Surgical Techniques and Technologies for the Management of Patients with Nonfunctioning Pituitary Adenomas

Sponsored by

Congress of Neurological Surgeons (CNS) and the AANS/CNS Tumor Section 

Endorsed by

Joint Guidelines Committee of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS)


John S. Kuo, MD, PhD1*, Garni Barkhoudarian, MD2*, Christopher J. Farrell, MD3*, Mary E. Bodach, MLIS4, Luis M. Tumialan, MD5, Nelson M. Oyesiku, MD, PhD6, Zachary Litvack, MD7, Gabriel Zada, MD8, Chirag G. Patil, MD9, Manish K. Aghi, MD, PhD10

1 Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin, USA

2 Brain Tumor Center & Pituitary Disorders Program, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA

3 Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

4 Guidelines Department, Congress of Neurological Surgeons, Schaumburg, Illinois, USA

5 Barrow Neurological Institute, Phoenix, Arizona, USA

6 Department of Neurosurgery, Emory University, Atlanta, Georgia, USA

7 Department of Neurosurgery, George Washington University, Washington, DC, USA

8 Department of Neurological Surgery, University of Southern California, Los Angeles, California, USA

9 Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

10 Department of Neurosurgery, University of California, San Francisco, San Francisco, California, USA

*These authors contributed equally to this work.


John S. Kuo, MD, PhD
Department of Neurological Surgery School of Medicine and Public Health University of Wisconsin
Box 8660 Clinical Science Center
600 Highland Ave.
Madison, WI 53792


Background: Numerous technological adjuncts are used during transsphenoidal surgery for non-functionomg pituitary adenomas (NFPAs), including endoscopy, neuronavigation, intraoperative magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) diversion, and dural closure techniques.

Objective: To generate evidence-based guidelines for the use of NFPA surgical techniques and technologies.

Methods: An extensive literature search spanning January 1, 1966, to October 1, 2014 was performed, and only articles pertaining to technological adjuncts for NFPA resection were included. The Clinical Assessment evidence-based classification was used to ascertain the class of evidence.

Results: Fifty-six studies met inclusion criteria, and evidence-based guidelines were formulated on the use of endoscopy, neuronavigation, intraoperative MRI, CSF diversion, and dural closure techniques.

Conclusion: Both endoscopic and microscopic transsphenoidal approaches are recommended for symptom relief in patients with NFPAs, with the extent of tumor resection improved by adequate bony exposure and endoscopic visualization. In select cases, combined transcranial and transsphenoidal approaches are recommended. Although intraoperative MRI can improve gross total resection, its use is associated with an increased false-positive rate and is thus not recommended. There is insufficient evidence to recommend the use of neuronavigation, CSF diversion, intrathecal injection, or specific dural closure techniques.


What is the role of technical aspects (adjuvants) of operative treatment of patients with nonfunctioning pituitary adenomas (NFPAs)?

Target Population
These recommendations apply to initial operative treatment of adult patients with NFPAs.

Do transsphenoidal or endoscopic surgical approaches lead to symptomatic relief for NFPA patients?

Level III: Transsphenoidal microsurgery or endoscopic resection is recommended for symptomatic relief of nonfunctioning pituitary adenoma patients.

What surgical approach is recommended for elderly NFPA patients?

Level III: The transsphenoidal approach is recommended for NFPA resection in ASA grade 1-3 elderly patients.

Does bony exposure alter the extent of NFPA resection?

Level III: Adequate bony exposure of the sphenoid and sellar regions is recommended to improve extent of NFPA resection.

Does endoscopic visualization improve visualization of NFPA tumors remaining after standard microsurgery?

Level III: Endoscopic approaches are recommended for better visualization of portions of tumors remaining after standard microsurgery, shown in multiple Class III studies in which direct endoscopic visualization revealed residual tumor tissue after initial microsurgery.

Is a surgical strategy of combined transsphenoidal and transcranial approaches useful in NFPA surgery?

Level III: For select, invasive NFPAs with significant suprasellar, frontal, and/or temporal extension, the combined surgical strategy of transsphenoidal and transcranial approaches is recommended.

Does use of intraoperative MRI technology improve gross total resection of NFPAs?

