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Background: Large and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed. Patients and methods: The primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%). Results: 42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection. Conclusions: Endoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures. [ABSTRACT FROM AUTHOR]

Background: Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas. Method: We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach. Conclusion: A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury. [ABSTRACT FROM AUTHOR]

Purpose: To identify differences in the presentation and surgical outcomes between very large (30–39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group). Methods: Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated. Results: Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004). Conclusions: PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge. [ABSTRACT FROM AUTHOR]

Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations. Part 1 of this consensus guideline includes 17 pragmatic management recommendations related to clinical care, neuroimaging, visual assessment, histopathology, genetics, pituitary surgery and radiotherapy. While in many aspects the care for CYP is similar to that of adults, key differences exist, particularly in aetiology and presentation. CYP with suspected pituitary adenomas require careful clinical examination, appropriate hormonal work-up, dedicated pituitary imaging and visual assessment. Consideration should be given to the potential for syndromic disease and genetic assessment. Multidisciplinary discussion at both the local and national levels can be key for management. Surgery should be performed in specialist centres. The collection of outcome data on novel modalities of medical treatment, surgical intervention and radiotherapy is essential for optimal future treatment. Evidence and guidance for the care of pituitary adenomas in children and adolescents is currently lacking. Part 1 of this two-part consensus guideline presents 17 general recommendations for diagnosis and management of pituitary adenomas in children and young people under 19 years of age. [ABSTRACT FROM AUTHOR]

We successfully removed a rare ectopic pituitary adenoma from a 64-year-old female patient initially misdiagnosed with a chordoma. The tumor was located in the slope region and posed a challenge due to its rarity and location. Using neuro-navigation and neuro-endoscopic techniques, we performed a transnasal transsphenoidal resection and confirmed postoperatively that the tumor was a non-functional pituitary adenoma. Although the patient experienced temporary cortisol deficiency after surgery, she recovered well. To accurately diagnose ectopic pituitary adenomas of clivus, doctors must carefully evaluate the patient's imaging results and hormone levels. If necessary, nuclear medicine scans can also aid in diagnosis. Endoscopic transnasal-transsphenoidal surgery is the preferred treatment method, and preoperative multimodal imaging evaluation and intraoperative neuro-navigation technology are essential for a successful surgery. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the invasiveness to surrounding structures and recurrence rate of each subtype of nonfunctioning pituitary neuroendocrine tumor (Pit-NETs) according to the WHO 2022 classification. Methods: This retrospective study utilized data from 292 patients with nonfunctioning Pit-NETs treated with initial transsphenoidal surgery. Recurrence was evaluated on 113 patients who were available for a magnetic resonance imaging follow-up ≥ 60 months. All tumors were assessed by immunohistochemical staining for Pit-1, T-PIT, and GATA3. Invasiveness to surrounding structures was evaluated based on intraoperative findings. Results: Cavernous sinus invasion was found in 47.5% of null cell tumors, 50.0% of Pit-1 lineage tumors, 31.8% of corticotroph tumors, and 18.3% of gonadotroph tumors. Dura mater defects in the floor of sellar turcica, indicating dural invasion, were found in 44.3% of null cell tumors, 36.4% of corticotroph tumors, 16.7% of Pit-1 lineage tumors, and 17.3% of gonadotroph tumors. In logistic regression analysis, Pit-1 (OR 5.90, 95% CI 1.71–20.4, P = 0.0050) and null tumors (OR 4.14, 95% CI 1.86–9.23, P = 0.0005) were associated with cavernous sinus invasion. Recurrence was found in 8 (4.9%) patients, but without significant differences between tumor subtypes. The presence of cavernous sinus invasion was correlated with recurrence (HR = 1.95, 95% CI 1.10–3.46, P = 0.0227). Conclusion: Among nonfunctioning Pit-NETs, Pit-1 lineage tumors tend to invade the cavernous sinus, corticotroph tumors may produce dura mater defects, and null cell tumors tend to cause both. Pit-NETs with cavernous sinus invasion require a careful attention to recurrence. [ABSTRACT FROM AUTHOR]

Purpose: The main purpose of this study is to understand the characteristics and management of sinonasal small round blue cell tumors and also to emphasise the role of immunohistochemistry in their diagnosis and on the outcomes after endoscopic/open excision in these patients. Methods: This is a retrospective study conducted at a tertiary care referral centre in India which included 38 patients with sino nasal for a period of 5 years. All the patients were evaluated clinically and radiologically. All cases were confirmed diagnostically with histopathological examination and immunohistochemistry following surgical excision either by endoscopic or open approach. Some of the cases underwent post operative radiotherapy. Results: In our study, among 176 cases diagnosed with Sino nasal malignancies, 38 (21.6%) cases were diagnosed with sinonasal small round blue cell tumors with male to female ratio 1.4:1. Most common histopathological type among all the sinonasal small round blue cell tumors that presented to us was esthesioneuroblastoma i.e., 8 (21%) patients followed by pituitary macroadenoma in 7(8.4%) patients. Other types are undifferentiated squamous cell carcinoma 10(13.1%), craniopharyngioma 8(10.5%), lymphoma 3(7.9%), synovial/spindle cell sarcoma, malignant melanoma and adenocarcinoma 1(2.6%) each. Schwannoma, rhabdomyosarcoma, neuroendocrine carcinoma and neurofibroma 2 (5.2%) each. Conclusion: Sinonasal small round blue cell tumors are extremely rare tumours. Histopathological diagnosis with immunohistochemistry is characteristic of various tumors and is conclusive for diagnosis. Knowledge of these tumor entity is essential as early diagnosis helps in further management in preventing spread to vital structures and improving outcome. Most of the tumors have a multimodality treatment approach which includes surgical excision, radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far. Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic. The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought. [ABSTRACT FROM AUTHOR]

