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Imaging of Adrenal Gland Disorders
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ADRENAL DISORDERS
IMAGING OF ADRENAL GLAND DISORDERS Amy S. Tidwell, DVM, Dominique G. Penninck, DVM, and Juliette G. Besso, DEDV
Hormonal disturbances associated with adrenal gland disease often cause morphologic changes in "target" organs that may be identified radiographically. Examples include hepatomegaly and skeletal osteopenia in patients with hyperadrenocorticism and microcardia and megaesophagus in patients with hypoadrenocorticism. Such findings, however, only provide circumstantial or corroborative evidence of an adrenal endocrinopathy because they are nonspecific. Because the adrenal (and pituitary) glands are small, radiographic detection of an abnormality usually relies on a significant alteration in size, shape, or density and is limited by superimposition of overlying structures. For this reason, direct visualization of these organs has awaited the development of more sophisticated imaging techniques such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). However, abnormal hormonal secretion by the adrenal and pituitary glands is not always accompanied by morphologic changes great enough to be recognized, even with the most precise methods. Furthermore, fully established criteria have not been documented for the use of such techniques. Thus, the approach to imaging of the adrenal gland remains a significant challenge. This article examines the current role of conventional and alternate imaging techniques in the evaluation of adrenal gland dysfunction. The approach to selected adrenal gland secretory disorders such as hypercatecholaminism, hyperaldosteronism, hypoadrenocorticism, and hyperadrenocorticism is discussed.
From the Department of Surgery, Section of Radiology, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts
VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 27 •NUMBER 2 •MARCH 1997
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REVIEW OF ADRENAL IMAGING METHODS Conventional Radiography
In animals with adrenal disease, imaging is typically performed to confirm a tentative diagnosis based on clinical and laboratory findings. Radiography has limited usefulness in this respect because visualization of the adrenal and pituitary glands is hampered by inadequate resolution and superimposition of overlying tissues. The right and left adrenal glands are small retroperitoneal structures located near the craniomedial aspect of the kidneys at the level of the last thoracic and second lumbar vertebrae, respectively. 23 The glands, however, cannot be seen with routine radiography unless enlarged or calcified. 36, 4o, 41 An enlarged left adrenal gland may appear as a soft tissue mass or be inferred if the left kidney is displaced caudally. A mass or mass effect created by an enlarged right adrenal gland is usually more difficult to identify because of its close proximity to the liver. Radiographic evaluation may be assisted using compression paddle techniques or linear tomography to relieve superimposed bowel, or angiography and intravenous urography to improve contrast of adjacent tissues. Prior to the development of CT, the pituitary gland could be evaluated indirectly using cavernous sinus venography and cerebral angiography. Pituitary tumors were suspected if displacement or deficient filling of nearby vessels was noted in the region of the hypophyseal fossa. 29 These angiographic procedures have since been supplanted by CT and MRI and are not recommended because they are invasive and poorly sensitive and specific. Despite its limitations, radiography provides useful information about the secondary effects of adrenal dysfunction as well as potentially identifying metastatic disease. Thoracic and abdominal radiographs are therefore recommended as part of the routine data base. Ultrasonography
Because it is relatively inexpensive, noninvasive, and does not require general anesthesia, ultrasonography is the most practical method of imaging the adrenal glands. However, it is highly dependent on the quality of instrumentation and requires a high level of operator skill and diligence. The procedure usually entails real-time scanning in a parasagittal, dorsal, or oblique and transverse plane of the body to depict the long and short axes of the gland, respectively. The highest frequency transducer that allows adequate penetration should be used. A 5-MHz transducer is usually required for larger dogs, although compression of the ventral abdominal wall with the transducer may allow the use of a 7.5-MHz probe in compliant patients. Most animals are scanned in dorsal recumbency, after the hair is clipped and the skin is moistened with alcohol and acoustic gel.
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The left adrenal gland is identified by first locating the cranial pole of the left kidney in the parasagittal long-axis plane, then fanning or sliding the transducer medially until the aorta is found . The left adrenal gland lies ventrolateral to the aorta and appears as a small peanut shell-shaped structure that is usually hypoechoic to surrounding retroperitoneal fat. Occasionally, an outer hypoechoic cortex can be distinguished from a hyperechoic medulla (Fig. 1). This layered appearance has been used to describe both the normal35 and hyperplastic22 gland. The right adrenal gland may be identified with the patient in dorsal recumbency but tilted to the left, by fanning medially after locating the cranial pole or hilus of the right kidney in the parasagittal long-axis plane. Once the caudal vena cava (eVC) is identified just caudal to the porta hepatis, the probe should be directed slightly laterally. Depending on the approach, the gland may not be seen in the same image as the eve and viewing the entire gland may require angling the transducer obliquely. As with the left adrenal gland, the right appears hypoechoic to surrounding fat or may have a layered appearance, but appears comma-shaped instead of peanut shell-shaped. Using a dorsal-plane right intercostal approach with the patient in left lateral recumbency, the right adrenal gland may appear as a triangular or comma-shaped structure on the near-field side of the eve. In the transverse plane, both adrenal glands appear oval and are located medial to the short axes of the kidneys. The left adrenal is located between the origin of the cranial mesenteric and left renal artery and the right adrenal just cranial to the right
Figure 1. Long-axis ultrasonogram of the left adrenal gland (between plus signs) of a normal dog. Note the peanut shell-shape and the faint layered appearance.
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renal vein; both glands are enveloped by the phrenicoabdominal arteries and veins. However, these smaller vessels may not be readily seen without the aid of color-flow Doppler techniques. If bowel gas interferes with the acoustic window, the animal should be repositioned or scanned from a different plane. Even then, one or both of the adrenal glands may not be visualized in normal patients. This is especially true for the right gland of larger dogs.18 This situation creates the dilemma of distinguishing atrophy from a nonvisualized normal adrenal gland. Other pitfalls in interpretation include variation in shape and size depending on the individual patient and the image orientation. Shape may vary from the above descriptions to include round in all planes, 35 oval, and worm-like. Normal size of the adrenal glands varies with the size of the patient, but useful internal controls have not been established. Changes in thickness (the ventrodorsal dimension perpendicular to the long-axis of the gland) appear to be more meaningful than those in length.1&-20 In recent studies, 19- 20 adrenals in normal young adult medium-sized dogs had a range of thickness from 2 to 5 mm (median, 4 mm). 19 In middle-aged to older dogs, thickness ranged from 4 to 7 mm (median, 6 mm).20 In another study of healthy dogs and those having nonendocrine disease,3 the maximum diameters were found to be up to 8.1mmand11 mm, respectively, for the right gland, and up to 7.4 mm and 10.6 mm, respectively, for the left gland. Ultrasonography also permits evaluation of other organs such as the liver, kidney, and eve for secondary effects and/ or for the presence of local or distant neoplastic spread. It also facilitates percutaneous guided biopsy. Computed Tomography
Visualization of the adrenal glands with CT is not restricted by patient size or by gas in overlying bowel. Therefore, compared to ultrasonography, CT provides a more consistent window and can be used to evaluate the pituitary gland concurrently. Veterinarians have limited access to CT, however, and its use requires general anesthesia. Thus, CT is often only used when the results of other imaging methods are indeterminate. Typically, 5-mm thick transverse CT images of the abdomen are obtained in the region of the adrenal glands. Water-soluble iodinated contrast medium may be administered intravenously to help distinguish vessels from adrenal tissue. A bolus injection of 400 to 800 mg of iodine per kilogram of body weight may be given and the adrenal scan repeated immediately. On the transverse abdominal images, the right adrenal gland is located dorsolateral to the caudal vena cava, ventral to the right diaphragmatic crus, and medial to the cranial pole of the right kidney. The left adrenal gland is ventrolateral to the aorta and psoas minor muscle and medial to the cranial pole of the left kidney. The adrenal glands appear as oval, triangular, or round soft-tissue structures depending on the CT slice location and orientation relative to
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the long axis of the gland.42 Portions of the right adrenal gland may appear bipartite.42 Orientation of each gland within the transverse plane also affects their measured width and thickness; therefore, these dimensions may not be comparable to those obtained with ultrasonography. The ventrolateral-to-dorsomedial dimension provides an estimation of the short axis of the gland. In a study of 10 healthy dogs,42 the maximum ventrolateral-to-dorsomedial dimension was 11.1 mm for the right gland and 14.6 mm for the left gland. For the pituitary region, the use of intravenous contrast medium is essential. Although transverse 2-mm thick images usually suffice, direct sagittal images of the brain may be obtained by laying the animal in lateral recumbency, gently rotating the head sideways, and tilting the CT gantry until it is in alignment with the midsagittal plane of the head. The normal CT appearance of the pituitary gland in dogs and cats has been described as slightly hyperdense compared to the thalamus and cerebral hemispheres17 and contrast-enhancing, 26• 44 because it is outside of the blood brain barrier. In a study of nine normal dogs, the pituitary gland measured 4.3 to 6 mm in height on the midsagittal image. 44 This is in agreement with a reported height of 5 mm observed in the gross unpreserved gland of adult mesaticephalic breeds. 23 Unlike the concave or flat appearance of that in humans, its dorsal border was described as convex. 44 Unfortunately, precise criteria for the normal CT appearance and size of the pituitary gland has not been determined in a large population of dogs and cats. In the authors' experience, the degree of contrast enhancement and size of the gland differ among normal individuals. Typically, the enhanced gland "fills" the hypophyseal fossa within the confines of the sella turcica. In some instances, the CT window or grayscale level must be electronically altered to help distinguish the gland from this complex of bones. On the transverse image, depending on the precise location and thickness of the CT slice, several millimeters of the gland are visible above the basisphenoid bone. The dorsal margin of the gland usually appears below or level with the cavernous sinuses on the transverse image and the dorsum sella on the midsagittal image (Fig. 2). This appearance, however, would not rule out the presence of a small tumor, thus it should be interpreted cautiously in a patient with clinical evidence of pituitary dysfunction. Magnetic R.esonance Imaging In humans, MRI of the abdomen is performed to detect and further characterize adrenal masses and to identify extraadrenal involvement. Because of overlapping results, however, the use of MRI to characterize tissues as benign or malignant has not achieved widespread acceptance. 3o, 38 Because of its superior resolution, MRI is the preferred technique for evaluation of the pituitary gland. The appearance of sellar and
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Figure 2. Pre-contrast (A) and postcontrast (B) transverse and postcontrast mid-sagittal reformatted (C) CT images of the brain of a dog with no clinical or laboratory (complete blood count, chemistry profile, and urinalysis) evidence of endocrine disease. B, A portion of the enhanced pituitary gland (arrow) is visible dorsal to the basisphenoid bone (b) and is flanked on each side by the enhanced cavernous sinuses (arrowheads). The height (dorsal to ventral dimension) of the visible portion of the gland is 2.7 mm. C, The gland (arrow) sits within the hypophyseal Iossa and is enclosed caudally by a bony projection, the dorsum sella (curved arrow), and rostrally (to the left) by a sloping ridge of bone, the tuberculum sella (arrowheads). These structures, along with the floor of the hypophyseal Iossa, are the components of the basisphenoid bone comprising the sella turcica. At postmortem, the pituitary gland was grossly normal, measuring 8 mm in length, 7 mm in width, and 4 mm in height. No histopathologic abnormalities were found.
