CURRENT APPROACHES TO IMAGING OF THE SELLAR REGION AND PITUITARY

ADVANCES IN PITUITARY TUMOR THERAPY

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CURRENT APPROACHES TO IMAGING OF THE SELLAR REGION AND PITUITARY Michelle J. Naidich, MD, and Eric J. Russell, MD

The articles on imaging of the pituitary gland that have been published in issues of the Endocrinology and Metabolism Clinics during the last 21 years provide a history lesson on the progression of technologic advances in radiology. Early issues outlined the multitude of findings seen in pituitary disease on plain skull films and conventional t ~ m o g r a p h y With . ~ ~ the development of CT, one could directly see the pituitary gland rather than drawing conclusions based on abnormalities of the surrounding structures. CT findings of various disease processes involving the pituitary were described in subsequent editions.&,lo* In the most recent issue on the pituitary,I0' the potential of MR imaging of the pituitary gland was discussed. Since that publication in 1987, a large body of work has detailed the imaging of normal and pathologic disease states of the pituitary gland. Despite this experience accumulated during the last 10 years, controversies still remain. TECHNIQUES AND NORMAL APPEARANCE

Although MR imaging is considered by many investigators to be the first choice for imaging of the pituitary, there is still a role for CT, particularly in patients with contraindications to MR imaging. Typically, CT technique consists of contiguous 1-mm images in the transverse axial and coronal planes. Sagittal reconstructions can be performed using the data acquired from either of these two scan sequences. On CT, the sella turcica is seen as a bony depression within the sphenoid bone. The anterior margin (tuberculum sellae), the posterior margin (dorsum sellae), and the superolateral angles of the dorsum (posterior clinoid

From the Division of Neuroradiology, Department of Radiology, Northwestern University Medical School, Chicago, Illinois

ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA

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VOLUME 28 NUMBER 1 * MARCH 1999

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Figure 1. Normal CT appearance of the pituitary gland. A postcontrast coronal image through the sella demonstrates the normal enhancing pituitary gland centrally (open black arrows) with the enhancing cavernous sinus laterally (open white arrows). The infundibulum (solid arrow) arises from the midaspect of the gland and extends superiorly. Bone landmarks include the sphenoid sinus (s) and the anterior clinoids (c).

processes) are well-defined. The anterior clinoids are posterior bony projections that arise from the posteromedial aspect of the lesser wing of the sphenoid bone, bordering the sella bilaterally. The pituitary gland (within the sella) has an attenuation (or CT density) equivalent to that of gray matter. The diaphragma sellae, which separates the sellar contents from the superiorly located cranial cavity, is not well-delineated on CT. The pituitary stalk, or infundibulum, is seen on CT extending from the superior central aspect of the pituitary gland through the diaphragma to the hypothalamus below the infundibular recess of the third ventricle. Following the administration of iodinated contrast, the normal gland, which has no vascular blood-brain barrier, appears as a homogenously enhancing structure partly filling the sella (Fig. 1).The adjacent enhanced cavernous sinus frequently is inseparable from the gland. Occasionally, small nonenhancing structures are seen in the lateral dural reflection of the cavernous sinus, corresponding to the traversing cranial nerves 111, IV,and VL90 The standard protocol for evaluating the pituitary gland with MR imaging consists of precontrast thin (1 to 2 mm) slices through the sella in both the sagittal and coronal planes using a sequence with a short time of repetition (TR) and short time of echo (TE),which produces T1-weighted images. The patient usually then receives an intravenous contrast agent containing gadolinium. Gadolinium-based media are paramagnetic agents that shorten T1 relaxation times, resulting in normal glandular enhancement. Repeat sagittal and coronal T1 sequences are performed postinfusion. On precontrast T1 images, the pituitary gland appears as a crescentic area of soft tissue along the floor of the sella (Fig. 2A, C). The majority of the gland visuaLized is the anterior lobe, and its signal is equivalent to that of the gray matter?7 The smaller posterior lobe usually appears as a focal area of high signal (short T1) at the posterior aspect of the sella, best seen on thin midline sagittal scans. The infundibulum or pituitary stalk extends from the midaspect of the top of the gland, toward the median eminence of the hypothalamus, coursing through the suprasellar cistern.

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Figure 2. Magnetic resonance imaging demonstrates the normal pituitary gland and surrounding structures. A, A noncontrast T1-weighted sagittal midline image through the sella demonstrates the normal appearance of the anterior lobe of the pituitary gland (open arrow) and the bright spot of the posterior pituitaty lobe (curved arrow). Arising from the midaspect of the gland is the infundibulum (narrow solid arrow). Other structures seen include the pons (P), sphenoid sinus (S),clivus (C), third ventricle (V), and optic chiasm (Heavy solid arrow). B, A postcontrast T1-weighted sagittal midline image demonstrates the same structures. Both the anterior (open arrow) and posterior (curved solid arrow) lobes are of

higher signal secondary to interval enhancement. Illustration continued on following page

Other normal suprasellar structures, such as the optic chiasm and optic nerves, third ventricle, and mamillary bodies, are seen as well. On coronal images, the pituitary gland has a broad rectangular contour. The infundibulum is seen extending vertically from the midportion of the gland to the hypothalamus. The infundibulum is slightly wider at the level of the hypothalamus and gradually tapers in width as it joins the gland. The width of the normal infundibulum should not exceed 4 mm. The superior dural reflection, the diaphragma sellae, may also appear as a band of low-signal intensity in some cases.21If the parameters of the imaging sequence are altered such that there is a long TR and long TE, a T2-weighted image is produced. The anterior lobe again is isointense to gray matter, but the posterior lobe is lower in signal relative to its appearance on T1-weighted images. T2-weighted images are not generally used in the routine evaluation of the pituitary gland, although they are useful for the detection of cystic changes and hemorrhage. On either side of the gland lies the cavernous sinus, a network of venous spaces enclosing the cavernous segment of the internal carotid artery (Fig. 3). The lateral dural margin of the cavernous sinus is a thin linear structure of low signal. The medial dural reflection, which separates the cavernous sinus from the adjacent pituitary gland, is not reliably seen. The precontrast signal of much of the cavernous sinus is equivalent to that of the adjacent brain.83With T1weighted spin echo imaging, rapidly flowing blood appears as absence of signal (flow void). Consequently, the intracavernous portion of the internal carotid

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Figure 2 (Continued). C, A noncontrast T1-weighted coronal image through the sella demonstrates the rectangular-shaped anterior lobe (open arrow) with the infundibulum extending superiorly (narrow solid arrow). The cavernous sinus (small paired arrows) lies on either side of the gland. The intracavernous portion of the internal carotid artery appears as a flow void within the cavernous sinus (curved arrows). Also seen are the sphenoid sinus (S) and optic chiasm (Heavy solid arrow). 0,A postcontrast T1-weighted coronal image shows enhancement of the pituitary gland (open arrow) and the more densely enhanced cavernous sinus (small paired arrows). Note that the intracavernous portion of the internal carotid artery remains black (curved arrows) because of the rapidly flowing blood.

artery is well-seen as a flow void, lying centrally within each cavernous sinus. Nonenhancing regions along the lateral wall of the cavernous sinus are the cranial nerves III, IV, and VI, which course through this regon toward the superior orbital fissure. The cranial nerves maintain a constant anatomic relationship to the cavernous sinus dura and to each other. The oculomotor (third cranial nerve) is supemlateral, the troddear (fourth cranial nerve) is lateral, and the ophthalmic division of the trigeminal nerve (fifth cranial nerve) is inferolateral. The maxillary division of V (V2)is inferior in position, located just below the Cavernous sinus as it extends to the foramen rotundurn. The sixth cranial

