Abstract
Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas.
Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order.
Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery.
Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.
Keywords: pituitary adenoma, acromegaly, growth hormone, cavernous sinus, invasion, Knosp, endoscopic, transsphenoidal surgery
Introduction
The term “acromegaly” was coined by the French neurologist Pierre Marie in 1886 and refers to a multisystem disease characterized by acral, soft tissue and organ overgrowth, glucose metabolic dysfunction, and increased risk of cardiovascular disease. 1 2 More than 95% of patients with acromegaly result from somatotrophin pituitary adenomas, which lead to excess circulating levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). 3
Surgical resection of somatotrophin pituitary adenomas is the preferred initial treatment of acromegaly in most patients for successful surgery producing immediate lowering of GH levels. 4 5 The favored surgical approach is via the transsphenoidal route, using either the microscope or the endoscope. 6 Although endoscopic surgery may provide a better visualization, there is no definitive evidence showing superiority of the endoscopic approach over the microscopic approach with regard to the biochemical remission rates until now, with main determinants of surgical cure being neurosurgeon's experience and cavernous sinus invasion. 6 7 8 However, the remission rates from endoscopic endonasal transsphenoidal surgery (EETS) for somatotrophin pituitary adenomas and its associated predictive factors are not well documented.
In this study, we reviewed the patients with acromegaly who underwent EETS in the Jinling Hospital from 2011 to 2020 and described the initial and long-term remission rates of the patients. We also analyzed the correlates (surgeon's experience, preoperative IGF-1 and GH levels, early postoperative IGF-1 and GH levels, suprasellar invasion, parasellar invasion, and sphenoidal invasion) that might predict the remission rates.
Methods
Patient Cohort and Evaluation Criteria
The patients with acromegaly who underwent EETS in Jinling Hospital were identified from 2011 to 2020. This time period was chosen because since 2011, the pituitary surgeries in our institute have been performed using EETS, by a single surgeon (C.M.). No surgeries were performed with the microscope, and no other surgeons participated in this series. One hundred and twenty-six patients who underwent EETS for resection of somatotrophin pituitary adenomas were identified, with five patients requiring reoperation. Twenty-three patients without follow-up magnetic resonance imaging (MRI) or IGF-1 levels were later excluded, leaving 98 patients for final analysis ( Fig. 1 ). To analyze the effects of surgical experience, they were divided into three groups according to the admission chronologic order: Group A: the first 33 patients, Group B: the median 33 patients, and Group C: the last 32 patients. Records were reviewed to determine pre- and postoperative GH and IGF-1 levels, tumor size and invasiveness, and clinical outcomes. All patients provided written informed consent. The Institutional Review Board at Jinling Hospital approved the study.
Fig. 1.
The flowchart of the study.
Acromegaly was diagnosed using standard criteria: (1) IGF-1 above the upper limit of normal (ULN) for age and gender and (2) failure to suppress GH to <1.0 ng/mL following an oral load of 75 g glucose. Similarly, criteria for remission were based on consensus guidelines and included an IGF-1 within normal range for age and gender and either a random GH < 1.0 ng/mL or a nadir GH level of <1 ng/mL after oral glucose tolerance test (OGTT). 4
Surgical Procedure
The patients underwent EETS using a binasal approach. The two-surgeon 3/4-handed technique was used. Intraoperative navigation was only used for unusual sphenoid pneumatization or other anatomic variations. The procedure was performed with a 4-mm 0-degree endoscope (Karl Storz Endoscopy, Tuttlingen, Germany). Sphenoidotomy was performed on both sides as lateral as possible. The optic nerve and the carotid canal buttresses were visualized as landmarks. The sellar floor was exposed and opened.
Ring curettes were used to remove the tumor. Once the tumor has been removed, a 30-degree endoscope is used to examine all sellar and suprasellar recesses for any remnant tumor to ensure complete achievement tumor resection. At the end of surgery, if intraoperative cerebrospinal fluid (CSF) leak occurred, the unilateral “rescue” nasoseptal flap was then fashioned to ensure a vascularized repair.
