ACTA ENDOCRINOLOGICA (BUC)

A certain degree of insulin resistance in patients with Gaucher disease type 1 (GD) under enzyme replacement therapy (ERT) was reported. Data on insulin sensitivity in treatment naïve patients are inconsistent. Objective. To analyse prospectively changes in parameters of insulin resistance under ERT and to estimate when they occur. Design. prospective, controlled study; three years follow-up. Patients and methods. 12 treatment naïve patients with GD type 1 (M/W 8/4), 29.5±12.9 years, without overweight, diagnosed enzymatically and by genotyping, without previous diabetes mellitus. Patients were evaluated before and every 6 months up to 3 years under ERT and compared at baseline and after 3 years with matched healthy controls. Fasting-glucose (FG), - insulin (FI), C-peptide, HOMA-IR, IRI, HOMA-B, blood count, hepatic and splenic volume, chitotriosidase, severity score index di Rocco (SSI) were assessed. Results. Baseline glycemic parameters did not differ from controls. FG increased from baseline after two years of ERT (+16.4%,p<0.010), FI (+40.3%,p=0.030), HOMA-IR (+61.2%,p=0.007) and IRI (+9.1%,p=0.010) after 18 months, HOMA-B after 2.5 years (+51%, p=0.015. After 3 years of ERT patients were more insulin resistant compared to controls (p<0.001): FG (96.0±6.2 vs. 73.2±6.4 mg/dL), FI (11.2±2.4 vs. 5.6±1.3 μU/L), HOMA-IR (2.7±0.6 vs. 1.0+0.3), IRI (3.02±0.10 vs. 2.62±0.13). FG, FI, HOMAIR, IRI, HOMA-B correlated with disease severity markers. Conclusions. This is the first controlled study which evaluates prospectively insulin resistance in GD patients, finding significant differences compared to baseline starting with 18 months ERT.

Background. Recent experimental data show that increased plasma adiponectin in chronic kidney disease could be a response to inflammation.\r\nObjective. To identify factors influencing adiponectinemia in patients with type 2 diabetes (T2DM) and microalbuminuria or low grade proteinuria.\r\nDesign. 32 patients with urinary albumin excretion rate (UAER)> 30 mg/g creatinine but without significant proteinuria (< trace COMBUR) were included and compared to 59 normalbuminuric T2DM controls. History, anthropometric measurements, laboratory analysis, total plasma adiponectin were obtained.\r\nResults. In our patients with UAER of 273.51?57.26 mg/g creatinine and estimated glomerular filtration rate (eGFR) 64.92?4.56 mL/min, in simple regression, adiponectinemia\r\ncorrelates inversely to eGFR (p=0.02, r= -0.38), triglyceridemia (p=0.03, r=-0.37) and hemoglobin\r\n(Hb -p= 0.01, r=-0.45) and positively to HDL cholesterol (p=0.001, r=0.54) and UAER (p<0.0001, r=0.71); the two latter parameters remain significant in multiple regression. In controls, adiponectinemia correlates inversely to age (p=0.04, r=-0.26) and BMI (p=0.04, r=-0.24); these and UAER predict adiponectinemia in multiple regression. 11 patients have UAE superior to 300 mg/g creatinine and 21 are strictly microalbuminuric (mean UAER 653.16?97.02 and 83.68?10.28mg albumin/g creatinine respectively). In microalbuminuric patients serum C reactive protein (CRP) correlates positively (p=0.0008, r=0.68) and Hb negatively (p=0.04, r=-0.41) to adiponectinemia; in multiple regression adiponectinemia only depends on CRP. In proteinuric patients CRP and\r\nglycated Hb correlate to adiponectinemia in stepwise multiple regression.\r\nConclusion. Adiponectinemia is mainly predicted by UAER in our cohort whereas it depends on age and BMI in normalbuminuric T2DM controls; in strictly microalbuminuric\r\npatients CRP is a major predictor of adiponectinemia.

Objective. This study aimed to investigate the effect of symptoms of diabetes on the quality of life of individuals with Type 2 diabetes. Method. The study used a cross-sectional design. No sampling procedure was employed in the study; instead, 410 individuals presenting to the Balikesir Atatürk City Hospital Endocrinology and Internal Medicine Polyclinics between December 2016 and July 2017, diagnosed with Type 2 diabetes, and meeting the inclusion criteria were enrolled in the study sample. The study data were collected with a “Socio-demographic Characteristics Questionnaire”, the “Diabetes Symptom Checklist”, and the “SF-36 Quality of Life Questionnaire”. Results. The participants obtained the highest mean scores from the hyperglycemia subscale of the Diabetes Symptoms Checklist (3.35±0.60) and the mental health subscale of the SF-36 Quality of Life Questionnaire (50.65±8.10). The hypoglycemia, cardiology, psychology, and neurology variables included in the model were statistically significant and predicted 35% of the mental subscale score of the SF 36 questionnaire. SF 36 physical subscale score increased as the hypoglycemia, cardiology, psychology, and neurology scores decreased (p<0.05). Conclusion. The participants obtained high scores from the hyperglycemia subscale of the diabetes symptom checklist and mental health subscale of the quality of life questionnaire. Diabetes symptoms were found to affect the quality of life of individuals with diabetes.

