Predictive Model of Delayed Hyponatremia after Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenoma

Predictive Model of Delayed Hyponatremia after Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive Model of Delayed Hyponatremia after Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenoma YuKang Pei, Faan Miao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4228558/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective This study aims to establish the risk factors and predictive model for the occurrence of delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma. Methods Data from 155 patients who underwent endoscopic endonasal transsphenoidal resection of pituitary adenoma at the affiliated hospital of Xuzhou Medical University from January 2018 to May 2023 were analyzed. These patients were randomly divided into a training group (108 cases, 70%) and a validation group (47 cases, 30%). Univariate and Multivariate Logistic regression analysis were conducted on the training group to identify risk factors for delayed hyponatremia after surgery. A predictive model was established using R software and validated. Results After conducting Univariate and Multivariate Logistic regression analysis, factors influencing the occurrence of delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma were identified as follows: elevated preoperative prolactin levels, higher preoperative suprasellar cistern height, and hyponatremia in the first 1-2 days after surgery. The area under the receiver operating characteristic (ROC) curve for forecasting delayed postoperative hyponatremia (DPH) in training and validation sets was 0.943 and 0.959 respectively. The DCA curve indicated a higher benefit in clinical application. Conclusions The risk prediction model for delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma, developed in this study, demonstrates favorable predictive performance. The nomogram can be utilized for early identification of high-risk individuals for DPH. Pituitary adenoma Transsphenoidal surgery Delayed hyponatremia Nomograms Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduce Pituitary adenoma (PA) is a tumor that grows in the sellar region of the anterior pituitary gland. Its incidence ranks only after gliomas and meningiomas [ 1 ][ 2 ] . Most pituitary adenomas can be removed through transsphenoidal surgery (TSS) using an endoscopic endonasal approach. This surgical technique not only avoids traction on brain tissue and cranial nerves but also maximizes tumor removal while reducing postoperative complications, thereby shortening hospital stays [ 3 ] . Delayed postoperative hyponatremia (DPH) refers to hyponatremia occurring on or after the third day following surgery [ 4 ] . The incidence of DPH after transsphenoidal surgery for pituitary adenoma varies between 7.4% and 14.7% [ 5 ] . Patients with hyponatremia may present with various clinical symptoms, and severe cases can lead to altered mental status, seizures, coma, and even death [ 6 ] . Additionally, research suggests that DPH is a major risk factor for readmission within 30 days postoperatively for pituitary adenoma [ 7 ] . The objective of this study is to explore the risk factors for DPH after endoscopic endonasal transsphenoidal resection of pituitary adenoma and to construct a predictive model to identify and screen high-risk patients, thereby assisting clinical decision-making. Materials and methods Patient cohort A retrospective analysis was conducted on clinical data collected from 155 patients who underwent endoscopic endonasal transsphenoidal surgery at the affiliated hospital of Xuzhou Medical University between January 2018 and May 2023. Inclusion criteria were: a) patients diagnosed with pituitary adenoma based on clinical and pathological confirmation; b) first-time recipients of endoscopic endonasal transsphenoidal resection of pituitary adenoma; c) availability of complete clinical data. Exclusion criteria were: a) history of previous pituitary surgery or radiotherapy; b) preoperative hyponatremia; c) patients with concomitant other pituitary lesions or endocrine disorders. All surgeries were performed by the same surgical team. Ethical approval was obtained from the Ethics Committee of the affiliated hospital of Xuzhou Medical University, and all patients were exempt from informed consent (XYFY2023-KL250-01). Research Data Collected and compiled clinical data, including demographic information, surgical procedures, and postoperative outcomes. Laboratory data encompassed hormone levels before and after surgery: adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone, and insulin-like growth factor, as well as serum sodium levels (preoperatively and postoperatively for the first 1 to 3 days; in case of hyponatremia, daily monitoring until normalization, otherwise every three days). Imaging data included pre- and postoperative pituitary MRI scans (plain and enhanced scans) for evaluating tumor size, Knosp grading, pre- and postoperative angle of pituitary stalk deviation, height increase of the diaphragma sellae before and after surgery, and extent of tumor resection. Diagnostic Criteria and Definitions Considering potential variations in reference values across different laboratories [ 8 ] , low serum sodium concentration is defined as below 137 mmol/L based on the laboratory settings of our institution. Upon admission, all patients undergo radiological examination to observe tumor location and its relationship with surrounding tissues, classified into Knosp grades 0–4 [ 9 ] . The angle of deviation of the pituitary stalk is recorded on T1 + C scans, defined as the angle at which the pituitary stalk deviates from the midline at its point of origin [ 10 ] (Fig. 1). On T2W1 scans, the height of the diaphragma sellae elevation (the distance between the plane where the elevation of the diaphragma sellae begins and the plane of the highest point of the sellae) is calculated (Fig. 2). Tumor volume is calculated using the simplified ellipsoid volume formula V = ABC/2. Statistical analysis The data analysis was performed using SPSS 25.0 software. Patients were randomly divided into two groups: a training group (108 cases, 70%) and a validation group (47 cases, 30%). Continuous variables were expressed as mean ± standard deviation ( \(\stackrel{-}{x}\) ± s), and differences between the two groups were compared using the t -test. Categorical variables were presented as case numbers, and intergroup comparisons were made using the chi-square test (χ² test). Non-parametric tests were used for comparing ordinal data. Logistic regression analysis was conducted to determine independent risk factors in the training group. Differences were considered statistically significant when p-values were less than 0.05. The identified independent risk factors were then imported into R software (version 4.3.3) for analysis. Based on this, a nomogram predictive model was constructed for the training group. The predictive performance of this model was evaluated in the validation group by calculating the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). These assessments were used to evaluate the predictive ability of the nomogram generated from the training group. Figure 1 The difference in pituitary stalk deviation angle before and after transsphenoidal surgery. a Before surgery, the pituitary stalk deviates 20.893° to the right. b After surgery, the tumor was totally removed, and the pituitary stalk deviation angle was 9.246°. Results The basic characteristics of the