Asian-specific 3'UTR variant in CDKN2B associated with risk of pituitary adenoma.

BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.

Case report: A rare case of thyrotropin-secreting pituitary macroadenoma with diffuse calcification presenting with hyperthyroidism and literature review.

Background: Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHomas) are rare and usually present with hyperthyroidism. Calcification in pituitary tumors is an infrequent finding. Herein, we report an extremely rare case of TSHoma with diffuse calcification. Case description: A 43-year-old man was admitted to our department with a complaint of palpitations. An endocrinological examination revealed elevated serum levels of TSH, free triiodothyronine (FT3), and free thyroxin, whereas the physical examination revealed no obvious abnormality. Computerized tomography (CT) showed a sellar mass with diffuse calcification. Contrast-enhanced T1-weighted images revealed a less-enhancing tumor without obvious suprasellar or parasellar expansion. The tumor was completely removed via endoscopic transnasal-sphenoidal surgery. Microscopically, nests of cells were inconspicuous among the diffuse psammoma bodies. Expression of TSH was patchy, and only several TSH-positive cells were observed. Postoperatively, the serum levels of TSH, FT3, and FT4 decreased to their normal range. Follow-up MR images showed no evidence of residual tumor or regrowth after the resection. Conclusions: Herein, we report a rare case of TSHoma with diffuse calcification that presented with hyperthyroidism. A correct and early diagnosis was made according to the European Thyroid Association guidelines. This tumor was completely removed via endoscopic transnasal-transsphenoidal surgery (eTSS), and thyroid function was normalized after the operation.

Pituitary stalk changes on magnetic resonance imaging following pituitary adenoma resection using a transsphenoidal approach.

Objective: We aimed to investigate the magnetic resonance imaging (MRI) findings and clinical significance of position and changes in morphology of the pituitary stalk following pituitary adenoma (PA) resection using a transsphenoidal approach. Methods: We collected clinical and MRI data of 108 patients with PA after transsphenoidal surgery. Diameter, length, and coronal deviation of the pituitary stalk were measured pre-, post-, and mid-term post-operatively, to observe pituitary stalk morphology. Results: Of 108 patients, 53 pituitary stalks were recognisable pre-operatively. The angle between the pituitary stalk and the median line was 7.22°-50.20° (average, 25.85°) in 22 patients with left-sided pituitary stalks and 5.32°-64.05° (average, 21.63°) in 20 patients with right-sided pituitary stalks. Of 42 patients with preoperative pituitary stalk deviation, 41 had an early postoperative recovery and 1 had increased deviation. In the mid-term postoperative period, 21 of 42 patients had pituitary stalks located centrally. In 53 patients, the pituitary stalk length was 1.41-11.74 mm (mean, 6.12 mm) pre-operatively, 3.61-11.63 mm (mean, 6.93 mm) in the early postoperative period, and 5.37-17.57 mm (mean, 8.83 mm) in the mid-term postoperative period. In the early postoperative period, 58 (53.70%) patients had posterior pituitary bright spots (PPBS) and 28 (25.92%) had diabetes insipidus (DI). Conclusion: Pre-operatively, the pituitary stalk was compressed and thinned. Post-operatively, it could be stretched to a "normal state", and its position showed a gradual centring trend. Post-operatively, the length of the pituitary stalk gradually increased. The PPBS in the early postoperative period negatively correlated with postoperative DI.

Prognostic indicators in pituitary adenoma surgery: a comprehensive analysis of surgical outcomes and complications.

Objective: The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success. Methods: A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis. Results: Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004). Conclusion: This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management.

Analysis of perioperative negative emotion risk factors in patients with pituitary adenoma and its impact on prognosis: a retrospective study.

Background: Pituitary adenoma (PA) is the third most common tumor in craniocerebral surgery. Most patients will experience varying degrees of negative emotions before and after surgery, which may affect the prognosis of surgery. This study analyzed the perioperative negative emotional risk factors of patients with different characteristics of PA and their impact on prognosis, so as to provide a reference for improving the prognosis of patients with PA. Methods: A total of 234 patients who underwent PA surgery in the Affiliated Hospital of Nantong University from January 2017 to January 2022 were selected as the observation population. The general characteristics of the subjects were collated using a general information questionnaire designed by the researchers. The negative emotions of the patients were evaluated using a Self-rating Anxiety Scale (SAS) and a Self-rating Depression Scale (SDS). The prognosis of patients was determined by assessing the hypophyseal hormone levels. Multiple regression analysis and logistic regression were used to analyze the risk factors of perioperative negative emotions and the effects of negative emotions on patient prognosis. Results: Multiple regression analysis showed that with and without children, education, income, PA type, PA size, and surgical approach were independent factors influencing negative emotions in patients after PA surgery (P<0.05). Logistic regression analysis showed that negative emotion was an independent prognostic factor (P<0.05). Conclusions: There are many factors that affect the anxiety and depression of patients after PA surgery. The family members and medical staff of the patients should take effective measures to relieve the anxiety and depression of the patients so as to improve the prognosis of patients according to the influencing factors.

