Endokrynologia Polska最新文献

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Introduction: In previous studies on thyroid hormones and frailty, most of the target population were elderly, and there were relatively few studies on elderly patients with coronary heart disease (CHD). Inflammation, oxidative stress, and haemodynamic instability in cardiovascular disease (CVD) can influence fluctuations in thyroid hormone (TH) levels and increase the incidence of frailty. The purpose of the present study was to explore the effect of TH on the risk of frailty in elderly patients with CHD.

Material and methods: The Fried scale was used to assess the frailty of participants. The predictive value of TH for frailty was determined using the patient's operating characteristic curve. Multivariate logistic regression model was utilised to analyse the relationship between TH and frailty.

Results: A total of 277 elderly patients with CHD were included in the study, of whom 29.96% were in a state of frailty. Free triiodothyronine (FT3)/free thyroxine (FT4) predicted frailty with the largest area under the curve of 0.634. Unordered multinomial logistic regression analysis showed that a lower T3 level was a risk factor for pre-frailty (p < 0.05). Lower levels of T3, FT3, and FT3/FT4 were risk factors for frailty (p < 0.05) after adjusting for demographic variables and blood indexes.

Conclusion: The predictive value of FT3/FT4 for frailty was more accurate than that of a single index. Moreover, T3 ≤ 1.095 nmol/L, FT3 ≤ 4.085 pmol/L, and FT3/FT4 ≤ 0.336 were shown to be the influencing factors of frailty, while T3 ≤ 1.095 nmol/L is an independent risk factor pre-frailty. Clinicians should focus on timely identification of the risk of frailty in order to improve patient quality of life and to reduce the risk of complications.

Anaplastic thyroid carcinoma (ATC) is reckoned as an infrequent but extremely advanced neoplasm of the endocrine system. Diaphanous-related formin 3 (DIAPH3) has been extensively implicated in carcinogenic events, but it has not been introduced in ATC. Herein, the role of DAPIH3 and the interrelated functional mechanism are characterised in ATC. The Gene Expression Omnibus (GEO) database was checked for differential DIAPH3 expression in ATC samples and noncancerous samples. Western blotting examined DIAPH3 and forkhead box M1 (FOXM1) expression in ATC cells. In vitro cell counting kit 8 (CCK-8) method, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Scratch, Matrigel invasion, and terminal-deoxynucleotidyl transferase mediated nick end labelling (TUNEL) assays were used to assess the potential of cells to proliferate, migrate, and invade as well as the cellular apoptotic rate. Co-IP was applied to access DIAPH3-FOXM1 protein interaction. Western blotting also disclosed the expression of proteins associated with apoptosis and Wnt/β-catenin signalling. DIAPH3 was hyper-expressed in papillary cell carcinoma (PTC) tissues and cells. Depleting DIAPH3 strongly eliminated the proliferative, migratory, as well as invasive capabilities of PTC cells while intensifying the apoptotic ability. FOXM1 also harboured elevated expression in PTC cells. FOXM1 was the binding partner with DIAPH3, and the 2 were positively correlated. FOXM1 upregulation again exacerbated the potentials to proliferate, migrate, and invade but it repressed the apoptotic rate of DIAPH3-depleted cells. Furthermore, loss of DIAPH3 downregulated FOXM1 to block Wnt/b-catenin signalling in PTC cells. Combined with these findings, DIAPH3 might favour the aggressive advancement of ATC and motivate the Wnt/β-catenin signalling via binding with FOXM1.

Introduction: Insulin resistance (IR) is confirmed as an important feature among polycystic ovary syndrome (PCOS) patients. Anti-Müllerian hormone (AMH), a vital marker of ovarian dysfunction, is proposed for inclusion in the diagnosis of PCOS in adolescents. We sought to investigate the relationship between the AMH level and IR in Chinese girls with PCOS.

Material and methods: 92 girls with PCOS aged 14-18 years were enrolled and divided into 2 subgroups: PCOS with IR group (n = 25) and PCOS without IR group (n = 67). A homeostasis model assessment-insulin resistance (HOMA-IR) value ≥ 2.5 was defined as IR. Clinical data and biochemical indexes were compared between the 2 groups. Multivariate logistic regression analysis and multivariate linear regression analysis were performed to determine which clinical variables were independently associated with IR and AMH level, respectively.

