when present an alternate pathologic diagnosis (especially meningioma) should be considered.

IMAGING OF PITUITARY ADENOMAS

Magnetic Resonance Imaging

MRI has revolutionized the visualization of intracranial lesions in general and pituitary tumors in

particular. Useful pulse sequences for imaging the sella include T1 coronal and sagittal imaging before

and after gadolinium administration. Other sequences (e.g., T2 coronal) may be useful, especially in the

evaluation of cystic structures (fluid is generally hyperintense on T2) and previous hemorrhage (which

may be dark on T2). Because of the relative decreased vascularity of adenomas as opposed to normal

gland, timing of scanning relative to the administration of gadolinium is important; adenomas are

generally focally hypointense to normal gland. Dynamic scanning using thin section gradient echo

sequences may improve the sensitivity of visualization with small microadenomas (e.g., in Cushing

disease), but gland heterogeneity may lead to decreased specificity.

Computerized Tomography

CT scanning has largely been supplanted by MRI, but remains useful in the delineation of bony anatomy

for surgical planning and navigation. In those patients who cannot have an MRI, thin section coronal CT

after contrast administration can be used to demonstrate a pituitary lesion. The presence of calcification

on CT scanning can assist with the differential diagnosis, for example, a calcified cystic lesion, especially

in a child, is highly likely to represent a craniopharyngioma.

MRI Characteristics

The normal gland enhances relatively homogenously. It should be no greater than about 8 mm in

coronal height in males and 10 mm in females. The infundibulum should be midline. The posterior

pituitary may be bright on T1 without contrast (thought to represent secretory granules in axon

terminals), although this is not a constant finding.

Pituitary adenomas should be focally hypointense relative to normal gland on T1 sequences after

contrast. Microadenomas (<1 cm) may not significantly disrupt gland architecture. Macroadenomas

(>1 cm) show upward bowing of the diaphragm sella associated with stalk deviation, and larger

macroadenomas will demonstrate compression of the chiasm. The normal gland can be compressed,

usually superiorly and posteriorly. The cavernous sinus is variably involved; it can be difficult to

distinguish invasion as opposed to compression. Lesions surrounding the cavernous carotid are

obviously invasive; lesions which circumscribe less than 25% are usually compressive. It has been

suggested than lesions which circumscribe less than 67% of the carotid diameter are not invasive, but

this is very variable. Adenomas can also be cystic, which may show T1 bright signal before contrast

consistent with high protein fluid or hemorrhage.

Craniopharyngiomas may be cystic or solid, and intra- or suprasellar. Characteristics of the cyst fluid

can vary with the protein content, with greater T1 hyperintensity associated with higher protein. The

cyst wall is commonly calcified on CT, especially in children. Since the tumor is often suprasellar or

arises along the stalk, the gland is typically compressed inferiorly from above.

Pituitary cysts can demonstrate variable imaging characteristics also depending upon their protein

content. Rathke cleft cysts arise posteriorly in the sella, or sometimes along the stalk. They can be T1

hypo- or hyperintense depending on protein content, and can compress the gland anteriorly or from

above. The cyst wall is usually thin with minimal enhancement. If there is a solid component or

calcification, the diagnosis is more likely to represent a craniopharyngioma. Arachnoid cysts of the sella

contain fluid isointense to CSF. There will be minimal if any enhancement of the wall, as the cyst is

lined with a thin arachnoid layer. The gland is usually compressed inferiorly or anteriorly.

Other Sellar Lesions

Germinomas usually involve the posterior gland, stalk, and/or hypothalamus. They are typically brightly

enhancing, and the borders are relatively indistinct. An enhancing lesion of the posterior sella associated

with a pineal mass is highly likely to represent a germinoma. Germ cell tumors may disseminate along

CSF pathways, leading to enhancement around the fourth ventricle. Meningiomas are usually brightly

enhancing, often more so than the gland itself. As they arise from the dura, they can be variably located

in and around the sella. If they arise from the diaphragm, they can be difficult to distinguish from

2216

adenomas, but usually compress the gland from above. Meningiomas are often associated with a dural

“tail,” which spreads out from the central mass of the tumor, and sometimes with focal hyperostosis.

Meningiomas of the cavernous sinus can lead to carotid constriction, best seen on coronal images when

comparing the transverse diameter of the intracavernous carotids, while adenomas rarely do. Metastases

are typically locally invasive, brightly enhancing, and rapidly growing. They can spread

hematogenously to the gland, or represent focal metastases to parasellar bony structures. When

invading the cavernous sinus they can lead to a cavernous sinus syndrome, while adenomas rarely do.

