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Extended endonasal transsphenoidal surgery (eTSS) offers a wide surgical field for various parasellar lesions; however, intraoperative high-flow cerebrospinal fluid (CSF) leakage is inevitable. Therefore, secure sellar reconstruction methods are essential to prevent postoperative CSF leakage. Although collagen matrix has been applied for dural reconstruction in neurosurgery, its suitability for application in extended eTSS remains unclear.Fifteen patients underwent modified shoelace dural closure using collagen matrix after lesionectomy via extended eTSS. In this technique, a collagen matrix, which was placed subdurally (inlay graft), was continuously sutured with both open dural edges like a shoelace. Then, another collagen matrix was placed epidurally (onlay graft), and rigid reconstruction was performed using the septal bone and a resorbable fixation mesh. Postoperative CSF leakage did not occur in fourteen patients, but did in one patient with tuberculum sellae meningioma. In this case, the CSF leakage point was detected just around the area between the coagulated dura and the adjacent collagen matrix. The collagen matrix harvested from this area was pathologically examined; neovascularization and fibroblastic infiltration into the collagen matrix were not detected. On the other hand, neovascularization and fibroblast infiltration into the collagen matrix were apparent on the surface of the collagen matrix harvested from the non-CSF leakage area.Our novel dural closure technique using collagen matrix could be an effective option for sellar reconstruction in extended eTSS; however, it should be applied in patients in whom normal dural edges are preserved.Clinical trial registrationNot applicable

Background Pituitary apoplexy is a rare clinical syndrome. Only a few studies have examined factors associated with recovery of neuro-endocrine functions following transsphenoidal surgery. This study aimed to identify factors associated with neuro-endocrine recovery following surgery for pituitary apoplexy. Methods The records of pituitary apoplexy patients who underwent transsphenoidal surgery at Songklanagarind Hospital between January 2005 and December 2020 were retrospectively reviewed. The primary outcomes were the recoveries of preoperative visual acuity (VA), visual field (VF), cranial nerve function, and pituitary hormone deficits. Using logistic regression analysis, various factors were analyzed for their associations with recovery of neuro-endocrine functions. Results The study included 98 patients. Multivariate analysis showed that older age and greater suprasellar extension were associated with no recovery of VA (P = 0.042 and P = 0.018, respectively). Only 33% of patients aged > 55 years and suprasellar extension of lesion ≥ 25 mm gained recovery of VA, while 100% of patients with neither of these factors had recovery. Underlying hypertension was associated with no recovery of preoperative VF defect (P = 0.027). Wilson-Hardy classification-invasion grades 3-4 and lower preoperative serum prolactin level were associated with no recovery from preoperative hypoadrenalism and hypothyroidism (P = 0.016 and P = 0.007, respectively). Conclusions Older age, higher suprasellar extension, and hypertension were poor prognostic factors for visual recovery. Wilson-Hardy inferior invasion grade 3-4 and lower preoperative serum prolactin level were poor prognostic factors for recovery from hypopituitarism. Stratifying patients according to these prognostic factors may assist in selecting patients for surgery.

OBJECTIVE Giant pituitary adenoma is considered a challenging pathology for surgery owing to its complications and low resection rate. In this study, the authors present their experience of using the endoscopic endonasal approach to treat patients with giant pituitary adenoma, and they aimed to develop a classification system for prediction of extent of resection. METHODS The institutional medical records of patients diagnosed with giant pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery between August 1997 and December 2019 were retrospectively reviewed. Surgical and clinical outcomes were evaluated in detail. The effects of tumor characteristics on extent of resection were analyzed. The findings were used to develop two classification systems that could preoperatively predict extent of resection. Morphological score was based on tumor characteristics, and landmark-based classification was defined according to surgical zones based on neurovascular landmarks. The effects of change in surgical strategy, which aimed to maximize tumor resection and capsule dissection, on rates of resection and complications were evaluated before and after 2017. RESULTS This study included 205 patients, with a mean patient age of 46.95 years and mean preoperative tumor diameter of 46.56 mm. Gross-total resection (GTR) was achieved in 35.12% of patients, near-total resection (NTR) in 39.51%, and subtotal resection (STR) in 25.36%. Extent of resection differed significantly between the grades and zones of the classification systems (p < 0.001 for both). Among patients with grade 3 tumor, 75.75% of patients achieved STR, 21.21% achieved NTR, and 3.03% achieved GTR. Among patients with zone 3 tumor, 65.75% achieved STR, 32.87% achieved NTR, and 1.36% achieved GTR. Both grade 3 and zone 3 indicated limited extent of resection. The mean (range) follow-up duration was 50.16 (9–247) months. Postoperative recovery of at least one hormone axis was seen in 15.24% of patients with pituitary deficiency, and development of new hormonal deficiency was observed in 22.43% of patients. Complications included permanent diabetes insipidus (7.80%), cerebrospinal fluid leakage (3.90%), postoperative apoplexy (3.90%), meningitis (3.41%), and epistaxis (3.41%). The surgical mortality rate was 1.46%. Among 85 patients treated before 2017, 27.05% of patients achieved GTR, 37.64% achieved NTR, and 35.29% achieved STR; among 120 patients treated after 2017, 40.83% achieved GTR, 40.83% achieved NTR, and 18.33% achieved STR. Seven patients in the pre-2017 cohort had postoperative apoplexy versus only 1 patient in the post-2017 cohort. There were no statistically significant differences between the two periods in terms of the incidence rates of other complications. CONCLUSIONS Capsule dissection and GTR are valuable for preventing serious complications and reducing recurrence of giant adenoma. Treatment of giant pituitary adenoma may be better managed with the help of a classification system that provides information about extent of resection that can be achieved with an endoscopic approach.