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juxtasellar tissues in humans has been described in detail. 13• 47 Standard sequences include thin-slice (3 mm), high-resolution (256 X 256 matrix, small field of view), Tl-weighted sagittal and coronal spin-echo images before and immediately after administration of a paramagnetic contrast agent such as gadolinium-diethylenetriamine pentaacetic acid (GdDTPA, Magnevist, Berlex Laboratories, Wayne, New Jersey). 13• 47 Precontrast T2-weighted and dynamic Tl-weighted postcontrast techniques may also be performed.13 In our experience, the MRI appearance of the pituitary gland in animals mimics that of CT; that is, it is a normally enhancing structure confined to the limits of the sella turcica. Scintigraphy
Functional imaging of the adrenal glands can be achieved using iodine-labeled pharmaceuticals that have an affinity for the adrenal cortex and catecholamine-secreting tissues. 1311-68 iodomethylnorcholesterol (NP-59) and 1311- or 1231-metaiodobenzylguanidine (mlBG) are the agents of choice to evaluate the adrenal cortex and medulla in humans, respectively.Ji They are primarily used to identify or confirm abnormalities of aldosterone, cortisol, and sex-steroid secretion and to localize intra- and extraadrenal pheochromocytoma. To prevent uptake of free iodine by the thyroid gland, Lugol's solution must be administered during adrenal scintigraphy. In patients with primary hyperaldosteronism, dexamethasone may be administered to increase the specificity of NP-59 studies by suppressing the adrenocorticotropic hormone (ACTH)dependent zona fasciculata and reticularis, thus accentuating uptake into the ACTH-independent zona glomerulosa. Abnormal scintigraphic patterns of NP-59 or mIBG scans usually appear as increased unilateral, bilateral, or extradrenal uptake, depending on the disorder.Ji Use of both corticaPJ and medullary5 scintigraphy in the dog has been described. Cortical studies usually require image acquisition over the course of several days (up to 15). This disadvantage and adrenocortical scintigraphy's limited availability will likely prevent its widespread clinical use in dogs and cats. A 1231-mIBG study, however, is less time consuming, usually requiring 24 hours to complete, and should be considered to diagnose, localize, and determine the extent of pheochromocytoma or other neuroendocrine tumors in difficult cases. Scintigraphy plays a larger role in the management of respiratory distress associated with hyperadrenocorticism. 99mTechnetium (99mTc)labeled perfusion studies may be used in conjunction with thoracic radiography to diagnose pulmonary thromboembolism. Perfusion scanning uses 99 mTc tagged to small particles of albumin (99mTc-macroaggregated albumin), which is injected intravenously. The radioactive particles travel to the lung via the pulmonary arteries and are then trapped in the capillary bed. Areas of vascular occlusion due to thromboembolism therefore show deficient radioactivity. Ideally, a ventilation scan is used
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in conjunction with the perfusion scan to increase specificity. It is usually performed using a radioactive gas or an agent such as 99 mTc-labeled diethylenetriamine pentaacetic acid (DTPA) that is aerosolized by a nebulizer and then inhaled by the patient. Distribution of the radioactive aerosol in the air spaces is a measure of ventilatory function; disease processes that impair ventilation thus show deficient radioactivity on the scan. Recently, bone-seeking agents such as 99mTc-methylene diphosphonate (MDP) have been used to document diffuse pulmonary mineralization in Cushingoid dogs having normal perfusion. 6 Delayed static images are obtained of the thoracic region similar to those of a bone scan.
SELECTED SECRETORY DISORDERS Hypercatecholaminism
Pheochromocytoma is an uncommon catecholamine-secreting tumor arising from chromaffin cells of the adrenal medulla. Those located outside the gland are termed paragangliomas or extra-adrenal pheochromocytoma. The excessive vasoactive catecholamines produce hypertension, which may be paroxysmal or sustained. Imaging has a significant role in the diagnosis of this disorder because clinical signs may also be sporadic and nonspecific and laboratory findings are sometimes inconclusive. In patients with known or suspected pheochromocytoma, thoracic radiography is indicated to rule out the presence of pulmonary metastasis. Cardiac enlargement secondary to the effects of excessive catecholamine production is sometimes present. If large, a mass in the retroperitoneal space may be identified with routine abdominal radiography. The presence of ascites may indicate venous obstruction due to invasion or thrombosis of the caudal vena cava. If ultrasonography is not available, this complication can be confirmed using a caudal venacavogram. This is performed by injecting water-soluble iodinated contrast medium into the saphenous vein and obtaining sequential lateral and ventrodorsal views of the abdomen. To lessen the hemodynamic response, low osmolar contrast medium such as iohexol (Omnipaque, Winthrop Pharmaceuticals, New York, NY) or iopamidol (Isovue, Squibb Diagnostics, Princeton, NJ) is recommended. Obstruction or displacement of contrast media flow or a filling defect is observed with invasion or thrombosis of the caudal vena cava. Likewise, a nonselective aortogram obtained after the injection of contrast medium into the cephalic or jugular vein may help identify invasion of the aorta by a left-sided mass. Unlike routine radiography, ultrasonography, CT, and MRI allow direct visualization of the pheochromocytoma and often detect local or distant spread. mIBG scintigraphy localizes the tumor by depicting abnormal function of the adrenal medulla. In humans, MRI and/or
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mlBG are typically used in problem situations27 in which pheochromocytoma is suspected but is not found with ultrasonography or CT, or when a mass needs further characterization. Use of MRI may help to distinguish pheochromocytoma from other tumors by its characteristically high signal intensity on T2-weighted images. 27• 30 Magnetic resonance imaging also appears to be more sensitive than CT for the detection of small or extraadrenal pheochromocytoma and does not require the use of iodinated contrast medium, a contraindication in human patients with this disease. 30 mlBG scintigraphy likewise distinguishes pheochromocytoma from a cortical mass and allows screening of the entire body for an extraadrenal source or metastasis. 27• 31 In animals, ultrasonography should be selected preferentially over CT or MRI to avoid the use of anesthesia in these hemodynamically unstable patients. As in humans, MRI or mlBG scintigraphy may be useful in problem cases. In a retrospective study of 26 dogs at the Tufts University School of Veterinary Medicine (TUSVM),8 nine pheochromocytomas tended to be well-defined unilateral mass lesions having a wide range of size and variable echotexture. Consistent with previous descriptions,37 five tumors were quite large (up to 7 X 3.8 cm). However, four tumors were less than 2 cm in maximum width. In fact, one appeared as a nodule or a focal increase in width measuring 1.4 cm. Tumor echogenicity compared to the ipsilateral renal cortex was hypoechoic, isoechoic, hyperechoic, and mixed. Occasionally anechoic, farenhancing regions were found within the mass as part of a mixed pattern, likely representing foci of necrosis or hemorrhage. In one dog, the tumor appeared as an amorphous 4 X 3 cm mass having poorly defined borders. Other features included the presence of abdominal effusion secondary to tumor rupture, local invasion and distant tumor thrombus of the caudal vena cava, and liver metastasis. Additional pathologic changes found at necropsy in the abdomen of dogs with pheochromocytoma9 include the presence of bilateral involvement; compression or mural invasion of the aorta, renal and adrenal vessels, and hepatic vein; invasion of the vertebrae with compression of the spinal cord; and metastasis to the spleen, contralateral adrenal gland, ovary, and diaphragm. These abnormalities may be discovered during an ultrasound examination. A scan of the entire abdomen is, therefore, always indicated. The ultrasonographic features described above do not rule out the possibility of other adrenal neoplasms. If pheochromocytoma is clinically suspected, however, biopsy of the adrenal gland should not be performed because it may produce a sudden hypertensive episode that is sometimes fatal. In humans, urine catecholamines and vanillylmandelic acid levels are obtained before every adrenal gland biopsy, even if the clinical signs of pheochromocytoma are absent. 15 If these tests are positive, the biopsy is not performed; if equivocal, the blocking agent phentolamine and an intravenous catheter are made available at the time of biopsy.
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Hyperaldosteronism
Overproduction of aldosterone by the zona glomerulosa of the adrenal cortex leads to a recognized syndrome of electrolyte disturbances in humans, 27 cats, 1' 12 and dogs. 16 In approximately 70% of human patients, a solitary aldosterone-producing adenoma is present. 27 Otherwise, it is idiopathic and associated with bilateral adrenal hyperplasia. 27 Because the pathologic changes associated with small adenomas or bilateral hyperplasia may not be detected with anatomic imaging such as CT,31 functional imaging using NP-59 scintigraphy31 or selective adrenal vein sampling for aldosterone levels27, 30 may be required. Hyperaldosteronism in animals was originally reported in a cat having a large (4 x 5 X 3 cm) adrenal cortical adenocarcinoma on postmortem examination. 12 The contralateral adrenal gland was not found. An adenoma and two adenocarcinomas were detected during abdominal surgery in three dogs with this syndrome. 16 Imaging was not mentioned as part of the diagnostic workup in these animals. At TUSVM, we have detected small adrenal masses ultrasonographically in two clinically affected cats, one having a surgical excision biopsy of an adrenal adenoma of zona glomerulosa origin, the other having a postmortem diagnosis of adenocarcinoma. In both cases, a small (9- to 12-mm), rounded hypoechoic mass of the right adrenal gland was found. The only difference between the two tumors was preservation of the normal caudal pole of the adrenal gland in the patient with the adenoma (Fig. 3). Because of its relative simplicity, abdominal ultrasonography should be considered in animal patients having clinical signs characteristic of hyperaldosteronism. Thoracic radiographs and echocardiography may also be warranted to identify metastasis and hypertension-induced cardiac enlargement. Hypoadrenocorticism
To our knowledge, no characteristic imaging features of primary hypoadrenocorticism occur in animals other than the well-documented secondary effects. In imaging studies in humans, the adrenals are often undetected or diminished in size.27 Similar findings in animals with idiopathic adrenal insufficiency would seem likely, because bilateral adrenal gland atrophy with fibrosis is noted histopathologically. 21 Other less-common causes of hypoadrenocorticism include infection, hemorrhagic infarction, metastatic neoplasia, amyloidosis, and trauma. 4, 21 Although its value in animals with uncomplicated adrenal insufficiency has yet to be determined, imaging of the adrenal glands may prove useful to rule out these unusual causes. Thoracic and abdominal radiographs may document the secondary effects of hypoadrenocorticism such as microcardia, pulmonary hypoperfusion, and megaesophagus. After treatment, resolution of these ab-
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Figure 3. Long-axis ultrasonogram of the right adrenal gland (between plus signs) in a cat with hyperaldosteronism. The cranial pole is focally enlarged by a round hypoechoic nodule measuring 9 mm in diameter. The architecture of the caudal pole is preserved. Length of the entire gland is 15 mm. Diagnosis was adenoma of zona glomerulosa origin. eve caudal vena cava.
