ACTA ENDOCRINOLOGICA (BUC)

Background. The cytotoxic T lymphocyteassociated molecules-4 (CTLA-4) is related to the relapse of Graves’ disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results. The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis. In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion. This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.

Objective. This study examined the glycemic control among adult patients with type 2 diabetes mellitus (T2DM) and their ongoing antidiabetic therapy focusing on potential differences in attaintment of glycemic control associated with the use of specific antidiabetic regimens (ADR). Design. This was a cross sectional study conducted between September 2019 and March 2020 at a tertiary hospital, department of Internal Medicine. Subjects and Methods. Patients with T2DM who had a diagnosis of T2DM for at least one year and used their prescribed ADR for at least 3 months were included in the study. Glycated hemoglobin (HbA1c) was used for evaluation of glycemic control. Results. A total of 500 patients aged 59.4 (±10.2) years, with 9.9 (±6.7) years of diabetes duration (54% women, BMI: 29.6±5.1kg/m2) were analysed. The mean HbA1c was 8.3% (±1.9) and 34.2% of patients had a HbA1c level ≤7 %. 12%, 20% and 15.4% of diabetic patients were prescribed one, two or more than three antidiabetic drugs, 6.4% were on glucagon-like peptide 1 receptor agonists (GLP-1RA) only and 46% received insulin. Education level (OR=0.79; 95 % CI 0.66-0.94 p=0.009) and use of GLP-1RA (OR=0.19; 95 % CI 0.07-0.51 p=0.001) were associated with improved glycemic control while longer diabetes duration (OR=1.06; 95 % CI 1.02-1.11 p=0.004), use of basal insulin (OR=2.91; 95 % CI 1.70-6.88 p=0.010) and basal-prandial regiments (OR=2.49; CI 1.54-5.38 p=0.020) were associated with HbA1c >7%. Conclusions. Despite the introduction of novel drugs in the treatment of T2DM a majority of our patients fail to reach therapeutic goals.

Context. As the life expectancy prolongs, malignancy has become an important issue in renal transplant recipients (RTRs). Thyroid cancer is the most common endocrine malignancy with ongoing increase in incidence all over the world. Objective and design. This is a cross-sectional study that investigates the thyroid disorders and the prevalence of thyroid nodule and cancer in RTRs. Subjects and methods. 204 RTRs were evaluated for the thyroid diseases with ultrasonography, serum thyroid stimulating hormone, free T4, free T3 levels, antithyroglobulin antibody and anti-thyroid peroxidase antibody levels; FNAB was carried if required. Results. 191 patients (94.1%) had normal thyroid function. Subclinical hypothyroidism was diagnosed in 11 patients, subclinical hyperthyroidism in 1 patient and low T3 syndrome in 4 patients. The FNAB was performed in 17 (27.9%) from 61 patients with thyroid nodule. The cytological examination of biopsy materials revealed that 2 (11.8%) nodules were suspicious for malignancy, 13 (76.5%) were benign, and 2 (11.8%) with non diagnostic cytology. Thyroid cancer prevalence was 0.2% in Turkey but we detected that 0.98% of RTRs had thyroid cancer. Conclusions. Screening the RTRs for thyroid disorders is necessary, so that early diagnosis and appropriate treatment of thyroid disease and cancer may improve the quality of life.

Introduction: There is a large agreement about the positive effect of GH therapy in patients with panhypopituitarism. Objective: We investigated the potential psychological effect of GH replacement in hypopituitary patients secondary to surgery + radiotherapy for pituitary tumors. The study design was prospective, non-placebo controlled.\r\nPatients and methods: after informed consent, we enrolled 14 subjects with pituitary tumor, submitted to transfrontal (FS) or transsphenoidal (SS) surgery and with GH < 1 ng/mL after insulin-induced hypoglycemia. Our subjects were aged 50.2 + 14 years, 11 men, 3 women, with craniopharyngioma (n=3, all postfrontal surgery=post FS), nonfunctioning pituitary adenoma (n=10, 6 post FS, 4 post SS) and 1 macroprolactinoma (post FS). Seven subjects were submitted to radiotherapy. GH (Norditropin) was provided by Novonordisk, in 5 mg vials, self-administered by a specific device (pen) provided by manufacturer in a dose of 0.01 mg/kg/day. GH and IGF 1 were assayed monthly, using a commercial kit. Quality of Life (QoL) was assessed monthly by a 22 item questionnaire provided by Novonordisk, which measures a total QoL score, as well as subscores for depression, anxiety, personal well being and self perceived sense of energy. A statistically significant improvement of QoL score is indicative of positive effect of therapy. Fasting glucose and tumoral dimensions were monitorised every 3 months; 2 patients were excluded from study after diabetes mellitus occurrence; one additional patient discontinued therapy for fears of tumoral outgrowth.\r\nResults: a positive effect could be noticed concerning QoL total score and subscores, concerning auto-perceived level of energy and personal well being. Prior radiotherapy tends to blunt this beneficial effect. IGF 1 increased first 2 months, then we noticed a significant and sustained increase of IGF 1 with frequent upper normal values, especially in more obese and in men rather than in women. Adiposity and BMI decreased during therapy, which favorably influence QoL.\r\nConclusions: patients benefit psychologically from GH therapy. We found an unexpected high rate of metabolic complication (2 out of 14 subjects drop out study because of diabetes mellitus). Prior radiotherapy might blunt the psychological effect of GH.