Objectives: Pituitary adenomas can exhibit aggressive behavior, characterized by rapid growth, resistance to conventional treatment, and early recurrence. This study aims to evaluate the clinical value of shape-related features combined with textural features based on conventional MRI in evaluating the aggressiveness of pituitary adenomas and develop the best diagnostic model. Methods: Two hundred forty-six pituitary adenoma patients (84 aggressive, 162 non-aggressive) who underwent preoperative MRI were retrospectively reviewed. The patients were divided into training (n = 193) and testing (n = 53) sets. Clinical information, shape-related, and textural features extracted from the tumor volume on contrast-enhanced T1-weighted images (CE-T1WI), were compared between aggressive and non-aggressive groups. Variables with significant differences were enrolled into Pearson's correlation analysis to weaken multicollinearity. Logistic regression models based on the selected features were constructed to predict tumor aggressiveness under fivefold cross-validation. Results: Sixty-five imaging features, including five shape-related and sixty textural features, were extracted from volumetric CE-T1WI. Forty-seven features were significantly different between aggressive and non-aggressive groups (all p values < 0.05). After feature selection, four features (SHAPE_Sphericity, SHAPE_Compacity, DISCRETIZED_Q3, and DISCRETIZED_Kurtosis) were put into logistic regression analysis. Based on the combination of these features and Knosp grade, the model yielded an area under the curve value of 0.935, with a sensitivity of 94.4% and a specificity of 82.9%, to discriminate between aggressive and non-aggressive pituitary adenomas in the testing set. Conclusion: The radiomic model based on tumor shape and textural features study from CE-T1WI might potentially assist in the preoperative aggressiveness diagnosis of pituitary adenomas. Key Points: • Pituitary adenomas with aggressive behavior exhibit rapid growth, resistance to conventional treatment, and early recurrence despite gross resection and may require multiline treatments. • Shape-related features and texture features based on CE-T1WI were significantly correlated with the Ki-67 labeling index, mitotic count, and p53 expression, and the proposed model achieved a favorable prediction of the aggressiveness of PAs with an AUC value of 0.935. • The prediction model might provide valuable guidance for individualized treatment in patients with PAs. [ABSTRACT FROM AUTHOR]

Li-Fraumeni syndrome is a cancer predisposition condition associated with various tumor types. We present the case of a 6-year-old boy who initially presented with a pituitary adenoma that was successfully treated with surgery. It ultimately recurred, requiring further surgical intervention followed by proton beam therapy. He later developed a medulloblastoma, and genetic testing revealed TP53 germline mutation. The patient underwent gross total resection of this medulloblastoma, followed by proton-based craniospinal irradiation and adjuvant chemotherapy. He remained disease-free 12 months after radiation and 7 months after chemotherapy. Current literature does not report pituitary adenoma as the initial central nervous manifestation in Li-Fraumeni syndrome. Early genetic testing should be considered in pediatric patients who present with such rare tumor types to help identify cancer predisposing conditions. Furthermore, as evidenced by our case, the management of multiple brain tumors in the pediatric population poses challenges. A multidisciplinary approach involving neurosurgery, pediatric oncology, pathology, and radiation oncology remains crucial to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in adulthood (aPAs). Methods: A retrospective chart review was conducted for all patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for pPA at NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) from 2005–2020. Eleven patients were identified, and information pertaining to age, sex, adenoma characteristics, procedural details, and outcomes was reviewed. A systematic review of the literature was also performed to compare outcomes of EETS versus microscopic endonasal transsphenoidal surgery (METS) for pPA. Results: From 2005–2020, 11 patients underwent EETS for pPA at NYP/WCM. Mean age at operation was 14.9 ± 2.7 years, and 5 patients (45.5%) were male. 10 adenomas (90.9%) were hormone-producing. Of the functional adenomas, 8 (80.0%) were PRL-secreting and 2 (20.0%) were GH-secreting. Maximum adenoma diameter (MAD) ranged from 1.2–5.1 cm, with a median of 1.55 cm. Cavernous sinus invasion (CSI) occurred in 2 patients with macroprolactinoma. Gross total resection (GTR) was achieved in 10 (90.9%). Biochemical remission occurred in 5/10 (50.0%). Post-operative complications were documented in 8 cases (72.7%) and included diabetes insipidus, hypopituitarism, sinusitis, weight gain, cerebrospinal fluid leak, meningitis, and hydrocephalus. Systematic literature review of 105 microscopic and 175 endoscopic cases revealed high frequency of hormone-producing tumors (83.6%) and similar rates of GTR (82.4% vs 85.1%) and biochemical cure (75.8% vs 64.3%). Conclusions: pPAs are more likely to be hormone producing and may be more aggressive and difficult to cure than aPAs. EETS is an effective treatment, although complication rates may be higher than in adult populations. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative magnetic resonance imaging (iMRI) improves the intraoperative detection of adenoma remnants in transsphenoidal surgery. iMRI might be redundant in endoscopic pituitary surgery in non-invasive tumors (Knosp 0–2) due to a superior visualization of anatomical structures in the periphery of the sella turcica compared to the microscopic technique. We identified the anatomical location of tumor remnants in iMRI and evaluated risk factors for secondary resection after iMRI and hereby selected patients with pituitary adenomas who may benefit from iMRI-assisted resection. Methods: We conducted a retrospective monocenter study of patients who underwent iMRI-assisted transsphenoidal surgical resection of pituitary adenomas at our department between 2012 and 2020. A total number of 190 consecutive iMRI-assisted transsphenoidal surgeries of pituitary adenomas graded as Knosp 0–2 were selected for analysis. Exclusion criteria were missing iMRI availability or pathologies other than adenomas. Of these 190 cases, 46.3% (N = 88) were treated with microscopic, 48.4% (N = 92) with endoscopic, and 5.3% (N = 10) with endoscopic-assisted technique. Volumetric measurement of preoperative, intraoperative, and postoperative tumor extension was performed. Demographic data, tumor characteristics, and MRI features were evaluated. Additionally, analysis of adenoma remnants identified by iMRI was performed. Results: An additional resection after iMRI was performed in 16.3% (N = 31). iMRI helped to reach gross total resection (GTR) in 83.9% (26/31) of these cases. False-positive resection was found in 1 patient (0.5%). Multivariable logistic analysis identified tumor volume (OR = 1.2, p = 0.007) recurrence (OR = 11.3, p = 0.002) and microscopic technique (OR = 2.8, p = 0.029) as independent risk factors for additional resection. Simultaneously, the endoscopic technique was significantly associated with GTR as evaluated by iMRI (OR = 2.8, p = 0.011) and postoperative MRI (OR = 5.8, p = 0.027). The detailed analysis of adenoma remnants on iMRI revealed the suprasellar location in a diaphragm fold, penetrating tumor above the diaphragm, or undetected invasion of cavernous sinus as well as in case of microscopic resection tumor location outside the line of sight as the main reasons for incomplete resections. Conclusion: Tumor volume, recurrence, and microscopic technique were identified as independent predictors for additional resection in patients with Knosp 0–2 adenomas. iMRI might increase the extent of resection (EOR) safely even after the endoscopic visualization of the sella with very low risk for false-positive findings. Remnants of tumors hidden within the diaphragmic folds, intrathecally, or behind the infiltrated wall of cavernous sinus not recognized on preoperative MRI were the most common findings in iMRI. [ABSTRACT FROM AUTHOR]

