ACTA ENDOCRINOLOGICA (BUC)

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.

Context. Anti-Mullerian hormone (AMH) assay is becoming the best indicator of successful IVF treatment response to fertility drugs and could be a useful marker of embryo implantation potential. Various protocols are being used for controlled ovarian stimulation (COS), but there is an uncertainty regarding the implementation of the best protocol for endometriosis patients and also little evidence is available concerning the clinical value of AMH levels in endometriosis. Objective. This study aimed to evaluate the prognostic value of serum AMH levels for pregnancy in COS using GnRH-agonist(GnRH-a) and GnRHantagonist( GnRH-ant) protocols in endometriosis patients. Design. This is a cross-sectional study between March 2012 and November 2015. Subjects and Methods. Data were collected from 249 COS cycles of endometriosis patients, including 129 cycles with GnRH-a and 120 cycles with GnRH-ant. Patients in each group were classified into three subgroups based on their serum AMH levels. The outcomes of ICSI program were evaluated. Results. The ROC curve analysis showed that embryo and oocyte counts and AMH were equally predictive for pregnancy, as demonstrated by a similar area under the curve (AUC) of 0.69, 0.66 and 0.64, respectively. The sensitivity and specificity for prediction of positive pregnancy were 70.91% and 67.01% for embryo counts, 70.91% and 67.53% for oocyte counts at the cutoff values of 5 and 7, respectively, and 83.64% and 52.58% for AMH levels at the cutoff values of 1.3ng/mL. Conclusions. This study demonstrates that AMH as a single test has substantial accuracy in the prediction of pregnancy using the GnRH antagonist protocol for patients with endometriosis. In other words, AMH assay prior to ovarian stimulation initiation guides the clinicians to choose the antagonist stimulation protocol for the patients with two extreme AMH levels. AMH levels can be used to individualize control ovarian stimulation in endometriosis patients.

Context. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Background. The transport of gametes and embryos is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone regulates ciliary beat frequency (CBF) through multiple types of progesterone receptors in the fallopian tube. Membrane progesterone receptors beta and gamma (mPRβ and mPRγ) are both expressed in the ciliated cell lining of the fallopian tubes of humans. This study aimed at exploring the mRNA expression of mPRβ and mPRγ in the fallopian tubes of women with ectopic pregnancy. Materials and Methods. In this Case control study, a quantitative reverse transcriptase polymerase chain reaction was performed to determine the mRNA expression of mPRβ and mPRγ in the fallopian tubes obtained from 12 women with ectopic pregnancies, 12 women with normal pregnancies, and 12 healthy nonpregnant women in the luteal phase of their menstrual cycle. Results. It was indicated that mPRβ and mPRγ were expressed in the fallopian tube of the three groups of participants. However, the expression of mPRβ and mPRγ mRNA in the fallopian tube of women with ectopic pregnancy was not significantly different from that of the nonpregnant and normal pregnant women. Conclusion. These results suggest that mPRs might play no role in etiology of ectopic pregnancies associated with disturbed progesterone signalling.