Sellar and perisellar meningiomas: effects on pituitary function in a Spanish observational study

Sellar and perisellar meningiomas: effects on pituitary function in a Spanish observational study | 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 Sellar and perisellar meningiomas: effects on pituitary function in a Spanish observational study Fernando Guerrero-Pérez, Betina Biagetti, Miguel Paja Fano, Edelmiro Luis Menéndez-Torre, and 28 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5146945/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Dec, 2024 Read the published version in Pituitary → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose Studies focused on the effects of sellar and/or perisellar (S/PS) meningiomas on pituitary function are scarce. We evaluate the clinical characteristics, therapeutic outcomes, and the effects that S/PS meningiomas and their treatments have on pituitary function. Methods A multicenter and retrospective study of patients with S/PS meningiomas attended in 20 tertiary Spanish centers. Results 171 patients, 129 (75.4%) females, with median age of 61.5 [51–71] years were analyzed. At presentation, 118 (69.1%) had visual disturbance, 66 (38.6%) headache, 46 (26.9%) cranial nerve palsy and 35 (25.7%) hypopituitarism. Median tumor diameter was 29 [22-35.5] mm and cavernous sinus infiltration was detected in 99 (59.3%) of which 77 (77.8%) had Knosp grades 3 or 4. As initial treatment, 134 (78.4%) underwent surgery, 25 (14.6%) received radiotherapy and 12 (7%) were clinically and radiologically monitored. Among operated patients, gross total resection (GTR) was achieved in 45 (33.6%), whereas in 89 (66.4%) the tumor was incompletely removed. Overall median follow-up was 5.7 [2.9–9.2] years. After treatments, hypopituitarism increased significantly in the whole series (n = 86, 53.1%) respect to diagnosis (n = 35, 25.7%), p < 0.001. Development of hypopituitarism was not associated with surgery extension (subtotal or GTR), histological subtype, type of radiotherapy or radiation dose received. Conclusions S/PS meningiomas affect the pituitary function in 25% of the cases. However, after the implementation of treatments, hypopituitarism prevails in more than 50% of the cases. They are relatively large tumors and often locally invasive, and GTR is achieved in only one third of the cases. sellar meningioma perisellar meningioma tuberculum sellae meningioma cavernous sinus meningioma hypopituitarism Figures Figure 1 Figure 2 Introduction Meningiomas comprise a group of neoplasms derived from the meningothelial cells of the arachnoid [ 1 ]. They are the most frequent primary brain tumors and represent one-third of all intracranial tumors in adults [ 2 ]. Most meningiomas are low-grade and slow-growing neoplasms. However, their location in the central nervous system (CNS) can cause serious morbidity and mortality [ 3 ]. The estimated incidence of meningiomas is around 9.5 cases per 100,000 population and is more common in women around 60 years of age [ 4 ]. Although most meningiomas are of unknown etiology and sporadic, some predisposing factors such as ionizing radiation, obesity, breast cancer or head trauma have been proposed [ 3 ]. Furthermore, there may be a genetic predisposition to meningioma in patients with schwannomatosis related to neurofibromatosis type 2 (NF2), other forms of schwannomatosis and multiple endocrine neoplasia (MEN) [ 3 ]. Unlike other intracranial locations, meningiomas affecting the sellar and/or perisellar (S/PS) region are uncommon. A study conducted at a tertiary center reviewed 2,598 patients with S/PS masses and found 32 meningiomas (1.2%). Nevertheless, these lesions were the most frequent after pituitary adenomas, Rathke's cleft cysts and craniopharyngiomas [ 5 ]. S/PS meningiomas are usually detected by mass effect symptoms, pituitary hormone deficiencies, or are discovered incidentally [ 6 ]. Overall, the main strategies for management of patients with meningiomas consist of clinical surveillance, surgery and/or radiotherapy (RT) [ 6 ]. In this regard, various studies have showed the surgical outcomes in these patients, most of which are focused on surgical aspects such as the type of approach or visual outcomes [ 7 – 12 ]. Similarly, several studies report the results of RT, also focusing on the type of RT, dosage, and effects on the optic pathway [ 13 – 18 ]. However, studies detailing the clinical characteristics and the effects of S/PS meningiomas and their treatments on pituitary function are scarce [ 19 ]. Therefore, the aim of the present study was to determinate the clinical characteristics, therapeutic outcomes, and the effects that S/PS meningiomas and their treatments have on pituitary function across a cohort of adult Spanish patients. Materials And Methods Study design and patients This was a retrospective study including patients with presumptive or confirmed diagnosis of S/PS meningioma. The patients come from specialized outpatient clinics belonging to 20 referral Spanish hospitals. Inclusion criteria were (1) age older than 18 years at the time of diagnosis; (2) sellar, suprasellar, parasellar, and/or infrasellar lesion diagnosed by magnetic resonance imaging (MRI) with typical neuroimaging characteristics of meningioma and/or histological confirmation of meningioma in patients who underwent surgery or biopsy; and (3) follow-up period ≥ 6 months. Surgical specimens were evaluated by neuropathologists and cases that fulfilled the World Health Organization (WHO) classification of CNS tumor criteria for histological diagnosis of meningioma were included [ 1 ]. In cases where meningioma was not histologically confirmed, presumptive diagnosis was considered in S/PS well-demarcated lesions with lobar architecture, contrast-enhancing and dural tail sign at the tumor perimeter [ 3 ]. In all these cases, radiological diagnosis was made by an expert neuroradiologist. Study variables Demographics and clinical data, biochemical parameters and imaging studies were obtained from medical records. Corticotropin (ACTH) deficiency was established when normal/low plasma ACTH was associated with low morning serum cortisol (< 5 µg/dl) or insufficient response (< 18 µg/dl) to 250 µg cosyntropin stimulation test or insulin tolerance test (0.1 IU/kg intravenously). Thyrotropin (TSH) deficiency was diagnosed by the presence of low serum free thyroxin (fT4) and normal/low serum TSH. Gonadotropin deficiency was established with low/normal serum gonadotropins levels and serum testosterone levels below the lower limit of the reference range (men) or low serum estradiol levels (women). Growth hormone (GH) deficiency (GHD) was diagnosed when serum GH level was < 3 µg/l after insulin tolerance test or glucagon stimulation test or when serum insulin-like growth factor-1 (IGF-1) was below normal range in patients with ≥ 3 pituitary hormone deficiencies. Arginine vasopressin deficiency (AVD) was established based on hypotonic polyuria (urine output > 3.5 liters per day associated with urinary osmolality < 100 mOsm/kg) with elevated plasma osmolality and polydipsia. Hormonal measurements were performed using standard immunoradiometric assay or enzyme immunometric assay methods. Ethical aspects This investigation was accepted by the board of directors of the Spanish Society of Endocrinology and Nutrition (SEEN) and was disseminated to all members of the Neuroendocrinology Task Force of the SEEN. Informed consent of the participants was not required, as this was a retrospective analysis of data from routine clinical practice. The research was conducted according to Declaration of Helsinki, good clinical practices mandates and the study was approved by the Research Ethics Committee of Bellvitge University Hospital (reference: PR061/24). Statistical Analysis Categorical variables were described by number of cases and percentages in parenthesis. Continuous variables with normal distribution were described by mean ± standard deviation. Variables that did not follow a normal distribution were described by median [interquartile range]. Normality was checked using the Kolmogorov-Smirnov test. The student t-test was used for mean comparisons between two independent groups of subjects for normally distributed data, and the Mann-Whitney test for nonparametric data. Categorical variables were compared using Chi-square test and quantitative variables using ANOVA test for normally distributed variables and Kruskal–Wallis test was applied for non-normally distributed variables. Comparison of data of three independent groups was performed using Chi-square test from contingency table for categorial variables and repeated measures ANOVA for continuous variables. The presence of statistical significance was considered for values of p < 0.05. Results Clinical characteristics A total of 171 patients, 129 (75.4%) females, with median age of 61.5 [51–71] years, ranging from 25 to 