Pituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Several studies have shown N-myc downstream regulated gene 2 (NDRG2) as a tumor suppressor gene, but the role of NDRG2 gene in pituitary adenoma pathogenesis has not been elucidated. The aim of our research has been to examine NDRG2 mRNA expression in PA and to determine the associations between the NDRG2 gene epigenetic changes and the development of recurrence or invasiveness of PA and patient clinical data. The MS-PCR was used for NDRG2 promoter methylation analysis and gene mRNA expression levels were evaluated by qRT-PCR in 68 non-functioning and 73 functioning adenomas. Invasiveness was evaluated using magnetic resonance imaging with Hardy’s modified criteria. Statistical analysis was performed to find correlations between NDRG2 gene mRNA expression, promoter methylation and patient clinical characteristics and PA activity. The NDRG2 mRNA expression was significantly lower in the case of acromegaly (GH and IGF-1 hypersecretion) than in other diagnoses of PAs (p < 0.05). Also, the NDRG2 expression was significantly higher in prolactinoma (PRL hypersecretion) than in in other diagnoses of PAs (p < 0.05). The promoter of NDRG2 was methylated in 22.69% (12/58 functioning and 15/61 non-functioning) of patients with PA. However, the NDRG2 gene mRNA expression was not significantly related to its methylation status. Clinical factors, such as: age, gender, relapse and diagnoses of Cushing syndrome were of no significance for NDRG2 promoter methylation and mRNA expression levels, as well as secreting or non-secreting PAs and the invasiveness of PAs. The different NDRG2 promoter methylation and expression levels in PA samples showed tumor heterogeneity and indicates a potential role of this gene in pituitary adenoma pathogenesis, but the corresponding details require intensive research.

The aim and objective of this study is to determine the association between the rs1800871, rs1800872, and rs1800896 polymorphisms of the gene IL-10 and the serum levels of IL-10 in patients with pituitary adenoma. Methods: Data from 106 patients with pituitary adenoma and 192 control patients were used for the study. DNA was isolated from peripheral blood using the salt precipitation method. The samples were genotyped in real-time using the polymerase chain reaction method. IL-10 serum levels were evaluated using an ELISA kit. The data obtained were systematized using the computer program IBM SPSS Statistics. Results: The AG genotype of IL-10 rs1800871 was statistically significantly lower in the inactive PA group than in the control group (22.7% vs. 40.6%, p = 0.027). The TG genotype of IL-10 rs1800872 was also statistically significantly lower in the inactive PA group than in the control group (22.7% vs. 40.6%, p = 0.027). A binary logistic regression analysis of the polymorphisms in the IL-10 gene in PA and control groups based on the pituitary adenoma activity showed that the AG genotype of IL-10 rs1800871 increased the chance of inactive PA by 2.2-fold in codominant (OR: 2.272, CI: 1.048–4.925, p = 0.038) and overdominant (OR: 2.326, CI: 1.086–4.982, p = 0.030) models. Moreover, the TG genotype of IL-10 rs1800872 increased the probability of inactive PA by 2.2-fold in codominant (OR: 2.272, CI: 1.048–4.925, p = 0.038) and overdominant (OR: 2.326, CI: 1.086–4.982, p = 0.030) models. The association of the IL-10 polymorphisms with PA invasiveness and recurrence in PA and control groups did not yield statistically significant results. Conclusions: IL-10 rs1800871 and IL-10 rs1800872 may be associated with the development of inactive PA.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with features of demyelination and axonal degeneration at a young age. Genetic factors may play an important role in the development of multiple sclerosis. (1) Objective: To investigate IL-10 rs1800871, rs1800872, rs1800896, and IL-10 serum levels in patients with multiple sclerosis. (2) Methods: Our study included patients with multiple sclerosis (n = 127) and healthy volunteers (n = 195). The subjects’ DNA was extracted from peripheral blood leukocytes and genotyped by real-time polymerase chain reaction. The results were analyzed using the program “IBM SPSS Statistics 27.0”. (3) Results: The IL-10 SNPs were analyzed between the MS and control groups; however, no statistically significant results were found. The serum levels of IL-10 in the groups of MS and healthy subjects were not statistically significantly different (median (IQR): 0.828 (1.533) vs. 0.756 (0.528), p = 0.872). (4) Conclusions: IL-10 rs1800871, rs1800872, and rs1800896 and serum IL-10 levels are not likely to be associated with MS development. However, individuals carrying the rare haplotypes of rs1800871, rs1800872, and rs1800896 were associated with increased odds of MS (p = 0.006).

