ACTA ENDOCRINOLOGICA (BUC)

Introduction. First election treatment in Cushing’s syndrome is the surgical therapy (pituitary or adrenal). Pharmacotherapy is used: before surgery, when the surgery was ineffective, in association with radiotherapy or in cases of refuse or contraindications for surgery. Aim of the study. Testing the effectiveness and safety of Ketoconazole treatment in patients with Cushing’s syndrome. Methods. We studied 12 patients with Cushing’s syndrome treated with Ketoconazole between 2010 and 2013. We followed cortisol levels before and during treatment, the doses of Ketoconazole and the time required for normalization of cortisol, “the escape syndrome” and the adverse effects. Results. Eleven (91,66%) patients had ACTH – dependent Cushing’s syndrome. The mean basal cortisol before initiation of the therapy was 404.4 ± 71 ng/ml. Two thirds (eight) patients presented a normalization of serum cortisol levels with 300-800 mg Ketoconazole/day, during a mean of 8.5 weeks. Only one patient presented an “escape syndrome” and one presented adrenal insufficiency. None of the patients showed significant side effects under the treatment. Conclusions. Ketoconazole therapy is well tolerated and is effective in most patients with Cushing’s syndrome even in long term use. The resistance and the escape from the effect of the treatment is possible, but rare, patients requiring close monitoring during therapy.

Context. Studies of platelet function in diabetics are inconsistent, some studies reporting higher platelet reactivity, while others showed no change. Objective. We aimed to evaluate platelet indices and in vitro platelet aggregation in rats with long-lasting (28 weeks) diabetes mellitus. Design. Twelve controls and 14 diabetic rats were investigated. Diabetes was induced in 11-week-old rats using streptozotocin (60 mg/kg,i.p.). Platelet indices and in vitro adenosine diphosphate (ADP)-, protease-activated receptor 4 (PAR4) agonist-, and arachidonic acid (AA)-induced platelet aggregation were assessed at the age of 38 weeks. Results. Compared to controls, diabetic rats presented lower platelet count and plateletcrit (both p≤0.001), and higher mean platelet volume (p<0.01). ADP- (p=0.04) and AA-induced (p<0.01) platelet aggregation were lower in diabetic compared with control rats, whereas PAR4 agonistinduced platelet aggregation was similar between the two groups (p=1.00). Conclusions. This study demonstrates a paradox of high intrinsic platelet reactivity and low in vitro ADP- and AA-induced platelet aggregation in diabetic rats compared with non-diabetic controls. The relevance of in vitro platelet aggregation to the contribution of platelets to in vivo thromboembolic events in diabetic rats remains questionable.

Context. Four major modifiable behavioral risk factors are considered responsible for the current burden of the non-communicable diseases: tobacco use, physical inactivity, unhealthy diet and excessive alcohol consumption. Limited data on the lifestyle habits in Romanian population is currently available. Objective. To assess the eating patterns and physical activity habits and other lifestyle components in various age groups in the population included in the ORO study. Design. ORO was a cross-sectional, epidemiologic, multicenter non-interventional study conducted from January 2014 until August 2014 in 8 study centers spread in the main historical regions of Romania Results. Eating 3 meals/day every day was more frequently reported in the 60-79 years and ≥ 80 years age groups (53.0% and 51.7%) than in the 18-39 years and 40- 59 years age groups (26.8% and 35.8%), p <0.001. The frequency of eating breakfast every day increased with age from 43.5% in the youngest age group to 79.3% in the oldest one (p <0.001). Intense and moderate leisure-time physical activity was more frequent among participants in the 18- 39 years age group. Leisure time physical activities were associated with younger age groups, male sex, rural area, higher educational level and non-smoking status. Regular breakfast and regular consumption of 3 meals/day was associated with older age group, male sex and non-smoking status. Conclusions. Our analysis showed a high frequency of unhealthy lifestyle habits among the younger age groups as compared to the older ones, with the highest frequency of these unhealthy behavior reported in the 18-39 years age group.

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.

Context. Thyrotoxicosis is an important cause of secondary osteoporosis, but the extent of bone loss and its\r\nreversibility with therapy have not been clearly determined yet.\r\nObjective. We assessed the impact of thyrotoxicosis on bone mineral density (BMD) and the recovery of bone loss with\r\ntherapy. We also tested, in this context, the hypothesis that low TSH levels, even within reference range, increase fracture risk.\r\nDesign, Subjects and Methods. In this retrospective study we compared 78 women with thyrotoxicosis and osteopenia /\r\nosteoporosis (TX ? study group), with 82 age matched, euthyroid women with primary osteopenia /osteoporosis (C-control group). All patients had a baseline and at least one follow-up assessment of lumbar spine BMD by dual-emission X-ray absorptiometry (DXA) and thyroid function (thyrotropin ? TSH and free thyroxine ? fT4, measured by electrochemiluminescence immunoassay).\r\nResults. Mean BMD and T scores were similar at baseline (0.764 g/cm2, -2.50 SD in the TX group 0.747 g/cm2, -2.59 SD\r\nin C group); 17 thyrotoxic patients and 17 patients with primary osteoporosis had previous fractures. Both groups showed a significant BMD increase with therapy, over a similar period of time (TX ? mean 10.38 months; C ? 10.74 months). BMD gain was significantly higher in the study\r\ngroup (p = 0.04). In hyperthyroid patients, the best predictor for bone density increase was the TSH raise, while in controls the main determinant was treatment duration.\r\nConclusions. In comparison to primary osteoporosis, bone loss recovery rate with appropriate therapy is higher in\r\nthyrotoxicosis, confirming its contribution to the pathogenesis of osteoporosis.

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.

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.