SURGICAL TECHNIQUE

Although the first reported pituitary operation was a craniotomy done in 1889 by Sir Vincent Horsley,19

the first transsphenoidal approach was described in 1907 by Hermann Schloffer, a Viennese

otolaryngologist, when he reached the sphenoid via a lateral rhinotomy incision.20 Less disfiguring

approaches were devised by the American neurosurgeon Harvey Cushing, who, with William Halsted,

devised the sublabial approach in 1910, and another Viennese otolaryngologist, Oscar Hirsch, who

described a fully endonasal procedure.21 Variants of these approaches remain in use today. Cushing

performed over 200 transsphenoidal operations with an overall mortality rate of 5% – amazingly low

given the lack of imaging, antibiotics, hormone replacement, and modern visualization – but decided in

1927 that the craniotomy was the more preferred procedure. With his decision, the transsphenoidal

approach fell into relative disfavor, although kept alive by Dott in Edinburgh and Guiot in Paris, who

introduced the use of intraoperative fluoroscopy as a navigation technique. When Jules Hardy of

Montreal described the use of the operating microscope and reported the first removal of a pituitary

microadenoma in 1962, pituitary surgery entered the modern era.22

The transsphenoidal approach is relatively noninvasive, as it employs the nasopharynx and sphenoid

sinus to access the skull base, but the surgeon is constrained to operate through a narrow corridor, to a

relatively deep target, surrounded by important structures (carotids and optic apparatus). The surgeon

must (1) approach and navigate to the tumor, (2) visualize the pathology, and (3) maximally resect the

tumor while minimizing damage to the adjacent structures, that is, normal gland.

Approach

There are three transsphenoidal approaches to the sella in use today, in addition to the seldom necessary

subfrontal craniotomy (Fig. 78-2). The sublabial approach, described by Cushing and Halsted, employs

an incision in the gingiva with a submucosal dissection to the bony nasal aperture, and then a

submucosal dissection along the septum to the sphenoid. Because the approach is not constrained by the

width of the nares, the degree of access is relatively wide, but the gingival incision is painful, can be

associated with numbness of the teeth and gums, and usually requires nasal packing to reapproximate

the mucosa. The two endonasal approaches are constrained by the width of the nasal aperture, but avoid

the complications associated with a gingival incision. The approach described by Hirsch uses a

submucosal tunnel along the septum through an anterior mucosal incision immediately posterior to the

columella; Hirsch felt that the submucosal tunnel gave him a relatively sterile field through which to

access the sphenoid, important in the days prior to antibiotics, but this approach also requires nasal

packing to reapproximate the mucosa to the septum, which patients find uncomfortable. The direct

endonasal approach described by Griffith and Veerapen23 and Cooke and Jones

24 uses either an incision

at the insertion of the septum into the face of the sphenoid, or an enlargement of the natural ostia, with

a posterior septectomy. Because there is no submucosal tunnel, nasal packing is usually not required.

Figure 78-2. Surgical approaches to the sella.

Navigation

2217

It is critical to maintain accurate orientation in the sellar approach, as the face of sella is bounded

immediately laterally by the carotid protuberances, and superolaterally by the optic canals. The

insertion of the nasal septum posteriorly is usually a midline structure and can be used for orientation,

while the sphenoid septations are very variable, and can be used for orientation only when correlated

with preoperative imaging. Lateral intraoperative fluoroscopy as introduced by Guiot gives immediate

real-time two-dimensional (2D) orientation in a sagittal plane, although it does not provide orientation

in the coronal plane. Neuronavigational devices establish a three-dimensional (3D) reference plane by

registering facial anatomy with preoperative imaging, and can be used to correlate intraoperative

anatomy with preoperative imaging by means of a navigational “wand” recognized by the device in real

time. This gives 3D information to guide the approach, but is dependent on the accuracy of the

registration, and is less valuable in determining the adequacy of resection and orientation within the

tumor, as tumor anatomy can change during resection. It is used routinely at many institutions, and is

especially valuable in cases where normal bony anatomy has been destroyed by tumor growth or

previous surgery.

VISUALIZATION

Hardy introduced the use of the intraoperative microscope to pituitary surgery and it remains in

widespread use today. After the introduction of the rigid endoscope to field of sinus surgery by

otolaryngologists, its use in transsphenoidal surgery was reported by Janowski in 199225; it has now

been the topic of multiple reviews and has become widely accepted. Advantages of the microscopic

approach are the superb optics and binocular vision; a major disadvantage is the requirements for direct

line-of-sight viewing, though for smaller tumors, that is, the microadenomas of Cushing disease, this

disadvantage may not be significant. The endoscope gives a wider field of view and has the ability to

see at angles off the primary visual axis. However, most endoscopes offer only monocular vision with

no depth of field, though 3D endoscopes are under development. Although the endoscopic technique has

been touted as “less invasive,” the need to supply sufficient access for both the endoscope and working

instruments may actually require greater dissection of the sphenoid, ethmoids, and possibly resection of

the turbinate(s). A number of meta-analyses have been published comparing the two techniques, usually

using recent endoscopic results compared to older historical microscopic series. The overall results for

secretory tumors, where there are defined biochemical criteria for remission, appear similar, with a

possible edge to endoscopy in larger secretory tumors in association with perhaps a small increased risk

of vascular complications.

