(Radiographics. 2001;21:995-1012.)
© RSNA, 2001
State-of-the-Art Adrenal Imaging1
William W. Mayo-Smith, MD,
Giles W. Boland, MD,
Richard B. Noto, MD and
Michael J. Lee, MD
1 From the Departments of Radiology of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903 (W.W.M-S., R.B.N.); Harvard University, Massachusetts General Hospital, Boston, Mass (G.W.B.); and Royal College of Surgeons, Beaumont Hospital, Dublin, Ireland (M.J.L.). Received October 25, 2000; revision requested November 15 and received December 28; accepted December 29. Address correspondence to W.W.M-S. (e-mail: william_mayo-smith@brown.edu).
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Abstract
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The adrenal gland is a common site of disease, and detection of adrenal masses has increased with the expanding use of cross-sectional imaging. Radiology is playing a critical role in not only the detection of adrenal abnormalities but in characterizing them as benign or malignant. The purpose of the article is to illustrate and describe the appropriate radiologic work-up for diseases affecting the adrenal gland. The work-up of a suspected hyperfunctioning adrenal mass (pheochromocytoma and aldosteronoma) should start with appropriate biochemical screening tests followed by thin-collimation computed tomography (CT). If results of CT are not diagnostic, magnetic resonance (MR) and nuclear medicine imaging examinations should be performed. CT has become the study of choice to differentiate a benign adenoma from a metastasis in the oncology patient. If the attenuation of the adrenal gland is over 10 HU at nonenhanced CT, contrast material–enhanced CT should be performed and washout calculated. Over 50% washout of contrast material on a 10-minute delayed CT scan is diagnostic of an adenoma. For adrenal lesions that are indeterminate at CT in the oncology patient, chemical shift MR imaging or adrenal biopsy should be performed. Certain features can be used by the radiologist to establish a definitive diagnosis for most adrenal masses (including carcinoma, infections, and hemorrhage) based on imaging findings alone.
Index Terms: Adrenal gland, biopsy, 86.1261 • Adrenal gland, CT, 86.1211 • Adrenal gland, MR, 86.121414 • Adrenal gland, neoplasms, 86.317, 86.328, 86.33
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LEARNING OBJECTIVES FOR TEST 6
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After reading this article and taking the test, the reader will be able to:
- Differentiate adrenal adenomas from metastases at nonenhanced CT.
- Describe the enhancement patterns of adenomas and metastases.
- Differentiate adrenal masses based on CT and MR imaging features.
- Describe the appropriate radiologic work-up of a suspected pheochromocytoma.
- Describe three different CT techniques for performing an adrenal biopsy.
I am unaware that any modern authority has ventured to assign to them any special function or influence whatever.
Thomas Addison, 1855
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Introduction
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Remarkable progress has been made in elucidating the structure and function of the adrenal gland since the time of Thomas Addison. More recently, a large amount of radiologic research has been performed on both the detection and characterization of adrenal abnormalities. The purpose of this article is to (a) give an overview of adrenal diseases and their imaging appearances, (b) describe the current concepts of differentiating a benign from a malignant adrenal mass with particular attention to computed tomography (CT) and magnetic resonance (MR) imaging, (c) describe techniques of adrenal biopsy, and (d) present an imaging algorithm for characterizing an adrenal mass.
The adrenal gland is named for its location adjacent to the kidneys: adrenal. The normal gland weighs 5 g and has a characteristic inverted Y, V, or T shape (Figs 1, 2). The adrenal gland is made of cortex that is derived from the mesoderm and medulla derived from the neural crest. The adrenal cortex secretes cortisol, aldosterone, and androgens, and the medulla secretes epinephrine and norepinephrine. The adrenal gland is routinely identified at abdominal CT and MR imaging examinations (1).
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Figure 1. Normal adrenal gland. Coronal reformatted image from helical CT data shows the triangular shape of the adrenal gland (arrows) and its relationship to the kidneys and diaphragms.
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Abnormalities of the adrenal gland include primary neoplasm, metastases, hemorrhage, or enlargement of the adrenal gland from external hormonal stimulation. Adrenal masses can be divided into two physiologic categories based on whether they hypersecrete a hormone. Hyperfunctioning adrenal masses produce a hormone that results in a chemical imbalance and include pheochromocytomas, aldosteronomas, and cortisol or androgen-producing tumors. Nonfunctioning adrenal masses cause enlargement of the adrenal gland but no significant increased hormone production. Adrenal adenomas and metastases are the most common nonfunctioning adrenal masses.
There are numerous imaging modalities including CT, MR imaging, ultrasonography (US), and nuclear medicine imaging that can be used to evaluate the adrenal gland (Fig 3). CT is the primary modality for both detection and characterization of adrenal masses. If an adrenal mass is suspected, CT technique should be tailored to optimize visualization of the adrenal gland. We recommend use of 3-mm helical collimation with the field of view targeted to the adrenal gland. A nonenhanced examination should be performed followed by a contrast material–enhanced study if necessary, as described later in this article. Chemical shift MR imaging is useful as a problem-solving modality when evaluating the adrenal gland, and T2-weighted imaging may be helpful for detecting a pheochromocytoma. Nuclear medicine imaging is primarily a problem-solving modality for lesions not adequately characterized with CT and MR imaging. Iodine-131 meta-iodobenzylguanidine (MIBG) and indium-111 octreotide are used to evaluate for pheochromocytoma, and I-131 6-beta-iodomethyl-19-norcholesterol (NP-59) can be used to detect aldosteronomas and other hyperfunctioning cortical tumors. Positron emission tomography (PET) shows promise in differentiating benign from malignant masses.