Context. Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction. Aim. The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats. Animals and Methods. Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured. Results. The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-α, miR- 126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group. Conclusion. GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

Context. Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. Objective. We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. Design. Cross-sectional, observational study. Subjects and Methods. 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. Results. Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. Conclusions. Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Introduction. Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states,\r\nosteoporosis included, arise when this delicate balance is disrupted such as in menopause.\r\nThe aim of the present work was to study the effect of leptin supplementation on bone metabolism in ovariectomized adult female rats, by measuring indices of bone biomarkers.\r\nMaterial and methods. Forty adult female albino rats were chosen as an animal model for this study and divided into the four equal groups (n=10/group): Group I (control SHAM-operated group), Group II (ovariectomy group). Group III (alendronate group): Ovariectomized rats that received\r\nalendronate 0.1 mg/kg body weight i.p. daily for eight weeks. Group IV (leptin group): Ovariectomized rats that received leptin (10&#956;g/kg body weight) i.p. daily for eight\r\nweeks. The obtained serum is required for determination of: Serum osteocalcin, alkaline phosphatase, calcium and phosphorus levels.\r\nResults. The obtained data revealed that: Treatment with alendronate or leptin caused significant decrease of serum\r\nosteocalcin, specific bone alkaline phosphatase and urinary deoxypyridinoline levels compared to ovariectomy group.\r\nConclusions. The results obtained in the present study provide evidence that daily administration of leptin contributes significantly to improve the bone biomarkers\r\nof ovariectomy in rats. Leptin prevents ovariectomy induced increases in bone turnover in rats.

Graves&#8217; orbitopathy usually occurs in thyrotoxic patients at the presentation of the\r\nhyperthyroidism.\r\nAim: we conducted a cross sectional study over 8 and a half years of the relation\r\nbetween Graves&#8217; orbitopathy and thyroid status in patients presenting to our joint thyroidophthalmology\r\nclinic at University Hospital of Wales.\r\nMethods: Patients with active orbitopathy were diagnosed clinically and with\r\nappropriate imaging where necessary. This series excluded patients previously treated with\r\nradioiodine or surgery for Graves&#8217; disease. Of 259 patients 140 (54%) had not had 131I or\r\nsurgical therapy. Thirty four percent of the 140 had never been hyperthyroid of whom 19\r\n(13.5%) were euthyroid. Twenty nine of the 140 (20.7%) were hypothyroid receiving\r\nlevothyroxine at referral. There were no significant differences between the hyperthyroid\r\nand non hyperthyroid groups in the incidence of cigarette smoking, family history of thyroid\r\ndisease or maximum proptosis at presentation.\r\nResults: We found a higher prevalence of smokers than reported in the literature in\r\nmoderate and severe TAO across all thyroid status groups including hypothyroid only\r\npatients. This study has emphasized the occurrence of Graves&#8217; orbitopathy in hypothyroid\r\npatients as well as euthyroid individuals.

Background. Dual-energy X-ray absorptiometry (DXA) allows measurement of whole body (WB) and regional bone mineral content (BMC) and density (BMD). Objective. To measure WB and regional bone area, BMC and BMD (arms, legs, ribs and pelvis) in women of different ages. Subjects and Methods. 140 women participated (age range 20-75 yrs). Three subgroups were built: 20-44 yr (30 premenopausal women), 45-59 (80 women), and 60-75 (30 women). WB DXA was performed on a Hologic QDR 4500 A bone densitometer (Hologic Inc., Bedford MA). WB BMD T-scores were calculated by using the manufacturerprovided and the NHANES 1999-2004 reference databases, while the WB BMC Z-scores - based on the latter. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). Results. WB BMC and BMD Z-scores were consistently lower than the reference databases showing a difference of about 0.4 – 0.5 SD. The arms, legs and ribs lost more BMC after the age of 50-55, while the pelvis – much earlier. The total decreases in BMC were highest in the pelvis (26.36 %), followed by the arms (16.81 %) and whole body (15.91 %), while the bone area decreased mostly in the pelvis (13.23 %). Conclusion. The age-related declines in regional BMC, bone areas and BMD follow different patterns in appendicular and axial bones.

Background. ThyPRO is a recently developed thyroid-specific quality of life (QoL) questionnaire applicable to patients with benign thyroid disorders(BTD). The aim of the present study was to translate ThyPRO and ThyPRO-39 into Romanian, and to evaluate reliability and cross-cultural validity. Methods. Standard methodology for translation and linguistic validation of patient-reported outcomes (PRO) was applied. The questionnaire was completed by 130 patients with benign thyroid diseases seen at Department of Endocrinology in the Emergency County Hospital, Tîrgu Mureș, Romania, between October 2015 and March 2016. Internal reliability of the Romanian version of the ThyPRO (ThyPROro) scales was assessed for multi-item scales using Cronbach’s alpha coefficient. An efficient method for testing cross-cultural validity is analysis of differential item functioning (DIF). Uniform DIF between the Romanian and the original Danish sample was investigated using ordinal logistic regression. The translation process proceeded without difficulties, and any disagreements were revised by one of the developers and the language coordinator. Results. Internal reliability for ThyPRO was satisfactory. Cronbach`s alpha coefficients for the 13 scales ranged from 0.78 to 0.93 for the ThyPROro and 0.78 to 0.87 for the ThyPROro-39. In the 85-item ThyPRO, nine instances of DIF were found. Most were minor, explaining <3% of the variation in scale score, but DIF in positively worded items were larger, with explained variance (R2’s) around 10-15%. Conclusion. The ThyPROro questionnaire is ready for assessment of health-related quality of life in Romanian patients with benign thyroid diseases.