Endocrinological Evaluation
Postoperatively, serum basal GH and IGF-1 were tested on the morning of postoperative day 1. For patients in remission, serum basal GH and IGF-1 were assessed every 6 months thereafter. For patients not in remission, serum basal GH and IGF-1 were checked at 3-month intervals until remission was achieved either spontaneously or with medical therapy. Biochemical remission was considered when age- and sex-normalized IGF-1 levels fall within normal limits at 6 months. Once a patient met all criteria for remission, typically only IGF-1 was monitored, with OGTT repeated after 12 weeks postoperatively if IGF-1 levels suggested possible recurrence. Patients with discordant IGF-1 and OGTT results were closely monitored for biochemical evidence of recurrence or remission (rising or diminishing levels of IGF-1 on repeated testing, typically at 3-month intervals).
Any preoperative somatostatin receptor ligands were discontinued at least 2 weeks prior to surgery and restarted only if testing (3-month OGTT and IGF-1) indicated clearly persistent acromegaly.
Radiographic Evaluation
T1-weighted MRI with gadolinium contrast was used to classify tumors as microadenoma (<10 mm) and macroadenoma (≥10 mm) and assess for extent of tumor invasion. We used the Knosp score (grades 0–IV) to classify cavernous sinus invasion by tumors based on coronal T1-weighted gadolinium contrast-enhanced images. 9 The Hardy classification was used to grade suprasellar invasion (types A–D) and sphenoidal invasion (grades 0–IV) with T1-weighted MRI with gadolinium contrast and CT scans. Patients underwent MRI at 3 months postoperatively to assess extent of resection, and then annually to monitor tumor progression or recurrence.
Statistical Methods
Normally distributed data were expressed as mean ± standard deviation, and skewed variables were expressed using median and interquartile ranges. Wilcoxon's rank-sum test was used for discrete variables and t -test for continuous variables comparison. Chi-square test is used for binomial distribution data. The learning curves are drawn through cumulative summation (CUSUM) analysis. The target remission probabilities of CUSUM analysis were set to be 60, 65, 70, and 72.5%. The four learning curves were drawn according to operation cases and CUSUM value. In order not to miss any important factor, p -values ≤0.05 were considered significant in the single factor analysis. All statistics were calculated using SPSS software (IBM, Armond, New York, United States).
Results
Patient Demographics
Demographics of patients are shown in Table 1 . A total of 98 (35 males) patients were included in the analysis. The mean age was 45.6 ± 12.0 years, ranging from 15 to 83. There were 13 (13.27%) microadenomas and 85 (86.73%) macroadenomas. There were 54 (55.10%) Knosp grades 0 to 2 and 44 (44.90%) Knosp grades 3 to 4 tumors. There were 23 (23.47%) Hardy 0 to 1 and 75 (76.53%) Hardy 2 to 4 grades tumor. There were 66 (67.35%) Hardy A and 32 (32.65%) Hardy B to D grades tumor. To simplify interpretation of data, IGF-1 results were expressed as a percentage of the ULN for that person's age and gender. The mean preoperative IGF-1 was 2.7 ± 1.0 times ULN. The preoperative basal GH was 16.1 (6.4–29.2) ng/mL and the preoperative nadir GH was 14.7 (5.0–33.4) ng/mL. The mean postoperative IGF-1 was 2.0 ± 1.0 times ULN. The postoperative basal GH was 1.2 (0.5–2.8) ng/mL and the postoperative nadir GH was 0.8 (0.2–2.1) ng/mL.
Table 1. Patient demographics and endocrine characteristics.
| Variable | Number (%) |
|---|---|
| Age (y) | |
| Mean (SD) | 45.6 (12.0) |
| Gender | |
| Female | 63 (64.29%) |
| Male | 35 (35.71%) |
| Follow-up (mo) | |
| Mean (SD) | 17.7 (21.3) |
| Tumor size | |
| Micro | 13 (13.27%) |
| Macro | 85 (86.73%) |
| Knosp grade | |
| 0–2 | 54 (55.10%) |
| 3–4 | 44 (44.90%) |
| Hardy grade | |
| 0–1 | 23 (23.47%) |
| 2–4 | 75 (76.53%) |
| A | 66 (67.35%) |
| B–D | 32 (32.65%) |
| Preoperative IGF-1 | |
| Mean (SD) | 2.7 (1.0) |
| Preoperative basal GH | |
| Median (IQR) | 16.1 (6.4–29.2) |
| Preoperative nadir GH | |
| Median (IQR) | 14.7 (5.0–33.4) |
| Postoperative IGF-1 | |
| Mean (SD) | 2.0 (1.0) |
| Postoperative basal GH | |
| Median (IQR) | 1.2 (0.5–2.8) |
| Postoperative nadir GH | |
| Median (IQR) | 0.8 (0.2–2.1) |
Abbreviations: GH, growth hormone; IGF-1, insulin-like growth factor 1; IQR, interquartile range; SD, standard deviation.
