1
Fully Endoscopic Transnasal-Transsphenoidal Pituitary Stalk Surgery
Joseph B. Eby M.D., Sung Tae Cha M.D., Hrayr K. Shahinian M.D.
Skull Base Institute, California, USA
Corresponding author:
Hrayr K. Shahinian M.D.
Skull Base Institute
8635 West Third Street, 1170W
Los Angeles, CA 90048
310.691-8888 (phone)
310.691-8877 (fax)
2
Abstract:
Advances in CT and MRI technology allow for the early recognition of pituitary stalk
pathology. However, imaging characteristics may not provide an accurate diagnosis, and the
differential of a pituitary stalk abnormality often remains quite broad. A biopsy to confirm the
diagnosis is frequently delayed due to concerns regarding a surgical procedure.
Historically, a transcranial approach was used to access all suprasellar pathology.
However, limitations and complications inherent to this procedure have led to a search for a less
invasive approach. Adaptation of the microscopic transsphenoidal technique to pituitary stalk
surgery has addressed many of the disadvantages of the transcranial approach. More recently,
endoscopic pituitary surgery has demonstrated advantages over the microscopic approach. In
this article we describe our surgical technique and report the first cases of completely endoscopic
transnasal-transsphenoidal pituitary stalk surgery. From our results we conclude that the
endoscopic procedure is a safe and minimally invasive method to biopsy or resect pituitary stalk
abnormalities.
Key Words: Pituitary stalk, Endoscopic surgery, Minimally invasive
3
Introduction:
Over the past 20 years advances in CT and MRI technology including the addition of
dynamic contrast scanning, have led to an improved recognition and characterization of pituitary
stalk abnormalities.1, 2 However, the overall incidence of pituitary stalk abnormalities in the
general population remains unknown. Often pituitary stalk lesions are discovered during the
workup for endocrine abnormalities, or in relation to specific symptoms such as visual changes
or headaches. In addition to masses and cystic lesions, pituitary stalk thickening as defined by
specific criteria is also a significant finding.3-5 Once identified, the process of properly
diagnosing and treating a pituitary stalk abnormality requires experience, a high index of
suspicion, and the persistence to obtain a proper diagnosis prior to instituting any treatment
regimen. Over the past century surgeons have reported a variety of pituitary stalk lesions as
depicted in Table 1.5-28 Without a biopsy many patients undergo hormonal replacement and
empiric therapy, especially if there are no compressive symptoms such as visual disturbance.
Occasionally, follow up scans are used to assess the growth pattern of the lesion. These
measures are used to avoid a surgical biopsy, to avoid the risk of pituitary stalk disruption with
resultant panhypopituitarism, damage to the optic chiasm, or the potential complications of a
transcranial operation.4
However, it must be noted that misdiagnosis and incorrect therapy can also result in
adverse consequences, as the standard treatment for many of these disorders is extremely
diverse. Therapy for pituitary stalk abnormalities may involve steroid administration,
radiosurgery, surgical resection, or serial observation. Even with a thorough work up and careful
evaluation of the imaging studies, several case reports have documented that the preoperative
diagnosis of pituitary stalk abnormalities often differs from the pathology revealed at the time of
surgery.6, 11, 27 Acquiring a tissue diagnosis via biopsy or excision of the lesion remains the only
way to definitively identify many of these lesions. Therefore, it is imperative that in all but the
most straightforward cases, such as those with systemic manifestations, classic presentation, and
4
pathognomonic imaging results; treatment should be withheld until a tissue diagnosis via biopsy
or excision is performed.
