ACTA ENDOCRINOLOGICA (BUC)

Background. It is important to protect recurrent laryngeal nerve (RLN) during thyroid surgery. Thus, intraoperative neuromonitoring (IONM) has got popularity. But, the half life of neuromuscular blocking agents used has a reverse correlation with reliability and effectiveness of IONM. This study aimed to research the effect of Sugammadex Sodium, a specific nemuromuscular blocking agent antagonist, on nerve conduction and IONM. Materials and methods. Twenty patients who underwent thyroidectomy under IONM followed an enhanced NMB recovery protocol-rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the beginning of operation. To prevent laryngeal nerve injury during the surgical procedures, all patients underwent intraoperative monitoring. At the same time, the measurement of TOFWatch acceleromyograph of the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥ 0.9. Age, sex, recurrent laryngeal nerve transmission speeds prior to and after operation, BMI, duration of surgery, the change in nerve transmission after drug administration and complications were analyzed. Results. The mean age and the mean BMI were 47.6±11.82 years and 28.74±3.20, respectively. The mean operation duration was 52.65±5.51 minutes. There was no difference in either right or left RLN monitoring values before and after surgery. Following the drug injection, the TOF guard measurements on the 1st, 2nd, 3rd and 4th minutes were 23.5±4.90; 69.5±6.86; 88±4.1 and 135.9±10.62, respectively. Conclusion. Neuromuscular blocking antagonist use and monitoring nerve transmission speed with TOFguard can provide a safer resection.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. It is generally considered weight-neutral with chronic use and does not increase the risk of hypoglycaemia. Most patients eventually require more than one antihyperglycemic agent to achieve target blood glucose levels. The primary objective of this non-interventional study was to describe and compare the main criteria used by physicians from regular outpatient setting in selecting the add-on therapy in patients with inadequately metformincontrolled type 2 diabetes in 2 time points at 1-year distance by assessment of patient, and/or agent characteristics and/or physician decision. At the end of phase one of the study, the mean duration of type 2 diabetes was 6.8 years. The majority of patients included in the study were overweight (32%) and obese (62%), and presented diabetes complications (59.6%). In 50% of the cases, the major reason for selecting the second-line therapy was related to patient characteristics, while agent characteristics and physician decision were the main categories in 38% and 12%, respectively. Importance to achieve glycemic control and estimated treatment efficacy were selected in 73.9% and 82.4% of patients, calculated as percentage in the respective categories.

Objective. This study aims to investigate the factors affecting development of acute kidney injury (AKI) in patients with severe hypothyroidism. Methods. This retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Factors affecting the development of AKI were examined by logistic regression analysis. Results. A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3–68.5) was significantly higher than the control group (49 years, IQR 32.3–60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955–598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491–118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602– 82.848; p = 0.015) were predictors for the development of AKI in patients with severe hypothyroidism. Conclusion. We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if patients who are diagnosed at age > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

Background. Alpha lipoic acid (ALA) acts as essential co-factor for mitochondrion respiratory enzymes. It has an increasing importance in diabetic neuropathy treatment. Its positive effects on weight gain and metabolic parameters have also been discussed. In this study, we aimed to search for the effect of ALA on weight, appetite, adiponectin and metabolic parameters in type 2 diabetes mellitus patients. Methods. This study is designed as a randomised, double-blind, placebo controlled, prospective study. 23 type 2 diabetes mellitus patients with peripheral neuropathy (6 normal weight, 17 obese) and 21 normal weight control group were included in the study. Patients were given 600mg/day oral ALA for 6 weeks, added to their routine therapy. Body mass index (BMI), adiponectin, fasting plasma glucose, HbA1C, lipid parameters and CRP levels were tested before and after ALA treatment. Results were evaluated using SPSS 15.0 for Windows. Results. Adiponectin levels were statistically significantly lower and CRP levels were higher in diabetes group when compared to control group. Although ALA treatment caused a slight weight loss, it was not statistically significant. Appetite scores were decreased in the diabetes group but it did not cause statistically significant weight loss. There was no significant change in metabolic parameters or adiponectin after the treatment. Conclusions. 600mg/dL ALA treatment for 6 weeks did not favor for metabolic parameters in type 2 diabetes patients. This result might be due to the dose or the duration of the treatment, genetic predisposition or dietery habits. Trial of higher doses for long terms might be needed for recovery.