The Learning Curves of CUSUM Analysis
The continuous learning curves constructed through CUSUM analysis reflected the relationship between the case number and the remission probability ( Fig. 2A, B ). The learning curves of CUSUM analysis exhibited initial rising slope, which revealed that the actual nonremission probability was greater than the target one. The segments of gentle slope revealed that the actual nonremission probability was approximately equal to the target one. The downward slope of learning curves revealed that the actual nonremission probability was less than the target one. When the curves were relatively stable or indicated a continuous downward slope, the corresponding X -axis value was the cumulative cases required to achieve the target remission probability.
Fig. 2.
(A) The learning curves based on the four target remission probabilities. (B) The learning curves after smoothing. CUSUM, cumulative summation.
We calculated the cumulative sum of target remission probability, respectively, 60, 65, 70, and 72.5%. The nonremission probability was relatively frequent at the initial stage. The condition began to improve after continuous 21 cases. After a short platform period, we found that the surgeon achieved the four target remission probabilities after accumulation of 40 operations. The first 39 cases were at the stage of learning improvement, and the last 59 cases were at the stage of technological maturity.
Remission Rates and Complications of Different Periods of Surgical Experience
Of the 98 patients, 87 (89%) underwent gross-total resection, and 11 (11%) underwent subtotal resection. The overall remission rate of the patients was 57% (56/98) and the annual remission rate was on the rise year by year ( Fig. 3A, B ).
Fig. 3.
The biochemical remission rates of 10 years. (A) The remission and nonremission patient numbers of 10 years. (B). The remission rates of 10 years. (C). The remission rates of Group A (the first 33 patients), Group B (the median 33 patients), and Group C (the last 32 patients), and the remission rate of the last 65 patients was higher than that of the first 33 patients.
The remission rates were 42.42% (14/33), 63.64% (21/33), and 65.63% (21/32) for Group A, Group B, and Group C, respectively. The remission rates of Groups B and C were similar and higher than that of the Group A (64.62 vs. 42.42%, p = 0.036), indicating that the patients had better endocrine outcomes as the surgeons gained experience ( Fig. 3C ).
Of our patients, 33.7% (33/98) had different postoperative complications, which include epistaxis, CSF leakage, intracranial infection, and diabetes insipidus. The rates of complications in Groups A to C were 48.5% (16/33), 33.3% (11/33), and 18.8% (6/32), respectively. The incidence of postoperative complications has decreased obviously over time. The incidences of epistaxis, CSF leakage, and intracranial infection in Group C were significantly lower than in Groups A and B ( Table 2 ).
Table 2. Postoperative complications.
| Groups/complications | Epistaxis | CSF leakage | Intracranial infection | Diabetes insipidus |
|---|---|---|---|---|
| A | 6.1% (2/33) | 27.3% (9/33) | 6.1% (2/33) | 15.2% (5/33) |
| B | 0% (0/33) | 24.2% (8/33) | 12.1% (4/33) | 12.1% (4/33) |
| C | 0% (0/32) | 3.1% (1/32) | 3.1% (1/32) | 15.6% (5/32) |
Abbreviation: CSF, cerebrospinal fluid.
Predictive Factors for the Endocrine Outcomes
The outcome was divided into remission and nonremission groups for predictive analytics ( Table 3 ). To identify the factors associated with the patients' endocrine outcomes, we first performed the single factor analysis and found that the remission rate was significantly different between the microadenoma group and the macroadenoma group ( p = 0.032). The p -value was significant regarding the remission rates between the Knosp grades 0 to 2 group and the Knosp grades 3 to 4 group ( p = 0.001). As for the sellar and suprasellar invasion, no significant difference was found between the noninvasive group (Hardy grades 0–1 and A) and the invasive group (Hardy grades 2–4 and B–D) ( Fig. 4 ).
