Ilhan Tarkun

Hemostatic System as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

Hypothyroidism has been associated with atherosclerosis. The mechanisms of atherosclerosis in patients with thyroid failure remain controversial. Hypofibrinolysis might be a risk factor for thromboembolic disease in subclinical hypothyroidism (SH). We measured fibrinolytic activity in patients with SH before and after levothyroxine (LT(4)) treatment and compared it to those of controls. We prospectively included 35 patients with SH and 30 healthy controls. We treated patients with LT(4) until almost 6 months after the euthyroid state has been achieved. We measured fibrinogen, D-dimer, antithrombin III (ATIII), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) activity, and factor VII. Clinical and anthropometric variables were recorded for both groups. We found increased levels of fibrinogen, PAI-1, and factor VII and decreased levels of ATIII activity in patients compared to control (p < 0.001 and p < 0.05). Decrease of tPA was not significant (p > 0.05). At the end of the LT(4) treatment, significant decreases were determined in PAI-1 and factor VII (p < 0.05). In conclusion, our data suggest an important role of hypofibrinolytic and hypercoagulable state on the development of atherosclerosis in patients with SH and beneficial effects of LT(4 )treatment for decreasing the risk of atherosclerosis.

Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria:

Background: High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria. Methods: Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects. Results: MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P<0.0001, P<0.0001; GSH: P<0.0001, P<0.0001; GPx: P<0.0001, P<0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria (P<0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria (P<0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients (P>0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria (P<0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients (r=0.549, P<0.0001; r=0.385, P<0.01). Conclusion: Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.

Association between Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

BACKGROUND Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance. METHODS Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured. RESULTS TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05). CONCLUSIONS The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.

Homocysteine Concentrations in Subclinical Hypothyroidism

Hyperhomocysteinemia is considered to be an independent risk factor for atherosclerotic heart disease, including coronary artery disease (CAD). It is already known that overt hypothyroidism gives rise to a slight hyperhomocysteinemia. However, the effects of subclinical hypothyroidism on the levels of homocysteine are not known. In this study, we have evaluated homocysteine levels and the effect of L‐thyroxine treatment in patients with subclinical hypothyroidism. For the purpose of the study we selected 33 women patients with the diagnosis of subclinical hypothyroidism but without clinical CAD. After a euthyroidism development period of almost four months, a further study was done on patients who had been treated with thyroid hormone. The patient group was compared with 25 healthy control female subjects who were of similar age. In the patient group, homocysteine levels prior to treatment were significantly higher than in the control group (P < 0.001). After L‐thyroxine treatment, homocysteine levels were reduced significantly. In summary, we found that homocysteine levels were in the normal range in subclinical hypothyroidism. However, when compared with the healthy control group, the difference between them was significant. On the other hand, therapy to produce euthyroidism caused a significant reduction in homocysteine levels.

Serum Ferritin Levels in Poorly‐ and Well‐Controlled Diabetes Mellitus

Serum ferritin level is related to body iron stores and is influenced by several diseases. We aimed to evaluate the association between serum ferritin concentration and the complications and nature of diabetes mellitus (DM). We examined association of ferritin concentration, fasting and post‐prandial glucose levels and glycated hemoglobin in 329 patients with type 2 diabetes mellitus and 269 healthy controls. In the present study, 41 of 150 poorly controlled diabetic patients and 31 of 119 cases had hyperferritinemia. We confirmed that serum ferritin was increased in diabetic patients as long as glycemic control is not achieved. There was also a correlation between ferritin level and diabetic retinopathy. In conclusion, this study showed an independent positive association between serum ferritin concentration and markers of glucose homeostasis.

Lipid Profile and Lipoprotein (a) as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

This study evaluated changes of lipids and lipoprotein (a) [Lp (a)] as atherosclerotic risk factors and the effects of levothyroxine (LT4) treatment on these parameters in patient with subclinical hypothyroidism (SH), defined by increased concentrations of thyrotropin (TSH) and normal thyroid hormone concentrations. We prospectively included 35 female patients with SH and 30 healthy controls. Serum lipid measurements and clinical score as well as fT3, fT4, and TSH levels were assessed at baseline. Body mass index (BMI) was also calculated. Women with proven SH received LT4 treatment that continued for 6 months. Twenty‐six of 35 patients completed the study. At the end of treatment period, the same parameters were determined. Total cholesterol was significantly increased in patients with SH when compared with those of controls (p < 0.01), but increase of LDL‐cholesterol (LDL‐C) and Lp (a) were not significant (p > 0.05). In the levothyroxine‐treated group, total cholesterol and LDL‐C were significantly reduced when compared with the baseline values of women with SH (p < 0.05). Zulewski clinical score assessing symptoms and signs of hypothyroidism improved significantly with treatment (p < 0.001). In conclusion, serum lipids as important atherosclerotic risk factors increased before treatment and decreased with treatment. Levothyroxine therapy is effective in SH and improvements in serum lipids suggests that LT4 treatment also decreases the risk of atherosclerotic diseases.

Plasma visfatin level in women with polycystic ovary syndrome.