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Figure 3. Sagittal US scan demonstrates an enlarged right adrenal gland (arrow) lying posterior to the right lobe of the liver. Although US may reveal adrenal masses, CT is the modality of choice for initial adrenal mass characterization.
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Hyperfunctioning Adrenal Neoplasms
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Hyperfunctioning diseases of the adrenal gland originate from either the adrenal medulla (pheochromocytoma) or the adrenal cortex (Cushing syndrome, Conn syndrome, or hyperandrogenism). The clinical sequelae depend on the type of hormone produced and its target organs.
Hyperfunctioning Adrenal Medullary Neoplasms
Pheochromocytoma is a neoplasm of the adrenal medulla. Although they are typically unilateral and benign, pheochromocytomas may be bilateral and malignant in 10% of patients (3). The tumor secretes catecholamines that can result in hypertension and palpitations. The clinical diagnosis is suspected in a younger patient with hypertension. The first-line tests for evaluating a patient with suspected pheochromocytoma are plasma catecholamine levels and 24-hour urine vanillylmandelic acid and metanephrine levels. These tests have sensitivities ranging from 89% to 100%, although false-negative values may result from exogenous drugs or episodic catecholamine production (2). Although hypertension is one of the most common symptoms of pheochromocytoma, pheochromocytomas are the cause of hypertension in less than 1% of hypertensive patients.
When a pheochromocytoma is suspected on clinical and laboratory grounds, CT is the study of choice to confirm the diagnosis. Typically, an adrenal mass is identified at CT (Fig 4). Three-dimensional imaging and coronal reconstructions may be helpful to demonstrate adjacent vessels, particularly with the recent advent of laparoscopic adrenalectomy (4). If an adrenal mass is identified at CT in a patient with a suspected pheochromocytoma, the treatment is surgical resection. If an adrenal mass is not seen, attention should be directed to the paraspinous region because 10% of pheochromocytomas are extraadrenal. Paraganglioma is the preferred term for such tumors, rather than extraadrenal pheochromocytoma.
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Figure 4a. Pheochromocytoma in a 30-year-old man evaluated with CT. (a) Contrast-enhanced axial CT scan demonstrates an enlarged right adrenal gland with internal calcifications (arrow). (b) Coronal reformatted image from the axial data set demonstrates the relationship of the right adrenal pheochromocytoma (arrow) to the upper pole of the right kidney and the liver.
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Figure 4b. Pheochromocytoma in a 30-year-old man evaluated with CT. (a) Contrast-enhanced axial CT scan demonstrates an enlarged right adrenal gland with internal calcifications (arrow). (b) Coronal reformatted image from the axial data set demonstrates the relationship of the right adrenal pheochromocytoma (arrow) to the upper pole of the right kidney and the liver.
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The MR imaging appearance of a pheochromocytoma has typically been described as T2 hyperintense (Fig 5); however, not all pheochromocytomas have this imaging characteristic (5,6). MR imaging is useful for detecting extraadrenal paragangliomas and recurrences after resection, given their increased signal intensity on T2-weighted images.
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Figure 5a. Pheochromocytoma in a 45-year-old woman evaluated with MR imaging. (a) Axial T2-weighted image with fat saturation demonstrates a bright mass in the right adrenal gland (arrow). (b) Coronal T2-weighted image with fat saturation helps confirm the location of the mass in the adrenal gland (arrow) and that it is separate from the liver and the kidney.
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Figure 5b. Pheochromocytoma in a 45-year-old woman evaluated with MR imaging. (a) Axial T2-weighted image with fat saturation demonstrates a bright mass in the right adrenal gland (arrow). (b) Coronal T2-weighted image with fat saturation helps confirm the location of the mass in the adrenal gland (arrow) and that it is separate from the liver and the kidney.
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For patients in whom a pheochromocytoma is suspected and an adrenal mass is not identified at CT or MR imaging, nuclear medicine imaging can be used. I-131 MIBG and In-111 octreotide are the two radiopharmaceuticals used to evaluate for a pheochromocytoma. I-131 MIBG is a structural analog of norepinephrine, which is stored in neurosecretory granules of the adrenal medulla. Abdominal imaging is performed 24–72 hours after administration of the agent, and whole-body imaging should be performed to detect extraadrenal lesions. If there is a high clinical suspicion of a perivesicular paraganglioma, bladder catheterization may be necessary as the agent is excreted in the urine. When pheochromocytoma is suspected, any focal uptake of I-131 MIBG in the adrenal gland is abnormal (Fig 6). The reported sensitivity of I-131 MIBG for detection of a pheochromocytoma is 80%–90%, with a specificity of 90%–100% (7–9). I-131 MIBG scintigraphy is useful to detect the 10% of pheochromocytomas that are extraadrenal and to document metastatic disease or residual tumor after surgery.
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Figure 6. Pheochromocytoma in a patient evaluated with nuclear medicine imaging. Posterior image obtained 48 hours after intravenous administration of I-131 MIBG demonstrates increased activity in the right adrenal gland (arrow).