Table 3. Predictive factors of biochemical remission.
| Factors | Biochemical remission | Nonremission | p -Value |
|---|---|---|---|
| Age (y), mean (SD) | 47.2 (12.5) | 43.4 (11.1) | 0.609 |
| Gender, male:female | 18:38 | 17:25 | 0.397 |
| Tumor size | |||
| Micro | 11 | 2 | 0.032 a |
| Macro | 45 | 40 | |
| Cavernous sinus invasion (Knosp) | |||
| 0–2 | 39 | 15 | 0.001 a |
| 3–4 | 17 | 27 | |
| Sellar invasion (Hardy) | |||
| 0–1 | 16 | 7 | 0.169 |
| 2–4 | 40 | 35 | |
| Suprasellar invasion (Hardy) | |||
| A | 38 | 28 | 0.901 |
| B–D | 18 | 14 | |
| Preoperative IGF-1 level, mean (SD) | 2.6 (1.1) | 2.8 (0.9) | 0.166 |
| Preoperative basal GH level, median (IQR) | 9.9 (4.9–18.2) | 22.8 (12.8–34.5) | 0.001 a |
| Preoperative nadir GH level, median (IQR) | 8.9 (3.9–16.4) | 17.4 (9.0–34.5) | 0.004 a |
Abbreviations: GH, growth hormone; IGF-1, insulin-like growth factor 1; IQR, interquartile range; SD, standard deviation.
p < 0.05 was considered significant.
Fig. 4.
The remission rate of different groups which were classified by tumor imaging characteristics.
As for the preoperative hormonal levels, no significant difference was found between the remission group and the nonremission group in the preoperative IGF-1 level ( p = 0.166). However, the preoperative basal GH level ( p = 0.001) and nadir GH level ( p = 0.004) were different between the remission group and the nonremission group.
To better understand the relationship, we applied the regression analysis to identify the preoperative predictive factors. According to the results, we included the tumor size, Knosp grade, surgical experience, and the preoperative basal GH and nadir GH level in the analysis. The age and gender were also included for adjustment. Before that, we analyzed the collinearity of these factors and discovered a moderate degree of multicollinearity ( Table 4 ). Since the value of variance inflation factor (VIF) was between 3 and 10, we chose logistic regression to further determine the preoperative predictive factors.
Table 4. Variables of binary logistic regression model.
| Tolerance | VIF | |
|---|---|---|
| Gender | 0.840 | 1.191 |
| Age | 0.769 | 1.300 |
| Tumor size | 0.868 | 1.153 |
| Knosp grade | 0.801 | 1.248 |
| Surgical experience | 0.756 | 1.323 |
| Preoperative basal GH | 0.252 | 3.975 |
| Preoperative nadir GH | 0.235 | 4.250 |
Abbreviations: GH, growth hormone; VIF, variance inflation factor.
The variables in Table 4 were added to binary logistic regression model. We obtained their statistical significance by forward likelihood ratio method. After adjustment with logistic regression, the results showed that the model could correctly classify 67.1% of the subjects with a sensitivity of 84.1%, a specificity of 43.8%, a positive predictive value of 67.3%, and a negative predictive value of 66.7%. Among the seven variables included in the model, the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was statistically significant and an independent predictor of postoperative biochemical remission.
Discussion
Excision of somatotrophin pituitary tumors by EETS achieves appreciable biochemical remission rate. The incidence of postoperative complications was also controlled at a low level as surgical experience accumulated. Besides, EETS is also cost-effective compared with other modalities of treatment. 10 11
The biochemical remission rate of patients in our study was not lower than some previous studies or even higher. While some studies have demonstrated remission rates less than 50%, 12 13 the overall remission rate in our study was 57%. In addition, the postoperative remission rate reached 53% in our patients with macroadenoma. This result agreed with the 40 to 60% biochemical remission rates of macroadenoma surgery in previous studies. 14 15 16 The use of the endoscopic endonasal approach (EEA) for resection of somatotrophin pituitary adenomas is associated with shorter operative time, decreased blood loss, pain, infection rate, and length of hospital stay, which has been supported by literature. 8 17 In this study, we found that there were only two cases of epistaxis and one case of headache. Additionally, not only did patients included in Group C exhibit a higher rate of postoperative biochemical remission than other two groups but they also experienced a low rate of postoperative complications. In Fig. 3B , we could also find that the remission rate of patients was gradually increasing from 2011 to 2015 and reached a stable plateau from 2016 to 2019. As reported before, 18 the surgeons' experience was an important factor that would affect the patients' outcomes.