normalities may be illustrated with follow-up radiography. Because these findings are subjective and nonspecific, they should only be considered supportive evidence. Hyperadrenocorticism
Imaging may contribute to the initial diagnosis of hyperadrenocorticism or may differentiate pituitary-dependent hyperplasia from an adrenal tumor by depicting the systemic effects of excessive cortisol or by revealing an adrenal or pituitary mass. This information can then be used to direct medical, surgical, or radiation therapy management. Radiographic features of hyperadrenocorticism include a pendulous abdomen, hepatomegaly, distended urinary bladder, skeletal osteoporosis, and dystrophic calcification of soft tissues. The latter typically appears as ill-defined mineral opacities within the skin (calcinosis cutis) and occasionally of the renal pelvis, liver, gastric mucosa, and branches of the aorta. 16 Calcification of the tracheal rings and bronchi may also occur but is nonspecific. Diffuse pulmonary mineralization may cause a mild to moderate generalized increase in interstitial markings. 6 The interstitial pattern may be barely detectable or may mimic pulmonary edema.6
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Although often seemingly mild, this pattern should not be dismissed as clinically insignificant because diffuse mineralization may impair adequate diffusion of gases leading to respiratory distress and/ or hypoxemia despite normal perfusion. 6 Respiratory compromise may also occur in animals with hyperadrenocorticism due to pulmonary thromboembolism (PTE). Although PTE may result in pulmonary consolidation and pleural effusion from lung infarction, blunted pulmonary arteries, or regions of oligemia, thoracic radiographs are sometimes normal. Scintigraphy may be used in these circumstances to help distinguish PTE from diffuse mineralization. Pulmonary thromboembolism results in hypoxemia because areas of normal ventilation are not adequately perfused, preventing exchange of oxygen and carbon dioxide between alveoli and pulmonary capillaries. Thus, ventilation to this region of the lung is "wasted" and a ventilation/ perfusion mismatch occurs. The approach to diagnosis of PTE is somewhat complicated and controversial. If all imaging modalities are available, combined ventilation and perfusion scintigraphy is ideal. However, perfusion scintigraphy alone, if performed in conjunction with normal thoracic radiographs, is still useful. Perfusion scanning usually eliminates the diagnosis of PTE if results are negative (i.e., a normal scan). In this circumstance, bone scintigraphy using 99 mTc-methylene qiphosphonate may demonstrate abnormal generalized isotope uptaljce within the lungs, 6 implicating diffuse mineralization, not PTE, as tM source of the respiratory di.stress. When perfusion deficits are found but ventilation scintigraphy is not available, normal ventilation is often presumed if thoracic radiographs are normal. In other words, if a lobar perfusion deficit is found in a region of lung that appears radiographically normal, a mismatch is presumed and a diagnosis of PTE is made. If infiltrates are present in areas of perfusion deficits, however, this supposition should not be made because pneumonia or other primary ventilatory disturbances (causing reflex vasoconstriction) are still serious considerations. Angiography after selective catheterization of the pulmonary arteries is then required to confirm PTE. If positive, intraluminal filling defects or abrupt vessel cut-off due to thrombi is present. Selective angiography, however, is an invasive procedure having risks that may outweigh the benefits in some patients. Once a diagnosis of hyperadrenocorticism is made, pituitary-dependent hyperplasia (PDH) must be distinguished from an adrenal cortical tumor (ACT) to institute proper treatment. A high-dose dexamethasone test does not suppress cortisol levels in every dog with PDH, and plasma ACTH concentrations in the two groups of dogs have some degree of overlap. 16 Thus, making a distinction between PDH and ACT when laboratory tests are indeterminate becomes a primary goal of imaging. Routine radiography may be used to screen for adrenal masses or metastasis in dogs with laboratory evidence of hyperadrenocorticism. In one study,36 50% of ACT had some degree of calcification; all of these tumors were visible on abdominal radiographs. The presence of calcifi-
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cation could not reliably distinguish carcinoma from adenoma, however. 36 Adrenal gland enlargement without calcification may also permit detection. A study comparing survey radiographs with CT40' 41 concluded that visualization of an adrenal gland mass with a diameter of 20 mm (based on CT measurement) on survey radiographs is possible but is influenced by the size of the dog, whereas larger tumors may be visualized regardless of the size of the dog. Although intravenous urography combined with linear tomography improves the sensitivity of radiography, 43, 45 it requires anesthesia, intravenous contrast media injection, and specialized equipment, making it less practical. Ultrasonography, once believed to have limited usefulness in adrenal gland evaluation, has now become an essential part of the diagnostic workup of hyperadrenocorticism in animals.3, a, 16, 1s-20, 22, 24, 35, 37, 39, 42, 43, 45, 46 Ultrasonography may support a diagnosis of hyperadrenocorticism by detecting . abnormal adrenal glands or systemic effects such as steroid hepatopathy, soft tissue mineralization, and metastasis, but its greatest role appears to be distinguishing PDH from ACT. Occasionally, a poor acoustic window prevents adequate evaluation of the glands, however. In this circumstance, interpretation of the findings rests on the confidence level of the sonographer. This is especially true when an adrenal gland is not seen; the sonographer must decide if the gland is truly atrophied or artifactually absent. During a retrospective study at TUSVM of 26 dogs with histopathologically confirmed adrenal lesions,8 ultrasonographic features of hyperplasia, adenoma, and adenocarcinoma in 16 dogs were identified and the following deductions were made. A hyperplastic adrenal gland may appear normal in size and shape or enlarged (increased in thickness or "plump") with a normal shape or may have a focal enlargement or "nodule." Very infrequently, hyperplasia may appear as a rounded mass. In this study, all of the adenocarcinomas appeared either as a rounded mass (diameter usually greater than 2 cm) or as a nodule (diameter usually less than 2 cm) and all of the adenomas appeared as a nodule; therefore, the absence of these features should most often exclude ACT. Atrophy of the adrenal cortex secondary to a contralateral functional tumor may not be apparent ultrasonographically. Therefore, the presence of a normal-appearing gland opposite a mass should not lower suspicion of ACT. Adenocarcinoma cannot be distinguished from other malignant tumors such as metastasis (Fig. 4) or pheochromocytoma without a biopsy. Identification of lesions in multiple organs may raise suspicion of malignancy, but again requires biopsy confirmation. Although vascular invasion and thrombosis point to malignancy, thrombosis secondary to hypercoagulability may be detected with PDH. Bilateral lesions are most often seen with hyperplasia, but not exclusively. Concurrent ACT and pheochromocytoma have been reported in the dog, as have concurrent PDH and ACT. 16• In our opinion, CT plays its greatest role in dogs with confirmed hyperadrenocorticism when the sonographer has a low level of confi-
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Figure 4. Long-axis ultrasonogram of the left adrenal gland (between plus signs) in a dog with bilateral adrenal gland metastasis from a pulmonary adenocarcinoma. As noted with some primary adenocarcinomas, the adrenal gland maintains its normal shape except at the cranial pole, where it is thickened (arrows). The cranial aspect of the gland also appears hyperechoic to the caudal aspect. The largest dimensions of the gland were 33 mm in length and 11 mm in thickness.
