also evaluated with ROC curves.

Results

In the group of 29 patients with benign adrenal masses there were 34 lesions assessed with application of new ultrasound techniques: 12 adenomas, 10 nodular hyperplasias of adrenal cortex, 7 myelolipomas, 3 pheochromocytomas, a hemangioma with hemorrhage and a cyst.

The mean diameter of all tumors was 38.5 mm (9.7–102 mm). The mean diameter of the nodular hyperplasias of adrenal cortex was 26.6 mm (9.7–58.5 mm) and the mean diameter of adenomas was 35.5 mm (16.3–56 mm); the difference was not statistically significant (p = 0.075) (Tab. 2).

Tab. 2

Analysis of diameters of benign adrenal masses

Mean diameter	N	Mean	Med.	Min.	Max.	SD	p*
Nodular hyperplasia	10	26,6	26,3	9,7	58,5	13,8	0,075
Adenoma	12	35,5	34,5	16,3	56,0	12,2
All benign	34	38,5	34,0	9,7	102,0	19,9

Mann–Whitney U test.

The echostructure of benign adrenal masses is presented in Tab. 3.

Tab. 3

Echostructure of benign adrenal masses

	Echogenicity	Homogeneity
Nodular hyperplasia (10)	10 hypo	10 homogenous
Adenoma (12)	7 hypo, 5 mix	7 homogenous, 5 inhomogenous
Myelolipoma (7)	3 hyper, 3 mix, 1 hypo	3 homogenous, 4 inhomogenous
Pheochromocytoma (3)	3 hypo	3 homogenous
Hemangioma with hemorrhage (1)	1 hypo	1 homogenous
Cyst (1)	1 hypo	1 inhomogenous

All nodular hyperplasia lesions were characterized by low echogenicity in comparison with their surroundings. As far as adenomas are concerned, over half of them (58.3%) also had low echogenicity, while the remaining ones had mixed echogenicity (41.7%). These differences turned out to be statistically significant (p = 0.03). The property of hypoechogenicity used to differentiate between nodular hyperplasia and adenoma had a sensitivity and specificity of 100% and 41.7%, respectively.

The comparison of homogeneity of echogenicity also revealed statistically significant differences (p = 0.03). All nodular hyperplasias were echogenically homogenous, while 58.3% of adenomas were homogenous. The remaining adenomas were echogenically inhomogenous. The property of homogenous echogenicity used to differentiate between nodular hyperplasia and adenoma had a sensitivity and specificity of 100% and 41.7%, respectively.

Further analysis concerned the relationship between the mean diameter of an adrenal focal lesion and mixed echogenicity as well as inhomogenous echogenicity. In both cases the results obtained turned out to be statistically significant (p < 0.05) and ROC areas under the curves were 0.832 and 0.805, respectively.

The larger the adrenal tumor was, the more frequently did it have a mixed and inhomogenous echogenicity. In both cases the cut-off point was similar: 34.33 mm and 33.67 mm, respectively.

Figures 1, 2, 3 and 4 B show examples of echogenicity of benign adrenal lesions in the B-mode presentation with a combined use of new ultrasound techniques such as harmonic imaging and spatial compound sonography. By way of comparison Figures 5 and 4 A present the image of malignant adrenal tumors (metastasis to the adrenal gland and primary carcinoma of the adrenal cortex).

Fig. 1

Nodular hyperplasia of adrenal cortex in a patient with three masses of both glands. Hypoechogenic mass of the right adrenal gland (calipers) with a mean diameter of 23 mm.

Fig. 2

Adenoma of the right adrenal gland. Mixed-echogenicity mass (calipers) with a mean diameter of 53 mm.

Fig. 3

Myelolipoma of both adrenal glands. A. Mixed-echogenicity mass (calipers) with a mean diameter of 102 mm. B. Hypoechogenic mass (calipers) with a mean diameter of 29 mm.

Fig. 4

Patient with bilateral masses of the adrenal glands. A. Primary carcinoma of the right adrenal cortex – hypoechogenic mass (calipers) with a mean diameter of 26 mm. B. Myelolipoma of the left adrenal gland – hyperechogenic mass (calipers) with a mean diameter of 28 mm

Fig. 5

Metastases of right kidney carcinoma to both adrenal glands in a patient with Addison's disease. The image shows a metastasis to the left adrenal gland with mixed echogenicity (calipers) and a mean diameter of 134 mm.

Discussion

New techniques which enhance the visualization of adrenal masses in transabdominal sonography include harmonic imaging, spatial compound imaging and three-dimensional sonography.