Level III: Although intraoperative MRI (low-field or high-field) helps improve immediate overall gross total resection of nonfunctioning pituitary adenomas, intraoperative MRI for estimating residual tumor is not recommended due to a reported variable false-positive rate. This false-positive rate may contribute to the higher rate of gross total resection occurring with intraoperative MRI (but at the cost of removing normal tissue) and underscores the importance of incorporating surgical experience in the interpretation of intraoperative MR imaging for surgical decision-making.

Level of Evidence: Insufficient evidence

Is stereotactic neuronavigation a useful adjunct for NFPA surgery?

There is insufficient evidence to recommend the use of neuronavigation as a useful adjunct for NFPA transsphenoidal surgery.

Does introduction of intrathecal saline or air improve resection of suprasellar NFPAs?

There is insufficient evidence to recommend the use of intrathecal saline or air introduction for suprasellar tumor delivery to augment NFPA resection.

Does perioperative CSF diversion decrease the risk of postoperative CSF leak for NFPA surgeries?

There is insufficient evidence to recommend the use of perioperative CSF diversion to prevent postoperative CSF leak.

Is there a superior dural closure technique to prevent CSF leaks?

There is insufficient evidence to recommend the use of specific dural closure techniques to prevent postoperative CSF leak for NFPA resection.



Transsphenoidal surgery with microscopic visualization has been the standard for nonfunctioning pituitary adenoma (NFPA) resection for many decades, with technological advances in endoscopic visualization technology driving the advent of endoscopic surgical approach as a major alternative. In addition, intraoperative MRI technologies are now available at numerous sites for intraoperative imaging. This chapter surveys the literature for evidence concerning the surgical approaches of transsphenoidal microsurgery, endoscopic resection, and transcranial surgery, as well as adjunctive technological innovations such as intraoperative MRI, neuronavigation, plus technical concerns of CSF diversion and dural closure.


Process Overview

The evidence-based clinical practice guideline task force members and the Tumor Section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) conducted a systematic review of the literature relevant to the management of NFPAs. Additional details of the systematic review are provided below and within the introduction and methodology chapter of the guideline.

Disclaimer of Liability

This clinical systematic review and evidence-based guideline was developed by a physician volunteer task force as an educational tool that reflects the current state of knowledge at the time of completion. The presentations are designed to provide an accurate review of the subject matter covered. This guideline is disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in its development are not meant to replace the individualized care and treatment advice from a patient’s physician(s). If medical advice or assistance is required, the services of a physician should be sought. The recommendations contained in this guideline may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in this guideline must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

Potential Conflicts of Interest

All NFPA Guideline Task Force members were required to disclose all potential COIs prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Committee (JGC). The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guidelines Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs.

Literature Search

The task force collaborated with a medical librarian to search for articles published from January 1, 1966, to October 1, 2014. Authors searched 2 electronic databases, PubMed and The Cochrane Central Register of Controlled Trials. Strategies for searching electronic databases were constructed by the evidence-based clinical practice guideline taskforce members and the medical librarian using previously published search strategies to identify relevant studies (Appendix A).1-8


The medical literature was searched using search terms encompassing surgical resection strategies specific to transsphenoidal and intraoperative MRI techniques. Abstracts from the results of these searches were screened, and full-text articles from potentially significant articles were reviewed.

Articles found on literature review based on the above criteria include 35 Class III studies involving transsphenoidal microscopic surgery, 20 Class III studies for endoscopic surgery, and 9 Class III studies involving transcranial surgery for NFPA resection. A flow chart summarizing study selection can be found in Figure 1. Studies that included results from multiple or combined surgical approaches were included in several of the above categories. For this paper, transsphenoidal surgery is a broad term that includes both microscopic and endoscopic approaches. Specifically, microscopic transsphenoidal surgery or transsphenoidal microsurgery refer to surgeries performed with microscope visualization and tumor resection via either sublabial or endonasal pathways, whereas endoscopic transsphenoidal surgery refers to using endoscope visualization and resection via various anatomical corridors (usually variations of the endonasal and endosinus corridors); the transcranial approach consists of supratentorial craniotomy microscopic tumor resections.