Traditionally, a transcranial approach has been used to biopsy or excise pituitary stalk
lesions.6, 7, 9, 11, 18, 20-22, 29-32 In a recent article Dyer reflects the feeling of many of his collogues
when he declares: “the cranial approach remains the only operative approach to lesions in the
supradiaphragmatic region”.30 However, the transcranial method is not without its critics, and the
morbidity associated with this approach has led to a continued search for a less invasive and
more direct route to pituitary stalk abnormalities. More recently, surgeons have used a
microscopically assisted transsphenoidal method, demonstrating adequate exposure for selected
lesions, and citing a decreased risk of operative complications.8, 10, 16, 22, 33, 34
Our group has been performing endoscopic pituitary surgery since 1996 and have
published our results; noting that the endoscope provides excellent visualization of the supraand parasellar anatomy.35, 36 Based on our observations, we propose that the endoscope is ideal
for accessing the pituitary stalk via a transnasal-transsphenoidal approach. This technique would
provide a minimally invasive method to obtain a definitive tissue diagnosis in the difficult case
of an unidentified pituitary stalk lesion, with the additional possibility of complete resection if
appropriate.
5
Patients:
Case 1
History - 30 year-old female with 13-year history of diabetes insipidus and irregular menses and
recurrent headaches. The patient has been treated with intranasal DDAVP, estrogen, and
progesterone.
Examination/Preoperative Testing: The patient had no visual field deficits or other focal
neurologic abnormalities noted. Two months prior to our evaluation the patient had a positive
water deprivation test. Her laboratory at that time included: luteinizing hormone 0.06mIU/ml
(normal 2-49mIU/ml), follicle stimulating hormone level 0.79mIU/ml (normal 1.8-35mIU/ml),
estradiol 1.2ng/dl (normal 3-30ng/dl), prolactin and thyroid stimulating hormone were within
normal limits. An MRI of the pituitary fossa and hypothalmus demonstrated marked thickening
of the pituitary stalk and mild asymmetry of the optic chiasm with slight enlargement of the right
side.
Operation – The patient underwent a completely endoscopic transnasal biopsy of the pituitary
stalk, as well as the anterior and posterior pituitary gland as outlined in the surgical technique
section.
Pathology – Biopsy specimens of the anterior and posterior pituitary as well as the pituitary stalk
revealed no tumor, granuloma, or histiocytosis, nor did there appear to be an infectious etiology
evidenced by the absence of viral inclusions, acid-fast bacteria, fungi, or eosinophilic infiltrate.
The biopsy specimen of the pituitary stalk and posterior gland did however demonstrate a
lymphoid infiltrate composed of (CD 20) B cells, (CD 3) T cells, and fibrous tissue, resembling
lymphocytic hypophysitis (LH). However, this infiltrate differed from LH in that it did not
involve the anterior pituitary gland and did not demonstrate the prominent plasma cell infiltrate
typically seen with LH.
Postoperative Course – The patient was transferred to the surgical intensive care unit for
overnight monitoring. Her diabetes insipidus was managed with her usual regimen of intranasal
6
DDAVP. The patient was transferred to the floor on postoperative day one and discharged home
on postoperative day two. The patient presented six weeks postoperatively with headache,
nausea, and sinus pain with minimal nasal drainage. Lumbar puncture demonstrated no evidence
of meningitis. The patient underwent endoscopic re-exploration and closure of a small
cerebrospinal fluid (CSF) fistula. The patient was subsequently discharged home postoperative
day three.
In the ten months since her biopsy the patient remains on DDAVP and has had no
worsening of her endocrine function, nor has she demonstrated any additional compressive
effects of this lesion. Several reports have documented similar pituitary stalk and infundibular
inflammatory infiltrates, which do not specifically meet the criteria for LH.14, 15, 21, 37 Having
ruled out a malignant or infectious etiology, if the patient’s endocrine function deteriorates, or
she demonstrates any compressive symptoms, she can now safely undergo a trial of steroid
administration to determine if the lymphocytic infiltrate will respond similarly to LH.
Case 2
History – 56-year-old male with a history of an uncharacterized movement disorder, thought to
resemble Parkinson’s Disease, which began in 1996. The patient also complained of intermittent
visual disturbance (loss of binocular vision) and recurrent headaches, night sweats and tactile
fevers. The patient had a medical history significant for hypertension (35 years), controlled with
diovan; as well as primary hypothyroidism (30 years) managed with thyroxine.
