Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

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hyperfunction, consisting of hypercortisolism, hyperaldosteronism, and medullary hyperfunction (9); in patients with bilateral incidental tumors, abnormal adrenal function was detected in 29%, consisting of hypercortisolism, hyperaldosteronism, adrenal insufficiency, and congenital adrenal hyperplasia. A not uncommon incidental functioning adrenal tumor is a pheochromocytoma. Some of these tumors function subclinically and appropriate endocrine testing is useful. Most initially discovered metastases are unilateral and do not produce adrenal insufficiency; bilateral involvement suggests adrenal hemorrhage, especially in a setting of a coagulopathy, and possible lymphoma.

An incidental adrenal tumor discovered in a workup for another condition, without a known primary cancer, has only about a 1% rate of being malignant; most of these malignancies will be larger tumors. As a result, some investigators suggest that smaller tumors, for instance those <3cm or so in diameter, can be followed with imaging; an exception is with those exhibiting subtle hormone production or in a patient with hypertension or diabetes, and these should be resected. On the other hand, risk of malignancy is increased in a setting of a known primary cancer in another organ, but here also the prevalence of malignancy varies with tumor size.

Both CT and MRI are helpful in defining adrenal tumors (differentiation of benign and malignant tumors is discussed in more detail in the next section). A biopsy is helpful, especially for larger tumors. Similar to other sites, a positive biopsy is diagnostic but a negative one needs to be placed in the proper perspective. One biopsy caution: a pheochromocytoma should be excluded before a biopsy is performed.Also,biopsy rather than cytology is necessary; cytology often cannot differentiate a benign from a malignant tumor.

2-[18F]-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) appears to have a role in distinguishing benign from malignant adrenal tumors. Benign tumors show no FDG uptake; on the other hand, malignant adrenal tumors have increased FDG uptake, indicative of high glucose metabolism. Whole-body PET also identifies primary extraadrenal tumor sites, thus providing staging.

Occasionally prenatal US identifies a suprarenal tumor, at times even containing small cysts; eventually these tumors tend to disappear and thus a conservative approach with US followup appears reasonable in otherwise healthy neonates.Presumably some of these findings represent congenital adrenal hyperplasia.

Adenoma Versus Nonadenoma

A major problem in clinical practice is to differentiate an adrenal adenoma from other tumors, usually a metastasis. Although most adenomas are small, smooth in outline, and homogeneous, while metastases are larger, have an irregular outline, and are heterogeneous, sufficient overlap exists in these characteristics that they are of limited use in any one patient. With a nonfunctioning adenoma or carcinoma the contralateral gland is not atrophic.

Two specific imaging characteristics are useful in differentiating adrenal adenomas from nonadenomas. Initially, emphasis was placed on detecting an adenoma’s increased lipid content. While still a useful concept, some overlap exists, and this technique has been supplanted by another almost unique adenoma property—a more rapid contrast washout compared to nonadenomas. Computed tomography and MR differentiation of adenomas from nonadenomas rely primarily on these findings.

Using a variety of techniques, including chemical shift imaging and dynamic contrast enhancement, MRI could differentiate between benign and malignant adrenal tumors with a 89% sensitivity and 99% specificity (10). Sensitivity and specificity can be increased by combining results from several MR sequences, such as dynamic contrast enhanced sequences and chemical shift imaging.

Lipid Content

Most adrenocortical adenomas contain considerable lipid (lipid rich), but the amount of fat is still considerably less than in a myelolipoma.An inverse linear relationship exists between the percentage of lipid-rich cortical cells in adrenal adenomas and their unenhanced CT attenuation; a similar inverse linear relationship exists with MR chemical shift changes. It should be kept in mind, however, that about 20% of adenomas contain little or no lipid (lipid poor).

The reverse is also true—an occasional adrenal cortical carcinoma and metastasis contains sufficient fat to be detectable by CT and MRI, but these tend to be large and irregular in outline at initial presentation.

In general,unenhanced CT attenuation values of a nonfunctioning adrenal tumor are more useful in differentiating between an adenoma and a nonadenoma than size or CT homogeneity. Due to their fat content, most adenomas have lower attenuation values than malignant tumors, with the published sensitivities in making this differential varying depending on the assumed threshold HU; thus in 60 patients with single adrenal nodules, a CT threshold of 19HU on unenhanced and 41HU on late postcontrast scans achieved a sensitivity of 93% and specificity of 100% in differentiating benign from malignant tumors (11). As a rough guide, adrenal tumors having a CT density of 0 Houndsfield units (HU) or less can be assumed to be benign and those having a density >20HU can be assumed to be malignant. It is those with intermediate densities that present a diagnostic dilemma.