The tumor size and invasiveness are important predictors of postoperative biochemical remission in many studies. 19 20 21 22 23 Specifically, pituitary adenomas invading the cavernous sinus are more difficult to be completely removed. Based on the complex anatomy of the cavernous sinus, the surgeons often avoid excessive removal of tumors in the cavernous sinus to protect the normal vascular structure. In current studies, Unal et al 21 and Cardinal et al 22 observed that cavernous sinus invasion, preoperative IGF-1, and early postoperative GH were correlated with postoperative remission rate of patients who received EETS. Besides, many studies have shown that early postoperative GH levels, postoperative IGF-1 levels, and postoperative nadir GH levels are predictors of postoperative biochemical remission. 8 20 24 25 26 Our results were similar to previous studies that include cases of microscopic and endoscopic surgeries, but we focused more on preoperative factors. 19 20 21 22 24 Unlike previous studies, the logistic regression analysis suggested that preoperative nadir GH is also an independent predictor of surgical remission. The role of preoperative IGF-1/GH levels on biochemical remission rates has been already well established. However, the studies about preoperative nadir GH are few. Based on our results of regression analysis, we think that more cases should be added to this model to further understand the effect of the preoperative factor. One-week postoperative OGTT was considered as a good predictor with high specificity, and the relationships between them may be worth further analyzing. 24
Although the current literature supports preoperative IGF-1 levels as a predictor of postoperative biochemical remission, we did not observe a significant correlation between them in our study. Cardinal et al 22 found similar problems and explained that their data may not capture the inherent tumor characteristics. Another hypothesis was that their tumors were more frequently atypical adenomas that have been proved to be more aggressive and hormonal hypersecretory. 22 In our study, the rate of K i -67 (>3%) in nonremission group (26.1%) was close to the rate of K i -67 (>3%) in remission group (28.6%). There was no significant difference between the two groups. Perhaps, their hypothesis of atypical adenomas could explain our results about IGF-1. In addition, our previous study proposes that gsp oncogene mediates maternally expressed gene 3 (MEG3)-regulating GH hypersecretion. 27 This study indicated that MEG3 levels were positively correlated with GH and IGF-1 levels and negatively correlated with the tumor volume of somatotrophin pituitary tumors. 27 The smaller the tumor volume is, the easier it is to be completely removed to achieve postoperative remission; however, due to the lack of gene analysis and detailed tumor sizes, the current data were not available for analysis. The previous studies and our studies showed that preoperative IGF-1/GH levels are not a predictor all time in some models. When preoperative IGF-1 could not be used as an effective predictor, our results suggested that preoperative nadir GH levels also has reference value for postoperative biochemical remission. In addition, these results also reminded us that preoperative nadir GH levels should be considered to achieve more accurate outcomes of biochemical remission.
In this study, we observed that higher rate of biochemical remission and less postoperative complications were associated with the accumulation of surgeon's experience. For patients with high preoperative nadir GH levels, stricter postoperative hormonal levels monitoring and drug adjuvant therapy should be considered. The preoperative IGF-1 is not always a predictor, and preoperative nadir GH levels should be a significant complement for predicting postoperative biochemical remission.
A limitation of this retrospective study is comparatively shorter follow-up duration and possible selection bias. The deficiency of long-term outcomes analysis resulted from patients who were lost to follow-up after their first postoperative clinic visit. Additionally, although our study contained 10 years of endoscopic somatotrophin pituitary adenomas cases, the relatively small patient size may have limited us to achieve statistical significance when determining predictors of postoperative outcomes. Other limitations of our study are that we lacked the complete information about medical treatment during follow-up duration. Actually, the medical treatment for patients is important for us to analyze the biochemical remission rate and predictors. When we studied the changes of patients' physiological indicators in purely endoscopic somatotrophin pituitary series, the medication history should be considered into influencing factors.