Figure 78-3. A: The coronal view (T1-weighted image with contrast) of a large nonfunctioning macroadenoma with significant

chiasm compression. B: The intraoperative MRI (T1-weighted image with contrast) shows tumor removal with fat packing and

hemostatic material in place. The chiasm is decompressed. C: The postoperative MRI at 8 weeks shows partial resorption of the fat

packing and hemostatic material.

Determining the Adequacy of Resection

As most pituitary tumors are removed by internal decompression allowing collapse of the tumor

capsule, there may be no direct visualization of the adequacy of resection. Endoscopic inspection of the

tumor capsule can sometimes provide an indication, but prolapse of the diaphragm as the capsule

collapses (itself an indication of adequacy of decompression) can make thorough internal visualization

difficult. Intraoperative MRI (iMRI) imaging has proven useful in the determination of resection

2218

adequacy, as the technique allows the surgeon to visualize areas of residual tumor not seen with direct

inspection. A comparison of preoperative, intraoperative, and postoperative imaging in a patient with a

large nonfunctioning macroadenoma is shown in Figure 78-3. A number of studies have reviewed the

utility of intraoperative imaging. Most report that additional tumor resection can be achieved in about

20% of cases, but this is partly a function of when, during the course of the procedure, the surgeon

chooses to image, and premature imaging may bias the results in favor of demonstrating the utility of

the iMRI.26 In addition, imaging can show whether the chiasm has been adequately decompressed,

which correlates with postoperative visual improvement, and may assist in the avoidance of

postoperative complications. The iMRI equipment is costly, however, and requires significant alterations

in surgical workflow and operative time, with the risk of operating in close proximity to a high-strength

magnetic field. It has been debated whether resection can be better optimized with the use of the iMRI

versus the endoscope, and each approach has its adherents. In those few studies combining the use of

endoscopy with the iMRI, most showed that some degree of additional resection can be achieved after

imaging.27,28

Surgical Technique

7 There are a number of variations in surgical technique, determined by the preference of the surgeon

and the dictates of the anatomy. The patient is given preoperative broad-spectrum antibiotic coverage

and stress-dose steroids (except for patients with Cushing disease, where preoperative steroid coverage

can be held). After the induction of general endotracheal anesthesia, the patient is positioned in a

semirecumbent position. The head may be turned toward the surgeon or in a neutral position if two

surgeons will together be performing an endoscopic approach. The head can be held in a gel headrest or

pinned using the Mayfield clamp. If neuronavigation is used, the reference fiducials are affixed and

registered, or the lateral fluoroscope is positioned. The area of the proposed incision is infiltrated with

local anesthesia with epinephrine as a vasoconstrictor. With a direct endonasal approach the incision is

made along the posterior septum, and either the septum is fractured and deviated contralaterally, or a

posterior septectomy is performed. With a microscopic approach, a nasal speculum is introduced,

compressing the turbinates laterally. With the endoscopic approach, the middle turbinate may require

removal to increase access. The face of the sphenoid is opened, and any septations impeding access are

removed. Anatomy of the sphenoid septations gleaned from preoperative imaging can be useful in

guiding the approach to the midline sella, which is drilled to dura. The dura is lightly cauterized and

incised. For macroadenomas, the tumor is usually immediately evident, and can be removed with ring

curettes back to normal gland. With microadenomas, especially those causing Cushing disease, detection

can be difficult. The gland is hemisected into quadrants, with biopsies taken from each quadrant guided

by the preoperative IPSS lateralization. If no tumor is found on frozen section analysis, a

hemihypophysectomy can be performed. It is important to preserve normal gland; this can usually be

distinguished by color and consistency, and, in macroadenomas, is usually compressed posteriorly and

superiorly. As the resection proceeds, the diaphragm should prolapse into the field in cases of

preoperative chiasm compression. After tumor removal, the resection cavity is inspected for residual

tumor; 30-degree or 70-degree endoscopes are useful in visualizing areas not in direct line-of-sight.

Hemostasis is achieved by packing with any number of available hemostatic materials. After hemostasis,

most surgeons pack the tumor cavity with fat, muscle or absorbable hemostatic material; a water-tight

seal is especially important if a CSF leak has been created. The fat is buttressed in place and the sellar

floor reconstructed with septal cartilage or bone, titanium mesh, or proprietary plastic materials. Fibrin

glue or other sellar sealant can be used if needed. The septum is returned to the midline. With a direct

endonasal approach, nasal packing is usually not required. If a submucosal tunnel was created during

the approach, nasal packing is placed; if a sublabial incision was used, the gingival mucosa is closed

with a few absorbable sutures. The use of iMRI can be timed at the discretion of the surgeon. Some

surgeons will maintain the sterile field and image before closure; others complete the closure (since

reopening is usually straightforward) and image prior to anesthesia reversal.

Postoperative Management

Careful monitoring in the postoperative period is essential. Most patients require only one to two nights

of hospitalization; an ICU stay is usually not necessary. Potential complications include postoperative

hemorrhage, CSF leakage, meningitis, epistaxis, and endocrine dysfunction.

1. Postoperative hemorrhage can occur into the tumor resection cavity with resulting visual

2219