cases The study retrospectively analyzed 155 patients who underwent endoscopic endonasal transsphenoidal resection of pituitary adenoma at the affiliated hospital of Xuzhou Medical University from January 2018 to May 2023. Among them, 50 patients (32%) developed delayed hyponatremia. These patients were randomly divided into a training group (108 cases) and a validation group (47 cases) at a ratio of 7:3. In the training group, 39 patients developed delayed hyponatremia, while in the validation group, there were 11 cases. A comparison of clinical data between the training and validation groups showed no significant differences ( Table 1 ) . Table 1 Comparison of the characteristics between the training and validation cohorts. Factors training group(n = 108) validation group(n = 47) t / χ ²/Z P Age, yrs 47.9 ± 12.5 50.9 ± 15.6 1.617 0.106 Sex 1.166 0.243 Male 51(47.2) 27(57.4) Female 57(52.8) 20(42.6) Dizziness and Headache 64(59.3) 26(55.3) 0.455 0.649 Visual damage and optic filed defect 51(47.2) 23(48.9) 0.196 0.845 Altered menstrual period 9(8.3) 6(12.8) 0.855 0.392 Galactorrhea 1(0.9) 1(2.1) 0.607 0.544 Changes in sexual function 0(0.0) 1(2.1) 1.516 0.130 Acromegalia 4(3.7) 3(6.4) 0.736 0.462 Preoperative ACTH (pg/ml) 25.6(19.8, 34.8) 29.1(19.2, 35.6) 1.094 0.274 Preoperative cortisol (ug/dl) 9.9(7.5, 13.1) 11.2(7.2, 15.4) 0.938 0.348 Preoperative PRL (ng/ml) 24.6(15.7, 256.8) 22.9(12.5, 40.1) 1.308 0.108 Preoperative GH (ng/ml) 0.6(0.2, 1.6) 0.3(0.1, 0.9) 1.829 0.067 Postoperative ACTH(pg/ml) 22.4(15.6, 35.9) 28.3(16.3, 35.9) 1.633 0.102 Postoperative cortisol (ug/dl) 14.8(7.9, 18.7) 18.6(8.9, 25.1) 2.423 0.015 Postoperative PRL (ng/ml) 21.3(9.5, 139.5) 19.1(7.0, 66.4) 1.030 0.303 Postoperative GH (ng/ml) 0.9(0.6, 1.6) 0.8(0.5, 1.6) 0.152 0.879 Preoperative sodium levels(mmol/L) 141.5(139.0, 142.3) 141.5(140.5, 142.5) 1.712 0.087 Sodium levels 1–2 days after surgery(mmol/L) 139.7(136.5, 141.9) 141.6(139.3, 142.8) 1.937 0.053 Sodium levels 3 days after surgery(mmol/L) 139.5(134.7, 141.9) 141.1(139.4, 143.0) 2.934 0.003 Maximum tumor diameter(mm) 25(16, 34) 20(16, 25) 2.548 0.011 Tumor volume(cm³) 4.7(2.2, 10.0) 3.2(2.0, 5.4) 2.067 0.039 Preoperative pituitary stalk deviation angle(°) 37.0(20.0, 45.7) 29.2(20.1, 38.9) 1.681 0.093 Postoperative pituitary stalk deviation angle(°) 20.0(2.1, 29.1) 12.3(0.0, 22.0) 1.681 0.120 Preoperative elevation of the diaphragma sellae(mm) 13.5(5.0, 20.0) 8.0(5.0, 15.0) 1.719 0.097 Postoperative elevation of the diaphragma sellae(mm) 4.5(0.0, 10.0) 3.0(0.0, 8.0) 1.824 0.068 Knosp grade 1.659 0.097 Grade 0 ~ 2 62(57.5) 36(76.6) Grade 3 ~ 4 46(42.5) 11(23.4) Extent of tumor resection 1.486 0.137 Total resection 92(85.2) 44(93.6) Subtotal resection 14(13.0) 3(6.4) Partial resection 2(1.9) 0(0.0) Intraoperative CSF leakage 14(13.0) 7(14.9) 0.322 0.748 Postoperative diabetes insipidus 49(45.4) 12(25.5) 2.316 0.021 Hyponatremia 1–2 days after surgery 32(29.6) 7(14.9) 1.937 0.053 Hyponatremia 3 days after surgery 39(36.1) 11(23.4) 2.934 0.121 ACTH, adrenocorticotropic hormone; PRL prolactin; GH: growth hormone; CSF, cerebral spinal fluid Univariate and Multivariate Logistic regression analysis of delayed hyponatremia Comparison of Univariate analysis between the delayed hyponatremia group (39 cases) and the normal sodium group (69 cases) in the training group revealed significant differences in pre- and postoperative prolactin levels, maximum tumor diameter, tumor volume, pre- and postoperative pituitary stalk deviation angle, pre- and postoperative elevation of the diaphragma sellae, tumor invasiveness, preoperative serum sodium levels, hyponatremia on the first 1–2 days postoperatively, and postoperative diabetes insipidus (P < 0.05). Further logistic regression analysis identified preoperative hyperprolactinemia, higher preoperative elevation of the diaphragma sellae, and occurrence of hyponatremia on the first 1–2 days postoperatively as independent risk factors for delayed hyponatremia following transsphenoidal surgery in patients with pituitary adenoma (P < 0.05) (Table 2) . Table 2 Univariate and Multivariate Logistic regression analysis of delayed hyponatremia after transsphenoidal surgery for pituitary adenomas[n(%)] Univariate analysis Logistic regression analysis Factors delayed hyponatremia group(n = 39) normal sodium group(n = 69) t / χ ²/Z P Odds ratio 95%CI P Preoperative PRL (ng/ml) 506.7(24.3, 1897.5) 21.1(13.9, 35.9) 5.280 0.000 1.010 1.003 ~ 1.018 0.005 Postoperative PRL (ng/ml) 111.9(10.6, 323.3) 18.6(9.2, 27.6) 3.682 0.000 Maximum tumor diameter(mm) 34(26, 41) 20(14, 27) 5.536 0.000 Tumor volume(cm³) 10.0(5.4, 16.5) 3.8(1.3, 6.2) 5.149 0.000 Preoperative pituitary stalk deviation angle(°) 45.6(40.1, 56.4) 28.7(11.4, 39.7) 5.663 0.000 Postoperative pituitary stalk deviation angle(°) 24.1(17.6, 32.8) 12.7(0.0, 24.6) 3.691 0.000 Preoperative elevation of the diaphragma sellae(mm) 20(15, 25) 8(5, 15) 6.062 0.000 1.651 1.190 ~ 2.290 0.003 Postoperative elevation of the diaphragma sellae(mm) 7(3, 17) 3.0(0.0, 8.0) 3.697 0.000 Knosp grade 4.799 0.000 Grade 0 ~ 2 12(30.7) 50(72.5) Grade 3 ~ 4 27(69.3) 19(27.5) Postoperative diabetes insipidus 49(45.4) 12(25.5) 4.929 0.000 Preoperative sodium levels(mmol/L) 140.2(138.0, 141.7) 141.3(139.7, 142.3) 2.329 0.020 Hyponatremia 1–2 days after surgery 32(29.6) 7(14.9) 5.434 0.000 32.650 2.188 ~ 487.280 0.011 ACTH, adrenocorticotropic hormone; PRL prolactin; GH: growth hormone; CSF, cerebral spinal fluid Development of Prediction Model in the Training Cohort Using R software (version 4.3.3), a predictive model was constructed based on the three variables selected from the logistic regression analysis conducted on the training set. This model is represented by a nomogram, which is used to estimate the likelihood of delayed hyponatremia occurrence after endoscopic transsphenoidal surgery for pituitary adenoma. The nomogram assigns a composite score based on the parameter values in the nomogram, which is then mapped to corresponding risk levels to estimate the risk of developing hyponatremia postoperatively (Fig. 3) . Validation of the Nomogram for Delayed Hyponatremia External validation of the model was performed using data from the validation group comprising 47 patients. The area under the receiver operating characteristic (ROC) curve for the nomogram model in the training set was 0.943 (95% CI 0.898–0.987), while in the validation set, it was 0.959 (95% CI 0.910–0.979) (Fig. 4). These results indicate that the model has good discriminative ability on both internal and external data. In the calibration curve analysis, the predicted results of the model closely matched the observed outcomes in both groups, demonstrating a high level of fit (Fig. 5 ). Additionally, decision curve analysis (DCA) revealed that the application of this model within the threshold range of 0.01 to 0.93 (training group) and 0.01 to 0.87 (validation group) could lead to improved clinical utility, indicating its practical value in the clinical setting (Fig. 6 ). Figure 3 Nomogram of delayed hyponatremia after transsphenoidal adenoma surgery. The predictor points can be found on the uppermost point scale that correspond to each patient variable and can be added up. The total points projected to the bottom scale indicate the risk of delayed hyponatremia. (For Hyponatremia 1–2 days after surgery, 0 means “No”, 1 means “Yes”). Fig 4 the ROC curves of the nomogram model (Left: Training set, Right: Validation set). Discussion Delayed Postoperative Hyponatremia (DPH) is a common complication following