Endoscopic pituitary surgery: a systematic review and meta-analysis

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Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes.


The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes.


Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67–89%). Hormone resolution was achieved in 81% (95% CI 71–91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76–92%) of growth hormone secreting tumors, and 82% (95% CI 70–94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0–4%) for CSF leak and 1% (95% CI 0–2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%.


The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

Abbreviations used in this paper: ACTH = adrenocorticotropic hormone; GH = growth hormone; LOS = length of stay; PRL = prolactin.

Victor Horsley26 is credited with the first successful transcranial approach for a pituitary tumor in 1889. The first reported transsphenoidal removal of a pituitary tumor is attributed to Schloffer37 in 1907. Cushing further developed the sublabial, transseptal, transsphenoidal technique over the next 2 decades and reported a 5.2% mortality rate in a series of > 400 patients.11–13 This approach, however, was largely abandoned for the transcranial route until the mid-20th century. The introduction of operative microscopy and radiofluoroscopy in the 1950s and 1960s heralded the era of modern transsphenoidal pituitary surgery.16,22,24,25 Since that time, multiple large series have reported the efficacy, safety, and limitations of this approach.1,2,6,7,9,10,14,17–21,23,27,30,32–34,36,39–41,44,45 The emergence of endoscopic transsphenoidal pituitary surgery over the past decade represents the latest development in surgery of the sella. The application of endoscopy to pituitary surgery is based on multiple theoretical advantages including improved visualization, preservation of sinonasal function, reduced hospital LOS, increased patient comfort, and reduced complications. The visualization afforded by straight and angled endoscopes may enhance the identification of critical neurovascular and arachnoid violation and thus decrease the rate of complications. Additionally, advancement of the endoscope into the tumor cavity at the end of the case may allow for identification and removal of residual tumor, improving the completeness of the resection.38 Transnasal endoscopic skull base approaches through the planum sphenoidale and tuberculum sellae permit the removal of giant suprasellar macroadenomas that would otherwise require a craniotomy.31

The impact of endoscopic surgery on outcomes, however, remains incompletely defined. A description of the complications and short-term outcomes of endoscopic pituitary surgery is critical for the propagation of this technique. Although the collective experience is currently too brief to describe long-term tumor control, important information such as operative time, LOS, perioperative complications, hormonal control, and extent of resection are all available. Several series have reported the techniques and short-term outcomes at individual institutions.3–6,8,28,29,35,38,42,46 These reports, however, are limited by small sample sizes, retrospective and nonrandomized study designs, heterogeneous patient populations, and varying definitions of outcomes. Pooling of the individual series in the form of a systematic review and meta-analysis allows for an improved understanding of the role of the endoscopic approach to pituitary tumors.


Inclusion/Exclusion Criteria and Search Strategy

We performed a systematic review of the English-language literature published before April 2006. There was no lower date limit. A primary MEDLINE literature search was performed using the following terms: “pituitary adenoma,” “sella,” “endoscopy,” “transsphenoidal,” “Cushing's disease,” “prolactinoma,” “acromegaly,” “endonasal,” “minimally invasive surgery,” “sublabial,” “microscopic,” “complication,” “skull base,” and “surgery.” The “related articles” function was used to obtain any relevant articles. Additionally, the references of the articles included in the analysis were reviewed for any other citations. The search was performed independently by 2 members of the study team (A.T. and D.H.H.). Inclusion criteria included purely endoscopic approaches to the pituitary gland in the study arm. Endoscopic assisted or microscopic approaches were excluded unless they represented the control arm of a study also reporting purely endoscopic surgery. Eligible study designs included randomized, retrospective, observational, and case series. Case reports and case series with < 10 patients were not included.

Data from the articles obtained were extracted independently by 2 authors (A.T. and D.H.H) and were reviewed by a third (Y.B.). Eight articles that reported outcomes on purely endoscopic pituitary surgery were identified, 3 of which included a control group that underwent sublabial, microscopic transsphenoidal surgery. We also reviewed the senior authors' (V.K.A. and T.H.S.) institutional series and included the information in this study after obtaining institutional review board approval. This yielded a total of 9 independent series. Data collected from the articles included the number of patients, study design (randomized vs retrospective), surgery dates, institution, patient demographics, history of prior surgeries, tumor size, tumor type (secreting vs nonsecreting adenoma, macro- vs microadenoma), duration of surgery time, and hospital LOS. Outcome measures included extent of gross tumor removal (complete vs subtotal), hormone resolution for secreting adenomas, and resolution of visual symptoms. The perioperative complications that were described included CSF leak, neurovascular injury, new-onset anterior pituitary dysfunction (including temporary and permanent diabetes insipidus), new onset cranial nerve and visual deficits, nasal septum perforation, epistaxis, meningitis, medical complications, and death. If no data were reported on a certain variable of interest, they were recorded as not available, except in the case of major complications such as epistaxis, CSF leak, and death, where zero occurrences were assumed even if they were not explicitly mentioned, because these complications are expected to be routinely reported as part of the surgical results for this type of operation.