Magnetic resonance signal intensities of both benign and malignant tumors vary, presumably due to their inhomogeneous histologic appearance. Nonfunctioning adenomas range from hypoto mostly isointense to liver parenchyma on both T1and T2-weighted sequences and show mild-to-moderate postcontrast enhancement. Most adenomas contain insufficient fat to produce a major change on fat-suppressed MR images, and a major decrease in intensity should suggest a myelolipoma. Nevertheless, chemical shift MRI is useful in differentiating lipid-rich adenomas from nonadenomas, achieving sensitivities and specificities similar to those of CT enhancement washout techniques (see next section). This technique is insensitive in characterizing lipid-poor adenomas.

An internal standard is needed to meaningfully evaluate adrenal MR signal intensity. Although liver signal intensity is readily measured, it varies considerably depending on liver fat content. The adrenal-to-spleen ratio appears more useful. Metastases have an adrenal-to- spleen ratio >0.8, while most adenomas have a lower ratio. An overlap exists, however, and the ratio is of limited value in establishing the benign or malignant nature of an adrenal

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lesion. Some investigators prefer muscle as their standard.

Most adenomas are isointense to muscle or spleen on in-phase spoiled gradient echo (SGE) images and appear hypointense on opposedphase images. With a chemical shift technique, most adenomas have a loss of signal intensity on opposed-phase images while most benign nonadenomas, pheochromocytomas, and metastases do not. Loss in signal intensity in bone marrow in an adjacent vertebral body is useful confirmation of this technique. With a tendency of adrenal adenomas to contain fat and the high sensitivity of opposed-phase imaging for detecting fat, in a setting of a known malignancy and an adrenal tumor, MRI can be sufficient to differentiate these entities and save these patients a biopsy.

Another option is to use a signal intensity (SI) index, defined as:

(SI in-phase - SI opposed-phase)/SI in-phase

This index differentiates adenomas, metastases and pheochromocytomas (12). One study achieved 100% accuracy in distinguishing adenomas from metastases if the SI index cutoff value was 11.2–16.5% (13); this index was more reliable in differentiating adenomas from metastases than an adrenal-to-liver, spleen, or muscle ratio for signal change on opposedphase MR imaging..

Which modality is more accurate in differentiating benign from malignant tumors—unen- hanced CT attenuation or chemical shift MRI? For most tumors both yield similar results; most adenomas measuring >10H on unenhanced CT can be characterized with chemical shift MRI (14). Nevertheless, diagnostic uncertainty still exists with a minority of these tumors.

Contrast Washout

Very useful in differentiating adrenal adenomas from nonadenomas is washout of contrast enhancement. Enhancement washout is equal to initial enhanced attenuation minus delayed enhanced attenuation. More rapid washout is a characteristic finding in a majority of adenomas (compared to nonadenomas). Mean CT attenuation measured at specific time delays postcontrast (10 to 30 minutes), is lower for adenomas than for nonadenomas. In one study, the per-

tumor of undetermined nature (19); 4 months later the patient presented with a metastatic cortisol and androgen-producing adrenocortical carcinoma.

Pain is more common with carcinomas. Precocious puberty develops in an occasional patient. About half of these tumors have some type of endocrine abnormality, but in general, endocrine testing per se does not differentiate between benign and malignant tumors.

The role of percutaneous ablation for adrenal tumors is mostly anecdotal.

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vena cava results in an acute Budd-Chiari syndrome. Imaging, including magnetic resonance angiography (MRA), is useful in evaluating malignant tumor extension into the adrenal veins and inferior vena cava.

A carcinoma tends to have patchy CT contrast enhancement, a somewhat nonspecific finding.

Nonfunctioning adenomas are hypointense to liver on T1and vary in intensity on T2weighted MR images (Fig. 16.1). Magnetic resonance is useful in distinguishing a cyst from an adenoma; on T2-weighted images fluid in a cyst is hyperintense.

Imaging

Regions of hemorrhage and necrosis are common in carcinomas and result in a heterogeneous appearance. Necrosis is not specific for a carcinoma and is also seen in adrenal hemangiomas and other larger tumors. Some adenomas and carcinomas develop calcification. Calcifications are more common in larger, heterogeneous-appearing tumors containing central necrosis or hemorrhage; the imaging appearance of these larger tumors does not permit ready differentiation between adenomas and carcinomas.