Transsphenoidal Microsurgery

The efficacy of transsphenoidal microsurgery for NFPA resection is well documented and accepted. Twenty-four studies provide Class III evidence that transsphenoidal microsurgery is effective for removing most or all of the NFPA and improves symptoms (Table 1).9-15

Lillehei and colleagues showed gross total resection in 84% of patients, with only 6% recurrence after 5 years. Gross total resection was achieved in 75% of NFPA patients on early and delayed MRI assessments in Yoon’s 2001 study, with only nodular residual tumor detected in the remaining 25% of patients. Kremer and colleagues reported in 2 papers that between 30%-50% of postop patients showed residual tumor at delayed (3 months and 1 year) MRI studies. With intraoperative MRI, Fahlbusch and colleagues reported successful gross total resection in 70% of NFPA patients. Regarding endocrine improvement, Arita et al reported restoring regular menstruation in 7 of 15 women (46%), with gonadotropin secretion normalized in 2 of 7 patients and prolactin level normalized in 4 of 6 patients. Flitsch et al performed a prospective study that showed postoperative improvement in emotional measures via positive changes in depression, fatigue, and excitability.

Thirteen additional studies provide Class III evidence to support the effectiveness of transsphenoidal microsurgery (Table 1).16-28 Young et al reported on 100 NFPA surgeries (98 resected via transsphenoidal approach, 2 resected via transcranial approach), with 90% gross total resection reported, but 42% residual/recurrent tumor found after 5 or more years on follow-up CT imaging. Complications included 24% postoperative hypopituitarism and 1 death due to hemorrhage. At 73 months follow-up, Ebersold et al reported an 84% gross total NFPA resection using transsphenoidal microsurgery with intraoperative fluoroscopy in 100 patients, with 3% surgically related mortality, 1% CSF leak, and 2% need for permanent CSF shunting. Seventy-four percent (53/72 patients) with preoperative visual problems experienced postop visual improvement.16 Zhang and colleagues reported 70% gross total resection in a total of 208 suprasellar NFPAs, and postoperative complications of diabetes insipidus (14%), CSF leak (5%) and 13% required subsequent trans-cranial craniotomy to completely remove tumor.

Tumor size and cavernous sinus invasion are factors that adversely impact the rate of gross total resection of NFPAs for all surgical approaches. Honegger et al reported that NFPAs with greater than 2 cm suprasellar extension and irregular or multilobulated shapes correlated with incomplete resections in 105 patients. Lamproulos et al reported 63% gross total resection in 97 NFPA patients, with cavernous sinus invasion, tumor size greater than 2.5 cm, and repeat operations correlated with worse outcomes. Postoperative visual improvement was found in 38% of patients and anterior pituitary function normalized in 14 of 75 patients, with improvement in 24 of 75 patients. In 1995, Greenman and colleagues reported significant postoperative anterior pituitary dysfunction in 68% of 26 NFPA patients who underwent transsphenoidal surgery. The same group reported a later 2003 study with a cohort of 122 NFPA patients that had gross total resection in 30 patients (25%) at 3 months, and showed that cavernous sinus invasion and suprasellar and infrasellar tumor extension were factors associated with diagnosis of tumor recurrence or progression at a mean of 51 months follow-up after surgery. Meij et al described the correlation of biopsy-proven dural invasion in 46 out of 81 patients correlated with tumor size and observation of residual tumor, but not associated with recurrence. Interestingly, Scheithauer described 23 cases of nonfunctioning corticotroph-staining pituitary tumors that were associated with higher residual tumor and tumor progression after surgery.

Alahmadi et al found that inadequate bony sphenoid and/or sellar exposure found during repeat transsphenoidal surgery likely limited the initial surgery, and expanded exposure resulted in gross total resection of the majority of NFPAs without cavernous sinus invasion. Mattozo et al also reported that suboptimal bony sphenoid exposure was found in 97% and suboptimal sellar exposure was found in 93% of patients needing repeat transsphenoidal surgery.

Use of lateral rhinotomy approach in 48 NFPA surgeries reported by Petruson et al was associated with only 1 recurrence on CT imaging at 5 years, 12% postoperative pituitary dysfunction, and 79% visual improvement.

