The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential.

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications.

Comprehensive transcriptomic analysis identifies three distinct subtypes of pituitary adenomas: insights into tumor behavior, prognosis, and stem cell characteristics.

BACKGROUND: Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features. METHODS: We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs). RESULTS: Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK-STAT signaling pathway and the PI3K-Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K-Akt signaling pathway and Ras signaling pathway. CONCLUSION: Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.

Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

The diverging role of O-GlcNAc transferase in corticotroph and somatotroph adenomas.

PURPOSE: Molecular mechanisms involved in the pathogenesis and tumor progression of pituitary adenomas (PA) remain incompletely understood. Corticotroph and somatotroph PA are associated with a high clinical burden, and despite improved surgical outcomes and medical treatment options, they sometimes require multiple surgeries and radiation. Preliminary data suggested a role for O-GlcNAc Transferase (OGT), the enzyme responsible for the O-GlcNAcylation of proteins. O-GlcNAcylation and OGT have been found elevated in other types of tumors. METHODS: We evaluated 60 functioning and nonfunctioning PA (NFPA) from operated patients and postmortem normal and tumoral pituitary tissue by immunohistochemistry. We performed transcriptomic analyses to explore the relevance of the O-GlcNAc Transferase (OGT) in PAs. We detected OGT in immunobiological analysis and define its level in PA tissue in patients. RESULTS: OGT was strongly associated with PA hormone secretory capacity in functioning PA and with tumor growth in NFPAs. In NFPAs, OGT was positively associated with tumor size but not with cavernous sinus invasion (Knosp grading). In GH-secreting PA, OGT expression was negatively correlated with circulating Insulin-like Growth Factor 1 level. In adrenocorticotropic hormone (ACTH)-secreting PA, OGT expression was positively associated with circulating ACTH levels. OGT did not correlate with tumor size in secreting PAs. OGT levels were higher in gonadotroph PA compared to normal glands. CONCLUSION: O-GlcNAcylation can be downregulated in non-cancerous tumors such as GH-secreting adenomas. Future studies are warranted to elucidate the role of OGT in the pathogenesis of PAs.

Clinicopathological analysis of non-functioning pituitary adenomas (PAs) according to the 2022 WHO classification.

PURPOSE: For asymptomatic non-functioning pituitary adenomas (NFPAs), conservative approaches such as observation are preferred. However, some NFPAs exhibit poor prognoses. Thus, the purpose of this study was to investigate clinicopathological characteristics of tumors for identifying those with unfavorable prognoses. METHODS: A total of 125 patients with NFPAs who underwent surgery between November 2017 and December 2022 at our institution were retrospectively analyzed. Clinical, radiological, and pathological data, including hormone profiles, tumor size, presence of cavernous sinus invasion, and Ki-67 index levels, were reviewed. High-risk PAs were identified according to 2022 WHO criteria. Statistical analyses including Kaplan-Meier survival analysis and Cox regression were performed to evaluate factors associated with tumor progression or recurrence. RESULTS: A high-risk group demonstrated a significantly higher rate of tumor progression/recurrence than a low-risk group (p-value = 0.004). In multivariate analysis, the high-risk group at the time of diagnosis remained as an independent prognostic factor for NFPAs (p-value = 0.0148). The high-risk group also had a higher percentage of younger patients (80.0% in the high-risk group vs. 62.2% in the low-risk group, p-value = 0.016) and female patients (91.4% vs. 34.4%, p< 0.001). The presence of cavernous sinus invasion and higher Ki-67 index levels were more commonly observed in the high-risk group, although these factors did not significantly impact the overall prognosis. CONCLUSION: Our findings indicate that patients with high-risk NFPAs have a more aggressive disease course and a higher rate of progression or recurrence. This high-risk group has higher prevalence of younger and female patients. They may benefit from closer monitoring and possibly more aggressive treatment approaches.

"Intrasellar tumor-to-tumor metastasis: A single center experience with a systematic review".

PURPOSE: This study investigates the rare occurrence of tumor-to-tumor metastasis in Pituitary Neuroendocrine Tumors (PitNETs), also known as pituitary adenomas, aiming to enhance understanding of its diagnostic and therapeutic challenges. We report two cases from our institution of tumor-to-tumor metastasis involving PitNETs, followed by a systematic literature review. METHODS: We conducted a comprehensive literature review using PubMed and Google Scholar databases. This review provides insights into patient demographics, clinical presentations, primary tumor origin, management approaches and outcomes. RESULTS: We identified 38 documented cases of tumor-to-tumor metastasis involving the pituitary gland in the literature. This revealed a diverse range of primary tumor origins, with lung, breast, and renal carcinomas being the most prevalent. Clinical presentations varied, with visual disturbances emerging as the most frequently reported symptom. Surgical interventions predominantly resulted in subtotal resection. Kaplan-Meier survival analysis demonstrated that endoscopic endonasal approaches (EEA) are associated with longer median survival times compared to other surgical methods. CONCLUSION: Tumor-to-tumor metastasis to PitNETs must be considered in differential diagnoses of sellar masses. Prompt and accurate diagnosis, coupled with a multidisciplinary treatment strategy, is essential. Our study contributes to the scarce literature on such metastases, providing a foundation for further understanding of this complex pathological entity.