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Figure 3. Coronal diagram of the cavernous sinus. The pituitary gland (P) is central within the sella, with the sphenoid sinus (S) inferior and the cavernous sinus laterally. The intracavernous portion of the internal carotid artery (A) lies within the cavernous sinus along with the sixth cranial nerve (6). The third (3),fourth (4) and first two divisions of the fifth (V1 , V2) cranial nerves maintain a constant relationship with each other as they course through

the cavernous sinus dura. Anteriorly, V2 courses more inferiorily to enter the foramen rotundum. The supraclinoid portion of the internal carotid artery (a) also is illustrated.

nerve is unique because it does not travel within the lateral dural margin of the cavernous sinus but more medially within the cavernous sinus near the carotid artery. The sixth cranial nerve is less frequently seen on MR imaging because of its location and small size.2O At the posterior aspect of the cavernous sinus is Meckel's cave. This is a dural diverticulum extending from the posterior fossa through a gap in the temporal bone called the poms trigeminus to lie in the posteromedial portion of the middle cranial fossa. Meckel's cave contains cerebrospinal fluid (CSF) and the efferent branches of the Gasserian ganglion. The third division (mandibular) of the trigeminal nerve exits from Meckel's cave to course inferiorly through the foramen ovale, whereas the remaining two divisions pass more superiorly in relation to the cavernous sinus. When seen on imaging, Meckel's cave has a signal similar to CSF, although high-resolution, thin-section MR images can delineate the smaller efferent branches of the fifth cranial nerve.43 Images performed following the administration of contrast show homogenous enhancement of the gland and the adjacent cavernous sinus (Fig. 2B, D). Because of rapid blood flow, the carotid artery tends to remain black. The pattern and sequence of enhancement of the various portions of pituitary gland mirror the circulation. The arterial supply to the neurohypophysis is the inferior hypophyseal artery, a branch of the cavernous portion of the internal carotid artery. The superior hypophyseal artery arises more distally from the supraclinoid portion of the internal carotid artery. The superior hypophyseal artery supplies the median eminence and most of the infundibulum; branches from this vessel create the primary bed of the hypophyseal portal system. The portal veins run along the infundibulum and terminate in the sinusoids of the secondary capillary bed. The adenohypophysis receives its blood supply from the portal system. The temporal sequence of enhancement follows this pattern of arterial supply, with the earliest enhancement seen in the posterior lobe. Next, there is enhance-

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ment of the median eminence and the infundibulum. Finally, the anterior lobe begins to enhance in an orderly fashion, starting at the junction of the anterior lobe with the infundibulum and then extending to the more peripheral portions of the 95 Dynamic imaging is a technique whereby the acquisition of images occurs on a fast time scale synchronous with the microcirculation. Bonneville and co-~orkers'~ first described this technique for CT scanning. They noted that approximately 10 seconds after enhancement of the supraclinoid carotid arteries, focal enhancement could also be detected in a 3- to 4-mm region in the midanterior aspect of the pituitary gland just ventral to the stalk. This was thought to represent the secondary capillary bed of the hypophyseal portal system, and its visualization was called the "tuft." Displacement or compression of the tuft (the "tuft sign") was described as a secondary marker for pituitary pathology. Subsequently, several other investigators have described dynamic sequential enhancement of the pituitary on M R imaging.76,95* lffi As the capabilities of M R scanners have improved, the time required to acquire images has decreased such that the temporal resolution is now on the order of seconds. With each improvement, adjustments have been made to assigned time values for normal enhancement. Currently, it is believed that the infundibulum enhances approximately 4 seconds following enhancement of the posterior lobe; 10 to 15 seconds later, there is enhancement of the anterior lobe'" (Fig. 4).Any alteration in this sequence of enhancement may signify underlying pathology. NORMAL VARIATIONS OF THE ANTERIOR LOBE

The shape, size, and signal of the normal anterior lobe vary with the age, sex, and physiologic state of an individual. The pituitary gland of the neonate has a convex superior margin. Unlike the pituitary in an adult, the anterior lobe in the neonate has homogenously high signal on T1-weighted precontrast MR images (Fig. 5). This appearance reflects intense hormonal activity that begins during fetal life and that continues into the neonatal period.19,24, lo2By 2 months of age, the convexity of the superior margin of the gland flattens out, the signal intensity of the anterior lobe decreases, and the anterior lobe can now be clearly discriminated from the bright spot of the posterior lobe. The gland may have a slightly concave superior margin throughout childhood but is not expected to reach a height (measured on the midline sagittal image) of greater than 6 mm. The pituitary stalk diameter is approximately 2 mm and should never exceed the diameter of the basilar arteryY At puberty, the gland increases in size, reflecting a period of high hormonal activity. At this time, gender variation is noted. The height of the gland in males reaches a maximum of 8 mm. In females, the gland may become markedly convex in contour and reach 10 mm in height.2& 45, *l Hormonal activity at puberty is not as intense as in the neonatal period, and there is no concurrent increase in signal of the gland as seen in neonates.24In central precocious puberty, the gland increases in height and obtains the convex superior border seen at the time of normal puberty. In a child with premature secondary sex characteristics, this appearance of the gland indicates a problem with the hypothalamic pituitary axis and may help exclude peripheral gonadohpin-independent causes.% Following adolescence, the pituitary slowly decreases in size. With the exception of pregnancy, the gland rrmains relatively stable in appearance for most of adult life. There is gradual involution of the gland starting at appmxi-

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Figure 4. Dynamic enhancement of a normal pituitary gland. Three selected sagittal MR images (A). posterior lobe, (B),infundibulum, and (C), anterior lobe obtained from a dynamic examination following bolus administration of gadolinium contrast demonstrate normal

sequential enhancement. Normal enhancement also is seen in posterior clival veins (open arrow in part C).

mately 50 years of 81 Tsunoda and co-worker~~~ demonstrated slight increase in height of the gland in women aged 50 to 59 years old. They suggest that this represents compensatory hypertrophy responding to increased gonadotropin-releasing hormone resulting from decreased feedback of circulating gonadal steroids, which are diminished in the perimenopausal period. Physiologic hypertrophy of the gland during pregnancy is reflected on imaging as well. The gland obtains a markedly convex superior margin and increases in height (up to 10 mm). The signal intensity of the anterior lobe increases as well. This is presumably related to the same factors accounting for the hyperintense signal of the anterior lobe in neonates.60This high signal persists into the immediate postpartum period, when the gland may reach heights as great as 12 mm. Postpartum, a large hyperintense gland is normal

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Figure 5. The newborn pituitary. A midline T1-weighted sagittal MR image in a newborn shows homogenous high signal throughout the pituitary gland (arrow). It is difficult to discern the anterior lobe from the posterior lobe.

and does not represent pathology. The pituitary stalk may increase in size but should not exceed 4 mm in diameter.31, During the second postpartum week, the pituitary gland returns to its normal adult appearance. Fluctuations of the height and appearance of the pituitary have been noted under several other situations unrelated to the aging process. Uniform enlargement of the gland can occur as a compensatory response to hypothyroidism. Frequently, these patients undergo imaging because they have symptoms related to elevated prolactin, which is released from the anterior lobe along with thyroidstimulating hormone (TSH) as a result of elevated hypothalamic thyrotropinreleasing hormone (TRH) (responding to diminished feedback from lower levels of circulating thyroid hormones). The gland may become as great as 15 mm in height, and care must be taken to exclude an underlying adenoma or other space-occupying lesion. One must consider the possibility of hypothyroidism in such cases because images can be readily misinterpreted as neoplasm. Following thyroid hormone replacement, there is regression to a normal-sized gland.37,lW Changes may also be seen with psychiatric and nutritional problems.3l THE POSTERIOR PITUITARY