Conclusion
In summary, we found that the resection of somatotrophin pituitary adenomas via EEA could lead to biochemical remission in up to 57% of patients. The accumulation of surgeon's experience is closely related to the postoperative outcomes. The learning curves showed that the surgeon entered the stage of technological maturity after accumulation of 40 operations. The biochemical remission rate tended to stabilize or further improve. In addition, the preoperative nadir GH level is an important predictor for biochemical remission after surgery. In our study, we also found the problem that preoperative IGF-1 cannot be used as a predictor, which indicated that this problem was not only related to the quality of data but also related to the characteristics of tumor. Our previous research on GH pituitary adenoma may support this opinion, but it requires data such as tumor genotype for more detailed analysis.
Conflict of Interest None declared.
Ethical Approval and Consent to Participate
All patients provided written informed consent. The Institutional Review Board at Jinling Hospital approved the study.
Consent for Publication
The authors declare that the manuscript has not been submitted for publication elsewhere, in whole or in part, in any language. All authors have contributed to, read, and approved the enclosed manuscript.
Authors' Contributions
Y.G., Q.D., Z.C., J.Z., Z.L., C.D., F.Y., X.Z., A.A., J.Y., C.T., and C.M. all contributed to the review of relevant literature, writing, editing, and/or revising of the manuscript.
These authors contributed equally to this work and share first authorship.
References
- 1.de Herder W W. The history of acromegaly. Neuroendocrinology. 2016;103(01):7–17. doi: 10.1159/000371808. [DOI] [PubMed] [Google Scholar]
- 2.Melmed S, Bronstein M D, Chanson P et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(09):552–561. doi: 10.1038/s41574-018-0058-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest. 2009;119(11):3189–3202. doi: 10.1172/JCI39375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Endocrine Society . Katznelson L, Laws E R, Jr, Melmed S et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–3951. doi: 10.1210/jc.2014-2700. [DOI] [PubMed] [Google Scholar]
- 5.Antunes X, Ventura N, Camilo G B et al. Predictors of surgical outcome and early criteria of remission in acromegaly. Endocrine. 2018;60(03):415–422. doi: 10.1007/s12020-018-1590-8. [DOI] [PubMed] [Google Scholar]
- 6.Starke R M, Raper D M, Payne S C, Vance M L, Oldfield E H, Jane J A., Jr Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab. 2013;98(08):3190–3198. doi: 10.1210/jc.2013-1036. [DOI] [PubMed] [Google Scholar]
- 7.Fathalla H, Cusimano M D, Di Ieva Aet al. Endoscopic versus microscopic approach for surgical treatment of acromegaly Neurosurg Rev 20153803541–548., discussion 548–549 [DOI] [PubMed] [Google Scholar]
- 8.Chen C J, Ironside N, Pomeraniec I J et al. Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications. Acta Neurochir (Wien) 2017;159(11):2193–2207. doi: 10.1007/s00701-017-3318-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Knosp E, Steiner E, Kitz K, Matula C.Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings Neurosurgery 19933304610–617., discussion 617–618 [DOI] [PubMed] [Google Scholar]
- 10.Eseonu C I, ReFaey K, Garcia O, Salvatori R, Quinones-Hinojosa A. Comparative cost analysis of endoscopic versus microscopic endonasal transsphenoidal surgery for pituitary adenomas. J Neurol Surg B Skull Base. 2018;79(02):131–138. doi: 10.1055/s-0037-1604484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Gao H, Liu C, Zhang Y. Neuro-endoscope for skull base tumors. Clin Neurol Neurosurg. 2018;170:102–105. doi: 10.1016/j.clineuro.2018.05.009. [DOI] [PubMed] [Google Scholar]