Background. Blood glucose levels in the human body continuously fluctuate within a certain range. Intermittent hyperglycemia has adverse effects on vascular endothelial\r\ncells and pancreatic beta cells. A few studies have found that blood glucose fluctuation induced apoptosis of both endothelial cells and pancreatic beta cells, possibly due to oxidative stress. This study aimed to determine the\r\neffects of blood glucose fluctuation on hepatocytes in vivo.\r\nMaterials and Methods. To induce intermittent hyperglycemia, rats were intermittently treated with 50% glucose\r\ninjection to fluctuate blood glucose between 5.5 mmol/L and 20.0 mmol/L. The rats with intermittent hyperglycemia were treated with either low dose (0.35 mg/kg?min) or high dose\r\n(0.70 mg/kg?min) N-acetylcysteine (NAC). The rats infused with saline were used as control. Apoptosis was assessed by TUNEL assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver, as well as plasma ALT, AST, TBIL, and IBIL, were examined using colorimetric kits.\r\nResults. Liver function was lower in the rats with intermittent hyperglycemia than in control rats. Hepatocytes exposed to blood glucose fluctuation were more likely\r\nto undergo apoptosis compared to control group (0.07?0.016 vs. 0.015?0.009, P<0.01). The expression of Caspase-3 and\r\ncleaved Caspase-3 was significantly higher in the IHG group than in the SAL group (0.111?0.015 vs. 0.07?0.011; 0.064?0.012 vs. 0.004?0.001, P<0.05).The expression of\r\nBax and the ratio of Bax to Bcl-2 were significantly higher in the IHG group than in the SAL group (0.20?0.05 vs. 0.10?0.02; 0.55?0.20 vs. 0.20?0.05, both P<0.01). When treated with NAC, the liver function of rats with intermittent hyperglycemia improved remarkably, and hepatocyte apoptosis decreased.\r\nConclusion. Blood glucose fluctuation appears to be detrimental to liver function, but this effect can be ameliorated by NAC.

Introduction. The most frequent abdominal tumors in newborn girls are ovarian cysts, with an incidence of more than 30%. Smaller cysts (<4-5 cm) can regress spontaneously within the first 1-6 months after birth and usually require periodic follow-up, while larger cysts have a greater risk of torsion (50-70% of cases), rupture, hemorrhage or can determine compression on nearby organs. There still is no general consensus regarding the optimal management of ovarian cysts in newborns and infants Patients. Methods. Seven newborn female patients were referred to our hospital from maternity wards with a prenatal diagnosis of abdominal mass, over a period of 4 years (2011-2015). In all cases the postnatal ultrasound confirmed the presence of a cystic mass pertaining to the right or left ovary. We divided the patients into 2 groups taking into account the size of the cystic masses and their radiological characteristics: if the cyst was smaller than 4 cm, we followed the patient with periodic ultrasounds and in cases where the cyst was greater than 4 cm, surgical management was considered if the patient presented with complications. Of the 7 cases, 4 underwent surgery, while in 3 cases the decision was made to perform periodic followups. Conclusion. Ovarian cysts are frequently encountered in the neonatal period. No precise guide to the management of this pathology has been established. Close follow-up should be performed and surgical intervention should be done in order to avoid complications.