On T1-weighted M R imaging sequences, there is a focal area of high signal posteriorly within the sella, which is now known to be most often related to the posterior lobe of the pituitary. When this area was first identified on M R imaging, there was debate as to what this “bright spot” represented. Mark and co-workersS suggested that it represented fat (which is also high-signal on T1weighted sequences) either within the sella or within the marrow of the dorsum sellae and not part of the gland itself. This idea was challenged when other studies pointed out that the bright spot does not usually image as fat is expected to on all M R sequences.’8 In addition, in patients with sickle cell disease and replacement of fatty marrow, there is persistence of the bright spot.” With the

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realization that this bright spot was, in fact, almost always equivalent to the posterior lobe of the pituitary gland, investigations were undertaken to determine its nature, that is, what caused the posterior pituitary to be high signal on T1-weighted MR images. Researchers observed that the bright spot was absent in persons who had central diabetes i n s i p i d ~ sThis . ~ ~ led to several elegant studies that proved that the presence or absence of the bright spot was related to the concentration of vasopressin stored in the posterior lobe.35,49, Nevertheless, the question remains as to what intrinsically is responsible for the high signal. Two theories have been proposed. Oxytocin and vasopressin synthesized in the hypothalamus are linked to neurophysins, which are carrier proteins. This compound is then packaged within phospholipid membranes to become the neurosecretory granules that are stored in the posterior Some investigators believe that the phospholipid membrane of the neurosecretory granules is responsible for the high ~ignal.4~ Kurokawa and colleagues53believe that this is unlikely because oxytocin and vasopressin are released via exocytosis whereby the phospholipid membranes become incorporated into the axon terminal. If the phospholipid theory were correct, the depletion of vasopressin induced experimentally should not cause absence of the bright signal because the phospholipid membranes of the released granules would remain. This is contrary to what is observed. A second theory suggests that the high signal is related to the hormone-neurophysin complex within the granule itself. Although several studies support that theory, the exact identity of the substance within the granule that causes the 38, 53 hyperintensity remains PATHOLOGY

Congenital

Congenital abnormalities such as transsphenoidal encephalocele, pituitary gland duplication, and aplasia are extremely rare. Pituitary agenesis may be limited to the anterior gland or may include absence of the posterior gland and hypothalamus as well. Pituitary hypoplasia is a less severe form of this anomaly. Both agenesis and hypoplasia of the pituitary are frequently associated with other abnormalities of the midline craniofacial structures such as anencephaly, 31, 74 septo-optic dysplasia, holoprosencephaly, and simple cleft lip and ~a1ate.I~. Imaging demonstrates a small shallow sella with a diminished amount of glandular tissue. Rathke's pouch normally forms the anterior lobe of the pituitary. Remnants of this pouch can form very small cysts of the pars intermedia or larger Rathke's cleft cysts.5O These cysts are commonly seen at autops)t'5 and are most commonly intrasellat3I The typical location is intrapituitary or at the upper margin of the gland just anterior to the stalk. The cyst has a single cell wall layer and variable internal c0ntent.4~. If predominately comprised of CSF-type material, the lesion is low-signal on T1-weighted and high-signal on T2-weighted MR images. If there is cholesterol or mucopolysaccharide in the cyst, high signal on T1weighted images and isointense to hypointense signal on T2-weighted MR images is observed (Fig. 6 ) . Hemorrhagic cysts may have high signal on both T1 and T2 sequences8 Rathke's cleft cysts usually have an imperceptible wall but occasionally exhibit a thin rim of enhancement?I, Thick or nodular enhancement should raise the possibility of other pathology, such as a craniopharyngioma or cystic hemorrhagic pituitary adenoma.

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Figure 6. Rathke’s cleft cyst. There is a rounded lesion within the pituitary gland on this T1-weighted noncontrast sagittal MR image that has a diffuse homogenous high signal. There was no enhancement and the lesion was isointense on the T2-weighted sequence. This MR image pattern is consistent with a Rathke’s cleft cyst, with high T1 signal related to mucopolysaccharide, cholesterol components, or hemorrhage.

Tumors Adenomas

Because pituitary adenomas represent 10% to 15% of all intracranial tumors,3l much research has focused on determining the best means to diagnose these lesions. Macroadenomas are more easily depicted because of their larger size (10 mm or greater), frequently associated with extrasellar extension that distorts the normal surrounding structures (Fig. 7). As macroadenomas extend into the suprasellar region, they may acquire a “waist” or “figure-eight” appearance, from constriction, as the lesion crosses the diaphragma ~ellae.6~ Microadenomas are more of a diagnostic challenge. On CT, the only direct sign of a microadenoma is a focal area of different attenuation relative to the surrounding pituitary gland. Most often, this is a small area of low density within the pituitary. This discrepancy in attenuation commonly becomes more apparent following the administration of contrast because the normal gland enhances more intensely than most turn0rs.5~. lo3Secondary CT signs of microadenoma, such as sellar floor erosion, elevation of the diaphragma sellae, and infundibular displacement, are helpful but not diagnostic.3l. 51 Noncontrast T1weighted M R imaging of the pituitary shows a similar appearance to CT; the microadenoma is usually a focal area of low signal within the pituitary gland. Initial comparisons of the sensitivity of CT and MR imaging for the detection of microadenoma initially favored CT; however, with the advent of MR contrast media and more refined sequences, MR imaging has become the preferred moda1ity.W 31.51. 103 Sakomoto and c o - ~ o r k e r swere ~ ~ one of the first groups to describe the enhancement pattern of adenomas, noting that the peak enhancement of adenomas occurs at a time later than the peak enhancement of the normal gland. Consequently, the best technique to obtain the greatest degree of contrast be-

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Figure 7. Macroadenoma on CT. Coronal postcontrast CT demonstrates a focal area of lower attenuation in the left aspect of the pituitary gland (arrows) relative to the homogenously enhancing surrounding gland. Note the abnormal superiorly convex contour, which is a secondary sign of underlying tumor.

tween the tumor and the normal gland is to scan immediately after the contrast bolus when the normal gland is enhancing and the adenoma has yet to enhance (Fig. 8A-E). In fact, if imaging is delayed too long, the signal from the delayed enhancing adenoma may be equal to (a source of potential false-negatives), or possibly greater than, that of the surrounding gland (which is diminishing in 65,76 enhancement),the so-called “flip-flop” phen~menon.~, Sakomoto and colleagues76did not describe any differences in enhancement patterns between microadenomas and macroadenomas. Studies performed using dynamic imaging of macroadenomas (very fast image acquisition during the time of the contrast bolus) demonstrate that these tumors enhance slightly before the posterior lobe and well before the anterior lobe.33,Io6 These findings imply that macroadenomas have a direct arterial supply. This is not surprising. Conventional angiographic studies performed nearly 20 years earlier revealed several diagnostic findings for pituitary adenomas, including the presence of tumor vessels.71The use of contrast in the imaging of macroadenomas is not to establish their presence, which can be detected on noncontrast examinations by their size and displacement of adjacent structures, but rather to distinguish tumor from residual normal pituitary gland and to detect possible extension into the adjacent cavernous sinus.33 As mentioned previously, early work demonstrated slow enhancement of microadenomas relative to normal surrounding pituitary gland.61This suggests that microadenomas are supplied by the portal system that supplies the adenohypophysis. B~nneville’~ retrospectively reviewed dynamic CT imaging of 260 patients with microadenomas and found that the majority (65.4%) of tumors showed peak enhancement at a point in time later than the adjacent adenohypophysis. The remaining 34.6% of microadenomas enhanced before normal portal enhancement, suggesting arterial supply to these tumors. Several studies were subsequently performed to examine dynamic MR enhancement patterns in microadenomas; the results were similar to dynamic CT.9, 33, 48 Specifically, although there is a predictable pattern of enhancement of the normal pituitary