Examination/Preoperative Testing – Preoperative evaluation revealed mask-like faces, with a
fine resting tremor of his left hand. Deep tendon reflexes were 3/4 in all extremities, and the
patient had a negative Romberg’s sign. Visual fields and EOMs were intact. An MRI performed
prior to our evaluation revealed a 0.8x0.8x0.9cm enhancing mass within the pituitary stalk
(Figures 1 & 2). Laboratory testing revealed normal values for GH, PRL, FSH, LH, and cortisol.
Operation - The patient underwent a completely endoscopic transnasal resection of a Rathke’s
cleft cyst as outlined in the surgical technique section (Figure 3).
7
Pathology – Pathology was consistent with Rathke’s Cyst Wall.
Postoperative Course – The patient monitored in the surgical intensive care unit for overnight,
and was transferred to the floor on post-operative day 1. The patient was out of bed ambulating
and was tolerating a regular diet on post-operative day 1. Over the next several days the patient
experienced a mild form of DI, requiring DDAVP on two occasions. The patient subsequently
developed an equally mild form of SIADH, which responded well to fluid restriction. Once the
patient’s serum sodium stabilized the patient was discharged home and has done well postoperatively. The patient remains only on his pre-operative antihypertensive and supplemental
thyroid medication. Following his surgery the patient has noted a subjective improvement in his
vision and a decrease in the frequency and intensity of his prior headaches.
Methods:
Surgical Technique
Under general anesthesia in a supine position the patient’s head is placed in a radiolucent
Mayfield apparatus, as fluoroscopy is utilized during the operative procedure to verify anatomic
landmarks and help guide the dissection. A 2.7 mm Storz 00 (Karl Storz of America, Culver
City, CA, USA) endoscope fitted with an irrigation sheath and attached to a pneumatic holding
arm is introduced into the right nostril and advanced to the anterioinferior border of the middle
turbinate. An elevator is used to outfracture the middle turbinate and displace the septum
providing a widened nasal passage to allow the endoscope and dissecting instruments to pass
easily into the sellar region. The location of the sphenoid sinus is verified with fluoroscopy. The
mucosa is then cauterized and stripped off the anterior wall of the sphenoid sinus. The anterior
wall of the sphenoid sinus is resected using a combination of Kerrison and Decker rongeurs, and
then both sinuses are entered and the septum between them is removed. The mucosa of the
sphenoid sinus is removed, and the posterior wall of the sinus (anterior wall of the sella) is
visualized and confirmed with fluoroscopy. The sella is entered, and a 1.5cm opening is made in
8
the sella exposing the dura overlying the pituitary gland. The dura is incised using a modified #
11 blade and the anterior lobe of the pituitary gland is identified. Using microdissecting
instruments the pituitary gland is completely mobilized from all surrounding arachnoid and dural
adhesions. Small biopsy specimens of the anterior and posterior pituitary gland are obtained and
sent for frozen section to rule out infiltration of the pituitary gland by the stalk abnormality. The
diaphragma sella is incised in the midline to access the superior aspect of the pituitary stalk. The
gland is gently retracted inferiorly as the anesthesiologist performs a valsalva maneuver to better
expose the pituitary stalk. Additional visualization of the suprasellar region during the procedure
is obtained through the use of a 300angled endoscope. Using the 1mm Kerrison rongeurs
between one and three biopsy specimens are obtained from the pituitary stalk, one of which is
sent for frozen section in the operating room. During the second case the Rathke’s cyst was
opened and the wall of the cyst resected and sent to pathology. Hemostasis is obtained using
Gelfoam and gentle pressure. Once enough tissue is obtained for histologic analysis and
hemostasis is adequate, the dural opening is plugged with an abdominal fat graft. This is then
reinforced with fibrin glue. Unlike the transseptal technique, nasal packing is not necessary.
Only a small gauze sponge is placed below the nose to collect any drainage or debris. The
patient is awoken from general anesthesia, extubated and taken to the surgical intensive care unit
for overnight observation.
Results:
The two cases outlined above demonstrate some of the difficulties in diagnosing and
treating pituitary stalk abnormalities. In both cases the endoscopic approach provided excellent
exposure of the pituitary stalk and the supradiaphragmatic region, allowing adequate biopsy
specimens to be obtained in the first case, and complete resection of the Rathke’s cyst to be
performed in the second case. Both patients had complete recovery from their procedure with no
long-term pituitary dysfunction or visual disturbance.