Background: The main mechanism of optic nerve damage in patients with pituitary adenoma (PA) is the pressure of optic chiasm. The retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL)+, and GCL++ thickness measurement by optical coherence tomography (OCT), visual function evaluation, and magnetic resonance imaging (MRI) can be used to predict visual function recovery. In our study, we investigated the associations between visual acuity (VA), visual field (VF), RNFL, GCL changes, and the findings of MRI in patients with PA. Methods: This study was conducted in the Departments of Ophthalmology and Neurosurgery of the Lithuanian University of Health Sciences Hospital. A total of 25 patients diagnosed with PA were included in the study group, and 27 healthy subjects were included in the control group. The thickness of the RNFL and ganglion cell layer (GCL+, GCL++) and optic nerve disc diameter was analysed with OCT. Moreover, an MRI was performed for patients with PA. Results: The RNFL thickness around the optic disk measured preoperatively was reduced significantly in the temporal quadrant in PA patients compared with the control group (median (min; max); mean rank: 73.5 (52; 109); 58.39 vs. 69.5 (16; 168); 46.14; p = 0.038). We found that it was reduced significantly only in the inferior quadrant of the macro-PA group compared to the micro-PA group (median (min; max); mean rank: 99.5 (61; 115); 21.07 vs. 106.5 (90; 121); 32.15), p = 0.008, respectively). The RNFL thickness was reduced significantly only in the inferior quadrant of the non-active PA group compared to the active PA group (median (min; max); mean rank: 118.5 (49; 144); 17.42 vs. 130.5 (77; 156); 28.05), p = 0.028, respectively). RNFL thickness was reduced significantly only in the temporal quadrant in the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 67.5 (16; 99); 21.66 vs. 72 (58; 168); 30.39), p = 0.036, respectively). Furthermore, GCL++ thickness was reduced significantly in total and in superior and inferior sectors of the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 98.5 (57; 113); 21.8; 101 (61; 121); 21.48 and 102.5 (59; 116); 21.71 vs. 103.5 (95; 115); 30.2; 106.5 (90; 115); 30.61 and 104.5 (95; 113); 30.32), p = 0.043; p = 0.028 and p = 0.038, respectively). In the control group, significant positive correlations were found between optic disc area and the total RNFL thickness (r = 0.440, p < 0.001). In the PA group, significant correlations were observed between optic rim area and total RNFL thickness (r = 0.493, p < 0.001) and all quadrants, with the strongest in the nasal quadrant (r = 0.503, p < 0.001). A moderate to strong negative correlation was found between visual field (VF) defects and RNFL thickness, with the strongest correlation observed in the superior quadrant. Conclusions: OCT offers a detailed insight into the microscopic structural and functional changes throughout the entire visual pathway in patients with PA. Our findings demonstrate a significant negative correlation between RNFL thickness and visual field defects, highlighting the clinical relevance of OCT measurements in visual function assessment. Moreover, the results suggest that optic rim area may be a more reliable indicator of RNFL thickness variations than optic disc area in patients with PA.

Pituitary adenoma (PA) is the most common benign tumor of the pituitary gland. The pathogenesis of most PA is considered as a multifactorial process, that involves genetic mutations, alterations in gene transcription, and epigenetic factors. Their interaction promotes tumorigenesis. The processes are increasingly focused on changes in telomere length. Our study enrolled 126 patients with PA and 368 healthy subjects. DNA samples from peripheral blood leukocytes were purified by the DNA salting-out method. The RT-PCR carried out SNPs and relative leukocyte telomere lengths (RLTL). ELISA determined the level of TEP1 in blood serum. Binary logistic regression revealed that TERC rs35073794 is likely associated with increased odds of PA development and macro-PA development. It is also associated with decreased odds of active PA, non-invasive PA, and PA without relapse development. Also, we discovered that PA patients with at least one G allele of the TEP1 gene polymorphism rs1713418 have lower serum TEP1 levels than healthy individuals (p = 0.035). To conclude, the study revealed that TERC rs35073794 might be a potential biomarker for PA development.

Background and Objectives: To evaluate the association of relative leukocyte telomere length (RLTL) and telomerase complex regulatory markers with Leber’s hereditary optic neuropathy (LHON). Material and Methods: A case-control study was performed in patients with LHON (≥18 years) and healthy subjects. The diagnosis of LHON was based on a genetic blood test (next-generation sequencing with Illumina MiSeq, computer analysis: BWA2.1 Illumina BaseSpace, Alamut, and mtDNA Variant analyzer 1000 were performed) and diagnostic criteria approved by the LHON disease protocol. Statistical analysis was performed using the standard statistical software package, IBM SPSS Statistics 27. Statistically significant results were considered when p < 0.05. Results: Significantly longer RLTL was observed in LHON patients than in healthy controls (p < 0.001). RLTL was significantly longer in women and men with LOHN than in healthy women and men in the control group (p < 0.001 and p = 0.003, respectively). In the elderly group (>32 years), RLTL was statistically significantly longer in LHON patients compared with healthy subjects (p < 0.001). The GG genotype of the TERC rs12696304 polymorphism was found to be statistically significantly higher in the LHON group (p = 0.041), and the C allele in the TERC rs12696304 polymorphism was found to be statistically significantly less common in the LHON group (p < 0.001). The RLTL of LHON patients was found to be statistically significantly longer in the TERC rs12696304 polymorphism in all tested genotypes (CC, p = 0.005; CG, p = 0.008; GG, p = 0.025), TEP1 rs1760904 polymorphism in the GA genotype (p < 0.001), and TEP1 gene rs1713418 in the AA and AG genotypes (p = 0.011 and p < 0.001, respectively). Conclusions: The RLTL in LHON patients was found to be longer than in healthy subjects regardless of treatment with idebenone. The TERC rs12696304 polymorphism, of all studied polymorphisms, was the most significantly associated with changes in LHON and telomere length.