92 years at diagnosis of S/PS meningiomas were collected. Initially, 44 (25.7%) patients had obesity, 6 (3.6%) previous breast cancer, 3 (1.8%) brain radiation exposure and 3 (1.8%) severe head trauma. No patient had NF2, schwannomatoses or MEN. At presentation, 66 (38.6%) patients had headache, 118 (69.1%) visual disturbance of which 64 (37.4%) had bitemporal hemianopia and 32 (18.7%) quadrantanopia. Other visual symptoms were decreased visual acuity (n = 14, 8.2%), diplopia (n = 9, 5.3%) and proptosis (n = 4, 2.3%). Also, 46 (26.9%) had cranial nerve palsy being the third (n = 20, 11.7%) and sixth (n = 8, 4.7%) the most affected. In 29 (16.9%) patients diagnosis was incidental and radiological explorations were most frequently performed by neurological symptoms (n = 9, 5.3%), epilepsy (n = 6, 3.5%) and head trauma (n = 4, 2.3%). Radiological findings MRI was available in all cases and meningioma radiological topography is shown in Fig. 1 . Overall median maximum diameter was 29 [22-35.5] mm. There was T-weighted signal data from 150 (87.7%) patients. On T1-weighted, meningioma was isointense in 113 (75.3%) cases, hyperintense in 22 (14.6%) and hypointense in 15 (10%). On T2-weighted, the tumor was hyperintense in 71 cases (47.3%), isointense in 62 (41.3%), and hypointense in 17 (11.3%). Information about optic chiasm compression and cavernous sinus involvement was available in 167 (97.7%) patients. Chiasmatic compression was present in 113 (67.7%) cases while cavernous sinus infiltration was detected in 99 (59.3%) of which 77 (77.8%) had Knosp grades 3 or 4. No patient had distant metastasis. Pituitary function at presentation Hormonal evaluation at diagnosis was available in 136 (79.5%) cases and a normal pituitary function was observed in 101 (74.3%). Among the remaining 35 (25.7%) patients, 20 (57.1%) had ACTH deficiency, 23 (65.7%) TSH deficiency, 23 (65.7%) gonadotropin deficiency, 13 (37.1%) GHD and 2 (5.7%) AVD. In patients with hypopituitarism, tumor mean maximum diameter was higher (34.7 ± 14.1 mm) compared to those with normal pituitary function (28.2 ± 9.7), p = 0.018. Further, in 36 (26.5%) cases, hyperprolactinemia was documented, and it was more frequent in cases with larger tumors (35.7 ± 13.3) mm compared to those with smaller meningiomas (27.9 ± 9.9) mm, p < 0.001. Similarly, hyperprolactinemia was most common in patients with hypopituitarism (n = 22, 62.9%) compared to those with normal pituitary function (n = 13, 12.9%), p < 0.001. No association between hypopituitarism or hyperprolactinemia with age, gender, radiological tumor localization and cavernous sinus infiltration at diagnosis was found. Treatments outcomes As initial treatment, 134 (78.4%) patients underwent surgery, 25 (14.6%) received RT and 12 (7%) were clinically and radiologically monitored. Among those surgically treated, 76 (56.7%) had an endoscopic endonasal transsphenoidal approach and 58 (43.3%) were operated via craniotomy. Postsurgical complications occurred in 44 (32.8%) patients and included 10 (7.5%) new onset of cranial nerve palsy, 8 (5.9%) visual disturbance, 6 (4.5%) intra-operative bleeding, 6 (4.5%) cerebrospinal fluid fistula and 5 (3.4%) meningitis. The pathology report was available for all operated patients. Histological meningioma subtypes are shown in Fig. 2 . Information related to the WHO grade classification of meningioma was available in 124 (92.5%) reports. In 117 patients (94.4%) meningioma was grade 1, in 6 (4.8%) was grade 2 and one (0.8%) patient had grade 3. Ki67 index was evaluated in 80 (59.7%) patients and most frequently values were 1% (29.1%), 2% (24.1%) and 3 (17.7%). Immunohistochemical study was available in 54 (40.3%) cases, of which endothelial membrane antigen was positive in 51 (94.4%). Also, vimentin was positive 12/12 and somatostatin receptors in 3/6 tumor samples. According to their origin, 52 (30.4%) were tuberculum sellae meningioma (TSM), 27 (15.8%) cavernous sinus meningioma (CSM), 26 (15.2%) planum sphenoidale meningioma (PSM), 6 (3.5%) olfactory meningioma, 4 (2.3%) diaphragm sellae meningioma, while in 56 (32.8%) cases, the origin of the tumor could not be determined. As a result of the initial treatment, among the 134 patients who underwent surgery, in 45 (33.6%) a gross total resection (GTR) was achieved whereas in 89 (66.4%) the tumor was incompletely removed. Among those with residual tumor, in 51 (57.3%) patients, clinical and radiological monitoring was chosen, 27 (30.3%) received only RT, 12 (13.5%) were reoperated of which 9 (10.1%) were also treated with RT. Among those with initial GTR, in 5 out of the 45 cases (11.1%), the tumor recurred with a median time of 4.3 [1.9–9.5] years. In 4/5 cases meningioma was WHO grade 1 and 1/5 was WHO grade 2. Two cases were treated with RT, in 2 other cases, clinical and radiological surveillance was decided, and one patient underwent surgery, being obtained a partial tumor resection. Among patients originally managed with only RT, in 1/25 (4%) cases the remnant grew. Therefore, a transsphenoidal surgery was performed achieving partial resection. Lastly, among 12 patients initially managed with clinical and radiological surveillance, in 2 (16.7%) of them, the tumor grew. Consequently, surgery was done, achieving a GTR in one case and a reduction of tumor volume in the other. Taking together nonsurgical group, in 34/37 meningioma remained stable. In all cases initially managed non-surgically and later operated on, the histological study confirmed the diagnosis of meningioma. Globally, 61 (35.7%) were treated with RT, 49 (80.3%) with fractionated stereotactic RT and 12 (19.7%) with radiosurgery, receiving a median dose of 50 [26.5–50.4] Gy. In 52 (85.2%) patients, meningioma remained stable after RT while in 9 (14.8%) cases, tumor slightly increased in size. No significant complication associated with RT were reported. When, according to their origin, most prevalent meningiomas types (TSM, CSM and PSM) were analyzed separately; decision for surgery, transsphenoidal approach and GTR was achieved lower in patients with CSM (Table 1 ). Therefore, more cases were treated with RT in this group. In addition, proportion of WHO grade 2 meningiomas was higher in PSM, in relation to the other two groups (Table 1 ). Table 1 Clinical, pathologic characteristics and management of the most prevalent types of meningiomas according to their origin. Tuberculum sellae meningioma (n = 52) Cavernous sinus meningioma (n = 27) Planum sphenoidale meningioma (n = 26) p -value Age, year [IQR] 60.5 [49–68] 59 [51–70] 67 [52–73] 0.324 Gender, F/M 45/7 22/4 20/7 0.386 Incidental, n (%) 7 (13.5) 3 (11.1) 3 (11.5) 0.945 Visual disturbance, n (%) 39 (75) 17 (63) 21 (80.8) 0.318 Max tumor size, mm [IQR] 26 [ 21 – 30 ] 33 [ 26 – 42 ] 32 [ 23 – 42 ] 0.080 Surgery, n (%) 48 (92.3) 15 (55.6) 25 (96.2) < 0.001 Overall GTR, n (%) 31 (64.6%) 0 10 (40) < 0.001 Transsphenoidal approach 34 (70.8) 5 (33.3) 11 (44) 0.012 GTR 23 (67.6) 0 5 (20) 0.013 Transcranial approach 14 (29.2) 10 (66.7) 14 (56) 0.012 GTR 6 (42.9) 0 5 (20) 0.058 WHO classification grade I/II, n * 47/0 13/0 17/4 0.002 Radiotherapy, n (%) 8 (15.4) 22 (81.5) 11 (42.3) < 0.001 Visual improvement, n (%) 16 (41) 8 (47.1) 5 (23.8) 0.280 Visual damage, n (%) ** 2 (15.4) 1 (10) 0 0.637 Chi 2 test from contingency table and Repeated measures ANOVA were performed. F, female; GTR, gross total resection; IQR, interquartile range; M, male; Max, maximum; WHO, World Health Organization; *, cases with information available; ** new onset of visual symptoms after treatments. Overall median follow-up was 5.7 [2.9–9.2] years. At last visit, 83 (48.5%) patients had visual disturbance, being bitemporal hemianopia (n = 39, 22.8%) and quadrantanopia (n = 24, 14%) the most frequent symptoms. In 36 (78.3%) of 46 patients with initial cranial nerve disorder, the paralysis or paresis persisted at last evaluation, and third cranial nerve was the most affected (n = 15, 41.7%). Pituitary functions after treatments In 162 (94.7%) patients, hormonal evaluation was available at last visit. Among the 28 patients with hypopituitarism at diagnosis of meningioma, 16 (45.7%) cases recovered hormone deficiencies after surgery. Globally, prevalence of hypopituitarism was higher at last evaluation compared to diagnosis (Table 2 ). Pituitary deficiencies according to the treatment received (surgery alone, RT alone or surgery plus RT) are shown in Tables 3 , 4 and 5 , respectively. According to their origin, hypopituitarism at last evaluation was more prevalent in patients with PSM (n = 15, 68.2%) compared to those with TSM (n = 17, 33.3%), p = 0.003. Development of hypopituitarism after treatments was not associated with surgery outcome (incomplete or GTR), histological subtypes, type of RT or radiation dose received. Table 2 Pituitary hormone deficiencies at diagnosis and last evaluation in all patients. At diagnosis (n = 136*) At last evaluation (n = 162*) p -value Any deficiency, n (%) 35 (25.7) 86 (53.1) < 0.001 Corticotropin, n (%) 20 (14.7) 62 (38.3) < 0.001 Thyrotropin, n (%) 23 (16.9) 65 (40.1) < 0.001 Gonadotropin, n (%) 23 (16.9) 58 (35.8) < 0.001 Somatotropin, n (%) 13 (9.6) 46 (28.4) < 0.001 Arginine vasopressin, n (%) 2 (1.5) 25 (15.4) 0.01 Chi 2 test was performed; *, patients with hormonal study available. Table 3 Pituitary hormone deficiencies in patients only treated with surgery before and after treatment. Before (n = 82*) After (n = 96*) p -value Any deficiency, n (%) 18 (22) 56 (58.3) 0.001 Corticotropin, n (%) 10 (12.2) 44 (45.8) 0.015 Thyrotropin, n (%) 12 (15) 44 (45.8) < 0.01 Gonadotropin, n (%) 11 (13.4) 35 (36.4) < 0.01 Somatotropin, n (%) 7 (8.5%) 34 (35.4) < 0.01 Arginine vasopressin, n (%) 1 (1.2) 19 (19.8) < 0.01 Chi 2 test was performed; *, patients with hormonal study available. Table 4 Pituitary hormone deficiencies in patients only treated with radiotherapy before and after treatment. Before (n = 17*) After (n = 18*) p -value Any deficiency, n (%) 6 (35.3) 9 (50) 0.010 Corticotropin, n (%) 3 (17.5) 4 (22.2) 0.423 Thyrotropin, n (%) 4 (24) 7 (38.9) 0.038 Gonadotropin, n (%) 3 (17.6) 5 (27.8) 0.171 Somatotropin, n (%) 1 (5.9) 3 (16.7) 0.038 Arginine vasopressin, n (%) 1 (5.9) 1 (5.6) 0.998 Chi 2 test was performed; *, patients with hormonal study available. Table 5 Pituitary hormone deficiencies in patients treated with surgery plus radiotherapy before and after treatments. Before (n = 29*) After (n = 34*) p -value Any deficiency, n (%) 9 (31) 19 (55.9) 0.008 Corticotropin, n (%) 6 (20.7) 12 (35.3) 0.003 Thyrotropin, n (%) 7 (24.1) 13 (38.2) 0.002 Gonadotropin, n (%) 7 (24.1) 16 (47.1) 0.017 Somatotropin, n (%) 5 (17.2) 8 (24) 0.289 Arginine vasopressin, n (%) 0 4 (11.8) 0.117 Chi 2 and Fisher's exact test were performed; *, patients with hormonal study available. Mortality Thirteen (7.6%) patients died during the follow-up of which 7 (4.1%) were related to meningioma. In patients who died because of meningioma, median age at diagnosis was 70 [45–85] years and median tumor size was 50 [38–62] mm. Six patients underwent surgery (an 89-year-old patient refused to receive treatment), 5/6 had multiple surgical interventions and 4/6 received RT. Regarding histological subtype, 2/6 cases had WHO grade 2 and 4/6 WHO grade 1. According to the origin, 4/7 were CSM, 2/7 were PSM, and this information was unavailable in one patient. Discussion This study provides a comprehensive description of the most relevant clinical, radiological, histological aspects and therapeutic results in a wide series of meningiomas affecting the S/PS region. Moreover, our work provides detailed information on the effects that S/PS meningiomas and their treatments have on pituitary function. In this regard, we found that S/PS meningiomas affect pituitary function in a quarter of the patients. However, because of the treatments applied, hypopituitarism ends up affecting more than 50% of the cases. Overall, cranial meningiomas appear frequently at sixth decade of life with a female/male incidence rate of 3:1 [ 4 ]. In our series, S/PS meningiomas showed similar age at diagnosis and identical gender distribution. Also, majority of meningiomas are idiopathic and sporadic [ 3 ]. Nevertheless, exposure to ionizing radiation is considered the most important risk factor for meningiomas [ 20 , 21 ]. In a cohort of 4,221 childhood cancer survivors exposed to cranial RT, 169 (4%) developed meningiomas after 25 years of surveillance [ 22 ]. In our study, few patients had previous cranial RT (1.8%), but follow-up time was shorter. Moreover, a possible relationship between meningioma and obesity has been established [ 23 – 28 ]. In our patients, a quarter of the cases had obesity, but this prevalence is comparable to similar Spanish population [ 29 ]. Other predisposing factors (breast cancer, head trauma) and genetic diseases (NF2, MEN, schwannomatosis) have been postulated for meningioma development [ 3 ]. In our cohort, few cases had breast cancer or severe head trauma, and no patients had hereditary diseases. The WHO classification of meningiomas recognize 3 grades and 15 morphologic subtypes [ 1 ]. Population studies estimate that 80–85% of meningiomas are grade 1, 15–18% grade 2, and 1–3% grade 3 [ 4 ]. WHO grading system correlates with treatments outcome and patients with grade 2 or 3 meningiomas are more likely to have invasive disease or recurrence after surgery [ 3 ]. Overall reported recurrence ranges from 7–25% (grade 1), 30–50% (grade 2) to 50–94% (grade 3) [ 30 – 32 ]. Although grade 3 meningiomas are considered malignant, distant metastasis are very rare [ 33 ]. In our cohort of S/PS meningiomas, proportion of WHO grade 1 was higher (95%), and only 8 morphological subtypes were represented. Furthermore, recurrence after the GTR in our series was around 10%, and it is important to note that 80% of the recurring meningiomas were WHO grade 1. Clinical presentation of meningiomas depends on the size and location. Many meningiomas are asymptomatic and are detected incidentally [ 34 – 36 ]. In some cases, visual defects, seizures or mental changes are the presentation symptoms [ 3 ]. In our cohort and given the peculiar characteristics of the S/PS region, the diagnosis was made incidentally in only 16% of the cases and, as expected, visual symptoms were the most common (70%). It is important to highlight that in 75% of the cases, pituitary function was preserved at diagnosis, despite an average tumor size of almost 3 cm. On MRI study, meningiomas have a characteristic appearance which allows the diagnosis to be presumed with reasonable accuracy. They typically are well-defined extra-axial masses and most of them show the distinctive marginal dural thickening that taper peripherally (the tail sign). Additionally, meningiomas are mainly isointense or hypointense on T1 and isointense or hyperintense on T2-weighted [ 3 ]. In our series, in all cases with initial presumptive diagnosis who underwent surgery, the pathological diagnosis of meningioma was confirmed. Also, and similarly to meningiomas in other locations, S/PS meningiomas in our cohort were mostly isointense or hypointense (85%) on T1-weighted and isointense or hyperintense (88%) on T2-weighted. Management of patients with meningiomas requires a balance between therapeutic intervention and avoidance of neurological damage from the treatment. Therefore, a proper individual assessment is essential in determining the optimal therapeutic strategy [ 3 ]. Excluding rare cases with metastatic disease, management of patients with meningiomas consist of clinical surveillance, surgery plus RT or RT alone [ 3 ]. Due to the specific characteristics of the sellar region, most S/PS meningiomas are symptomatic at diagnosis (85% in our series). Consequently, early active treatments are elected in many cases (93% in our cohort). Although surgery is the treatment of choice for symptomatic patients, obtain a GTR could be difficult in most cases [ 3 ]. TSM is one of the most common S/PS meningioma (the most prevalent in our series) and there has been controversy regarding the best surgical approach for these patients [ 7 ]. A study including 51 patients with TSM (85% operated via craniotomy) showed similar GTR in patients who underwent transsphenoidal approach (83.3%) compared to those with transcranial surgery (86.4%) [ 11 ]. Another study in 33 patients with TSM managed surgically (62% via endonasal) showed GTR in 80% and 39% of patients after transsphenoidal and transcranial surgery, respectively. However, tumors were larger and more laterally extended in the transcranial group [ 37 ]. In our cohort, patients with TSM predominantly underwent transsphenoidal surgery (70%) and GTR was achieved in 67% (endonasal) and 43% (transcranial). The relatively small number of cases reported (including our cohort), the variability in tumor size, location, surgeon experiences, could explain the diversity of outcomes. CSM is another relatively frequent perisellar meningioma whose surgical resection poses a significant challenge [ 38 ]. Therefore, multimodality treatments and tumor debulking addressed to improve clinical symptoms, appear to be the best therapeutic options [ 38 – 41 ]. A series of 17 patients with CSM that underwent decompression surgery obtained visual normalization in 62% of the cases [ 39 ]. In our 16 patients with CSM, GTR was not achieved in any of the cases, but nearly 50% of the patients experienced normalization of visual symptoms after treatment. Fractionated RT or radiosurgery are effective to achieve both tumor control and low morbidity and are used for cases with residual tumors following surgery, or as initial treatment in patients with surgical risk [ 3 ]. A study in 763 patients with S/PS meningiomas treated with radiosurgery (50% had prior surgery) showed a remnant stabilization in 90% of the cases after 