Background. The loss of reproductive function is one of the mostimportant adverse effects of chemotherapy. Folic acid deficiency may be harmful in pregnancy. Hence, it is imperative to investigate if leucovorin (LCN), a folinic\r\nacid supplementation and withdrawal of MTX treatment facilitate maintenance of pregnancy in albino rats.\r\nAim. The aim of this study was to examine the role of leucovorin (LCN) and withdrawal of MTX treatment in the\r\nprotection of pregnancy at very early stage of pregnancy in MTX treated rats.\r\nAnimals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows: Control,\r\nMTXLD (low dose), MTXHD (high dose), MTXHD + LCN (leucovorin), and MTXHD + WD (withdrawal). Animals were treated intramuscularly (im) on days 1-5 of pregnancy. MTXHD treatment was withdrawn and female rats showing regular cycle were caged with male rats. Laparotomy was performed on day 8 of pregnancy to note the number of implantation sites. Rats were sacrificed on day 20.\r\nResults. MTX significantly reduced maternal weights, number of corpora lutea, and implantation sites. 100% foetal\r\nresorption was prevalent in MTX treated groups. LCN supplementation did not help maintain pregnancy. While approximately 45% foetal resorption was observed in\r\nwithdrawal group.

Context. Genetic factors are responsible for up to 80% of height variation in humans. SHOX gene mutation could be an important etiologic factor in short stature, being observed in up to 15% of patients. Aim. Our aim was to evaluate the genetic causes of short stature, using classical and molecular cytogenetic techniques by analyzing a group of Romanian patients diagnosed with short stature. Material and methods. Seventy nine patients were analyzed and the main criteria for inclusion in the study was the presence of a height below -2DS. For each of these patients a karyotype was performed. In those with normal karyotype it was indicated FISH technique using probes for SHOX and centromeric regions. Results and discussion. The karyotype revealed the presence of abnormalities in 13 patients (16%), 62% (8 patients) of these being represented by heterosomal abnormalities. SHOX deletion was seen in one patient (2.3%) with short stature and normal karyotype. The initial analysis of the cases with short stature directly by FISH technique can be proposed, using probes for X chromosome centromere and SHOX gene, because it allows, approximately at the same costs with the karyotype, but faster and at a higher rate of mosaicism detection, the explanation of short stature by sex chromosomes abnormalities.

Context. There are evidences that excessive production of reactive oxygen species is one of important abnormalities that contribute to development of chronic diabetic complications. Objective. To test the effect of intensive insulin therapy with analogues through the examining the level of oxidative stress parameters. Subjects and Methods. Comparison of data obtained by prospective analysis in 49 patients with T1DM was used, before and after six months of intensive insulin analog therapy. Results. The values of all three investigated parameters of oxidative stress malondialdehyde (MDA); xanthine oxidase (XO) and nitrates and nitrites (NOx) in our population with T1DM compared to the control (group of 42 voluntary blood donors) are statistically higher. The levels of antioxidant protection parameters compared to the control group also differ; the activities of catalase and glutathione peroxidase (GPx) are statistically higher in our population of T1DM patients compared to the control and superoxide dismutase (SOD) activities are statistically lower. The values of all three examined parameters of oxidative stress decrease after six months of intensive insulin analog therapy and were statistically lower after the therapy: for MDA p<0.001, for XO p<0.01 and for NOx p<0.05. The activities of catalase (p<0.001) and GPx (p<0.01) both decrease with therapy, while the activity of SOD is highest after the sixth month of therapy (p<0.001). Conclusion. In our patients with T1DM compared to the control the level of oxidative stress is significantly higher. Intensive insulin analog therapy with aspart and glargine promotes predominantly the improvement of oxidative stress, and in a less degree antioxidant protection.

It is known that antithyroid drugs have been associated with development of agranulocytosis or secondary autoimmune neutropenia. Aplastic anemia is an unusual but severe form of haematological complication after antithyroid drugs. We are presenting a case of a 34-year old woman diagnosed with Graves&#8217; disease, based on ophthalmopathy, symptoms and signs of hyperthyroidism, a diffuse enlargement of the thyroid gland; TSH level= 0.17 mU/L, fT4= 28 pmol/L, T3= 4.92 nmol/L, thyroglobulin antibodies= 117 IU/mL. The patient developed, after six weeks of treatment with Carbimazole 60 mg daily, a moderate aplastic anemia (pancytopenia: haemoglobin level= 8.2 g/dL, granulocytes= 800/mmc, platelets= 40,000/mmc; hypocellular bone marrow with increased fat cells and lymphocytosis, plasmocytosis and mastocytosis, in the absence of neoplastic or infectious infiltrations, possibly with immune aetiology suggested by disturbance of CD4/CD8 and favourable response after immunosuppressive therapy). Therapy was represented by: stopping the administration of carbimazole, broad spectrum antibiotics, antiviral and antifungal prophylaxis,general and dental hygiene, high doses of methylprednisolone followed by Cyclosporin A 12 mg/kg/day, with favourable evolution. The serum T3 and T3/T4 ratio increased after the antithyroid drug regimen was stopped . After 3 months of therapy, the patient was in complete haematological response with haemoglobin value= 11.8g/dL, granulocytes= 2.200/mmc, platelets = 130,000/mmc and was submitted to subtotal thyroidectomy.