OBJECTIVE Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5–16 years), stable disease was achieved in 91% of cases. CONCLUSIONS ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Purpose Cerebro-spinal fluid leak after transsphenoidal surgery for pituitary adenomas may be prevented by skull base reconstruction with fat autograft. However, graft changes may interfere with the interpretation of postoperative images. Our aim is to describe the radiological evolution of the fat autograft. Methods A retrospective analysis was performed, including patients undergoing a transsphenoidal surgery for pituitary adenomas with a fat autograft for skull base reconstruction. Clinical and radiological data were collected, with assessment of fat autograft and extent of resection. Statistical analysis was performed using Kruskal–Wallis and Wilcoxon signed-rank test while Spearman’s Rho was used to analyze the relationship between variables. Results Seventy-two patients were included. Macroadenomas were diagnosed in 62 cases (86.1%) and in 21 cases an invasion of the cavernous sinus was described (29%). Gross total resection was achieved in 84.7% of cases. The volume of the fat graft significantly decreased between 3 months and 1 year after surgery (p = 0.01) and between 1 year and the last follow-up (mean 4.63 years, p Conclusion Fat resorbs with time: almost 50% of the fat volume is lost during the first year after surgery and 60% is resorbed at 4.6 years. T1-signal, before and after gadolinium injection, also decreases during the first year, probably because of the progressive fibrosis of the graft. This information will contribute to the interpretation of postoperative images.

Background Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses. Case presentation We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed. Conclusion PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.

Non-functioning pituitary adenomas (NFPA) usually present with symptoms of mass effect. Thus, the first-line treatment generally consists of transsphenoidal surgery. Since these tumors are usually large and invasive, post-surgical tumor remnants are common. Active surveillance is the follow-up strategy adopted by most pituitary centers, although the prevalence of residual tumor growth may reach 50% in 5–10 years, often leading to repeat surgery, radiation therapy, or both. NFPA remain the only pituitary tumor type for which no medical therapy has been approved. In this debate, we consider the evidence in favor and against using cabergoline to treat progressing NFPA.

Objective: Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors. Methods: We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at 1 year after operation, respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (ORs) were calculated, stratified by radiologic size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis. Results: Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission (OR, 0.20; 95% confidence interval [CI], 0.16–0.24) and lower rates of remission at follow-up (OR, 0.11; 95% CI, 0.053–0.22). Postoperative remission was less likely in tumors with extrasellar or suprasellar extension (OR, 0.16; 95% CI, 0.06–0.43) and tumors with cavernous sinus invasion (OR, 0.03; 95% CI, 0.01–0.13). Female gender and absence of preoperative dopamine agonist treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission, I2 = 94%; follow-up remission, I2 = 86%; recurrence, I2 = 68%). Conclusions: Transsphenoidal surgery for prolactinomas may be particularly effective in small, noninvasive, treatment-naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.

Context Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. Objective To describe predictive performance of preoperative biochemical and imaging data relative to post-operative remission and clinical characteristics in patients with presumed CD. Design, Setting, Patients, Interventions Patients (n = 105; 86% female) who underwent surgery from 2007 through 2020 were classified into 3 groups: group A (n = 84) pathology-proven ACTH adenoma; group B (n = 6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (n = 15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. Main outcomes Group A + B was compared with group C regarding predictive performance of preoperative 24-hour urinary free cortisol (UFC), late night salivary cortisol (LNSC), 1-mg dexamethasone suppression test (DST), plasma ACTH, and pituitary magnetic resonance imaging (MRI). Results All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (P Conclusions Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.

Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's disease (CD). However, the reported remission rates of patients who received TSS vary widely between different studies, and the predictors of surgical outcomes remain controversial. The present study analyzed the early outcome of TSS in a large population of patients with CD at a single center, and identified potential predictors of initial remission of TSS in patients with CD.The clinical features and surgical outcomes of CD patients who underwent TSS between 1988 and 2018 at Peking Union Medical College Hospital (PUMCH) were collected and analyzed from their medical records.Of the 1604 CD patients who underwent TSS at PUMCH between February 1988 and October 2018, 1106 patients had complete medical data and pathological results. After surgery, the overall postoperative initial remission rate was 72.5, and 27.5% of patients maintained persistent hypercortisolism. The initial remission rate of patients with preoperative noninvasive adenoma based on MRI (77.1%), intraoperative noninvasiveness (72.5%), microadenoma (74.3%), pathological confirmation (76.4%), and first TSS (73.9%) was significantly higher than that in patients with preoperative invasive adenoma (53.0%), intraoperative invasiveness (60.7%), macroadenomas (65.9%), pathologically negative (49.7%), and repeat TSS (56.0%), respectively (all P 0.05). The initial remission rate in patients with pseudocapsule-based extracapsular resection (88.1%), MRI-visible adenoma (74.2%) was higher than that in patients without pseudocapsule-based extracapsular resection (77.1%), and with MRI-negative results (64.5%), respectively, but did not reach statistical significance (All P 0.05). Striking, there was no significant differences in initial remission rates between patients who underwent selective adenomectomy and enlarged adenomectomy (P 0.05). Whereas, the initial remission rates in patients who underwent partial hypophysectomy only was 51.0%, which was much lower than that in patients underwent selective adenomectomy and enlarged adenomectomy (P 0.05).The TSS is a safe and effective procedure for the treatment of CD. Whereas, preoperative invasiveness based on MRI, intraoperative invasiveness, macroadenomas pathologically negative, and repeat TSS are related to lower initial remission rates.

Background Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship. Objective To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery. Methods Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery. They were monitored for 12 wk. The primary outcome measure was sinonasal QOL at 2 wk on the Anterior Skull Base Nasal Inventory-12. Supplementary end points included sinonasal QOL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores to assess nasal healing according to the Lund-Kennedy method. Results A total of 461 patients were screened, 131 were randomized, and 113 (placebo arm: 55; antibiotic arm: 58) were analyzed. There was no clinically meaningful or statistically significant difference in sinonasal QOL at any measured time point (P ≥ .24) using either instrument. Nasal cavity endoscopy scores were not significantly different at 1 to 2 wk after surgery (P = .25) or at 3 to 4 wk after surgery (P = .08). Conclusion Postoperative prophylactic oral antibiotics did not result in superior sinonasal QOL compared with placebo among patients who underwent standard endoscopic transsphenoidal surgery.