Of note, the report from Abe et al describes successful gross total resection via staging of serial transsphenoidal resections of fibrous or dumbbell-shaped NFPAs in 7 of 8 patients over 5 months without complications. In a large series, Wilson reported a postoperative CSF leak rate of 4.3% in 530 patients despite the use of a lumbar drain.29

The safety and efficacy of NFPA transsphenoidal surgery in elderly patients were reported in 2 Class III studies. Benbow et al showed in 38 patients (greater than 64 years old) that perioperative complications were higher in the transcranial group (5 of 6 patients) compared to the transsphenoidal group (6 of 32 patients). Kurosaki and colleagues reported a 75% gross total resection rate via transsphenoidal approach in 32 elderly patients (greater than 70 years old) who meet the American Society of Anesthesia (ASA) criteria of grades 1-3 for surgery.30 Visual disturbances were improved in 19 of 23 cases, and complications included 5 CSF leaks, transient oculomotor palsy in 1 patient, and new adrenocorticotropic deficit in 5 of 11 patients.30

Endoscopic Surgical Resection

NFPA surgery with endoscopic visualization is a more recent technological innovation. There are 14 reports offering Level Class III evidence in studies of endoscopic NFPA surgery (Table 1).31-44

Class III evidence is found in Jho and Carrau’s 1997 report including 19 NFPA surgeries with 16 gross total resections, and 3 noted cavernous sinus residuals. Postoperative visual improvement was observed in all 11 patients showing preoperative impairment, and new hypopituitarism was found postop in 3 of 10 preoperatively normal patients.

In 2000, Shen et al retrospectively reported achieving gross total resection of 12 out of 15 endoscopic NFPA surgeries with visual improvement in all previously impaired patients. Lasio et al reported successful use of repeat surgery using endoscopic visualization with or without image guidance in 2002. In 2005, Kabil et al showed, at a mean follow-up of 38 months, 93% of 161 NFPA patients had no residual tumor after endoscopic surgery. Schwartz and colleagues reported on combining endoscopic tumor visualization and resection with iMRI guidance in 2006. Frank et al also reported gross total resection in 20 of 35 (60%) endoscopic NFPA resections. In 2008, Dehdashti et al reported on retrospective review of 200 consecutive endonasal endoscopic surgeries that included 111 NFPAs. Gross total resection was achieved in 98 of 111 patients, with 97% of patients without cavernous sinus invasion having complete resection. Full visual recovery was observed in 36 (57%) patients, partial visual recovery in 21 (34%) patients, and only 6% had no visual improvement. Three reports were released in 2010. Gondim et al showed 75% of 93 NFPA patients had a gross total resection via endoscopic surgery, with 10 patients achieving gross total resection at a second surgery. In contrast, Santos et al showed that endonasal endoscopic NFPA surgery only achieved gross total resection in 3 of 12 patients. Leach et al showed that additional technical experience from 15-30 months versus the early 0-15 months’ experience was associated with decrease in operative time from 120 minutes to 90 minutes. Hwang et al reported a small series from Korea of gross total resection in 50% of 27 patients and improved vision in 79% of patients, with 2 patients suffering complications.

In 2014, Dallapiazza et al and Chone et al reported retrospective series of endoscopically resected NFPAs. Dallapiazza and colleagues showed 71% gross total resection with tumors less than 10 cc volume and Knosp grades of 0 to 2. Chone et al reported a small study of 30 patients with 94% gross total resection but 10% surgical complications, including 1 death, 2 carotid artery lesions, and 2 CSF leaks. In a large consecutive endoscopic surgery patient series, the Pittsburgh group reported 84% gross total resection in NFPAs without cavernous sinus invasion and 35% gross total resection in tumors with cavernous sinus invasion. Visual improvement was found in 81% of previously impaired patients. Gross total resection was lower at 74% in recurrent NFPAs without cavernous sinus invasion, and 19% in tumor recurrences with cavernous sinus invasion. Barazi et al reported using extended endoscopic transplanum-transtuberculum approach to achieve 40% (6 of 15 patients) gross total resection, and complications in 6 of 15 patients (2 CSF leaks, 1 chronic subdural hematoma, 1 epistaxis, 1 surgical hematoma, 1 capsular ischemia).

Comparisons between Transsphenoidal and Endoscopic Approaches

There are 5 studies with Class III evidence that compare the more recently developed endoscopic approach with microscopic transsphenoidal craniotomy for NFPA surgery, with most showing comparable efficacy but 1 study providing Class III evidence of cases in which endoscopy was able to remove residual tumor left after microsurgery (Table 1).45-49 Messerer et al studied 82 endoscopic surgeries performed by a single surgeon compared with 82 transsphenoidal surgeries performed mostly by the same surgeon and another surgeon at 1 year postoperative follow-up.45 No difference in complications was observed, with 50% gross total resection achieved with transsphenoidal approach and 74% gross total resection achieved via endonasal endoscopic approach.

