ACTA ENDOCRINOLOGICA (BUC)

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.

Aim. Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. Materials and Methods. In this study, 238 adult LT patients were evaluated in terms of PTDM development. Results. Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/ m2 : 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p<0.001 p= 0.028). PTDM and t-HG patients mean age was higher than non-PTDM patients (51.5± 9.68, 48.2± 11.1 and 41.5± 14 years, respectively, p= 0.002 p= 0.023). In the univariate analysis, the only independent risk factor for PTDM was age (OR 1.93, 95% CI 1.31-2.97). Conclusion. Age is the most important risk factor for PTDM development after LT. PTDM was found more common in the patient group with greater body weight. Patients with older age and greater body weight should be examined more carefully for PTDM before LT.

Context. Human zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto’s thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied. Objective and design. This pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto’s thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics. Subjects and methods. A group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method. Results. Age, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively). Conclusions. There is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.

Introduction. Insulin resistance or dysfunction of pancreatic beta cells represents one of the important worldwide endocrine disease challenges. In fact, vascular endothelial dysfunction (VED) is involved in the pathogenesis of one of the most significant causes of diabetes-induced morbidity; diabetic nephropathy (DN). Asymmetric dimethyl arginine (ADMA) is one among other incriminating mechanisms of VED. The aim of this study was to assess whether ADMA modulation could be achieved by taurine or rosiglitazone, and whether they could improve tubulo-interstitial ischemia and subsequent renal damage in experimental DN in rats. Material and methods. 40 male Wistar rats were randomly assigned into 4 groups: normal saline-injected control, diabetic control induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg), and two diabetic groups daily treated orally with rosiglitazone (3 mg/kg) and taurine (500 mg/kg) respectively, for 12 weeks after STZ injection. Results. Both rosiglitazone and taurine treatments significantly decreased fasting blood glucose, renal functions (serum creatinine, blood urea nitrogen, albuminuria), and renal oxidant potential (Malondialdehyde), as well as, tumor necrosis factor-alpha (TNF-α). They also significantly improved renal antioxidant capacity (reduced glutathione) and histopathological changes. Furthermore, taurine significantly diminished serum ADMA, while rosiglitazone showed no significant effect. Conclusion. The present study suggests that the treatment with rosiglitazone or taurine can reduce the progression of renal damage in streptozotocin-induced diabetic nephropathy in rats by different mechanisms. However, reducing ADMA could be a potential therapeutic target.

Autoimmune diseases are a heterogeneous group that involves almost any tissue and organ, a patient could frequently present more than one autoimmune disease. Type 1 diabetes mellitus is frequently associated with other autoimmune diseases in polyglandular autoimmune syndrome. Aim of the study is to evaluate a phenotype of diabetic patients with autoimmune diseases. There is a retrospective study; we analyzed type 1 diabetes inpatients from our department in late 4 years based on clinical records. We state that type 1 diabetes mellitus diagnosis is established based on insulin treatment at onset or less than 1 year from onset. We analyzed the presence of the following autoimmune diseases: Graves&#8217; disease, Hashimoto thyroiditis, autoimmune hypothyroidism, Addison&#8217;s disease, vitiligo, psoriasis, systemic lupus erythematosus, pernicious anemia. We recorded 151 patients with type 1 diabetes mellitus: 91 (60.3%) women. Mean age was 38.4?15.8 years, mean span of type 1 DM was 12 years, mean age at the onset of DM was 26.5 years, and mean BMI was 23.4 kg /m2. Patients were insulin treated with 2 doses of insulin 11.3%, 3 doses of insulin 41.6%, 4 doses of insulin 45%, and insulin pump 2%. 41 patients (27.2%) associated other autoimmune diseases, most frequently being chronic thyroiditis. Type 1 DM preceded autoimmune disease in 60%. Patients that associated autoimmune disease have mean age at the onset of type 1 DM 29.1 years. Mean glycated hemoglobin among patients with autoimmune diseases was 10.1% vs. 9.9% among patients without autoimmune diseases (NS); mean insulin needs were respectively 0.78 u/kgc vs. 0.72 u/kgc (NS). In conclusion, type 1 DM is frequently associated with other autoimmune diseases, patients being mainly women. The most frequent association is Graves&#8217; disease. In over 50% of cases type 1 DM precedes autoimmune disease with several years. Even though more than half of patients were treated with multiple doses of insulin, glycated hemoglobin was high, slightly higher among patients with autoimmune diseases but the differences were not statistically significant.

Published data sustain the involvement of diet on pathogenesis of immune-mediated diseases.\r\nAim. To determine if the high fat diet (HFD), in the absence of obesity, could modulate the altered pulmonary arteries\r\nreactivity associated to allergic lung diseases.\r\nMaterials and Methods. Obese resistant rats were divided into 2 groups: standard chow diet and HFD. Randomly chosen rats from both groups were sensitized against ovalbumin. The histological aspect and reactivity of pulmonary arteries were comparatively assessed. Taking into account the involvement of adipokines on obesity associated vascular reactivity alteration we also studied the vasomotor effects of few adipokines on pulmonary vessels.\r\nResults. Lung histological examination revealed that HFD aggravated the remodelling of pulmonary arteries and\r\ninflammation of lung parenchyma. The HFD amplified the phenylephrine - induced contractions. Angiotensinogen amplified and apelin inhibited the Phe contractile effects on sensitized HFD fed rats.\r\nConclusion.These effects could be at least mediated, by both the alteration of adipokines vasomotor effects and\r\ninflammation associated to pulmonary allergic disease.