5.5 years of follow-up [ 13 ]. Another study in 143 S/PS meningiomas revealed a progression-free survival rate of 90% (95% confidence interval, 78–96) at 8 years [ 42 ]. In the same line, our study showed that 85% of S/PS meningiomas (with or without prior surgery) remained stable after 5.7 years of follow-up. Hypopituitarism is one of the most important complications of S/PS meningiomas and their treatments. However, studies that have evaluated pituitary function before and after meningioma treatments are limited. In a study with 57 patients with S/PS meningiomas, postsurgical hypopituitarism occurred in 15.6% and AVD in 10.5% [ 43 ]. In another study, 4/17 patients with sellar meningiomas showed preoperative hypopituitarism. During postsurgical follow-up, 10/17 patients developed anterior hypopituitarism and 2/17 permanent AVD [ 44 ]. A meta-analysis which included 8 studies (406 patients) reported the development of anterior hypopituitarism in 3.6% and AVD in 1.6% of cases [ 19 ]. However, it is important to highlight that hormone data were unavailable in 50% of analyzed series, and the methodological quality of the included studies was rated as “low” by the authors [ 19 ]. Our study offers valuable information in this regard since a complete hormone evaluation was available in 80% (at diagnosis) and 95% of patients (at last evaluation). In our cohort, S/PS meningiomas cause hypopituitarism in 25% of the cases. Despite the recovery of hormone deficiencies after surgery in half of them, more than 50% of patients exhibited hypopituitarism at last evaluation because of treatments received. The main strengths of our study lie in (1) the size of our series, which represents a large cohort of patients with a relatively uncommon tumor (2) the detailed information provided on the clinical, radiological, and histological aspects of a wide variety of meningiomas affecting the S/PS region (3) the comprehensive information provided regarding the effects of S/PS meningiomas and their treatments on pituitary function. The limitations of our study include (1) the retrospective design (2) the lack of histological confirmation of meningioma in nonsurgical group (20% of the cases) (3) the multicentric nature, which may introduce some variability regarding the radiological diagnosis, therapeutic decision, or surgical outcomes. In conclusion, S/PS meningiomas are mostly diagnosed in women in their 60s based on clinical symptoms. In a quarter of the patients, pituitary function is affected by the tumor. However, after treatments, hypopituitarism prevails in more than half of the cases. They usually are low-aggressive tumors, but relatively large and often locally invasive. As a result, GTR is achieved in only one third of the cases. As an alternative to surgery, or in those patients with residual tumor after surgical intervention, RT is effective in tumor control with an excellent safety profile. Declarations Acknowledgments : Georgina F. Caulfield for the language review of the paper. Grand and Funds : No author has received any grant for this research. Author contributions : Conceptualization, methodology (FG-P, PI, AZ, MIGB). Data curation, original draft preparation (FG-P). Writing review and supervision (PI). All the authors participated in the data collection, critical review of the manuscript and approved the submitted version. Conflict of interest : Authors declare that they have not conflict of interest (financial or non-financial). 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1","display":"","copyAsset":false,"role":"figure","size":139019,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of sellar/perisellar meningiomas according to their radiological topography.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5146945/v1/8b880564127db284486d752b.jpg"},{"id":68531766,"identity":"2cf73890-02ef-4fce-8655-9b4709690fc4","added_by":"auto","created_at":"2024-11-08 09:17:25","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":124564,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of sellar/perisellar meningiomas according to the histologic subtype.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5146945/v1/275652eeddbbb227057fef83.jpg"},{"id":72641218,"identity":"304ea603-2fe1-424d-b7e9-fbe26c76fe07","added_by":"auto","created_at":"2024-12-30 16:11:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1034989,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5146945/v1/a40da1d6-2110-4ee0-81b5-ae310d4597e7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sellar and perisellar meningiomas: effects on pituitary function in a Spanish observational study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMeningiomas comprise a group of neoplasms derived from the meningothelial cells of the arachnoid [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. They are the most frequent primary brain tumors and represent one-third of all intracranial tumors in adults [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most meningiomas are low-grade and slow-growing neoplasms. However, their location in the central nervous system (CNS) can cause serious morbidity and mortality [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe estimated incidence of meningiomas is around 9.5 cases per 100,000 population and is more common in women around 60 years of age [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although most meningiomas are of unknown etiology and sporadic, some predisposing factors such as ionizing radiation, obesity, breast cancer or head trauma have been proposed [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Furthermore, there may be a genetic predisposition to meningioma in patients with schwannomatosis related to neurofibromatosis type 2 (NF2), other forms of schwannomatosis and multiple endocrine neoplasia (MEN) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnlike other intracranial locations, meningiomas affecting the sellar and/or perisellar (S/PS) region are uncommon. A study conducted at a tertiary center reviewed 2,598 patients with S/PS masses and found 32 meningiomas (1.2%). Nevertheless, these lesions were the most frequent after pituitary adenomas, Rathke's cleft cysts and craniopharyngiomas [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eS/PS meningiomas are usually detected by mass effect symptoms, pituitary hormone deficiencies, or are discovered incidentally [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Overall, the main strategies for management of patients with meningiomas consist of clinical surveillance, surgery and/or radiotherapy (RT) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this regard, various studies have showed the surgical outcomes in these patients, most of which are focused on surgical aspects such as the type of approach or visual outcomes [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Similarly, several studies report the results of RT, also focusing on the type of RT, dosage, and effects on the optic pathway [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, studies detailing the clinical characteristics and the effects of S/PS meningiomas and their treatments on pituitary function are scarce [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Therefore, the aim of the present study was to determinate the clinical characteristics, therapeutic outcomes, and the effects that S/PS meningiomas and their treatments have on pituitary function across a cohort of adult Spanish patients.\u003c/p\u003e"},{"header":"Materials And Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients\u003c/h2\u003e \u003cp\u003eThis was a retrospective study including patients with presumptive or confirmed diagnosis of S/PS meningioma. The patients come from specialized outpatient clinics belonging to 20 referral Spanish hospitals. Inclusion criteria were (1) age older than 18 years at the time of diagnosis; (2) sellar, suprasellar, parasellar, and/or infrasellar lesion diagnosed by magnetic resonance imaging (MRI) with typical neuroimaging characteristics of meningioma and/or histological confirmation of meningioma in patients who underwent surgery or biopsy; and (3) follow-up period\u0026thinsp;\u0026ge;\u0026thinsp;6 months.\u003c/p\u003e \u003cp\u003eSurgical specimens were evaluated by neuropathologists and cases that fulfilled the World Health Organization (WHO) classification of CNS tumor criteria for histological diagnosis of meningioma were included [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In cases where meningioma was not histologically confirmed, presumptive diagnosis was considered in S/PS well-demarcated lesions with lobar architecture, contrast-enhancing and dural tail sign at the tumor perimeter [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In all these cases, radiological diagnosis was made by an expert neuroradiologist.