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Figure 8. MR imaging of pituitary microadenoma. Case 1. Prolactinoma. A, A noncontrast T1-weighted coronal image shows an enlarged pituitary gland with an abnormal superiorly convex contour. No focal area of abnormal signal can be appreciated within the gland. Following administration of contrast, both the sagittal (6) and coronal (C) T1-weighted images demonstrate homogenous enhancement of the normal gland with a focal area of less enhancement (arrow) in the posterior left aspect of the gland that represents the adenoma. This patient presented with galactorrhea and was found to have an elevated level of prolactin. Case 2. Prolactinoma. No focal contour or signal abnormality is present on the noncontrast T1-weighted sagittal image (D). Illustration continued on opposite page

gland, the time course of enhancement of the microadenoma is less consistent. The majority of tumors will enhance at a point later than peak enhancement of the anterior lobe, and a lesser percentage will enhance earlier (Fig. 8F-H). The ability to detect microadenomas depends o n the imaging technique that will best exploit these varying patterns of enhancement. In a commentary addressing whether dynamic imaging should be performed in a l l patients with symptoms suggesting pituitary adenoma, E l s t e P states that if the diagnosis is certain based on other clinical tests and if the treatment is medical, the rationale for imaging should be to exclude an unexpected cause of pituitary abnormality or a large tumor that m y q u i r e swgery. This screening imaging study could be CT or u n e c e d MR imaging, which will provide the necessary information a t lower cost. If s q e q is considered, a detailed (postcontrast) imaging study is q u i d to direct the surgical appmch. Although it does not follow that the contrast-mhmced examination must in-

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Figure 8 (Continued). After administration of contrast (f)the microadenoma appears as an area of less enhancement (arrow). This patient also had elevated prolactin. Case 3. Marked enhancement in microadenoma. Noncontrast T1-weighted sagittal (F) and coronal (G) MR images show the microadenoma as an area of low signal (arrow) in the anterior left aspect of the gland. In this case, the postinfusion scan (H)reveals that the microadenoma has more avid enhancement (arrow) than the surrounding normal pituitary gland.

clude a dynamic sequence, Elster reports the following sensitivities for the detection of pituitary lesions: high-resolution unenhanced MR imaging, 60% to 80%; enhanced MR imaging, an additional 5% to 10%; and dynamic MR imaging, al. daditional 5% to 20%, for an overall sensitivity of approximately 90%. One approach in a surgical case would be to evaluate the patient initially with conventional contrast-enhanced MR imaging. If this fails to show the tumor and cannot distinguish it from normal pituitary tissue, dynamic MR imaging could be performed at a separate date. With access to a contemporary MR scanner, a dynamic enhanced sequence could be performed routinely during a contrast bolus, with static images to follow immediately. Imaging Findings in Specific Tumor Types

Preliminary data from an in vitro study indicate a correlation between the types of secreting and nonsecreting adenomas and particular MR imaging

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fh1dings.8~Although the various types of adenomas cannot be reliably differentiated by imaging, certain trends are noteworthy. Nonsecreting or clinically silent secreting adenomas often are macroadenomas at the time of detection. If present, symptoms are related to the mass effect exerted on adjacent ~tructures.'~ Tumors that secrete and that produce clearly recognizable symptoms, such as adrenocorticotropin hormone (ACTH) tumors with Cushing's syndrome, present as small intrasellar masses (microadenomas).An exception to the rule, growth hormonesecreting tumors are frequently macroadenomas at presentation.%This is most likely explained, in part, by the fact that although an adenoma may produce a significant amount of hormone, if the effect of that hormone is subtle and not recognized by the individual, the adenoma will have a longer unrecognized period of growth. Tumors producing hormones that result in easily recognizable clinical patterns are detected earlier and, consequently, when smaller. With the exception of gonadotroph-producing cells, the hormone-producing cells are not evenly distributed throughout the gland. Prolactin and growth hormoneproducing cells predominate laterally, whereas ACTH and TSH-producing cells are found centrally. This distribution correlates with tumor location when these cells give rise to adenomas. Prolactinomas and growth hormonesecreting microadenomas are more often laterally located in the gland and ACTH tumors centrally.&,59 (Fig. 9). Tumors secreting ACTH that are responsible for Cushing's disease are often small at the time of detection and are therefore difficult to detect with imaging. Only 40% to 50% of patients who are surgically cured of hypercortisolism have a microadenoma visualized preoperatively. The reported sensitivity of MR imaging for the detection of ACTH microadenoma is 45% to 71%.16 When imaging is negative, petrosal sinus venous sampling is a valuable, albeit, invasive test to help with this diagnosis. The method involves selective bilateral

Figure 9. ACTH microadenoma. A midline postcontrast T1-weighted coronal MR image shows an area of less enhancement (arrows) centrally within the superiorly convex gland. The central location correspondswith the predominant location of ACTH-producing pituitary cells. This patient presented with hirsutism and was clinically found to have other signs and symptoms of Cushing's syndrome. She had elevated levels of ACTH.

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catheterization of the inferior petrosal sinuses via percutaneous femoral venous puncture. Each inferior petrosal sinus tends to drain its respective half of the pituitary gland. Venous flow is then directed into the ipsilateral jugular bulb (although several variations in this drainage pattern exist). Simultaneous sampling must occur from each inferior petrosal sinus as well as from the peripheral blood. Ratios of the level of ACTH from the inferior petrosal sinuses relative to peripheral blood levels determine whether the pituitary is the source of the elevated ACTH. A comparison of the levels from each of the two petrosal sinuses will often determine on which side the lesion is located and thereby direct the surgical resection plan.62The same procedure has been used successfully for the work-up of acromegaly with equivocal imaging although lateralization to a side is less precise. As MR imaging has improved, the need for this invasive procedure has declined. Some studies have assessed the ability of intraoperative ultrasound to help localize ACTH-secreting microadenomas. Preliminary findings show it is useful to visualize the tumor and appropriately guide resection, with 80% remission postoperatively.28 Pituitary Apoplexy

Pituitary apoplexy most commonly occurs in macroadenomas, although it may occur in the normal gland in postpartum women (Sheehan's Spontaneous intratumoral hemorrhage, with or without tumor infarction, results in acute expansion of the gland, with compromise of surrounding structures resulting in the clinical ~ y n d r o m e .On ~ ~CT , ~ in ~ the acute stages, there may be high attenuation within an expanded pituitary mass as the result of recent hemorrhage. As the blood hemolyzes beyond the acute period, the high attenuation will be replaced by low density. If imaging occurs beyond this narrow window of time, the diagnosis may not be easily made because the lesion may appear as a nonspecific cystic mass (with a differential diagnosis that includes cystic or necrotic tumors such as craniopharyngiomas, abscesses, or vascular lesions). Magnetic resonance imaging more accurately pictures the hemorrhagic event.7,54 The age of the hemorrhage can be determined by its appearance on various MR sequences. In the acute stage, the bleed will be characteristically hypointense to isointense on T1 sequences, and initially isointense, then hypointense on T2 sequences. T2-weighted images obtained with gradient echo techniques are more sensitive to hemorrhage than those employing spin-echo sequences. With time, the blood begins to break down to methemoglobin, which exhibits high signal on T1-weighted images. T2-weighted sequences may show low or high intensity at this stage, depending on the integrity of the red blood cell membrane.66Using this temporal pattern to document the presence of prior hemorrhages, Ostrov and co-workers68demonstrated prior bleeds in pituitary adenomas in the absence of any clinical signs of pituitary apoplexy. Various theories exist concerning the underlying cause of pituitary apoplexy. Armstrong and colleagues7suggest that the adenoma may outgrow its vascular supply or may exert a mass effect on its own feeding vessels. Alternatively, the blood supply may be somewhat tenuous such that mitigating factors such as trauma, elevated intracranial pressure, or diabetic ketoacidosis may result in the event. Yousem and c o - ~ o r k e r sreviewed '~~ the findings of MR imaging to determine the incidence of hemorrhage in 68 adenomas. Twenty-six percent of the pituitary tumors showed signs of a prior bleed; 55% of these patents were asymptomatic. In this group, 45% of the adenomas treated with bromocriptine had hemorrhage. Thirty-three percent of the prolactinomas demonstrated intra-

