Juškienė, Martyna

Background: Pituitary adenomas are slow-growing tumors that originate from the anterior part of the pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long non-coding RNA (lncRNA) that has been implicated in the regulation of cell proliferation, gene expression, apoptosis, differentiation, and cell cycle transition in various tumors, including pituitary adenomas (PA).

Objective: To evaluate the impact of MALAT1 gene variants (rs3200401, rs619586, and rs1194338) and immunohistochemical markers (Ki-67 and p53) on the susceptibility and clinical characteristics of PA.

Methods: a case-control study included patients with PA and age- and gender-matched controls. PA diagnosis was confirmed through MRI/CT imaging and/or histopathological examination. DNA was extracted from peripheral blood samples, and three MALAT1 variants (rs3200401, rs619586, and rs1194338) were genotyped using TaqMan® real-time PCR. The expression of Ki-67 and p53 were evaluated immunohistochemically using digital image analysis. Statistical analyses included chi-square tests to compare genotype and allele distributions, logistic regression to estimate PA risk (odds ratios, 95% confidence intervals), and nonparametric tests for biomarker evaluation.

Results: Among 390 participants (145 PA and 245 controls), only the MALAT1 rs619586 variant showed statistically significant associations after Bonferroni correction (p < 0.016). The rs619586 G allele was more frequent in PA patients than in controls (4.1% vs. 0.8%, p = 0.001) and increased the odds of developing PA by 4.1-fold under the additive model (OR = 4.139, 95% CI: 1.365- 12.551, p = 0.012). The G allele remained significantly associated across several clinical subgroups, including microadenomas, macroadenomas, invasive PAs, and PAs with recurrence (p ≤ 0.015). In PA tissues, p53 H-scores were higher in macroadenomas compared with microadenomas (p = 0.047), and patients with the rs619586 AA genotype showed significantly higher p53 expression than those with the AG genotype (p = 0.008). A moderate positive correlation was observed between Ki-67 LI and p53 expression (ρ = 0.268, p = 0.035).

Conclusions: MALAT1 rs619586 G allele is significantly associated with an increased risk of PA and its more aggressive clinical features, including invasiveness and recurrence. These findings suggest that rs619586 may serve as a potential genetic marker linked to PA susceptibility. Additionally, the observed relationship between p53 expression and tumor proliferation highlights its potential role in PA tumorigenesis. Further studies are needed to confirm these associations and clarify the underlying molecular mechanisms.

Nutukimas - viena aktualiausių dabartinės visuomenės problemų, neigiamai veikianti daugelį organizmo sistemų ir trikdanti sergančiojo šia liga gyvenimo kokybę, darbingumą bei trumpinanti gyvenimą. Tai - metaboliškai aktyvi ir recidyvuojanti liga, kurios metu kūno masė didėja riebalinio audinio sąskaita. Nutukimą kaip ligą Amerikos medicinos asociacija oficialiai pripažino 2013 metais. Nutukimas pastaruoju metu yra labiausiai aptarinėjama tema tiek medicinos, tiek plačiojoje visuomenėje. Kalbant apie nutukimą, dažnai ši būklė siejama su asmeniniu kaltės priskyrimu: „reikia tik noro“, „reikia suimti save į rankas“ ir t. t. Įvairiais istoriniais laikotarpiais požiūris į žmogaus kūno formas keitėsi nuo Rubenso tipo moterų iki anoreksinių mados manekenių formų. Menamų kūno formų standartų neatitinkantis žmogus gali būti pavadintas putliu, stambiu, apkūniu, didelio dydžio ar net storuliu ar apsileidusiu. Medicinos bendruomenėje vyrauja terminai: antsvoris, hipotalaminis, pilvinis, centrinio tipo, kušingoidinis, morbidinis nutukimas ir kt. Nutukimas turi kompleksines pasekmes - skatina lėtines ligas, galinčias sutrumpinti žmogaus amžių 10-15 metų. Per pastaruosius 5 dešimtmečius nutukimo paplitimas pasaulyje padidėjo daugiau nei 3 kartus, ir dabar tai įvardijama kaip nutukimo pandemija. Klinikinėje praktikoje nustatomos įvairiausios nutukimo priežastys - nuo genetinių (Prader-Willi sindromas, Aistrom sindromas, LEPR (leptino receptoriaus) ar LEP (leptino) geno mutacijos ir kt.), endokrininių (hipotirozė, hiperkorticizmas, hipogonadizmas ir kt.) iki valgymo priklausomybių. Skirtingos yra ir nutukusių kūno formos bei kūno kompozicija. Todėl kūno masės indeksas (KMI) klinikiniu požiūriu jau nebetenka prasmės. KMI tikslinga naudoti populiaciniams, palyginamiesiems tyrimams. Statistiniais duomenimis (HIS Lietuva, Eurostat, 2019-2022 m.), pagal KMI nutukusių suaugusių Lietuvoje buvo 21-23 proc. Skaičiuojama, kad apie 60 proc. suaugusiųjų Lietuvoje turi antsvorio ar yra nutukę. Tai - tik statistika, neatspindinti konkrečios individo būklės. 2025 m. pasaulio 58 ekspertų grupė, atstovaujanti įvairioms medicinos specialybėms ir šalims, išanalizavo turimus įrodymus ir, pritarus 75 medikų ir pacientų organizacijoms, rekomendavo klasifikaciją, kurioje išskiriamas ikiklinikinis ir klinikinis nutukimas. Pagal epidemiologinius ir klinikinius duomenis, nutukimas susijęs su daugiau nei 200 skirtingų ligų ir sveikatos sutrikimų. [...]