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy variables\u003c/h3\u003e\n\u003cp\u003e Demographics and clinical data, biochemical parameters and imaging studies were obtained from medical records. Corticotropin (ACTH) deficiency was established when normal/low plasma ACTH was associated with low morning serum cortisol (\u0026lt;\u0026thinsp;5 \u0026micro;g/dl) or insufficient response (\u0026lt;\u0026thinsp;18 \u0026micro;g/dl) to 250 \u0026micro;g cosyntropin stimulation test or insulin tolerance test (0.1 IU/kg intravenously). Thyrotropin (TSH) deficiency was diagnosed by the presence of low serum free thyroxin (fT4) and normal/low serum TSH. Gonadotropin deficiency was established with low/normal serum gonadotropins levels and serum testosterone levels below the lower limit of the reference range (men) or low serum estradiol levels (women). Growth hormone (GH) deficiency (GHD) was diagnosed when serum GH level was \u0026lt;\u0026thinsp;3 \u0026micro;g/l after insulin tolerance test or glucagon stimulation test or when serum insulin-like growth factor-1 (IGF-1) was below normal range in patients with \u0026ge;\u0026thinsp;3 pituitary hormone deficiencies. Arginine vasopressin deficiency (AVD) was established based on hypotonic polyuria (urine output\u0026thinsp;\u0026gt;\u0026thinsp;3.5 liters per day associated with urinary osmolality\u0026thinsp;\u0026lt;\u0026thinsp;100 mOsm/kg) with elevated plasma osmolality and polydipsia. Hormonal measurements were performed using standard immunoradiometric assay or enzyme immunometric assay methods.\u003c/p\u003e\n\u003ch3\u003eEthical aspects\u003c/h3\u003e\n\u003cp\u003e This investigation was accepted by the board of directors of the Spanish Society of Endocrinology and Nutrition (SEEN) and was disseminated to all members of the Neuroendocrinology Task Force of the SEEN. Informed consent of the participants was not required, as this was a retrospective analysis of data from routine clinical practice. The research was conducted according to Declaration of Helsinki, good clinical practices mandates and the study was approved by the Research Ethics Committee of Bellvitge University Hospital (reference: PR061/24).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were described by number of cases and percentages in parenthesis. Continuous variables with normal distribution were described by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Variables that did not follow a normal distribution were described by median [interquartile range]. Normality was checked using the Kolmogorov-Smirnov test. The student t-test was used for mean comparisons between two independent groups of subjects for normally distributed data, and the Mann-Whitney test for nonparametric data. Categorical variables were compared using Chi-square test and quantitative variables using ANOVA test for normally distributed variables and Kruskal\u0026ndash;Wallis test was applied for non-normally distributed variables. Comparison of data of three independent groups was performed using Chi-square test from contingency table for categorial variables and repeated measures ANOVA for continuous variables. The presence of statistical significance was considered for values of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eA total of 171 patients, 129 (75.4%) females, with median age of 61.5 [51\u0026ndash;71] years, ranging from 25 to 92 years at diagnosis of S/PS meningiomas were collected. Initially, 44 (25.7%) patients had obesity, 6 (3.6%) previous breast cancer, 3 (1.8%) brain radiation exposure and 3 (1.8%) severe head trauma. No patient had NF2, schwannomatoses or MEN.\u003c/p\u003e \u003cp\u003eAt presentation, 66 (38.6%) patients had headache, 118 (69.1%) visual disturbance of which 64 (37.4%) had bitemporal hemianopia and 32 (18.7%) quadrantanopia. Other visual symptoms were decreased visual acuity (n\u0026thinsp;=\u0026thinsp;14, 8.2%), diplopia (n\u0026thinsp;=\u0026thinsp;9, 5.3%) and proptosis (n\u0026thinsp;=\u0026thinsp;4, 2.3%). Also, 46 (26.9%) had cranial nerve palsy being the third (n\u0026thinsp;=\u0026thinsp;20, 11.7%) and sixth (n\u0026thinsp;=\u0026thinsp;8, 4.7%) the most affected. In 29 (16.9%) patients diagnosis was incidental and radiological explorations were most frequently performed by neurological symptoms (n\u0026thinsp;=\u0026thinsp;9, 5.3%), epilepsy (n\u0026thinsp;=\u0026thinsp;6, 3.5%) and head trauma (n\u0026thinsp;=\u0026thinsp;4, 2.3%).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRadiological findings\u003c/h3\u003e\n\u003cp\u003eMRI was available in all cases and meningioma radiological topography is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Overall median maximum diameter was 29 [22-35.5] mm. There was T-weighted signal data from 150 (87.7%) patients. On T1-weighted, meningioma was isointense in 113 (75.3%) cases, hyperintense in 22 (14.6%) and hypointense in 15 (10%). On T2-weighted, the tumor was hyperintense in 71 cases (47.3%), isointense in 62 (41.3%), and hypointense in 17 (11.3%). Information about optic chiasm compression and cavernous sinus involvement was available in 167 (97.7%) patients. Chiasmatic compression was present in 113 (67.7%) cases while cavernous sinus infiltration was detected in 99 (59.3%) of which 77 (77.8%) had Knosp grades 3 or 4. No patient had distant metastasis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePituitary function at presentation\u003c/h3\u003e\n\u003cp\u003eHormonal evaluation at diagnosis was available in 136 (79.5%) cases and a normal pituitary function was observed in 101 (74.3%). Among the remaining 35 (25.7%) patients, 20 (57.1%) had ACTH deficiency, 23 (65.7%) TSH deficiency, 23 (65.7%) gonadotropin deficiency, 13 (37.1%) GHD and 2 (5.7%) AVD. In patients with hypopituitarism, tumor mean maximum diameter was higher (34.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1 mm) compared to those with normal pituitary function (28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018. Further, in 36 (26.5%) cases, hyperprolactinemia was documented, and it was more frequent in cases with larger tumors (35.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3) mm compared to those with smaller meningiomas (27.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9) mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Similarly, hyperprolactinemia was most common in patients with hypopituitarism (n\u0026thinsp;=\u0026thinsp;22, 62.9%) compared to those with normal pituitary function (n\u0026thinsp;=\u0026thinsp;13, 12.9%), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001. No association between hypopituitarism or hyperprolactinemia with age, gender, radiological tumor localization and cavernous sinus infiltration at diagnosis was found.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTreatments outcomes\u003c/h2\u003e \u003cp\u003eAs initial treatment, 134 (78.4%) patients underwent surgery, 25 (14.6%) received RT and 12 (7%) were clinically and radiologically monitored. Among those surgically treated, 76 (56.7%) had an endoscopic endonasal transsphenoidal approach and 58 (43.3%) were operated via craniotomy. Postsurgical complications occurred in 44 (32.8%) patients and included 10 (7.5%) new onset of cranial nerve palsy, 8 (5.9%) visual disturbance, 6 (4.5%) intra-operative bleeding, 6 (4.5%) cerebrospinal fluid fistula and 5 (3.4%) meningitis.\u003c/p\u003e \u003cp\u003eThe pathology report was available for all operated patients. Histological meningioma subtypes are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Information related to the WHO grade classification of meningioma was available in 124 (92.5%) reports. In 117 patients (94.4%) meningioma was grade 1, in 6 (4.8%) was grade 2 and one (0.8%) patient had grade 3. Ki67 index was evaluated in 80 (59.7%) patients and most frequently values were 1% (29.1%), 2% (24.1%) and 3 (17.7%). Immunohistochemical study was available in 54 (40.3%) cases, of which endothelial membrane antigen was positive in 51 (94.4%). Also, vimentin was positive 12/12 and somatostatin receptors in 3/6 tumor samples.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to their origin, 52 (30.4%) were tuberculum sellae meningioma (TSM), 27 (15.8%) cavernous sinus meningioma (CSM), 26 (15.2%) planum sphenoidale meningioma (PSM), 6 (3.5%) olfactory meningioma, 4 (2.3%) diaphragm sellae meningioma, while in 56 (32.8%) cases, the origin of the tumor could not be determined.\u003c/p\u003e \u003cp\u003eAs a result of the initial treatment, among the 134 patients who underwent surgery, in 45 (33.6%) a gross total resection (GTR) was achieved whereas in 89 (66.4%) the tumor was incompletely removed. Among those with residual tumor, in 51 (57.3%) patients, clinical and radiological monitoring was chosen, 27 (30.3%) received only RT, 12 (13.5%) were reoperated of which 9 (10.1%) were also treated with RT. Among those with initial GTR, in 5 out of the 45 cases (11.1%), the tumor recurred with a median time of 4.3 [1.9\u0026ndash;9.5] years. In 4/5 cases meningioma was WHO grade 1 and 1/5 was WHO grade 2. Two cases were treated with RT, in 2 other cases, clinical and radiological surveillance was decided, and one patient underwent surgery, being obtained a partial tumor resection.