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In-111 octreotide, the second agent used to detect pheochromocytomas, is a synthetic octapeptide analog of somatostatin that shows uptake in a variety of tumors that contain somatostatin receptors. A total of 5 mCi (185 MBq) of In-111 octreotide is administered intravenously, and whole-body imaging is performed at 4 and 24 hours after injection. In-111 octreotide has a sensitivity of 75%–90% for detection of pheochro-mocytomas (10). There is a complementary role for In-111 octreotide and I-131 MIBG, since 25% of pheochromocytomas are seen only with I-131 MIBG and another 25% are seen only with In-111 octreotide. The remaining 50% of pheochromocytomas are visualized with both agents.
Hyperfunctioning Adrenal Cortical Neoplasms
The adrenal cortex is composed of three separate zones: the zona fasciculata, the zona glomerulosa, and the zona reticularis. The zona fasciculata produces cortisol, the zona glomerulosa produces aldosterone, and the zona reticularis produces androgens. All three are produced in response to adrenocorticotropic hormone (ACTH) produced by the pituitary gland; however, only cortisol has negative feedback on ACTH production (11). Hyperfunctioning tumors of the adrenal cortex can produce Cushing syndrome from cortisol overproduction, Conn syndrome from production of aldosterone, or hyperandrogenism from overproduction of androgens.
Cushing Syndrome.
Cushing syndrome is defined as increased glucocorticoid levels from any cause and may be divided into ACTH-dependent and ACTH-independent forms. In Cushing disease, which accounts for approximately 80% of Cushing syndrome cases, a pituitary adenoma secretes excess ACTH, which stimulates the adrenal gland.
Appropriate work-up of patients with suspected Cushing disease includes measurement of serum ACTH levels, a dexamethasone suppression test, and pituitary MR imaging. The adrenal glands are often symmetrically enlarged in patients with ACTH-dependent Cushing syndrome; however, up to 30% of patients will have normal-size adrenal glands (12) (Fig 7). In 15%–25% of cases of Cushing syndrome, the cause is a primary adrenal neoplasm, usually a benign adenoma (13). Adrenal adenomas causing Cushing syndrome are usually greater than 2.0 cm in diameter and often readily visualized on CT scans. The role of scintigraphy for the evaluation of patients with Cushing syndrome is limited, particularly with the advances in CT and MR imaging. Adrenal cortical scintigraphy is sensitive for localization of adrenal remnants in patients who have persistent elevated cortisol levels after adrenalectomy (14).
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Figure 7. Adrenal hyperplasia in a woman with Cushing disease. Contrast-enhanced CT scan demonstrates thickening of the limbs of the left adrenal gland but a normal right adrenal gland. The prominent intraabdominal fat and hepatic steatosis seen here are typical findings in this disease.
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Hyperaldosteronism.
Primary aldosteronism is characterized clinically by hypertension and hypokalemia. The cause is an adrenal adenoma in about 80% of patients and adrenal gland hyperplasia in 20% (15). Adrenal carcinoma is an extremely rare cause of primary aldosteronism.
After the diagnosis of hyperaldosteronism has been established through clinical and laboratory tests, a dedicated CT study of the adrenal gland performed with thin (3-mm) collimation is usually the first-line imaging examination (Fig 8). Adrenal adenomas are often small and difficult to detect, since over 20% are less than 1 cm in diameter (16).
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Figure 8. Left adrenal aldosteronoma in a 43-year-old woman. Contrast-enhanced helical CT scan shows a 5-mm well-circumscribed left adrenal mass (arrow), which proved at surgery to be an aldosterone-secreting adenoma.
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Adrenal cortical scintigraphy is rarely needed, given the improvements in CT technology, but it can be useful to determine whether the abnormality is unilateral or bilateral (17). NP-59 is a cholesterol analog that binds to the low-density lipoprotein receptors of the adrenal cortex and is the primary radiopharmaceutical used for adrenal cortical scintigraphy. It is available only through the University of Michigan (Ann Arbor) radiopharmacy and is still considered investigational by the U.S. Food and Drug Administration despite many years of safe use. A normal result of NP-59 imaging is visualization of both adrenal glands on day 5 after the injection or thereafter. Bilateral early adrenal visualization before day 5 suggests adrenal gland hyperplasia. Unilateral early adrenal visualization before day 5 is indicative of an adenoma (Fig 9). If these examinations are not diagnostic, adrenal venous sampling should be performed (Fig 10) to determine whether aldosterone secretion lateralizes to one side (suggestive of an adenoma) or is symmetric (suggestive of bilateral hyperplasia).
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Figure 9. Functioning right aldosteronoma in a patient with hyperaldosteronism. Posterior image obtained 5 days after intravenous administration of NP-59 shows increased activity in the right adrenal gland (arrow), a finding consistent with a functioning adenoma. Normal activity is seen in the bowel, bladder, and liver.
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Figure 10. Adrenal venous sampling in a 51-year-old man with biochemically proved aldosteronoma. Angiogram shows the catheter, which was placed in the right adrenal vein (arrow) via the inferior vena cava. The adrenal veins were opacified by using gentle hand injection of contrast material, thus confirming correct placement for adrenal venous sampling. Cortrosyn-stimulated aldosterone levels were four times higher on the left than the right. The patient’s symptoms resolved after left adrenalectomy.
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Characterization of an Adrenal Mass: Is It Benign or Malignant?