dence in the ultrasound exam. Unless severely atrophied or absent, the adrenal glands should be consistently visualized on a CT image. 2• 14• 42• 43 As a general rule, if a unilateral rounded adrenal mass or nodule is absent, ACT is unlikely to be present. As with ultrasonography, a nodule may indicate either hyperplasia, ACT, or an (incidental) nonfunctional tumor. Computed tomography does not allow distinction of benign and malignant tumors, although current research in humans indicates that precontrast CT attenuation values (Hounsfield units) may be characteristically lower for adenomas than for nonadenomas. 28 Invasion of adjacent vessels by a mass may be detected with CT, especially after contrast media injection. However, if the mass merely touches the vessel, the presence of invasion, adhesion, or simple abutting cannot be predicted. Computed tomography may also be performed to evaluate the pituitary gland as an aid in the diagnosis of PDH. However, CT of the pituitary gland should not be the sole means of diagnosing PDH, because ACTH-secreting tumors may be microscopic or within the range of normal. Furthermore, specific criteria for the normal CT appearance based on a large population of dogs and cats has not been determined. Until this is done, results may be prone to misinterpretation. Likewise, although an obvious enhancing mass (i.e., one that clearly exceeds the limits of the sella turcica) most likely represents a pituitary adenoma or
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adenocarcinoma, one must be aware that not all are secretory32 and occasionally tumors such as meningioma arising from the calvarial floor may mimic a pituitary mass. In dogs with confirmed PDH and neurologic signs, alternative treatment methods such as radiation therapy or, less commonly, surgical excision of the pituitary gland should be considered.to, 32 While CT is certainly indicated in dogs with neurologic signs compatible with a compressive pituitary mass, whether CT should be performed in dogs without neurologic signs is less clear. The argument in favor of CT is that the absence of neurologic signs does not rule out a large pituitary mass.to, 25• 32• 34 Because neurologic signs may eventually develop, radiation therapy may be warranted. Arguments against performing CT in all dogs with PDH are related to its cost, relative inaccessibility, and anesthesia requirements. A thorough neurologic exam performed every few months during medical treatment may suffice. 25• 34 Once neurologic signs develop, however, CT should be performed and radiation therapy considered.25• 32• 34 The role of MRI in the diagnostic evaluation of hyperadrenocorticism is not clearly defined. Because of its limited availability relative to other techniques, MRI of the adrenal glands in animals has not achieved widespread use. Because of its superior resolution, the use of MRI to evaluate the pituitary gland seems to be a logical alternative to CT in animals with PDH. Before this is feasible, however, the normal appearance of the pituitary gland must be established in a large number of dogs and cats. In humans, the pituitary gland is normally contrast enhancing and has a vertical dimension ranging from 5 to 12 mm, depending on the age and hormonal status of the individual.1 3• 47 In our experience, the MRI appearance of the pituitary gland of dogs seems to follow that of humans, except for the relatively smaller size. Until detailed MRI studies of the normal sellar and parasellar tissues in the dog are completed, we recommend following the criteria described for CT; that is, the normal enhanced pituitary gland should reside within the confines of the sella turcica on the midsagittal view and should not rise above the level of the cavernous sinuses on the transverse view. In the future, MRI may play an important role in the management of and treatment planning for animals with PDH due to a pituitary adenoma or adenocarcinoma. As with the normal gland, the MRI manifestations of these lesions require further documentation. In humans, a pituitary tumor exceeding the normal limits of size (greater than 1 cm in height or "macrotumor") is generally homogenously enhancing47 and is a candidate for nonmedical therapy due to compression of suprasellar tissues. A "microtumor" is within the range of normal pituitary size (less than 1 cm in height) and often appears as a focal hypointensity relative to the rest of the gland on immediate postcontrast Tl-weighted images.47 Because the pituitary gland in dogs and cats does not normally achieve a size of 1 cm, prior use of this classification scheme in animals is merely arbitrary and should be reconsidered. Although speculating that MRI may eventually establish a threshold (based on tumor size)
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below which neurologic signs will not develop is tempting, preliminary studies using MRI7' 11 have shown that significant overlap in tumor size exists between dogs with and without neurologic signs. Until more information is gathered on the growth patterns of these tumors and their relationship to surrounding brain structures, criteria based solely on tumor size will most likely continue to be unrewarding. CONCLUSION
When evaluating an animal with suspected adrenal gland disease, the clinician must have a clear appreciation of the role of imaging in order to use it appropriately. In this article, we have attempted to illustrate the strengths and limitations of several imaging modalities for the evaluation of four adrenal gland disorders. Although imaging characteristics for each disorder are described, significant overlap exists between normal and abnormal and between the various types of disease processes. For this reason, imaging should be used to complement, not replace, clinical and laboratory evaluation. Likewise, future investigation should concentrate on the ability to image not only morphologic but also functional and subgross alterations. References 1. Ahn A: Hyperaldosteronisrn in cats. Sernin Vet Med Surg (Small Anirn) 9:153-157, 1994
2. Bailey MQ: Use of x-ray-cornputed tomography as an aid in localization of adrenal masses in the dog. J Arn Vet Med Assoc 188:1046--1049, 1986 3. Barthez PY, Nyland TG, Feldman EC: Ultrasonographic evaluation of the adrenal glands in dogs. J Arn.Vet Med Assoc 207:1180-1183, 1995 4. Berger SL, Reed JR: Traumatically induced hypoadrenocorticisrn in a cat. J Arn Anirn Hosp Assoc 29:337-339, 1993 5. Berry CR, Wright KN, Breitschwerdt EB, et al: Use of 123Iodine rnetaiodobenzylguanidine scintigraphy for the diagnosis of a pheochrornocytorna in a dog. Vet Radio! Ultrasound 34:52-55, 1993 6. Berry CR, Ackerman N, Monce K: Pulmonary mineralization in four dogs with Cushing's syndrome. Vet Radio! Ultrasound 35:10-16, 1994 7. Bertoy EH, Feldman EC, Nelson RW, et al: Magnetic resonance imaging of the brain in dogs with recently diagnosed but untreated pituitary-dependent hyperadrenocorticisrn. J Arn Vet Med Assoc 206:651-656, 1995 8. Besso JG, Penninck DG, Gliatto JM: Ultrasonographic evaluation of adrenal lesions in dogs: A retrospective study of 26 dogs. Radio! Ultrasound, in press 9. Bouyad H, Feeney DA, Caywood DD, et al: Pheochrornocytorna in dogs: 13 cases (1980-1985). J Arn Vet Med Assoc 191:1610-1615, 1987 10. Duesberg CA, Bertoy EH, Feldman EC: Diagnosis and treatment of rnacroturnors in dogs with pituitary-dependent hyperadrenocorticisrn. In Bonagura JD (ed): Current Veterinary Therapy XII. Philadelphia, WB Saunders, 1995, pp 351-355 11. Duesberg CA, Feldman EC, Nelson RW, et al: Magnetic resonance imaging for diagnosis of pituitary rnacroturnors in dogs. J Arn Vet Med Assoc 206:657-662, 1995 12. Eger CE, Robinson WF, Huxtable CRR: Primary aldosteronisrn (Conn's syndrome) in a cat: A case report and review of comparative aspects. J Small Anirn Pract 24:293-307, 1983
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13. Elster AD: Modem imaging of the pituitary. Radiology 187:1-14, 1993 14. Emms SG, Wortman JA, Johnston DE, et al: Evaluation of canine hyperadrenocorticism using computed tomography. J Am Vet Med Assoc 189:432-439, 1986 15. Feld R: Controversial issues in ultrasound-guided abdominal biopsy (course notes). 40th Annual American Institute of Ultrasound in Medicine Convention, New York, 1996 16. Feldman EC: Hyperadrenocorticism. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders, 1995 pp 1538-1578 16a. Feldman EC, Nelson RW: Hyperadrenocorticism (Cushing's syndrome). In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, ed 2. Philadelphia, WB Saunders, 1996, pp 187-265 17. Fike JR, LeCouteur RA, Cann CE: Anatomy of the canine brain using high resolution computed tomography. Vet Radio) 22:236--243, 1981 18. Grooters AM, Biller OS, Miyabayashi T, et al: Evaluation of routine abdominal ultrasonography as a technique for imaging the canine adrenal glands. J Am Anim Hosp Assoc 38:457-462, 1994 19. Grooters AM, Biller OS, Merryman J: Ultrasonographic parameters of normal canine adrenal glands: Comparison to necropsy findings. Vet Radio) Ultrasound 36:126-130, 1995 20. Grooters AM, Biller OS, Theisen SK, et al: Ultrasonographic characteristics of the adrenal glands in dogs with pituitary-dependent hyperadrenocorticism: Comparison with normal dogs. J Vet Intern Med 10:110--115, 1996 21. Hardy RM: Hypoadrenal gland disease. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders, 1995 pp 1579-1592 22. Homco LO: Adrenal glands. In Green RW (ed): Small Animal Ultrasound. Philadelphia, Lippincott-Raven, 1996, pp 211-226 23. Hullinger RL: The endocrine system. In Evans HE, Christensen GC (eds): Miller's Anatomy of the Dog, ed 2. Philadelphia, WB Saunders, 1979, pp 602--631 24. Kantrowitz BM, Nyland TG, Feldman EC: Adrenal ultrasonography in the dog. Vet Radio) 27:91-96, 1986 25. Kipperman BS, Feldman EC, Dybdal NO, et al: Pituitary tumor size, neurologic signs, and relation to endocrine test results in dogs with pituitary-dependent hyperadrenocorticism: 43 cases (1980--1990). J Am Vet Med Assoc 201:762-767, 1992 26. Kornegay JN: Imaging brain neoplasms: Computed tomography and magnetic resonance imaging. Vet Med Report 2:372-390, 1990 27. Korobkin M, Francis IR: Adrenal imaging. Semin Ultrasound CT MR 16:317-330, 1995 28. Korobkin M, Brodeur FJ, Yutzy GG, et al: Differentiation of adrenal adenomas from nonadenomas using CT attenuation values. AJR Am J Roentgenol 166:531536, 1996 29. Lee R, Griffiths IR: A comparison of cerebral arteriography and cavernous sinus venography in the dog. J Small Anim Pract 13:225-238, 1972 30. Lubat E, Weinreb JC: Magnetic resonance imaging of the kidneys and adrenals. Top Magn Reson Imaging 2:17-36, 1990 31 . Malinoff HL, Gross MD, Shapiro B: Adrenal gland. In Early PJ, Sodee DB (eds): Principles and Practice of Nuclear Medicine, ed 2. St. Louis, Mosby-Year Book, 1995, pp 652...(,77 32. Mauldin GN, Burk RL: The use of diagnostic computerized tomography and radiation therapy in canine and feline hyperadrenocorticism. Problems Vet Med 2:557-564, 1990 33. Mulnix JA, Van den Brom WE, Lubberink AAME, et al: Gamma camera imaging of bilateral adrenocortical hyperplasia and adrenal tumors in the dog. Am J Vet Res 37:1467-1471, 1976 34. Nelson RW, Ihle SL, Feldman EC: Pituitary macroadenomas and macroadenocarcinomas in dogs treated with mitotane for pituitary-dependent hyperadrenocorticism: 13 cases (1981-1986). J Am Vet Med Assoc 194:1612-1617, 1989 35. Nyland TG, Mattoon JS, Wisner ER: Ultrasonography of the urinary tract and adrenal glands. In Nyland TG, Mattoon JS (eds): Veterinary Diagnostic Ultrasound. Philadelphia, WB Saunders, 1995, pp 95-124 36. Penninck DG, Feldman EC, Nyland TG: Radiographic features of canine hyperadreno-
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corticism caused by autonomously functioning adrenocortical tumors: 23 cases (19781986). J Am Vet Med Assoc 192:1604-1608, 1988 37. Poffenbarger EM, Feeney DA, Hayden DW: Gray-scale ultrasonography in the diagnosis of adrenal neoplasia in dogs: Six cases (1981-1986) J Am Vet Med Assoc 192:228-232, 1988 38. Reinig JW, Stutley JE, Leonhardt CM, et al: Differentiation of adrenal masses with MR imaging: Comparison of techniques. Radiology 192:41-46, 1994 39. Schelling CG: Ultrasonography of the adrenal gland. Problems Vet Med 3:604-617, 1991 40. Voorhout G, Stolp R, Rijnberk A, et al: Assessment of survey radiography for the
41. 42.