endoscopic endonasal transsphenoidal surgery (TSS) for pituitary adenoma and is a leading cause of unplanned readmission within 30 days postoperatively [ 11 ] . Studies suggest that the primary cause may be syndrome of inappropriate antidiuretic hormone secretion (SIADH) [ 12 ] , with cerebral salt-wasting syndrome (CSWS) being a rare cause in some cases [ 13 ] . Manipulation of the pituitary stalk and posterior pituitary during surgery may lead to uncontrolled release of antidiuretic hormone [ 14 ] . This study investigated the risk factors for DPH after pituitary adenoma surgery and identified preoperative hyperprolactinemia, higher preoperative elevation of the diaphragma sellae, and occurrence of hyponatremia on the first 1–2 days postoperatively as independent risk factors for DPH following TSS in patients with pituitary adenoma. The establishment and validation of a risk prediction model based on these findings hold significant clinical relevance for the prevention of DPH. Huang et al. [ 15 ] demonstrated that preoperative hyperprolactinemia is an independent risk factor for delayed hyponatremia following endoscopic transsphenoidal surgery for non-functioning pituitary adenomas. Our study shares a similar viewpoint. Although the hypothalamus can secrete prolactin inhibitory and releasing factors, it primarily suppresses prolactin secretion through the release of inhibitory factors such as dopamine and gamma-aminobutyric acid [ 16 ] . Mechanical compression of the pituitary stalk by pituitary adenomas can lead to a so-called "stalk effect " or "pituitary stalk compression syndrome," resulting in decreased dopamine release and corresponding increase in prolactin [ 17 ] . During tumor resection, the close proximity of the tumor to the pituitary stalk makes it more susceptible to interference or damage, leading to uncontrolled release of antidiuretic hormone (ADH). In Lin's study [ 10 ][ 18 ] , the descent of the diaphragma sellae is of significant importance in predicting the occurrence of DPH. In our study, preoperative elevation of the diaphragma sellae was found to be associated with DPH after TSS. High preoperative elevation of the diaphragma sellae during surgery leads to a rapid decrease in intrasellar pressure and a rapid reduction in tumor cavity height after tumor resection, resulting in passive traction of the pituitary stalk during surgery and mechanical injury, which may trigger the occurrence of SIADH. Similarly, changes in the pituitary stalk deviation angle can also predict the occurrence of DPH after TSS [ 19 ][ 20 ][ 21 ] . The more pronounced the changes in the pituitary stalk, the greater the likelihood of pituitary stalk injury. However, in our study, the pituitary stalk deviation angle was not identified as an independent risk factor for DPH. This may be due to the use of gelatin sponge packing in the tumor cavity and artificial dura reconstruction at the sellar floor during surgery, which takes approximately 4–6 weeks to be completely absorbed by the body [ 22 ] . As a result, changes in the pituitary stalk may not be significant when pituitary MRI is performed approximately 3 days postoperatively. In our study, patients who developed hyponatremia on the first 1–2 days postoperatively had an approximately 32.6-fold increased risk of (DPH. Yoon et al. [ 23 ] found that patients with serum sodium concentration < 138 mmol/L within 1–2 days after TSS had approximately 2.8 times higher risk of developing delayed hyponatremia, and similar results were reported by Krogh et al. [ 24 ] . Therefore, close monitoring of early postoperative serum sodium levels in TSS patients is crucial to identify the etiology of hyponatremia, implement preventive measures promptly, and reduce the risk of delayed hyponatremia. In statistics, an AUC value of 0.70 to 0.79 is considered acceptable for predictive models, while a value of 0.80 to 0.89 indicates excellent predictive performance [ 25 ] . The predictive model constructed in our study achieved AUC values of 0.943 and 0.959 in the two groups, respectively, demonstrating excellent discriminative ability for predicting delayed hyponatremia after surgery. The calibration curves showed high consistency between the predicted and observed outcomes within a certain range, with a slope close to 1. Additionally, the decision curve analysis (DCA) curves in both groups indicated that adopting relevant preventive measures for high-risk patients could lead to better clinical benefits within a larger threshold range, demonstrating good clinical utility. Although this study has incorporated relatively comprehensive and thorough clinical information, it is limited by being a single-center study with a limited sample size, and the model has not been validated in other centers. Therefore, our next step will be to conduct a broader, multicenter study to further refine the fitted model and validate it using data from external institutions, thereby expanding the applicability of the model. Conclusion This study utilized three key indicators: preoperative prolactin levels, preoperative elevation of the diaphragma sellae, and postoperative hyponatremia on the first 1–2 days to construct a nomogram predictive model for predicting delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenoma. This model has good reference value for early identification of high-risk patients, and it can help reduce the incidence of postoperative delayed hyponatremia and improve patient outcomes. Declarations Funding This project was supported by the National Natural Science Foundation of China (Grant No.82002632). Conflict of interest The authors have no conflict of interest. Informed consent With the consent of the Ethics Committee of the affiliated Hospital of Xuzhou Medical University, all patients were exempted from informed consent (XYFY2023-KL250-01). References GHEORGHIU ML, NEGREANU F, FLESERIU M. Updates in the Medical Treatment of Pituitary Adenomas[J]. 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(in Chinese). YOON HK, LEE HC, KIM YH, et al. Predictive Factors for Delayed Hyponatremia After Endoscopic Transsphenoidal Surgery in Patients with Nonfunctioning Pituitary Tumors: A Retrospective Observational Study[J]. World Neurosurg. 2019 Feb;122:e1457-e1464. KROGH J, KISTORP CN, JAFAR-MOHAMMADI B, et al. Transsphenoidal surgery for pituitary tumours: frequency and predictors of delayed hyponatraemia and their relationship to early readmission. Eur J Endocrinol[J]. 2018 Mar;178(3):247-253. ZHANG D, XIE ZB. Analysis of factors causing hemorrhagic transformation in patients with acute cerebral infarction after intravenous thrombolysis in plateau area and establishment of a nomogram prediction model [J]. Journal of International Neurology and Neurosurgery, 2021, 48(5): 461-465. (in Chinese). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4228558","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":288899662,"identity":"2b5e8a02-92f9-4cc9-99c4-c5af276553bb","order_by":0,"name":"YuKang Pei","email":"","orcid":"","institution":"Affiliated Hospital of Xuzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"YuKang","middleName":"","lastName":"Pei","suffix":""},{"id":288899663,"identity":"ccd42d64-c6b9-41c9-9597-4f4c0a57812d","order_by":1,"name":"Faan Miao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYFACxgcMDAY2cvbtDQzMEJEEQlqYDRgYCtKMDXgOkKTlw+HEDRIJRGrRbWBm/FxgkMa4XfKN8efCnMMM/Ow5Bgw/d+DWYnaAmVl6hoENs+XstATjmdsOM0j2vDFg7D2DTwv/AWkegzQ2htvJB5J5gVoMbuQYMDO24bflN4/BYR6GmwcbDoO02BOhhQ1oy2EJgxvMB5vBtkgQocUa6DADyZ60ZGbebek8EmeeFRzsJeCw2zx/bOr72c8Yf+bdZi3H35688cFPPFoY5B+g8nlAxAE8GkbBKBgFo2AUEAEAjKRLsCEYG90AAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Hospital of Xuzhou Medical College","correspondingAuthor":true,"prefix":"","firstName":"Faan","middleName":"","lastName":"Miao","suffix":""}],"badges":[],"createdAt":"2024-04-06 19:14:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4228558/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4228558/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54524283,"identity":"a1630ce9-c315-49fc-b085-3f3afbfda211","added_by":"auto","created_at":"2024-04-11 19:20:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":219926,"visible":true,"origin":"","legend":"\u003cp\u003eThe difference in pituitary stalk deviation angle before and after transsphenoidal surgery. a Before surgery, the pituitary stalk deviates 20.893° to the right. b After surgery, the tumor was totally removed, and the pituitary stalk deviation angle was 9.246°.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/09394ac368582925f5be18d6.png"},{"id":54523736,"identity":"b73cf9db-3bc1-40ab-8814-3d3180d5910b","added_by":"auto","created_at":"2024-04-11 19:12:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":210034,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in the diaphragma sellae (DS) before and after transsphenoidal surgery. a Preoperative elevation of DS was 8.77mm. b After resection of the tumor, the elevation of DS was 0mm.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/e275f4f0af132c4e26e51200.png"},{"id":54523735,"identity":"56cae1da-986f-4fbf-a563-631f7a17027a","added_by":"auto","created_at":"2024-04-11 19:12:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47176,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram of delayed hyponatremia after transsphenoidal adenoma surgery. The predictor points can be found on the uppermost point scale that correspond to each patient variable and can be added up. The total points projected to the bottom scale indicate the risk of delayed hyponatremia. (For Hyponatremia 1-2 days after surgery, 0 means “No”, 1 means “Yes”).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/46f1c554eaa5c16a5a09bfb5.png"},{"id":54523737,"identity":"62bfae9a-d0e6-4e69-9e86-d7ed10f55362","added_by":"auto","created_at":"2024-04-11 19:12:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":46862,"visible":true,"origin":"","legend":"\u003cp\u003ethe ROC curves of the nomogram model (Left: Training set, Right: Validation set).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/07b5b81dd39e04213ce01d97.png"},{"id":54523738,"identity":"b9798be6-603c-4784-bb9e-7027da68dd0b","added_by":"auto","created_at":"2024-04-11 19:12:51","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":60377,"visible":true,"origin":"","legend":"\u003cp\u003ethe calibration curves of the nomogram model (Left: Training set, Right: Validation set).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/81df01bcde8dbafadd585b5b.png"},{"id":54523740,"identity":"7f743631-e43d-4da8-9d75-7ac421fa5494","added_by":"auto","created_at":"2024-04-11 19:12:51","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":51771,"visible":true,"origin":"","legend":"\u003cp\u003ethe DCA (Decision Curve Analysis) curves (Left: Training set, Right: Validation set).\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/dd1ebc612859024e4d5ee6e9.png"},{"id":54693710,"identity":"de4e3d43-67c3-4736-8d54-214edbafcdba","added_by":"auto","created_at":"2024-04-15 10:43:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1135316,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4228558/v1/a242dd67-bfad-4a91-b2c1-9133c7689e04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Model of Delayed Hyponatremia after Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenoma","fulltext":[{"header":"Introduce","content":"\u003cp\u003ePituitary adenoma (PA) is a tumor that grows in the sellar region of the anterior pituitary gland. Its incidence ranks only after gliomas and meningiomas \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Most pituitary adenomas can be removed through transsphenoidal surgery (TSS) using an endoscopic endonasal approach. This surgical technique not only avoids traction on brain tissue and cranial nerves but also maximizes tumor removal while reducing postoperative complications, thereby shortening hospital stays \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDelayed postoperative hyponatremia (DPH) refers to hyponatremia occurring on or after the third day following surgery \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The incidence of DPH after transsphenoidal surgery for pituitary adenoma varies between 7.4% and 14.7% \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Patients with hyponatremia may present with various clinical symptoms, and severe cases can lead to altered mental status, seizures, coma, and even death \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Additionally, research suggests that DPH is a major risk factor for readmission within 30 days postoperatively for pituitary adenoma \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The objective of this study is to explore the risk factors for DPH after endoscopic endonasal transsphenoidal resection of pituitary adenoma and to construct a predictive model to identify and screen high-risk patients, thereby assisting clinical decision-making.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient cohort\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted on clinical data collected from 155 patients who underwent endoscopic endonasal transsphenoidal surgery at the affiliated hospital of Xuzhou Medical University between January 2018 and May 2023. Inclusion criteria were: a) patients diagnosed with pituitary adenoma based on clinical and pathological confirmation; b) first-time recipients of endoscopic endonasal transsphenoidal resection of pituitary adenoma; c) availability of complete clinical data. Exclusion criteria were: a) history of previous pituitary surgery or radiotherapy; b) preoperative hyponatremia; c) patients with concomitant other pituitary lesions or endocrine disorders. All surgeries were performed by the same surgical team. Ethical approval was obtained from the Ethics Committee of the affiliated hospital of Xuzhou Medical University, and all patients were exempt from informed consent (XYFY2023-KL250-01).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eResearch Data\u003c/h2\u003e \u003cp\u003eCollected and compiled clinical data, including demographic information, surgical procedures, and postoperative outcomes. Laboratory data encompassed hormone levels before and after surgery: adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone, and insulin-like growth factor, as well as serum sodium levels (preoperatively and postoperatively for the first 1 to 3 days; in case of hyponatremia, daily monitoring until normalization, otherwise every three days). Imaging data included pre- and postoperative pituitary MRI scans (plain and enhanced scans) for evaluating tumor size, Knosp grading, pre- and postoperative angle of pituitary stalk deviation, height increase of the diaphragma sellae before and after surgery, and extent of tumor resection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic Criteria and Definitions\u003c/h2\u003e \u003cp\u003eConsidering potential variations in reference values across different laboratories \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, low serum sodium concentration is defined as below 137 mmol/L based on the laboratory settings of our institution. Upon admission, all patients undergo radiological examination to observe tumor location and its relationship with surrounding tissues, classified into Knosp grades 0\u0026ndash;4 \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The angle of deviation of the pituitary stalk is recorded on T1\u0026thinsp;+\u0026thinsp;C scans, defined as the angle at which the pituitary stalk deviates from the midline at its point of origin \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e (Fig.