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources. [ABSTRACT FROM AUTHOR]

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20–88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53–10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92–0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71–0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research. Methods: A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms "pituitary hyperplasia" or "pituitary hypertrophy" and "hypothyroidism" was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years. Results: The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic. [ABSTRACT FROM AUTHOR]

Endoscopic pituitary surgery has shown promising results. This study reports the experiences of experienced microscopic pituitary surgeons changing to the endoscopic technique, and the beneficial effects on the postoperative outcomes. 45 transsphenoidal endoscopic-assisted surgeries performed in 2016–2017 were compared with 195 microscope-assisted surgeries performed in 2007–2017 for pituitary adenoma. Tumour size, hormonal status and vision were assessed preoperatively and 3–5 months postoperatively. Cases were identified through electronic patient records. GTR was achieved in 39% of the endoscopic operations vs. 22% of microscopic operations, p = 0.018. Mean duration of surgery was 86 min (77–95) with the endoscopic technique vs. 106 min (101–111) with the microscopic technique, p < 0.001. New hypothalamus–pituitary–adrenal axis deficiencies were observed after 3% of endoscopic vs. 34% microscopic operations, p = 0.001, and overall fewer postoperative pituitary deficiencies were observed in the endoscope-assisted group. Complications within 30 days of surgery occurred in 17% of endoscopic operations vs. 27% of microscopic operations (p > 0.05). Normalization of visual impairment occurred in 37% of the cases with preoperative visual impairment in the endoscopic group vs. 35% of those in the microscopic group (p > 0.05). The endoscopic technique performed better as a surgical procedure for pituitary adenomas. We found no statistically significant differences in complication rate or visual improvement between the two techniques. [ABSTRACT FROM AUTHOR]

Background: Giant and large pituitary adenomas (PA) constitute a specific subset of PAs, with gross total resection (GTR) rates frequently not exceeding 50%. Both an anatomical inaccessibility and an inadequate tumor visualization are thought to play a role. This study analyzes risk factors for postoperative residuals after endoscopic transsphenoidal pituitary surgery for large and giant pituitary adenomas. Methods: A retrospective analysis of patients with giant and large PA operated between 2015 and 2018 was performed. Results: Forty patients (13 females, 27 males) were included in the analysis (30 large and 10 giant PAs). The mean MRI follow-up time was 5.9 ± 6.54 months. Overall, GTR was achieved in 29 patients (72.5%), subtotal resection in 9 (22.5%), and the inconclusive result was in 2 (5%). Unexpected residuals represented 7 (77.7%) of all 9 residual tumors. The most frequent intraoperative factor associated with unexpected residual tumors was improper identification of residual tumor due to obstruction of view in 2 (28.5%) cases and inability to distinguish normal tissue from tumor in the other two (28.5%). Sub-analysis based on tumor size revealed that with large PAs, GTR was achieved in 25 (83.3%), STR in 4 (13.3%), and inconclusive in 1 (3.3%) patient. In patients with giant PAs, GTR was achieved in 4 (40%), STR in 5 (50%), and inconclusive in 1 (10%). Analysis of preoperative factors showed a significant association of residual tumors with larger suprasellar AP distance (p = 0.041), retrosellar extension (p = 0.007), and higher Zurich Score (p = 0.029). Conclusion: Large and giant PAs are challenging lesions with high subtotal resection rates. Suprasellar AP distance, retrosellar extension, and higher Zurich Score seem to be significant predictors of degree of resection in these tumors. Improving the intraoperative ability to distinguish tumor from a normal tissue might further decrease the number of unexpected residuals. [ABSTRACT FROM AUTHOR]

Objective: To explore the programmed death-ligand 1 (PD-L1) expression in varied subtypes of pituitary neuroendocrine tumors with assessment of their clinical behavior at diagnosis and follow-up. Methods: We conducted a retrospective monocentric study, including all patients operated in the Academic Hospital of Angers (France) for a pituitary neuroendocrine tumor between 2012 and 2018. PDL-1 immunostaining was performed using a European Conformity—In Vitro Diagnostic-labeled anti-PDL1 antibody (clone 22C3). PD-L1 immunostaining was evaluated as the percentage of tumor cells showing positive membrane staining, into four grades: grade 0 = < 1%, grade 1 = 1 to 5%, grade 2 = 6 to 49% and grade 3 = ≥ 50%. PD-L1 expression was compared with tumor features (secretion, proliferation, invasion) and outcome. Results: The study included 139 pituitary neuroendocrine tumors, including 84 (60%) nonfunctioning adenomas. Twenty-five pituitary neuroendocrine tumors were PD-L1 positive (18%), including 3 grade 3, 8 grade 2 and 14 grade 1. PD-L1 expression was not different between functioning and nonfunctioning adenomas (p = 0.26). Among 16 tumors with proliferative markers (Ki-67 ≥ 3% and p53 positive), only one was PD-L1 positive. Conclusion: In our series, PD-L1 was expressed in a rather small proportion of PitNET (18%), and this immune marker was not associated with any biological characteristic or behavior of the pituitary tumors. Thus, PD-L1 staining may be necessary before considering PD-L1 blockage in pituitary neuroendocrine tumors, in case of therapeutic impasse. [ABSTRACT FROM AUTHOR]

