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Hypothyroidism is associated with an increased risk for obesity and cardiovascular diseases. Resistin and leptin exert proinflammatory actions by activating a specific receptors which are expressed in human endothelial cells. The aim of the study was to investigate whether the relations between the leptin, resistin, and high-sensitivity C-reactive protein (hs-CRP), which is a marker of low-grade inflammation, in patients with subclinical (SH) and overt hypothyroidism (OH). The levels of leptin, resistin, and hs-CRP were measured in 25 patients with OH, 30 patients with SH, and in 25 healthy subjects, using enzyme-linked immunosorbent assay method. The leptin and resistin levels in patients with OH and SH were similar to those in the control group. The hs-CRP level in OH group was significantly higher than SH and control groups (P

It is well demonstrated that obesity is an independent risk factor for cardiovascular diseases. Recent studies have shown that obesity, insulin resistance and atherosclerosis are closely related phenomena in which low-grade inflammatory state and prothrombotic condition has pivotal roles. It has been shown that CD40-soluble CD40 ligand (sCD40L) interactions might constitute an important mediator for vascular inflammation. The aim of the present study was to assess sCD40L in relation to hs-CRP and cardiovascular risk factors in relation to body mass index (BMI).Serum sCD40L and hs-CRP concentrations were measured in 52 obese patients and 28 non-obese subjects by ELISA. Insulin resistance was calculated by homeostasis model assessment-insulin resistance (HOMA-IR). We divided the participants into three groups depending in their BMI levels (Group 1: BMI25 kg/m(2), Group 2: BMI 30-34.9 kg/m(2), Group 3: BMIor =35 kg/m(2)).We determined that the mean sCD40L of group 3 was significantly higher than group 1 and group 2 (p0.05, p0.05, respectively). However, there was no significant correlation between plasma sCD40L levels and BMI. Plasma levels of hs-CRP were higher in obese group than the non-obese group (p0.001). The levels of sCD40L were not significantly different between the two groups. The mean hs-CRP levels increased gradually in accordance with groups of BMI, there was a strong correlation between hs-CRP levels and BMI (r=0.724, p0.001). There was no significant correlation between sCD40L and hs-CRP levels in all participants.It is still a subject for debate whether sCD40L levels are increased or not in obesity. However, the results of this study showed that sCD40L is substantially increased in patients with severe obesity. In terms of causality, the relatively small sample size and cross-sectional design of this study are considered to be the limitation factors.

Arterial calcification is associated with increased risk of cardiovascular events. Osteoprotegerin (OPG) is a cytokine involved in the bone metabolism and vascular calcification. Recent data support a relationship between high serum levels of OPG and increased risk for cardiovascular disease in human. The aim of this study was to evaluate the OPG serum levels in acute ischemic stroke. Our study was further designed to detect differences in serum OPG levels between subtypes of ischemic stroke.The study consisted of 51 patients with acute ischemic stroke and 28 control subjects. Stroke subtypes were defined by the TOAST classifications. Serum OPG levels were measured with the ELISA method.OPG serum levels were significantly higher in patients with ischemic stroke than in control subjects (p0.001). OPG serum levels were significantly higher in large-vessel disease (LVD) subtype compared with small-vessel disease (SVD) subtype and controls (p0.001, p0.001). There was no significant difference in OPG serum levels between SVD group and control subjects. Serum OPG levels were correlated with age (r=0.407, p=0.005) and fasting glucose levels (r=0.542, p=0.001) in ischemic stroke group. Logistic regression analysis showed that plasma OPG levels (OR 2.1, 95% CI, 1.16 to 3.4, p=0.01) associated with presence of stroke independently of the other risk factors.High serum OPG levels were associated with the LVD stroke subtype, suggesting that OPG levels may play role in pathogenesis of atherothrombotic stroke. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.

