Treatment Of Pituitary Adenomas Research Articles

6823 A Puzzling Case: Complete Regression of Pituitary Macroadenoma

Abstract Disclosure: N.T. Mazengia: None. D.R. Vangipuram: None. S.K. Majumdar: None. Introduction: The natural course of nonfunctioning pituitary macroadenomas remains poorly understood, largely because the majority are surgically treated [1]. There are a few case reports describing the spontaneous regression of nonfunctioning pituitary macroadenomas. Here we describe a case of pituitary macroadenoma which completely regressed following childbirth and two months of cabergoline therapy. Case Presentation: A 25-year-old female presented with bilateral nipple discharge and persistently elevated prolactin levels ranging from 31µg/liter to 45.9 µg/liter (NV <25 µg/L). She did not have any signs and symptoms of hypo or hypersecretion of the pituitary hormones. All her pituitary hormone levels were within normal range. Initial MRI revealed a pituitary mass measuring 9x13x9mm (AP, TR, CC). Given her lack of symptoms, the decision was made to follow up without any intervention. A repeat MRI after one year showed the size of the mass to be 11x13x11mm. Two years after her initial diagnosis, the patient had a spontaneous pregnancy, during which she remained asymptomatic with normal pituitary hormone levels. She had Cesarean delivery at term with no complication. She was lost to follow-up for about two years after childbirth then presented with breast discomfort and galactorrhea at which time, she was started on cabergoline. A subsequent MRI done two months after the start of cabergoline showed asymmetric fullness of the pituitary gland on the right with no discrete measurable lesion. Conclusion: We currently lack a comprehensive explanation for the regression observed in our patient. Silent ischemia may have played a role, particularly considering the natural increase in pituitary gland size during pregnancy. We are not sure if the regression can be solely attributed to the two months of cabergoline treatment. In asymptomatic patients diagnosed with nonfunctioning pituitary macroadenoma, tumor regression can potentially occur through either a "wait and watch" strategy or medical management using dopamine agonists, specifically cabergoline. However, the use of cabergoline as a primary treatment for asymptomatic nonfunctioning pituitary adenoma warrants further investigation. This is especially crucial given that, in most cases, nonfunctioning pituitary macroadenomas tend to increase in size during follow-up without any intervention.

Sinonasal Complications of Combined Transseptal–Transnasal and Bilateral Transnasal Approaches for Endoscopic Endonasal Transsphenoidal Pituitary Surgery

BackgroundThe endoscopic combined transseptal–transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach. MethodsUtilizing a retrospective cohort from a preeminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal–transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), Sino-Nasal Outcome Test-22 (SNOT-22), and nasal obstruction symptom evaluation (NOSE) ResultsThe transseptal–transnasal approach exhibited reduced rates of postoperative ear fullness (p < 0.001), along with fewer subjective complaints of smell/taste loss (p = 0.022) and thick nasal discharge (p = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the two approaches (p = 0.243 and p = 0.454 for CCCRC and CCSIT, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal–transnasal approach (p = 0.067). ConclusionFor the surgical treatment of pituitary adenomas, the transseptal–transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation.

Distinct clinical characteristics and prognosis of pediatric-onset growth hormone-secreting pituitary adenoma (GHPA) patients compared to adult-onset patients.

To explore the clinical characteristics, treatment, and prognosis of growth hormone-secreting pituitary adenoma (GHPA) patients with pediatric-onset, so as to facilitate clinical management. A retrospective cohort study was carried out between 102 pediatric-onset GHPA patients admitted to our hospital from January 2013 to June 2022 and 204 adult-onset GHPA patients who were randomly matched. GHPA with pediatric-onset was predominantly male, associated with higher proportion of genetic syndromes, longer course, and delayed diagnosis. Clinical symptoms of visual field defects and menstrual abnormality were more common. The pediatric-onset group exhibited higher growth hormone (GH) nadir during oral glucose tolerance test (OGTT), higher rates of hyperprolactinemia, larger maximum diameter of adenoma, and higher rates of optic chiasm compression, suprasellar invasion, and pituitary apoplexy. Hypertension, diabetes, and obstructive sleep apnea-hypopnea syndrome (OSAHS) were more common in the adult-onset group. Echocardiography results were similar between the two groups. The pediatric-onset group owned significantly higher treatment scores and proportions of multimodal therapy modality, more surgical complications, and a higher proportion of ki67 ≥ 3%. There was no significant difference in the final cure rate, but male patients with adult-onset had a worse prognosis. The recurrence rate was also similar between two groups. Hypopituitarism was more prevalent in the pediatric-onset group, while the adult-onset group had a higher incidence of other tumors. Pediatric-onset GHPA patients exhibit distinct clinical characteristics compared to adult-onset patients. Multimodal therapy modalities could help to achieve a cure rate comparable to that of adult-onset patients.