- 12.Sarkar S, Rajaratnam S, Chacko G, Chacko A G. Endocrinological outcomes following endoscopic and microscopic transsphenoidal surgery in 113 patients with acromegaly. Clin Neurol Neurosurg. 2014;126(126):190–195. doi: 10.1016/j.clineuro.2014.09.004. [DOI] [PubMed] [Google Scholar]
- 13.Wagenmakers M A, Netea-Maier R T, van Lindert E J, Pieters G F, Grotenhuis A J, Hermus A R. Results of endoscopic transsphenoidal pituitary surgery in 40 patients with a growth hormone-secreting macroadenoma. Acta Neurochir (Wien) 2011;153(07):1391–1399. doi: 10.1007/s00701-011-0959-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Campbell P G, Kenning E, Andrews D W, Yadla S, Rosen M, Evans J J. Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus. 2010;29(04):E5. doi: 10.3171/2010.7.FOCUS10153. [DOI] [PubMed] [Google Scholar]
- 15.Hofstetter C P, Mannaa R H, Mubita L et al. Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus. 2010;29(04):E6. doi: 10.3171/2010.7.FOCUS10173. [DOI] [PubMed] [Google Scholar]
- 16.Shin S S, Tormenti M J, Paluzzi A et al. Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary. 2013;16(04):435–444. doi: 10.1007/s11102-012-0440-6. [DOI] [PubMed] [Google Scholar]
- 17.Phan K, Xu J, Reddy R, Kalakoti P, Nanda A, Fairhall J. Endoscopic endonasal versus microsurgical transsphenoidal approach for growth hormone-secreting pituitary adenomas-systematic review and meta-analysis. World Neurosurg. 2017;97(97):398–406. doi: 10.1016/j.wneu.2016.10.029. [DOI] [PubMed] [Google Scholar]
- 18.Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol. 2005;152(03):379–387. doi: 10.1530/eje.1.01863. [DOI] [PubMed] [Google Scholar]
- 19.Shen M, Tang Y, Shou Xet al. Surgical results and predictors of initial and delayed remission for growth hormone-secreting pituitary adenomas using the 2010 consensus criteria in 162 patients from a single center World Neurosurg 20182018S1878–8750.(18)32738-4 [DOI] [PubMed] [Google Scholar]
- 20.Kempf J, Schmitz A, Meier A et al. Adenoma size and postoperative IGF-1 levels predict surgical outcomes in acromegaly patients: results of the Swiss Pituitary Registry (SwissPit) Swiss Med Wkly. 2018;148:w14653. doi: 10.4414/smw.2018.14653. [DOI] [PubMed] [Google Scholar]
- 21.Unal T C, Aydoseli A, Ozgen U et al. A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission. Br J Neurosurg. 2021;2021:1–6. doi: 10.1080/02688697.2021.1947977. [DOI] [PubMed] [Google Scholar]
- 22.Cardinal T, Rutkowski M J, Micko A et al. Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly. Neurosurg Focus. 2020;48(06):E10. doi: 10.3171/2020.3.FOCUS2080. [DOI] [PubMed] [Google Scholar]
- 23.Shen S C, Shen C C, Pu T W, Cheng W Y. Long-term effects of intracapsular debulking and adjuvant somatostatin analogs for growth hormone-secreting pituitary macroadenoma: 10 years of experience in a single institute. World Neurosurg. 2019;126(126):e41–e47. doi: 10.1016/j.wneu.2019.01.125. [DOI] [PubMed] [Google Scholar]
- 24.Kim E H, Oh M C, Lee E J, Kim S H.Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly Neurosurgery 201270051106–1113., discussion 1113 [DOI] [PubMed] [Google Scholar]
- 25.Albarel F, Castinetti F, Morange I et al. Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients. Clin Endocrinol (Oxf) 2013;78(02):263–270. doi: 10.1111/j.1365-2265.2012.04492.x. [DOI] [PubMed] [Google Scholar]
- 26.Jane J A, Jr, Starke R M, Elzoghby M A et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab. 2011;96(09):2732–2740. doi: 10.1210/jc.2011-0554. [DOI] [PubMed] [Google Scholar]
- 27.Tang C, Zhong C, Cong Z et al. MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH-secreting adenomas. Oncol Lett. 2019;17(03):3495–3502. doi: 10.3892/ol.2019.10006. [DOI] [PMC free article] [PubMed] [Google Scholar]