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Author: Gervais Wansaicheong, MBBS, Registrar, Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore

Gervais Wansaicheong is a member of the following medical societies: American Roentgen Ray Society and Royal College of Radiologists

Coauthor(s): Jeffrey Goh, MBBS, FRCR, Registrar, Consulting Staff, Department of Diagnostic Radiology, Tan Tock Seng Hospital

Editors: Glenn Krinsky, MD, Chief of Abdominal Imaging Section, Associate Professor, Department of Radiology, New York University School of Medicine; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Arnold C Friedman, MD, FACR, Associate Chairman, Department of Radiology, University of Florida Health Science Center; Chief, Department of Radiology, Shands-Jacksonville Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center

Author and Editor Disclosure

Synonyms and related keywords: secondaries to the adrenal glands, adrenal gland metastases, adrenal metastasis

Background

The adrenal gland is a common site of metastatic disease. Modern cross-sectional imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has revealed that adrenal metastases occur more frequently than previously believed.

A diagnosis of adrenal metastasis is important in examining patients with cancer because metastasis indicates stage IV disease. (In this article, references to staging refer to tumor, nodes, and metastases [TNM] staging, unless otherwise stated.) Except in ipsilateral renal cancer, the presence of metastases almost always influences the choice of treatment.

Related eMedicine topics:
Adrenal Adenoma
Adrenal Carcinoma
Adrenal Surgery

Related Medscape topics:
CME Endocrine Emergencies
CME Endoscopic Ultrasound in GI Oncology
Evaluation and Management of Adrenal Masses

Pathophysiology

Adrenal metastases may be unilateral or bilateral. The tumors vary in size. Central necrosis and hemorrhage may occur, but calcification is rare.

The adrenal gland is the fourth most common site of metastasis, after the lung, liver, and bone. The most common primary sites are the lung,1 breast, skin (melanoma),2 kidney,3 thyroid, and colon.

Frequency

International

The reported frequency of adrenal metastases depends on the incidence of the primary tumor; however, for each primary malignancy, the frequency of adrenal metastases is different. Some malignancies are more likely to metastasize to the adrenal glands. About 50% of melanomas, 30-40% of breast and lung cancers, and 10-20% of renal and gastrointestinal tumors metastasize to the adrenal glands.

Mortality/Morbidity

Most often, the lesions are clinically silent, but cases of hypoadrenalism have occurred.

Race

No specific race-based predilections for adrenal metastases exist.

Sex

No specific sex-based predilections for adrenal metastases exist.

Age

No specific age-based predilections for adrenal metastases exist.

Anatomy

The paired adrenal glands are located at the level between vertebrae T11 and L2, lateral to the body of the L1 vertebra. The gland has an anteromedial ridge and 2 limbs, or “wings.” The maximum width of the body just before the limbs is 0.79 mm on the right side (standard deviation, 0.21 mm) and 0.6 mm on the left side (standard deviation, 0.2 mm). The length of the adrenal limbs varies; they may be as long as 4 cm. The width of the limbs is usually less than 1 cm. The right limbs (0.14-0.49 mm) are usually thinner than the left limbs (0.13-0.52 mm) (see Images 1-2).

The adrenal glands are surrounded by fatty areolar tissue with fibrous extensions into the gland; these cause the position of the gland to be relatively fixed. The glands separate from the kidneys during inspiration.

The right adrenal gland lies behind the inferior vena cava and above the right kidney. Its medial limb is parallel to the right crus, and its lateral limb is parallel to the liver.

The left adrenal gland lies in front of the upper pole of the left kidney. It extends to the renal hilum in 10% of individuals. Its medial limb is related to the aorta and the left crus. The cephalic two thirds of the anterior surface is posterior to the stomach, and the caudal one third of the anterior surface is posterior to the pancreas.

Clinical Details

Adrenal metastases are almost always clinically silent. In the event of extensive bilateral metastatic disease, hypoadrenalism may occur. This is often accompanied by nonspecific symptoms, such as faintness, dizziness, weakness,1 fatigue, and weight loss. At least 50% of patients have vague stomachaches or other gut symptoms, although these symptoms may also result from the malignancy. For these reasons, detailed investigations are not often performed unless proof of adrenal metastases exists.

Preferred Examination

In adults, CT is the ideal imaging modality for detecting abnormal adrenal glands (see Images 3-4). In patients with primary malignancies that have known predilections for adrenal metastases (especially melanoma, lung cancer, and breast cancer), CT of the abdomen is useful for staging to exclude metastatic disease.4

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.

Often, MRI is expensive and not widely available. MRI is useful for further noninvasive characterization of adrenal masses.

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

Positron emission tomography (PET) may be helpful for 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 findings do not help in conclusively diagnosing benign conditions.

Limitations of Techniques

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

Benign adrenal tumors may occur in the general population and in patients with cancer. Noninvasive characterization is important because it prevents unnecessary biopsy. The specificity of noninvasive characterization must be high to prevent attempted curative resection in a patient with metastatic disease.



