ACTA ENDOCRINOLOGICA (BUC)

Aim. The efficacy of various treatment regimens in severe premenstrual syndrome, (PMS), and premenstrual dysphoric disorder, (PMDD).\r\nStudy design. The study group of 92 patients, aged 20-36 years, was assessed for 2 months before and at the end of one of the following 4 months treatment regimens, randomly assigned: A - combined oral contraceptives with drospirenone; B - oral contraceptives without drospirenone; C - selective serotonin reuptake inhibitors; D - EPO and vitamin B6. A not blinded control group of 92 age-matched patients with severe PMS, without medication, was used.\r\nMethods. All 184 patients completed the Prospective Record of the Impact and Severity of Mastodynia (PRISM) calendar published in 1985 (11) for every of the 6 months of the study. We did not manage or analyze PMDD separately from severe PMS. Simple t test of the initial PRISM results was used, as well as Student t test, or the chi2 test / Fisher test for qualitative data for subgroup analysis.\r\nResults. Oral contraceptives with drospirenone (treatment A) significantly improved the breast tenderness (average severity score was 14.5 ? 0.6 before and 8.9 ? 0.7, p< 0.05, after treatment) and the lack of self-control (average severity score was 14.3 ? 0.7 before and 9.1 ? 0.5, p< 0.05 after treatment). However, oral contraceptives without drospirenone (treatment B) also significantly improved the same parameters of PMS: breast tenderness (average severity score was 15.3 ? 0.4 before and 9.2 ? 0.5, p< 0.05 after treatment) and the lack of self-control (average severity score was 15.5 ? 0.5 before and 9.8 ? 0.7, p< 0.05 after treatment). The subgroup on drospirenone oral contraceptives did not show any premenstrual weight gain, unlike the other subgroups. SSRIs (treatment C) significantly improved the lack of self-control (p< 0.01), but without significant effect on breast tenderness and without any effect on the weight gain. EPO and vitamin B6 (treatment D) showed no significant effects.\r\nConclusion. Concerning the number of patients, drospirenone containing oral contraceptives showed effective improvement of PMS in 67.9% (remission) versus 35.9% (remission in the control group without any medication). However, the authors suggest that SSRIs (and not oral contraceptives with or without drospirenone) might be the treatment of choice in cases where mood / behavioral symptoms prevail over physical symptoms.

Aims. The aims of our study were to assess the prevalence of prostate tumors in patients with metabolic syndrome.\r\nMaterial and methods. Subjects were patients recruited from three medical centers in Bucharest, Romania. For this study we selected men over 45 years of age with metabolic syndrome. The anthropometric measurements included height, weight, waist circumference and hip circumference. We calculated the body mass index (BMI) and measured the\r\nblood pressure. Biochemical tests included fasting plasma glucose (FPG), HbA1c, total cholesterol (TC), TG, HDL-C, fasting plasma insulin (FPI), prostate-specific antigen (PSA)and free-PSA. The prostate gland volume was measured by transrectal ultrasound. The diagnosis of prostatic cancer was based on a positive finding of the histological\r\nexamination obtained from 14-core biopsy.\r\nResults. There was a high prevalence of prostate tumors (benign and malignant) - 82.85% (n=343). Prostate cancer was\r\ndiagnosed in 7.9% of patients (n=33) using DRE, PSA, free PSA/PSA ratio and TRUS. The prevalence of BHP was 74.9% (n=310). The results of the present study indicate that\r\nPSA detects a significant number of prostate tumors missed in DRE. The use of DRE, PSA and TRUS, in combination, provided the highest rate of detection of prostatic tumors in patients with metabolic syndrome without infectious diseases of the prostate.\r\nConclusions. The prevalence of prostatic tumors, prostate cancer and benign prostatic hyperplasia in metabolic syndrome patients is high. Due to its increased prevalence, the BPH can be considered as a feature of metabolic syndrome.