Background: Pituitary tumor-transforming gene 1 (PTTG1) is a proto-oncogene implicated in pituitary neuroendocrine tumors (PitNETs) pathogenesis through regulation of the cell cycle, genomic instability, and angiogenesis. Overexpression of PTTG1 promotes tumor growth, but the impact of its genetic variants in PitNETs size is insufficiently defined.

Objective: To evaluate the impact of PTTG1 gene variants (rs1895320, rs2910200, and rs6882742), circulating PTTG1 levels, and immunohistochemical markers (Ki-67 and p53) on PitNETs susceptibility and clinical features.

Methods: case–control study included patients with PitNETs and age- and gender-matched controls. Diagnosis of PitNETs was confirmed by MRI/CT and/or histopathology. Genomic DNA was extracted from peripheral blood, and three PTTG1 variants (rs1895320, rs2910200, rs3811999) were genotyped using TaqMan® real-time PCR assays. Serum PTTG1 levels were measured by ELISA, while Ki-67 and p53 expression were assessed immunohistochemically with digital image analysis. Statistical analyses included chi-square comparisons of genotype/allele distributions, logistic regression for PitNETs risk (odds ratios, 95% CI), and nonparametric tests for biomarker evaluation.

Results: A total of 340 participants were enrolled, comprising 120 PitNET patients and 220 controls. Median age (53.5 vs. 54 years) and gender distribution did not differ between the groups. Among patients, 35% had microadenomas and 65% had macroadenomas. Logistic regression revealed that the PTTG1 rs3811999 TT genotype was associated with increased odds of microadenoma occurrence (OR = 2.53, 95% CI: 1.17-5.48, p = 0.018). The PTTG1 rs2910200 TT genotype and T allele were significantly more common in tumors with lower proliferative activity Ki-67 LI < 3% (p = 0.013 and p = 0.004), suggesting a potential association with reduced proliferation. In contrast, the rs3811999 TT genotype and T allele were more frequent in tumors with Ki-67 LI > 3% (p = 0.015 and p = 0.011), indicating a relationship with higher proliferative potential. Macroadenomas exhibited significantly higher p53 H-scores than microadenomas (27.34 vs. 16.00, p = 0.012), while no associations were observed with gender, invasiveness, activity, or recurrence.

Conclusions: Results suggest that PTTG1 rs3811999 may influence tumor size or growth pattern, possibly contributing to early tumorigenesis. We can hypothesize that the variant may alter gene expression or protein function, thereby predisposing to PitNETs development at an earlier stage (microadenomas). Future research should integrate molecular studies with larger genetic datasets to clarify how PTTG1 variants contribute to PitNETs’ pathophysiology.

Purpose: To determine the association between FGFR4 (rs351855 and rs7708357) gene polymorphisms and serum levels association with pituitary adenoma (PA). Methodology: A case-control study was conducted involving 279 subjects divided into two groups: the control group (n = 199) and a group of PA (n = 80). The genotyping of FGFR4 rs351855 and rs7708357 were carried out using the real-time polymerase chain reaction method. The serum concentration of FGFR was measured using the ELISA method. Statistical analysis of the data was performed using IBM SPSS Statistics 29.0 data analysis software. Results: There were no statistically significant results after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity and recurrence of pituitary adenoma and the control groups, the analysis revealed no statistically significant differences between the groups (p > 0.05). For FGFR4 levels: PA patients vs. control group: median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121. Conclusions: While this study did not find statistically significant associations, further research with larger sample sizes, additional genetic markers, and functional studies could provide deeper insights into the role of FGFR4 in PA development.

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment.

TEMOS AKTUALUMAS Hipofizės apopleksija (HA) - reta, gyvybei pavojinga büklė, atsirandanti dėl staigaus kraujavimo ar išemijos hipofizėje. Dažniausia priežastis yra hipofizės neuroendokrininis navikas (HNN). Kai kurių tyrimų duomenimis, gydymas somatostatino receptorių ligandais (SRL) gali būti siejamas su padidėjusia HA rizika dėl jų sukeliamų išeminių pokyčių hipofizėje. DARBO TIKSLAS Pristatyti Kušingo liga sergančios pacientės klinikinį atvejį, kai gydymo pasireotidu metu išsivystė hipofizės apopleksija. TYRIMO METODAI Atlikta pacientės, gydytos Lietuvos sveikatos mokslų universiteto ligoninės Kauno klinikų (LSMUL KK) Endokrinologijos klinikoje dėl Kušingo ligos recidyvo pasireotidu, klinikinio atvejo analizė. Duomenys surinkti iš ligos istorijos. [...].

TEMOS AKTUALUMAS Kušingo liga (KL) yra reta endokrininė patologija, kurią sukelia adrenokortikotropinį hormoną sekretuojantis hipofizės navikas. Šios ligos diagnostika sudėtinga dėl nespecifinių ir lėtai progresuojančių simptomų. Pavėluota diagnozė didina sunkių komplikacijų, tokių kaip širdies ir kraujagyslių ligos, cukrinis diabetas, osteoporozė, infekcijų ir psichikos sutrikimų riziką. DARBO TIKSLAS Išanalizuoti pacientų, sergančių KL, tirtų ir gydytų viename specializuotame retų endokrininių ligų centre, epidemiologinius ir gydymo aspektus Lietuvoje. [...].

Nuo neatmenamų laikų žmogus ieškojo būdų, kaip pailginti gyvenimą Dabar, kai gyvenimo trukmė ilgėja, o visuomenė sensta, taip pat svarstoma kaip būtų galima atitolinti senatvę. Vienas iš daug diskusijų šiuo klausimu keliančių veiksnių yra augimo hormonas (AH) ir jo įtaka raumenims bei senėjimui.