Statistical Analysis

Only 3 studies reported data from a control group,5,8,46 and not all of these studies reported the same outcomes and complications of interest; hence, it was not possible to compare the results of endoscopic pituitary surgery to sublingual transsphenoidal surgery. However, analysis was performed to obtain the surgical outcomes and complication rates following endoscopic pituitary surgery. Weighted summary rates were determined using meta-analysis models if a given result was reported by ≥ 4 studies. If the result of a particular outcome was reported by ≤ 3 studies, only the raw data are presented.

Tests for heterogeneity were performed for each meta-analysis. Random effects models were used to account for the heterogeneity among the studies in some of the analyses. By using random effects models, we assume that the studies found in the literature are a random sample from a hypothetical population of endoscopic surgery studies, whereas fixed-effects models would give success and complication rates estimates for only these 9 studies. Furthermore, random effects models tend to give more conservative estimates, given that the interstudy variation is larger than the intrastudy variation (that is, studies are more heterogeneous). Each study is weighted more similarly, rather than giving more weight to those studies with larger sample sizes (as in fixed effects). The rmeta package from the R statistical language for Windows was used to perform these analyses.15

Continuous outcomes such as duration of surgery and hospital LOS could not be pooled using meta-analyses because standard deviations were not reported by or could not be computed for most of the papers. Pooled estimates using meta-analytical techniques were obtained only for outcome and postoperative complication rates, which were assumed to follow binomial distributions. However, in instances in which 100% success rates and/or 0% complication rates were reported, the variances were estimated as the pooled variances obtained from the other studies with success rates < 100% and complication rates > 0%, respectively, because the variances obtained from the binomial assumption in these cases could not be computed. These results are denoted by asterisks in Figs. 110.

Fig. 1.
Fig. 1.

Graphic representation showing pooled rates of gross tumor removal.

Fig. 2.
Fig. 2.

Graphic representation showing pooled hormone resolution rates for ACTH-secreting tumors.

Fig. 3.
Fig. 3.

Graphic representation showing pooled hormone resolution rates for GH-secreting tumors.

Fig. 4.
Fig. 4.

Graphic representation showing pooled hormone resolution rates for PRL-secreting tumors.

Fig. 5.
Fig. 5.

Graphic representation showing pooled hormone resolution rates for all hormone-secreting tumors.

Fig. 6.
Fig. 6.

Graphic representation showing pooled complication rates for CSF leak.

Fig. 7.
Fig. 7.

Graphic representation showing pooled complication rates for both any diabetes insipidus events.

Fig. 8.
Fig. 8.

Graphic representation showing pooled complication rates for permanent diabetes insipidus.

Fig. 9.
Fig. 9.

Graphic representation showing pooled complication rates for epistaxis.

Fig. 10.
Fig. 10.

Graphic representation showing pooled complication rates for anterior pituitary dysfunction.


The study type and patient demographics of the 9 studies (821 patients) are presented in Table 1.3,5,8,28,29,35,42,46 All studies were published on or after the year 2000, and all surgeries were performed between 1993 and 2006. Table 2 shows the characteristics of the tumors reported in each study. The postoperative outcomes are described in Table 3. Among patients who underwent endoscopic surgery, the reported rate of visual field improvement in patients with preoperative deficits ranged from 62 to 100%. The mean duration of surgery ranged from 102 to 255 minutes, and the average hospital LOS ranged from 1.4 to 4.4 days. Pooling of this data could not be performed due to inadequate reporting of data as described in Methods. The incidence of the various studied complications is described in Table 4.