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tumoral blood; all of these patients had received bromocriptine. This suggests that bromocriptine may predispose to intratumoral hemorrhage (Fig. 10). lnvasive Adenomas

A subgroup of adenomas are classified as invasive. These adenomas destructively infiltrate surrounding structures. This is different from extension, which is tumor growth with compression of surrounding structures, which often occws in a suprasellar direction. The invasive lesion need not be malignant (pituitary carcinoma); malignancy is suggested by evidence of discontinuous craniospinal or extraneural spread.@,82 Selman and co-workerss5examined dural specimens

Figure 10. Macroadenoma with subsequent pituitary hemorrhage. The macroadenoma (arrows) appears as an enlarged mass within the sella on the noncontrast TI-weighted sagittal MR image (A). B, Repeat imaging obtained 2 years later shows that there is a new high signal (arrows) within the macroadenoma secondary to subacute hemorrhage. The patient had been receiving bromocriptine and was asymptomatic. C, On the examination performed in the same patient 1 year later, the macroadenoma is no longer present and there is a partially empty sella. Presumably, there has been necrosis of the tumor following the episode of hemorrhage.

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taken during the resection of pituitary adenomas and found evidence of microscopic dural invasion in 85%. The incidence of invasion was related to the size of the tumor, with invasion detected in 66% of the microadenomas, 87% of the intrasellar macroadenomas, and 94% of macroadenomas with suprasellar extension. No correlation of invasiveness with immunohistochemical classification of the tumor could be identified. Despite the relatively common occurrence of microscopic invasiveness, there is only a 40% incidence of invasiveness found at surgery.69,82,85 Because the extent of gross macroscopic invasion at the time of surgery will partially determine the success of tumor resection, work has been performed to determine imaging criteria that can predict the presence and degree of invasiveness. Invasive adenomas can infiltrate in any direction. Preferential invasion into the inferior and posterior bony structures may occur, with the tumors becoming These tumors can “giant” in size, that is, greater than 4 cm prior to mimic any other skull base neoplasm (Fig. 11A-C). A predominately central location within the sphenoid bone with extension to all adjacent structures and the absence of cystic regions or calcifications may be helpful in differentiating this lesion from other bony destructive tumors.3,99 Lateral invasion into the cavernous sinus, especially in the early stages, is particularly difficult to determine with imaging because the medial wall of the cavernous sinus is not clearly seen. Advanced signs of invasion include cavernous sinus expansion, abnormal intracavemous signal, encasement of the intracavemous portions of the internal carotid arteries, obliteration or displacement of the cranial nerves, and invasion beyond the lateral wall of the cavernous sinus (Fig. 11C).Bilateral displacement of the carotid arteries is not usually associated with invasion and represents, instead, displacement by a noninvasive ma~roadenoma.~,Several classification systems have been proposed, often using the intracavernous carotid artery as a landmark, which help predict the likelihood of in~asion.~’ The aggressive tendency of an adenoma cannot be determined accurately based on imaging findings or endocrinologic activity. Even pathologic analysis with standard markers of aggressiveness such as pleomorphism, cytologic atypia, and mitotic activity cannot predict the aggressiveness of pituitary adenomas. Recent work has focused on other markers. Researchers have found a higher degree of expression of certain cell growth markers (i.e., p53, Ki-67) in invasive adenomas in comparison with noninvasive a d e n o m a ~93, . ~ ~ ,It is hoped that by identifying those adenomas that are aggressive and that possibly have a higher potential for recurrence, postoperative management and imaging surveillance can be facilitated. POSTOPERATIVE IMAGING

The radiologist must anticipate the expected postoperative imaging appearance following pituitary adenoma resection, otherwise a mistaken diagnosis of incomplete tumor resection or complications may occur. In brief, the standard transsphenoidal resection consists of opening the floor of the sella turcica after traversing the sphenoid sinus. A dural defect is created through which the tumor is removed. Attempts are made to leave normal gland. Depending on the size of the resected tumor and the resulting cavity, packing may be placed. This packing may be fat, muscle, or Gelfoam. The floor of the sella is often reconstructed with a piece of nasal cartilage or bone. The sphenoid sinus may or may not be additionally packed.=,75 The findings on CT and MR imaging are similar. Immediately following the

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Figure 11. lnvasive macroadenomas. A, A T1-weighted postcontrast sagittal MR image demonstrates a large mass centered in the sella and sphenoid. The mass extends superiorly into the suprasellar region (open arrow), anteriorly into the sphenoid sinus (arrows), and inferiorly within the clivus (arrowheads). B, Another invasive adenoma (solid arrows) destroying the normal sella and sphenoid. The part of the clivus not involved is seen by preservation of the normal fatty marrow inferiorly (open arrow). C,A T1-weighted postcontrast coronal MR image shows a large, homogenously enhancing adenoma arising from the sella. The tumor is invading the third ventricle (heavy arrow). There is encasement of the intracavernous portion of the left internal carotid artery (curved arrow).

resection of a microadenoma, there may be an increase in the height of the gland,= which subsequently resolves over a few months. Similarly, following the resection of a macroadenoma, there m a y be n o reduction in the height of the sellar/suprasellar mass. This is often a result, in part, of the packing materials. The CT attenuation of the packing wiU vary and is often heterogenous, with some high density as a result of the presence o f postoperative blood. On M R imaging, fat packing is high signal on T1 sequences and low signal on T2 sequences. Gelfoam is isohtense on T1 sequences and mixed signal on T2 sequences. Over the next few months, the packing materials may resorb, and the volume of the residual mass effect will decrease (Fig. 12). On M R imaging, some residual fat packing may persist within the sella and must be diffem-ttiated from areas of hemorrhage. With resorption of the packing material, a partially

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Figure 12. Postoperative imaging. A, A noncontrast T1-weighted sagittal MR image demonstrates an enlarged mass within the sella (arrows) extending superiorly. The mass has a large rounded area of high signal corresponding to subacute blood. A hemorrhagic macroadenoma was confirmed at resection. B, A postcontrast T1-weighted sagittal MR image obtained 2 days following surgery shows persistence of a sellar/suprasellar mass (arrows) related to packing material. C, A postcontrast T1-weighted sagittal MR image obtained several months later shows interval decrease in volume of the mass (arrow) within the sella due to resorption of fluid and the packing material.

empty sella may develop, and, occasionally, the suprasellar visual system (optic chiasm) may herniate into the defect. Traction on the optic chiasm may produce visual field cuts, producing the empty sella syndrome. If the sphenoid sinus has been packed, its imaging characteristics will be similar to those of the packed sella. Even in the absence of packing, the sphenoid sinus and the maxillary and ethmoid sinuses often are at least partially opacified by thickened mucosa, blood, and postoperative debris. These findings also resolve with time.26On CT,