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P P = 0.002, − 27.2%). Three months postoperative copeptin level

[Introduction] Water and electrolyte disturbances are common after pituitary surgery and can generally be classified into transient hypotonic polyuria and transient or permanent diabetes insipidus (DI). The prevalence varies in the literature between 31-51% for transient hypotonic polyuria, 5.1-25.2% for transient DI, and 1-8.8% for permanent DI., [Objective] The aim of this study was to identify the prevalence of water and electrolyte disturbances with polyuria and the preoperative and postoperative predictive factors in patients undergoing surgery with an extended endoscopic endonasal approach., [Material and methods] This retrospective observational descriptive study included 203 patients with a diagnosis of pituitary adenoma who underwent their first transsphenoidal surgery via the extended endoscopic endonasal approach between April 2013 and February 2020. The diagnosis of water and electrolyte disturbances was based on the criterion for polyuria (>4 ml/kg/h). Postoperative polyuria was defined as those cases diagnosed during the immediate postsurgical period that resolved prior to discharge. Transient DI included all cases with a duration of less than 6 months but still present at hospital discharge, and permanent DI included cases lasting more than 6 months., [Results] The overall prevalence of water and electrolyte disorders was 30.5% (62), and the prevalence of postoperative polyuria was 23.6% (48). The median number of desmopressin doses administered to patients with postoperative polyuria was one dose (interquartile range [IQR] 1-2), and thus the median duration of treatment was 0 days. The median initiation of desmopressin was the second day after surgery (IQR 1-2). The overall prevalence of DI was 6.89%. Among the patients with transient DI, the duration was less than 3 months in three patients (1.47%), and between 3 and 6 months in two (0.98%). Nine patients had permanent DI (4.43%). (4.43%)., [Conclusions] The prevalence of electrolyte disturbances in our study was high, although similar to that found in the literature. Most of the cases were transient hypotonic polyuria that resolved within one day. The prevalence of transient DI in our cohort was lower than that described in the literature, while permanent DI was similar.

Funder: Wellcome Trust, PURPOSE: Pituitary adenomas affect patients' quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While clinical outcomes can assess treatment efficacy, they do not capture variations in QoL. We present the development and validation of a patient reported outcome measure (PROM) for patients with pituitary adenomas undergoing transsphenoidal surgery. METHODS: The COSMIN checklist informed the development of the pituitary outcome score (POS). Consecutive patients undergoing surgical treatment for suspected pituitary adenoma at a single centre were included prospectively. An expert focus group and patient interviews informed item generation. Item reduction was conducted through exploratory factor analysis and expert consensus, followed by assessment of the tool's validity, reliability, responsiveness, and interpretability. RESULTS: 96 patients with a median age of 50 years validated the POS. The final questionnaire included 25 questions with four subscales: EQ-5D-5L-QoL, Visual Symptoms, Endocrine Symptoms and Nasal Symptoms. CONCLUSION: The POS is the first validated PROM for patients undergoing transsphenoidal surgery for a pituitary adenoma. This PROM could be integrated into contemporary practice to provide patient-centred outcomes assessment for this patient group, aligning more closely with patient objectives.

Dopamine agonists (DA) comprise first-line treatment for prolactinomas. However, some patients show no response to DA and are considered resistant. In this study, we retrospectively analyzed the outcomes of DA-resistant prolactinoma patients after transsphenoidal surgery (TSS). A total of 94 consecutive patients with DA-resistant prolactinomas who underwent TSS were retrospectively enrolled in the present study. Early postoperative remission rate, prolactin (PRL) levels, and recurrence rate were analyzed. Of 94 DA-resistant patients, 47 (50%) achieved early remission 1 week post-surgery, including 41.18% of macroprolactinoma patients and 73.08% of microprolactinoma patients. PRL levels on the first postoperative day were significantly lower than preoperative PRL levels (p

Background Dopamine agonists such as bromocriptine and cabergoline have been found to be an effective treatment for hyperprolactinemia, not only inducing adenoma shrinkage but also lowering serum prolactin levels. Among known dopamine agonists, cabergoline is the drug of choice due to its enhanced tolerability compared with bromocriptine. This study aimed to evaluate cabergoline's effectiveness, along with transsphenoidal surgery, in the treatment of hyperprolactinemia. Methods We retrieved all patients with a diagnosis of prolactinoma who were treated in our hospital during 2000-2018. A total of 208 patients were enrolled in the analysis after applying exclusion criteria. Patients were divided into four groups according to the treatments received. The demographic data, dosage and duration of cabergoline, and serum prolactin levels at different time points were collected for analysis. Results Normalization was achieved in 59 patients (83.10%) within a short median duration of 2.80 months among those treated with cabergoline only. Although cabergoline alone was effective and well-tolerated, our data showed that long-term remission rates were more favorable when surgery was involved. The long-term remission rate of all patients enrolled was 53.8% (112 patients among 208 patients). The long-term remission rates for the different treatment groups were 17.8% (8 of 45 patients) in Group 1 (Operation→Drug), 83.3% (5 of 6 patients) in Group 2 (Drug→Operation), 79.0% (68 of 86 patients) in Group 3 (Operation only), and 43.7% (31 of 71 patients) in Group 4 (Drug only). Conclusion Cabergoline has been demonstrated to be effective and should be considered as a first-line treatment for hyperprolactinemia. In our study, transsphenoidal surgery was also demonstrated to achieve good results compared with medical treatment. Surgical intervention may resurface as an alternative first-line treatment. When used in combination with cabergoline, surgery offers a higher disease remission rate than either drug or operation alone.

Objective Acromegaly is a syndrome of metabolic alterations secondary to increased growth hormone levels from a somatotroph pituitary adenoma. A multidisciplinary approach beginning with surgery, followed by adjuvant radiation or medical therapy for residual disease, is considered standard of care. Several factors affect the likelihood of remission after surgery, but the impact of surgical experience on remission rates has not been adequately assessed. Methods Retrospective review of 203 patients, divided into 2 eras (era 1, 102 patients; era 2, 101 patients) of patients who underwent transsphenoidal surgery for acromegaly by a single surgeon over 11 years, was performed, determining the effect of surgical experience on rates of remission and various complications. Remission was defined according to the 2014 Endocrine Society Clinical Practice Guideline. Results The rate of surgical remission was 40.6% (62.9% among noninvasive adenomas). Rates of surgical remission significantly improved in the latter half of this cohort (31.2% in the first half vs. 50% in the second half), despite other factors being comparable. On multivariate analysis, surgeon experience, cavernous sinus invasion, and preoperative growth hormone levels affected the rates of surgical remission. Rates of cerebrospinal fluid leak and hypopituitarism were lower in the second half, whereas resolution of acromegaly-associated comorbidities was increased. Conclusions We report, in this large single-surgeon review of endoscopically operated acromegaly cases, increased rates of surgical remission and reduced complications with increasing surgeon experience. The overall experience of the treating team in dealing with perioperative and intraoperative factors also contributes to improved outcomes.