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detection of hyperfunctioning adrenocortical tumors in dogs: A comparison with computed tomography. In Voorhout G (ed): Diagnostic imaging of the pituitary and adrenal glands in hyperadrenocorticoid dogs (dissertation). Rijksuniversiteit te Utrecht, The Netherlands, 1988 Voorhout G, Stolp R, Rijnberk A, et al: Assessment of survey radiography and comparison with x-ray computed tomography for detection of hyperfunctioning adrenocortical tumors in dogs. J Am Vet Med Assoc 196:1799-1803, 1990 Voorhout G: Computed tomography, nephrotomography and ultrasonography of the adrenal glands of healthy dogs. In Voorhout G (ed): Diagnostic imaging of the pituitary and adrenal glands in hyperadrenocorticoid dogs (dissertation). Rijksuniversiteit te Utrecht, The Netherlands, 1988 Voorhout G: X-ray computed tomography, nephrotomography and ultrasonography of the adrenal glands of healthy dogs. Am J Vet Res 51:625-631, 1990 Voorhout G: Cistemography combined with linear tomography for the visualization of the pituitary gland in healthy dogs: A comparison with computed tomography. In Voorhout G (ed): Diagnostic imaging of the pituitary and adrenal glands in hyperadrenocorticoid dogs (dissertation). Rijksuniversiteit te Utrecht, The Netherlands, 1988 Voorhout G, Rijnberk A, Sjollema BE, et al: Nephrotomography and ultrasonography for the localization of hyperfunctioning adrenocortical tumors in dogs. In Voorhout G (ed): Diagnostic imaging of the pituitary and adrenal glands in hyperadrenocorticoid dogs (dissertation). Rijksuniversiteit te Utrecht, The Netherlands, 1988 Widmer WR, Guptill L: Imaging techniques for facilitating diagnosis of hyperadrenocorticism in dogs and cats. J Am Vet Med Assoc 206:1857-1864, 1995 Woodruff WW: Sellar and juxtasellar anatomy and pathology. In Woodruff WW (ed): Fundamentals of Neuroimaging. Philadelphia, WB Saunders, 1993, pp 335-380
Address reprint requests to Amy S. Tidwell, DVM Tufts University School of Veterinary Medicine Section of Radiology 200 Westboro Road North Grafton, MA 01536
ADRENAL DISORDERS
IMAGING OF ADRENAL GLAND DISORDERS Amy S. Tidwell, DVM, Dominique G. Penninck, DVM, and Juliette G. Besso, DEDV
Hormonal disturbances associated with adrenal gland disease often cause morphologic changes in "target" organs that may be identified radiographically. Examples include hepatomegaly and skeletal osteopenia in patients with hyperadrenocorticism and microcardia and megaesophagus in patients with hypoadrenocorticism. Such findings, however, only provide circumstantial or corroborative evidence of an adrenal endocrinopathy because they are nonspecific. Because the adrenal (and pituitary) glands are small, radiographic detection of an abnormality usually relies on a significant alteration in size, shape, or density and is limited by superimposition of overlying structures. For this reason, direct visualization of these organs has awaited the development of more sophisticated imaging techniques such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). However, abnormal hormonal secretion by the adrenal and pituitary glands is not always accompanied by morphologic changes great enough to be recognized, even with the most precise methods. Furthermore, fully established criteria have not been documented for the use of such techniques. Thus, the approach to imaging of the adrenal gland remains a significant challenge. This article examines the current role of conventional and alternate imaging techniques in the evaluation of adrenal gland dysfunction. The approach to selected adrenal gland secretory disorders such as hypercatecholaminism, hyperaldosteronism, hypoadrenocorticism, and hyperadrenocorticism is discussed.
From the Department of Surgery, Section of Radiology, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts
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REVIEW OF ADRENAL IMAGING METHODS Conventional Radiography
In animals with adrenal disease, imaging is typically performed to confirm a tentative diagnosis based on clinical and laboratory findings. Radiography has limited usefulness in this respect because visualization of the adrenal and pituitary glands is hampered by inadequate resolution and superimposition of overlying tissues. The right and left adrenal glands are small retroperitoneal structures located near the craniomedial aspect of the kidneys at the level of the last thoracic and second lumbar vertebrae, respectively. 23 The glands, however, cannot be seen with routine radiography unless enlarged or calcified. 36, 4o, 41 An enlarged left adrenal gland may appear as a soft tissue mass or be inferred if the left kidney is displaced caudally. A mass or mass effect created by an enlarged right adrenal gland is usually more difficult to identify because of its close proximity to the liver. Radiographic evaluation may be assisted using compression paddle techniques or linear tomography to relieve superimposed bowel, or angiography and intravenous urography to improve contrast of adjacent tissues. Prior to the development of CT, the pituitary gland could be evaluated indirectly using cavernous sinus venography and cerebral angiography. Pituitary tumors were suspected if displacement or deficient filling of nearby vessels was noted in the region of the hypophyseal fossa. 29 These angiographic procedures have since been supplanted by CT and MRI and are not recommended because they are invasive and poorly sensitive and specific. Despite its limitations, radiography provides useful information about the secondary effects of adrenal dysfunction as well as potentially identifying metastatic disease. Thoracic and abdominal radiographs are therefore recommended as part of the routine data base. Ultrasonography
Because it is relatively inexpensive, noninvasive, and does not require general anesthesia, ultrasonography is the most practical method of imaging the adrenal glands. However, it is highly dependent on the quality of instrumentation and requires a high level of operator skill and diligence. The procedure usually entails real-time scanning in a parasagittal, dorsal, or oblique and transverse plane of the body to depict the long and short axes of the gland, respectively. The highest frequency transducer that allows adequate penetration should be used. A 5-MHz transducer is usually required for larger dogs, although compression of the ventral abdominal wall with the transducer may allow the use of a 7.5-MHz probe in compliant patients. Most animals are scanned in dorsal recumbency, after the hair is clipped and the skin is moistened with alcohol and acoustic gel.
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The left adrenal gland is identified by first locating the cranial pole of the left kidney in the parasagittal long-axis plane, then fanning or sliding the transducer medially until the aorta is found . The left adrenal gland lies ventrolateral to the aorta and appears as a small peanut shell-shaped structure that is usually hypoechoic to surrounding retroperitoneal fat. Occasionally, an outer hypoechoic cortex can be distinguished from a hyperechoic medulla (Fig. 1). This layered appearance has been used to describe both the normal35 and hyperplastic22 gland. The right adrenal gland may be identified with the patient in dorsal recumbency but tilted to the left, by fanning medially after locating the cranial pole or hilus of the right kidney in the parasagittal long-axis plane. Once the caudal vena cava (eVC) is identified just caudal to the porta hepatis, the probe should be directed slightly laterally. Depending on the approach, the gland may not be seen in the same image as the eve and viewing the entire gland may require angling the transducer obliquely. As with the left adrenal gland, the right appears hypoechoic to surrounding fat or may have a layered appearance, but appears comma-shaped instead of peanut shell-shaped. Using a dorsal-plane right intercostal approach with the patient in left lateral recumbency, the right adrenal gland may appear as a triangular or comma-shaped structure on the near-field side of the eve. In the transverse plane, both adrenal glands appear oval and are located medial to the short axes of the kidneys. The left adrenal is located between the origin of the cranial mesenteric and left renal artery and the right adrenal just cranial to the right
Figure 1. Long-axis ultrasonogram of the left adrenal gland (between plus signs) of a normal dog. Note the peanut shell-shape and the faint layered appearance.
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renal vein; both glands are enveloped by the phrenicoabdominal arteries and veins. However, these smaller vessels may not be readily seen without the aid of color-flow Doppler techniques. If bowel gas interferes with the acoustic window, the animal should be repositioned or scanned from a different plane. Even then, one or both of the adrenal glands may not be visualized in normal patients. This is especially true for the right gland of larger dogs.18 This situation creates the dilemma of distinguishing atrophy from a nonvisualized normal adrenal gland. Other pitfalls in interpretation include variation in shape and size depending on the individual patient and the image orientation. Shape may vary from the above descriptions to include round in all planes, 35 oval, and worm-like. Normal size of the adrenal glands varies with the size of the patient, but useful internal controls have not been established. Changes in thickness (the ventrodorsal dimension perpendicular to the long-axis of the gland) appear to be more meaningful than those in length.1&-20 In recent studies, 19- 20 adrenals in normal young adult medium-sized dogs had a range of thickness from 2 to 5 mm (median, 4 mm). 19 In middle-aged to older dogs, thickness ranged from 4 to 7 mm (median, 6 mm).20 In another study of healthy dogs and those having nonendocrine disease,3 the maximum diameters were found to be up to 8.1mmand11 mm, respectively, for the right gland, and up to 7.4 mm and 10.6 mm, respectively, for the left gland. Ultrasonography also permits evaluation of other organs such as the liver, kidney, and eve for secondary effects and/ or for the presence of local or distant neoplastic spread. It also facilitates percutaneous guided biopsy. Computed Tomography
Visualization of the adrenal glands with CT is not restricted by patient size or by gas in overlying bowel. Therefore, compared to ultrasonography, CT provides a more consistent window and can be used to evaluate the pituitary gland concurrently. Veterinarians have limited access to CT, however, and its use requires general anesthesia. Thus, CT is often only used when the results of other imaging methods are indeterminate. Typically, 5-mm thick transverse CT images of the abdomen are obtained in the region of the adrenal glands. Water-soluble iodinated contrast medium may be administered intravenously to help distinguish vessels from adrenal tissue. A bolus injection of 400 to 800 mg of iodine per kilogram of body weight may be given and the adrenal scan repeated immediately. On the transverse abdominal images, the right adrenal gland is located dorsolateral to the caudal vena cava, ventral to the right diaphragmatic crus, and medial to the cranial pole of the right kidney. The left adrenal gland is ventrolateral to the aorta and psoas minor muscle and medial to the cranial pole of the left kidney. The adrenal glands appear as oval, triangular, or round soft-tissue structures depending on the CT slice location and orientation relative to
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the long axis of the gland.42 Portions of the right adrenal gland may appear bipartite.42 Orientation of each gland within the transverse plane also affects their measured width and thickness; therefore, these dimensions may not be comparable to those obtained with ultrasonography. The ventrolateral-to-dorsomedial dimension provides an estimation of the short axis of the gland. In a study of 10 healthy dogs,42 the maximum ventrolateral-to-dorsomedial dimension was 11.1 mm for the right gland and 14.6 mm for the left gland. For the pituitary region, the use of intravenous contrast medium is essential. Although transverse 2-mm thick images usually suffice, direct sagittal images of the brain may be obtained by laying the animal in lateral recumbency, gently rotating the head sideways, and tilting the CT gantry until it is in alignment with the midsagittal plane of the head. The normal CT appearance of the pituitary gland in dogs and cats has been described as slightly hyperdense compared to the thalamus and cerebral hemispheres17 and contrast-enhancing, 26• 44 because it is outside of the blood brain barrier. In a study of nine normal dogs, the pituitary gland measured 4.3 to 6 mm in height on the midsagittal image. 44 This is in agreement with a reported height of 5 mm observed in the gross unpreserved gland of adult mesaticephalic breeds. 23 Unlike the concave or flat appearance of that in humans, its dorsal border was described as convex. 44 Unfortunately, precise criteria for the normal CT appearance and size of the pituitary gland has not been determined in a large population of dogs and cats. In the authors' experience, the degree of contrast enhancement and size of the gland differ among normal individuals. Typically, the enhanced gland "fills" the hypophyseal fossa within the confines of the sella turcica. In some instances, the CT window or grayscale level must be electronically altered to help distinguish the gland from this complex of bones. On the transverse image, depending on the precise location and thickness of the CT slice, several millimeters of the gland are visible above the basisphenoid bone. The dorsal margin of the gland usually appears below or level with the cavernous sinuses on the transverse image and the dorsum sella on the midsagittal image (Fig. 2). This appearance, however, would not rule out the presence of a small tumor, thus it should be interpreted cautiously in a patient with clinical evidence of pituitary dysfunction. Magnetic R.esonance Imaging In humans, MRI of the abdomen is performed to detect and further characterize adrenal masses and to identify extraadrenal involvement. Because of overlapping results, however, the use of MRI to characterize tissues as benign or malignant has not achieved widespread acceptance. 3o, 38 Because of its superior resolution, MRI is the preferred technique for evaluation of the pituitary gland. The appearance of sellar and
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Figure 2. Pre-contrast (A) and postcontrast (B) transverse and postcontrast mid-sagittal reformatted (C) CT images of the brain of a dog with no clinical or laboratory (complete blood count, chemistry profile, and urinalysis) evidence of endocrine disease. B, A portion of the enhanced pituitary gland (arrow) is visible dorsal to the basisphenoid bone (b) and is flanked on each side by the enhanced cavernous sinuses (arrowheads). The height (dorsal to ventral dimension) of the visible portion of the gland is 2.7 mm. C, The gland (arrow) sits within the hypophyseal Iossa and is enclosed caudally by a bony projection, the dorsum sella (curved arrow), and rostrally (to the left) by a sloping ridge of bone, the tuberculum sella (arrowheads). These structures, along with the floor of the hypophyseal Iossa, are the components of the basisphenoid bone comprising the sella turcica. At postmortem, the pituitary gland was grossly normal, measuring 8 mm in length, 7 mm in width, and 4 mm in height. No histopathologic abnormalities were found.