\u0026nbsp;1). On T2W1 scans, the height of the diaphragma sellae elevation (the distance between the plane where the elevation of the diaphragma sellae begins and the plane of the highest point of the sellae) is calculated (Fig.\u0026nbsp;2). Tumor volume is calculated using the simplified ellipsoid volume formula V\u0026thinsp;=\u0026thinsp;ABC/2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data analysis was performed using SPSS 25.0 software. Patients were randomly divided into two groups: a training group (108 cases, 70%) and a validation group (47 cases, 30%). Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\stackrel{-}{x}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn; s), and differences between the two groups were compared using the \u003cem\u003et\u003c/em\u003e-test. Categorical variables were presented as case numbers, and intergroup comparisons were made using the chi-square test (χ\u0026sup2; test). Non-parametric tests were used for comparing ordinal data. Logistic regression analysis was conducted to determine independent risk factors in the training group. Differences were considered statistically significant when p-values were less than 0.05.\u003c/p\u003e \u003cp\u003eThe identified independent risk factors were then imported into R software (version 4.3.3) for analysis. Based on this, a nomogram predictive model was constructed for the training group. The predictive performance of this model was evaluated in the validation group by calculating the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). These assessments were used to evaluate the predictive ability of the nomogram generated from the training group.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1\u003c/b\u003e The difference in pituitary stalk deviation angle before and after transsphenoidal surgery. a Before surgery, the pituitary stalk deviates 20.893\u0026deg; to the right. b After surgery, the tumor was totally removed, and the pituitary stalk deviation angle was 9.246\u0026deg;.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eThe basic characteristics of the cases\u003c/h2\u003e \u003cp\u003eThe study retrospectively analyzed 155 patients who underwent endoscopic endonasal transsphenoidal resection of pituitary adenoma at the affiliated hospital of Xuzhou Medical University from January 2018 to May 2023. Among them, 50 patients (32%) developed delayed hyponatremia. These patients were randomly divided into a training group (108 cases) and a validation group (47 cases) at a ratio of 7:3. In the training group, 39 patients developed delayed hyponatremia, while in the validation group, there were 11 cases. A comparison of clinical data between the training and validation groups showed no significant differences \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the characteristics between the training and validation cohorts.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003etraining group(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003evalidation group(n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003et /\u003cem\u003eχ\u003c/em\u003e\u0026sup2;/Z\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e47.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e51(47.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27(57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e57(52.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(42.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness and Headache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e64(59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26(55.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.649\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual damage and optic filed defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e51(47.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23(48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.845\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAltered menstrual period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9(8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGalactorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1(0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChanges in sexual function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.516\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcromegalia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.736\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.462\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative ACTH (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e25.6(19.8, 34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.1(19.2, 35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.094\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.274\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative cortisol (ug/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.9(7.5, 13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.2(7.2, 15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.938\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.348\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative PRL (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e24.6(15.7, 256.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.9(12.5, 40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative GH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.6(0.2, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3(0.1, 0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.829\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative ACTH(pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e22.4(15.6, 35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.3(16.3, 35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative cortisol (ug/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e14.8(7.9, 18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.6(8.9, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative PRL (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e21.3(9.5, 139.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.1(7.0, 66.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative GH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.9(0.6, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8(0.5, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative sodium levels(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141.5(139.0, 142.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e141.5(140.5, 142.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.712\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium levels 1\u0026ndash;2 days after surgery(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139.7(136.5, 141.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e141.6(139.3, 142.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium levels 3 days after surgery(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139.5(134.7, 141.