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Adrenal masses are common, estimated to occur in 9% of the population (18,19). However, the adrenal gland is also a common site of metastasis, particularly from lung carcinoma. With the proliferation of cross-sectional imaging, detection of an incidental adrenal mass has become a common problem. In patients with no known primary cancer, an adrenal mass is almost always a benign adenoma. However, in a patient with a known neoplasm, particularly lung cancer, the finding of an adrenal mass is problematic, since metastasis to the adrenal gland indicates advanced disease that is not amenable to surgical resection and potential cure. Thus, differentiating an adrenal mass as benign or malignant is critical in the oncology patient, since it will greatly affect patient treatment and prognosis. One study has shown that 27% of oncology patients have microscopic adrenal metastases (20). When the imaging task is differentiating an adenoma from metastasis, the high specificity of the modality used is critical (21). Herein, we discuss the use of nonenhanced CT, contrast-enhanced CT, MR imaging, and PET to characterize adrenal masses in the oncology patient.
CT in Differentiating Benign from Malignant Adrenal Masses
At CT, certain imaging findings are helpful in differentiating benign from malignant lesions. Larger lesions have a greater likelihood of being malignant. In particular, lesions greater than 4 cm in diameter tend to be either metastasis or a primary adrenal carcinoma. Change in lesion size is a useful indicator of malignancy because adenomas are slow growing and tend not to change size. The shape of the adrenal gland can also be helpful in predicting malignancy. Adenomas tend to have smooth margins and a homogeneous density, whereas metastases can be heterogeneous and have an irregular shape. However, although these findings are helpful in differentiating a benign from a malignant adrenal mass, they are not specific.
Currently, there are two main CT criteria (histologic and physiologic) used to differentiate benign adenomas from malignant adrenal masses. Intracellular lipid content of the adrenal mass represents the anatomic difference between adenomas and metastases, and differences in vascular enhancement patterns represent the physiologic difference. Adenomas have abundant intracytoplasmic fat in the adrenal cortex and thus have low attenuation at CT (Fig 11). Conversely, metastases have little intracytoplasmic fat and thus do not have low attenuation at nonenhanced CT (Fig 12). Korobkin et al (22) performed a study quantifying adrenal fat and showed a high correlation between adrenal fat content and low attenuation at CT and signal loss at chemical shift MR imaging.
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Figure 11. Typical nonenhanced CT findings of an adrenal adenoma in a 64-year-old man with no known malignancy. The left adrenal adenoma (arrow) has smooth margins, is well defined, and has a attenuation of 5 HU, all findings characteristic of an adenoma.
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Figure 12. Typical nonenhanced helical CT findings of metastasis in a 76-year-old man with lung carcinoma. On the CT scan, the right adrenal gland (arrow) is enlarged, has irregular contours, and has an attenuation of 36 HU, all findings characteristic of metastasis. Adrenal masses with attenuation values over 10 HU at nonenhanced CT require further evaluation with either CT contrast material washout, chemical shift MR imaging, or adrenal biopsy.
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Nonenhanced CT.
The first study to use nonenhanced CT to characterize adrenal masses as benign and malignant was performed by Lee et al (23). In this study, the mean attenuation of adenomas was -2.2 HU and metastasis was 29 HU. At a threshold of 0 HU, the sensitivity of nonenhanced CT for characterizing adrenal adenomas was 47%, with a specificity of 100%. At a threshold of 10 HU, the sensitivity changed to 79%, with a specificity of 96%. Subsequent studies have corroborated these findings (24,25). Thresholds to differentiate benign from malignant lesions have ranged from 0 to 18 HU. Boland et al (25) performed a meta-analysis of 10 studies to determine an optimal threshold for differentiating benign from malignant lesions. From this study, a threshold of 10 HU had a 71% sensitivity and 98% specificity for characterizing adrenal masses. This specificity approached 100% when other features such as adrenal size, shape, and change in lesion size were considered. When measuring the attenuation of the adrenal gland, it is important to use as large a region of interest as possible to fill the gland but to not include adjacent periadrenal fat.
Contrast-enhanced CT.
Although the finding of lower attenuation is useful to characterize an adenoma, it is estimated that up to 30% of adenomas do not contain sufficient lipid to have low attenuation at CT (26,27). The problem is that adenomas represent a heterogeneous population: Approximately 70% of them have intracellular lipid but 30% do not. Thus, although nonenhanced CT can be used to identify 70% of adenomas, it does not allow the 30% that do not contain lipid to be reliably differentiated from metastases. In addition, although nonenhanced CT is useful to differentiate adenomas from metastases, the majority of CT examinations in oncology patients use intravenous contrast material.
The second imaging parameter to differentiate adenomas from metastases relies on physiologic differences in perfusion. Adenomas enhance rapidly with intravenous contrast media (either iodinated agents used at CT or gadolinium chelates used at MR imaging) and wash out the agent rapidly (Fig 13). Metastases also enhance vigorously with contrast material, but the washout of the agent is more prolonged than with adenomas (Fig 14). This difference in washout of contrast media has been exploited to further differentiate benign from malignant adrenal lesions.
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Figure 13a. Typical attenuation and washout of intravenous contrast material in a left adrenal adenoma in a 54-year-old woman with a history of breast carcinoma. (a) Nonenhanced CT scan shows a left adrenal adenoma (arrow), which has an attenuation of 4 HU. (b) On the dynamic enhanced phase image, the adrenal gland (arrow) enhances vigorously to 54 HU. (c) On the 10-minute delayed image, the attenuation of the left adrenal gland (arrow) is 23 HU (lower than that of the normal right adrenal gland, kidneys, and liver). There is greater than 50% washout between the dynamic phase of contrast enhancement and the 10-minute delay, which is diagnostic of an adenoma and confirms the finding on the nonenhanced CT scan. Quantitative region-of-interest measurements (in Hounsfield units) are important because degree of enhancement is difficult to quantify with the human eye.
