Transcript
Page 1: Overview of adrenal imaging/adrenal CT

Urol Radiol l 1:221-226 (1989) Urologic Radiology

© Springcr-Verlag New York Inc. 1989

Overview of Adrenal Imaging/Adrenal CT

Melvyn Korobkin Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA

Abstract. CT is the imaging procedure of choice for the detection of most suspected adrenal masses. But except for some patients with acute adrenal hemorrhage or fat-containing myelolipoma, the pre- cise histologic nature of an adrenal mass is not ap- parent from the CT image. MIBG radionuclide scanning is useful in some patients with pheochrom- ocytoma, whereas bilateral adrenal venous sampling for hormone assay is necessary for correct laterali- zation in some patients with a small aldosterone- producing adenoma. The potential value of MR imaging in the characterization of adrenal masses, especially to distinguish benign adrenal cortical adenomas from metastatic disease, is now under investigation. Currently percutaneous aspiration bi- opsy is still necessary to make this distinction in patients with an adrenal mass and a known extra- adrenal primary neoplasm.

Key words: Adrenal mass -- Computerized to- mography -- Magnetic resonance imaging.

Several factors combine to make computed tom- ography (CT) the imaging procedure of choice for the detection of a suspected adrenal mass: (1) it can be performed quickly, safely, and at a moderate cost; (2) normal adrenals can be demonstrated in ap- proximately 100% of patients, except in the virtual absence ofretroperitoneal fat; and (3) adrenal masses as small 10 mm can be reliably detected. CT is

Address reprint requests to: M. Korobkin, M.D., Department of Radiology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0030, USA

routinely used to detect and lateralize an adrenal mass in functional endocrine disorders, as well as to search for adrenal and other abdominal metas- tases in oncologic patients. Other less common ad- renal masses, such as cysts, granulomas, myeloli- pomas, and hematomas can occur in symptomatic or asymptomatic patients and are easily detected by CT. The major limitation of CT is its lack of tissue specificity; except in cases of fat-containing mye- lolipoma and some cases of unequivocal adrenal cyst, CT cannot differentiate the various kinds of solid adrenal masses.

Magnetic resonance (MR) imaging demon- strates normal adrenals and adrenal masses with spatial and contrast resolution similar to CT. Pre- l iminary studies using low- and medium-fie ld strength magnets suggest a potential role in char- acterizing the nature of an adrenal mass; most ad- renal adenomas have a different signal intensity compared with malignant masses. Unfortunately significant overlap exists, and in addition there is insufficient data available on the higher field strength magnets to determine what overall role MR will play in the imaging evaluation of adrenal masses. Ra- dionuclide scanning with MIBG is valuable in se- lected patients with biochemically proven pheo- chromocytoma, and adrenal vein sampling is essential in selected patients with primary hyper- aldosteronism.

Normal Anatomy

The remarkable accuracy of CT detection of adrenal masses is highly dependent on a detailed knowledge of the variations in normal morphology of the two glands. Several publications have emphasized the

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222 M. Korobkin: CT and MRI for Detection of Adrenal Masses

CT appearance of normal adrenal glands. The nor- mal right adrenal gland is located on sections ceph- alad to the right kidney, medial to the posterior segment of the right lobe of the liver, and lateral and parallel to the right crus of the diaphragm. The left adrenal gland is located anteromedial to the up- per pole of the left kidney, posterior to the splenic vein and body and tail of the pancreas, and antero- lateral to the left crus of the diaphragm.

In cross section both adrenal glands have a sim- ilar appearance, that of an inverted letter Y, al- though frequently all three limbs are not equally visible on each CT image. The right adrenal gland is the more variable: the anterior limb is often small or indistinct, and sometimes only one of the two posterior limbs is demonstrable. In section through its more caudal portion, a single limb is often visible paralleling the posterior aspect of the inferior vena cava. The left adrenal gland has a more constant appearance, all three limbs of the inverted Y are frequently well demonstrated. If the separate limbs are not well defined a more triangular configuration sometimes results. When distinct limbs of the ad- renal glands are clearly defined by CT they are nor- mally thin or filamentous in appearance; their max- imum thickness rarely exceeds 5 mm.