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e141.1(139.4, 143.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum tumor diameter(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(16, 34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e20(16, 25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor volume(cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7(2.2, 10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3.2(2.0, 5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative pituitary stalk deviation angle(\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0(20.0, 45.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e29.2(20.1, 38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative pituitary stalk deviation angle(\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0(2.1, 29.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e12.3(0.0, 22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative elevation of the diaphragma sellae(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.5(5.0, 20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e8.0(5.0, 15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.719\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative elevation of the diaphragma sellae(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5(0.0, 10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3.0(0.0, 8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.824\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKnosp grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade 0\u0026thinsp;~\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62(57.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e36(76.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade 3\u0026thinsp;~\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e11(23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of tumor resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(85.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e44(93.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtotal resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartial resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative CSF leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e7(14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.748\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative diabetes insipidus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49(45.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e12(25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.316\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia 1\u0026ndash;2 days after surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e7(14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia 3 days after surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e11(23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eACTH, adrenocorticotropic hormone; PRL prolactin; GH: growth hormone; CSF, cerebral spinal fluid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and Multivariate Logistic regression analysis of delayed hyponatremia\u003c/h2\u003e \u003cp\u003eComparison of Univariate analysis between the delayed hyponatremia group (39 cases) and the normal sodium group (69 cases) in the training group revealed significant differences in pre- and postoperative prolactin levels, maximum tumor diameter, tumor volume, pre- and postoperative pituitary stalk deviation angle, pre- and postoperative elevation of the diaphragma sellae, tumor invasiveness, preoperative serum sodium levels, hyponatremia on the first 1\u0026ndash;2 days postoperatively, and postoperative diabetes insipidus (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Further logistic regression analysis identified preoperative hyperprolactinemia, higher preoperative elevation of the diaphragma sellae, and occurrence of hyponatremia on the first 1\u0026ndash;2 days postoperatively as independent risk factors for delayed hyponatremia following transsphenoidal surgery in patients with pituitary adenoma (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) \u003cb\u003e(Table\u0026nbsp;2)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2 Univariate and Multivariate Logistic regression analysis of delayed hyponatremia after transsphenoidal surgery for pituitary adenomas[n(%)]\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eLogistic regression analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003edelayed hyponatremia group(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enormal sodium group(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003et /\u003cem\u003eχ\u003c/em\u003e\u0026sup2;/Z\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePreoperative PRL (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e506.7(24.3, 1897.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.1(13.9, 35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e1.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.003\u0026thinsp;~\u0026thinsp;1.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePostoperative PRL (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.9(10.6, 323.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.6(9.2, 27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMaximum tumor diameter(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34(26, 41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(14, 27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor volume(cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0(5.4, 16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.8(1.3, 6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePreoperative pituitary stalk deviation angle(\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.6(40.1, 56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.7(11.4, 39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePostoperative pituitary stalk deviation angle(\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.1(17.6, 32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.7(0.0, 24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePreoperative elevation of the diaphragma sellae(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(15, 25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(5, 15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e1.651\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.190\u0026thinsp;~\u0026thinsp;2.290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePostoperative elevation of the diaphragma sellae(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(3, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0(0.0, 8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eKnosp grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.799\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGrade 0\u0026thinsp;~\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50(72.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGrade 3\u0026thinsp;~\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(69.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19(27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePostoperative diabetes insipidus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49(45.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePreoperative sodium levels(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140.2(138.0, 141.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e141.3(139.7, 142.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHyponatremia 1\u0026ndash;2 days after surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e32.650\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.188\u0026thinsp;~\u0026thinsp;487.