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juxtasellar tissues in humans has been described in detail. 13• 47 Standard sequences include thin-slice (3 mm), high-resolution (256 X 256 matrix, small field of view), Tl-weighted sagittal and coronal spin-echo images before and immediately after administration of a paramagnetic contrast agent such as gadolinium-diethylenetriamine pentaacetic acid (GdDTPA, Magnevist, Berlex Laboratories, Wayne, New Jersey). 13• 47 Precontrast T2-weighted and dynamic Tl-weighted postcontrast techniques may also be performed.13 In our experience, the MRI appearance of the pituitary gland in animals mimics that of CT; that is, it is a normally enhancing structure confined to the limits of the sella turcica. Scintigraphy
Functional imaging of the adrenal glands can be achieved using iodine-labeled pharmaceuticals that have an affinity for the adrenal cortex and catecholamine-secreting tissues. 1311-68 iodomethylnorcholesterol (NP-59) and 1311- or 1231-metaiodobenzylguanidine (mlBG) are the agents of choice to evaluate the adrenal cortex and medulla in humans, respectively.Ji They are primarily used to identify or confirm abnormalities of aldosterone, cortisol, and sex-steroid secretion and to localize intra- and extraadrenal pheochromocytoma. To prevent uptake of free iodine by the thyroid gland, Lugol's solution must be administered during adrenal scintigraphy. In patients with primary hyperaldosteronism, dexamethasone may be administered to increase the specificity of NP-59 studies by suppressing the adrenocorticotropic hormone (ACTH)dependent zona fasciculata and reticularis, thus accentuating uptake into the ACTH-independent zona glomerulosa. Abnormal scintigraphic patterns of NP-59 or mIBG scans usually appear as increased unilateral, bilateral, or extradrenal uptake, depending on the disorder.Ji Use of both corticaPJ and medullary5 scintigraphy in the dog has been described. Cortical studies usually require image acquisition over the course of several days (up to 15). This disadvantage and adrenocortical scintigraphy's limited availability will likely prevent its widespread clinical use in dogs and cats. A 1231-mIBG study, however, is less time consuming, usually requiring 24 hours to complete, and should be considered to diagnose, localize, and determine the extent of pheochromocytoma or other neuroendocrine tumors in difficult cases. Scintigraphy plays a larger role in the management of respiratory distress associated with hyperadrenocorticism. 99mTechnetium (99mTc)labeled perfusion studies may be used in conjunction with thoracic radiography to diagnose pulmonary thromboembolism. Perfusion scanning uses 99 mTc tagged to small particles of albumin (99mTc-macroaggregated albumin), which is injected intravenously. The radioactive particles travel to the lung via the pulmonary arteries and are then trapped in the capillary bed. Areas of vascular occlusion due to thromboembolism therefore show deficient radioactivity. Ideally, a ventilation scan is used
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in conjunction with the perfusion scan to increase specificity. It is usually performed using a radioactive gas or an agent such as 99 mTc-labeled diethylenetriamine pentaacetic acid (DTPA) that is aerosolized by a nebulizer and then inhaled by the patient. Distribution of the radioactive aerosol in the air spaces is a measure of ventilatory function; disease processes that impair ventilation thus show deficient radioactivity on the scan. Recently, bone-seeking agents such as 99mTc-methylene diphosphonate (MDP) have been used to document diffuse pulmonary mineralization in Cushingoid dogs having normal perfusion. 6 Delayed static images are obtained of the thoracic region similar to those of a bone scan.
SELECTED SECRETORY DISORDERS Hypercatecholaminism
Pheochromocytoma is an uncommon catecholamine-secreting tumor arising from chromaffin cells of the adrenal medulla. Those located outside the gland are termed paragangliomas or extra-adrenal pheochromocytoma. The excessive vasoactive catecholamines produce hypertension, which may be paroxysmal or sustained. Imaging has a significant role in the diagnosis of this disorder because clinical signs may also be sporadic and nonspecific and laboratory findings are sometimes inconclusive. In patients with known or suspected pheochromocytoma, thoracic radiography is indicated to rule out the presence of pulmonary metastasis. Cardiac enlargement secondary to the effects of excessive catecholamine production is sometimes present. If large, a mass in the retroperitoneal space may be identified with routine abdominal radiography. The presence of ascites may indicate venous obstruction due to invasion or thrombosis of the caudal vena cava. If ultrasonography is not available, this complication can be confirmed using a caudal venacavogram. This is performed by injecting water-soluble iodinated contrast medium into the saphenous vein and obtaining sequential lateral and ventrodorsal views of the abdomen. To lessen the hemodynamic response, low osmolar contrast medium such as iohexol (Omnipaque, Winthrop Pharmaceuticals, New York, NY) or iopamidol (Isovue, Squibb Diagnostics, Princeton, NJ) is recommended. Obstruction or displacement of contrast media flow or a filling defect is observed with invasion or thrombosis of the caudal vena cava. Likewise, a nonselective aortogram obtained after the injection of contrast medium into the cephalic or jugular vein may help identify invasion of the aorta by a left-sided mass. Unlike routine radiography, ultrasonography, CT, and MRI allow direct visualization of the pheochromocytoma and often detect local or distant spread. mIBG scintigraphy localizes the tumor by depicting abnormal function of the adrenal medulla. In humans, MRI and/or
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mlBG are typically used in problem situations27 in which pheochromocytoma is suspected but is not found with ultrasonography or CT, or when a mass needs further characterization. Use of MRI may help to distinguish pheochromocytoma from other tumors by its characteristically high signal intensity on T2-weighted images. 27• 30 Magnetic resonance imaging also appears to be more sensitive than CT for the detection of small or extraadrenal pheochromocytoma and does not require the use of iodinated contrast medium, a contraindication in human patients with this disease. 30 mlBG scintigraphy likewise distinguishes pheochromocytoma from a cortical mass and allows screening of the entire body for an extraadrenal source or metastasis. 27• 31 In animals, ultrasonography should be selected preferentially over CT or MRI to avoid the use of anesthesia in these hemodynamically unstable patients. As in humans, MRI or mlBG scintigraphy may be useful in problem cases. In a retrospective study of 26 dogs at the Tufts University School of Veterinary Medicine (TUSVM),8 nine pheochromocytomas tended to be well-defined unilateral mass lesions having a wide range of size and variable echotexture. Consistent with previous descriptions,37 five tumors were quite large (up to 7 X 3.8 cm). However, four tumors were less than 2 cm in maximum width. In fact, one appeared as a nodule or a focal increase in width measuring 1.4 cm. Tumor echogenicity compared to the ipsilateral renal cortex was hypoechoic, isoechoic, hyperechoic, and mixed. Occasionally anechoic, farenhancing regions were found within the mass as part of a mixed pattern, likely representing foci of necrosis or hemorrhage. In one dog, the tumor appeared as an amorphous 4 X 3 cm mass having poorly defined borders. Other features included the presence of abdominal effusion secondary to tumor rupture, local invasion and distant tumor thrombus of the caudal vena cava, and liver metastasis. Additional pathologic changes found at necropsy in the abdomen of dogs with pheochromocytoma9 include the presence of bilateral involvement; compression or mural invasion of the aorta, renal and adrenal vessels, and hepatic vein; invasion of the vertebrae with compression of the spinal cord; and metastasis to the spleen, contralateral adrenal gland, ovary, and diaphragm. These abnormalities may be discovered during an ultrasound examination. A scan of the entire abdomen is, therefore, always indicated. The ultrasonographic features described above do not rule out the possibility of other adrenal neoplasms. If pheochromocytoma is clinically suspected, however, biopsy of the adrenal gland should not be performed because it may produce a sudden hypertensive episode that is sometimes fatal. In humans, urine catecholamines and vanillylmandelic acid levels are obtained before every adrenal gland biopsy, even if the clinical signs of pheochromocytoma are absent. 15 If these tests are positive, the biopsy is not performed; if equivocal, the blocking agent phentolamine and an intravenous catheter are made available at the time of biopsy.