It has been reported that some patients with Type 2 diabetes mellitus (DM) have latent autoimmune diabetes in adults (LADA) and may show different clinical characteristics than those with Type 2 DM. We aimed to determine the ratio and clinical features of LADA in patients with diagnosed initially as Type 2 DM. We measured glutamic acid decarboxylase antibodies (GADA) in 54 patients, diagnosed clinically with Type 2 DM. Of 54 patients, 17 (31%) were GADA positive. GADA-positive patients had significantly earlier diabetes onset age (P

Subclinical hypothyroidism (SH) represents the earliest stages of hypothyroidism but the benefits of detecting and treating SH are not well known. The aim of this study was to evaluate the alterations in global fibrinolytic capacity (GFC), which indicates the overall fibrinolytic activity, in patients with SH. The study group comprised of 15 patients with SH and 15 healthy controls. The GFC was significantly lower in patients with SH than in control group (p

We investigated the relationship between index of insulin resistance (IR) and exercise test variables in middle-aged asymptomatic patients with Type 2 diabetes.90 patients (48 men, 42 women; age: 49 +/- 6 yr) were included in the study. We used homeostasis model assessment for IR (HOMA-IR) index as index of IR. All patients were subjected to treadmill exercise test. Four subjects were tested positive (4.4%). Study patients were separated into three groups: group I (no.=26) HOMA-IR index2.24; group II (no.=26) index 2.24-3.59; group III (no.=38) index3.59.group I had less frequency of cardiovascular risk factors than group II and III (p=0.001). Systolic blood pressure baseline as well as peak exercise values, were higher in group III than in group I and II (p=0.048 vs p=0.01, respectively). Higher total exercise time and peak workload were found in group I than group II and III (p=0.04). The recovery of heart rate (delta HR(pr)) was similar among the study groups. We found significant negative correlations between HOMA-IR and total exercise time and peak workload. In addition we found significant negative correlations between age vs chronotrophic index (CI), delta HR(pr), and peak workload. There were also similar negative correlations between duration of diabetes vs CI and delta HR(pr).IR is associated with a variety of cardiovascular risk factors. Some exercise test variables point out changes of autonomic tone during exercise in elevated IR group. Negative correlation between HOMA-IR and peak exercise capacity (METs) may well confirm increased mortality in hyperinsulinemia.

Perchlorate, nitrate, and thiocyanate are competitive inhibitors of the sodium iodide symporter of the thyroid membrane. These inhibitors can decrease iodine uptake by the symporter into the thyroid gland and may disrupt thyroid function. This study assesses iodine status and exposure to iodide uptake inhibitors of non-pregnant and non-lactating adult women living in three different cities in Turkey (Istanbul, Isparta and Kayseri). We measured iodine and iodide uptake inhibitors in 24-hr urines collected from study participants (N = 255). All three study populations were mildly iodine deficient, with median urinary iodine (UI) levels of 77.5 mu g/L in Istanbul, 58.8 mu g/L in Isparta, and 69.8 mu g/L in Kayseri. Perchlorate doses were higher in the study population (median 0.13 mu g/kg/day), compared with a reference population (median 0.059 mu g/kg/day), but lower than the U. S. EPA reference dose (0.7 mu g/kg/day). Urinary thiocyanate levels increased with increasing exposure to tobacco smoke, with non-smokers (268 mu g/L) significantly lower than light smokers (1110 mu g/L), who were significantly lower than heavy smokers (2410 mu g/L). This pilot study provides novel data indicating that study participants were moderately iodine deficient and had higher intakes of the iodide uptake inhibitor perchlorate compared with a reference population. Further investigation is needed to characterize the thyroid impact resulting from iodine deficiency coupled with exposure to iodide uptake inhibitors such as perchlorate, thiocyanate and nitrate.

Objective It is well known that bromocriptine has a suppressive effect on the prolactin release in hyperprolactinemic patients. But it also has some adverse effects. The new, long-acting dopaminergic drug, cabergoline, has been reported to be an effective agent in these patients. However, there are relatively few reports comparing the beneficial and adverse effects of these drugs in the treatment of hyperprolactinemic patients. Therefore, here we studied and compared the efficacy and tolerability of cabergoline with bromocriptine in hyperprolactinemic patients. Patients Seventeen patients (7 with microprolactinoma, 4 with macroprolactinoma, 6 with idiopathic hyperprolactinemia) were given bromocriptine at a dose of 2.5 mg (or 5 mg for macroprolactinomas) twice daily, and 17 patients (8 with microprolactinoma, 4 with macroprolactinoma, 5 with idiopathic hyperprolactinemia) were given cabergoline at a dose of 0.5 mg twice weekly for 12 weeks. Results At the end of the study, the prolactin reduction was significantly greater in the cabergoline group than in the bromocriptine group (-93 vs. -87.5%, respectively, p

The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n= 38), 2) Hyperthyroid patients treated for three months (n=21), 3) Untreated hypothyroid patients (n=27), 4) Hypothyroid patients treated for three months (n= 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared to the euthyroid controls.