Background. Although androgen deficiency in men is associated with obesity, whether the deficiency is a consequence of the syndrome is still unclear. Aim. The aim of this study was to determine the association between low levels of sex hormones and development of the metabolic syndrome. Subjects and Methods. A total of 836 men, aged ≥ 20 years, participants of the Tehran Lipid Glucose Study, were assessed at baseline and after 6.5 years follow-up, based on both ATP III and IDF criteria for occurrence of metabolic syndrome. The association between serum total and free testosterone index and SHBG and metabolic syndrome was investigated using logistic regression models. Results. After 6.5 years of follow-up, the metabolic syndrome developed in 131 and 207 men based on ATP III and IDF criteria respectively. Multiple logistic regression analysis showed an inverse relationship for total testosterone in the lower tertile concentration, and serum triglycerides, according to both criteria mentioned (OR = 1.6; 95%CI 1.02-2.5). According to ATP III criteria, adjustment of waist circumference eliminated most of the correlations between total testosterone and metabolic syndrome (OR=1.34, 95% CI (0.8-2.3), while SHBG and free testosterone index were not significantly associated with the syndrome. According to IDF criteria, statistical adjustment of waist circumference eliminated most of the correlations between total testosterone and metabolic syndrome [(OR=1.45, 95% CI (0.9-2.3)], and adjustment with triglycerides eliminated all correlations between SHBG and metabolic syndrome (OR=1.5, 95% CI (0.9-2.5). Conclusions. Androgen deficiency may be related to poorly controlled serum triglycerides and increased waist circumference.

Objective. The aim of this study was to evaluate the possible protective effects of MT against gastric oxidative stress and dyslipidemia in streptozotocin (STZ) - induced diabetic rats. Methods. Forty male Wistar rats were randomly divided into five groups: control, diabetic, MT 5 mg/kg+ STZ, MT 10 mg/kg+ STZ and MT 20 mg/kg+ STZ. STZ (60 mg/kg) was intraperitoneally (ip) injected as a single dose for diabetes induction. One week after STZ administration, MT was injected daily as ip for 14 days. The levels of malondialdehyde (MDA), total thiol and glutathione, as well as superoxide dismutase (SOD) and catalase activities were measured in gastric tissue. Serum concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were also determined. Results. Serum glucose significantly increased in diabetic group compared to control group. STZ induced a significant decrease in gastric tissue levels of total thiol, glutathione, catalase and SOD activities and a significant increase in MDA concentration. In diabetic rats, serum TG, LDL and TC were significantly higher and HDL was significantly lower than in the control group. Treatment of diabetic rats with MT caused a significant increase in gastric total thiol content and glutathione concentration as well as SOD and catalase activities. Gastric MDA concentration and serum LDL, TG and TC were significantly lower in MTtreated groups when compared with diabetic group. Conclusion. These data suggested that MT has a therapeutic effect on gastric oxidative damage and dyslipidemia induced by diabetes that possibly may be due to its antioxidant effects.

Context and Objective. The risk of needing lifelong thyroid hormone supplementation is an important factor affecting treatment decisions for both patients and clinicians ahead thyroid lobectomy. The purposes of this study were to assess the predictive factors of levothyroxine medication after thyroid lobectomy. Methods. We retrospectively reviewed 252 patients who had undergone lobectomy for benign thyroid nodules between April 2009 and April 2017. We conducted two independent analyses: patients who started taking levothyroxine after surgery were compared with those who did not, and patients who did not need levothyroxine at last follow-up were compared with those who required continued treatment. We investigated the correlations of patient clinicopathological characteristics and levothyroxine medication after lobectomy. Results. Ninety-eight patients started levothyroxine after surgery. Of these, 34 patients successfully ceased medication and 64 patients continued treatment as of their last follow-up. In multivariate analysis, older age and preoperative TSH ≥2.0mIU/L were associated with levothyroxine initiation after surgery. In terms of continuity of levothyroxine, both older age and TSH ≥ 3.0mIU/L showed a significant correlation with continuous medication. We created a risk-scoring system to predict likelihood of starting and maintaining levothyroxine using the two significant factors in each comparison. A risk score of 3 or more indicated an increased risk of starting levothyroxine (specificity = 81.8%; sensitivity = 48.0%). A risk score of 3 or more indicated increased risk of continuous medication, (specificity = 94.2%; sensitivity = 35.9%). Conclusions. Greater age and higher preoperative TSH levels correlated with initiation and continuity of levothyroxine medication after lobectomy.

Introduction. The definition of severity and activity of Graves' ophthalmopathy (GO)comprises different parameters.\r\nThe aim of this study is to select the most appropriate severity and activity criteria, respectively scores and to investigate a possible correlation among them.\r\nSubjects and methods. The study included 51 patients with GO (43 females, 8 males), mean age 46.8?11.2 years. The patients were evaluated by: clinical exam, laboratory\r\nparameters (TSH, FT4, FT3, thyroid autoantibodies) and imagistic means, performed in selected cases (CT or MRI).\r\nResults. The GO activity was assessed by the clinical activity score (CAS). We quantified the EUGOGO severity criteria, by allotting points for each selected parameter.\r\nAccording to the recommended criteria, the cases were divided into active (n=26) and inactive forms (n=25). There were no significant statistical differences regarding CAS\r\nbetween euthyroid cases (n=14) and dysthyroid cases (n=37). Serum thyroid receptor antibodies (TRAb) levels did not correlate with CAS or severity scores. Severity scores\r\ncorrelated significantly with CAS (Pearson correlation index 0.546, r2=0.290, p=0.0001).\r\nConclusion. Active forms of GO showed higher severity scores than the inactive ones. The severity scores correlated significantly with CAS scores. Neither CAS, nor severity scores correlated significantly with the severity of thyrotoxicosis.