Approaches based on natural products and miRNAs in pituitary adenomas: unveiling therapeutic intervention.

Pituitary adenomas (PAs) are tumors originating in the pituitary gland, a small gland located at the base of the brain. They are the most common type of pituitary tumor, affecting approximately 1 in 10 people over their lifetime. Common symptoms include headaches, vision problems, hormonal imbalances, and weight changes. Treatment options depend on the type and size of the adenoma and may consist of medication, surgery, radiation therapy, or a combination. PAs are typically benign and slow-growing, but they can cause significant health issues if left untreated. Proper diagnosis and management by an experienced multidisciplinary team is important for achieving the best outcomes. Natural compounds like celastrol, curcumin, quercetin, apigenin, resveratrol, epigallocatechin gallate (EGCG), and genistein have shown the ability to inhibit cell growth, promote cell death, and suppress hormone activity in pituitary tumor cells, suggesting their potential as alternative or complementary treatments for PAs. MicroRNAs (miRNAs) are a kind of tiny RNA molecules that do not code for proteins and have a vital function in controlling gene expression. These 21-23 nucleotide-long molecules regulate gene expression by binding to complementary sequences in mRNA molecules, leading to mRNA degradation. miRNAs participate in a wide range of biological activities, including apoptosis, metastasis, differentiation, and proliferation. The research indicates that miRNAs play a crucial role in the pathogenesis, therapeutic approaches, diagnosis, and prognosis of PAs. This review article will provide a comprehensive analysis of the current understanding of the efficacy of naturally derived anti-cancer agents in the treatment of PAs. Furthermore, the study provides a comprehensive assessment of the miRNAs in PAs, their role in the development of PAs, and their potential application in the treatment of the condition.

Exosomal AFAP1-AS1 Promotes the Growth, Metastasis, and Glycolysis of Pituitary Adenoma by Inhibiting HuR Degradation.

Exosomal long noncoding RNAs (lncRNAs), which are highly expressed in tumor-derived exosomes, regulate various cellular behaviors such as cell proliferation, metastasis, and glycolysis by facilitating intercellular communication. Here, we explored the role and regulatory mechanism of tumor-derived exosomal lncRNAs in pituitary adenomas (PA). We isolated exosomes from PA cells, and performed in vitro and in vivo assays to examine their effect on the proliferation, metastasis, and glycolysis of PA cells. In addition, we conducted RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, and ubiquitination assays to investigate the downstream mechanism of exosomal AFAP1-AS1. Exosomes from PA cells augmented the proliferation, mobility, and glycolysis of PA cells. Moreover, AFAP1-AS1 was significantly enriched in these exosomes and stimulated the growth, migration, invasion, and glycolysis of PA cells in vitro, as well as tumor metastasis in vivo. It also enhanced the binding affinity between Hu antigen R (HuR) and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1), resulting in HuR ubiquitination and degradation accompanied by enhanced expression of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). Moreover, HuR overexpression alleviated the exosomal AFAP1-AS1-mediated promotion of growth, metastasis, and glycolysis effects. These findings indicate that tumor-derived exosomal AFAP1-AS1 modulated SMURF1-mediated HuR ubiquitination and degradation to upregulate HK2 and PKM2 expression, thereby enhancing PA cell growth, metastasis, and glucose metabolism. This suggests targeting exosomal AFAP1-AS1 may be a potential strategy for the treatment of PA.

Surgical outcome of endoscopic endonasal approach as a modality of management for large and giant pituitary adenomas: a retrospective case series

BackgroundLarge 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 methodsThe 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%).Results42 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.ConclusionsEndoscopic 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.

Surgical treatment of cystic pituitary adenomas: literature-based definitions and postoperative outcomes.