Neurocognitive and psychological dysfunctions associated with pituitary adenomas (PAs) are clinically relevant, though probably under-reported. The aim of the current review is to provide an update on neuropsychological status, psychopathology, and perceived quality of life (QoL) in patients with PAs. A systematic research was performed in PubMed and Scopus in order to identify reports on neurocognitive, psychiatric, and psychological disorders in PAs. Prevalence of alterations, QoL evaluation, and used tests were also recorded. PRISMA guidelines were followed. Of 62,448 identified articles, 102 studies were included in the systematic review. The prevalence of neurocognitive dysfunctions was 15–83% in Cushing's Disease (CD), 2–33% in acromegaly, mostly affecting memory and attention. Memory was altered in 22% of nonfunctioning (NF) PAs. Worsened QoL was reported in 40% of CD patients. The prevalence of psychiatric disorders in CD reached 77% and in acromegaly 63%, mostly involving depression, followed by psychosis, and anxiety. The prevalence of psychopathology was up to 83% in CD, and 35% in acromegaly. Postoperative improvement in patients with CD was observed for: learning processes, overall memory, visuospatial skills, and language skills. Short-term memory and psychomotor speed improved in NFPAs. Postoperative improvement of QoL, somatic symptoms, obsessive-compulsive disorder, and coping strategies was seen in CD and acromegaly. Reports after radiotherapy are discordant. There is wide variability in used tests. PAs have been recently shown to be associated with altered neurocognitive and neuropsychological functions, as well as QoL. These data suggest the importance of a multidisciplinary evaluation for an optimal management. [ABSTRACT FROM AUTHOR]

Background: Between 2010 and 2014, microscopic transsphenoidal surgery (mTSS) was performed more frequently than endoscopic TSS (eTSS) in the USA. However, few epidemiological studies on pituitary surgery are currently available. Methods: We performed a retrospective study on patients who had undergone pituitary surgery between July 2010 and March 2016. To this end, a nationwide inpatient database in Japan was used. Patients' characteristics, diagnoses, types of surgery, complications, and discharge status were examined. Results: A total of 16,253 inpatients who received pituitary surgery were identified. Patients were diagnosed with diseases for insurance claims described below: pituitary adenoma, hyperprolactinemia, other pituitary disorders (e.g., Rathke's cleft cyst), hyperpituitarism, craniopharyngioma, acromegaly, Cushing's disease, and pituitary cancer. Among them, pituitary adenomas, primarily the non-functioning ones, were the most frequent (66.9%). A total of 14,285 (88%) patients underwent TSS, while 1968 (12%) patients were treated using transcranial surgery. The number of patients undergoing TSS increased each year. The number of eTSS operations was 8140 (77%) and that of mTSS operations was 2419 (23%). Of note, eTSS increased each year. We found that high-volume hospitals more frequently selected eTSS. Compared with mTSS, eTSS was associated with a reduction of hyponatremia incidence (odds ratio, 0.69; p = 0.019). Additionally, it was not associated with other major complications. Conclusion: The present study showed that both TSS and eTSS increased on a yearly basis. We believe that the present study will be the basis of future epidemiological investigations of pituitary surgery. [ABSTRACT FROM AUTHOR]

Radiation therapy is associated with the subsequent development of cerebral aneurysms; however, stereotactic radiosurgery (SRS)-associated aneurysm cases have not been well documented, with only 18 cases reported to date. We present a case of intracranial aneurysms with the rupture occurring 20 years after SRS for a growth hormone-producing pituitary adenoma. This is the first report of aneurysms diagnosed following transsphenoidal surgery and SRS for pituitary adenoma. We believe that the aneurysm reported here is a consequence of the SRS treatment, and thus this may be a very rare long-term complication following radiation treatments. [ABSTRACT FROM AUTHOR]

We present a case report of a patient who presented with nausea and vomiting, as well as acromegalic features. Following testing, a pituitary adenoma and mediastinal non-Hodgkin’s lymphoma were diagnosed. Following two cycles of R-CHOP chemotherapy, imaging showed significant decrease in size of the sellar tumor. Following resection of tumor, both frozen and permanent section revealed only necrotic material. Further research into the potential utility of doxorubicin for the treatment of recurrent or refractory pituitary adenomas may be warranted. [ABSTRACT FROM AUTHOR]

Background: Microscopic transsphenoidal surgery (mTSS) is a well-established method to address adenomas of the pituitary gland. Endoscopic transsphenoidal surgery (eTSS) has become a viable alternative, however. Advocates suggest that the greater illumination, panoramic visualization, and angled endoscopic views afforded by eTSS may allow for higher rates of gross total tumor resection (GTR). The aim of this meta-analysis was to determine the rate of GTR using mTSS and eTSS.Methods: A meta-analysis of the literature was conducted using PubMed, EMBASE, and Cochrane databases through July 2017 in accordance with PRISMA guidelines.Results: Seventy case series that reported GTR rate in 8257 pituitary adenoma patients were identified. For all pituitary adenomas, eTSS (GTR=74.0%; I2 = 92.1%) was associated with higher GTR as compared to mTSS (GTR=66.4%; I2 = 84.0%) in a fixed-effect model (P-interaction < 0.01). For functioning pituitary adenomas (FPAs) (n = 1170 patients), there was no significant difference in GTR rate between eTSS (GTR=75.8%; I2 = 63.9%) and mTSS (GTR=75.5%; I2 = 79.0%); (P-interaction = 0.92). For nonfunctioning pituitary adenomas (NFPAs) (n = 2655 patients), eTSS (GTR=71.0%; I2 = 86.4%) was associated with higher GTR as compared to mTSS (GTR=60.7%; I2 = 87.5%) in a fixed-effect model (P-interaction < 0.01). None of the associations were significant in a random-effect model (all P-interaction > 0.05). No significant publication bias was identified for any of the outcomes.Conclusion: Among patients who were not randomly allocated to either approach, eTSS resulted in a higher rate of GTR as compared to mTSS for all patients and for NFPA patients alone, but only in a fixed-effect model. For FPA, however, eTSS did not seem to offer a significantly higher rate of GTR. These conclusions should be interpreted with caution because of the nature of the included non-comparative studies. [ABSTRACT FROM AUTHOR]