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Figure 13b. Typical attenuation and washout of intravenous contrast material in a left adrenal adenoma in a 54-year-old woman with a history of breast carcinoma. (a) Nonenhanced CT scan shows a left adrenal adenoma (arrow), which has an attenuation of 4 HU. (b) On the dynamic enhanced phase image, the adrenal gland (arrow) enhances vigorously to 54 HU. (c) On the 10-minute delayed image, the attenuation of the left adrenal gland (arrow) is 23 HU (lower than that of the normal right adrenal gland, kidneys, and liver). There is greater than 50% washout between the dynamic phase of contrast enhancement and the 10-minute delay, which is diagnostic of an adenoma and confirms the finding on the nonenhanced CT scan. Quantitative region-of-interest measurements (in Hounsfield units) are important because degree of enhancement is difficult to quantify with the human eye.
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Figure 13c. Typical attenuation and washout of intravenous contrast material in a left adrenal adenoma in a 54-year-old woman with a history of breast carcinoma. (a) Nonenhanced CT scan shows a left adrenal adenoma (arrow), which has an attenuation of 4 HU. (b) On the dynamic enhanced phase image, the adrenal gland (arrow) enhances vigorously to 54 HU. (c) On the 10-minute delayed image, the attenuation of the left adrenal gland (arrow) is 23 HU (lower than that of the normal right adrenal gland, kidneys, and liver). There is greater than 50% washout between the dynamic phase of contrast enhancement and the 10-minute delay, which is diagnostic of an adenoma and confirms the finding on the nonenhanced CT scan. Quantitative region-of-interest measurements (in Hounsfield units) are important because degree of enhancement is difficult to quantify with the human eye.
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Figure 14a. Typical attenuation and washout characteristics of a left adrenal metastasis in a 65-year-old man with lung carcinoma. (a) Nonenhanced CT scan demonstrates an enlarged left adrenal gland (arrow) with irregular margins and attenuation of 40 HU. (b) Dynamic enhanced CT scan of the adrenal gland (arrow) obtained 60 seconds after intravenous administration of contrast material demonstrates an increase in attenuation to 53 HU. (c) Ten-minute delayed image of the left adrenal gland (arrow) demonstrates persistent enhancement of the adrenal gland (56 HU). There is no significant washout of contrast media at 10 minutes, a finding consistent with an adrenal metastasis.
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Figure 14b. Typical attenuation and washout characteristics of a left adrenal metastasis in a 65-year-old man with lung carcinoma. (a) Nonenhanced CT scan demonstrates an enlarged left adrenal gland (arrow) with irregular margins and attenuation of 40 HU. (b) Dynamic enhanced CT scan of the adrenal gland (arrow) obtained 60 seconds after intravenous administration of contrast material demonstrates an increase in attenuation to 53 HU. (c) Ten-minute delayed image of the left adrenal gland (arrow) demonstrates persistent enhancement of the adrenal gland (56 HU). There is no significant washout of contrast media at 10 minutes, a finding consistent with an adrenal metastasis.
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Figure 14c. Typical attenuation and washout characteristics of a left adrenal metastasis in a 65-year-old man with lung carcinoma. (a) Nonenhanced CT scan demonstrates an enlarged left adrenal gland (arrow) with irregular margins and attenuation of 40 HU. (b) Dynamic enhanced CT scan of the adrenal gland (arrow) obtained 60 seconds after intravenous administration of contrast material demonstrates an increase in attenuation to 53 HU. (c) Ten-minute delayed image of the left adrenal gland (arrow) demonstrates persistent enhancement of the adrenal gland (56 HU). There is no significant washout of contrast media at 10 minutes, a finding consistent with an adrenal metastasis.
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Dynamic contrast-enhanced CT is usually performed in the portal venous phase of enhancement (60–80 seconds after starting the injection of contrast material). Although this timing is useful for detecting hepatic lesions, it is suboptimal for differentiating benign from malignant adrenal lesions because both adenomas and metastases enhance early. Thus, the attenuation values of adenomas and metastases significantly overlap, and dynamic CT is not sensitive for differentiating between the two. However, if delayed images are obtained after the administration of contrast media, washout of the agent can be determined. Several studies have investigated the use of delayed CT to characterize adrenal lesions (27–32).
Two features can be measured at delayed CT: the attenuation value of the adrenal gland and the washout of contrast media. A Hounsfield unit of less than approximately 30 at 10 minutes after injection has been shown to be diagnostic of a lipid-rich adenoma; however, most adenomas have an attenuation value higher than 30, and thus it is a specific but not a sensitive test (30). A more useful parameter is the percentage of washout of contrast material in which the attenuation of the adrenal gland at delayed CT is compared with its attenuation at dynamic CT. Loss of 50% of the attenuation value of the adrenal mass at delayed CT is specific for an adenoma; less than 50% washout is indicative of either a metastasis or an atypical adenoma. Percentage of washout is typically calculated by the following formula: (1 - delayed enhanced HU value/initial enhanced HU value) x 100. Quantitative region-of-interest measurements (in Hounsfield units) are important because degree of enhancement is difficult to quantify with the human eye. Recently, Caoili et al (26) studied a group of adenomas that had elevated attenuation values at nonenhanced CT and thus could not be differentiated from metastasis based on nonenhanced CT findings. They found that this subset of adenomas demonstrated washout features typical of all adenomas. This study (corroborated by the work of Pena et al [27]) is exciting, since it demonstrates that washout of contrast media may be more specific than low attenuation at CT.