Study types and demographics of 821 patients in 9 endoscopic pituitary surgery studies*

Authors & YearStudy LocationRandomizedYrs of OpOp TypeNo. of Patients Undergoing Pituitary OpsMean Age in Yrs (Range)No. of Females (%)No. of Patients w/Prior Op (%)
Shen et al., 2000Taiwanno1997–1999endoscopic4039 (22–70)27 (68)2 (5)
Jho, 2001Pittsburgh, USno1993–1999endoscopic12843 (14–88)90 (56)§33 (21)§
Cappabianca et al., 2002Italyno1997–2001endoscopic14646 (16–74)78 (53)20 (14)
Cho & Liau, 2002Taiwan?1996–2000endoscopic2245 (22–60)22 (100)NA
sublabial transsphenoidal2246 (18–56)21 (95)NA
White et al., 2004North Carolina, USno1996–1999endoscopic5041 (NA)26 (52)11 (22)
2000–2002sublabial transsphenoidal5044 (NA)17 (34)3 (6)
Rudnik et al., 2005Polandno2000–2002endoscopic6348 (11–77)38 (54)||NA
Casler et al., 2005Washington DC, USno1996–2003endoscopic1542 (29–60)9 (60)NA
sublabial transsphenoidal1551 (26–79)5 (33)NA
Kabil et al., 2005California, USno1998–2004endoscopic30046 (16–75)189 (63)72 (24)
current studyNew York, USno2004–2006endoscopic5748 (12–77)28 (49)8 (14)

* NA = not available; ? = unknown.

† These authors reported results for a control group of sublabial transsphenoidal surgeries.

‡ Median age.

§ The total number of surgeries reported was 160 (denominator for these calculations), with 128 being pituitary surgeries.

|| The total number of surgeries reported was 70 (denominator for this calculation), with 63 being pituitary surgeries.


Tumor characteristics*

Authors & YearNo. of Cases (%)
 Sec AdenomaNonsec AdenomaMicroMacroSec MicroNonsec MicroSec MacroNonsec Macro
Shen et al., 200025 (63)15 (37)21 (53)19 (47)21 (53)0 (0)4 (10)15 (37)
Jho, 200160 (47)68 (53)30 (23)98 (77)NANANANA
Cappabianca et al., 200266 (45)80 (55)21 (14)125 (86)21 (14)045 (31)80 (55)
Cho & Liau, 200222 (100)011 (50)11 (50)110110
22 (100)012 (55)10 (45)120100
White et al., 2004NANANANANANANANA
Rudnik et al., 200526 (41)37 (59)11 (17)52 (83)10 (16)1 (2)16 (25)36 (57)
Casler et al., 2005NANANANANANANANA
Kabil et al., 2005139 (46)161 (54)NANANANANANA
current study21 (37)36 (63)7(12)50 (88)7 (12)0 (0)14 (24)36 (63)

* Macro = macroadenoma; Micro = microadenoma; Nonsec = nonsecreting; Sec = secreting.


Postoperative outcomes

Authors & YearNo. of Cases (%)Mean ± SD (Range)
 Gross Tumor RemovalVisual Field ImprovementHormone Resolution of ACTH-Sec AdenomaHormone Resolution of GH-Sec AdenomaHormone Resolution of PRL-Sec AdenomaHormone Resolution of All Sec Adenomas  
       Duration of Op (min)Hospital LOS (days)
Shen et al., 200012 (80)*11/11 (100)0/05/7 (71)12/18 (67)17/25 (68)NA3§ (2–5)
Jho, 200153 (78)NA11/16 (69)7/9 (78)24/35 (68)42/60 (70)NA1.6 ± 0.99 (1–4)
Cappabianca et al., 200291 (62)NANANANANANANA
Cho & Liau, 2002NA5/8 (62)0/00/014/22 (64)14/22 (64)102§ (60–180)3.2§ (2–5)
NA6/10 (60)0/00/016/22 (73)16/22 (73)162§ (90–260)5.3§ (4–8)
White et al., 2004NANANANANANANA3.7§ (NA)
Rudnik et al., 200545 (71)NA4/5 (80)10/12 (83)9/9 (100)23/26 (88)NANA
Casler et al., 200510 (67)NANANANANA255§ (184–337)4.4§ (2–6)
12 (80)NANANANANA245§ (160–397)5.7§ (3–8)
Kabil et al., 2005278 (93)NA24/28 (86)41/48 (85)56/63 (89)121/139 (87)NA1.4§ (1–4)
current study51 (89)22/24 (92)3/4 (75)5/6 (83)11/11 (100)19/21 (90)177 ± 64 (78–330)4.1 ± 2.5 (2–15)

* Reported for the 15 nonsecreting adenomas only.

† Reported for the 68 nonsecreting adenomas only.

‡ Estimated from frequency distribution cited in paper for the 160 surgeries.

§ Standard deviation was not available.