Background. The pathogenesis of pre-eclampsia involves inflammation, endothelial\r\ndysfunction and enhanced oxidative stress. Interleukin (IL)-6 is a major pro-inflammatory\r\ncytokine, while leptin is released in large amounts by the adipose tissue, but also by placenta.\r\nAim. The present study aims to evaluate total maternal serum leptin and IL-6 levels in\r\npre-eclampsia compared to normal pregnancy and non-pregnant status.\r\nMethods. We enrolled 65 women in a transversal study; pre-eclampsia was diagnosed\r\nin 25 (group 1), 25 women had a normal pregnancy (group 2), while in 15 pregnancy was\r\nexcluded. Groups were matched for chronological and gestational age and body mass index\r\n(BMI) accordingly. Total serum leptin and serum IL-6 were determined using ELISA, after\r\nan overnight fasting period of at least 12 hours.\r\nResults. Both leptin and IL-6 concentrations were significantly higher in women in the\r\nthird trimester of pregnancy developing pre-eclampsia compared to normotensive pregnant\r\nwomen (p=0.001). Normal pregnancy was characterized by increased serum leptin levels\r\n(p=0.001) as well as increased IL-6 levels (p=0.001) in comparison to non-pregnant status.\r\nIn women with pre-eclampsia, leptin was positively and significantly correlated with\r\ndiastolic blood pressure (r=0.45, p=0.02), proteinuria (r=0.48, p=0.01) and uric acid values\r\n(r=0.39, p=0.04) and inversely related to HDL cholesterol levels (r=-0.64, p=0.0001).\r\nLikewise, IL-6 was positively related to systolic and diastolic blood pressure (r=0.41,\r\np=0.008 and r=0.60, p=0.00003, respectively), proteinuria (r=0.38, p=0.01) and uric acid\r\nvalues (r=0.43, p=0.004). However, leptin had no correlation with pregnancy outcome in\r\nwomen with or without pre-eclampsia. In contrast, IL-6 was negatively correlated with both\r\nfetal birth at weight (r=-0.35, p=0.02) and Apgar score (r=-0.38, p=0.01).\r\nConclusions. In conclusion pre-eclampsia associates significantly increased serum\r\nleptin concentrations and IL-6 production compared to normal pregnancy. In contrast to\r\nleptin, IL-6 may predict pregnancy outcome (fetal birth weight and Apgar score) in women\r\nwith pre-eclampsia.

Background. Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. Objective. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. Setting. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. Methods. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. Main outcome measure. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. Results. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. Conclusions. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

sitive period in terms of thyroid hypofunction. Iron deficiency has been associated with both thyroid function and thyroid autoimmunity. Objective. We aimed to investigate whether iron deficiency is a risk factor for thyroid autoimmunity in nonpregnant women at childbearing age. Design. This cross- sectional study was conducted in non-pregnant women who presented to the Internal Medicine Policlinic between January 2018 and December 2018 in the University of Health Sciences “Fatih Sultan Mehmet” Training and Research Hospital. Methods. Three hundred fifty-eight non-pregnant women of reproductive ages (203 iron deficient-ID, 155 control) participated in this study. Women with known thyroid disease, currently undergoing treatment for thyroid disease or whose thyroid function tests were outside the reference range were excluded from the study. Blood sample was taken after at least 8-10 hours of fasting for measurement of serum iron (Fe), total iron binding capacity (TIBC), serum ferritin (SF), whole blood count, thyroid function tests (fT4, TSH), anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibody (TgAb). The patients with SF levels ≤ 15 ng/dL were accepted as iron deficiency. Results. The group with ID had higher TSH and lower T4 values that did not reach statistical significance compared to the control group (p=0.101 and p=0.098, respectively). Antibody positivity was more frequent in the ID group than in the control group (35.96% vs. 20.65%, p = 0.002). Conclusions. Iron deficiency is associated with thyroid autoimmunity and it should be considered as a risk factor for screening thyroid antibody, particularly in pregnancy planning women.