\u003c/p\u003e \u003cp\u003eAmong patients originally managed with only RT, in 1/25 (4%) cases the remnant grew. Therefore, a transsphenoidal surgery was performed achieving partial resection. Lastly, among 12 patients initially managed with clinical and radiological surveillance, in 2 (16.7%) of them, the tumor grew. Consequently, surgery was done, achieving a GTR in one case and a reduction of tumor volume in the other. Taking together nonsurgical group, in 34/37 meningioma remained stable. In all cases initially managed non-surgically and later operated on, the histological study confirmed the diagnosis of meningioma.\u003c/p\u003e \u003cp\u003eGlobally, 61 (35.7%) were treated with RT, 49 (80.3%) with fractionated stereotactic RT and 12 (19.7%) with radiosurgery, receiving a median dose of 50 [26.5\u0026ndash;50.4] Gy. In 52 (85.2%) patients, meningioma remained stable after RT while in 9 (14.8%) cases, tumor slightly increased in size. No significant complication associated with RT were reported.\u003c/p\u003e \u003cp\u003eWhen, according to their origin, most prevalent meningiomas types (TSM, CSM and PSM) were analyzed separately; decision for surgery, transsphenoidal approach and GTR was achieved lower in patients with CSM (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Therefore, more cases were treated with RT in this group. In addition, proportion of WHO grade 2 meningiomas was higher in PSM, in relation to the other two groups (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003eClinical, pathologic characteristics and management of the most prevalent types of meningiomas according to their origin.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTuberculum sellae meningioma\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCavernous sinus meningioma\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlanum sphenoidale meningioma\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.5 [49\u0026ndash;68]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 [51\u0026ndash;70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 [52\u0026ndash;73]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.324\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, F/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncidental, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.945\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual disturbance, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.318\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMax tumor size, mm [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 [\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 [\u003cspan additionalcitationids=\"CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 [\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (92.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (96.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall GTR, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (64.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTranssphenoidal approach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTranscranial approach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO classification grade I/II, n *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (81.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual improvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual damage, n (%) **\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eChi\u003csup\u003e2\u003c/sup\u003e test from contingency table and Repeated measures ANOVA were performed.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eF, female; GTR, gross total resection; IQR, interquartile range; M, male; Max, maximum; WHO, World Health Organization; *, cases with information available; ** new onset of visual symptoms after treatments.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOverall median follow-up was 5.7 [2.9\u0026ndash;9.2] years. At last visit, 83 (48.5%) patients had visual disturbance, being bitemporal hemianopia (n\u0026thinsp;=\u0026thinsp;39, 22.8%) and quadrantanopia (n\u0026thinsp;=\u0026thinsp;24, 14%) the most frequent symptoms. In 36 (78.3%) of 46 patients with initial cranial nerve disorder, the paralysis or paresis persisted at last evaluation, and third cranial nerve was the most affected (n\u0026thinsp;=\u0026thinsp;15, 41.7%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePituitary functions after treatments\u003c/h2\u003e \u003cp\u003eIn 162 (94.7%) patients, hormonal evaluation was available at last visit. Among the 28 patients with hypopituitarism at diagnosis of meningioma, 16 (45.7%) cases recovered hormone deficiencies after surgery. Globally, prevalence of hypopituitarism was higher at last evaluation compared to diagnosis (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Pituitary deficiencies according to the treatment received (surgery alone, RT alone or surgery plus RT) are shown in Tables \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, respectively. According to their origin, hypopituitarism at last evaluation was more prevalent in patients with PSM (n\u0026thinsp;=\u0026thinsp;15, 68.2%) compared to those with TSM (n\u0026thinsp;=\u0026thinsp;17, 33.3%), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003. Development of hypopituitarism after treatments was not associated with surgery outcome (incomplete or GTR), histological subtypes, type of RT or radiation dose received.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePituitary hormone deficiencies at diagnosis and last evaluation in all patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt diagnosis\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;136*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAt last evaluation\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;162*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny deficiency, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86 (53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyrotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65 (40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58 (35.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSomatotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (28.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArginine vasopressin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eChi\u003csup\u003e2\u003c/sup\u003e test was performed; *, patients with hormonal study available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePituitary hormone deficiencies in patients only treated with surgery before and after treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;96*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny deficiency, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44 (45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyrotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44 (45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSomatotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArginine vasopressin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eChi\u003csup\u003e2\u003c/sup\u003e test was performed; *, patients with hormonal study available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePituitary hormone deficiencies in patients only treated with radiotherapy before and after treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny deficiency, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.423\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyrotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSomatotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArginine vasopressin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eChi\u003csup\u003e2\u003c/sup\u003e test was performed; *, patients with hormonal study available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePituitary hormone deficiencies in patients treated with surgery plus radiotherapy before and after treatments.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;34*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny deficiency, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (55.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyrotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (38.