Incidence of various complications

Authors & YearNo. of Cases (%)
 CSF LeakDiabetes InsipidusEpistaxisAnterior Pituitary DysfunctionNasal Septum PerforationMeningitisMedical ComplicationsDeath
Shen et al., 200002 (5)2 (5)000NA000
Jho, 200110 (8)11 (9)6 (5)5 (4)018 (14)NA0NA1*
Cappabianca et al., 20023 (2)13 (9)8 (5)5 (3)2 (1)20 (14)NA0NA0
Cho & Liau, 200200NA0000000
01 (5)NA1 (5)1 (5)1 (5)1 (5)000
White et al., 20046 (12)11 (22)9 (18)2 (4)1 (2)001 (2)00
7 (14)11 (22)9 (18)2 (4)8 (16)01 (2)000
Rudnik et al., 200503 (5)NA3 (5)0NANA001
Casler et al., 20054 (27)3 (20)3 (20)01 (7)03 (20)010
3 (20)2 (13)2 (13)0000000
Kabil et al., 20055 (2)16 (5)12 (4)4 (1)4 (1)8 (3)2 (1)000
current study3 (5)2 (4)NA2 (4)2 (3)0 (0)0 (0)02§0

* Bilateral internal carotid artery occlusion.

† Intraventricular bleed.

‡ Myocardial infarction.

§ Deep vein thrombosis and dehydration.

We used meta-analytical techniques to obtained pooled estimates of postoperative outcomes and complication rates. A pooled estimate of the gross tumor removal rate was computed from the 7 studies reporting this information. A random effects estimate analysis was used because there was evidence of heterogeneity (p < 0.0001). The pooled gross tumor removal rate was 78% (95% CI 67–89%) (Fig. 1). The fixed effects pooled rate (p = 0.64, test for heterogeneity) of hormonal resolution for ACTH-secreting tumors as reported in 4 studies was 81% (95% CI 71–91%) (Fig. 2). Four studies reported data on hormone resolution for GH-secreting tumors (Fig. 3), yielding a fixed effects pooled estimate (p = 0.94, test for heterogeneity) of 84% (95% CI 76–92%). Random-effects pooled rates of hormone resolution for PRL (p = 0.003, test for heterogeneity) and all hormone secreting tumors (ACTH, GH, and PRL) (p = 0.01, test for heterogeneity) were 82% (95% CI 70–94%) (Fig. 4) and 79% (95% CI 71–88%) (Fig. 5), respectively.

Random-effects pooled rates were computed for all complications except for epistaxis, because study rates were found to be heterogeneous (tests for heterogeneity probability values were 0.0013, 0.029, 0.026, 0.405, and < 0.0001 for CSF leak, diabetes insipidus, permanent diabetes insipidus, epistaxis, and anterior pituitary dysfunction, respectively). The pooled complication rates were 2% (95% CI 0–4%) for CSF leak (Fig. 6), 6% (95% CI 4–9%) for diabetes insipidus (Fig. 7), 1% (95% CI 0–2%) for permanent diabetes insipidus (Fig. 8), < 1% (95% CI 0–1%) for epistaxis (Fig. 9), and < 1% (95% CI 0–1%) for anterior pituitary dysfunction (Fig. 10). Overall, 2 deaths (0.24%) were reported, both as a result of vascular injury.


The development of endoscopic pituitary surgery represents the natural extension of endoscopic sinonasal procedures and has paralleled innovations in technology and instrumentation. The potential benefits of the endoscopic technique include improved visualization of the surgical field throughout the procedure. In comparison with the conical view of the microscope, which is limited by the placement of the lens and illumination outside of a long narrow tube (the retractor or nasal passage), endoscopes can be passed endonasally to advance the lens and illumination into the sphenoid sinus or sella. With the use of wide-angled 0, 30, 45, and 70° endoscopes, the operating surgeon has a significantly larger field of view, even around corners to areas out of the field of view of the microscope. Improved visualization theoretically leads to a greater extent of resection and improved safety. Additionally, avoidance of a sublabial incision and retraction of nasal tissue decreases trauma to the nasal mucosa and may facilitate postoperative recovery. Finally, extended transnasal approaches into the suprasellar cistern and third ventricle permit removal of giant macroadenomas under direct visualization.31 However, scientific validation of the procedure is required prior to widespread adoption. Specifically, the safety and effectiveness of the procedure must compare favorably to traditional, sublabial transsphenoidal surgery.