The non-endocrine TtT/GF mouse pituitary cell line was derived from radiothyroidectomy-induced pituitary adenoma. In addition to morphological characteristics, because the cells are S100β-positive, they have been accepted as a model of folliculostellate cells. However, our recent microarray analysis indicated that, in contrast to folliculostellate cells, TtT/GF cells might not be terminally differentiated, as they share some properties with stem/progenitor cells, vascular endothelial cells and pericytes. The present study investigates whether transforming growth factor beta (TGFβ) can elicit further differentiation of these cells. The results showed that canonical ( Tgfbr1 and Tgfbr2) and non-canonical TGFβ receptors ( Tgfbr3) as well as all TGFβ ligands ( Tgfb1-3) were present in TtT/GF cells, based on reverse transcription PCR. SMAD2, an intercellular signaling molecule of the TGFβ pathway, was localized in the nucleus upon TGFβ signaling. Furthermore, TGFβ induced cell colony formation, which was completely blocked by a TGFβ receptor I inhibitor (SB431542). Real-time PCR analysis indicated that TGFβ downregulated stem cell markers ( Sox2 and Cd34) and upregulated pericyte markers ( Nestin and Ng2). Double immunohistochemistry using mouse pituitary tissue confirmed the presence of NESTIN/NG2 double-positive cells in perivascular areas where pericytes are localized. Our results suggest that TtT/GF cells are responsive to TGFβ signaling, which is associated with cell colony formation and pericyte differentiation. As pericytes have been shown to regulate angiogenesis, tumorigenesis and stem/progenitor cells in other tissues, TtT/GF cells could be a useful model to study the role of pituitary pericytes in physiological and pathological processes. [ABSTRACT FROM AUTHOR]

Background: A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation. Method: Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [ $$ \frac{4}{3}\pi\ (a.b.c) $$], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume). Results: Ellipsoid and perimeter methods of tumour volume estimation strongly correlated ( R = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were −0.11 (95 % CI, −0.35, 0.14), −0.74 (95 % CI, −2.2, 0.74) and −1.4 (95 % CI, −6.4, 3.7) for micro-tumours, macro-tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, following a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong. Conclusions: Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities. [ABSTRACT FROM AUTHOR]

Aim: To report the results of a series of patients undergoing pure endoscopic endonasal pituitary surgery and to evaluate the efficacy and safety of this procedure. Materials and methods: The data of 1,166 patients that underwent endoscopic endonasal transsphenoidal adenoma removal between December 2006 and June 2013 were retrospectively reviewed. Pre- and postoperative hormonal status (3 months after surgery) were analyzed and compared with the clinical parameters originally presented by the patients. The incidences of tumor removal, hormonal control, and tumor removal complications were retrospectively analyzed. Result: Out of 577 nonfunctioning adenomas, 180 were growth hormone (GH) secreting, 308 prolactin (PRL) secreting, 26 mixed GH/PRL adenomas, 68 adrenocorticotropin secreting, and 7 thyroid-stimulating hormone-secreting adenomas. The gross total removal of pituitary adenomas was achieved in 98 % of microadenomas, 92 % of macroadenomas, and 76 % of giant adenomas. Hormonal control was achieved in 47 (69 %) cases of ACTH adenomas, 119 (66 %) GH adenomas, 262 (85 %) PRL adenomas, and 6 (86 %) TSH adenomas. Postoperative complications were observed in 168 (14.4 %) patients. The most frequent complications were diabetes insipidus (7 %), epistaxis (1.7 %), hyposmia (1.5 %), anterior lobe insufficiency (1.3 %) ,and CSF leaks (0.6 %). Conclusion: The pure endoscopic approach is a safe, efficacious, and minimally invasive technique for the removal of pituitary adenomas. A higher gross total resection rate is vital for non-functional and functional adenomas. For patients with functional adenomas, while hormonal remission is unlikely to be achieved by surgery, the use of adjuvant therapy is advocated to obtain long-term hormonal control. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor gene underlying the pituitary adenoma predisposition. Thus far, the exact molecular mechanisms by which inactivated AIP exerts its tumor-promoting action have been unclear. To better understand the role of AIP in pituitary tumorigenesis, we performed gene expression microarray analysis to examine changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in signaling cascades associated with developmental and immune-inflammatory responses. In vitro experiments showed that AIP deficiency increases intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell lines. Based on knockdown of various G protein α subunits, we concluded that AIP deficiency leads to elevated cAMP concentrations through defective Gαi-2 and Gαi-3 proteins that normally inhibit cAMP synthesis. Furthermore, immunostaining of Gαi-2 revealed that AIP deficiency is associated with a clear reduction in Gαi-2 protein expression levels in human and mouse growth hormone (GH)-secreting pituitary adenomas, thus indicating defective Gαi signaling in these tumors. By contrast, all prolactin-secreting tumors showed prominent Gαi-2 protein levels, irrespective of Aip mutation status. We additionally observed reduced expression of phosphorylated extracellular signal-regulated kinases 1/2 and cAMP response element-binding protein levels in mouse and human AIP-deficient somatotropinomas. This study implies for the first time that a failure to inhibit cAMP synthesis through dysfunctional Gαi signaling underlies the development of GH-secreting pituitary adenomas in AIP mutation carriers. [ABSTRACT FROM AUTHOR]

Cases of moyamoya disease or intracranial arterial stenosis around the circle of Willis (M/IAS) associated with hyperthyroidism have been reported. However, most of these previous reports were of the ischemic form of M/IAS and primary hyperthyroidism. To the best of our knowledge, no studies have documented therapy for M/IAS associated with hyperthyroidism. We discuss four previously unreported cases, including those involving the intracerebral hemorrhage form and thyroid-stimulating hormone (TSH) secretion from a pituitary adenoma (secondary hyperthyroidism). We analyzed data from 52 previously reported cases, including the 4 cases presented here, and discuss M/IAS associated with hyperthyroidism, treatment options, pathophysiology, the ischemic and hemorrhagic forms, secondary hyperthyroidism, and the relevant literature. Hyperthyroidism results in thyrotoxicosis and the stimulation of the superior cervical ganglion by TSH antibodies and f-T3/f-T4. Consequently, hypercoagulability and stenosis of the cerebral artery can occur. There are many reports of ischemic M/IAS associated with hyperthyroidism. A conservative approach to treatment is important in such cases; for example, antithyroid therapy should be the first choice to treat ischemic M/IAS. There have been only a limited number of reports on hemorrhagic M/IAS. We presume that hemorrhagic M/IAS tears the weakened vasculature in a manner similar to that of normal M/IAS (with no complicating hyperthyroidism). The authors also reported M/IAS associated with secondary hyperthyroidism due to pituitary thyroid secreting hormone secreting adenoma. [ABSTRACT FROM AUTHOR]