It is important to stress that if a lesion in an oncology patient cannot be definitively called an adenoma after CT examination, the patient should undergo further evaluation with MR imaging or an adrenal biopsy to confirm a benign or malignant adrenal lesion. Thus, although an attenuation value of less than 10 HU at nonenhanced CT is diagnostic of an adenoma, an attenuation value of greater than 10 HU is not diagnostic of a metastasis. A lesion greater than 10 HU at nonenhanced CT may be either an adenoma or metastasis.
MR Imaging in Differentiating Benign from Malignant Masses
Various MR imaging parameters can be used to characterize adrenal masses, including T1 and T2 characteristics, calculated T2 values, enhancement patterns, and chemical shift characteristics. In general, metastases and carcinomas contain larger amounts of fluid than adenomas and thus appear bright on T2-weighted images. However, there is significant overlap in T1 and T2 signal intensity between adenomas and metastases, and thus signal intensity is not useful to reliably differentiate between them. Enhancement patterns have also been investigated as a means of differentiating benign adrenal adenomas from metastases, and, similar to their appearance at CT, adenomas vigorously enhance and exhibit early washout of contrast material compared with metastases on MR images (33,34). Given the increased cost of MR imaging, CT is probably more cost effective to assess enhancement patterns. As stated earlier, intracellular lipid is high in most adrenal adenomas and low in metastases. Chemical shift imaging is an MR imaging technique used to detect lipid within an organ and is the most sensitive method for differentiating adenomas from metastases (35). In studies that have compared T1, T2, enhancement patterns, and chemical shift imaging for differentiating adenomas from metastases, the latter has demonstrated a high sensitivity and specificity (19,36–40).
Chemical shift imaging relies on the different resonance frequency rates of protons in fat and water molecules. The chemical environment of a proton in water is different than a proton in lipid because of the proximity of hydrogen and oxygen atoms and their electrons. Electrons surrounding the proton shield it from the applied external field. Thus, the effective magnetic field experienced by a shielded proton is less than that experienced by an unshielded proton. Fat protons are more shielded than water protons, experience less external magnetic field, and thus resonate at a slower frequency. It is this difference in resonance rate of protons in fat and water that is exploited in chemical shift imaging. The net effect of this physical phenomenon is that there is cancellation of signal between lipid and water protons within a voxel. Thus, tissues containing lipid and water have signal loss (ie, appear darker) on out-of-phase images. Two studies have shown that the amount of signal drop-off within a voxel depends on the amount of lipid in the tissue (22,41).
To obtain chemical shift images, two breath-hold T1-weighted acquisitions are performed. The first uses a short echo time (2.2 msec at 1.5 T) when the fat and water protons are out of phase, and a second in-phase acquisition uses a longer echo time (4.4 msec). The echo time chosen to obtain in-phase and out-of-phase images varies as a function of field strength. On out-of-phase images, there is signal drop-off in adenomas due to the intra-voxel signal cancellation of the lipid and water protons. Thus, on out-of-phase images, the adenoma appears darker than on in-phase images (Fig 15). In adrenal masses that do not contain lipid (eg, metastases), there is no significant signal loss on out-of-phase images, and thus the signal intensity of the adrenal gland is the same on in-phase and out-of-phase images (Fig 16). With the chemical shift technique, the sensitivity and specificity for differentiating adenomas from metastases ranges from 81% to 100% and 94% to 100%, respectively (42–47).
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Figure 15a. Indeterminate right adrenal mass found at CT in a 45-year-old woman with breast cancer. (a) T1-weighted in-phase MR image demonstrates a right adrenal mass (arrow). (b) T1-weighted out-of-phase MR image shows signal drop-off in the adrenal gland (arrow), which is diagnostic of an adenoma.
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Figure 15b. Indeterminate right adrenal mass found at CT in a 45-year-old woman with breast cancer. (a) T1-weighted in-phase MR image demonstrates a right adrenal mass (arrow). (b) T1-weighted out-of-phase MR image shows signal drop-off in the adrenal gland (arrow), which is diagnostic of an adenoma.
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Figure 16a. Left adrenal metastases in a 74-year-old man with lung cancer. (a) T1-weighted in-phase MR image demonstrates a left adrenal mass (arrow). (b) T1-weighted out-of-phase MR image shows no significant signal loss in the adrenal gland compared with that of the spleen. The mass is either a metastasis or atypical adenoma, and biopsy was recommended.
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Figure 16b. Left adrenal metastases in a 74-year-old man with lung cancer. (a) T1-weighted in-phase MR image demonstrates a left adrenal mass (arrow). (b) T1-weighted out-of-phase MR image shows no significant signal loss in the adrenal gland compared with that of the spleen. The mass is either a metastasis or atypical adenoma, and biopsy was recommended.
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When in-phase and out-of-phase images are compared, an internal standard is useful to visually quantify signal drop-off. In general, the liver is a less reliable internal standard because intrinsic liver disease (eg, steatosis, hemochromatosis) can cause variable hepatic signal intensity on in-phase and out-of-phase images (Fig 17). We find it useful to compare signal intensity of the adrenal gland with that of the spleen as the internal standard (42). It is also helpful for the technologists to use one prescan value for both in-phase and out-of-phase acquisitions, since variable prescan values can vary the signal intensity of the adrenal gland. Finally, it is important for the technologist to use the same window and level values on both in-phase and out-of-phase images.