Background. Patients with type 2 diabetes mellitus (T2DM) have a higher risk of developing obstructive sleep apnea (OSA) compared to the general population. Our study aims to analyze the usefulness of the STOP-BANG score, tool which was not yet validated in patients with diabetets, as a tool that estimates the severity of OSA, in patients with T2DM. Methods. 120 patients, who answered the STOPBANG questionnaire and underwent polysomnography, were included in the study. The patients were divided into 3 groups, depending on the severity of OSA, defined by the apnea/hypopnea index (AHI). Results. A significant percentage of participants (42.1%) had a severe form of OSA (AHI ≥30) and a high percentage of subjects had a STOP-BANG score ≥5 (58.7%), equivalent to a severe form of the disease. The STOP-BANG score increased proportionally with AHI (p<0.001). The area under the ROC curve for the STOP-Bang score indicated an optimal cut-off value of 4.5, with a sensitivity of 88.2% and a specificity of 62.9% (p <0.001), STOP-BANG score ≥5 being an independent predictor for severe OSA in patients with T2DM. Conclusions. The STOP-BANG score can be used in patients with diabetes to detect severe OSA in order to establish appropriate therapeutic measures.

Background. We know that mortality had increased in diabetic patients with COVID-19 pneumonia. The aim of this study was to compare the mortality and inflammation parameters difference in critically ill COVID-19 patients according to their admission HbA1c levels and diabetes mellitus status. Secondary aim was to evaluate the effect of the first week hyperglycemic episode frequency on mortality. Methods. Critically ill COVID-19 patients who were tested for HbA1c levels on ICU admission were analyzed retrospectively. Results. Of 218 COVID PCR(+) patients, 139 met the inclusion criteria in study period. The median age was 67[57-76] years and 55(40%) of them were female. Seventy-six (55%) of the patients required invasive mechanical ventilation (IMV). The IMV requirement was higher in diabetic patients (p=0.01). When the groups were compared in terms of inflammatory parameters no significant difference was found except for admission and first week’s highest fibrinogen levels (p=0.02 and p=0.03, respectively). In multivariate analysis, fibrinogen levels were not determined as a risk factor for mortality. Overall ICU mortality was 43% (60/139). In group-1 23(37%), in group-2 27(57%), and in group-3 10(34%) patients had died. There was no statistically significant difference between groups in terms of mortality (p=0.05). Records of 96(69%) patients revealed there were more than five glucose readings over 180mg/dL during the first week. Mortality was higher in patients with more frequently hyperglycemic recordings (p=0.03). Conclusions. There was no significant mortality and inflammatory parameters difference in patients with and without diabetes. However, more than five glucose readings over 180mg/dL during the first week were found with increased mortality.

Context. Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. Objective. We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. Subjects and Method. We conducted a crosssectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot’s arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. Results. RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. Conclusions. RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Objectives. It was aimed to evaluate the relationship of Dehydroepiandrosterone-sulphate(DHEAS) level with pregnancy, fertility, abortion, ovarian reserve and endothelial functions. Patients and Method. Ninety-six fertile women aged 20-35 years whose DHEAS levels were measured and 28 women aged 40-55 years with oligomenorrheaamenorrhea were included in the study.The DHEAS values of the patients,which were measured at least 12 months apart,were recorded. Results. The first measured mean DHEAS level was 208.34±119.7ug/dL and the last measured mean DHEAS level was 187.5±101.7ug/dL. Among 28 patients with oligomenorrhea-amenorrhea, the levels of DHEAS increased in 10 patients and decreased in 18 patients. Although the annual decrease in DHEAS levels was greater in those who had pregnancy than in those who had not given birth, the difference was not statistically significant (p=0.085). Although the initial DHEAS level in 5 patients who had an abortion was higher than in those who did not have an abortion, the difference was not statistically significant (p=0.427). The increase in systolic blood pressure was statistically significant in patients with decreased DHEAS levels (p=0.03). While the mean DHEAS level was 85.3±47.3ug/dL in menopausal patients, the DHEAS level was 82.1±49.2ug/dL in non-menopausal patients (p=0.435). Conclusion. The age at which the DHEAS level reaches its peak level shows individual differences. While pregnancy slows down the decrease in DHEAS levels,abortion accelerates the decrease in DHEAS levels. A decrease in serum DHEAS levels can increase systolic blood pressure.

Context. Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. Objective. We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Design. We conducted a cross-sectional casecontrol study for the period of 2008-2012. Subjects and methods. Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. Results. We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found – increased deceleration time and decreased e/a tric ratio. Conclusions. In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.