Context. Sleeve gastrectomy is an effective method for management of obesity. The Bariatric Analysis and Reporting Outcome System (BAROS) is a comprehensive and standard system for the assessment of outcomes of weight loss surgery. It is consisted of weight loss, changes in obesityrelated comorbidities and quality of life measurements. We investigated results of the sleeve gastrectomy based on the BAROS. Material and Methods. Outcomes of laparoscopic sleeve gastrectomy surgery was studied in 45 patients with obesity (11 male, 34 female), after 45 months in Turkey. Results. Total weight loss was 26.4±0.1% of body weight at 45 months. Weight regain was seen in 97.8% of the patients with an average 14.5 kg and 13.7% body mass index points. The surgery caused 76% decrease in incidence of obstructive sleep apnea, 73% decrease in type 2 diabetes, 63% decrease in hyperlipidemia and 62% decrease in hypertension. Significant improvement is observed in all quality-of-life parameters. The final score of the BAROS was 4.23±1.02. Conclusion. Based on BAROS, sleeve gastrectomy provides significant improvements in weight loss, incidence of medical comorbidities and quality of life after surgery. Future studies should address prevention of weight regain after the surgery.

Aims. We investigated the prevalence of micro and macro-vascular complications and how these patients perform with respect to current treatment goals. \r\nMethods. We performed a cross-sectional study in type 2 diabetes subjects treated with biguanides in monotherapy, attending a standard diabetes outpatient clinic during 2008-2009. We used the latest available visit at the Clinic for data regarding demographics, anthropometrics, biochemistry, micro and macrovascular complications of diabetes. \r\nResults. We investigated 814 subjects, 463 (56.9%) females, mean age 62.6?10.5 years, age at diabetes onset 60?10.4 years, and a disease duration at study inclusion 2.6?3.9 years. Only 5.2% of females and 17.7% (p<0.01) of males had a waist circumference <80/<94 cm and 40.4% of cases had a fasting plasma glucose <7.21 mmol/l. The therapeutic target for blood pressure was achieved in 14.7% of cases for systolic blood pressure (<130 mmHg) and 29.6% for diastolic blood pressure (<80 mmHg). \r\nConclusion. Individuals with type 2 diabetes treated with biguanides in monotherapy are poorly controlled, have a high prevalence of metabolic syndrome components as well as micro and macrovascular complications.

Newborn screening of phenylketonuria (PKU) is performed in many countries, including Romania, in addition to screening for congenital hypothyroidism. Patients affected by PKU require frequent measurements of phenylalanine (Phe) level in blood plasma. Such a determination is important not only in early diagnostic, but also in monitoring the treatment of PKU to maintain phenylalaninemia within limits that will not affect the brain. A simple, highly sensitive, accurate and rather inexpensive procedure for the simultaneous determination of Phe and Tyr plasma concentrations was previously described in this journal. The new procedure may be applied in many clinical laboratories, including those with no previous experience in diagnosis of inherited amino acid metabolic disorders. In this way the major public health problems linked to PKU not being detected in the first weeks of life (including the burden of institutionalized children with preventable mental retardation) may be avoided.

Objective. We aimed to investigate the prevalence of obesity and visceral obesity (VO) within children living on the small Greek island of Tinos and their associated factors. Methods. Three hundred and fifty two healthy children and pre-adolescents (54% boys) attending the primary schools of Tinos island were evaluated, aged (mean±SD) 8.53±1.72 years (range 6-11), from which 286 (81.25%) were of Greek origin and 65 (18.46%) foreign immigrants. Body weight, height and waist circumference (WC) were measured, plus BMI and WC percentiles were calculated. Children with WC > 90th percentile were categorized as having VO. Results. Among our patients, 235 (66.76%) were of normal weight, 88 (25%) overweight and 29 (8.2%) obese. Obese children, as opposed to their normal weight counterparts, were more likely to be of younger age (p=0.009). VO was found in 65 (18.47%) children, with a higher prevalence among the obese than overweight ones (96.43% vs. 42%, p<0.001). There was no difference in the prevalence of VO between children and pre-adolescents. However, foreign immigrants had lower frequency of overweight and obese children (p=0.026) and less viscerally obese children (9.09% vs. 20.63%, p=0.018) than the Greek participants. Conclusions. The prevalence of childhood obesity in rural Tinos was 8.24%, which was lower than the reported national prevalence of obesity in Greece, whilst almost all of the obese and 42% of the overweight children presented VO. The low prevalence of childhood obesity and VO on this small island could possibly be attributed to a more healthy diet and natural way of life.