The morphologic features of normal adrenal glands on MR images are essentially identical to those seen on CT. On medium-field strength mag- nets (0.3-0.6 T), normal adrenal tissue has a low- signal intensity similar to normal liver tissue on both standard T l- and T2-weighted images. The adrenals are clearly outlined by high-intensity retro- peritoneal fat. Although experience with the MR features of normal adrenals on the newer high-field strength magnets is still limited, no major differ- ences in appearance have been described.

Cushing's Syndrome

It is essential to differentiate those patients with Cushing's syndrome due to an autonomous func- tioning adrenal neoplasm from those with bilateral adrenal hyperplasia secondary to excessive adreno- corticotropic hormone (ACTH) production (Cush- ing's disease) from either a pituitary or ectopic source. Biochemical studies often allow this distinction but are occasionally inconclusive or contradictory. Due largely to the excessive retroperitoneal fat present in patients with hypercortisolism, detection or ex- clusion of a unilateral adrenal mass in patients with Cushing's syndrome is accurate in almost every pa- tient using CT. In patients with ACTH-dependent Cushing's disease, the adrenal glands can appear

either normal or can be enlarged, while maintaining their normal configuration. The most grossly en- larged adrenal glands occur in those patients with an ectopic source of ACTH production, usually a pheochromocytoma, thymic or bronchial carcinoid, islet cell tumor of the pancreas, or a medullary car- cinoma of the thyroid.

Rarely, the bilateral adrenal hyperplasia asso- ciated with ACTH-dependent Cushing's disease can assume a macronodular appearance. Usually the presence of bilateral nodules and associated hyper- plasia in the ipsilateral or contralateral gland will suggest the correct diagnosis in these cases. If the process is largely unilateral with a single or predom- inant nodule, an erroneous diagnosis of Cushing's syndrome secondary to an autonomous adenoma has been made leading to inappropriate unilateral adrenalectomy.

Primary Aldosteronism

In patients with primary hyperaldosteronism it is especially important to distinguish those with a sol- itary unilateral adrenal adenoma (80%) from those with idiopathic aldosteronism (bilateral adrenal hy- perplasia). The disease is usually cured by unilateral adrenalectomy when a tumor is present, but is typ- ically not cured by bilateral adrenalectomy even with the idiopathic form. CT is less accurate in detection of aldosterone-producing adenoma than in most other adrenal tumors, primarily because the tumors are typically between l0 and 20 mm in diameter, and many are even less than 5 mm in size. The literature reports an overall accuracy of about 70% in detection of aldosterone producing adrenal ad- enomas. Unlike most adrenal CT scans, 5-ram slice thickness scans are required in patients with primary aldosteronism, either as contiguous slices or with 2-ram overlap. In the absence of unequivocal dem- onstration of a unilateral adrenal mass, bilateral ad- renal vein sampling will often be required to distin- guish unilateral aldosteronoma from the bilateral hyperplasia. Very little data is available yet on the value of MR scanning in this disorder.

Pheochromocytoma

The diagnosis of pheochromocytoma is based on a combination of clinical and biochemical features. Systemic hypertension is present in the vast major- ity of patients. Once the diagnosis of pheochromo- cytoma has been documented biochemically, it is of paramount importance to localize the site of the

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M. Korobkin: CT and MRI for Detection of Adrenal Masses 223

functioning tumor. It is crucial to determine whether the tumor is single or multiple, adrenal or extra- adrenal, and if extra-adrenal to localize its precise site in the abdomen, pelvis, chest, or neck.

CT is a highly accurate method of detecting pheochromocytoma. Surrounding retroperitoneal fat is sufficient, in all but the most emaciated patients, to outline the normal adrenals when contiguous sec- tions are obtained every 5 to 10 mm. Intravenous contrast material is usually unnecessary using CT because evaluation is based almost entirely on mor- phologic criteria, but it is occasionally helpful in young or emaciated patients to more optimally lo- calize the inferior vena cava and upper pole of the kidney.