Endoscopic transcavernous approach for functional pituitary adenomas.

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.

Clinical presentation and surgical outcomes of very large and giant pituitary adenomas: 80 cases in a cohort study of 306 patients with pituitary adenomas.

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.

Intraoperative prevention of nasal mucosal injury and surgical field contamination during single-nostril transnasal endoscopic pituitary adenomas resection.

BACKGROUND: The common complications of transnasal endoscopic pituitary adenomas resection include nasal hemorrhage, olfactory disorder, nasal adhesion, and intracranial infection. Consequently, the protection of nasal mucosa and the prevention of surgical field contamination are critical. METHOD: We presented a step-by-step description of the methods of the disinfection and protection of nasal mucosa and the prevention of surgical field contamination during transnasal endoscopic pituitary adenomas resection, and these comprehensive measures to prevent these complications have not been documented. CONCLUSION: These measures effectively reduce the risk of nasal mucosal injury and surgical field contamination, and are easy to perform.

Pre-and post-surgical non-functional pituitary adenomas and their relationship with high levels of serum glucose.

OBJECTIVES: This clinical, analytical, retro-prospective, auto-controlled, not randomized, and not blinded study, aimed to investigate the association of changes in the serum glucose levels with the pre-and-post changes in the size tumor in mm3 in the Non-Functional pituitary adenomas. METHODS: Pre-and post-surgical MRI, as well as the measurements in the serum glucose levels and immunohistochemical techniques were performed in all the patients in the study, with a mean followed-up until 208.57 days. A comparison was made between the reductions in tumor size of hormonally active pituitary adenomas (HSPAs) vs NFPAs. RESULTS: Seventy-four patients were included in this study, of whom, 46 were NFPAs. The decrease in the NFPAs tumor size after surgery was statistically significant (P ≤ 0.0001). The Mean of the differences of both type of tumors in mm3 were -9552 ± 10287. Pre-surgery, the mean of the HSPAs were 8.923 ± 2.078; and the NFPAs were 14.161 ± 1.912. The differences in the tumor size were statistically significant (p = 0.039). Post-surgical, the mean of the HSPAs were 2.079 ± 971, with a (p = 0.14): and the NFPAs were 4.609 ± 1.205. After surgery of the NFPAs, most of the patients-maintained serum levels ≤ 100 mg/dL, with a statistical significance (P ≤ 0.0003). CONCLUSION: This study demonstrates for the first time the correlation between the presence of pre-and post- surgical changes in the NFPAs, with modifications in the levels of serum glucose, and the comparison, pre- and post-surgical between the tumor size of HSPAs and NFPAs.

Fatigue, sleep and physical activity in postoperative patients with pituitary adenomas: A survey.

BACKGROUND: The condition and correlation of fatigue, sleep and physical activity in postoperative patients with pituitary adenomas remain unclear. This survey aimed to evaluate the current status and influencing factors of fatigue, sleep and physical activity in postoperative patients with pituitary adenomas. METHODS: Patients undergoing pituitary adenoma resection in two tertiary hospitals from November 2019 to November 2021 were included. The general data questionnaire, Multidimensional Fatigue Inventory (MFI-20), Pittsburgh Sleep Quality Index (PSQI) and international physical activity questionnaire were used for data analysis. RESULTS: In total, 184 patients with pituitary adenomas were included. The postoperative patients with pituitary adenomas had a high level of fatigue. In total, 34 (18.5%) patients had low level of physical activity, 76(41.3%) patients had medium level of physical activity and 74 (40.2%) had high level of physical activity. Postoperative time, PSQI, physical activity level and gender were the influencing factors of fatigue in patients with pituitary adenomas (all P < 0.05). CONCLUSIONS: Postoperative patients with pituitary adenomas have a higher level of fatigue, and it is related to reduced sleep quality and activity. Relevant nursing measures should be taken according to the influencing factors of fatigue to reduce the fatigue of postoperative patients with pituitary adenomas.