To survey the applied definitions of 'cystic' among pituitary adenomas and evaluate whether postoperative outcomes differ relative to non-cystic counterparts. A literature search and meta-analysis was performed using PRISMA guidelines. Studies were eligible if novel data were reported regarding the applied definition of 'cystic' and postoperative outcomes among cases of surgically treated pituitary adenomas. Data were pooled with random effects meta-analysis models into cohorts based on the applied definition of 'cystic'. Categorical meta-regressions were used to investigate differences between cohorts. Among studies comparing cystic and non-cystic pituitary adenomas, meta-analysis models were applied to determine the Odds Ratio [95% Confidence Interval]. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA, 4.0), with a priori significance defined as P < 0.05. Ten studies were eligible yielding 283 patients with cystic pituitary adenomas. The definitions of 'cystic' mainly varied between the visual appearance of cystic components on preoperative magnetic resonance imaging and a volumetric definition requiring 50% or greater of tumor volume exhibiting cystic components. Tumor diameter was seldom reported with an associated standard deviation/error, limiting meta-analyses. When the data were pooled in accordance with the definition applied, there were no significant differences in the rates of gross total resection (P = 0.830), endocrinologic remission (P = 0.563), and tumor recurrence (P = 0.320). Meta-analyses on studies comparing cystic versus non-cystic pituitary adenomas indicated no significant difference in the rates of gross total resection (P = 0.729), endocrinologic remission (P = 0.857), and tumor recurrence (P = 0.465). Despite some individual studies describing a significant influence of pituitary adenoma texture on postoperative outcomes, meta-analyses revealed no such differences between cystic and non-cystic pituitary adenomas. This discrepancy may be explained in part by the inconsistent definition of 'cystic' and between-group differences in tumor size. A notion of a field-standard definition of 'cystic' among pituitary adenomas should be established to facilitate inter-study comparisons.

Simultaneous resection of pituitary adenoma and clipping of aneurysm through endoscopic endonasal approach: a case report

Pituitary adenomas and intracranial aneurysms are prevalent neurosurgical conditions, but their simultaneous presence is uncommon, affecting only 0.5%-7.4% of those with pituitary adenomas. The strategy of treating aneurysms endovascularly before removing pituitary adenomas is widely adopted, yet reports on addressing both conditions at once through an endoscopic endonasal approach (EEA) are scarce. We present a case involving a pituitary adenoma coupled with an anterior communicating artery aneurysm. Utilizing the EEA, we excised the adenoma and clipped the aneurysm concurrently. The patient recovered well post-surgery, with follow-up assessments confirming the successful resolution of both the adenoma and aneurysm. We proved the feasibility of the EEA in the treatment of pituitary adenomas with anterior communicating artery aneurysms under specific anatomical relationships and close intraoperative monitoring.

Medical treatment of functional pituitary adenomas, trials and tribulations.

Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy. Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research. An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life.

Proton beam radiotherapy for treatment of functional pituitary adenomas

Proton beam radiotherapy for treatment of functional pituitary adenomas

TNF-α can promote membrane invasion by activating the MAPK/MMP9 signaling pathway through autocrine in bone-invasive pituitary adenoma.

A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear. We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in invivo experiments. Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. Invivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression. Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.

Temozolomide on Aggressive Pituitary Adenomas: About 4 Cases and Review of the Literature

Pituitary adenomas represent 15 to 20% of all brain tumors . They affect 1/1000 of the world population, some pituitary adenomas with high Ki-67 indexes exhibit aggressive behaviors, such as rapid growth, early and frequent recurrence, and resistance to conventional treatment, even in the absence of metastasis . Many trials have focused on the role of chemotherapy in the treatment of these aggressive and atypical adenomas The objective: Monitoring of patients on temozolomide . we report the follow-up of 4 patients (pts) of 10 pts treated in our department during the period (2012-2019), 2 women / 2 men presenting an aggressive pituitary macro-adenoma, having benefited from excision surgery, radiotherapy and received medical treatment with temozolomide initiated with clinical, biological and radiological evaluation of the therapeutic response and search for p53 and ki 67 in the diagnosis. A clinical improvement was noted in our 4 pts; Radiologically: a partial response was obtained in 1pts, two stabilities and one progression . The average duration of treatment is 26 months (12 - 40) with manageable side effects .Temozolomide appears to be effective in the treatment of aggressive pituitary adenomas and may currently constitute a therapeutic alternative when all resources are exhausted, thus allowing control of the disease.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Association between county-level socioeconomic status and the incidence of and surgical treatment for pituitary adenoma.