Adrenal pheochromocytoma, like any adrenal mass, can have one of three possible CT appear- ances: (1) a small mass, less than 2 cm in diameter, arising from one of the three limbs or wings of the normal adrenal; (2) a round or ovoid mass, usually 2-5 cm in diameter, in the expected position of the adrenal gland; and (3) a larger mass, approximately greater than 8 cm in diameter, which may displace or compress adjacent structures so that the precise organ of origin is uncertain.

Most adrenal pheochromocytomas have a non- cystic homogenous appearance on CT. It is not un- usual, however, for central regions of lower atten- uation, due to hemorrhage or necrosis, to be identified. These foci ofhypodensity are more com- mon in larger tumors and more easily appreciated on CT images obtained after intravenous injection of contrast material. Rarely, the area of hemorrhage or necrosis can become so large that a cystic mass can be simulated. The CT diagnosis of a noncystic adrenal mass is nonspecific; a variety of lesions other than pheochromocytoma can produce a similar ap- pearance, including adrenal cortical carcinoma (when larger than 5 cm), hemorrhage (especially when bi- lateral), and both functioning and nonfunctioning adrenal cortical adenoma.

Because most extra-adrenal pheochromocyto- mas occur in the abdomen and pelvis, especially in the paraaortic sympathetic chain, CT is also useful and accurate in evaluating patients with normal ap- pearing adrenal glands who have compelling clinical and biochemical evidence of functioning chromaffin tumor. When contiguous CT sections are obtained through the entire abdomen and pelvis using 8- to 10-mm slice thickness, the majority of extra-adrenal pheochromocytomas below the diaphragm can be identified.

Special attention to technical details is necessary when CT is used to detect extra-adrenal pheochro- mocytoma. Small bowel loops should be sufficiently

opacified with oral contrast material so that small paraaortic tumors are not misinterpreted as unpa- cified bowel. Scans through the abdomen and pelvis should be performed first prior to intravenous in- jection of contrast agent, so that tumors of the blad- der wall (and to a lesser extent of the renal sinus) are not obscured by dense contrast material in the renal pelvis or the bladder.

Although many extra-adrenal pheochromocy- tomas in the chest are readily seen as a paravertebral mass on conventional chest radiographs, recent re- ports indicate the tumor can occur within the peri- cardial sac requiring sophisticated methods for de- tections. Dynamic (rapid sequence) scanning after a bolus injection of an intravenous contrast agent is often necessary--at a single tomographic plane sus- pected from a prior MIBG study or contour abnor- mality or unenhanced CT, or using table incremen- tation through the cardiac region if no suspected plane is apparent.

The initial reports of CT scanning for adrenal disease suggested a high accuracy for evaluation of suspected pheochromocytoma. This initial enthu- siasm has been confirmed by several large series; when results from several studies are combined pheochromocytomas were correctly localized in 94 of 104 tumors. This figure almost certainly under- estimates the true sensitivity of current CT equip- ment, because almost all of the false-negative di- agnoses in these reports were from the earlier 18-s scanners, far inferior to the widely employed sub- 5-s CT scanners now being used. Adrenal masses as small as 5-10 mm in diameter can now be detected. Detection of recurrent pheochromocytoma by CT is less accurate than with evaluation of initial dis- ease, primarily because the metallic surgical clips in the surgical bed sometimes result in streak artifacts which tend to degrade the CT image in that region.

Pheochromocytoma can now be accurately im- aged scintigraphically using I- 131 metaiodobenzyl- guanidine (MIBG). Developed and evaluated over the past several years at the University of Michigan, MIBG is a physiologic analog ofnorepinephrine and quanethidine, which is taken up by the intracellular storage granules ofchromaffin tissue. More than 450 patients with known or suspected pheochromocy- toma have been evaluated at the University of Michigan, but other series from the United States and Europe have shown similar results. Intraadrenal pheochromocytomas are manifested as intense focal uptake, often being the most intense area in the body. Extra-adrenal or metastatic lesions are visu- alized as focal areas of I-131 MIBG uptake in sites not seen in normal patients. The results from all five reported series are remarkably similar. In the largest

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224 M. Korobkin: CT and MRI for Detection of Adrenal Masses

reported series I-131 MIBG had an overall sensi- tivity of 87% and specificity of 99%. It is particularly noteworthy that the sensitivity for suspected pri- mary benign nonfamilial pheochromocytoma (78%) was much less than for the malignant and familial varieties (93%).