Expression of cAMP and oxidative phosphorylation-related lncRNAs in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are benign lesions in the pituitary gland with important morbidities. In this study, based on a bioinformatics analysis to identify the genes and pathways that display significant differences between tumour tissues of NFPA patients and normal pituitary tissues, we selected lncRNAs related to cAMP and oxidative phosphorylation pathways, namely DNAH17-AS1, LINC00706 and SLC25A5-AS1. Then, we aimed to investigate by means of RT-qPCR, the expression of these lncRNAs along with two other lncRNAs, namely CADM3-AS1 and MIR7-3HG in NFPA samples compared to that in healthy tissues adjacent to the tumours. Transcripts of DNAH17-AS1, LINC00706 and MIR7-3HG were lower in NFPA samples compared with controls (Expression ratios (95% CI) = 0.43 (0.23-0.78), 0.58 (0.35-0.96) and 0.58 (0.35-0.96); p-values = 0.009, 0.025 and 0.036, respectively). AUC values of ROC curves of DNAH17-AS1, LINC00706 and MIR7-3HG were 0.62, 0.61 and 0.62, respectively. Expression of CADM3-AS1 was associated with the gender of patients in a way that it was lower in female patients (p-value = 0.04). The level of SLC25A5-AS1 was lower in subjects with disease duration lower than 1 year (p-value = 0.048). We showed dysregulation of three lncRNAs in NFPA tissues and potentiates these lncRNAs as important regulators of pathogenic events in these tumours.

Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

OBJECTIVE: The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. DESIGN AND PATIENTS: Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. MEASUREMENTS: Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. RESULTS: The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. CONCLUSION: Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.

Characteristics and response cutoff of octreotide suppression test in thyrotrophin (TSH)-secreting pituitary adenomas.

CONTEXT: Somatostatin analogs are recommended for preoperative therapy in thyrotrophin secreting pituitary adenomas (TSHomas). Octreotide suppression test (OST) was designed to differentiate TSHomas with resistance to thyroid hormones, while its ability to test the sensitivity of SSA has not been fully studied. OBJECTIVE: To test the sensitivity of SSA in TSHomas with OST. PATIENTS: We collected 48 pathologically confirmed TSHoma patients with complete 72 h' data of OST into analysis. INTERVENTION: Octreotide suppression test. MAIN OUTCOME: Sensitivity timepoint and cutoff of OST. RESULTS: During the entire OST, the TSH descended maximally 89.07% (73.85%, 96.77%), while the FT3 and FT4 declined slowly [43.40% (37.80%, 54.44%) and 26.59% (19.01%, 33.13%), respectively]. The 24th hour was the timepoint wherein the stability occurs for TSH, and the 48th hour for FT3 and FT4 during OST. In the patients who received both short- and long-acting somatostatin analogs (SSA), the 24-h timepoint was the most predictive timepoint for the percentage of TSH decline (Spearman's rank correlation analysis, r = .571, p < .001), while the 72-h timepoint was optimal for predicting the magnitude of TSH decline (Spearman's rank correlation analysis, r = .438, p = .005). In the 24th timepoint, a positive correlation was also observed between TSH suppression rate and the percentage decrease and absolute value decrease of FT3 and FT4. Furthermore, in patients treated with long-acting SSA, the 72-h timepoint was optimal for predicting both the percentage (Spearman's rank correlation analysis, r = .587, p = .01) and magnitude (Spearman's rank correlation analysis, r = .474, p = .047) of TSH decline. The 24th hour was the optimal timepoint with 44.54% (50% of median value of TSH in 72-hOST) decrease of TSH being the observing cutoff. The adverse effect of OST was predominantly occurred in the gastrointestinal system and no severe event occurred during OST. Paradoxical response could occur in OST and it did not influence the effect of SSA as long as sensitivity was confirmed. A high level of hormonal control was achieved in the SSA-sensitive patients. CONCLUSION: OST can be used as an efficient tool to guide the adequate use of SSA.

Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.

PURPOSE: Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). METHODS: In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. RESULTS: We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. CONCLUSION: In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.

High-resolution contrast-enhanced MRI with three-dimensional fast spin echo improved the diagnostic performance for identifying pituitary microadenomas in Cushing's syndrome.