Coexistence of Pituitary Adenoma and Primary Pituitary Lymphoma: A Case Report and Review of the Literature.

In the pituitary sella, the coexistence of pituitary adenoma and primary pituitary lymphoma is exceedingly rare. Thus far, only six cases have been reported. Here, we present the seventh case of coexisting pituitary adenoma and primary pituitary lymphoma, which was difficult to differentiate from other sellar tumors. To our knowledge, this is the first case of the prolactin subtype of the pituitary adenoma in literature. We have also systematically reviewed the literature and summarized the characteristics of coexisting pituitary adenoma and lymphoma. We believe this report provides a new clinical reference for the diagnosis and treatment of collision tumors of pituitary adenoma and lymphoma.

Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment.

Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to be caused by elevated growth hormone (GH) levels and Cushing disease's elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.

Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks.

Objective: Despite advancements of intraoperative visualization, the difficulty to visually distinguish adenoma from adjacent pituitary gland due to textural similarities may lead to incomplete adenoma resection or impairment of pituitary function. The aim of this study was to investigate optical coherence tomography (OCT) imaging in combination with a convolutional neural network (CNN) for objectively identify pituitary adenoma tissue in an ex vivo setting. Methods: A prospective study was conducted to train and test a CNN algorithm to identify pituitary adenoma tissue in OCT images of adenoma and adjacent pituitary gland samples. From each sample, 500 slices of adjacent cross-sectional OCT images were used for CNN classification. Results: OCT data acquisition was feasible in 19/20 (95%) patients. The 16.000 OCT slices of 16/19 of cases were employed for creating a trained CNN algorithm (70% for training, 15% for validating the classifier). Thereafter, the classifier was tested on the paired samples of three patients (3.000 slices). The CNN correctly predicted adenoma in the 3 adenoma samples (98%, 100% and 84% respectively), and correctly predicted gland and transition zone in the 3 samples from the adjacent pituitary gland. Conclusion: Trained convolutional neural network computing has the potential for fast and objective identification of pituitary adenoma tissue in OCT images with high sensitivity ex vivo. However, further investigation with larger number of samples is required.

Dysregulated miR-137 and its target EGFR contribute to the progression of pituitary adenomas.

Pituitary adenomas (PAs) hypersecrete hormones or cause mass effect symptoms, with 10%-35% patients showing resistance to standard therapies. Targeting epidermal growth factor receptor (EGFR) has significantly improved the clinical outcome in many cancers. In this study, immunochemistry results showed that EGFR associated H-scores in 116 PA samples were higher than those in pituitary glands, and that p21, p27-and Wif-1 associated H-scores were lower (P < 0.05 for all). Patients with high levels of EGFR had increased PA invasion, lower total resection, and lower p21 and p27 expression than those with low levels of EGFR expression. Dual-luciferase reporter gene assays showed that EGFR was the target gene of miR-137, and miR-137 mimic could inhibit the cell proliferation of GH3 cells and induce apoptosis and G1-phase arrest of GH3 cells. A combination of miR-137 mimic and AZD9291 had stronger inhibition on GH3 cells compared with miR-137 mimic or AZD9291 alone; furthermore, miR-137 inhibitor partially reversed the inhibition of AZD9291. p21 and p27 were shown to be involved in the miR-137- and AZD9291-mediated effects on GH3 cells. In all, activation of EGFR in PAs was related to tumor invasive behavior, which reduced the total resection of PAs in patients. A combination of miR-137 and AZD9291 provided a potential treatment for PAs, especially for patients who show resistance to standard treatment.

The fatigue, sleep and physical activity in postoperative patients with pituitary adenoma: what we can do.