The objective of this study was to evaluate the association between county-level socioeconomic status (SES) and the incidence of and surgical treatment for pituitary adenoma (PA). Using the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results database, the authors identified the average annual age-adjusted incidence rates and calculated odds ratios (ORs) for surgical treatment of PA, stratified by a county-level index for SES, race/ethnicity, metropolitan status, and other confounders. From 2006 to 2018, 167,121 PA cases were identified. There was no significant trend in the incidence of PA by county-level SES overall (incidence rate ratio [IRR] 0.98, 95% CI 0.96-1.00, p = 0.05, comparing highest to lowest quintile of SES). Among Asian or Pacific Islander (API; IRR 0.82, 95% CI 0.71-0.95, p = 0.007) and American Indian/Alaska Native (AIAN) participants (IRR 0.82, 95% CI 0.71-0.95, p = 0.009), the incidence of PA was statistically significantly lower with higher SES, while among Black individuals, the incidence of PA was higher with higher SES (IRR 1.10, 95% CI 1.05-1.15, p < 0.001, comparing 5th to 1st quintile of SES). Higher SES quintile was associated with surgical treatment of PA (OR 1.04, 95% CI 0.99-1.09, comparing highest to lowest quintile, p value for trend = 0.02). Males were more likely than females to undergo surgery (OR 1.50, 95% CI 1.47-1.53, p < 0.001), and Black (OR 0.89, 95% CI 0.86-0.91, p < 0.001) and AIAN individuals (OR 0.88, 95% CI 0.78-0.99, p = 0.04) were less likely to undergo surgery than White individuals, whereas API individuals were more likely to undergo surgery (OR 1.15, 95% CI 1.09-1.21, p < 0.001). Higher county-level SES in the US was associated with a higher incidence of PA among Black individuals, but not among White individuals, while API and AIAN individuals had a lower PA incidence with higher SES. After multivariable adjustment, higher county-level SES was associated with surgical treatment of PA, and White and API individuals were significantly more likely to undergo surgery than Black or AIAN individuals.

Strategy for Identifying a Robust Metabolomic Signature Reveals the Altered Lipid Metabolism in Pituitary Adenoma.

Despite the well-established connection between systematic metabolic abnormalities and the pathophysiology of pituitary adenoma (PA), current metabolomic studies have reported an extremely limited number of metabolites associated with PA. Moreover, there was very little consistency in the identified metabolite signatures, resulting in a lack of robust metabolic biomarkers for the diagnosis and treatment of PA. Herein, we performed a global untargeted plasma metabolomic profiling on PA and identified a highly robust metabolomic signature based on a strategy. Specifically, this strategy is unique in (1) integrating repeated random sampling and a consensus evaluation-based feature selection algorithm and (2) evaluating the consistency of metabolomic signatures among different sample groups. This strategy demonstrated superior robustness and stronger discriminative ability compared with that of other feature selection methods including Student's t-test, partial least-squares-discriminant analysis, support vector machine recursive feature elimination, and random forest recursive feature elimination. More importantly, a highly robust metabolomic signature comprising 45 PA-specific differential metabolites was identified. Moreover, metabolite set enrichment analysis of these potential metabolic biomarkers revealed altered lipid metabolism in PA. In conclusion, our findings contribute to a better understanding of the metabolic changes in PA and may have implications for the development of diagnostic and therapeutic approaches targeting lipid metabolism in PA. We believe that the proposed strategy serves as a valuable tool for screening robust, discriminating metabolic features in the field of metabolomics.

Single Versus Fractionated Gamma Knife Radiosurgery for Nonfunctioning Pituitary Adenomas Close to the Optic Pathway: A Multicenter Propensity Score Matched Study.

Gamma Knife radiosurgery (GKRS), typically administered in a single session (S-GKRS), is an effective treatment for nonfunctioning pituitary adenoma (NFPA). For lesions close to the optic pathway, the use of hypofractionated radiosurgery is growing. This study seeks to compare the results of S-GKRS vs fractionated-GKRS (F-GKRS) for NFPAs adjacent to the optic pathway. Two cohorts of patients with residual or recurrent NFPAs in contact to the optic pathway were retrospectively included in this study: (1) a group of patients who underwent a 3-day course of F-GKRS in Europe and (2) a group of patients treated with S-GKRS in the United States. A propensity score matching (ratio 1:1) was carried out to obtain and compare 2 homogeneous groups of patients with NFPA. A total of 84 patients were included for analysis (42 in the S-GKRS cohort and 42 in the F-GKRS group). The 2 cohorts did not differ for age, sex, number of previous surgical procedure, tumor volume, and follow-up. The mean follow-up was 60.2 ± 37.0 months and 62.4 ± 37.4 months for F-GKRS and S-GKRS cohort, respectively ( P = .38). The overall tumor control at last follow-up was achieved in 95.2% and 92.9% of patients in F-GKRS and S-GKRS, respectively ( P = .64). The 1-year, 3-year, 5-year, and 7-year progression-free survival rate after F-GKRS was 100%, 97.1%, 97.1%, and 91%, respectively. In the S-GKRS sample, progression-free survival rates were 100%, 100%, 92.5%, and 92.5% at 1, 3, 5, and 7 years after treatment, respectively. Two patients (4.7%) from the F-GKRS cohort and 2 (4.7%) from the S-GKRS cohort sustained visual worsening after radiosurgery ( P = 1.0). In the management of NFPAs adjacent to the optic pathway both F-GKRS and S-GKRS had comparable outcomes and risks at 7 years. Future prospective studies including larger cohorts with longer follow-up are needed to confirm our results.