OBJECTIVES: To assess the diagnostic performance of high-resolution contrast-enhanced MRI (hrMRI) with three-dimensional (3D) fast spin echo (FSE) sequence by comparison with conventional contrast-enhanced MRI (cMRI) and dynamic contrast-enhanced MRI (dMRI) with 2D FSE sequence for identifying pituitary microadenomas. METHODS: This single-institutional retrospective study included 69 consecutive patients with Cushing's syndrome who underwent preoperative pituitary MRI, including cMRI, dMRI, and hrMRI, between January 2016 to December 2020. Reference standards were established by using all available imaging, clinical, surgical, and pathological resources. The diagnostic performance of cMRI, dMRI, and hrMRI for identifying pituitary microadenomas was independently evaluated by two experienced neuroradiologists. The area under the receiver operating characteristics curves (AUCs) were compared between protocols for each reader by using the DeLong test to assess the diagnostic performance for identifying pituitary microadenomas. The inter-observer agreement was assessed by using the κ analysis. RESULTS: The diagnostic performance of hrMRI (AUC, 0.95-0.97) was higher than cMRI (AUC, 0.74-0.75; p ≤ .002) and dMRI (AUC, 0.59-0.68; p ≤ .001) for identifying pituitary microadenomas. The sensitivity and specificity of hrMRI were 90-93% and 100%, respectively. There were 78% (18/23) to 82% (14/17) of the patients, who were misdiagnosed on cMRI and dMRI and correctly diagnosed on hrMRI. The inter-observer agreement for identifying pituitary microadenomas was moderate on cMRI (κ = 0.50), moderate on dMRI (κ = 0.57), and almost perfect on hrMRI (κ = 0.91), respectively. CONCLUSIONS: The hrMRI showed higher diagnostic performance than cMRI and dMRI for identifying pituitary microadenomas in patients with Cushing's syndrome. KEY POINTS: • The diagnostic performance of hrMRI was higher than cMRI and dMRI for identifying pituitary microadenomas in Cushing's syndrome. • About 80% of patients, who were misdiagnosed on cMRI and dMRI, were correctly diagnosed on hrMRI. • The inter-observer agreement for identifying pituitary microadenomas was almost perfect on hrMRI.

Dopamine agonists for the treatment of pituitary tumours: From ergot extracts to next generation therapies.

Dopamine agonists are a key tool in the therapeutic arsenal of endocrinologists worldwide. They exert their effects by binding to dopamine-2 (D2) receptors expressed by pituitary tumour cells to modulate hormonal secretion and tumour size. They are the established first-line treatment for prolactinomas which express high levels of D2 receptors. Growing data support their use as an adjuvant treatment option for other pituitary tumours including growth hormone, adrenocorticotrophic hormones, thyroid hormone secreting adenomas and nonfunctional pituitary tumours, all of which have been shown to express D2 receptors as well, albeit to varying extents. For those pituitary tumours inadequately treated by dopamine agonist alone, combined agonism of D2 and somatostatin receptors represent a new frontier in clinical development. Here we review the development and role of dopamine agonist for the treatment of prolactinomas, the literature supporting their adjuvant use for the treatment of all other pituitary tumours, and recent progress in the development of the next generation of chimeric compounds that target D2 and other receptor subtypes highly expressed on pituitary tumour cells.

The effect of preoperative short-term octreotide treatment to surgery in thyrotropin-secreting pituitary adenomas: a retrospective cohort study.

BACKGROUND: To prevent thyroid storm and ensure surgical safety, it is imperative to regulate excessive thyroid hormone levels in patients with thyrotropin-secreting pituitary adenomas (TSHoma) prior to surgery. Somatostatin analogues (SSAs), such as octreotide, have showed efficacy in shrinking tumors, which may facilitate surgical resection. This retrospective study aimed to investigate the effect of shortterm preoperative octreotide treatment on the surgical outcome of TSHoma. METHODS: A total of 65 TSHoma patients from January 2010 to July 2019 were included in the study. Of these,41 patients received short-term preoperative octreotide (Sandostatin, intermittent subcutaneous injection) treatment and all patients subsequently underwent surgery. The following data were recorded: clinical manifestations, laboratory examinations, sellar region MRI, postoperative pathological and electron microscopy data, intraoperative situation, and follow-up (> 3 months) regarding hormone levels and tumor recurrence. RESULTS: There was no significant difference in the consistency and blood supply of the tumor between patients who received short-term preoperative octreotide treatment and those who did not. Additionally, preoperative short-term octreotide treatment (median of 10 days with a range of 6-18 days) did not significantly improve the rates of gross total resection (GTR) or biochemical remission. Moreover, electron microscopy revealed subcellular level impairments and cell apoptotic in the octreotide treated TSHoma specimens. CONCLUSION: Preoperative octreotide treatment for the purpose of reducing excessive thyroid hormones may not enhance surgical outcomes, and the duration of octreotide treatment needs to be extended to fully benefit from the tumor-shrinking effects of SSAs.

An update on, and genetics of refractory adenomas of childhood.

Pituitary adenomas in childhood tend to be more frequently due to germline genetic changes and are often diagnosed at late stages due to delayed recognition by pediatricians and other caretakers who are not familiar with this rare disease in childhood. As a result, often, pediatric pituitary adenomas are aggressive or remain refractory to treatment. In this review, we discuss germline genetic defects that account for the most common pediatric pituitary adenomas that are refractory to treatment. We also discuss some somatic genetic events, such as chromosomal copy number changes that characterize some of the most aggressive pituitary adenomas in childhood that end up being refractory to treatment.