BACKGROUND: To evaluate the current status of fatigue, sleep and physical activity in postoperative patients with pituitary adenoma (PA). METHODS: Postoperative patients undergoing PA resection from November 2017 to November 2018 were identified. A multi-centered survey was conducted with questionnaires on the characteristics of included PA patients, multidimensional fatigue inventory (MFI-20), the Pittsburgh sleep quality index (PSQI) questionnaire, and the international physical activity (IPA) questionnaire. The related scores and potentially influencing factors were analyzed accordingly. RESULTS: A total of 184 patients were included. The time course after operation, PSQI were correlated with the scores of general fatigue, physical fatigue, reduced activity and reduced motivation (all P<0.05); PSQI and IPA, the time course after operation and gender were the independent factors associated with the level of general fatigue (all P<0.05); PSQI, IPA and the time course after operation, adenoma size and gender were the independent factors influencing the level of physical fatigue (all P<0.05); the time course after operation, IPA, PSQI and gender were the independent factor influencing the level of reduced activity (all P<0.05); the time course after operation, IPA, PSQI and adenoma size were the independent factor influencing the level of reduced motivation (all P<0.05); the time course after operation was the independent factor influencing the level of mental motivation (P=0.030). CONCLUSIONS: Fatigue in PA patients after surgery is inversely associated with the time course after surgery and physical activity, future studies on the related interventions are warranted.

Postoperative complications and quality of life in patients with pituitary adenoma.

BACKGROUND: Pituitary adenomas (PAs) are tumors that arise from the cells of the anterior pituitary gland. PAs are the most common tumors to occur in the sella area and the third most common intracranial neoplasm in surgery. Due to developments such as microscopy and neuroendoscopy, the curative effect of PA surgery continues to improve. However, postoperative complications may still occur. PA surgery can result in iatrogenic trauma, which is a primary cause of cerebrospinal fluid (CSF) rhinorrhea. PA surgery can affect the posterior pituitary gland, causing decreased antidiuretic hormone secretion and increased urine output, which can lead to hyponatremia. The nasal cavity and sphenoid sinuses may also be damaged during PA surgery, causing the sphenoethmoidal recess to be blocked. This increases the risk of infection. The purpose of this study was to analyze quality of life in PA patients post-resection, and to provide references for the development of early targeted risk assessment programs and intervention measures. METHODS: We selected patients who underwent neuroendoscopic transnasal PA resection at the Affiliated Hospital of Nantong University between January 2017 and October 2019. These patients' hospital records were retrospectively obtained, including details of any postoperative complications. The patients were followed up by telephone 12 weeks following discharge, and we used the EuroQol 5 Dimensions (EQ-5D) health scale to assess the patients' quality of life. RESULTS: At follow-up 3 months after discharge, 68 people (41.72%) had experienced at least one common complication, including 7 cases of infection (4.29%), 56 cases of hypopituitarism (34.36%), 18 cases of CSF rhinorrhea (11.04%), 28 cases of diabetes insipidus (17.18%), and 25 cases of hyponatremia (15.34%). Patients that experienced complications reported having more serious problems on the dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) than patients without complications. The scores of patients with complications on the EQ-5D visual analog scale (EQ-VAS) were lower than that of patients without complications. CONCLUSIONS: Postoperative complications are negatively associated with quality of life in PA patients. Actively preventing common complications could therefore improve these patients' quality of life and reduce their burden of disease.

Long-noncoding RNA IFNG-AS1 exerts oncogenic properties by interacting with epithelial splicing regulatory protein 2 (ESRP2) in pituitary adenomas.

Despite the enormous development of medical technologies in recent decades, pituitary adenoma (PA) remains among the most refractory cancers in the world. Elucidating the molecular mechanisms underlying the pathology of PA is essential to identify new treatments for PA. In the present study, we found that IFNG-AS1 expression was significantly higher in PA tissues than in nontumor tissues via qRT-PCR and RNA fluorescence in situ hybridization (FISH). shRNA-mediated IFNG-AS1 knockdown in HP75 cells significantly inhibited tumor progression, and IFNG-AS1 overexpression remarkably promoted tumor progression. Epithelial splicing regulatory protein 2 (ESRP2) was demonstrated to be a target protein of IFNG-AS1 in PA; knocking down ESRP2 reversed the tumor-inhibitory effects of IFNG-AS1 knockdown, and overexpressing ESRP2 abolished the tumor-promoting effects of IFNG-AS1 overexpression in HP75 cells. In conclusion, our findings suggested that IFNG-AS1 may function as an oncogene in PA by interacting with ESRP2.