In most patients with suspected or confirmed pituitary adenomas (PAs), MRI, performed using T1- (with or without gadolinium enhancement) and T2-weighted sequences, provides sufficient information to guide effective clinical decision making. In other patients, additional MR sequences (e.g., gradient recalled echo, fluid-attenuation inversion recovery, MR elastography, or MR angiography) may be deployed to improve adenoma detection, assess tumoral consistency, or aid distinction from other sellar/parasellar lesions (e.g., aneurysm, meningioma). However, there remains a small but important subgroup of patients in whom primary or secondary intervention (e.g., first or redo transsphenoidal surgery, stereotactic radiosurgery) is limited by the inability of MRI to accurately localize the site(s) of de novo, persistent, or recurrent PA. Emerging evidence indicates that hybrid imaging, which combines molecular (e.g. 11C-methionine PET) and cross-sectional (MRI) modalities, can enable the detection and precise localization of sites of active tumor to guide targeted intervention. This not only increases the likelihood of achieving complete remission with preservation of remaining normal pituitary function but may mitigate the need for long-term (even lifelong) high-cost medical therapies. Here, we review published evidence supporting the use of molecular imaging in the management of PAs, including our own 10-y experience with 11C-methionine PET.

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.

Frailty is a state of physiological vulnerability that negatively influences surgical outcomes. The effect of frailty on pituitary adenoma surgery, however, is not clear, and patients may be wrongly denied surgery because they are “too frail”. We examined the effects of frailty on surgical outcome and quality-of-life (QoL) in patients undergoing endoscopic transsphenoidal resection of pituitary adenomas. A prospective, consecutive cohort of surgically managed pituitary adenoma was analysed. Frailty was defined by the 5-factor modified Frailty Index (mFI-5) and the Charlson Comorbidity Index (CCI). QoL was measured by the anterior skull base questionnaire (ASBQ) and sinonasal outcomes test (SNOT). Of 304 patients with pituitary adenomas, 42 (13.8%) were frail (mFI5 of > 1). Frail patients tended to have smaller adenomas (p

11-C-methionine (MET)-positron emission tomography (PET) as an adjunct to magnetic resonance imaging (MRI) has been proposed as a suitable molecular imaging modality for localizing pituitary adenomas in Cushing’s disease. 18-F-Fluoroethyl-L-tyrosine (FET)-PET, which is more widely available has not yet been reported in this context. Retrospective double-center cohort study on 15 patients who underwent transsphenoidal surgery for biochemically proven Cushing’s disease between 2011 and 2019. Preoperative MET-PET/MRI and/or FET-PET/MRI were compared with intraoperative and histopathological examinations using the Mann Whitney U test and the Fisher’s Exact test, along with positive predictive value calculations. Fifteen patients were included, with a mean age of 47.2 (18–69) years. Six patients received either a MET-PET/MRI or a FET-PET/MRI and 3 patients both exams, respectively. 67% of the tumors were detected by MRI (MET-PET-group [56%]; FET-PET-group [78%]). All tumors were microadenomas with a mean adenoma volume of 0.19 cm3 (0.02–0.78), all of which displayed a circumscribed pathological FET- and/or MET-uptake. FET-PET/MRI results positively correlated with the localization of the tumor confirmed intraoperatively and histopathologically in all cases, resulting in a sensitivity and specificity of FET-PET/MRI for tumor localization of 100% (95% CI 66.37–100%). One MET-PET/MRI suggested a localization contralateral to the expected spot. The sensitivity and specificity of MET-PET for tumor localization hence was 89% (95% CI 51.75–99.72%). Preoperative hybrid FET-PET/MRI and MET-PET/MRI have a high predictive value in localizing corticotroph adenoma for selective adenomectomy in Cushing’s disease.

Background Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. Methods We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. Results The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. Conclusions Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

Introduction Pituitary surgery has shifted in recent years from microscopic surgery(MS) to endoscopic endonasal surgery (EES). However, the comparative long-term outcome of these surgical approaches, including the need for subsequent re-operation has never been reported. We present our experience in a high-volume referral center experienced in both endoscopic and microscopic approaches to compare the need for re-operation after initial resection of non-functioning pituitary macroadenomas using these surgical approaches. Methods 684 patients (398 with NF adenomas) underwent trans-sphenoidal pituitary surgery in our institution between 2006 and 2017. Complete follow-up (mean 72 months, minimum two years) was available in 87 newly diagnosed patients with non-functioning pituitary macroadenomas (NFPMA; 48-microscopic and 39-endoscopic). The EES approach has been used almost exclusively since 2012. The need for repeat operation for tumor resection during the follow-up period was assessed as the primary end-point of the study. Extracted data included various demographic and clinical parameters, radiographic findings as well as the extent of resection (EOR). Results The EOR was similar for both groups, with a trend towards better EOR in the EES group. The rate of surgical complications was also similar for both groups. There was a strong trend towards lower need for re-operation in the EES group compared to the MS group (12.8% vs. 29.2%, p = 0.056). In a multivariate analysis, only EOR and Knosp grade were independently associated with the need for re-operation surgery. Conclusion Our data indicate that EES in NFPMA tends to be associated with a lower need for re-operation compared to the MS approach, with a similar rate of EOR and complications.

