Adrenal Metastases (Carcinoma) Imaging

Updated: Nov 06, 2020
  • Author: Jeffrey M Lemons, MD; Chief Editor: Eugene C Lin, MD  more...
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Practice Essentials

The adrenal gland is a common site of metastatic disease, with a reported prevalence of 3.1%. [1]  A diagnosis of adrenal metastasis is important in examining patients with cancer, because metastasis indicates stage IV disease. Except in ipsilateral renal cancer, the presence of metastases almost always influences the choice of treatment. Benign adrenal tumors may occur in the general population and in patients with cancer. In the general population, it has been estimated that 2-3% of incidentally found adrenal masses are malignant. [2]  The original tumors are usually those of lung cancer, renal cancer, colorectal cancer, hepatocellular carcinoma (HCC), or malignant melanoma. Autopsy studies have identified adrenal metastases in up to 27% of patients with known malignancies. [3]

Imaging findings can demonstrate metastasis only if an alteration occurs in the outline, the size, or the internal characteristics of the adrenal gland. A normal-appearing gland does not exclude microscopic involvement.

(CT scans of normal right and left adrenal glands are shown in the images below.)

Contrast-enhanced axial CT scan of a normal right Contrast-enhanced axial CT scan of a normal right adrenal gland. Note the inverted Y-shaped body with 2 limbs that point posteriorly.
Contrast-enhanced axial CT scan of a normal left a Contrast-enhanced axial CT scan of a normal left adrenal gland. Note the lambda-shaped body and the 2 limbs.

Preferred examination

Noninvasive characterization is important, because it prevents unnecessary biopsy. In adults, CT scanning is the ideal imaging modality for detecting abnormal adrenal glands(see the images below). [4]  In patients with primary malignancies that have known predilections for adrenal metastases (especially melanoma, lung cancer, and breast cancer), CT scanning of the abdomen is useful for staging to exclude metastatic disease. [5]

Contrast-enhanced axial CT scan. A right adrenal a Contrast-enhanced axial CT scan. A right adrenal adenoma has enlarged the gland, giving it a bulbous appearance.
Contrast-enhanced axial CT scan. A left adrenal ad Contrast-enhanced axial CT scan. A left adrenal adenoma expands the tips of the gland limbs.

Cross-sectional imaging, such as computed tomography (CT) scanning and magnetic resonance imaging (MRI), has shown that adrenal metastases occur more frequently than previously believed. [6, 7] The usefulness of ultrasonography is limited to detecting large tumors in adults. Children, in whom imaging is less difficult, may be suitable candidates for US. [8]  Adrenal metastases cannot be reliably differentiated from adrenal adenomas with single-phase contrast-enhanced CT. [9]

To determine whether quantitative computed tomography texture analysis (CTTA) can be used to differentiate metastases from benign adrenal masses on single-energy CT images, Shi et al performed a retrospective study of 225 patients with 265 histologically confirmed adrenal masses (101 metastases, 98 pheochromocytomas, and 66 lipid-poor adenomas). Six texture parameters were used: mean, SD of pixel distribution histogram, mean of positive pixels, entropy, kurtosis, and skewness. Compared to benign adrenal masses, metastases had significantly lower mean gray-level intensity, SD, entropy, mean of positive pixels, and kurtosis on unenhanced images. On contrast-enhanced CT images, except for skewness and kurtosis, texture parameters were lower in the metastatic group. [10]

Adrenal metastases are usually hypointense on T1-weighted images and relatively hyperintense on T2-weighted images. [7, 11] In a study by Schieda et al, MRI features of clear cell renal cell carcinoma (RCC) adrenal metastases were compared with those of adrenal adenomas. Increased T2-weighted signal intensity and heterogeneity were found to be features that helped differentiate clear cell RCC adrenal metastases from adenomas. In addition, metastases were larger than adenomas (mean, 5.0 ± 4.2 cm [range, 1.1-15 cm] vs 2.0 ± 0.7 cm [range, 1.2-3.7 cm]). [12]

Radionuclide studies may help demonstrate that a lesion is a functioning adenoma, although false-negative results are known.

Positron emission tomography (PET) scanning may be helpful in differentiating incidental adrenal adenomas (the lipid-poor variety) from small metastases.

A finding of a focal mass in the adrenal glands does not necessarily indicate metastasis. Percutaneous biopsy often is the next step if CT and MRI scan findings do not help in conclusively diagnosing benign conditions.

One study of patients with small-cell lung cancer showed that as many as 17% of adrenal glands with morphologically normal CT scan findings had positive results for metastasis on fine-needle aspiration. Small adrenal metastases (< 2 cm) are difficult to detect with ultrasonography.