Exosomal CircMFN2 Enhances the Progression of Pituitary Adenoma via the MiR-146a-3p/TRAF6/NF-κB Pathway.

Pituitary adenoma (PA) is a common intracranial endocrine tumor, but no precise target has been found for effective prediction and treatment of PA. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) analysis showed that circMFN2 could affect the expression of miR-146a-3p in PA samples. Moreover, we used Western blotting to evaluate the expression levels of TRAF6 and NF-κB markers. The EdU assay, scratch wound healing assay, and Matrigel invasion assay were performed to assess the potential function of this pathway in PA cells. Based on the bioinformatic analysis including KEGG, gene ontology (GO) analysis, and microarray analysis, we evaluated the efficacy of circMFN2 as a potential biomarker for diagnosing PA, and we aimed to determine the mechanism of action in PA cells. Our findings indicate that there is a significant increase in the expression of circMFN2 in tissues, serum, and exosomes in the invasive group compared with the noninvasive and normal groups. Furthermore, this difference was statistically significant both preoperatively and postoperatively. To clarify its function, we downregulated this gene, and the experimental results suggested that the motility and proliferative capacity were reduced in vitro. In addition, rescue assays showed that miR-146a-3p could successfully reverse the inhibitory effect of circMFN2 knockdown on motility and proliferation in PA cells. Moreover, downregulation of circMFN2 and miR-146a-3p significantly changed the expression of TRAF6 and NF-κB. This study identified that circMFN2 regulates miR-146a-3p to promote adenoma development partially via the TRAF6/NF-κB pathway and may be a potential therapeutic target for PA.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

Prognostic factors for surgical treatment of prolactin-secreting pituitary adenomas.

Usually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy. This study aims to determine the early and late outcomes of surgery, with particular emphasis on developing prognostic factors for surgical treatment and analyzing risk factors affecting the recurrence of hyperprolactinemia and prolactinoma. This retrospective study was conducted at the Feofaniya Clinical Hospital of the State Administration of Affairs (Kyiv, Ukraine), evaluating 109 patients' records from 2009 to 2019. The main patients' inclusion criteria were: serum prolactin (PRL) level of more than 100 ng/ml, presence of pituitary adenoma (PA) on MRI, histologically approved PA by microscopy. According to the size of the prolactin-secreting PA (PSPAs) the selected 109 patients were divided into two groups: micro- (≤10 mm, n = 75) and macroadenoma group (10-40 mm, n = 34). 1 month after the operation, PRL levels decreased by 87% (p < 0.001), 12 months-by 93% (p < 0.001). After receiving surgery and DA therapy for 12 months 77.1% of patients achieved biochemical remission. Out of the total number of patients observed, 15.6% (n = 17) had a Knosp score greater than 3. Additionally, in the macroadenoma group, the percentage of patients with a Knosp score greater than 3 was 41,2%, which was significantly higher as compared to the microadenoma group (4%, p < 0.001). In patients with microadenomas a weak reverse correlation between patients' age (r = -0.258, p < 0.026) and positive with tumor size (r = 0.251, p < 0.030) was revealed. In the macroadenoma group significant association was found only between preoperative serum PRL level and tumor size (r = 0.412, p < 0.016). The preoperative PRL can be used as a diagnostic marker for lack of early biochemical remission in patients with PSPAs with diagnostic accuracy 66.9%. This study found that primary transsphenoidal surgery is an effective treatment in reaching PRL level control in patients with both micro- and macroprolactinomas. The correct and thorough selection of candidates for surgery is crucial to achieve postoperative serum PRL normalization in the vast majority of patients.

Pathogenesis, clinical features, and treatment of plurihormonal pituitary adenoma.

Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.