Gene coexpression patterns can reveal gene collections with functional consistency. This study systematically constructs regulatory networks for pituitary tumours by integrating gene coexpression, transcriptional and posttranscriptional regulation. Through network analysis, we elaborate the incidence mechanism of pituitary adenoma. The Pearson's correlation coefficient was utilized to calculate the level of gene coexpression. By comparing pituitary adenoma samples with normal samples, pituitary adenoma-specific gene coexpression patterns were identified. For pituitary adenoma-specific coexpressed genes, we integrated transcription factor (TF) and microRNA (miRNA) regulation to construct a complex regulatory network from the transcriptional and posttranscriptional perspectives. Network module analysis identified the synergistic regulation of genes by miRNAs and TFs in pituitary adenoma. We identified 142 pituitary adenoma-specific active genes, including 43 TFs and 99 target genes of TFs. Functional enrichment of these 142 genes revealed that the occurrence of pituitary adenoma induced abnormalities in intracellular metabolism and angiogenesis process. These 142 genes were also significantly enriched in adenoma pathway. Module analysis of the systematic regulatory network found that three modules contained elements that were closely related to pituitary adenoma, such as FGF2 and SP1, as well as transcription factors and miRNAs involved in the tumourigenesis. These results show that in the occurrence of pituitary adenoma, miRNA, TF and genes interact with each other. Based on gene expression, the proposed method integrates interaction information from different levels and systematically explains the occurrence of pituitary tumours. It facilitates the tracing of the origin of the disease and can provide basis for early diagnosis of complex diseases or cancer without obvious symptoms. [ABSTRACT FROM AUTHOR]

Infarction in the artery of Percheron territory is a rare phenomenon in which occlusion of an unpaired perforating artery arising from the P1 segment on one side results in infarcts in the bilateral paramedian thalami with or without midbrain infarcts. We describe the case of a 40-year-old male who developed this complication following re-exploratory trans-sphenoidal surgery for a pituitary adenoma. In this first report of its kind in endoscopic pituitary surgery, the pathogenesis and clinico-radiological features of this rare vascular event are discussed. [ABSTRACT FROM AUTHOR]

Pituitary tumor transforming gene (PTTG1) was isolated from rat pituitary tumor cells, and subsequently identified as a securin protein as well as a transcription factor. We show here a global transcriptional effect of PTTG1 in human choriocarcinoma JEG-3 cells by simultaneously assessing 20 000 gene promoters using chromatin immunoprecipitation (ChIP)-on-Chip experiments. Seven hundred and forty-six gene promoters (P<0.001) were found enriched, with functions relating to cell cycle, metabolic control and signal transduction. Significant interaction between PTTG1 and Sp1 (P<0.000001) was found by transcriptional pattern analysis of ChIP data and further confirmed by immunoprecipitation and pull-down assays. PTTG1 acts coordinately with Sp1 to induce cyclin D3 expression ∼threefold, and promotes G1/S-phase transition independently of p21. PTTG1 deletion was also protective for anchorage-independent cell colony formation. The results show that PTTG1 exhibits properties of a global transcription factor, and specifically modulates the G1/S-phase transition by interacting with Sp1. This novel signaling pathway may be required for PTTG1 transforming activity.Oncogene (2007) 26, 5596–5605; doi:10.1038/sj.onc.1210339; published online 12 March 2007 [ABSTRACT FROM AUTHOR]

Objective. To describe delayed massive epistaxis, a rare but serious complication after transsphenoidal surgery. Patients. Two patients underwent microscopic transsphenoidal surgery through a right endonasal approach for nonfunctioning pituitary adenoma. Severe epistaxis suddenly developed on day 8 and on day 13, respectively, after uneventful surgery. In each patient, the epistaxis was due to arterial haemorrhage from the left posterior nasal cavity. Otolarygologists failed to detect the origin of bleeding which was refractory to conservative treatment. Emergency internal carotid or external carotid angiography, performed during tight packing of the posterior nasal cavity, did not show abnormal findings; nevertheless, each patient was treated successfully by endovascular embolisation of the external carotid artery without further complication. Conclusion. When severe delayed epistaxis follows transsphenoidal surgery and damage to the internal carotid artery has been ruled out, endovascular embolisation of the external carotid artery should be considered in patients refractory to conservative treatment. [ABSTRACT FROM AUTHOR]

Metastatic spread into the brain is not infrequently seen in association with epithelial neoplasms such as lung and breast cancer, among others. In the majority of cases such spread entails a poor prognosis. Metastasic spread to the pituitary gland, specifically to the area of the infundibulum is, however, a more rare presentation. Most reported cases of metastatic disease to the pituitary are confined to the posterior lobe, probably related to the richer blood supply as compared to the anterior counterpart. The detection of pituitary metastasis is further complicated by the lack of specific associated symptomatology or definite radiologic diagnostic findings. We here describe the different clinical presentations of two patients with symptomatic pituitary stalk metastasis resulting from primary breast cancer; we also provide a systematic review of the literature. [ABSTRACT FROM AUTHOR]

Ki-67 antigen is used as a marker of proliferative activity that is linked to growth rate, invasiveness and prognosis of pituitary adenomas. So far the distribution of Ki-67 index within an individual adenoma has not been investigated. If Ki-67 antigen expression differs significantly within an individual pituitary adenoma, a sampling error may result when assessing small fragments of adenoma tissue. Such a potential error would diminish the value of Ki-67 as a tool for postoperative patient management considerations. The aim of the present study was to assess Ki-67 proliferation rates in different regions of pituitary adenomas and to statistically analyse these data for potential regional differences within each tumor.Ki-67 proliferation index was assessed in smear preparations of 100 specimens of 26 consecutive patients operated on for pituitary adenoma in the Department of Neurosurgery, Medical University Vienna. Depending on the size and extent of the tumor, a mean of 4 tissue samples (range 2-8) was selected intraoperatively from each adenoma from endosellar, suprasellar, parasellar, and basal sellar dural locations.Overall mean cell proliferation rate measured by Ki-67 was 1.81?±?0.90% (range 0.33-3.43%). Histologically invasive adenomas had significantly higher mean Ki-67 proliferation index in all samples from the same tumor than non-invasive adenomas (2.01?±?0.91% vs. 1.11?±?0.59%;P?=?0.024). Multiregional sampling revealed a homogenous distribution of Ki-67 index throughout an individual adenoma with no significant differences between any two different regions ont-test.Our data confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki-67 index of a single biopsy is representative for the whole individual adenoma. Thus Ki-67 index can be considered a reliable parameter for assessment of cell proliferation rate in adenoma biopsies and may be used for postoperative patient management considerations. [ABSTRACT FROM AUTHOR]

Adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors are associated with high morbidity due to excess glucocorticoid production. No suitable drug therapies are currently available, and surgical excision is not invariably curative. Here we demonstrate immunoreactive expression of the nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) exclusively in normal ACTH-secreting human anterior pituitary cells: PPAR-γ was abundantly expressed in all of six human ACTH-secreting pituitary tumors studied. PPAR-γ activators induced G[sub 0]/G[sub 1] cell-cycle arrest and apoptosis and suppressed ACTH secretion in human and murine corticotroph tumor cells. Development of murine corticotroph tumors, generated by subcutaneous injection of ACTH-secreting AtT20 cells, was prevented in four of five mice treated with the thiazolidinedione compound rosiglitazone, and ACTH and corticosterone secretion was suppressed in all treated mice. [ABSTRACT FROM AUTHOR]

Summary. Background: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas. Methods: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years. Results: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushing's disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowths occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours. Conclusions: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included. [ABSTRACT FROM AUTHOR]

Summary. Background and Purpose: In clinically non-functional pituitary macroadenomas, prospective follow-up magnetic resonance imaging (MRI) was conducted after transsphenoidal surgery both to study the changes of the sellar contents at the post-operative site over time and to assess the amount of residual adenoma tissue. Methods: A total of 50 patients with clinically non-functional pituitary macroadenomas were treated by transsphenoidal tumour resection and were examined by MRI before and directly after surgery (early MR) and 3 months (intermediate MR) and 1 year after surgery (late MR). Changes in the sellar contents over time and the degree of tumour excision were studied on T1-weighted enhanced and unenhanced scans. All patients underwent complete neuro-ophthalmological and endocrinological assessments before and 3 months after surgery. For the interpretation of the post-operative images the results of the endocrinological examinations after surgery were also taken into account. Results: The maximum size of tumour extension on coronal T1-weighted images ranged from 1.2 cm to 5.0 cm (mean 2.3 cm). Despite tumour resection, early post-operative images still showed a persistent mass in the sella in 83% that was usually caused by post-operative haemorrhage, fluid collection and implanted fat material. However, rapid improvement in visual symptoms was noted in 89%. Changes in the sellar region at the early post-operative site markedly hindered the interpretation of MR images for detecting residual tumour tissue, which was suspected in half of the patients (1 intrasellar, 13 suprasellar, and 11 parasellar). Regression of the post-operative mass in the sella was present 3 months after surgery, resulting in a 50% change in the volume of the coronal sellar extension, which also improved the reliability in interpreting the post-operative MR images. On the intermediate MR images residual tumour tissue was detected in 30% of the patients (4 intrasellar, 2 suprasellar and 9 parasellar). Because the suprasellar mass descended over time, an increasing rate of tumour remnant within the sella was seen 3 months following surgery. Before surgery the pituitary gland was visible superiorly or posterosuperiorly to the macroadenomas in 35 patients. However, at the early post-operative site the remaining gland was only visible in 12 patients. Under the condition that endocrinological function tests confirmed adequate hormonal function, the remaining gland was detectable by MRI in 36 patients 3 months after surgery. Conclusion: Delayed regression of the sellar contents after transsphenoidal surgery of pituitary macroadenomas was demonstrated by this prospective MR study. Owing to the changes at the post-operative site, it was difficult to interpret early post-operative images and detect residual adenoma tissue. With respect to the delayed regression of the sellar contents, the interpretation of post-operative images for detection of residual adenoma was improved 3 months after surgery. At this time, residual adenoma tissue was found in 30% of clinically non-functional macroadenomas, mostly at the parasellar and, after descent from the suprasellar space, at the intrasellar site. [ABSTRACT FROM AUTHOR]

Summary. p21/WAF1 blocks cell cycle progression through inhibition of cyclin/cyclin-dependent kinases (cdks) complexes and, simultaneously, has been associated with cell cycle exit and the process of differentiation. In this series, the expression of p21/WAF1 was assessed immunohistochemically in 47 cases of pituitary adenomas in relation to endocrine activity and cell proliferation. To evaluate cell proliferation, a monoclonal antibody, MIB-1, against Ki-67 antigen was used in all of the available cases. The study revealed positive p21/WAF1 staining in 24 cases of 26 functioning parenchymas, whereas 14 cases of 21 non-functioning parenchymas stained negative. The MIB-1 index ranged from less than 1% to 5.1% (mean: less than 1.7%) in functioning adenomas, and from less than 1% to 3.6% (mean: less than 1.6%) in non-functioning adenomas. Regardless of endocrine activity, p21/WAF1 positivity did not correlate with the MIB-1 index. Double staining techniques revealed the co-expression of p21/WAF1/GH or p21/WAF1/PRL in functioning adenomas. In 22 cases of p21/WAF1-positive functioning adenomas, p21/WAF1 immunoreactivity was seen in the cytoplasma as well as nuclei. These results indicate that in pituitary adenomas, p21/WAF1 expression is associated with endocrine activity, but not with cell proliferation. Taken together with recent findings demonstrating that cytoplasmic p21/WAF1 acts as an inhibitor of apoptosis, it is possible that pituitary adenomas expressing cytoplasmic p21/WAF1 have resistance against DNA-damaging agents such as ionizing radiation. [ABSTRACT FROM AUTHOR]