Especially with the larger adrenal carcinomas, the vena cava should be studied for possible invasion. A right adrenal gland adrenocortical carcinoma can grow as an intracaval tumor thrombus, at times even extending into the atrium. Or, a neoplasm invading the inferior

Metastases

An adrenal metastasis without a known primary tumor is sufficiently rare that it is generally not considered in the differential diagnosis of an incidental adrenal tumor. On the other hand, adrenal gland metastases are common in a setting of a known cancer in another organ. Given the known prevalence of adrenal adenomas, in a setting of a known primary malignancy the chance that an enlarged adrenal gland represents an incidental adenoma is roughly 50%.

Lung and breast carcinoma and melanoma are common metastases. Less common metastases to the adrenal glands include thyroid carcinoma and hepatocellular carcinoma.

Patients with a renal cell carcinoma are at approximately a 2% to 3% risk of ipsilateral

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adrenal metastasis or direct invasion, although these risks increase with larger tumors. Occasionally renal cell carcinoma metastases develop to the contralateral or even both adrenals. After a right radical nephrectomy in a 74-year-old patient CT identified a hypervascular tumor on the left, initially believed to be a splenic artery aneurysm, but arteriography suggested a hypervascular adrenal tumor and adrenalectomy confirmed a metastasis (20).

Small metastases blend into a normalappearing adrenal gland; with growth, a slight bulge in gland outline may be the only finding. The larger metastases are readily visualized by CT and MRI. Some eventually invade surrounding structures. Small metastases tend to be homogeneous; central necrosis develops with growth, and the imaging findings vary accordingly. Necrosis, however, is seen in both metastases and some primary adrenal neoplasms. Calcifications in a metastasis are rare.

Magnetic resonance signal intensity of metastases varies considerably and is,per se,not a useful guide. Most metastases exhibit heterogeneous contrast enhancement, and the homogeneous capillary blush seen with adenomas is uncommon. Their lack of lipid results in no appreciable signal loss on opposed phase MR images, thus distinguishing most metastases from adenomas. A possible exception is with some renal clear cell carcinomas, which contain intracytoplasmic lipid, and such an adrenal metastasis can potentially be confused with an adenoma.

Iodine-131–NP-59 scintigraphy reveals lack of tracer accumulation in most metastases. A word of caution is also necessary here: some adrenal metastases from renal cell carcinomas accumulate NP-59 (21). Some thyroid carcinoma metastases to the adrenal gland show I 131 uptake.

If needed, a percutaneous biopsy provides confirmation.As in other sites, a negative biopsy is less significant than a positive biopsy.

Whether an adrenal-sparing nephrectomy is a viable option in a setting of a renal cell carcinoma and a normal-appearing adrenal gland by imaging is controversial; preoperative CT does not detect adrenal invasion in some of these patients, because of metastases below the resolution of CT or other reasons.

Percutaneous ethanol injection has been performed on adrenal metastases from hepatocel-

lular carcinoma (22); preliminary results are encouraging. CT-guided radiofrequency ablation appears to be effective local control of adrenal metastases (23).

Cortical Hormone-Producing Tumors

Hyperfunctional cortical adrenal conditions include Cushing’s syndrome and aldosteronism. A single predominant hormone activity is evident in the majority of patients with hormone-producing gland hyperplasia or neoplasm. Occasionally encountered are unusual combinations, such as coexisting pheochromocytoma and primary adrenal Cushing’s syndrome.

Imaging is not a substitute for an appropriate clinical endocrinological investigation in a patient suspected of having a hyperfunctional adrenal condition.

Cushing’s Syndrome

Cushing’s syndrome, or hypercortisolism, results from excessive cortisol secretion by the adrenal cortex. Affected individuals have increased urinary free cortisol excretion and an elevated serum cortisol level, with loss of a circadian rhythm. Screening includes an overnight dexamethasone suppression test. It should be emphasized that not all patients appear clinically cushingoid.

Secondary Hyperplasia

Most often Cushing’s syndrome is due to adrenal hyperplasia secondary to excessive adrenocorticotropic hormone (ACTH) secretion. The most common cause of excessive ACTH secretion is a pituitary tumor (Cushing’s disease), although an occasional pancreatic neuroendocrine tumor, pheochromocytoma, bronchial carcinoid, gastrinoma, functioning ovarian tumor, or a tumor at some other site is responsible for ectopic ACTH production. A pituitary adenoma and an adrenocortical adenoma can coexist, resulting in a complex clinical presentation.

Computed tomography shows that only about 70% of patients with ACTH-dependent Cushing’s syndrome have enlarged adrenal glands (24); the adrenals are larger in patients with ectopic ACTH syndrome than in those with