ACTA ENDOCRINOLOGICA (BUC)

Background. Although cardiovascular risk is increased in patients with subclinical hypothyroidism (SCH), replacement therapy is not recommended in those with TSH levels\r\nbetween 5 and 10 mU/L.\r\nObjective. We aimed to evaluate the effects of levothyroxine (LT4) treatment on cardiovascular risk factors and carotid artery intima media thickness (CIMT) in patients with SCH who had TSH levels between 5 and 10 mU/L.\r\nSubjects and Methods. Sixty SCH patients with TSH levels between 5 and 10 mU/L were included in the study. Patients\r\nwere randomized into two groups as treatment (n=30) and control (n=30) groups. BMI, blood pressure, lipid profile, fibrinogen, homocysteine, hs-CRP and CIMT were measured in all patients at baseline and after six months. LT4 treatment was initiated and the dose was tapered according to TSH levels in treatment.\r\nResults. There was no significant difference between baseline and six month measurements in the control group. However, TSH, LDL-C, fibrinogen and mean CIMT measurements were decreased and HDL-C level was increased in the treatment group.\r\nConclusions. We suggest that LT4 therapy is necessary for the prevention of modifiable cardiovascular risk factors in\r\npatients with TSH levels between 5 and 10 mU/L.

Background. Saturated free fatty acids, such as palmitate, can cause pancreatic β-cell apoptosis. Although the toxicity of palmitate could be mediated partly through endoplasmic reticulum (ER) stress, the mechanism by which fatty acid over-accumulation led to lipoapoptosis in β-cells has not been fully understood. Recently, the fat mass and obesity associated (FTO) gene is proved to be related to obesity and type 2 diabetes, but its function in β-cells remains largely unknown. Whether or not FTO could counteract palmitate induced β-cell apoptosis remains to be investigated. Methods. INS-1 cells were infected with FTO expression adenovirus and incubated with palmitate. Then, viability and induction of apoptosis were measured by MTT assay and Hoechst-staining, respectively. Western blot analyses were performed for unfolded protein response specific proteins and mRNA expression of target molecules was determined by real time-PCR. Results. Palmitate incubation led to β-cell apoptosis, whereas adenovirus-mediated FTO overexpression significantly ameliorated the effect of palmitate. Increased activation of X-box binding protein 1 (Xbp1) mRNA and phosphorylation of eIF2α were also observed after palmitate treatment, whereas FTO overexpression significantly ameliorated the effect of palmitate. The proapoptotic transcription factor CHOP was significantly enhanced by palmitate incubation. In contrast, in accordance with sustained cell survival, FTO overexpression resulted in notably decreased CHOP levels. Interestingly, mRNA expression of the chaperones Pdi, Calnexin and Grp94 was not altered by palmitate treatment, while FTO overexpression notably increased the expression of Bip. Conclusion. Our data showed that FTO overexpression could protect β-cells from palmitate-induced apoptosis partly through suppression of ER stress.

Background. If not diagnosed at birth, congenital hypothyroidism (CH) can cause deleterious, irreversible neurodevelopmental sequels. The importance of thyroid newborn screening (NBS) is therefore well established. Objective. To evaluate the efficacy of NBS for CH in North-East Romania. Methods. Retrospective, descriptive study involving 271662 newborns screened between 2010 and 2019 for CH and phenylketonuria in maternities from six Romanian NorthEastern counties by measuring neonatal TSH (neoTSH) in the whole blood extracted from the heel between days 3 and 5 after birth. Values found higher than a cut-off level of 10 mIU/L were followed by serum evaluation of TSH and fT4 for the confirmation of CH. Thyroid ultrasound was further performed at children found with CH. Results. NeoTSH was found elevated in 417 newborns, but CH was subsequently confirmed in only 57 cases (1/4766 newborns). Mean age at the time when diagnosis was communicated was of 37.2 ± 15 days (between 9 and 157 days). Mean age when therapy was started was of 44.2 ± 17.9 days (between 13 and 160 days) with a mean delay of one week from diagnosis (between 0 and 62 days). Thyroid ultrasound revealed athyreosis in only 3 cases, atrophic thyroid gland in other 10 cases, whereas the thyroid was described as present in the remnant 44 cases. The number of first year follow-up visits greatly varied from 0 to 5, with an average of 2. Conclusions. NBS allowed rapid diagnosis of CH in North East Romania. The communication of diagnosis to families and therapy onset were however often delayed. Diagnosis and therapy onset before the age of two weeks, as well as a tighter follow-up should be assured by the healthcare system. Etiological diagnosis should be more accurate, for a better prognosis of disease severity, as well as the possibility of genetic advice in selected cases.