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"1\"\u003eACTH, adrenocorticotropic hormone; PRL prolactin; GH: growth hormone; CSF, cerebral spinal fluid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDevelopment of Prediction Model in the Training Cohort\u003c/h2\u003e \u003cp\u003eUsing R software (version 4.3.3), a predictive model was constructed based on the three variables selected from the logistic regression analysis conducted on the training set. This model is represented by a nomogram, which is used to estimate the likelihood of delayed hyponatremia occurrence after endoscopic transsphenoidal surgery for pituitary adenoma. The nomogram assigns a composite score based on the parameter values in the nomogram, which is then mapped to corresponding risk levels to estimate the risk of developing hyponatremia postoperatively \u003cb\u003e(Fig.\u0026nbsp;3)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eValidation of the Nomogram for Delayed Hyponatremia\u003c/h2\u003e \u003cp\u003eExternal validation of the model was performed using data from the validation group comprising 47 patients. The area under the receiver operating characteristic (ROC) curve for the nomogram model in the training set was 0.943 (95% CI 0.898\u0026ndash;0.987), while in the validation set, it was 0.959 (95% CI 0.910\u0026ndash;0.979) (Fig.\u0026nbsp;4). These results indicate that the model has good discriminative ability on both internal and external data. In the calibration curve analysis, the predicted results of the model closely matched the observed outcomes in both groups, demonstrating a high level of fit (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Additionally, decision curve analysis (DCA) revealed that the application of this model within the threshold range of 0.01 to 0.93 (training group) and 0.01 to 0.87 (validation group) could lead to improved clinical utility, indicating its practical value in the clinical setting (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;3 Nomogram of delayed hyponatremia after transsphenoidal adenoma surgery. The predictor points can be found on the uppermost point scale that correspond to each patient variable and can be added up. The total points projected to the bottom scale indicate the risk of delayed hyponatremia. (For Hyponatremia 1\u0026ndash;2 days after surgery, 0 means \u0026ldquo;No\u0026rdquo;, 1 means \u0026ldquo;Yes\u0026rdquo;).\u003c/p\u003e \u003cp\u003e Fig 4 the ROC curves of the nomogram model (Left: Training set, Right: Validation set).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDelayed Postoperative Hyponatremia (DPH) is a common complication following endoscopic endonasal transsphenoidal surgery (TSS) for pituitary adenoma and is a leading cause of unplanned readmission within 30 days postoperatively \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Studies suggest that the primary cause may be syndrome of inappropriate antidiuretic hormone secretion (SIADH) \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, with cerebral salt-wasting syndrome (CSWS) being a rare cause in some cases \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Manipulation of the pituitary stalk and posterior pituitary during surgery may lead to uncontrolled release of antidiuretic hormone \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. This study investigated the risk factors for DPH after pituitary adenoma surgery and identified preoperative hyperprolactinemia, higher preoperative elevation of the diaphragma sellae, and occurrence of hyponatremia on the first 1\u0026ndash;2 days postoperatively as independent risk factors for DPH following TSS in patients with pituitary adenoma. The establishment and validation of a risk prediction model based on these findings hold significant clinical relevance for the prevention of DPH.\u003c/p\u003e \u003cp\u003eHuang et al. \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e demonstrated that preoperative hyperprolactinemia is an independent risk factor for delayed hyponatremia following endoscopic transsphenoidal surgery for non-functioning pituitary adenomas. Our study shares a similar viewpoint. Although the hypothalamus can secrete prolactin inhibitory and releasing factors, it primarily suppresses prolactin secretion through the release of inhibitory factors such as dopamine and gamma-aminobutyric acid \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Mechanical compression of the pituitary stalk by pituitary adenomas can lead to a so-called \"stalk effect \" or \"pituitary stalk compression syndrome,\" resulting in decreased dopamine release and corresponding increase in prolactin \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. During tumor resection, the close proximity of the tumor to the pituitary stalk makes it more susceptible to interference or damage, leading to uncontrolled release of antidiuretic hormone (ADH).\u003c/p\u003e \u003cp\u003eIn Lin's study \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, the descent of the diaphragma sellae is of significant importance in predicting the occurrence of DPH. In our study, preoperative elevation of the diaphragma sellae was found to be associated with DPH after TSS. High preoperative elevation of the diaphragma sellae during surgery leads to a rapid decrease in intrasellar pressure and a rapid reduction in tumor cavity height after tumor resection, resulting in passive traction of the pituitary stalk during surgery and mechanical injury, which may trigger the occurrence of SIADH. Similarly, changes in the pituitary stalk deviation angle can also predict the occurrence of DPH after TSS \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e][\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e][\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The more pronounced the changes in the pituitary stalk, the greater the likelihood of pituitary stalk injury. However, in our study, the pituitary stalk deviation angle was not identified as an independent risk factor for DPH. This may be due to the use of gelatin sponge packing in the tumor cavity and artificial dura reconstruction at the sellar floor during surgery, which takes approximately 4\u0026ndash;6 weeks to be completely absorbed by the body \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. As a result, changes in the pituitary stalk may not be significant when pituitary MRI is performed approximately 3 days postoperatively.\u003c/p\u003e \u003cp\u003eIn our study, patients who developed hyponatremia on the first 1\u0026ndash;2 days postoperatively had an approximately 32.6-fold increased risk of (DPH. Yoon et al. \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e found that patients with serum sodium concentration\u0026thinsp;\u0026lt;\u0026thinsp;138 mmol/L within 1\u0026ndash;2 days after TSS had approximately 2.8 times higher risk of developing delayed hyponatremia, and similar results were reported by Krogh et al. \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Therefore, close monitoring of early postoperative serum sodium levels in TSS patients is crucial to identify the etiology of hyponatremia, implement preventive measures promptly, and reduce the risk of delayed hyponatremia.