In 1999, Sheehan et al reported preliminary comparison of endonasal endoscopic approach (26 NFPAs) with sublabial microsurgical transsphenoidal approach (44 matched patients) that showed no significant differences in extent of resection, visual or endocrinological outcomes, or complications. The endoscopic group had significantly less operative time.47 The University of Virginia group also found no significant differences in tumor resection extent or endocrine outcome between transsphenoidal and endoscopic cohorts, with higher intraoperative lumbar drain placement in 70% of microscopic resections versus 1.7% of endoscopic surgeries.46 Chen’s group reports a prospective series of 355 NFPA surgeries with mean 5.5-year follow-up that included both microscopic and endoscopic resections with 79.5% gross total resection rate.49 McLaughlin et al showed that 46% (33 of 71 NFPAs) of patients had residual tumor identified via endoscopy after initial microsurgery, and further resection was performed in 88% (29 of 33 patients).48

Transcranial Approach

The transcranial approach is now usually an infrequently used alternative or complementary approach to transsphenoidal NFPA resection. One Class III report from Nielsen et al in 2007 compares 32 transcranial NFPA cases with 160 transsphenoidal approaches and showed that transcranial patients had significantly worse mental health and depression outcomes. No differences in endocrine complications, number of surgeries, and need for radiotherapy were found between the 2 groups.50 Other studies all offered Class III evidence (Table 1). One report from van Lindert et al in 1991 describes a retrospective review of 53 patients who underwent only transcranial NFPA resection: 81% of 53 patients had symptomatic improvement, with a 6% surgical mortality rate. Thirty-six percent of patients thought to have gross total resections showed delayed tumor recurrence.51

Colao et al reported from 1- to 10-year follow-up on patients who underwent transsphenoidal or peritoneal craniotomies and combined with radiotherapy. Eighty-two percent of the 72 patients with subtotal resections underwent radiotherapy, and the incidence of hypopituitarism increased from 29% at 1 year to 92% at 10 years follow-up.52

In a large series of 721 patients (660 transsphenoidal, 61 transcranial surgeries), Nomikos et al reported normalization of preoperative pituitary deficits in 20% of transsphenoidal group versus none in the transcranial group. Deterioration of pituitary function was found in 1% of the transsphenoidal group versus 15% of the transcranial group.53 Similar results were reported by Wichers-Rother et al in 2004: no improvement in pituitary function was observed in both the transsphenoidal (109 patients) and transcranial (21 patients) surgery groups, with postoperative endocrine dysfunction higher at 2 years in the latter group. Visual improvement and headache relief occurred in both groups, but was earlier in the transsphenoidal group.54 Discussed above, Benbow et al showed in 1997 that elderly patients greater than 64 years old had fewer perioperative complications with transsphenoidal versus transcranial surgery.55 The strategy of simultaneous combined transsphenoidal and transcranial resections of NFPAs was described by Alleyne et al in 2002 and Leung et al in 2011 for small series of selected NFPAs.56,57 Alleyne et al retrospectively reviewed 10 patients undergoing both transsphenoidal and pterional craniotomies for giant NFPAs, with 4 gross total resections and 2 near total resections. All 9 patients presenting with visual impairment improved, with 5 achieving full visual recovery. Complications of transient oculomotor palsy (n = 3), mild hemiparesis (n = 3), and postoperative seizures (n = 2) were reported. With the goal of dissecting giant NFPAs (greater than 4 cm in height) away from optic apparatus and vascular structures, Leung et al utilized subfrontal or anterior interhemispheric craniotomy approaches simultaneously with transsphenoidal resection in 11 patients.57 They report 5 gross total resections, with 5 of 7 patients experiencing full visual recovery. Subsequently, 7 of 11 patients underwent radiotherapy due to residual or recurrent tumor.