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSomatotropin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArginine vasopressin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eChi\u003csup\u003e2\u003c/sup\u003e and Fisher's exact test were performed; *, patients with hormonal study available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMortality\u003c/h2\u003e \u003cp\u003eThirteen (7.6%) patients died during the follow-up of which 7 (4.1%) were related to meningioma. In patients who died because of meningioma, median age at diagnosis was 70 [45\u0026ndash;85] years and median tumor size was 50 [38\u0026ndash;62] mm. Six patients underwent surgery (an 89-year-old patient refused to receive treatment), 5/6 had multiple surgical interventions and 4/6 received RT. Regarding histological subtype, 2/6 cases had WHO grade 2 and 4/6 WHO grade 1. According to the origin, 4/7 were CSM, 2/7 were PSM, and this information was unavailable in one patient.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides a comprehensive description of the most relevant clinical, radiological, histological aspects and therapeutic results in a wide series of meningiomas affecting the S/PS region. Moreover, our work provides detailed information on the effects that S/PS meningiomas and their treatments have on pituitary function. In this regard, we found that S/PS meningiomas affect pituitary function in a quarter of the patients. However, because of the treatments applied, hypopituitarism ends up affecting more than 50% of the cases.\u003c/p\u003e \u003cp\u003eOverall, cranial meningiomas appear frequently at sixth decade of life with a female/male incidence rate of 3:1 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In our series, S/PS meningiomas showed similar age at diagnosis and identical gender distribution. Also, majority of meningiomas are idiopathic and sporadic [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Nevertheless, exposure to ionizing radiation is considered the most important risk factor for meningiomas [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In a cohort of 4,221 childhood cancer survivors exposed to cranial RT, 169 (4%) developed meningiomas after 25 years of surveillance [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In our study, few patients had previous cranial RT (1.8%), but follow-up time was shorter. Moreover, a possible relationship between meningioma and obesity has been established [\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In our patients, a quarter of the cases had obesity, but this prevalence is comparable to similar Spanish population [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Other predisposing factors (breast cancer, head trauma) and genetic diseases (NF2, MEN, schwannomatosis) have been postulated for meningioma development [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In our cohort, few cases had breast cancer or severe head trauma, and no patients had hereditary diseases.\u003c/p\u003e \u003cp\u003eThe WHO classification of meningiomas recognize 3 grades and 15 morphologic subtypes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Population studies estimate that 80\u0026ndash;85% of meningiomas are grade 1, 15\u0026ndash;18% grade 2, and 1\u0026ndash;3% grade 3 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. WHO grading system correlates with treatments outcome and patients with grade 2 or 3 meningiomas are more likely to have invasive disease or recurrence after surgery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Overall reported recurrence ranges from 7\u0026ndash;25% (grade 1), 30\u0026ndash;50% (grade 2) to 50\u0026ndash;94% (grade 3) [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Although grade 3 meningiomas are considered malignant, distant metastasis are very rare [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In our cohort of S/PS meningiomas, proportion of WHO grade 1 was higher (95%), and only 8 morphological subtypes were represented. Furthermore, recurrence after the GTR in our series was around 10%, and it is important to note that 80% of the recurring meningiomas were WHO grade 1.\u003c/p\u003e \u003cp\u003eClinical presentation of meningiomas depends on the size and location. Many meningiomas are asymptomatic and are detected incidentally [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In some cases, visual defects, seizures or mental changes are the presentation symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In our cohort and given the peculiar characteristics of the S/PS region, the diagnosis was made incidentally in only 16% of the cases and, as expected, visual symptoms were the most common (70%). It is important to highlight that in 75% of the cases, pituitary function was preserved at diagnosis, despite an average tumor size of almost 3 cm.\u003c/p\u003e \u003cp\u003eOn MRI study, meningiomas have a characteristic appearance which allows the diagnosis to be presumed with reasonable accuracy. They typically are well-defined extra-axial masses and most of them show the distinctive marginal dural thickening that taper peripherally (the tail sign). Additionally, meningiomas are mainly isointense or hypointense on T1 and isointense or hyperintense on T2-weighted [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In our series, in all cases with initial presumptive diagnosis who underwent surgery, the pathological diagnosis of meningioma was confirmed. Also, and similarly to meningiomas in other locations, S/PS meningiomas in our cohort were mostly isointense or hypointense (85%) on T1-weighted and isointense or hyperintense (88%) on T2-weighted.\u003c/p\u003e \u003cp\u003eManagement of patients with meningiomas requires a balance between therapeutic intervention and avoidance of neurological damage from the treatment. Therefore, a proper individual assessment is essential in determining the optimal therapeutic strategy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Excluding rare cases with metastatic disease, management of patients with meningiomas consist of clinical surveillance, surgery plus RT or RT alone [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Due to the specific characteristics of the sellar region, most S/PS meningiomas are symptomatic at diagnosis (85% in our series). Consequently, early active treatments are elected in many cases (93% in our cohort). Although surgery is the treatment of choice for symptomatic patients, obtain a GTR could be difficult in most cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTSM is one of the most common S/PS meningioma (the most prevalent in our series) and there has been controversy regarding the best surgical approach for these patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A study including 51 patients with TSM (85% operated via craniotomy) showed similar GTR in patients who underwent transsphenoidal approach (83.3%) compared to those with transcranial surgery (86.4%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Another study in 33 patients with TSM managed surgically (62% via endonasal) showed GTR in 80% and 39% of patients after transsphenoidal and transcranial surgery, respectively. However, tumors were larger and more laterally extended in the transcranial group [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In our cohort, patients with TSM predominantly underwent transsphenoidal surgery (70%) and GTR was achieved in 67% (endonasal) and 43% (transcranial). The relatively small number of cases reported (including our cohort), the variability in tumor size, location, surgeon experiences, could explain the diversity of outcomes.\u003c/p\u003e \u003cp\u003eCSM is another relatively frequent perisellar meningioma whose surgical resection poses a significant challenge [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Therefore, multimodality treatments and tumor debulking addressed to improve clinical symptoms, appear to be the best therapeutic options [\u003cspan additionalcitationids=\"CR39 CR40\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. A series of 17 patients with CSM that underwent decompression surgery obtained visual normalization in 62% of the cases [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In our 16 patients with CSM, GTR was not achieved in any of the cases, but nearly 50% of the patients experienced normalization of visual symptoms after treatment.\u003c/p\u003e \u003cp\u003eFractionated RT or radiosurgery are effective to achieve both tumor control and low morbidity and are used for cases with residual tumors following surgery, or as initial treatment in patients with surgical risk [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A study in 763 patients with S/PS meningiomas treated with radiosurgery (50% had prior surgery) showed a remnant stabilization in 90% of the cases after 5.5 years of follow-up [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Another study in 143 S/PS meningiomas revealed a progression-free survival rate of 90% (95% confidence interval, 78\u0026ndash;96) at 8 years [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In the same line, our study showed that 85% of S/PS meningiomas (with or without prior surgery) remained stable after 5.7 years of follow-up.