Objective. The aim of this study is to compare the serum level of visfatin between patients with polycystic ovary syndrome (PCOS) and control subjects matched for age and body mass index (BMI) and to assess the possible correlations of visfatin to the hormonal and metabolic parameters of the syndrome. Material and method. Fifty-five patients with PCOS diagnosis composed of 25 obese, 13 overweight, 17 normal weight subjects and 49 women without concomitant disease matched for age and BMI were included in this study. Results. Serum visfatin levels were similar in normal weight PCOS and control group. Visfatin levels in obese and overweight patients with PCOS were higher than that found in control women with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR. Obese women with PCOS had also significantly higher visfatin levels than normal weight women with PCOS. Conclusion. Visfatin levels in obese and overweight patients with PCOS were higher than that found in females without concomitant disease with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR.

Duration of the P wave and P wave dispersion in subclinical hyperthyroidism.

OBJECTIVE To determine whether the values for P wave dispersion (Pdis) and adjusted Pdis, which are simple noninvasive electrocardiographic markers to detect paroxysmal atrial fibrillation, differ in patients with endogenous subclinical hyperthyroidism in comparison with those in healthy control subjects. METHODS We measured the maximal P wave duration and the difference between the maximal and the minimal P wave duration (Pdis) from the 12-lead surface electrocardiogram of 36 patients with endogenous subclinical hyperthyroidism and of 22 age- and sex-matched healthy control subjects. Adjusted Pdis (Pdis/square root of the number of measured electrocardiographic leads) was also calculated from each electrocardiogram. RESULTS The minimal P wave duration was significantly shorter in patients with subclinical hyperthyroidism than in healthy control subjects (P<0.001). Pdis and adjusted Pdis were also significantly higher in the patient group than in the control subjects (P<0.05). By univariate analysis, only thyrotropin levels were found to be associated with adjusted Pdis (r = -0.28; P = 0.03). CONCLUSION Pdis and adjusted Pdis differed in patients with endogenous subclinical hyperthyroidism in comparison with those values in healthy control subjects. Thus, these simple electrocardiographic markers may be useful for identifying patients with endogenous subclinical hyperthyroidism who are at risk for paroxysmal atrial fibrillation.

Evaluation of exenatide versus insulin glargine for the impact on endothelial functions and cardiovascular risk markers

AIMS To demonstrate the efficacy of exenatide versus insulin glargine on endothelial functions and cardiovascular risk markers. METHODS Thirty-four insulin and incretin-naive patients with type 2 diabetes mellitus (body mass index 25-45 kg/m(2)) who received metformin for at least two months were randomized to exenatide or insulin glargine treatment arms and followed-up for 26 weeks. Measurements of endothelial functions were done by ultrasonography, cardiovascular risk markers by serum enzyme-linked immunosorbent assay, and total body fat mass by bioimpedance. RESULTS Levels of high sensitivity-C-reactive protein and endothelin-1 decreased (27.5% and 18.75%, respectively) in the exenatide arm. However, in the insulin glargine arm, fibrinogen, monocyte chemoattractant protein-1, leptin and endothelin-1 levels (13.4, 30.2, 47.5, and 80%, respectively) increased. Post-treatment flow mediated dilatation and endothelium independent vascular responses were significantly higher in both arms (p=0.0001, p=0.0001). Positive correlation was observed between the changes in body weight and endothelium-independent vasodilatation, leptin, plasminogen activator inhibitor type 1 and endothelin-1 in both arms (r=0.376, r=0.507, r=0.490, r=0.362, respectively). CONCLUSIONS Insulin glargine improved endothelial functions, without leading to positive changes in cardiovascular risk markers. Exenatide treatment of 26 weeks resulted in reduced body weight and improvement in certain cardiovascular risk markers and endothelial functions.

The utility of preoperative acth/cortisol ratio for the diagnosis and prognosis of cushing's disease

Purpose: Cushings syndrome (CS) is a rare disease having diagnostic difficulties. Many diagnostic tests have been defined but none of these are diagnostic alone. Determination of the cause is another problem which sometimes requires more sophisticated and invasive procedures. Therefore, we aimed to evaluate the utility of pretreatment plasma adrenocorticotropic hormone (ACTH)/cortisol ratios in patients with confirmed endogenous CS for the diagnosis and differential diagnosis of CS. Materials and Methods: This retrospective evaluation included 145 patients with the diagnosis of CS, 119 patients with Cushings disease (CD), and 26 patients with ACTH-independent CS (AICS), in a university hospital. Furthermore, 114 individuals in whom CS diagnosis was excluded with at least one negative screening test were enrolled to the study as control group. The clinical, laboratory, imaging, postsurgical pathologic records and also clinical follow-up data of all patients were evaluated. Results: The median basal ACTH/cortisol ratio of the patients with CD was significantly higher than AICS and controls. A cutoff ACTH/cortisol ratio >2.5 was found to be diagnostic for CD with 82% specificity and 63% sensitivity. Among CD group, patients with recurrent disease had higher preoperative ACTH levels and ACTH/cortisol ratio than patients with sustained remission. Furthermore, these patients had more invasive, atypical, and larger tumors. Conclusion: An ACTH/cortisol ratio >2.5 would be beneficial to diagnose CD together with other diagnostic tests. It is a simple test with no additional cost. Higher ratios might be related with larger, invasive, and atypical adenoma and also might be helpful to predict recurrence.