Guidelines

The European Society of Endocrinology (in collaboration with the European Network for the Study of Adrenal Tumors) recommended the following [13] :

  • Adrenal-focused imaging is recommended in all patients with suspected adrenocortical carcinoma (ACC).
  • In any case where there is a high suspicion of ACC, perform a chest CT, in addition to an abdominal-pelvic cross-sectional imaging (CT or MRI), because the results might influence therapeutic decision making.
  • Suggest performing additional imaging (eg, bone and brain imaging) only in case of clinical suspicion of metastatic lesions.
  • Only noncontrast CT is sufficiently reliable to rule out an ACC when the adrenal lesion is homogeneous and has low CT density ≤10 HU. In contrast, ACCs are usually large and of inhomogeneous appearance and characterized by low fat content (and hence higher HU density). FDG-PET has been proposed as possibly the best second-line test to assess indeterminate masses by unenhanced CT.
  • If adrenal imaging indicates an indeterminate mass, other parameters should be considered. For example, a tumor size >4 cm, combined adrenocortical hormone excess, and rapidly developing symptoms or young age (eg, < 40 yr) might point to an ACC. However, it is important to note that no single imaging method can definitively prove the diagnosis of ACC.
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Radiography

Plain-film imaging of adrenal masses is limited. Large masses are often indistinguishable from renal lesions, and the presence of calcium is not a specific finding (see the image below). The presence of phleboliths is suggestive of an adrenal hemangioma. 

If the plain-film radiographic findings suggest an adrenal lesion, further evaluation may be performed with CT scanning or MRI. The choice of investigation is determined by availability.

The negative predictive value of normal abdominal radiographic findings is low, because even images of relatively large adrenal lesions may not demonstrate changes.

Magnified plain abdominal radiograph of the right Magnified plain abdominal radiograph of the right hypochondrium demonstrates typical calcification of the right adrenal gland. This finding could be caused by granulomatous disease, old hemorrhage, or idiopathic causes. A calcified neoplasm is less likely in the absence of a soft-tissue mass.

 

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Computed Tomography

Adrenal metastases appear as focal masses (see the image below) or distortion of the contour of the adrenal gland. Larger lesions may have central necrosis or hemorrhage. These lesions are heterogeneous and may have thick, enhancing rims. They may also invade contiguous organs, such as the kidneys. Adrenal metastases of less than 3 cm may be homogeneous. [14, 15]

Contrast-enhanced CT scan depicts heterogeneously Contrast-enhanced CT scan depicts heterogeneously enhancing and partially necrotic bilateral adrenal metastases from a lung carcinoma.

Attenuation values of less than 10 HU on unenhanced CT scans of the adrenal glands are indicative of lipid-containing benign lesions, such as adrenal adenomas (specificity, 100%; sensitivity, 85%); however, lipid-poor adrenal adenomas have attenuation values of more than 10 HU. Attenuation values of 24-37 HU on enhanced CT scans obtained 15 minutes to 1 hour after the administration of contrast material are also indicative of benign lesions (specificity, 96%; sensitivity, 79%). Washout imaging is critical for the characterization of lipid-poor adrenal adenomas. [16]

The attenuation values of the adrenal glands are more useful than their size for making the diagnosis. The use of the size threshold alone has poor specificity regarding high thresholds (size >2.5 cm: specificity, 79%; sensitivity, 84%) and poor sensitivity regarding low thresholds (size < 1.5 cm: specificity, 93%; sensitivity, 16%). [5] Bilateral involvement may be seen in a number of benign conditions, such as adrenal adenomas, pheochromocytomas, and tuberculosis.

CT scan findings that may mimic those of left adrenal masses include a mass in the upper pole of the left kidney, gastric diverticulum, splenic lobulation, and a large mass in the tail of the pancreas. Adrenal metastases cannot be reliably differentiated from adrenal adenomas with single-phase contrast-enhanced CT. [9]

The image below demonstrates CT scan findings that confirm the absence of a mass.

Axial CT scan obtained without intravenous contras Axial CT scan obtained without intravenous contrast enhancement. This image shows bilateral adrenal calcification, and the findings confirm the absence of a mass. Patients with this type of adrenal calcification do not necessarily have adrenal insufficiency.

To determine whether quantitative computed tomography texture analysis (CTTA) can be used to differentiate metastases from benign adrenal masses on single-energy CT images, Shi et al performed a retrospective study of 225 patients with 265 histologically confirmed adrenal masses (101 metastases, 98 pheochromocytomas, and 66 lipid-poor adenomas). Six texture parameters were used: mean, SD of pixel distribution histogram, mean of positive pixels, entropy, kurtosis, and skewness. Compared to benign adrenal masses, metastases had significantly lower mean gray-level intensity, SD, entropy, mean of positive pixels, and kurtosis on unenhanced images. On contrast-enhanced CT images, except for skewness and kurtosis, texture parameters were lower in the metastatic group. [10]

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Magnetic Resonance Imaging

Adrenal metastases are usually hypointense on T1-weighted images and relatively hyperintense on T2-weighted images (see the first image below). [11] The exception is metastatic melanoma, which may be bright on T1-weighted images (see the second image below). [17] Occasionally, lesions may remain hyperintense on long–echo-time, T2-weighted images, mimicking pheochromocytomas.