Magnetic resonance imaging (MRI) is the new- est modality available for the localization of pheo- chromocytoma. One recent report described the use of MRI in seven patients with CT-documented pheochromocytomas. Images were obtained in the transverse, coronal and sagittal planes. MRI showed all primary pheochromocytomas, as well as recur- rent and metastatic lesions to the thorax, retroper- itoneum, and liver. All the tumors in this small series exceeded 3 cm in diameter. Coronal and sag- ittal scans were useful in evaluating the cephalic and caudal margins of the lesions, especially the inter- face of right adrenal tumors with the liver. The pres- ence or absence of liver invasion by right adrenal tumors is usually difficult to establish with CT; it will probably be easier using coronal and sagittal MR images. Coronal imaging was also reported to be effective in assessing the paraaortic sympathetic chain for extra-adrenal pheochromocytomas.

Even more interesting is the preliminary evi- dence suggesting that MRI may be useful in char- acterizing different categories of adrenal masses. Us- ing low- and intermediate-field strength magnets (0.35-0.5 T), two studies involving a total of 58 patients showed that the T2-weighted images of ad- renal adenomas were qualitatively and quantita- tively different from all other adrenal neoplasms. Most of the nonadenomas, including all 16 pheo- chromocytomas, were hyperintense compared with the liver, while all adenomas were equal to or less intense than the liver. Among the nonadenomas the pheochromocytomas had the highest relative signal intensity of all other neoplasms. This ability to dif- ferentiate masses would be especially useful in pa- tients whose biochemical studies for pheochromo- cytomas are either equivocal or misleading, since an adrenal mass demonstrated by CT might rep- resent a coincidental nonfunctioning adenoma. It should be noted, however, that the value of MR in characterizing pheochromocytoma at the higher field strength magnets, so common in the newer gener- ation of MR scanners, has yet to be determined.

Adrenal Metastasis

The adrenal gland is the fourth most common site for metastatic disease from all tumors after lung, liver, and bone. Metastasis from carcinoma of the

lung is the most common, followed by carcinoma of the breast, thyroid, colon, and melanoma. Me- tastases typically produce a solid round or oval mass in the adrenal gland on CT scans, which can be unilateral or bilateral, and are usually indistinguish- able from other benign or malignant masses--es- pecially a benign nonfunctioning cortical adenoma. CT detection of an adrenal mass is particularly im- portant in the initial staging of nonsmall cell car- cinoma of the lung. The median survival of patients undergoing "'curative" resection is only slightly bet- ter than in those patients not undergoing surgery, and in one series the adrenal glands were the most frequent site of metastases found at autopsy per- formed within 1 month of "curative" pulmonary resection. Approximately 20% of patients with nonsmall cell carcinoma of the lung will have an adrenal mass detected during preoperative staging using CT. Confirmation of adrenal metastases will preclude "curative" pulmonary resection and will usually lead to alternative palliative radiation ther- apy or chemotherapy.

The widespread use of abdominal CT for a large variety of clinical indications has resulted in the incidental detection of adrenal masses in patients without evidence of known primary neoplasms or functional endocrine disorders. The majority of these adrenal masses have proven to be benign cortical adenomas. Benign nonfunctioning adenomas are present in 2-8% of the population at autopsy, so it is not surprising that they are seen not uncommonly on CT scans of the upper abdomen. In the absence of a known primary malignancy or functional ad- renal disorder, a small (less than 3 cm) solid nonfatty adrenal mass can be assumed to be a benign cortical adenoma, requiring only follow-up scans to confirm their benign nature. Ifa primary neoplasm is known, percutaneous aspiration biopsy is required to detect or exclude adrenal metastasis. Even when discov- ered during preoperative staging of a nonsmall cell carcinoma of the lung, an adrenal mass is more likely to be a benign adenoma than a metastatic lesion.