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the bony stent at the floor of the reconstructed sella may be seen." Because of these confusing immediate postoperative findings, it may be unwise to make therapeutic decisions based on imaging early after surgery. A baseline examination is recommended 4 to 6 months after operation. At that time, the postoperative changes will have resolved, and the delay is not so long as to risk sigruficant interval growth from residual tumor. Residual tumor will have the same signal and enhancement pattern as shown preoperatively." Postoperative complications include excessive packing of the tumor cavity resulting in compression of adjacent visual structures or cranial nerves in the cavernous sinus, dislodgment of the packing material or bone stent, and CSF leakage.26Raymond and colleaguesRhave studied arterial injuries that occur as complications of transsphenoidal resection. These injuries include carotid artery stenosis, carotid and sphenopalatine artery pseudoaneurysms (with or without severe epistaxis), and carotid cavernous sinus fistulas. These injuries are welldemonstrated with angiography and can often be treated at the same time by the interventional neuroradiologist using an endovascular approach. Preoperative imaging (a limited coronal noncontrast CT scan) can easily identdy the location of the cavernous carotid arteries and the position of the sphenoid sinus septae so that a safe operative approach can be designed. FUNCTIONAL IMAGING

Nuclear medicine offers a new imaging modality for investigating pituitary adenomas. Positron emission tomography (PET) is a tool that employs a radioactive tracer linked to a normal substrate. Gamma rays are given off when the positrons of the radioactive tracer undergo annihilation. The resultant gamma rays are imaged, reflecting the distribution of the radioactive tracer-substrate complex. F-18 fluorodeoxyglucose (FDG), one popular PET agent, measures brain glucose utilization in vivo. Neoplastic cells characteristically have increased glucose utilizati0n.9~The normal pituitary gland is not visible on a PET FDG study. An area of increased activity visualized in the pituitary region is an indication of abnormal biologic activity and can be seen in pituitary tumors.88 Francavilla and co-workers34performed PET FDG imaging on 24 patients with various types of macroadenomas. They were able to differentiate hypermetabolic recurrent tumor from hypometabolic postoperative changes and scar when sectional imaging (CT) was equivocal. A higher metabolic activity was noted in nonfunctioning macroadenomas in comparison with the activity in hormonesecreting tumors. No sigruficant differences in the metabolic activities of any one particular hormone-producing tumor were found. The metabolic activity of tumors that had received radiation or medical therapy (bromocriptine and octreotide) was lower than that of untreated tumors, offering a potential way to monitor therapeutic success. By linking a radioactive tracer to ligands chosen for an affinity to bind certain receptors, more specific information is obtained. For example, C-11methionine selectively binds to dopamine receptors, which are p m n t in a high number in adenomas. Accumulation of C-11 methionhe in the sella m y help differentiate active tumor from other sellar pathology or postoperative changes. This also may be a means of p d c t i n g the response of various adenomas to bromocriptine by documenting the concentration of D2receptors. An immediate response to treatment could be determined by an interval decrease in tracer activity. W e r imaging modalities may take up to several months to show interval decrease in tumor sizeuMore recent work has focused on charaderizing

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the binding properties of tumors to other ligands for dopamine receptors,7O as well as looking at different types of receptors such as somato~tatin.~~ OTHER TUMORS

Less than 3% of adenomas occur in patients less than 18 years old. The most common sellar mass in children is craniopharyngioma. This tumor has a second peak of occurrence in adults in the fourth to sixth decade. Craniopharyngiomas, like Rathke’s cleft cysts, are derived from remnants of Rathke’s pouch, and these two lesions probably represent the ends of a c o n t i n ~ u r nUnlike .~~ Rathke’s cleft cysts, craniopharyngiomas rarely are entirely intrasellar, and 50% are both intrasellar and extrasellar. Cystic components are present in 85%. Rimlike or nodular calcifications are present in at least 80% of these tumors, although the frequency is less in the adult type.17,31 Calcification is better appreciated with CT. The appearance of craniopharyngiomaon imaging depends on the contents of the cyst and enhancement pattern. Enhancement of the wall is common.5oIt is typically thicker and more irregular than that seen with Rathke’s cleft cyst (Fig. 13). Meningiomas of the sella and parasellar regions arise from the diaphragma sellae, tuberculum sellae, clinoids, tentorial free margin, and cavernous sinuses. Meningiomas are the second most common sellar region neoplasm in adults, following parasellar extension of adenoma. The meningioma can secondarily grow down into the sella or, rarely, arise within the sella, occasionally leading to confusing imaging findings (Fig. 14). As is true for meningiomas found elsewhere, these lesions are often of slightly greater density relative to the adjacent brain parenchyma on CT. On MR imaging, lesions are generally isointense to gray matter on T1- and T2-weighted images. Following the administration of contrast, there is intense homogenous enhancement. Two findings frequently observed with meningiomas are a dural tail and hyperostosis. The dural tail sign is a linear extension of enhancement that may be seen at the periphery of the tumor along the dura. It usually represents nonneoplastic dural hypervascularity, although tumor may be found in this region. Hyperostosis (localized bone thickening) may occur as a reaction of the underlying bone to the presence of an adjacent meningi0ma.6~Focal low-signal intensity on all MR pulse sequences is seen in bone at the site of tumor attachment in such cases. Other masses seen with variable frequencies in the sellar/suprasellar region include optic/hypothalamic gliomas (Fig. 15), germinomas, cavernous hemangiomas, histiocytosis, dermoids/epidermoids, and hypothalamic hamartomas. Metastatic lesions represent 1%of sellar masses. These lesions frequently involve the stalk and the hypothalamus as well. Most metastases are from breast, lung, or gastrointestinal primaries. Metastatic lesions usually are isointense on precontrast T1 sequences and show enhancement. Metastases from melanoma, if melanotic, are an exception. These lesions are high signal on T1-weighted images prior to c o n t r a ~ t . ’Any ~ , ~of ~ these masses may also involve the infundibulum primarily (Fig. 16). Any change in the smooth contour, an increase in width and an abnormal enhancement of the stalk are indicators of pathology that may be neoplastic, infectious (tuberculosis),or inflammatory (sarcoid). OTHER PATHOLOGY Empty Sella

An empty sella is defined as a sella, regardless of size, that is completely or partially filled with CSF. It may secondarily develop following radiation or

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Figure 13. Craniophalyngiomas. Case 1. A, A postcontrast coronal CT demonstrates a low density, cystic mass (arrows) A, spanning both the sella and suprasellar regions. No calcificationsare appreciated and there is only faint enhancement of the thin margin. Other structures seen include the sphenoid sinus (S) and the anterior clinoids (C). B, A noncontrast T1-weighted coronal MR also demonstrates the mass. Note the extension across the diaphragma sella causing a “waist” (arrows) between the intrasellar and suprasellar components; an appearance that also can be seen in macroadenomas. The high signal intensity of the central contents of the lesion suggests either mucopolysaccharide/cholesterol contents or blood. Illustration continued on opposite page

operative removal of sellar contents. An empty sella has been found in 6% of autopsy specimens. It i s more common in women and increases in frequency with age?’, 97 On T1 sagittal M R images, this extension of CSF into the sella is easily identified. Any remaining gland is compressed along the floor (Fig. 17). The infundibulum should maintain its normal midline position, otherwise the empty sella may, in fact, represent a cystic lesion occupying the sella.17 The diaphragma sellae, the dural covering overlying the pituitary, has a n opening for the infundibulum.Twenty percent of the normal population have a rudimentary or absent diaphragm.’* Bjerre12has outlined many theories for the primary causes of an empty sella. It may be a normal variant, especially if the sella is not enlarged. Another theory proposes that it results from transmitted CSF

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Figure 13 (Continued). Case 2. C,An axial noncontrast CT demonstrates an abnormal soft-tissue density mass (arrows) filling the suprasellar cistern. This mass has scattered foci of higher density within it, corresponding to areas of calcification. 0,The noncontrast sagittal T1-weighted MR obtained from the same patient shows the mass to be multicystic with variable signal intensities. The lesion has invaded the third ventricle (higher signal cyst) and extends into the interpenduncular cistern (less intense cystic component seen inferiorly). Case 3. €, A postcontrast coronal T1-weighted image shows a low signal (cystic) round suprasellar mass that does not extend into the sella. There is only thin peripheral enhancement of the wall (arrows).