Both insulin, depending on the glycemic state, and nitric oxide (NO), depending on the experimental conditions, have been suggested to have either proconvulsant or anticonvulsant effects. It is also known that NO plays an important role in some of the peripheral effects of insulin. The aim of the present study was to investigate the effects of NO and insulin against convulsions produced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) in mice and whether NO plays a role in the effect of insulin. Nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME, 1-100 mg/kg, i.p.) shortened the onset of PTZ-induced convulsioins and increased the incidence and mortality rate, at the higher doses. Insulin (1 U/kg, i.p.), when given with dextrose (3 g/kg, i.p.) to counteract the hypoglycemic effect of the hormone, prolonged the onset of convulsions and decreased the incidence and mortality rate. L-NAME pretreatment (3 mg/kg, i.p.), at the dose which it produced no effect on PTZ-induced convulsions, attenuated the protective effect of 1 U/kg insulin + 3 g/kg dextrose combination significantly. Concomitant administration of the NO synthesis precursor, L-arginine (500 mg/kg), completely reversed this facilitatory effect of L-NAME. Our results indicate that NO has a protective effect against PTZ-induced convulsions in mice; insulin has a similar effect when given with dextrose; and, NO production may play an important role in the anticonvulsant effect of insulin.

Cushing's syndrome is characterized by endogenously increased production of glucocorticoids. The activity of immune system is regulated mainly by two systems in the body. Glucocorticoids and NF-kappaB counteract the effects of each other on the immune system. It has been reported that immune response is exaggerated after the amelioration of Cushing's syndrome. We report a rare case of exacerbation of Graves' disease after unilateral adrenalectomy for Cusing's syndrome. A 50-yr-obese woman with hypertension, dyslipidemia, impaired glucose tolerance and insulin resistance wasadmitted to outpatients clinic of endocrinology. The results of evaluation of glucocorticoids metabolism and adrenal magnetic resonance imaging revealed the Cusing's syndrome. We also assessed thyroid function tests because of the diagnosis of goiter and thyroid hormone replacement in her medical history, and the presence of exophthalmia and tachycardia in examination. Althoug TSH level was detected at the lower border of normal range, free T4 and free T3 were in normal range and autoantibody of thyroidal peroxidase and thyroglobulin was higer than normal reference range. An operation was performed and a mass was removed from her left adrenal gland. The pathologic examination confirmed adrenal adenoma. She was re-admitted to the outpatient clinic 9 months after with complaints of palpitation, malaise and weight loss. Tests carried out to determine the thyroid function revealed Graves' disease. We prescribed propylthiouracil and beta-blocker treatment.

Thyroid diseases may lead to endothelial dysfunction; however, the mechanism underlying the endothelial dysfunction in thyroid disease is not clear yet. Asymmetric dimethylarginine (ADMA), a novel inhibitor of endothelial nitric oxide synthase (eNOS), blocks nitric oxide (NO) synthesis from L-arginine. Symmetric dimethylarginine (SDMA) is the structural isomer of the eNOS inhibitor ADMA. SDMA does not directly inhibit eNOS but is a competitive inhibitor of arginine transport. Increased plasma ADMA, SDMA concentrations, and low L-arginine/ADMA ratio were considered as possible contributing factors for endothelial dysfunction in hyperthyroid patients. On the other hand, plasma ADMA, SDMA levels and L-arginine/ADMA ratio in the hypothyroid group were unexpectedly found to be similar to those of the control subjects. The aim of this study is to evaluate and compare the plasma ADMA levels in hyperthyroid, hypothyroid and healthy subjects. Plasma ADMA, SDMA, and L-arginine levels were measured by high performance liquid chromatography. Plasma ADMA levels were significantly higher in both patients with hyperthyroidism and hypothyroidism than in the control group. SDMA concentrations were significantly increased in hypothyroid patients compared to control subjects. Patients with hyperthyroidism and hypothyroidism had significantly higher plasma L-arginine levels compared with healthy controls. L-arginine/ADMA ratio, which shows NO bioavailability, was significantly lower in hyperthyroid patients than in both hypothyroid and control subjects. In hyperthyroidism, plasma ADMA levels were related to age, L-arginine, and SDMA levels. SDMA was associated with age and L-arginine. L-arginine/ADMA ratio was negatively associated with freeT4 levels. There was a relationship between ADMA and L-arginine in hypothyroid patients. SDMA was significantly related to L-arginine, total cholesterol, and LDL. In conclusion, not only hyperthyroidism but also hypothyroidism was associated with alterations of ADMA and SDMA metabolism.