Harmonic imaging consists in obtaining images from a wave received by a broadband ultrasound probe with a frequency of the second harmonic. This wave appears in the tissues as a result of the propagation of the ultrasound beam of a fundamental frequency and has a two times higher frequency from the wave sent. There are various ways to obtain harmonic images, which result in different final images. Harmonic imaging as a rule reduces the number of artifacts, increasing the contrast of the images. The improvement of quality consists in clearer visualization of characteristics of fluid structures, which enables one to differentiate them from solid lesions with a greater degree of confidence. Other advantages of harmonic imaging include more precise visualization of the margins of anatomical structures and focal lesions, increase in the contrast between different structures as well as highlighting shadows behind calcifications or fibrosis or boosting echo enhancement behind a fluid lesion, which represents diagnostically useful highlighting of artifacts(. Some harmonic imaging techniques may reduce the range of visualized structures, especially in the case of deeply located lesions or bad acoustic window for the right adrenal gland in the presence of a fatty liver.

Modern ultrasound scanners allow for real-time spatial compound images to be obtained. This technique consists in combining images obtained as a result of “looking” at an object by the ultrasound wave from different angles (and not only from a right angle as in the conventional sonography). This allows for despeckling of the image and improves the visibility of lesion margins and the signal-to-noise ratio (increasing the contrast between the visualized structures)(. It is important here to stress the fact that reducing the speckles in the image, has a significant impact on the assessment of a lesion or organ: the image is smoothened (although without the loss of important anatomical details), artifacts are eliminated from fluid areas (the areas thus become “darker and clearer”), while real tissue echoes originating from the non-fluid content of complex cysts such as septa, masses and calcifications are more visible (due to decreased noise). The disadvantage of this technique is the reduction of the posterior echo, or enhancement (e.g. behind a cyst) or a shadow (e.g. behind a stone or calcification), which may make diagnosis or differentiation between lesions more difficult. However, reducing the shadow behind structures such as fibrosis may be treated as an advantage, since it allows for a better visualization of tissues which are located deeper. The advantages and disadvantages of real-time compound sonography are also related to the initial number of component images, which may be adjusted in some devices.

New ultrasound devices allow for combining different image enhancement options. The concurrent use of e.g. compound and harmonic imaging may improve the parameters of the image in comparison with each of these techniques used separately, and especially with conventional sonography.

The paper demonstrates a variety of echogenicity patterns of benign adrenal focal lesions. The image of an adrenal tumor often depends on its size(. The assessment of echogenicity on B-mode images using new ultrasound techniques also demonstrated that as the diameter of tumors increased, the more frequently they were inhomogenous or had a mixed echogenicity. No statistically significant differences in the size of masses were demonstrated in differentiating between nodular hyperplasia of adrenal cortex and adenomas. However, the possibility of differentiating between nodular hyperplasia and adenoma using the parameters of hypoechogenicity and homogeneity was demonstrated, with the sensitivity and specificity of 100% and 41.7%, respectively. The question of differentiating between nodular hyperplasias of the adrenal cortex and adenomas is often missing from papers on diagnostic imaging of adrenal masses. It turned out to have a better sensitivity and specificity, than with the parameter of echogenicity, of 100% and 83%, respectively, based on the assessment of the inflow dynamics pattern of a third-generation ultrasound contrast agent (SonoVue) with parametric images(.

The group of myelolipomas in our material is characterized by a greater variety of images than in the literature(: from hyperechogenic masses, which are considered to be typical, through mixed-echogenicity masses, to a hypoechogenic tumor.

The ultrasound examination, apart from the indisputable usefulness in the detection and monitoring of adrenal masses, may suggest a differential diagnosis.

The most common adrenal masses, adenomas, which account for 80% of such lesions, are presented in the literature as small (<3 cm), hypoechogenic, oval, with well-defined margins and a homogenous echostructure. However, despite these characteristics, the need for further imaging verification of these lesions (computed tomography, magnetic resonance imaging) in order to confirm the diagnosis is emphasized(.

In summary it is important to point out that despite the generally accepted rules as regards the echostructure of adrenal masses, including benign tumors such as adenomas, myelolipomas and cysts(, the presented material with the image documentation indicates that in the case of incidentalomas there is a need to use the generally accepted algorithm of assessment with application of computed tomography or magnetic resonance imaging.

A unique capability of sonography (including applying a third-generation contrast agent and parametric imaging) is differentiation between nodular hyperplasia of adrenal cortex and adenomas (these masses should be confirmed as benign lesions containing lipids using computed tomography or magnetic resonance imaging). This is potentially particularly important for patients with Conn's syndrome, which may by the subject of further research (in our material there were no patients with primary hyperaldosteronism).