pulsations through a deficient diaphragma sellae with or without an associated arachnoid diverticulum. Other alternative explanations include pituitary hyperplasia, which subsequently resolves leaving a partially empty sella, and spontaneous necrosis of a preexisting pituitary adenoma (Fig. 18). Most persons with an empty sella are asymptomatic, although 10% complain of nonspecific headaches. Visual disturbances may occur owing to retraction of the optic chiasm downward, particularly when the empty sella occurs

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Figure 14. Meningioma resembling pituitary adenoma. There is a large mass within the sella extending into the suprasellar region. A, On the precontrast T1-weighted sagittal MR image, the mass (arrow) is isointense to the brain. B, Following administration of contrast, the mass demonstrates diffuse homogenous enhancement (arrows). The lesion is indistinguishable on these images from a macroadenoma, but was found to be a meningioma at the time of resection. Most sellar-region meningiomas demonstrate a significant extrasellar component and arise from the tuberculum sella, anterior clinoid process, or cavernous sinus dura.

following surgery on an intrasellar mass (Fig. 18). Delayed visual field defects occuring after sellar/suprasellar surgery may be related to chiasmatic retraction owing to scar formation. Variable degrees of hormonal deficiency have been described, but some investigators believe this is related to underlying pituitary infarction and not the subsequent development of an empty sella. In patients with a syndrome of hormone excess, the possibility of a coexisting micmadenoma within the compressed gland should be considered?' Spontaneous CSF rhinorrhea and pseudotumor cerebri are two syndromes associated with an empty sells.=

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Figure 15. Optic glioma. This patient presented with vision loss. A, A T1-weighted noncontrast MR image demonstrates a large mass in the posterior suprasellar region, with extension into the sella and interpeduncular cistern. 6,A postcontrast axial T1-weighted MR image shows a homogenously enhancing spherical mass arising from the optic chiasm. The normal optic nerve on the right is marked with an arrow.

Figure 16. lnfundibular histiocytosis. This 16-year-old male patient presented with diabetes insipidus. A noncontrast T1-weighted sagittal MR image demonstrates enlargement and thickening of the infundibulum (arrow). Histiocytosis with involvement of the stalk was proven by biopsy. Note absence of normal posterior pituitary bright spot.

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Figure 17. Empty sella. A T1-weighted postcontrast sagittal MR image demonstrates an empty sella. The normal gland (open arrow) is compressed along the floor of the sella. The infundibulum extends to the midportion of the gland (small arrows).

Figure 18. A postcontrast Tl-weighted sagittal MR image in a patient who had prior resection of a pituitary adenoma. The scan demonstrates hemiation of the optic chiasm (arrows) into the empty sella. This patient did not have visual changes associated with the empty sella syndrome.

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Infection/lnflammation

Infectious and inflammatory processes include abscesses, tuberculosis, sar31,45 The last entity is a rare, most coid, and lymphocytic adenohypophy~itis.’~, likely autoimmune disease, commonly seen in postpartum women. It may be misdiagnosed as a pituitary adenoma complicated by bleeding and infarction because it is occasionally associated with a mildly elevated prolactin leveL2 Although lymphocytic adenohypophysitis is classically described as an inflammatory process confined to the anterior lobe, there have been case reports of histologically similar lymphocytic infiltration spreading from the anterior lobe to involve the infundibulum and posterior pituitary, as well as case reports of isolated lymphocytic infiltration of the posterior lobe, presenting clinically with central diabetes in~ipidus.~,46 This process may spontaneously regress or respond to steroids.* Vascular Lesions

Aneurysms of the cavernous or supraclinoid portions of the internal carotid artery may be seen on imaging studies directed to the sella. Patent aneurysms often appear as bulbous extensions of normal arterial signal voids (Fig. 19). Occasionally, a large thrombosed or partially thrombosed aneurysm will resemble a solid suprasellar mass, although shell-like calcification and lamellated thrombus usually suggest the correct diagnosis. Carotid cavernous and dural arteriovenous fistulas may present with abnormal flow voids within, and enlargement of, the cavernous sinus. Other imaging findings associated with these fistulous lesions include enlargement of the superior ophthalmic vein, engorgement of the intercavernous sinuses, and enlargement or abnormal convexity of

Figure 19. lntrasellar aneurysm. A, A T1-weighted noncontrast sagittal MR image shows an apparent round mass within the sella that is of mixed signal (arrows). 6,A TP-weighted axial image shows that this “mass” is in continuity with the arterial signal void of the adjacent left intracavernous carotid artery (small arrows), suggesting the diagnosis of aneurysm. The central area of high signal (open arrow) within the aneurysm represents turbulent or slow-flowing blood within the patent aneurysm. Faster flow at the periphery of the aneurysm lumen also is seen as a signal void. The normal right intracavernous internal carotid artery is marked with a single black arrow.

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the involved cavernous s i n ~ s . 3Sat0 ~ and co-workerss0recently noted enlargement of the pituitary gland in the presence of dural arteriovenous fistulas. They suggest this is related to swelling of the pituitary from venous congestion and increased pressure in the cavernous sinus. Pituitary swelling may also occur in cases of dural venous engorgement related to intracranial hypotension.

Diabetes lnsipidus and the Pituitary Bright Spot

Initial studies mistakenly reported that the posterior sellar bright spot may be absent with some frequency on routine MR examinations in healthy individuals.15,l8 With the optimization of imaging techniques and the use of very thin sagittal sections to reduce partial volume artifact, the posterior pituitary bright spot is now demonstrated by MR imaging in virtually all normal individuals.3l.78 Occasionally, the bright spot may be identified not within the sella but along the infundibulum or median eminence. This has been termed an ectopic posterior pituitary and is thought to develop as a result of an injury or other compromise of the stalk such that transport of vasopressin to the posterior lobe is impeded. Accumulation of hormone proximal to the level of impedence results in abnormal location of the bright spot.U,37 The underlying pathologic process that disrupts the hypothalamic pituitary axis may be directly detected by imaging (tumor, trauma, postoperative, inflamrnat~ry).~~ Occasionally, the presence of an ectopic posterior pituitary is found incidentally in hormonally normal individuals with no known precipitating event9 (Fig. 20). A high incidence of ectopic posterior pituitary gland is seen in many patients with growth hormone deficiency. When the clinical backgrounds of these pituitary dwarfs are reviewed, approximately 50% have history of birth trauma. These individuals also commonly have a small sella and hypoplasia of the anterior lobe, with a variable degree of anterior pituitary hormonal dysfunction.', 31* 45, 52 Growth hormone-deficient patients with normal pituitary anatomy and gland height have less severe and sometimes transient hormone deficiencies.6 Patients who present with diabetes insipidus require an imaging study to rule out secondary causes such as tumor, trauma, inflammation, or infection. In 10% to 30% of patients with central diabetes insipidus, no underlying structural abnormality of the hypothalamic neurohypophyseal system can be detected. This subset of patients is classified as having idiopathic central diabetes insipidus.4O As mentioned previously, the presence of the posterior pituitary bright spot on T1 noncontrast MR sequences corresponds to the presence of stored vasopressin. In patients with central idiopathic diabetes insipidus, the bright spot is, not surprisingly, absenP (Fig. 21). On dynamic contrast-enhanced MR imaging, the posterior lobe is noted to have delayed enhancementm,96 in these patients as well. This suggests a possible vasculopathic etiology for central idiopathic diabetes insipidus.79Although the absence of high signal within the posterior lobe is an indication of inadequate vasopressin stores and most likely a dysfunctional neurohypophyseal system, Maghnie and c o - ~ o r k e r scaution ~~ that the presence of a bright spot does not prove that the system is functionally intact. Although the hypothalmic hormones may be appropriately packaged and stored within the posterior lobe, this does not exclude impaired secretion or local enzymatic destruction, which could also result in central diabetes insipidus. Finally, the pituitary bright spot normally is present in noncontrast forms of diabetic insipidus (nephrogenic, dipsogenic).