The use of intraoperative neuronavigation has been utilized for endonasal transsphenoidal surgery with varying prevalence. This has been a transition from the use of fluoroscopy for localizing the sella. We identified 1 article (Class III) that fit the inclusion and exclusion criteria for the surgical resection of nonfunctioning pituitary adenomas (Table 2). Lasio et al reported their experience with neuronavigation in a cohort of 11 patients for recurrent pituitary adenomas resected via the endoscopic endonasal transsphenoidal approach.32 They noted no difference in morbidity or mortality compared to a non-navigated (no fluoroscopy) control group. They did find longer set-up times, but shorter surgical and overall operating room times. They conclude that neuronavigation is a safe adjunct for transsphenoidal surgery and may result in faster operative times.

Intraoperative Imaging

The use of intraoperative imaging as an adjunct to transsphenoidal surgery has been necessary for safe and maximal resection of pituitary tumors since the 1960s.58 With the advent of intraoperative CT and MRI, intraoperative imaging technologies were further advanced to allow the real-time capacity to identify residual disease. With the inclusion and exclusion criteria for this section, we identified one article (Class III) evaluating fluoroscopy and nonfunctioning adenoma resection. Seven Class III articles were identified for the evaluation of intraoperative MRI (any field strength) (Table 3). No articles were identified evaluating intraoperative CT imaging for nonfunctioning adenoma surgery.

In a retrospective study evaluating the long-term results of transsphenoidal surgery in which intraoperative fluoroscopy was routinely utilized, Ebersold et al demonstrated surgical mortality of 3%, 1 postoperative CSF leak repair (1%), and 2 patients requiring CSF diversion due to subarachnoid hemorrhage and hydrocephalus.16 In tumors with suprasellar extension, subarachnoid air was injected via a lumbar puncture to facilitate descent of the tumor as well as fluoroscopic contrast.

Intraoperative MRI has been evaluated for nonfunctioning pituitary adenoma transsphenoidal surgery with both low-field (0.12-0.2T) and high-field (1.5T) devices. In a prospective study evaluating a 0.2T intraoperative MRI during transsphenoidal surgery, Fahlbusch et al reported the detection of residual disease in 27% of patients.9 They concluded that iMRI improved overall GTR from 43% to 70%. They also noted an approximately 30% rate of artifact obscuring imaging and a 16% false-positive rate.

A follow-up prospective study was performed by the same group evaluating the high-field intra-operative MRI (1.5T) in 106 patients with nonfunctioning pituitary adenomas.59 The authors note that residual tumor was identified during surgery in 42% of patients. They concluded that iMRI (1.5T) improved overall GTR from 58% to 82%. The false positive rate was 5.7%.

Six additional Class III articles were identified supporting the role of intraoperative MRI and transsphenoidal surgery. Three of these articles studied low-field iMRI devices (0.12-0.15T), and 3 studied high-field devices (1.5T).35,60-64 The overall rate of GTR at initial iMRI ranged from 36%-57% in the low-field studies and 44%-75% in the high-field studies. This improved to 82%-95% overall GTR in the low-field studies and 66% in the high-field study. There was a false positive rate of upwards of 64%.63

CSF Diversion

CSF diversion has been utilized with various purposes for transsphenoidal surgery. Primary applications include instillation of air for intraoperative pneumoencephalography, injection of volume to achieve suprasellar tumor descent, fluorescein injection for intraoperative CSF leak detection, and postoperative CSF diversion to augment the dural closure. For nonfunctioning pituitary adenomas, we identified 5 articles (Class III) that fit the inclusion and exclusion criteria (Table 4). Ebersold et al reported the use of preoperative lumbar puncture and instillation of air for pneumoencephalography.16 They note a GTR rate of 84% and a postoperative CSF leak rate of 1%. Two articles demonstrated the utility of intrathecal saline injection to assist in tumor descent (20-80 mL).17,65 They noted usefulness of saline injection in 70%-83% of tumor resections without catheter-related complications. Two articles reported the utility of perioperative CSF diversion to augment dural repair.29,46 Wilson et al reported a 4.3% postoperative CSF leak rate with the use of CSF diversion. Dallapiazza reported a 12% rate of postoperative CSF leakage, with the majority of patients (70%) undergoing CSF diversion in their microscopic surgery cohort. Interestingly, they noted a 7% postoperative CSF leak rate in their endoscopic surgery cohort in which the CSF diversion utilization was in 1.7% of patients. This difference between cohorts was not statistically significant.