Results: PCOS girls with IR had higher levels of AMH than those of PCOS girls without IR (p < 0.01). Moreover, body mass index, triglyceride, and AMH values were shown to be independent risk factors for HOMA-IR after multivariate analysis. Meanwhile, age, insulin, and follicle-stimulating hormone levels were significantly related to AMH levels in those girls.

Conclusions: Our findings show that AMH is an independent determinant of IR in PCOS adolescents, and the fasting insulin level is closely associated with the AMH level, which indicates that the AMH pathway might play a role in the development of IR in PCOS adolescents. The interaction between AMH and IR in PCOS girls warrants further large-scale evaluation.

Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper structure of many enzymes and supporting the transport of oxygen and electrons. Its deficiency can lead to anaemia, which is a common clinical condition often associated with thyroid diseases. Iron deficiency is one of the most common nutritional deficiencies, and its prevalence is strongly associated with socioeconomic status. It is the primary cause of anaemia in 42% of children and 50% of women. Importantly, iron deficiency is placed among the top 5 causes of disability in women. Thyroid peroxidase (TPO) is an enzyme essential for the production of thyroid hormones, and iron is a key factor in its proper functioning. Therefore, in the case of iron deficiency, the activity of this enzyme is also reduced. Iron is also a factor that is important in epigenetic modification processes, and its deficiency may contribute to genomic changes potentially promoting the development of autoimmune thyroid diseases. Adequate supplementation in patients with Hashimoto's disease is one of the crucial elements of effective therapy. In addition to iodine, selenium, and magnesium supplementation, attention should be paid to proper iron intake. Iron is an element that is a component of the heme enzyme- thyroid peroxidase, which owes its activity to the binding of haem, and its function is the production of thyroid hormones. Iron can be delivered to the body in haem and non-haem forms. The haem form is found particularly in haemoglobin-rich red meat, but also in eggs, fish, and poultry. On the other hand, non-haem iron can be found in legumes, grains, fruits, and vegetables. Our study aimed to gather and summarise knowledge from scientific literature regarding iron deficiency anaemia and its association with hypothyroidism in women, as well as the possible mechanisms and pathogenesis of these conditions. The paper also aims to highlight that considering the high risk of iron deficiency, assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease.

Introduction: Thyroid carcinoma is the most frequent malignancy in different endocrine-related tumours. In this study, we demonstrated a long non-coding RNA LINC00092-associated molecular mechanism in promoting the progression of papillary thyroid carcinoma (PTC).

Material and methods: The expression of LINC00092 was analysed in the The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) patient cohorts and further determined by q-PCR. (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay, and wound healing assay confirmed the function of LINC00092 in migration and proliferation. Q-ChIP validated the transcriptional target. Luciferase reporter assay validated the miRNA-mRNA target.

Results: The analysis in patient cohorts and in PTC TPC-1 cells showed that the expression of LINC00092 was repressed in thyroid carcinoma. In addition, the expression of LINC00092 was negatively associated with the advanced thyroid TNM stages. LINC00092 repressed epithelial-mesenchymal transition (EMT), migration, and proliferation of TPC-1 cells. Interestingly, we identified that MYB, a well-studied tumour promoter, is a transcription factor of LINC00092, thereby the expression of LINC00092 was directly repressed by MYB. Furthermore, miR-4741 was also validated as a direct target of MYB and was induced by MYB. Notably, LINC00092 was repressed by miR-4741 through the direct 3'-untranslational region (3'-UTR) target. Therefore, MYB induced EMT of TPC-1 cells by repressing LINC00092 directly or indirectly via miR-4741.

Conclusions: Our study validated that LINC00092 is a tumour suppressor lncRNA in PTC. MYB directly or indirectly represses LINC00092, which contributes to the PTC progression. MYB, LINC00092, and miR-4741 form a coherent feed forward loop. The axis of MYB-LINC00092 promotes progression of PTC.

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Introduction: We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population.

Material and methods: The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 μg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed.

Results: The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030).

Conclusions: We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.

Introduction: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients.

Material and methods: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways.

Results: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy.

Conclusions: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

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