Background. To investigate the association between inflammatory factors, such as complete blood count (CBC) components, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and gestational diabetes mellitus (GDM). Methods. A total of 635 pregnant women with GDM and 296 with normal pregnancies at 7–13 weeks of gestation who underwent prenatal examinations in the obstetrics department were enrolled (June 2020–December 2020). CBC parameters, including WBC, neutrophil, lymphocyte (LYM), monocyte (MON), red blood cell (RBC), hemoglobin (HGB), mean corpuscular volume (MCV), platelet (PLT), platelet accumulation (PCT), mean platelet volume (MPV), NLR, MLR, PLR, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and other parameters were assessed. The receiver operating characteristic (ROC) curve was used to analyze the screening effects of the variables on the development of GDM. Results. There were significant differences in the blood levels of WBC, NEU, LYM, MON, RBC, HGB, PCT, ALT, AST, GGT, NLR, and MLR between the GDM and control groups (P<0.05). The diagnostic level of MON was the highest among all factors. Conclusion. Inflammatory factors (WBC, NEU, LYM, MON, NLR, and MLR counts) were correlated with GDM.

Purpose. To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). Patients and Methods. Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. Results. We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). Conclusions. The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

Background. The research evidence have suggested that ghrelin, a neuropeptide containing 28 amino acids, plays an\r\nimportant role in glucose homeostasis and its concentration is increased in diabetes.\r\nObjective. To investigate the relationship between the serum levels of ghrelin, insulin, fasting glucose and glycated hemoglobin in patients with type 2 diabetes mellitus.\r\nMaterials and Methods. Fasting glucose, insulin, ghrelin and glycated hemoglobin were measured after a 12-14 hours overnight fasting in 48 adult males with type 2 diabeties. Pearson correlations were used to establish the relationship\r\nbetween ghrelin concentration and other variables. P-value of less than 0.05 was considered statistically significant.\r\nResults. There were no correlations between serum ghrelin and Systolic and diastole blood pressure and body mass index (p<0.05). Serum ghrelin is weakly associated with glycated hemoglobin (p=0.076, R=0.19). Serum ghrelin concentrations were positively correlated with fasting glucose (p=0.005, R=0.40). In addition, ghrelin correlated negatively with\r\nserum insulin (p=0.013, r=-0.36).\r\nConclusion. Our data demonstrate that high ghrelin concentration is accompanied with increase in blood glucose\r\nin type 2 diabetic patients, and support this hypothesis that this neuropeptide plays a pathophysiological role in this disease.

Context. Data are conflicting concerning risk for Alzheimer’s disease (AD) and 5,10-methylenetetrahydrofolate reductase genetic variant (MTHFR C677T). Objective. The aim of the study was to investigate the associations of MTHFR C677T and risk of developing AD. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis and statistical analyses were performed using Stata. Results. In 33 included studies which provided 4518 cases and 5476 controls, the analysis for investigating the association between C677T allele T and the risk of developing AD relative to the allele C revealed no heterogeneity (p=0.088, I2=26.1%) between the 33 studies; the random effects (RE) pooled OR was significant: [RE OR=1.13(1.05-1.22)]. In subgroup analysis, we only observed the significant results in Asian populations. The pooled analysis for MTHFR 677 CT+TT vs. 677CC revealed a significant result [fixed effect (FE) OR=1.22(1.10-1.34)]. However, we did not observe significant associations in Europeans when comparing MTHFR 677 CT+TT with 677CC in subgroup analysis. The pooled analysis for MTHFR 677 TT vs. 677CC+CT did not reveal significant results: [FE OR=1.08(0.95-1.22)]. Conclusion. The risk allele T of MTHFR C677T is associated with high risk of AD in Asian populations, but not in Europeans.

Context. Results concerning the relationship between the risk of developing diabetic retinopathy (DR) and methylenetetrahydrofolate reductase genetic variant (MTHFR C677T) are inconclusive. Objective. The aim of the present analysis was to investigate the associations of DR with MTHFR C677T. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis was performed using Stata. Results. The included 7 studies provided 535 cases of DR and 759 controls. The main analysis for investigating the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC did not reveal significant heterogeneity (p=0.227, I2=27.6%) between the studies; the fixed effects (FE) pooled OR was significant: FE OR=1.84(1.30-2.61). The analysis for the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC+CT revealed heterogeneity (p=0.082, I2=48.9%) between the studies; the random effects (RE) pooled OR was significant: RE OR=1.72(1.07-2.76). In addition, T carriers have 31% higher risk of developing DR compared with homozygotes for C [OR=1.31(1.03-1.66)]. Conclusions. The present metaanalysis suggested an association between MTHFR C677T and DR and provided evidence that the TT genotype of the MTHFR C677T contributes to susceptibility to DR.

Context and objective. Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown. Material and methods. In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated. Results. Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2. Conclusion. MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.