Dural Closure Techniques

There are numerous methods for dural closure following transsphenoidal microsurgery. These include allograft placement, autologous fat or fascia graft placement, rigid buttress placement, and pedicled, vascularized tissue transpositions. Little, however, has been reported specifically for nonfunctioning pituitary adenoma resection. With our inclusion and exclusion criteria, we identified only 1 article that discussed closure techniques (Table 5).66 In their series, Jho and Carrau reported 19 cases that were closed with autologous fat grafts for CSF leaks or large post-resection cavities. The fat grafts were supported with bone when possible or with absorbable buttress when bone could not be placed. With this technique, 1 postoperative CSF leak (5.3%) was reported in a recurrent pituitary adenoma with a large post-resection cavity where bone could not be placed. The patient underwent reoperation, and the defect was repaired with a larger autologous fat graft. CSF diversion was not routinely used.


Transsphenoidal microsurgery as the choice for NFPAs has now been supplemented and, in some centers, replaced with experienced adoption of endoscopic NFPA resections. Due to comparative efficacy and safety, the choice of surgical approach and techniques continues to be determined based on surgeon experience, tumor characteristics, and patient selection. Intraoperative imaging has also been advanced by introduction of various forms of the sophisticated intraoperative MRI, although it is relatively costly and not feasible at all hospitals. The judicious selection of surgical strategies (single or combined approaches), along with appropriate use of neuronavigation, intraoperative imaging, and CSF diversion or repair techniques continue to benefit NFPA patients. These surgical methodologies will continue to be practiced, improved, and passed to the next generation of neurosurgeons.


Future Research

Analysis of the safety and efficacy of endoscopic-guided versus microsurgical approaches will likely be a focus of clinical research, with further studies on the impact of the learning curve and determining factors influencing the learning curve for new surgeons. Factors affecting surgery for NFPAs in the elderly would also be interesting and important to study for our population, with longer lifespans living with slow-growing benign pituitary tumors.

Disclosure of Funding

These evidence-based clinical practice guidelines were funded exclusively by the CNS and the Tumor Section of the CNS and the AANS, which received no funding from outside commercial sources to support the development of this document.


The authors acknowledge the CNS Guidelines Committee for their contributions throughout the development of the guideline, the AANS/CNS Joint Guidelines Committee for their review, comments, and suggestions throughout peer review, and Pamela Shaw, MSLIS, MS, for assistance with the literature searches. Also, the authors acknowledge the following individual peer reviewers for their contributions: Sepideh Amin-Hanjani, MD, Kathryn Holloway, MD, Odette Harris, MD, Brad Zacharia, MD, Daniel Hoh, MD, Isabelle Germano, MD, Martina Stippler, MD, Kimon Bekelis, MD, Christopher Winfree, MD and William Mack, MD. Lastly, and most significantly, the authors would like to acknowledge Edward Laws, MD, for serving as an advisor on this nonfunctioning adenoma guidelines project and providing comprehensive critical appraisal.


 The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.  


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Search Strategies


1. (("Pituitary Neoplasms/surgery"[Majr] OR "Adenoma, Chromophobe/surgery"[Majr] OR "Sella Turcica/surgery"[Majr])

2. (microadenoma* OR adenoma* OR macroadenoma* OR incidentaloma* OR chromophobe*[Title/Abstract]) AND (pituitary OR hypophyse* OR sellar[Title/Abstract])

3. (1 or 2) AND (asymptomatic* OR nonfunction* OR non-function* OR nonsecret* OR non-secret* OR inactive OR null OR inert OR silent)

4. 3 AND ((transsphenoidal OR sublabial OR endoscopic OR endoscopy OR microscopic OR endonasal OR craniotomy OR stereotaxy OR neuronavigation OR "intraoperative MRI") AND surgery)

5. NOT Comment[pt] NOT Letter[pt]

6. Limit to English, Humans, publication date to 10/01/2014


1. MeSH descriptor Pituitary Neoplasms

2. MeSH descriptor Adenoma

3. 1 and 2

4. ((pituitary OR hypophyse* OR sellar) NEAR/4 (microadenoma* OR adenoma* OR macroadenoma* OR incidentaloma* or chromophobe*)):ti,ab,kw

5. 3 or 4 and (asymptomatic* OR nonfunction* OR non-function* OR nonsecret* OR non-secret* OR inactive OR null OR inert OR silent)

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