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Figure 17a. Right adrenal adenoma in a patient with hepatic steatosis. (a) T1-weighted in-phase MR image demonstrates a right adrenal mass (arrow), which is isointense relative to the liver (L) and slightly higher in signal intensity than the spleen (S). (b) T1-weighted out-of-phase MR image shows signal drop-off in both the liver (due to steatosis) and the mass. The adrenal mass has clearly lost signal compared with the spleen on out-of-phase images, a finding that is diagnostic of an adenoma.
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Figure 17b. Right adrenal adenoma in a patient with hepatic steatosis. (a) T1-weighted in-phase MR image demonstrates a right adrenal mass (arrow), which is isointense relative to the liver (L) and slightly higher in signal intensity than the spleen (S). (b) T1-weighted out-of-phase MR image shows signal drop-off in both the liver (due to steatosis) and the mass. The adrenal mass has clearly lost signal compared with the spleen on out-of-phase images, a finding that is diagnostic of an adenoma.
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Collision tumors are rare entities that result when a metastasis occurs in an adrenal gland that has a pre-existing adrenal adenoma (48). In this circumstance, signal intensity for each tissue type matches that expected for each pulse sequence. Thus, the adenomatous portion of the adrenal gland loses signal on out-of-phase images and a metastasis does not.
In summary, chemical shift MR imaging is the most sensitive technique for differentiating adenomas from metastases to the adrenal gland. When results of CT examinations are equivocal, MR imaging is the next imaging study of choice for characterizing adrenal lesions (49). One study has shown that MR imaging is more cost-effective than performing biopsies in all equivocal adrenal lesions (50). However, given the most recent CT literature, the role of MR imaging may be more limited since CT is more readily available and less expensive and as CT algorithms become refined.
PET in Differentiating Benign from Malignant Masses
More recently, PET has been suggested as a useful tool in the evaluation of the nonhyperfunctioning adrenal mass. Although still preliminary, the results of multiple recent studies suggest that PET performed with fluorine-18 fluorodeoxyglucose (FDG) is highly accurate in differentiating benign from malignant lesions. In general, malignant masses in the adrenal gland (and elsewhere) show increased uptake of FDG due to increased glucose utilization, but benign noninflammatory lesions show no evidence of increased FDG uptake (Figs 18, 19). Three recent studies demonstrated that FDG PET had 100% sensitivity and 80%–100% specificity for differentiating malignant from benign adrenal masses (51–53). If these results are corroborated, FDG PET could become part of the routine evaluation of the patient with a nonhyperfunctioning adrenal mass, especially since the study allows simultaneous whole-body imaging. PET may also be useful for localizing pheochromocytomas (54).
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Figure 18a. Right adrenal adenoma. (a) Contrast-enhanced CT scan demonstrates a smooth-margin, low-attenuation right adrenal mass (arrow). (b) FDG PET scan shows normal activity in the kidneys (arrows) but no increasing activity in the right adrenal gland.
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Figure 18b. Right adrenal adenoma. (a) Contrast-enhanced CT scan demonstrates a smooth-margin, low-attenuation right adrenal mass (arrow). (b) FDG PET scan shows normal activity in the kidneys (arrows) but no increasing activity in the right adrenal gland.
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Figure 19a. Right adrenal metastasis in a patient with lung carcinoma. (a) Nonenhanced CT scan demonstrates a right adrenal mass (arrow). (b) FDG-PET SPECT scan obtained at the same level shows increased activity in the right adrenal gland (arrow), a finding diagnostic of a metastasis.
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Figure 19b. Right adrenal metastasis in a patient with lung carcinoma. (a) Nonenhanced CT scan demonstrates a right adrenal mass (arrow). (b) FDG-PET SPECT scan obtained at the same level shows increased activity in the right adrenal gland (arrow), a finding diagnostic of a metastasis.
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Adrenal Biopsy
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Adrenal biopsy is the standard for diagnosis of adrenal pathologic conditions. When adrenal lesions cannot be accurately characterized with CT, MR imaging, or PET, adrenal biopsy should be performed to establish a definitive diagnosis.
Adrenal biopsies are safe procedures with a high degree of accuracy (83%–96%) and a low complication rate (3%) (55,56). CT is the modality of choice for guiding adrenal biopsies. In general, coaxial technique with a cutting core needle is useful, since many passes can be made through a single outer needle. Because of the proximity of the adrenal gland to the diaphragm, placing the patient in the prone position may cause increased ventilation of the lower lobes and inferior migration of the diaphragm. For this reason, we prefer to perform adrenal biopsies with the patient in the decubitus position with the ipsilateral side down. This position reduces ventilation of the dependent lung, which causes superior movement of the diaphragm, thus lessening the chance for a pneumothorax (Fig 20). In some patients, angling the gantry of the CT scanner allows one to choose a path that avoids the lung parenchyma (Fig 21). In rare cases, a decubitus position or an angled gantry may not allow safe access to the right adrenal gland. For these patients, a transhepatic approach may be used, guided either by US or CT (Fig 22).
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Figure 20. Decubitus position for a right adrenal biopsy in a 76-year-old man with metastatic lung carcinoma. Use of the decubitus position causes decreased ventilation of the dependent lung, allowing a larger window for access to the adrenal gland. As seen on the CT scan, the nondependent lung has markedly increased aeration (large straight arrow) compared with the dependent lung. In addition, use of a coaxial core biopsy system allows access to the adrenal gland (small arrow) while avoiding the adjacent inferior vena cava (curved arrow).