9
Discussion:
No large series reports have been published concerning the management of pituitary stalk
lesions, an obvious reflection of their infrequent occurrence. As physicians gain a better
understanding of the etiology and therapeutic options for treating pituitary stalk lesions, an
increasing number of reports advocate early surgical biopsy in patients where the diagnosis of a
pituitary stalk abnormality is unclear.5, 14, 15, 27
The difficulty of performing a diagnostically valuable yet safe biopsy of the pituitary
stalk has been addressed through advances in technology and the development of less invasive
surgical approaches.
Until recently, biopsy or excision of suprasellar lesions necessitated a transcranial
approach. Some surgeons still contend that this is the preferred method for accessing the
pituitary stalk, especially in patients with a normal sized sella. As Laws states: “A tumor may
arise high on the stalk above the diaphragm sellae and the sellae may be normal. This situation
effectively precludes a transsphenoidal approach.”11, 22, 34 There are the three (subfrontal,
pterional and subtemporal) major variations of the transcranial approach, and several reported
modifications, each with specific advantages and disadvantages in exposing the pituitary stalk.
The oft-cited advantages of the transcranial technique include better visualization of the
optic chiasm, anterior circle of Willis and depending on the approach the lateral extensions of the
suprasellar region. However, access to the pituitary stalk via a transcranial approach does have
several limitations, with some methods providing only unilateral exposure, others forcing the
operation to take place overtop of the optic nerve or between the optic chiasm. The various
angles of approach used in these procedures can be awkward and confusing, distorting anatomic
relationships and sometimes obscuring the lateral and posterior aspects of structures in this
region.8, 24, 32, 34 Another major disadvantage of the transcranial method is the brain retraction
required for adequate exposure of the pituitary stalk resulting in an estimated 10% incidence of
retraction related complications.8, 32, 38 Previous reports have also found a high incidence of
10
other complications including panhypopituitarism, anosmia, as well as visual field deficits.
32, 34, 39, 40
8, 24, 30,
Patients undergoing a transcranial approach to the pituitary stalk typically require
longer hospitalizations and have a more prolonged recovery period.24 In short, the transcranial
approach provides less than optimal exposure of this region, and has a high incidence of
complications. Therefore, in much the same way that surgeons moved away from the
transcranial approach to pituitary adenoma surgery in the early 1960’s, many surgeons have
converted to a less invasive and more direct microscopically assisted transsphenoidal approach to
the pituitary stalk in the 1990’s.8, 10, 24, 32-34
Recently, several case reports and a few small series reports have described microscopic
transsphenoidal approaches to biopsy or excise pituitary stalk lesions including adenomas,
craniopharyngiomas, hemangioblastomas, and Rathke’s cleft cysts among several others.8, 10, 15,
16, 22, 24, 33, 34
Many of these reports have documented successful transsphenoidal biopsy or
resection of pituitary stalk lesions even in the presence of a normal sized sella.8, 33, 34 Advantages
of the transsphenoidal method include improved visualization of the inferior portion of the
pituitary stalk and surrounding structures.8, 33, 34 In much the same way as transsphenoidal
pituitary gland surgery, the transsphenoidal approach to suprasellar pathology appears to require
less time, and reduces the incidence of complications compared to the traditional transcranial
method.32, 40, 41 Early reports have yielded excellent results regarding the preservation of
pituitary function, as well as allowing for more rapid recovery and shorter hospitalization.8, 33, 34
The morbidity of brain retraction is also avoided with the transsphenoidal approach to the
pituitary stalk. The most common complication of the transsphenoidal technique is
postoperative cerebrospinal fluid fistulae.8, 10, 34, 42, 43
The microscopic transsphenoidal approach has allowed access to a select number of
pituitary stalk lesions. However, the angled path through the sphenoid sinus hinders the direct
forward view of the operating microscope and limits exposure of abnormalities, which lie
completely above the diaphragm sellae, or in the narrow lateral recesses of the suprasellar region.