Purpose Preoperative diagnosis of pituicytomas is difficult, and management and prognostic factors remain ambiguous. The purpose of this study was to elucidate the radiological characteristics of pituicytoma, to assess the risk factors affecting tumor progression, and to propose the optimal treatment regimen based on comprehensive analysis. Methods We reviewed the clinical data of 22 patients with pituicytoma confirmed pathologically in our institution. In addition, 93 cases of pituicytoma in the previous literature were recruited. The individual data of 115 patients were analyzed to evaluate the adverse factors affecting pituicytoma progression. Results In the combined cohort, 3 of 61 patients who underwent gross-total resection (GTR) developed recurrence (4.9%); of the 54 patients who received non-GTR, 19 progressed (35.2%). Univariate and multivariate Cox regression analysis verified male gender (HR 2.855, 95% CI 1.008–8.089; p = 0.048), TS (transsphenoidal surgery; HR 3.559, 95% CI 1.015–12.476; p = 0.047), and non-GTR (HR 4.388, 95%CI 1.240–15.521; p = 0.022) were independent unfavorable factors for pituicytoma progression. A multivariate logistic regression model verified that tumor diameter ≥ 1.85 cm (OR 4.859, 95% CI 1.335–17.691; p = 0.016) was independent adverse factors for GTR. Compared with TS, OT (open transcranial) is more likely to have postoperative complications (OR 3.185, 95% CI 1.020–9.944; p = 0.046), especially vision deterioration (OR 37.267, 95% CI 4.486–309.595; p = 0.001). Conclusion Based on our findings, GTR was advocated as an optimal treatment for pituicytomas. However, in order to avoid damage to important structures, partial resection is acceptable. After that, adjuvant radiotherapy is recommended for male patients with high Ki-67 index, and the remaining patients can be followed up closely. When the tumor recurs or progresses, it is recommended to re-operate and remove the lesion completely as far as possible. If GTR is still not possible, postoperative radiotherapy for the residual tumor is recommended.

Purpose Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions. Methods A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases—non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)—were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint. Results All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome. Conclusion Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

Objectives Fluorescence-guided surgery may improve completeness of resection in transsphenoidal surgery for Cushing disease (CD) by enabling visualization of residual tumor tissue at the margins. In this review we discuss somatostatin receptors (SSTRs) as targets for fluorescence-guided surgery and overview existing SSTR-specific imaging agents. We also compare SSTR expression in normal pituitary and corticotrophinoma tissues from human and canine CD patients to assess canines as a translational model for CD. Methods A PubMed literature search was conducted for publications containing the terms canine, somatostatin receptor, Cushing's disease, and corticotroph adenoma. SSTR expression data from each study was documented as the presence or absence of expression or, when possible, the number of tumors expressing a given SSTR subtype within a group of tumors being studied. Studies that used reverse transcription polymerase chain reaction to quantify SSTR expression were selected for additional comparative analysis. Results SSTR5 is strongly expressed in human corticotroph adenomas and weakly expressed in surrounding pituitary parenchyma, a pattern not conclusively observed in canine patients. SSTR2 mRNA expression is similar in human normal pituitary and corticotrophinoma cells but may be significantly higher in canine normal pituitary tissue than in corticotroph tumoral tissue. Limited data were available on SSTR subtypes 1, 3, and 4. Conclusions Further studies must fill the knowledge gaps related to species-specific SSTR expression, so using canine CD as a translational model may be premature. We do conclude that the expression profile of SSTR5 (i.e., high local expression in pituitary adenomas relative to normal surrounding tissues) makes SSTR5 a promising molecular target for FGS.

Objective To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. Methods Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. Results Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01–0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). Conclusions Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.

Objective To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size. Methods This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma). Results CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m2; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005). Conclusion Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.

Rathke cleft cysts (RCCs) are benign sellar lesions originating from remnants of primitive ectoderm. They have not been previously linked to other cystic lesions, such as pineal cysts (PCs). Our objective was to perform a multicenter cross-sectional neuroimaging study to examine prevalence rates of coexisting RCC and PC.We retrospectively queried prospectively maintained, institutional review board-approved, databases from the authors' centers. All patients undergoing transsphenoidal surgery for RCC between the years of 2011 and 2020 were included for analysis. Preoperative magnetic resonance imaging was reviewed to identify the coexistence of a PC. Patient demographics and neuroimaging characteristics were recorded. A control cohort comprised of 100 age- and sex-matched patients with nonfunctional pituitary adenoma (NFPA) who also underwent surgical intervention was utilized.Eighty-four patients with RCC were identified for analysis. A coexistent PC was identified in 40.5% (n = 34) of patients with RCC compared with 14.3% (n = 12) in the NFPA cohort (P0.001). There was no significant difference in PC size between patients with RCC and PA (8 vs. 8.8 mm, respectively; P = 0.77). Although the majority (85.7%; n = 72) of the RCC cohort were female patients, there was no sex predominance with respect to coexisting PC in either the RCC or PA cohort.This is the first study to report an increased prevalence of coexisting PC and RCC, possibly because of an embryologic link or other propensity for intracranial cyst formation. Additional studies in more generalizable populations can further explore the relation between RCC and PC, or other cyst formation.

Objective The collision of pituitary adenoma and craniopharyngioma is extremely rare and thus there remains a paucity of data. Methods We described a patient from our institution. We also performed a systematic review and subsequent quantitative synthesis of the literature (n = 21) and our institutional case to yield an integrated cohort, and a descriptive analysis was carried out. Results Twenty-two patients (15 males and 7 females) were included in the integrated cohort. The median age was 47.0 years (range, 8–75 years). The tumor subtypes were 5 somatotropic, 5 lactotropic, 4 nonfunctioning, 3 gonadotropic, 2 corticotropic, 1 plurihormonal, and 1 silent subtype 3 for pituitary adenomas, and 19 adamantinomatous, 2 papillary, and 1 unknown subtype for craniopharyngiomas. Three different radiographic patterns were observed: solid mass with cystic component (n = 5), coexistence of two distinct solid components (n = 3), and a mixed-intensity solid mass (n = 5). The first 2 were consistent with histologically separate collision, whereas the third was consistent with histologically admixed collision. Among 19 patients in whom the postoperative course was recorded, a secondary intervention was required in 14 (73.7%) because of tumor progression or residual. The recurrence rate after gross total resection was 33.3%. Postoperative hormone replacement was required in 33.3%. The 10-year cumulative overall survival was 73.1%. Conclusions Most craniopharyngiomas were adamantinomatous. There are 2 types of collisions: separated and admixed. Tumor control, overall survival, and endocrinologic remission are more challenging to achieve than for solitary tumors, but gross total resection of both tumors is important for satisfactory tumor control.

PurposeValue-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients.MethodsWe retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs.Results271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke’s cleft cyst (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250).ConclusionsLength of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.