As described earlier, MRI has considerable promise in adrenal tissue characterization. Prelim- inary reports using low- and medium-strength mag- nets (0.35-0.5 T) suggested that, using T2-weighted images, the ratio of signal intensity of an adrenal metastasis (and other nonadenoma masses) to the liver is much higher than with most nonfunctioning adenomas. Subsequent larger series, however , showed a 20-30% overlap between benign and ma- lignant adrenal masses using either T l- or T2- weighted spin-echo imaging.

Preliminary studies using the newer high-field

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M. Korobkin: CT and MRI for Detection of Adrenal Masses 225

strength magnets (1.5 T) indicate that the adrenal mass/liver signal-intensity ratio on T2-weighted spin-echo images cannot be used to differentiate nonadenomas from adenomas. The absolute value of T2-relaxation time of the adrenal mass, however, was useful in distinguishing adenomas from nonad- enomas.

Adrenal Hemorrhage

Bilateral adrenal hemorrhage in the adult is an un- common condition that can lead to acute adrenal insufficiency and death if not properly diagnosed and treated. Prior to the onset of CT, the vast ma- jority of reported patients died without antemortem diagnosis. Although this disorder is usually associ- ated with stress caused by surgery, sepsis, trauma, or hypotension, it also can be related to a bleeding diathesis--especially with anticoagulant therapy.

Adrenal hemorrhage secondary to heparin or coumadin therapy apparently is not due to excessive anticoagulation; prothrombin levels are usually in the therapeutic range, and hemorrhage into the rest of the retroperitoneum or other organs usually does not occur. Most anticoagulant-associated adrenal hemorrhages occur during the first 3 weeks of treat- ment. Some evidence suggests that adrenal glands stressed by acute systemic illness may be at greater risk for hemorrhage than in a normal state.

The diagnosis is often clinically unsuspected be- cause adrenal hemorrhage may not produce insuf- ficiency, and the clinical manifestations of adrenal insufficiency often mimic more common condi- tions, such as myocardial infarction or an acute sur- gical abdomen. The symptoms often are incorrectly attributed to sepsis. Although the clinical diagnosis is sometimes suspected from an abnormally low plasma level of cortisol, biochemical confirmation is based on an abnormal ACTH stimulation test. In the appropriate clinical setting, the CT demonstra- tion of bilateral adrenal masses should lead to a presumptive diagnosis and treatment with intra- venous steroid therapy.

Only a few patients with CT demonstration of bilateral adrenal hemorrhage have been reported, all associated with adrenal insufficiency. Both ad- renal glands are enlarged, although often in an asym- metric manner, having an oval or rounded appear- ance in most cases. At the time of initial CT examination the adrenal masses usually have an at- tenuation value near 30 H, similar to muscle den- sity, probably reflecting a subacute stage of the hem- orrhagic process. Following appropriate treatment, CT scans usually show progressive diminution in

the size (and sometimes attenuation value) of the adrenal masses.

Bilateral solid adrenal masses are most often due to metastatic neoplasm, but in those patients a primary tumor is usually known and typically there is evidence of other sites of metastatic disease of the CT images. Enlarged adrenal glands in patients with adrenal hyperplasia accompanying Cushing's dis- ease retain their normal inverted "V" configuration. Adrenal pheochromocytomas are sometimes bilat- eral, but usually as part of the multiple endocrine neoplasia syndrome. Adrenal tuberculosis or other granulomatous disease is often bilateral and can also result in adrenal insufficiency, but is often calcified.

Unilateral adrenal hemorrhage in the adult has recently been described, always associated with blunt abdominal trauma. The CT features are similar to bilateral hemorrhage, except that streaky infiltration of the periadrenal fat is commonly present. Most of the lesions are on the right side. Associated injuries, such as rib fractures or liver injury, dominate the clinical picture. Up to 20% ofposttraumatic adrenal hemorrhages are bilateral.

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