Background: Elevated plasma concentrations of total homocysteine (tHcy) and obesity are risk factors for cardiovascular disease. The relationship between hyperhomocysteinemia and obesity has not been totally elucidated. Objective: The first aim of the study was to investigate whether anthropometric measurements and insulin resistance contribute to the variation in homocysteine levels in obese adults. Our second aim was to determine if any relationship exists between the carotid intima-media thickness (IMT) and plasma tHcy levels in obese subjects without traditional cardiovascular risk factors. Material and Methods: Fifty-five obese (15 male, 40 female) and 30 (11 male, 19 female) age- and sex-matched apparently healthy volunteers were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, hyperlipidemia, renal failure, liver disease, pregnancy, menopause and secondary obesity such as Cushing’s syndrome, hypothyroidism. tHcy, folate, vitamin B12 levels, fasting insulin, glucose, total cholesterol, triglycerides, HDL, LDL particles, uric acid, creatinine and creatinine clearance were measured. Non-invasive ultrasound measurements of carotid IMT were performed. Results: tHcy levels and carotid IMT were comparable between obese and nonobese subjects. Waist/hip ratio (WHR) was related to tHcy and carotid IMT. Hyperhomocysteinemic subjects (tHcy >19.2 μmol/l) had greater WHR than normo-homocysteinemic subjects. Both tHcy levels and carotid IMT were higher in male subjects both in obese and non-obese subjects. No association was observed between insulin resistance and tHcy and carotid IMT. Renal function and abdominal obesity were significant predictors of plasma tHcy levels. Conclusions: We concluded that, in obese subjects who are free from atherosclerosis and impaired renal function, plasma tHcy levels do not differ from healthy subjects. Plasma tHcy concentrations are not related to carotid IMT in obese subjects during the non-atherogenic stage. Although no significant difference was observed between insulin-resistant and insulin-sensitive subjects compared to the plasma tHcy levels, the relationship between tHcy levels and some components of the insulin resistance syndrome may support the opinion that tHcy may be considered a component of the insulin resistance syndrome.

We examined the relationships existing between serum cytokine levels and bone mineral density (BMD) in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. The study population consisted of 21 women with untreated hyperthyroid Graves' disease (group H) (age, 36 +/- 2 years), eight women with untreated subclinical hyperthyroid status (group SH) (age, 33 +/- 5 years) and 10 healthy women (group N) (age, 35 +/- 3 years). The following measurements were made in all patients: free T4 (fT4), free T3 (fT3), thyroid stimulating hormone (TSH), TSH receptor antibody (TRab), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), interleukin-2 receptor (IL-2r), interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-13 (IL-13). IL-2r and IL-8 levels significantly increased in group H compared with group SH (p0.01 and p = 0.05, respectively) and group N (p0.001 and p = 0.02, respectively). IL-4 and IL-13 levels tended to be lower in groups H and SH compared with group N, although this difference did not reach statistical significance. Bone mineral density was significantly reduced in only two areas of the femur in group H compared with group N. There was no difference in BMD between groups SH and N. There was no correlation between thyroid hormones, serum cytokine levels and BMD in either group. In conclusion, these results suggest that there were no relationships existing between the serum level of these cytokines and BMD in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism.

Purpose: This study aimed to determine the impaired glucose tolerance and diabetes prevalence in patients with essential hypertension (HT) and to compare the developed microvascular complications of these groups. Materials and Methods: An oral glucose tolerance test (OGTT) was performed on 338 essential hypertensive cases and glucose tolerances were classified according to ADA-2002 criteria. Results: Of the 338 cases, 32 people had diabetes (DM, 9.46%), 78 people had glucose intolerance (IGT, 23.1%), and 228 people had only hypertension but not IGT and DM (67.4%). Both the mean ages of the DM group (56.9 ± 6.7 years, p = 0.002) and IGT group (56.3 ± 8.4 years, p = 0.003) were older than the mean age of the control group (51.1 ± 6.4 years). The risk of IGT development was found to be four times greater in male cases than female cases when compared to the control group (p = 0.004, add ratio = 4.194). There were no significant differences in the body mass indexes (BMI’s), hypertension durations, and microvascular complications between the groups. Conclusion: In conclusion, the risk of IGT and DM development in hypertensive cases increases with aging and longer hypertension duration. The risk of IGT development in hypertensive cases is four times more in males.