Purpose To report the first experience of our multidisciplinary team with functional imaging using 11C-methionine positron emission tomography-computed tomography (11C-methionine PET-CT) co-registered with MRI (Met-PET/MRICR) in clinical decision making and surgical planning of patients with difficult to treat prolactinoma. Methods In eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRICR was used to aid decision-making regarding therapy. Results Met-PET/MRICR was positive in 94% of the patients. MRI and Met-PET/MRICR findings were completely concordant in five patients, partially concordant in nine patients, and non-concordant in four patients. In five patients Met-PET/MRICR identified lesion(s) that were retrospectively also visible on MRI. Met-PET/MRICR was false negative in one patient, with a cystic adenoma on conventional MRI. Thirteen patients underwent transsphenoidal surgery, with nine achieving full biochemical remission, two clinical improvement and near normalized prolactin levels, and one patient clinical improvement with significant tumour reduction. Hence, nearly all patients (94%) were considered to have a positive outcome. Permanent complication rate was low. Three patients continued DA, two patients have a wait and scan policy. Conclusion Met-PET/MRICR can provide additional information to guide multidisciplinary preoperative and intraoperative decision making in selected cases of prolactinoma. This approach resulted in a high remission rate with a low rate of complications in our expert centre.

A local sphenoid mucosal flap (SMF) is naturally raised during endonasal exposure of the sella. Typically, these flaps are repositioned; however, they could be used in place of a nasoseptal flap (NSF) for closure of low-grade CSF leaks. In this study, we aim to establish the safety and efficacy of SMF closure for low-grade CSF leaks and to assess the impact on sinonasal quality of life (QoL) compared to NSF closure. In a consecutive, prospective cohort of anterior skull base pathology, data regarding sellar and suprasellar extension (Hardy grade), cavernous sinus invasion (Knosp grade), intraoperative (Kelly grade) and postoperative CSF leak, and sino-nasal QoL data (SNOT-22) were analysed. Of 187 patients with no/low flow (Kelly 0-1) intraoperative CSF leak, 127 (67.9%) received a SMF and 60 (32.1%) received a NSF. A total of 141/187 (75.4%) had no intraoperative leak, while 46/187 (24.6%) had grade-1 leaks. SMF were used in 70.9% (100/141) of cases without intraoperative leak, and 58.7% (27/46) of cases with Kelly grade-1 leaks. Hardy grade 4, grade E and Knosp grade 4 lesions were all more commonly closed with a NSF (p

Nonfunctionning pituitary macroadenomas (NFPMA) are benign tumors that cause symptoms of mass effects including hypopituitarism. Their primary treatment is transsphenoidal surgery. We aimed to determine the outcome of pituitary hormone deficits after surgical treatment of NFPMA and to identify factors predicting hormonal recovery. We retrospectively included 246 patients with NFPMA diagnosed and operated in one of the two participating centers. All hormonal axes were evaluated except growth hormone (GH). Postoperative improvement of pituitary endocrine function was considered if at least one hormonal deficit had recovered and a lower total number of deficits was observed 1 year after surgery. 80% (n = 197) of patients had one or more pituitary deficits and 28% had complete anterior hypopituitarism. Besides GH, the gonadotropic and thyrotropic axes were the most commonly affected (68% and 62%, respectively). The number of hypopituitary patients dropped significantly to 61% at 1 year (p

OBJECTIVEDespite the rise of studies in the neurosurgical literature suggesting that patients with Medicaid insurance have inferior outcomes, there remains a paucity of data on the impact of insurance on outcomes after endonasal endoscopic transsphenoidal surgery (EETS). Given the increasing importance of complications in quality-based healthcare metrics, the objective of this study was to assess whether Medicaid insurance type influences outcomes in EETS for pituitary adenoma.METHODSThe authors analyzed a prospectively acquired database of EETS for pituitary adenoma from 2005 to 2018 at NewYork-Presbyterian Hospital, Weill Cornell Medicine. All patients with Medicaid insurance were identified. As a control group, the clinical, socioeconomic, and radiographic data of all other patients in the series with non-Medicaid insurance were reviewed. Statistical significance was determined with an alpha < 0.05 using Pearson chi-square and Fisher’s exact tests for categorical variables and the independent-samples t-test for continuous variables.RESULTSOf 584 patients undergoing EETS for pituitary adenoma, 57 (10%) had Medicaid insurance. The maximum tumor diameter was significantly larger for Medicaid patients (26.1 ± 12 vs 23.1 ± 11 mm for controls, p < 0.05). Baseline comorbidities including diabetes mellitus, hypertension, smoking history, and BMI were not significantly different between Medicaid patients and controls. Patients with Medicaid insurance had a significantly higher rate of any complication (14% vs 7% for controls, p < 0.05) and long-term cranial neuropathy (5% vs 1% for controls, p < 0.05). There were no statistically significant differences in endocrine outcome or vision outcome. The mean postoperative length of stay was significantly longer for Medicaid patients compared to the controls (9.4 ± 31 vs 3.6 ± 3 days, p < 0.05). This difference remained significant even when accounting for outliers (5.6 ± 2.5 vs 3.0 ± 2.7 days for controls, p < 0.05). The most common causes of extended length of stay greater than 1 standard deviation for Medicaid patients were management of perioperative complications and disposition challenges. The rate of 30-day readmission was 7% for Medicaid patients and 4.4% for controls, which was not a statistically significant difference.CONCLUSIONSThe authors found that larger tumor diameter, longer postoperative length of stay, higher rate of complications, and long-term cranial neuropathy were significantly associated with Medicaid insurance. There were no statistically significant differences in baseline comorbidities, apoplexy, endocrine outcome, vision outcome, or 30-day readmission.

The application of 3D printing in planning endoscopic endonasal transsphenoidal surgery is illustrated based on the analysis of patients with intracranial skull base diseases who received treatment in our department. Cranial computed tomography/magnetic resonance imaging data are attained preoperatively, and three-dimensional reconstruction is performed using MIMICS (Materialise, Leuven, Belgium). Models of intracranial skull base diseases are printed using a 3D printer before surgery. The models clearly demonstrate the morphologies of the intracranial skull base diseases and the spatial relationship with adjacent large vessels and bones. The printing time of each model is 12.52–15.32 h, and the cost ranges from 900 to 1500 RMB. The operative approach was planned in vitro, and patients recovered postoperatively well without severe complications or death. In a questionnaire about the application of 3D printing, experienced neurosurgeons achieved scores of 7.8–8.8 out of 10, while unexperienced neurosurgeons achieved scores of 9.2–9.8. Resection of intracranial skull base lesions is demonstrated to be well assisted by 3D printing technique, which has great potential in disclosing adjacent anatomical relationships and providing the required help to clinical doctors in preoperative planning.