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Figure 21a. Use of an angled gantry for adrenal biopsy in a 64-year-old patient with metastatic lung carcinoma. (a) Nonenhanced diagnostic CT scan obtained with the patient in the supine position demonstrates bilateral adrenal masses. (b) CT scan acquired with the patient in the prone position shows increased aeration of the lung bases (arrows), which makes access to the adrenal glands difficult. (c) With the CT gantry angled 20° and the patient in the prone position, the radiologist has a safer route of access to the left adrenal gland without transgressing a significant amount of pulmonary parenchyma (arrow).
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Figure 21b. Use of an angled gantry for adrenal biopsy in a 64-year-old patient with metastatic lung carcinoma. (a) Nonenhanced diagnostic CT scan obtained with the patient in the supine position demonstrates bilateral adrenal masses. (b) CT scan acquired with the patient in the prone position shows increased aeration of the lung bases (arrows), which makes access to the adrenal glands difficult. (c) With the CT gantry angled 20° and the patient in the prone position, the radiologist has a safer route of access to the left adrenal gland without transgressing a significant amount of pulmonary parenchyma (arrow).
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Figure 21c. Use of an angled gantry for adrenal biopsy in a 64-year-old patient with metastatic lung carcinoma. (a) Nonenhanced diagnostic CT scan obtained with the patient in the supine position demonstrates bilateral adrenal masses. (b) CT scan acquired with the patient in the prone position shows increased aeration of the lung bases (arrows), which makes access to the adrenal glands difficult. (c) With the CT gantry angled 20° and the patient in the prone position, the radiologist has a safer route of access to the left adrenal gland without transgressing a significant amount of pulmonary parenchyma (arrow).
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Adrenal biopsy is a safe and reliable technique for providing definitive diagnosis in patients in whom accurate staging is mandatory. A summary algorithm of the work-up of an enlarged adrenal gland in the oncologic patient is presented in Figure 23.
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Miscellaneous Diseases Affecting the Adrenal Gland
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Addison disease is the sequela of adrenal gland hypofunction in which over 90% of the gland is destroyed. Tuberculosis is the most common cause of Addison disease worldwide, but an auto-immune abnormality is the most common cause in developed countries. In Addison disease from an autoimmune abnormality, the adrenal gland is small at CT (57). A second cause of Addison disease is replacement of the adrenal gland by either neoplasm, hemorrhage, or infection. In these instances, the adrenal gland is often enlarged (58). The adrenal masses caused by granulomatous disease or hemorrhage may involute and subsequently calcify (Fig 24). Addison disease is a clinical diagnosis based on clinical and biochemical findings, not one that is reliably established by imaging methods.
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Figure 24. Addison disease in a 51-year-old man. Contrast-enhanced CT scan shows both adrenal glands, which appear small and with dense calcification. The cause of the calcification was not known but may have been due to remote hemorrhage or tuberculosis.
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Adrenal carcinoma is a rare adrenal neoplasm arising from the cortex and is bilateral in 10% of patients (59). Fifty percent of adrenal carcinomas are functioning neoplasms with secondary sequelae from the hormone produced, such as Cushing, virilization, feminization, or Conn syndromes. Adrenal carcinomas are usually large at presentation, ranging from 4 to 10 cm, and heterogeneous (Fig 25). They commonly have central necrosis, and calcification has been described in 30% of cases.
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Figure 25. Adrenal carcinoma in a patient who presented with left flank pain. Contrast-enhanced CT scan demonstrates an 11-cm necrotic mass in the left adrenal gland, which causes inferior displacement of the left kidney. There is stranding of the adjacent retroperitoneal fat.
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Myelolipomas are rare benign tumors estimated to occur in 0.2%–0.4% of the population based on autopsy series (60,61). These tumors are composed of myeloid, erythroid, and fatty elements and occasionally calcify. The imaging appearance of myelolipomas is based on the fat content of the lesion; thus, they appear echogenic at US, low attenuation at CT, and hyperintense on T1-weighted in-phase MR images. The presence of pure fat within an adrenal lesion at CT is diagnostic of a myelolipoma, and no further work-up is required (Fig 26).
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Figure 26. Bilateral myelolipomas in a 79-year-old man. Nonenhanced CT scan shows an exophytic mass of fat attenuation (straight arrow) in the right adrenal gland. The left adrenal gland has a soft-tissue mass containing calcifications and a central area of fat attenuation (curved arrow). These benign adrenal lesions were stable over 4 years.
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Adrenal hemorrhage results from trauma, systemic anticoagulation therapy, sepsis, or stress such as surgery (62). Trauma accounts for 80% of cases of adrenal hemorrhage. Bilateral hemorrhage occurs in 20% of cases, and adrenal insufficiency secondary to hemorrhage is extremely unusual. At CT, acute adrenal hemorrhage has increased attenuation (Fig 27). Adrenal hemorrhage also has a typical appearance at MR imaging, with T1 hyperintensity secondary to methemoglobin and a T2 dark rim along the peripheryfor chronic adrenal hemorrhage due to hemosiderin-laden macrophages. The MR imaging appearance depends on the age of the hemorrhage, which may be divided into acute and chronic based on the imaging findings (63).
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Abstract
LEARNING OBJECTIVES FOR TEST...