T2-weighted (left image) and contrast-enhanced T1- T2-weighted (left image) and contrast-enhanced T1-weighted (right image) MRIs show metastasis to the left adrenal gland in a patient who underwent hepatic resection for hepatocellular carcinoma.
A metastatic melanoma to the right adrenal gland a A metastatic melanoma to the right adrenal gland appears as a hyperintense mass on this T1-weighted MRI.

Chemical-shift imaging (CSI) with in-phase and out-of-phase imaging techniques is used to exclude metastatic disease by detecting the presence of intracellular lipid within adrenal gland lesions. On out-of-phase images, the lesions have lower signal intensity, because the signal from lipid cancels the signal from water by an amount that varies (depending on the quantity of fat present). [15]  

By comparing out-of-phase images with in-phase images (in which signals from lipid and water are summed), very small amounts of lipid that cannot be demonstrated with other methods can be detected; however, lipid-poor adenomas do not lose signal intensity on out-of-phase images. An adrenal metastasis might not contain lipid (see the image below).

T1-weighted chemical shift (left image) and T1-wei T1-weighted chemical shift (left image) and T1-weighted fat-saturated (right image) MRIs of metastatic melanoma to the left adrenal gland show increased signal intensity in the mass; the findings exclude the presence of microscopic and bulk lipid, respectively.

Conventional spin-echo MRI and contrast-enhanced MRI findings with benign and malignant conditions have too much overlap to be useful. A small number of malignant tumors, such as metastatic hepatocellular carcinoma, metastatic renal cell carcinoma, metastatic liposarcoma, and adrenocortical carcinoma, may contain enough fat to decrease the signal intensity on out-of-phase images. [11]

In a study by Schieda et al, MRI features of clear cell renal cell carcinoma (RCC) adrenal metastases were compared with those of adrenal adenomas. Increased T2-weighted signal intensity and heterogeneity were found to be features that helped differentiate clear cell RCC adrenal metastases from adenomas. In addition, metastases were larger than adenomas (mean, 5.0 ± 4.2 cm [range, 1.1-15 cm] vs 2.0 ± 0.7 cm [range, 1.2-3.7 cm]). [12]

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Ultrasonography

Adrenal metastases appear as solid lesions with heterogeneous echogenicity on sonograms, as seen in the image below. The echogenicity of the lesions is usually less than that of the surrounding fat (hypoechoic).

Axial sonogram demonstrates a hypoechoic liver neo Axial sonogram demonstrates a hypoechoic liver neoplasm and a metastasis to the right adrenal gland (indicated by the calipers) that are separate from and superior to the right kidney.

Ultrasonography of the adrenal glands in adults is technically difficult to perform. When performed by an experienced operator, ultrasonography has revealed the right adrenal gland in 92% of patients and the left adrenal gland in 71% of patients. Scanning is performed after the patient fasts to reduce bowel gas. In newborns, the adrenal glands are easily imaged. The medulla of the adrenal gland is highly echogenic, and the adrenal cortex is less echogenic. The adrenal glands are more easily visualized in typically sized adults (those with a thin habitus). [18, 19]

False-positive and false-negative findings may include the following:

  • Adrenal pseudomass

  • Thickened diaphragmatic crus

  • Accessory spleen

  • Gastric fundus

  • gastric diverticulum

  • Renal vein

  • Splenorenal varices

  • Retrocrural and retroperitoneal adenopathy

  • Upper-pole renal cyst and/or neoplasm

  • Pancreatic mass

  • Hypertrophic caudate lobe

  • Fluid-filled colon

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Nuclear Imaging

Nuclear scintigraphy with iodomethylnorcholesterol (NP-59) may be helpful in differentiating benign from malignant lesions. Gross et al showed that scintigraphy with NP-59 was 71% sensitive, 100% specific, and 93% accurate when determining whether an adrenal lesion was benign or malignant. [20] Benign lesions show uptake, although hemorrhage and inflammatory masses are confounding factors.

Imaging with fluorodeoxyglucose (FDG) is an alternative technique that is performed with positron emission tomography (PET). Various studies have shown evidence of success with FDG-PET scanning. [21, 22, 23, 24, 25, 26] . PET has been shown to be excellent at differentiating adrenal lesions detected by CT or MRI, with 93-100% sensitivity, 90-94% specificity, and 92-96% accuracy. [17]

PET-CT may lead to false-negative findings with lesions that are less than 10 mm in diameter or in the setting of hemorrhage or necrosis. PET-CT adrenal lesions are considered positive when the maximum standardized uptake value (SUVmax) is greater than that of the liver, although SUV greater than 3.1 has also been suggested. [17] (See the image below.)

PET-CT demonstrating a left adrenal mass, with an PET-CT demonstrating a left adrenal mass, with an SUVmax of 5.9 in a patient with known lung adenocarcinoma. Core biopsy confirmed the presence of metastatic disease.
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