Search Results (16)

When non-functioning pituitary adenomas (NFPAs) behave aggressively or recur after first-line surgical treatment, it can be challenging to decide whether and how to escalate therapy. Up to 47% of patients with residual tumor after transsphenoidal surgery will show disease recurrence or progression and may require an intervention. Repeat surgical resection can be attempted in select cases if the tumor is accessible; for the remainder of patients, non-surgical treatment options may need to be considered. Radiotherapy can control tumor growth in 75% of NFPAs, but confers increased risk of hypopituitarism and other disorders. Currently, there are no medical therapies approved for patients with recurrent or aggressive NFPA. However, several have been investigated, including temozolomide, somatostatin receptor ligands, dopamine agonists, immune checkpoint inhibitors, vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. We present a review of the available evidence to provide guidance for pituitary endocrinologists and neuro-oncologists when treating patients with recurrent or aggressive NFPA. Full article

The study aimed to analyze hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p expression in the serum of patients with invasive non-functioning pituitary adenomas (NFPAs) and prolactinomas, as candidates for non-invasive biomarkers. The study included 62 patients with NFPAs and 18 with macroprolactinoma who qualified for transsphenoidal surgical resection. MicroRNAs were isolated from serum samples. The expression levels of hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p were determined using TaqMan MicroRNA assays. The statistical analyses were performed with MedCalc. The total concentration of microRNA was significantly lower in NFPAs than in the CG (p = 0.0419). ROC curve analysis showed that the cutoff point of miRNA lower than 10.73 predicted the PA (sensitivity = 70.0%; specificity = 57.7%; AUC = 0.629; p = 0.052). No correlation between selected miRNAs and tumor type was found: hsa-miR-143-3p (p = 0.4610), hsa-miR-16-5p (p = 0.8767), and hsa-miR-423-5p (p = 0.1459). miRNA expression also did not correlate with invasiveness (cavernous or sphenoid sinus invasion, optic chiasm compression). Although the total expression of microRNA was significantly lower in NFPAs, hsa-miR-16-5p, hsa-miR-143-3p, and hsa-miR-423-5p are not useful as non-invasive biomarkers in patients with invasive non-functioning pituitary adenomas and prolactinomas. Full article

Background/Objectives: This prospective study evaluates the relationship between the ganglion cell–inner plexiform layer (GCIPL), retinal nerve fiber layer (RNFL), and photopic negative response (PhNR) in patients with newly diagnosed pituitary macroadenomas over 12 months. Methods: A total of 40 patients (80 eyes) were included, divided into a treatment group of 27 patients (54 eyes), receiving pharmacological and/or surgical intervention, and an observation group of 13 patients (26 eyes), with non-functional pituitary adenomas (NFPAs) that did not require treatment. Results: Key findings indicate a significant improvement in best corrected visual acuity (BCVA) after 12 months in the treatment group (p = 0.02) and a significant reduction in RNFL thickness in multiple quadrants (p < 0.01). Moreover, PhNR amplitude and W-ratio significantly increased in the treatment group (p < 0.0001). In the observation group, only GCIPL Inferior (p = 0.0470) and PhNR W-ratio (p = 0.0015) showed significant differences. Between-group comparisons showed significant differences in RNFL Nasal quadrant at baseline (p = 0.0017) and after 12 months (p = 0.0150). PhNR amplitude and W-ratio also differed significantly between groups at 12 months (p = 0.0012 and p = 0.0016, respectively). Correlations between OCT and ERG parameters were weak at baseline and diminished over time. Conclusions: These findings suggest that GCIPL, RNFL, and PhNR analyses may be useful for monitoring disease progression and guiding treatment decisions in patients with pituitary macroadenomas. Full article

Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of insomnia and sleep quality in a cohort of patients with a low risk of OSAS before and after therapies for acromegaly. A total of 27 naïve acromegalic patients (mean age 55.15 ± 10.53 years) were submitted to a psychometric sleep evaluation and compared to a matched control group of 24 Non-Functioning Pituitary micro-Adenoma patients (mean age 51.08 ± 11.02 years). A psychometric sleep evaluation was carried out 4 years later, after achieving acromegaly control in all patients. The role of different therapies for acromegaly (somatostatin analogues, pegvisomant, or adenomectomy) was evaluated. At the initial evaluation, most untreated acromegalic patients had a higher rate of impaired sleep quality and clinical insomnia than NFPA patients (p = 0.001 ES = 1.381, p = 0.001 ES = 1.654, respectively). Patients treated with somatostatin analogues or pituitary adenomectomy had an improvement in insomnia parameters (p = 0.046 ES = 0.777, p = 0.038 ES = 0.913, respectively). Conversely, in patients treated with pegvisomant, sleep quality and insomnia worsened (p = 0.028 ES = 1.002, p = 0.009 ES = 1.398, respectively). In summary, therapies for acromegaly seem to have divergent effects on perceived sleep disorders. Concerning sleep, somatostatin analogues and adenomectomy seem to have favorable effects on the psychometric parameters of sleep. Full article