\u003c/p\u003e \u003cp\u003eIn statistics, an AUC value of 0.70 to 0.79 is considered acceptable for predictive models, while a value of 0.80 to 0.89 indicates excellent predictive performance \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The predictive model constructed in our study achieved AUC values of 0.943 and 0.959 in the two groups, respectively, demonstrating excellent discriminative ability for predicting delayed hyponatremia after surgery. The calibration curves showed high consistency between the predicted and observed outcomes within a certain range, with a slope close to 1. Additionally, the decision curve analysis (DCA) curves in both groups indicated that adopting relevant preventive measures for high-risk patients could lead to better clinical benefits within a larger threshold range, demonstrating good clinical utility.\u003c/p\u003e \u003cp\u003eAlthough this study has incorporated relatively comprehensive and thorough clinical information, it is limited by being a single-center study with a limited sample size, and the model has not been validated in other centers. Therefore, our next step will be to conduct a broader, multicenter study to further refine the fitted model and validate it using data from external institutions, thereby expanding the applicability of the model.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study utilized three key indicators: preoperative prolactin levels, preoperative elevation of the diaphragma sellae, and postoperative hyponatremia on the first 1\u0026ndash;2 days to construct a nomogram predictive model for predicting delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenoma. This model has good reference value for early identification of high-risk patients, and it can help reduce the incidence of postoperative delayed hyponatremia and improve patient outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis project was supported by the National Natural Science Foundation of China (Grant No.82002632).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eInformed consent\u0026nbsp;\u003c/strong\u003eWith the consent of the Ethics Committee of the affiliated Hospital of Xuzhou Medical University, all patients were exempted from informed consent (XYFY2023-KL250-01).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGHEORGHIU ML, NEGREANU F, FLESERIU M. Updates in the Medical Treatment of Pituitary Adenomas[J]. Horm Metab Res. 2020 Jan;52(1):8-24. \u003c/li\u003e\n\u003cli\u003eZHANG J, WANG Y, XU X, et al. Postoperative complications and quality of life in patients with pituitary adenoma[J]. Gland Surg. 2020 Oct;9(5):1521-1529. \u003c/li\u003e\n\u003cli\u003eLIN L. Analysis of the therapeutic efficacy of endonasal endoscopic pituitary tumor resection in treating pituitary tumors. [J]. Primary Healthcare Forum,2024,28(05):55-57+69. (in Chinese).\u003c/li\u003e\n\u003cli\u003ePATEL KS, SHU CHEN J, YUAN F. Prediction of post-operative delayed hyponatremia after endoscopic transsphenoidal surgery[J]. Clin Neurol Neurosur. 2019 Jul;182:87-91. \u003c/li\u003e\n\u003cli\u003eLEE CC, WANG YC, LIU YT, et al. Incidence and Factors Associated with Postoperative Delayed Hyponatremia after Transsphenoidal Pituitary Surgery: A Meta-Analysis and Systematic Review[J]. Int J Endocrinol. 2021 Apr 10;2021:6659152. \u003c/li\u003e\n\u003cli\u003eADROGU\u0026Eacute; HJ, MADIAS NE. Hyponatremia [J]. N Engl J Med. 2000;342(21):1581-1589.\u003c/li\u003e\n\u003cli\u003eSHAFTEL KA, COLE TS, LITTLE AS. National trends in hospital readmission following transsphenoidal surgery for pituitary lesions[J]. Pituitary. 2020 Apr;23(2):79-91.\u003c/li\u003e\n\u003cli\u003eRONDON H, BADIREDDY M. Hyponatremia[M]. 2023 Jun 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan\u0026ndash;.\u003c/li\u003e\n\u003cli\u003eKNOSP E, STEINER E, KITZ K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings[J]. Neurosurgery. 1993 Oct;33(4):610-7; discussion 617-8. \u003c/li\u003e\n\u003cli\u003eLIN K, ZENG R, MU S, et al. Novel Nomograms to Predict Delayed Hyponatremia After Transsphenoidal Surgery for Pituitary Adenoma[J]. Front Endocrinol. 2022 Jun 28;13:900121. \u003c/li\u003e\n\u003cli\u003eBOHL MA, AHMAD S, JAHNKE H, et al. Delayed Hyponatremia Is the Most Common Cause of 30-Day Unplanned Readmission After Transsphenoidal Surgery for Pituitary Tumors[J]. Neurosurgery. 2016 Jan;78(1):84-90. \u003c/li\u003e\n\u003cli\u003eBARBER SM, LIEBELT BD, BASKIN DS. Incidence, Etiology and Outcomes of Hyponatremia after Transsphenoidal Surgery: Experience with 344 Consecutive Patients at a Single Tertiary Center[J]. J Clin Med. 2014 Oct 28;3(4):1199-219. \u003c/li\u003e\n\u003cli\u003eCERD\u0026Agrave;-ESTEVE M, CUADRADO-GODIA E, CHILLARON JJ, et al. Cerebral salt wasting syndrome: review[J]. Eur J Intern Med. 2008 Jun;19(4):249-54. \u003c/li\u003e\n\u003cli\u003eBLAIR ET, CLEMMER JS, HARKEY HL, et al. Physiologic Mechanisms of Water and Electrolyte Disturbances After Transsphenoidal Pituitary Surgery[J]. World Neurosurg. 2017 Nov;107:429-436. \u003c/li\u003e\n\u003cli\u003eHUANG Y, WANG M, WU J, et al. 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(in Chinese).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pituitary adenoma, Transsphenoidal surgery, Delayed hyponatremia, Nomograms","lastPublishedDoi":"10.21203/rs.3.rs-4228558/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4228558/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e This study aims to establish the risk factors and predictive model for the occurrence of delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eData from 155 patients who underwent endoscopic endonasal transsphenoidal resection of pituitary adenoma at the affiliated hospital of Xuzhou Medical University from January 2018 to May 2023 were analyzed. These patients were randomly divided into a training group (108 cases, 70%) and a validation group (47 cases, 30%). Univariate and Multivariate Logistic regression analysis were conducted on the training group to identify risk factors for delayed hyponatremia after surgery. A predictive model was established using R software and validated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eAfter conducting Univariate and Multivariate Logistic regression analysis, factors influencing the occurrence of delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma were identified as follows: elevated preoperative prolactin levels, higher preoperative suprasellar cistern height, and hyponatremia in the first 1-2 days after surgery. The area under the receiver operating characteristic (ROC) curve for forecasting delayed postoperative hyponatremia (DPH) in training and validation sets was 0.943 and 0.959 respectively. The DCA curve indicated a higher benefit in clinical application.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e The risk prediction model for delayed hyponatremia after endoscopic endonasal transsphenoidal resection of pituitary adenoma, developed in this study, demonstrates favorable predictive performance. The nomogram can be utilized for early identification of high-risk individuals for DPH.\u003c/p\u003e","manuscriptTitle":"Predictive Model of Delayed Hyponatremia after Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-11 19:12:46","doi":"10.21203/rs.3.rs-4228558/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41818f92-199f-4827-b657-7e0a5b5c5778","owner":[],"postedDate":"April 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-15T10:35:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-11 19:12:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4228558","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4228558","identity":"rs-4228558","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}