BACKGROUND Although transsphenoidal adenomectomy is the first treatment choice for Cushing's disease (CD), tumor recurrence rates are as high as 45%, resulting in a therapeutic challenge for endocrinologists and neurosurgeons. For recurrent/persistent CD (RCD/PCD), Repeat transsphenoidal surgery (RTSS), radiotherapy, gamma knife radiosurgery (GKRS) or bilateral adrenalectomy may be considered. The purpose of the study was to report the treatments and outcomes of RCD/PCD in a single center. METHODS A retrospective study was performed on 55 RCD/PCD patients from a single center between 2000 and 2012 at Peking Union Medical College Hospital (PUMCH). RESULTS Among the 55 RCD/PCD patients, 43 achieved remission (78%), and 11 maintained a PCD status (20%). The average times to recurrence after the initial treatment and Repeated treatment were 43.25±10.3 and 5.13±4.7 months, respectively (P=0.006); 17.6% of the patients experienced recurrence within the first year, and 52.9% of the patients experienced recurrence within 1.1-5.0 years. For the Repeated treatments, surgery was more effective for the biochemical remission of serum cortisol and adrenocorticotrophic hormone (ACTH) levels than radiotherapy. Delayed remission occurred in 28.9% (11/38) of the patients after Repeated surgery. Considering the previous biochemical levels after the initial surgery in RCD patients, 19.75% of patients experienced recurrence when serum cortisol levels were less than

Background The World Health Organization (WHO) classification of tumors of the endocrine organs was revised in 2017. The term atypical adenoma is no longer recommended, and tumors with rapid growth, radiologic invasion, and high Ki-67 labeling index are defined as high-risk adenomas. In this article, we present the case of an aggressive pituitary adenoma not fulfilling the new high-risk criteria with extraordinary rapid progression after very long stable disease, and discuss the remaining problem of the new criteria in terms of a complicated balance between pathologic findings and clinical features. Case Description A 67-year-old man was admitted with sellar tumor. Serum prolactin concentration was high at 4,552.2 ng/mL. Transsphenoidal surgery achieved subtotal removal. Histologic diagnosis was lactotroph cell adenoma, and Ki-67 labeling index was 2.6%. Postoperatively, magnetic resonance imaging revealed no evidence of tumor regrowth, but terguride or cabergoline administration was continued for slight hyperprolactinemia. Second surgery was performed 18 years after initial surgery because the tumor showed extraordinary rapid regrowth and hyperprolactinemia of 969 ng/mL. Histologic diagnosis was lactotroph cell adenoma with Ki-67 labeling index of 28.9% and positive immunoreactivity for p53. This case could be diagnosed as a high-risk adenoma from the beginning of treatment based on the WHO 2017 criteria, but the clinical course was unusually long and the indication of aggressive adjuvant therapy after initial surgery remained unsolved. Conclusion Pathologic confirmation for the present definition would be expected to assess the cutoff between typical adenomas and aggressive tumors.

Pituitary abscess is a rare lesion of the pituitary gland that can cause morbidity and mortality in the absence of appropriate treatment. They are classified as primary and secondary pituitary abscesses. Primary pituitary abscesses occur in patients with no previous pituitary pathology. Secondary pituitary abscesses are detected in patients with existing pituitary pathologies. We report a 16-year-old female patient with primary pituitary abscess who was misdiagnosed initially and treated as meningitis. Following the visual disturbances, pituitary abscess was diagnosed, and she underwent abscess drainage via endoscopic endonasal transsphenoidal surgery and antibiotic treatment. Primary pituitary abscess can be clinically confused with other pathologies affecting the central nervous system. In order to avoid permanent sequelae in such patients, it should be kept in mind by physicians in similar cases. Satisfying results are obtained in these patients after appropriate treatment and dramatic improvement is achieved.

Acromegaly is a rare, chronic disorder that mostly results from growth hormone (GH)-secreting pituitary adenoma. Transsphenoidal surgery is the first-line treatment of this adenoma. This study aimed to identify factors associated with remission outcome in patients with GH-secreting pituitary adenomas following transsphenoidal surgery.Patients with GH-secreting pituitary adenomas who underwent transsphenoidal surgery for tumor removal at Songklanagarind Hospital between January 2003 and December 2019 were retrospectively reviewed. The primary outcome was the remission of disease at the last follow-up using 2000 and 2010 consensus criteria. Using logistic regression analysis, various factors were analyzed for association with disease remission outcome.This study included 51 patients. The remission rate of GH-secreting pituitary microadenomas and macroadenomas following transsphenoidal surgery were 100% and 43.75%, respectively. Multivariate analysis showed that preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were significantly associated with nonremission outcome (P0.001 and P = 0.012, respectively). Patients with both of these factors had poor outcomes and never achieved remission after treatment, while patients with neither of these factors had high remission rates (87.5%) following surgery. Four of 6 (66.7%) patients who underwent repeat surgery gained remission.Preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were important prognostic factors that determined remission outcome after treatment. Patients who have both of these poor prognostic factors should be aggressively treated with surgery, medication, and probably radiation to optimally control the disease.

The evolution of pituitary surgery has made it a safe and effective form of treatment; however, risks of inadequate tumor resection, cerebrospinal fluid (CSF) leak, pituitary dysfunction, and vascular injury still exist. The use of intraoperative ultrasonography (IOUS) in pituitary surgery has been well described. Recent advancements in ultrasound technology have allowed for expanded utility as described here. A retrospective review was performed between January 2016 and December 2019. One hundred thirty-eight patients (mean age 53.7 years, 47% females) were identified undergoing transsphenoidal surgery for pituitary tumors. Thirty-four patients had IOUS performed using a side-firing ultrasound probe, while 104 did not. Data was analyzed for preoperative (demographics, clinical, and radiographic features), perioperative (blood loss, operative time), and postoperative (complications, length of stay, hormone remission, and extent of resection) outcomes. There were no significant differences in patient age, gender, tumor volume, Knosp grade, and hormone-secreting status between the two groups. Patients treated using IOUS had significantly higher rates of gross total resection (79% vs. 44%, p = 0.0008), shorter operative times (74 vs. 146 min, p < 0.0001), lower blood loss (119 vs. 284 cc, p < 0.0001), and hospital stays (2.9 vs. 4.2 days, p = 0.001). Overall complication rates were lower in the IOUS group compared to standard pituitary surgery but did not reach significance. Recent improvements in ultrasound technology have allowed for miniaturization of probes capable of delivering high-resolution images. The use of IOUS in transsphenoidal pituitary surgery may significantly increase rates of gross total resection, while decreasing blood loss, hospital LOS, and operative time.

Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution. We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005–2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed. The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively. Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up.

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Methods: Retrospective study at a referral center. The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019, were analyzed. Results: EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years) who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in 1 patient. In 2 of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) patients, it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%), but 4 (25%) of these patients had a recurrence during follow-up (biochemically and clinically silent in 2 patients). Three patients died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow-up, and a woman with a bronchial NEN. Conclusion:The course of EAS varies according to tumor type and grade. Some patients have a protracted course, whereas others may evolve into neuroendocrine carcinomas. Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; CV = coefficient of variation; EAS = ectopic ACTH syndrome; IQR = interquartile range; NEN = neuroendocrine neoplasm; SCCL = small cell carcinoma of the lung; TSS = transsphenoidal surgery; UFC = urinary free cortisol

Summary The aim of the study was to document an anatomical variation around the sella turcica which was unique and lacked any reference in the literature. A low lying osseous bar connecting the right middle clinoid process to the midpoint of the right lateral border of the dorsum sella was observed in a human skull specimen. The osseous bar was forming a foramen close to the floor of the sella, and the structure in association with this part of sella is the inferior intercavernous sinus. Measurements of the sella turcica bridge (STB), carotico–clinoid foramen (CCF), interclinoid foramen (ICF) on both sides and that of the ossified bar and foramen formed by itself were taken with the help of ImageJ software. The values observed for the measurements of different parameters of STB and its components, for CCF and ICF were bilaterally different. While the values for the osseous bar and foramen formed by it cannot be compared because of its unilateral occurrence. The presence of foramen around the inferior intercavernous sinus may lead to difficulty in performing procedures like transsphenoidal surgery (TSS) or extended TSS (eTSS) while extracting intradural lesions, thus increasing the chances of haemorrhage.

Background The endoscopic endonasal approach (EEA) has been accepted as an alternative option for diseases at the craniovertebral junction. However, the inferior destination through the endoscopic endonasal approach is anatomically higher than that of the transoral approach. Therefore, preoperative assessment of accessibility is mandatory for appropriate selection of indication. Using a navigation system, we examined the inferior limit through the endonasal route and evaluated the relationships between surrounding anatomicl structures and the lowest point. Methods This study included patients who underwent endoscopic transsphenoidal surgery for intrasellar lesions at our hospital (N = 23). At the start of surgery, the lowest point (target point [TP]) was marked with a straight probe under guidance of the navigation system. We measured 4 parameters on preoperative computed tomography: nasal length, hard palate length, anterior-posterior diameter of the nasopharynx, and nasopalatine angle. Patients were classified into groups depending on whether the TP was at or above (group A) or below (group B) the hard palatine line. Results TPs were above the hard palatine line in 15 patients (group A) and below the hard palatine line in 8 patients (group B). No TPs reached the nasopalatine line. Nasal length (P = 0.03) and nasopalatine angle (P = 0.01) were larger in group B than in group A. There were no significant differences in anterior-posterior diameter of the nasopharynx or hard palate length. Conclusions The hard palatine line is a reliable parameter for assessing the inferior limit of the endoscopic endonasal approach. Nostril size affects accessibility with surgical instruments.

Transsphenoidal surgery (TSS) is a first-line treatment for Cushing disease (CD). However, a subset of patients with CD have no visible adenoma on magnetic resonance imaging (MRI), and whether MRI results affect surgical outcomes is controversial. The aim of this study was to compare the surgical outcomes of CD patients with negative MRI findings to those of patients with positive MRI findings.The clinical features and outcomes of CD patients who underwent TSS between January 2000 and July 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinologic, histopathologic, surgical outcomes, and a minimum 12-month follow-up of 125 consecutive CD patients with negative MRI findings were compared with those of 1,031 consecutive CD patients with MRI-visible adenomas.The total remission rate was 73.3% after TSS, and 11.8% of patients experienced recurrence. Of 1,031 patients with MRI-visible adenomas, postoperative remission was achieved in 762 patients (73.9%), and the recurrence of CD was observed in 94 (12.3%) patients. Of the 125 patients with negative MRI findings, postoperative remission was achieved in 85 (68%) patients, and recurrence was observed in 6 (7.1%) patients. The remission rate and recurrence rate were not significantly different between patients with negative MRI findings and those with positive MRI findings (all P.05). The remission rate was not significantly different between patients who did or did not undergo bilateral inferior petrosal sinus sampling (BIPSS) in patients with negative MRI findings (P.05). In the patients with negative MRI findings who underwent BIPSS, the remission rate of patients with positive BIPSS results was not different from that in patients with negative BIPSS results (P.05). The lack of prior TSS, the detection of a tumor during operation, and pathologic confirmation of adenoma were associated with a higher surgical remission rate in patients with negative MRI findings (all P.05). Similar results were observed in the patients with positive MRI findings (all P.05). In addition, the major perioperative complications, including intraoperative cerebrospinal fluid leakage, hypopituitarism, and transient diabetes insipidus, were not related to the MRI results (all P.05).The remission rate and recurrence rate were not different between patients with negative MRI findings and those with positive MRI findings. If CD is clearly diagnosed according to biochemical tests, radiologic examinations, and BIPSS, we recommend TSS as the first-line treatment for patients, even if the MRI results are negative.

International audience; We report a case of malignant melanoma revealed by a metastasis to the pituitary gland. The tumor was misdiagnosed as a pituitary adenoma and aggressive transsphenoidal surgery was complicated by a cerebrospinal fluid fistula. Nine weeks later, the patient presented multiple leptomeningeal and brain metastases spreading from the sellar region. Regarding these observations, we conducted a systematic review of the literature in order to investigate clinicoradiological features that should lead clinicians to suspect pituitary metastasis and how it should impact the surgical management.

Purpose Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.