Adrenal Adenoma
Adrenal Carcinoma
Adrenal Hemorrhage

Other Problems to Be Considered

Unilateral adrenal mass or enlargement

Small masses (<1 cm): Adenoma, ganglioneuroma, hyperplasia, metastasis, and pheochromocytoma

Large masses (>4 cm): Carcinoma of adrenal cortex; cyst or pseudocyst; hematoma; infection; inflammation (eg, tuberculosis, histoplasmosis); metastasis (eg, lung or breast related); myelolipoma; neuroblastoma, ganglioneuroblastoma, or ganglioneuroma; pheochromocytoma (eg, multiple endocrine neoplasia)

Bilateral adrenal enlargement

Common causes: Hemorrhage (eg, in infants, trauma, bleeding disorder), histoplasmosis, hyperplasia, metastasis (eg, lung or breast related), neuroblastoma, and tuberculosis

Uncommon causes: Addison disease, adenomas, amyloidosis, carcinomas (eg, multiple, primary), infection, lymphoma, pheochromocytoma (multiple endocrine neoplasia), and Wolman disease (eg, familial xanthomatosis)



Findings

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 Image 5). The presence of phleboliths is suggestive of an adrenal hemangioma.

Degree of Confidence

If the plain-film radiographic findings suggest an adrenal lesion, further evaluation may be performed with CT or MRI (see Image 6). 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.



Findings

Adrenal metastases appear as focal masses (see Image 7) 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 <3 cm may be homogeneous.

Attenuation values of <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 >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.

Degree of Confidence

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%).4 Bilateral involvement may be seen in a number of benign conditions, such as adrenal adenomas, pheochromocytomas, and tuberculosis.

False Positives/Negatives

CT 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.



Findings

Adrenal metastases are usually hypointense on T1-weighted images and relatively hyperintense on T2-weighted images (see Image 8). The exception is metastatic melanoma, which may be bright on T1-weighted images (see Image 9). Occasionally, lesions may remain hyperintense on long–echo-time T2-weighted images, mimicking pheochromocytomas.

Degree of Confidence

Chemical-shift imaging 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). 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 Image 10).

False Positives/Negatives

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.



Findings

Adrenal metastases appear as solid lesions with heterogeneous echogenicity on sonograms (see Image 11). The echogenicity of the lesions is usually less than that of the surrounding fat (hypoechoic).

Degree of Confidence

Ultrasonography of the adrenal glands in adults is technically difficult to perform. When it is performed by an experienced operator, ultrasonography can reveal 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).

False Positives/Negatives

False-positive and false-negative findings may include an 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, and fluid-filled colon.



Findings

Nuclear scintigraphy with iodomethylnorcholesterol (NP-59) may be helpful in differentiating benign from malignant lesions. Benign lesions show uptake, although hemorrhage and inflammatory masses are confounding factors.

Imaging with fluorodeoxyglucose (FDG) is an alternative technique that is performed with PET. Although initial reports indicate the success of FDG PET,5 this examination is expensive.

Degree of Confidence

Nuclear imaging is not widely used.



Findings

Angiography is not useful for determining the diagnosis.



If an adrenal lesion cannot be characterized by using CT and MRI images, percutaneous biopsy may be needed to make the diagnosis. The reported accuracy of biopsy is 90-96%. The minor complications of biopsy include abdominal pain, hematuria, nausea, and small pneumothoraces. The major complications of biopsy (2.8-3.6%) include pneumothoraces that require treatment, hemorrhaging, abscesses, pancreatitis, and seeding along the needle track.

Medical/Legal Pitfalls

  • Failure to detect adrenal metastases may result in inappropriate treatment of the patient; many therapeutic options in the treatment of cancer are risky.

See also the Medscape topic Medical Malpractice and Legal Issues.



Media file 1:  Contrast-enhanced axial CT scan of a normal right adrenal gland. Note the inverted Y-shaped body with 2 limbs that point posteriorly.
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Media type:  CT

Media file 2:  Contrast-enhanced axial CT scan of a normal left adrenal gland. Note the lambda-shaped body and the 2 limbs.
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Media type:  CT

Media file 3:  Contrast-enhanced axial CT scan. A right adrenal adenoma has enlarged the gland, giving it a bulbous appearance.
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Media type:  CT

Media file 4:  Contrast-enhanced axial CT scan. A left adrenal adenoma expands the tips of the gland limbs.
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Media type:  CT

Media file 5:  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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Media type:  X-RAY

Media file 6:  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.
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Media type:  CT

Media file 7:  Contrast-enhanced CT scan depicts heterogeneously enhancing and partially necrotic bilateral adrenal metastases from a lung carcinoma.
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Media type:  CT

Media file 8:  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.
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Media type:  CT

Media file 9:  A metastatic melanoma to the right adrenal gland appears as a hyperintense mass on this T1-weighted MRI.
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Media type:  CT

Media file 10:  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.
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Media type:  CT

Media file 11:  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.
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Media type:  Image



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Adrenal Metastases excerpt

Article Last Updated: Mar 12, 2008