The high rates of gross tumor removal, hormone resolution for secreting tumors, and improvement in visual symptoms described by the meta-analysis support the effectiveness of endoscopic pituitary surgery. The safety of the procedure is similarly supported by the low reported incidence of complications. The pooled data for these outcomes represent a summary of the > 800 patients identified by our literature search. The reported numbers represent an early benchmark not only for individual institutions adopting the procedure but also for future outcomes literature in the field of endoscopic pituitary surgery.

The inadequate reporting of control groups precludes our ability to use meta-analysis to directly compare endoscopic with sublabial, transsphenoidal surgery. Examination of historical data on outcomes for traditional surgery, however, is relevant. Based on multiple large series, the reported mortality rate for traditional surgery is < 1% and is similar to the results of our study.1,2,10,27,33,39 The reported 1–4% incidence for both epistaxis and CSF leak and 0.5–15% incidence for permanent diabetes insipidus in sublabial, transsphenoidal reports are also similar.1,2,9,10,17,18,33 For hormonally secreting tumors, the following range of remission rates has been reported: 54–86% for prolactinomas,7,18,20,36 52–85% for GH-secreting tumors,19,30,32,40,41,45 and 70–86% for ACTH-secreting tumors.6,17,21,23,44 Although there is variability in the definition of biochemical cure, the preliminary results from endoscopic series as reported in the meta-analysis appear favorable.

Several interpretations of our results are possible. The individual studies comprising this meta-analysis represent the early literature in the field of endoscopic pituitary surgery. As with any technique, a learning curve is anticipated. Although these early results appear favorable, it is possible that a gradual improvement in outcomes will occur as the cumulative experience increases over time. Several authors have discussed the potential outcomes of improved tumor resection and avoidance of complications afforded by the improved visualization afforded by the endoscopic technique.3,4,28,29 Future studies addressing these issues are required as the field continues to evolve and the learning curve issues are resolved.

Several limitations are identified with the available literature in endoscopic pituitary surgery. Publications to date have focused on technical aspects of the procedure and short-term outcomes. The impact of endoscopic techniques on long-term tumor control represents the critical question and cannot be answered until the results of large patient series with adequate follow-up are available. Although the published reports on short-term outcomes are favorable as supported by the current study, there are inherent limitations in the literature. To date no large, prospective, randomized study has been performed to compare outcomes between endoscopic and traditional transsphenoidal surgery. The challenges in performing such a study include the large cohort size required to achieve statistical power, ethical issues in randomization, disease and institutional heterogeneity, and variability in the definition of outcomes. The nonrandomized, observational nature of the available literature is associated with several methodological issues common to retrospective data including selection bias, publication bias, incomplete data, and lack of standardization in the study intervention.43 These issues highlight the inherent limitations in any meta-analysis based on observational data and the need for future large prospective studies.


The theoretical advantages afforded by the endoscopic technique may enhance multiple aspects of pituitary tumor surgery. Evaluation of outcomes data, however, is critical to define the role of endoscopic versus traditional surgery. The results of this systematic review and meta-analysis support the safety and short-term effectiveness of endoscopic pituitary surgery. Favorable comparison of these parameters to historical results supports further development of this field. Long-term follow-up, however, is required to define tumor control.


The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

This paper was presented in poster form at the American Association of Neurological Surgeons Annual Meeting, Washington DC, April 2007.


Article Information

Address correspondence to: Abtin Tabaee, M.D., 10 Union Square East, Suite 4J, New York, New York 10003. email: atabaee@hotmail.com.

Please include this information when citing this paper: published online January 23, 2009; DOI: 10.3171/2007.12.17635.

© AANS, except where prohibited by US copyright law."



  • View in gallery

    Graphic representation showing pooled rates of gross tumor removal.

  • View in gallery

    Graphic representation showing pooled hormone resolution rates for ACTH-secreting tumors.

  • View in gallery

    Graphic representation showing pooled hormone resolution rates for GH-secreting tumors.

  • View in gallery

    Graphic representation showing pooled hormone resolution rates for PRL-secreting tumors.

  • View in gallery

    Graphic representation showing pooled hormone resolution rates for all hormone-secreting tumors.

  • View in gallery

    Graphic representation showing pooled complication rates for CSF leak.

  • View in gallery

    Graphic representation showing pooled complication rates for both any diabetes insipidus events.

  • View in gallery

    Graphic representation showing pooled complication rates for permanent diabetes insipidus.

  • View in gallery

    Graphic representation showing pooled complication rates for epistaxis.

  • View in gallery

    Graphic representation showing pooled complication rates for anterior pituitary dysfunction.



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