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Figure 20. Ectopic posterior pituitary bright spot. T1 -weighted noncontrast sagittal (A) and postcontrast coronal (B) MR images show that the posterior pituitary bright spot (arrow) is not in its expected position within the sella, but rather at the proximal aspect of the infundibulum. This was found incidentally in an 11-year-old female patient. There was no history of prior trauma or surgery.

Pituitary lncidentalomas

In a study of 1000 unselected autopsy specimens, 178 (18%)were found to have pituitary pathologyg1;61 of these lesions were larger than 2 mm. Approximately two thirds of these lesions were Rathke’s cleft cysts, and one third were subclinical microadenomas. Other uncommon lesions detected included areas of hemorrhage and infarct. This high percentage of pituitary abnormalities in normal patients raises the issue of how to approach and manage pituitary “incidentalomas” found in patients imaged for other reasons. Some clinicians suggest that in patients with no subjective symptoms referable to the pituitary, ophthalmic examinations and pituitary function tests should be performed. If

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Figure 21. Diabetes insipidus. A midline sagittal TI-weighted noncontrast image demonstrates absence of the expected posterior pituitary bright spot in a patient with central diabetes insipidus.

these tests are normal and assuming the patient remains asymptomatic, repeat imaging at 6 months to 1year can be performed. If the lesion demonstrates any change in size or appearance, the appropriate treatment can be undertaken. If the lesion is stable for 2 years, no further studies are necessary.63,73 As imaging techniques improve, there is greater detection of these small abnormalities, which may or may not be the cause of any clinical CONCLUSION

Although CT still has a role in the evaluation of the pituitary, the capabilities of MR imaging to evaluate both normal and pathologic states of the pituitary gland are tremendous. MR imaging has allowed a glimpse of the normally functioning gland in vivo. Questions such as the etiology of an empty sella, the cause of the high signal comprising the posterior pituitary bright spot, and the reason why some growth hormone-deficient patients have an ectopic pituitary whereas others do not are just a few that remain unanswered. Future use of PET imaging and intraoperative ultrasound seems promising. As technology advances and further insights are made into the disease processes and normal functioning of the pituitary gland, the need to investigate with imaging will increase. References 1. Abemathy LJ: Review article: Imaging of the pituitary in children with growth disorders. Eur J Radio1 26:102-108, 1998 2. Ahmadi J, Meyers G, Segall HD, et al: Lymphocytic adenohypophysitis: Contrast enhanced MRI in 5 cases. Radiology 195:30-34,1995

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3. Ahmadi J, North CM, Segall HD, et al: Cavernous sinus invasion by pituitary adenomas. AJR Am J Roentgenol 146957-262,1986 4. Ahmed SR, Aiello DP, Page R, et a1 Necrotizing infundibulo-hypophysitis:A unique syndrome of diabetes insipidus and hypopituitarism. J Clin Endocrinol Metab 76:1499-1504, 1993 5. Anson JA, Segal MN, Baldwin NG, et al: Resection of giant invasive pituitary tumors through a transfacial approach Technical case report. Neurosurgery 37541-546, 1995 6. Argyropoulou M, Perignon F, Brauner R, et a1 Magnetic resonance imaging in the diagnosis of growth hormone deficiency. J Pedriatr 120:88G391, 1992 7. Armstrong M, Douek D, Patronas N, et a1 Case report-regression of pituitary macroadenoma after pituitary apoplexy: CT and MR studies. J Comput Assist Tomogr 15:832-834, 1991 8. Asari S, Ito T, Tsuchida S, et a1 MR appearance and cyst content of Rathke cleft cysts. J Comput Assist Tomogr 14532-535, 1990 9. Bartynski W, Lin L Dynamic and conventional spin echo MR of pituitary microlesions. AJNR Am J Neuroradiol 18:965-972, 1997 10. Benshoff E, Katz B Ectopia of posterior pituitary gland as a normal variant: Assessment with MR imaging. AJNR Am J Neuroradiol 11:709-712, 1990 11. Bergstrom M, Muhr C, Lundberg P, et al: PET as a tool in the clinical evaluation of pituitary adenomas. J Nucl Med 32610-615,1991 12. Bjerre P: The empty sella: A reappraisal of etiology and pathogenesis. Acta Neurol Scand Suppl 1301-25,1990 13. Bonneville J: Pituitary microadenoma: Early enhancement with dynamic CT. Implication of arterial blood supply and potential importance. Radiology 187857-861, 1993 14. Bonneville J, Cattin F, Moussa-Bacha K, et al: Dynamic CT of pituitary gland: The ”tuft sign.” Radiology 149:145-148, 1983 15. Brooks B, Gamma1 T, Allison J, et al: Frequency and variation of posterior pituitary bright signal of MR images. AJNR Am J Neuroradiol 10943-948, 1989 16. Buchfelder M, Wister R, Fahlbusch R, et al: The accuracy of CT and MR evaluation of sella turcica for detection of adrenocorticotropic hormone: Secreting adenomas in Cushing Disease. AJNR Am J Neuroradiol 141183-1190, 1993 17. Chong BW, Newman T H Hypothalamic and pituitary pathology. Radiol Clin North Am 313147-1153, 1993 18. Colombo N, B e r e I, Kucharczyk J, et al: Posterior pituitary gland appearance on MR images in normal and pathologic states. Radiology 165:481485, 1987 19. Cox TD, Elster A D Normal pituitary gland: Changes in shape, size and signal intensity during first year of life at MR imaging. Radiology 179:721-724, 1991 20. Daniels DL, Pech P, Mark L, et al: Magnetic resonance imaging of the cavernous sinus. AJNR Am J Neuroradiol 6:187-192, 1985 21. Daniels D, Pojunas K, Kilgore D, et al: MR of the diaphragma sellae. AJNR Am J Neuroradiol 7765-769, 1986 22. Davis PC, Hoffman JC, Spencer T, et al: MR imaging of pituitary adenoma: CT, clinical and surgical correlation. AJNR Am J Neuroradiol 8:107-112, 1987 23. Denton E, Powrie J, Ayers A, et al: Posterior pituitary ectopia and hypopituitarism: MR appearance of 4 cases and a review of literature. Br J Radiol 69:402-406, 1996 24. Dietrich R, Lis L, Greensite F, et al: Normal MR appearance of pituitary gland in first two years of life. AJNR Am J Neuroradiol 16:1413-1419, 1995 25. Dina T, Feaster S, Laws E, et a1 MR of pituitary gland post surgery: Serial MR studies following transphenoidal resection. AJNR Am J Neuroradiol 14763-769, 1993 26. Dolinskas C, Simeone F Transphenoidal hypophysectomy: Postsurgical CT findings. AJNR Am J Neuroradiol 6:45-50, 1985 27. Doppman J, Miller D, Patronas N, et al: The diagnosis of acromegaly: Value of inferior petrosal sinus sampling. AJR Am J Roentgenol 154:1075-1077, 1990 28. Doppman J, Ram Z , Shawker T, et al: Intraoperative US of pituitary gland: Work in progress. Radiology 192:111-115, 1994 29. Doyle F, McLachlan M Radiological aspects of pituitary-hypothalamic disease. Clin Endocrinol Metab 653-81, 1977

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