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the “hook effect”), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. Full article

Background and Objectives: A magnetic resonance imaging (MRI) scan is part of the diagnostic protocol in pituitary adenoma patients. The goal of the present study is to present and analyse the MRI appearances of the sphenoid sinus (SS) in patients with non-functioning pituitary adenoma (NFPA). Materials and Methods: This is a retrospective case–control study conducted between January 2015 and December 2023 in a tertiary referral hospital. Forty NFPA patients were included in the study group, while the control group consisted of 30 age- and gender-matched cases. Results: The sellar type of SS pneumatization was the most frequently encountered pattern among both groups. The presence of the lateral recess of the SS, mucosal cysts, and sphenoethmoidal cells was similar in both patient groups. The proportion of patients with SS mucosal thickness greater than 3 mm was 42.5% in NFPA group and 3% in the control group, and this difference was statistically significant (p < 0.001). The space between the two optic nerves was significantly larger in the NFPA group as compared to the control group (p < 0.001). Conclusions: Our study was able to establish a statistically significant association between the presence of NFPA and both the thickening of the SS mucosa and increased space between optic nerves. Full article

Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing’s syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA. Full article

Post-operative endocrine outcomes in patients with non-functioning pituitary adenoma (NFPA) are variable. The aim of this study was to use machine learning (ML) models to better predict medium- and long-term post-operative hypopituitarism in patients with NFPAs. We included data from 383 patients who underwent surgery with or without radiotherapy for NFPAs, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree models, showed a superior ability to predict panhypopituitarism compared with non-parametric statistical modelling (mean accuracy: 0.89; mean AUC-ROC: 0.79), with SVM achieving the highest performance (mean accuracy: 0.94; mean AUC-ROC: 0.88). Pre-operative endocrine function was the strongest feature for predicting panhypopituitarism within 1 year post-operatively, while endocrine outcomes at 1 year post-operatively supported strong predictions of panhypopituitarism at 5 and 10 years post-operatively. Other features found to contribute to panhypopituitarism prediction were age, volume of tumour, and the use of radiotherapy. In conclusion, our study demonstrates that ML models show potential in predicting post-operative panhypopituitarism in the medium and long term in patients with NFPM. Future work will include incorporating additional, more granular data, including imaging and operative video data, across multiple centres. Full article

Background: Pituitary apoplexy (PA) can be symptomatic, namely acute apoplexy (APA), or asymptomatic or subclinical (SPA). Objective: To describe the clinical characteristics and evolution of the patients with APA compared to SPA Patients and methods: Retrospective, longitudinal database analysis. Results: We identified 58 patients with PA, and 37 accomplished the inclusion criteria (17 men, median age 47.7 years). A total of 29 (78.4%) had APA (17 underwent surgery, and 12 were conservatively managed), and 8 (21.6%) had SPA. The presence of non-functioning pituitary adenoma (NFPA) odds ratio (OR): 29.36 (95% confidence interval (CI): 1.86–462.36) and the largest size OR 1.10 (95% CI: 1.01–1.2) elevated the risk of having surgery. Hypopituitarism developed in 35.1% without significant differences between APA and SPA. In non-surgical patients, adenoma volume shrunk spontaneously at one year magnetic resonance imaging (MRI), without statistical differences between the conservatively treated and SPA group. Conclusions: APA is more frequent in larger NFPAs, and this subset of patients has a higher risk of surgery. Hypopituitarism is quite frequent even in patients with SPA, and, therefore, long-term follow-up is mandatory. In the non-surgical group, the pituitary tumour shrinkage is clinically relevant after one year of PA. Consequently, surgery indication in NFPA should be delayed and reassessed if patients remain asymptomatic. Full article

With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies. Full article

This study developed and evaluated nnU-Net models for three-dimensional semantic segmentation of pituitary adenomas (PAs) from contrast-enhanced T1 (T1ce) images, with aims to train a deep learning-based model cost-effectively and apply it to clinical practice. Methods: This study was conducted in two phases. In phase one, two models were trained with nnUNet using distinct PA datasets. Model 1 was trained with 208 PAs in total, and model 2 was trained with 109 primary nonfunctional pituitary adenomas (NFPA). In phase two, the performances of the two models were investigated according to the Dice similarity coefficient (DSC) in the leave-out test dataset. Results: Both models performed well (DSC > 0.8) for PAs with volumes > 1000 mm³, but unsatisfactorily (DSC < 0.5) for PAs < 1000 mm³. Conclusions: Both nnU-Net models showed good segmentation performance for PAs > 1000 mm³ (75% of the dataset) and limited performance for PAs < 1000 mm³ (25% of the dataset). Model 2 trained with fewer samples was more cost-effective. We propose to combine the use of model-based segmentation for PA > 1000 mm³ and manual segmentation for PA < 1000 mm³ in clinical practice at the current stage. Full article