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Hyperaldosteronism
Overproduction of aldosterone by the zona glomerulosa of the adrenal cortex leads to a recognized syndrome of electrolyte disturbances in humans, 27 cats, 1' 12 and dogs. 16 In approximately 70% of human patients, a solitary aldosterone-producing adenoma is present. 27 Otherwise, it is idiopathic and associated with bilateral adrenal hyperplasia. 27 Because the pathologic changes associated with small adenomas or bilateral hyperplasia may not be detected with anatomic imaging such as CT,31 functional imaging using NP-59 scintigraphy31 or selective adrenal vein sampling for aldosterone levels27, 30 may be required. Hyperaldosteronism in animals was originally reported in a cat having a large (4 x 5 X 3 cm) adrenal cortical adenocarcinoma on postmortem examination. 12 The contralateral adrenal gland was not found. An adenoma and two adenocarcinomas were detected during abdominal surgery in three dogs with this syndrome. 16 Imaging was not mentioned as part of the diagnostic workup in these animals. At TUSVM, we have detected small adrenal masses ultrasonographically in two clinically affected cats, one having a surgical excision biopsy of an adrenal adenoma of zona glomerulosa origin, the other having a postmortem diagnosis of adenocarcinoma. In both cases, a small (9- to 12-mm), rounded hypoechoic mass of the right adrenal gland was found. The only difference between the two tumors was preservation of the normal caudal pole of the adrenal gland in the patient with the adenoma (Fig. 3). Because of its relative simplicity, abdominal ultrasonography should be considered in animal patients having clinical signs characteristic of hyperaldosteronism. Thoracic radiographs and echocardiography may also be warranted to identify metastasis and hypertension-induced cardiac enlargement. Hypoadrenocorticism
To our knowledge, no characteristic imaging features of primary hypoadrenocorticism occur in animals other than the well-documented secondary effects. In imaging studies in humans, the adrenals are often undetected or diminished in size.27 Similar findings in animals with idiopathic adrenal insufficiency would seem likely, because bilateral adrenal gland atrophy with fibrosis is noted histopathologically. 21 Other less-common causes of hypoadrenocorticism include infection, hemorrhagic infarction, metastatic neoplasia, amyloidosis, and trauma. 4, 21 Although its value in animals with uncomplicated adrenal insufficiency has yet to be determined, imaging of the adrenal glands may prove useful to rule out these unusual causes. Thoracic and abdominal radiographs may document the secondary effects of hypoadrenocorticism such as microcardia, pulmonary hypoperfusion, and megaesophagus. After treatment, resolution of these ab-
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Figure 3. Long-axis ultrasonogram of the right adrenal gland (between plus signs) in a cat with hyperaldosteronism. The cranial pole is focally enlarged by a round hypoechoic nodule measuring 9 mm in diameter. The architecture of the caudal pole is preserved. Length of the entire gland is 15 mm. Diagnosis was adenoma of zona glomerulosa origin. eve caudal vena cava.
normalities may be illustrated with follow-up radiography. Because these findings are subjective and nonspecific, they should only be considered supportive evidence. Hyperadrenocorticism
Imaging may contribute to the initial diagnosis of hyperadrenocorticism or may differentiate pituitary-dependent hyperplasia from an adrenal tumor by depicting the systemic effects of excessive cortisol or by revealing an adrenal or pituitary mass. This information can then be used to direct medical, surgical, or radiation therapy management. Radiographic features of hyperadrenocorticism include a pendulous abdomen, hepatomegaly, distended urinary bladder, skeletal osteoporosis, and dystrophic calcification of soft tissues. The latter typically appears as ill-defined mineral opacities within the skin (calcinosis cutis) and occasionally of the renal pelvis, liver, gastric mucosa, and branches of the aorta. 16 Calcification of the tracheal rings and bronchi may also occur but is nonspecific. Diffuse pulmonary mineralization may cause a mild to moderate generalized increase in interstitial markings. 6 The interstitial pattern may be barely detectable or may mimic pulmonary edema.6
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Although often seemingly mild, this pattern should not be dismissed as clinically insignificant because diffuse mineralization may impair adequate diffusion of gases leading to respiratory distress and/ or hypoxemia despite normal perfusion. 6 Respiratory compromise may also occur in animals with hyperadrenocorticism due to pulmonary thromboembolism (PTE). Although PTE may result in pulmonary consolidation and pleural effusion from lung infarction, blunted pulmonary arteries, or regions of oligemia, thoracic radiographs are sometimes normal. Scintigraphy may be used in these circumstances to help distinguish PTE from diffuse mineralization. Pulmonary thromboembolism results in hypoxemia because areas of normal ventilation are not adequately perfused, preventing exchange of oxygen and carbon dioxide between alveoli and pulmonary capillaries. Thus, ventilation to this region of the lung is "wasted" and a ventilation/ perfusion mismatch occurs. The approach to diagnosis of PTE is somewhat complicated and controversial. If all imaging modalities are available, combined ventilation and perfusion scintigraphy is ideal. However, perfusion scintigraphy alone, if performed in conjunction with normal thoracic radiographs, is still useful. Perfusion scanning usually eliminates the diagnosis of PTE if results are negative (i.e., a normal scan). In this circumstance, bone scintigraphy using 99 mTc-methylene qiphosphonate may demonstrate abnormal generalized isotope uptaljce within the lungs, 6 implicating diffuse mineralization, not PTE, as tM source of the respiratory di.stress. When perfusion deficits are found but ventilation scintigraphy is not available, normal ventilation is often presumed if thoracic radiographs are normal. In other words, if a lobar perfusion deficit is found in a region of lung that appears radiographically normal, a mismatch is presumed and a diagnosis of PTE is made. If infiltrates are present in areas of perfusion deficits, however, this supposition should not be made because pneumonia or other primary ventilatory disturbances (causing reflex vasoconstriction) are still serious considerations. Angiography after selective catheterization of the pulmonary arteries is then required to confirm PTE. If positive, intraluminal filling defects or abrupt vessel cut-off due to thrombi is present. Selective angiography, however, is an invasive procedure having risks that may outweigh the benefits in some patients. Once a diagnosis of hyperadrenocorticism is made, pituitary-dependent hyperplasia (PDH) must be distinguished from an adrenal cortical tumor (ACT) to institute proper treatment. A high-dose dexamethasone test does not suppress cortisol levels in every dog with PDH, and plasma ACTH concentrations in the two groups of dogs have some degree of overlap. 16 Thus, making a distinction between PDH and ACT when laboratory tests are indeterminate becomes a primary goal of imaging. Routine radiography may be used to screen for adrenal masses or metastasis in dogs with laboratory evidence of hyperadrenocorticism. In one study,36 50% of ACT had some degree of calcification; all of these tumors were visible on abdominal radiographs. The presence of calcifi-
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cation could not reliably distinguish carcinoma from adenoma, however. 36 Adrenal gland enlargement without calcification may also permit detection. A study comparing survey radiographs with CT40' 41 concluded that visualization of an adrenal gland mass with a diameter of 20 mm (based on CT measurement) on survey radiographs is possible but is influenced by the size of the dog, whereas larger tumors may be visualized regardless of the size of the dog. Although intravenous urography combined with linear tomography improves the sensitivity of radiography, 43, 45 it requires anesthesia, intravenous contrast media injection, and specialized equipment, making it less practical. Ultrasonography, once believed to have limited usefulness in adrenal gland evaluation, has now become an essential part of the diagnostic workup of hyperadrenocorticism in animals.3, a, 16, 1s-20, 22, 24, 35, 37, 39, 42, 43, 45, 46 Ultrasonography may support a diagnosis of hyperadrenocorticism by detecting . abnormal adrenal glands or systemic effects such as steroid hepatopathy, soft tissue mineralization, and metastasis, but its greatest role appears to be distinguishing PDH from ACT. Occasionally, a poor acoustic window prevents adequate evaluation of the glands, however. In this circumstance, interpretation of the findings rests on the confidence level of the sonographer. This is especially true when an adrenal gland is not seen; the sonographer must decide if the gland is truly atrophied or artifactually absent. During a retrospective study at TUSVM of 26 dogs with histopathologically confirmed adrenal lesions,8 ultrasonographic features of hyperplasia, adenoma, and adenocarcinoma in 16 dogs were identified and the following deductions were made. A hyperplastic adrenal gland may appear normal in size and shape or enlarged (increased in thickness or "plump") with a normal shape or may have a focal enlargement or "nodule." Very infrequently, hyperplasia may appear as a rounded mass. In this study, all of the adenocarcinomas appeared either as a rounded mass (diameter usually greater than 2 cm) or as a nodule (diameter usually less than 2 cm) and all of the adenomas appeared as a nodule; therefore, the absence of these features should most often exclude ACT. Atrophy of the adrenal cortex secondary to a contralateral functional tumor may not be apparent ultrasonographically. Therefore, the presence of a normal-appearing gland opposite a mass should not lower suspicion of ACT. Adenocarcinoma cannot be distinguished from other malignant tumors such as metastasis (Fig. 4) or pheochromocytoma without a biopsy. Identification of lesions in multiple organs may raise suspicion of malignancy, but again requires biopsy confirmation. Although vascular invasion and thrombosis point to malignancy, thrombosis secondary to hypercoagulability may be detected with PDH. Bilateral lesions are most often seen with hyperplasia, but not exclusively. Concurrent ACT and pheochromocytoma have been reported in the dog, as have concurrent PDH and ACT. 16• In our opinion, CT plays its greatest role in dogs with confirmed hyperadrenocorticism when the sonographer has a low level of confi-
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Figure 4. Long-axis ultrasonogram of the left adrenal gland (between plus signs) in a dog with bilateral adrenal gland metastasis from a pulmonary adenocarcinoma. As noted with some primary adenocarcinomas, the adrenal gland maintains its normal shape except at the cranial pole, where it is thickened (arrows). The cranial aspect of the gland also appears hyperechoic to the caudal aspect. The largest dimensions of the gland were 33 mm in length and 11 mm in thickness.