Pituitary gland is an uncommon site of a primary cancer. Of more than 600 cases of pituitary tumors seen at the KFSH&RC between 1975 to 1998 only 3 patients had primary pituitary cancer. We have previously reported a case of pituitary fibrosarcoma arising as a rare complication of external radiotherapy (ERT) for GH-secreting pituitary adenoma (PA) [1]. We report now 2 cases of ACTH-producing primary pituitary carcinoma (ACTH-PPC); their follow-up data provide information on the natural history of this cancer. Patient #1; a 46 year old lady with Cushing's disease (CD) presented with an enlarged right cervical lymph node (LN) 2 years after having undergone a partial hypophysectomy through transsphenoidal surgery (PHYPX/TSS) and ERT for an invasive pituitary tumor. Patient #2; a 26 year old man presented with CD and underwent bilateral adrenalectomy (ADx) and pituitary ERT. Thirty-nine months later he developed Nelson's syndrome and a PHYPX/TSS was performed. Incidentally discovered hepatic metastases in this patient and an excisional biopsy of the LN in patient #1 showed histological features very similar to the pituitary tumor, and they stained strongly positive for ACTH. Perinuclear spherical hyalinized cytoplasmic inclusions were seen in the LN biopsy that corresponded to bundles of type 1 microfilaments (specific for pituitary ACTH-producing cells) seen by electron microscopy. A whole body 18-Fluoro-2-Deoxy-D-Glucose positron emission (FDG-PET) scanning, showed an intense uptake in the neck mass. A trial of octreotide did not change the exceedingly high levels of ACTH in patient #2, further supporting the diagnosis of ACTH-PPC. The clinical course of 102 months prior to his demise showed continued progression of the primary and the metastatic tumor. Patient #1, is alive at 15 months follow-up; hypercortisolemia is controlled using ketoconazole. ACTH-PPC should be entertained in a patient with CD presenting with persistent cervical lymphadenopathy. The clinical course in our patients suggests that the emergence of PC may involve a proliferative continuum from a pre-existing PA to an invasive tumor, culminating in a carcinoma. Adjunctive events such as ERT/ADx may predispose to the evolution of PC in genetically susceptible individuals. Because ERT is an effective treatment for PA its use will continue; it is important to be aware of the possible complication of primary pituitary carcinoma. [ABSTRACT FROM AUTHOR]

The purpose of the study is to evaluate the positive predictive value of the combined pituitary dynamic enhanced MRI (dMRI) and high-dose dexamethasone suppression tests (HDDST) in the diagnosis of Cushing's disease (CD) bypassing bilateral inferior petrosal sinus sampling (BIPSS). A total of 118 patients with Cushing's syndrome (CS), who underwent pituitary dMRI, HDDST and BIPSS were included. Positive predictive value of pituitary dMRI, HDDST, BIPSS and the combined test were calculated and tumor lateralization accuracy was further analyzed. The positive predictive value of the combined pituitary dMRI and HDDST was 98.6%, higher than that of BIPSS. There were 96.8% of patients, who had either negative findings in pituitary dMRI or HDDST, showing centralizing BIPSS results. For tumor lateralization, the accuracy by pituitary dMRI was 88.6%, whereas BIPSS was 57.5%. Therefore, CS patients with both positive findings in pituitary dMRI and HDDST need no further invasive evaluation to establish the definite diagnosis of CD. BIPSS will improve the diagnostic accuracy when negative findings were found in either pituitary dMRI or HDDST. [ABSTRACT FROM AUTHOR]

Background: Atypical pituitary adenoma has a high rate of recurrence and most of them need further treatment after surgery. This is why early detection is very important. Methods: In this study we examined the incidence and outcome of large atypical pituitary adenoma in our patient cohort. The study was a retrospective review of fifty consecutive patients at Assiut university hospital. They all had a large adenoma with supracellar and parasellar extension. They were considered unsuitable for transphenoidal approach. They all had craniotomy. This study was carried out during a thirty eight month period. Pathology reports were reviewed. All patients had MIB-1 immunohistochemical data. Patients with lesions showing excessive MIB-1immunoreactivity and mitotic features had p53 immunohistochemical data. Results: Ten (20%) of our patients had lesions that met all the criteria for atypical adenoma. Conclusion: Atypical pituitary adenoma tend to be aggressive and invasive macroadenomas. Following surgery, further treatment such as radiotherapy should be considered. [ABSTRACT FROM AUTHOR]

Background: Non-functioning pituitary adenomas have been treated by gross total resection with the microscopic transsphenoidal approach being the standard for decades. Recently, the endoscope has been utilized as alternative with its possible advantages and disadvantages. Methods: In this study, the authors retrospectively reviewed 58 cases who underwent transsphenoidal non-functioning pituitary adenomas resection, 25 via the microscopic approach (group 1) and 33 via the endoscopic approach (group 2). Different aspects of the procedures were compared, including duration of surgery, incidence of post-operative cerebrospinal fluid leak (being one of the common complications after such procedures), length of hospital stay postoperatively, and most importantly the tumor volume reduction being measured in a novel method by creating a computer-generated three-dimensional reconstruction of the tumor. Results: The length of hospital stay for group 1 ranged from 2 to 9 days (mean 3.6 days, SD 2.141) while in group 2, it ranged from 2 to 7 days (mean 3.727 days, SD 1.008). Operative time mean was 92.7 min in group 1 and 142.79 min in group 2. Intraoperative CSF leak was encountered in 40% (n = 10) of the cases in group 1 and in five cases (15.2%) from group 2. Volume reduction percentage had a mean of 82.4% in group 1 and 89.1% in group 2. Although the mean of volume reduction percentage was higher in group 2, yet this difference was found to be statistically insignificant with a p value of 0.141. Conclusion: Endoscopic approach showed superiority by having lower incidence of post-operative cerebrospinal fluid leak, length of hospital stay, and tumor volume reduction while the microscopic approach was only favored in having shorter mean duration of surgery. [ABSTRACT FROM AUTHOR]

A biography of Alfred Fuchs, a neurologist and psychiatrist, is presented. He was born on August 2, 1870, in Karolinenthal, outside of Prague, Czech Republic and studied at the Universities of Prague and Vienna, graduated from the later. During his tenure, his accomplishments include on the study of cerebrospinal fluid (CSF), the exact measurement of pupil size, and the diagnosis of pituitary tumors. Fuchs suffered a prolonged illness with calmness and died on October 5, 1927 in Vienna.

Presents continuing medical education questions related to the field of pediatric radiology. Central precocious puberty; Pituitary adenomas; Opticohypothalamic gliomas; Magnetization transfer ratio of the pediatric pituitary gland.

The article discusses several studies such as on metabolism, understanding the regulation of glucose in Drosophila melanogaster, on the mutations within sporadic pituitary adenoma, and on bone homeostasis and metastases.