11
The application of endoscopy to pituitary stalk surgery is a natural progression from its
use in pituitary gland surgery. The ability of the endoscope to better visualize suprasellar
pathology is a result of technological advances in optics, magnification, and illumination.
Angled endoscopes, allow the surgeon to gain exposure deep within the narrow confines of this
region, looking around corners and avoiding extensive dissection, which is often required for
adequate microscopic exposure.
In 1999 Spencer published a direct volumetric comparison of the area visualized by the
endoscope and microscope. In this report he demonstrated that the exposure of the suprasellar
region provided by even the 00 endoscope was greater than two-times that afforded by the
operating microscope.44 The improved endoscopic exposure should result in a greater ability to
biopsy or resect pituitary stalk lesions difficult or impossible to access using a microscopic
approach. As in all transsphenoidal approaches to the suprasellar region, exact knowledge of the
pituitary stalk’s arterial supply, anatomic boundaries, and surrounding structures are crucial to
avoid catastrophic results.33, 45, 46 The improved endoscopic visualization of the surrounding
structures including the carotid and optic protuberances, as well as the pituitary stalk itself
should also help reduce the incidence of other serious complications when compared to the
microscopic technique.
Early studies comparing the microscopic and endoscopic approaches to pituitary gland
tumors suggest that the endoscopic technique allows a smaller dissection, with improved
visualization, allowing for more complete pituitary tumor removal.35, 47-54 The transnasaltranssphenoidal method has also been shown to decrease postoperative pain, eliminate the need
for nasal packing, and avoid possible complications of a sublabial incision including lip
numbness and nasal-oral fistula.35, 47-54 All of these factors combine to result in a shorter
hospitalization and a more rapid recovery, especially when compared to the transcranial
approach.35, 47-54 The primary complication of endoscopic pituitary surgery as in the microscopic
12
transsphenoidal approach is postoperative cerebrospinal fluid fistula, which was realized in one
patient in this report.
The endoscopic technique does require some adjustment for the surgeon. Monitoring
three-dimensional movements on a two-dimensional video screen does not provide the depth of
view afforded by the operating microscope, and makes manipulating instruments in such a
confined space technically difficult. Various models have been described for obtaining technical
proficiency in this approach prior to clinical implementation.36
This report includes a very limited number of cases, from which it is impossible to draw
conclusions about the overall utility of the endoscopic technique. However, these cases should
serve as an introduction to the application of endoscopic surgery to abnormalities of the pituitary
stalk. Similar to the microscopic technique, preoperative planning will allow the surgeon to
decide if a lesion can be accessed via the endoscopic transsphenoidal approach.
Conclusions:
Pituitary stalk abnormalities although rare require a thorough evaluation and demand that
the clinician be cognizant of the myriad of pathologic entities which can occur in this region.
Therapy directed at a particular abnormality should be avoided unless the diagnosis is clear.
When the features of a lesion do not reveal a definitive diagnosis a surgical biopsy is often
necessary. Biopsy or resection of a pituitary stalk lesion using the endoscopic transnasaltranssphenoidal approach offers several advantages over both the transcranial and microscopic
transsphenoidal methods.
13
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20
Table 1
Reported cases of pituitary stalk pathology 5-28
Meningioma
Lymphoma
Microadenoma
Lymphocytic hypophysitis
Granulomatous hypophysitis
Plasma cell granuloma
Germinoma
Hemangioblastomas
Tuberculoma
Sarcoidosis
Metastasis
Granular cell tumor
Histiocytosis X granuloma
Inflammatory pseudotumors
Rathke’s cleft cyst
Craniopharyngiomas
21
Legend:
Figure 1 – (Case 2) MRI sagital image revealing a contrast enhancing mass within the pituitary
stalk (White arrow).
Figure 2 – (Case 2) MRI coronal image revealing a contrast enhancing mass within the
pituitary stalk (White arrow).
Figure 3 – (Case 2) Intra-operative photo demonstrating the excellent exposure of pituitary stalk
mass (Rathke’s Cyst) provided by the endoscope.