dence in the ultrasound exam. Unless severely atrophied or absent, the adrenal glands should be consistently visualized on a CT image. 2• 14• 42• 43 As a general rule, if a unilateral rounded adrenal mass or nodule is absent, ACT is unlikely to be present. As with ultrasonography, a nodule may indicate either hyperplasia, ACT, or an (incidental) nonfunctional tumor. Computed tomography does not allow distinction of benign and malignant tumors, although current research in humans indicates that precontrast CT attenuation values (Hounsfield units) may be characteristically lower for adenomas than for nonadenomas. 28 Invasion of adjacent vessels by a mass may be detected with CT, especially after contrast media injection. However, if the mass merely touches the vessel, the presence of invasion, adhesion, or simple abutting cannot be predicted. Computed tomography may also be performed to evaluate the pituitary gland as an aid in the diagnosis of PDH. However, CT of the pituitary gland should not be the sole means of diagnosing PDH, because ACTH-secreting tumors may be microscopic or within the range of normal. Furthermore, specific criteria for the normal CT appearance based on a large population of dogs and cats has not been determined. Until this is done, results may be prone to misinterpretation. Likewise, although an obvious enhancing mass (i.e., one that clearly exceeds the limits of the sella turcica) most likely represents a pituitary adenoma or
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adenocarcinoma, one must be aware that not all are secretory32 and occasionally tumors such as meningioma arising from the calvarial floor may mimic a pituitary mass. In dogs with confirmed PDH and neurologic signs, alternative treatment methods such as radiation therapy or, less commonly, surgical excision of the pituitary gland should be considered.to, 32 While CT is certainly indicated in dogs with neurologic signs compatible with a compressive pituitary mass, whether CT should be performed in dogs without neurologic signs is less clear. The argument in favor of CT is that the absence of neurologic signs does not rule out a large pituitary mass.to, 25• 32• 34 Because neurologic signs may eventually develop, radiation therapy may be warranted. Arguments against performing CT in all dogs with PDH are related to its cost, relative inaccessibility, and anesthesia requirements. A thorough neurologic exam performed every few months during medical treatment may suffice. 25• 34 Once neurologic signs develop, however, CT should be performed and radiation therapy considered.25• 32• 34 The role of MRI in the diagnostic evaluation of hyperadrenocorticism is not clearly defined. Because of its limited availability relative to other techniques, MRI of the adrenal glands in animals has not achieved widespread use. Because of its superior resolution, the use of MRI to evaluate the pituitary gland seems to be a logical alternative to CT in animals with PDH. Before this is feasible, however, the normal appearance of the pituitary gland must be established in a large number of dogs and cats. In humans, the pituitary gland is normally contrast enhancing and has a vertical dimension ranging from 5 to 12 mm, depending on the age and hormonal status of the individual.1 3• 47 In our experience, the MRI appearance of the pituitary gland of dogs seems to follow that of humans, except for the relatively smaller size. Until detailed MRI studies of the normal sellar and parasellar tissues in the dog are completed, we recommend following the criteria described for CT; that is, the normal enhanced pituitary gland should reside within the confines of the sella turcica on the midsagittal view and should not rise above the level of the cavernous sinuses on the transverse view. In the future, MRI may play an important role in the management of and treatment planning for animals with PDH due to a pituitary adenoma or adenocarcinoma. As with the normal gland, the MRI manifestations of these lesions require further documentation. In humans, a pituitary tumor exceeding the normal limits of size (greater than 1 cm in height or "macrotumor") is generally homogenously enhancing47 and is a candidate for nonmedical therapy due to compression of suprasellar tissues. A "microtumor" is within the range of normal pituitary size (less than 1 cm in height) and often appears as a focal hypointensity relative to the rest of the gland on immediate postcontrast Tl-weighted images.47 Because the pituitary gland in dogs and cats does not normally achieve a size of 1 cm, prior use of this classification scheme in animals is merely arbitrary and should be reconsidered. Although speculating that MRI may eventually establish a threshold (based on tumor size)
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below which neurologic signs will not develop is tempting, preliminary studies using MRI7' 11 have shown that significant overlap in tumor size exists between dogs with and without neurologic signs. Until more information is gathered on the growth patterns of these tumors and their relationship to surrounding brain structures, criteria based solely on tumor size will most likely continue to be unrewarding. CONCLUSION
When evaluating an animal with suspected adrenal gland disease, the clinician must have a clear appreciation of the role of imaging in order to use it appropriately. In this article, we have attempted to illustrate the strengths and limitations of several imaging modalities for the evaluation of four adrenal gland disorders. Although imaging characteristics for each disorder are described, significant overlap exists between normal and abnormal and between the various types of disease processes. For this reason, imaging should be used to complement, not replace, clinical and laboratory evaluation. Likewise, future investigation should concentrate on the ability to image not only morphologic but also functional and subgross alterations. References 1. Ahn A: Hyperaldosteronisrn in cats. Sernin Vet Med Surg (Small Anirn) 9:153-157, 1994
2. Bailey MQ: Use of x-ray-cornputed tomography as an aid in localization of adrenal masses in the dog. J Arn Vet Med Assoc 188:1046--1049, 1986 3. Barthez PY, Nyland TG, Feldman EC: Ultrasonographic evaluation of the adrenal glands in dogs. J Arn.Vet Med Assoc 207:1180-1183, 1995 4. Berger SL, Reed JR: Traumatically induced hypoadrenocorticisrn in a cat. J Arn Anirn Hosp Assoc 29:337-339, 1993 5. Berry CR, Wright KN, Breitschwerdt EB, et al: Use of 123Iodine rnetaiodobenzylguanidine scintigraphy for the diagnosis of a pheochrornocytorna in a dog. Vet Radio! Ultrasound 34:52-55, 1993 6. Berry CR, Ackerman N, Monce K: Pulmonary mineralization in four dogs with Cushing's syndrome. Vet Radio! Ultrasound 35:10-16, 1994 7. Bertoy EH, Feldman EC, Nelson RW, et al: Magnetic resonance imaging of the brain in dogs with recently diagnosed but untreated pituitary-dependent hyperadrenocorticisrn. J Arn Vet Med Assoc 206:651-656, 1995 8. Besso JG, Penninck DG, Gliatto JM: Ultrasonographic evaluation of adrenal lesions in dogs: A retrospective study of 26 dogs. Radio! Ultrasound, in press 9. Bouyad H, Feeney DA, Caywood DD, et al: Pheochrornocytorna in dogs: 13 cases (1980-1985). J Arn Vet Med Assoc 191:1610-1615, 1987 10. Duesberg CA, Bertoy EH, Feldman EC: Diagnosis and treatment of rnacroturnors in dogs with pituitary-dependent hyperadrenocorticisrn. In Bonagura JD (ed): Current Veterinary Therapy XII. Philadelphia, WB Saunders, 1995, pp 351-355 11. Duesberg CA, Feldman EC, Nelson RW, et al: Magnetic resonance imaging for diagnosis of pituitary rnacroturnors in dogs. J Arn Vet Med Assoc 206:657-662, 1995 12. Eger CE, Robinson WF, Huxtable CRR: Primary aldosteronisrn (Conn's syndrome) in a cat: A case report and review of comparative aspects. J Small Anirn Pract 24:293-307, 1983
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13. Elster AD: Modem imaging of the pituitary. Radiology 187:1-14, 1993 14. Emms SG, Wortman JA, Johnston DE, et al: Evaluation of canine hyperadrenocorticism using computed tomography. J Am Vet Med Assoc 189:432-439, 1986 15. Feld R: Controversial issues in ultrasound-guided abdominal biopsy (course notes). 40th Annual American Institute of Ultrasound in Medicine Convention, New York, 1996 16. Feldman EC: Hyperadrenocorticism. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders, 1995 pp 1538-1578 16a. Feldman EC, Nelson RW: Hyperadrenocorticism (Cushing's syndrome). In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, ed 2. Philadelphia, WB Saunders, 1996, pp 187-265 17. Fike JR, LeCouteur RA, Cann CE: Anatomy of the canine brain using high resolution computed tomography. Vet Radio) 22:236--243, 1981 18. Grooters AM, Biller OS, Miyabayashi T, et al: Evaluation of routine abdominal ultrasonography as a technique for imaging the canine adrenal glands. J Am Anim Hosp Assoc 38:457-462, 1994 19. Grooters AM, Biller OS, Merryman J: Ultrasonographic parameters of normal canine adrenal glands: Comparison to necropsy findings. Vet Radio) Ultrasound 36:126-130, 1995 20. Grooters AM, Biller OS, Theisen SK, et al: Ultrasonographic characteristics of the adrenal glands in dogs with pituitary-dependent hyperadrenocorticism: Comparison with normal dogs. J Vet Intern Med 10:110--115, 1996 21. Hardy RM: Hypoadrenal gland disease. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders, 1995 pp 1579-1592 22. Homco LO: Adrenal glands. In Green RW (ed): Small Animal Ultrasound. Philadelphia, Lippincott-Raven, 1996, pp 211-226 23. Hullinger RL: The endocrine system. In Evans HE, Christensen GC (eds): Miller's Anatomy of the Dog, ed 2. Philadelphia, WB Saunders, 1979, pp 602--631 24. Kantrowitz BM, Nyland TG, Feldman EC: Adrenal ultrasonography in the dog. Vet Radio) 27:91-96, 1986 25. Kipperman BS, Feldman EC, Dybdal NO, et al: Pituitary tumor size, neurologic signs, and relation to endocrine test results in dogs with pituitary-dependent hyperadrenocorticism: 43 cases (1980--1990). J Am Vet Med Assoc 201:762-767, 1992 26. Kornegay JN: Imaging brain neoplasms: Computed tomography and magnetic resonance imaging. Vet Med Report 2:372-390, 1990 27. Korobkin M, Francis IR: Adrenal imaging. Semin Ultrasound CT MR 16:317-330, 1995 28. Korobkin M, Brodeur FJ, Yutzy GG, et al: Differentiation of adrenal adenomas from nonadenomas using CT attenuation values. AJR Am J Roentgenol 166:531536, 1996 29. Lee R, Griffiths IR: A comparison of cerebral arteriography and cavernous sinus venography in the dog. J Small Anim Pract 13:225-238, 1972 30. Lubat E, Weinreb JC: Magnetic resonance imaging of the kidneys and adrenals. Top Magn Reson Imaging 2:17-36, 1990 31 . Malinoff HL, Gross MD, Shapiro B: Adrenal gland. In Early PJ, Sodee DB (eds): Principles and Practice of Nuclear Medicine, ed 2. St. Louis, Mosby-Year Book, 1995, pp 652...(,77 32. Mauldin GN, Burk RL: The use of diagnostic computerized tomography and radiation therapy in canine and feline hyperadrenocorticism. Problems Vet Med 2:557-564, 1990 33. Mulnix JA, Van den Brom WE, Lubberink AAME, et al: Gamma camera imaging of bilateral adrenocortical hyperplasia and adrenal tumors in the dog. Am J Vet Res 37:1467-1471, 1976 34. Nelson RW, Ihle SL, Feldman EC: Pituitary macroadenomas and macroadenocarcinomas in dogs treated with mitotane for pituitary-dependent hyperadrenocorticism: 13 cases (1981-1986). J Am Vet Med Assoc 194:1612-1617, 1989 35. Nyland TG, Mattoon JS, Wisner ER: Ultrasonography of the urinary tract and adrenal glands. In Nyland TG, Mattoon JS (eds): Veterinary Diagnostic Ultrasound. Philadelphia, WB Saunders, 1995, pp 95-124 36. Penninck DG, Feldman EC, Nyland TG: Radiographic features of canine hyperadreno-
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Address reprint requests to Amy S. Tidwell, DVM Tufts University School of Veterinary Medicine Section of Radiology 200 Westboro Road North Grafton, MA 01536