To describe and evaluate outcomes of Gamma Knife radiosurgery (GK) for the treatment of pituitary tumors over the past twenty years, a systematic review and meta-analysis according to PRISMA statement was performed. Articles counting more than 30 patients were included. A weighted random effects models was used to calculate pooled outcome estimates. From 459 abstract reviews, 52 retrospective studies were included. Among them, 18 reported on non-functioning pituitary adenomas (NFPA), 13 on growth hormone (GH)-secreting adenomas, six on adrenocorticotropic hormone (ACTH)-secreting adenomas, four on prolactin hormone (PRL)-secreting adenomas, and 11 on craniopharyngiomas. Overall tumor control and five-year progression free survival (PFS) estimate after one GK procedure for NFPA was 93% (95% CI 89–97%) and 95% (95% CI 91–99%), respectively. In case of secreting pituitary adenomas, overall remission (cure without need for medication) estimates were 45% (95% CI 35–54%) for GH-secreting adenomas, 64% (95% CI 0.52–0.75%) for ACTH-secreting adenomas and 34% (95% CI: 19–48%) for PRL-secreting adenomas. The pooled analysis for overall tumor control and five-year PFS estimate after GK for craniopharyngioma was 74% (95% CI 67–81%) and 70% (95% CI: 64–76%), respectively. This meta-analysis confirms and quantifies safety and effectiveness of GK for pituitary tumors. Full article

Acromegaly is a rare disease caused by overproduction of growth hormone (GH) by a pituitary adenoma, and consequently increased insulin-like growth factor 1 (IGF-1) concentration. The GH/IGF-1 axis and immune cells interactions are hypothesized to be involved in subclinical inflammation. This retrospective study aimed to investigate the differences in neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) ratios, and systemic immune-inflammation index (SII) in GH-secreting adenomas compared with non-functioning pituitary adenomas (NFPAs) concerning clinical and radiological findings. After evaluation of 665 patients with pituitary tumors, 62 individuals with newly diagnosed acromegaly and 134 with NFPAs were enrolled in the analysis. The control group consisted of 120 healthy individuals. Fifty-eight patients with acromegaly were re-evaluated after medical or surgical therapies. NLR, PLR, SII values, and neutrophil count were significantly higher (p ≤ 0.001), whereas lymphocyte count was lower in acromegaly than in NFPAs (p = 0.001). No significant differences between NFPAs and controls were observed in analyzed ratios. Higher preoperative NLR, PLR, SII values were found in patients who failed to achieve a cure with surgery (p < 0.05). Although NLR, PLR, and SII values were significantly higher in acromegaly, these indices cannot be used to discriminate GH-secreting pituitary tumors from NFPAs. Treatment of acromegaly decreased the value of NLR and SII, but it requires further studies to consolidate the real clinical role of these inflammation-related ratios. Full article

Mismatch repair genes mutS homologs 6/2 (MSH6/2) expressions are involved in tumor growth and programmed cell death 1 ligand 1 (PD-L1) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated MSH6/2 and PD-L1 mRNA expressions in NFPAs by real-time PCR (n = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. MSH6/2 expressions were positively associated with PD-L1 expression. PD-L1 expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although MSH6/2 expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed PD-L1 equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased PD-L1 expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in MSH6/2 and PD-L1 expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness. Full article

Gonadotroph nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors, but the role of aberrant epigenetic regulation in their development remains poorly understood. In this study, we investigated the effect of impaired CpG methylation in NFPAs. We determined DNA methylation and transcriptomic profiles in 32 NFPAs and normal pituitary sections using methylation arrays and sequencing, respectively. Ten percent of differentially methylated CpGs were correlated with gene expression, and the affected genes are involved in a variety of tumorigenesis-related pathways. Different proportions of gene body and promoter region localization were observed in CpGs with negative and positive correlations between methylation and gene expression, and different proportions of CpGs were located in ‘open sea’ and ‘shelf/shore’ regions. The expression of ~8% of genes differentially expressed in NFPAs was related to aberrant methylation. Methylation levels of seven CpGs located in the regulatory regions of FAM163A, HIF3A and PRSS8 were determined by pyrosequencing, and gene expression was measured by qRT-PCR and immunohistochemistry in 83 independent NFPAs. The results clearly confirmed the negative correlation between methylation and gene expression for these genes. By identifying which aberrantly methylated CpGs affect gene expression in gonadotrophinomas, our data confirm the role of aberrant methylation in pathogenesis of gonadotroph NFPAs. Full article