\u003c/p\u003e \u003cp\u003eHypopituitarism is one of the most important complications of S/PS meningiomas and their treatments. However, studies that have evaluated pituitary function before and after meningioma treatments are limited. In a study with 57 patients with S/PS meningiomas, postsurgical hypopituitarism occurred in 15.6% and AVD in 10.5% [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In another study, 4/17 patients with sellar meningiomas showed preoperative hypopituitarism. During postsurgical follow-up, 10/17 patients developed anterior hypopituitarism and 2/17 permanent AVD [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. A meta-analysis which included 8 studies (406 patients) reported the development of anterior hypopituitarism in 3.6% and AVD in 1.6% of cases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, it is important to highlight that hormone data were unavailable in 50% of analyzed series, and the methodological quality of the included studies was rated as \u0026ldquo;low\u0026rdquo; by the authors [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Our study offers valuable information in this regard since a complete hormone evaluation was available in 80% (at diagnosis) and 95% of patients (at last evaluation). In our cohort, S/PS meningiomas cause hypopituitarism in 25% of the cases. Despite the recovery of hormone deficiencies after surgery in half of them, more than 50% of patients exhibited hypopituitarism at last evaluation because of treatments received.\u003c/p\u003e \u003cp\u003eThe main strengths of our study lie in (1) the size of our series, which represents a large cohort of patients with a relatively uncommon tumor (2) the detailed information provided on the clinical, radiological, and histological aspects of a wide variety of meningiomas affecting the S/PS region (3) the comprehensive information provided regarding the effects of S/PS meningiomas and their treatments on pituitary function. The limitations of our study include (1) the retrospective design (2) the lack of histological confirmation of meningioma in nonsurgical group (20% of the cases) (3) the multicentric nature, which may introduce some variability regarding the radiological diagnosis, therapeutic decision, or surgical outcomes.\u003c/p\u003e \u003cp\u003eIn conclusion, S/PS meningiomas are mostly diagnosed in women in their 60s based on clinical symptoms. In a quarter of the patients, pituitary function is affected by the tumor. However, after treatments, hypopituitarism prevails in more than half of the cases. They usually are low-aggressive tumors, but relatively large and often locally invasive. As a result, GTR is achieved in only one third of the cases. As an alternative to surgery, or in those patients with residual tumor after surgical intervention, RT is effective in tumor control with an excellent safety profile.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: Georgina F. Caulfield for the language review of the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGrand and Funds\u003c/strong\u003e:\u0026nbsp;No author has received any grant for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e: Conceptualization, methodology (FG-P, PI, AZ, MIGB). Data curation, original draft preparation (FG-P). Writing review and supervision (PI). All the authors participated in the data collection, critical review of the manuscript and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: Authors declare that they have not conflict of interest\u0026nbsp;(financial or non-financial).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e: \u0026nbsp;The authors agree to make data and materials supporting the results or analyses presented in their paper available on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e-Sahm F, Brastianos PK, Claus EB et al (2021) In Meningioma. WHO Classification of Tumors Editorial Board. Central nervous system tumors (5th ed), Lyon (France), vol 6, pp 284\u0026ndash;298\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-Wiemels J, Wrensch M, Claus EB (2010) Epidemiology and etiology of meningioma. 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Pituitary 16:182\u0026ndash;188. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11102-012-0399-3\u003c/span\u003e\u003cspan address=\"10.1007/s11102-012-0399-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pituitary","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pitu","sideBox":"Learn more about [Pituitary]()","snPcode":"11102","submissionUrl":"https://submission.nature.com/new-submission/11102/3","title":"Pituitary","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"sellar meningioma, perisellar meningioma, tuberculum sellae meningioma, cavernous sinus meningioma, hypopituitarism","lastPublishedDoi":"10.21203/rs.3.rs-5146945/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5146945/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eStudies focused on the effects of sellar and/or perisellar (S/PS) meningiomas on pituitary function are scarce. We evaluate the clinical characteristics, therapeutic outcomes, and the effects that S/PS meningiomas and their treatments have on pituitary function.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA multicenter and retrospective study of patients with S/PS meningiomas attended in 20 tertiary Spanish centers.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e171 patients, 129 (75.4%) females, with median age of 61.5 [51\u0026ndash;71] years were analyzed. At presentation, 118 (69.1%) had visual disturbance, 66 (38.6%) headache, 46 (26.9%) cranial nerve palsy and 35 (25.7%) hypopituitarism. Median tumor diameter was 29 [22-35.5] mm and cavernous sinus infiltration was detected in 99 (59.3%) of which 77 (77.8%) had Knosp grades 3 or 4. As initial treatment, 134 (78.4%) underwent surgery, 25 (14.6%) received radiotherapy and 12 (7%) were clinically and radiologically monitored. Among operated patients, gross total resection (GTR) was achieved in 45 (33.6%), whereas in 89 (66.4%) the tumor was incompletely removed. Overall median follow-up was 5.7 [2.9\u0026ndash;9.2] years. After treatments, hypopituitarism increased significantly in the whole series (n\u0026thinsp;=\u0026thinsp;86, 53.1%) respect to diagnosis (n\u0026thinsp;=\u0026thinsp;35, 25.7%), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Development of hypopituitarism was not associated with surgery extension (subtotal or GTR), histological subtype, type of radiotherapy or radiation dose received.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eS/PS meningiomas affect the pituitary function in 25% of the cases. However, after the implementation of treatments, hypopituitarism prevails in more than 50% of the cases. They are relatively large tumors and often locally invasive, and GTR is achieved in only one third of the cases.\u003c/p\u003e","manuscriptTitle":"Sellar and perisellar meningiomas: effects on pituitary function in a Spanish observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-08 09:17:20","doi":"10.21203/rs.3.rs-5146945/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-19T06:15:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-18T21:27:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-11T19:36:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140927049420209874226110324745320099867","date":"2024-10-11T17:49:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167394068700314602022515166914322914570","date":"2024-09-27T14:12:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"168964172399812084802597630228823270340","date":"2024-09-26T06:35:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-26T06:30:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-26T05:44:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-26T05:43:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pituitary","date":"2024-09-24T17:20:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pituitary","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pitu","sideBox":"Learn more about [Pituitary]()","snPcode":"11102","submissionUrl":"https://submission.nature.com/new-submission/11102/3","title":"Pituitary","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d668a274-1ead-423b-ae77-6835dcd8feef","owner":[],"postedDate":"November 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T16:07:22+00:00","versionOfRecord":{"articleIdentity":"rs-5146945","link":"https://doi.org/10.1007/s11102-024-01484-y","journal":{"identity":"pituitary","isVorOnly":false,"title":"Pituitary"},"publishedOn":"2024-12-28 15:57:27","publishedOnDateReadable":"December 28th, 2024"},"versionCreatedAt":"2024-11-08 09:17:20","video":"","vorDoi":"10.1007/s11102-024-01484-y","vorDoiUrl":"https://doi.org/10.1007/s11102-024-01484-y","workflowStages":[]},"version":"v1","identity":"rs-5146945","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5146945","identity":"rs-5146945","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}