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ABSTRACT: Various abnormalities of coagulation-fibrinolytic system have been reported in patients with thyroid dysfunction. Several studies indicate that coagulation and fibrinolytic system is disturbed in the patients with hyperthyroidism. The levels of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and tissue factor pathway inhibitor (TFPI) have been very rarely investigated in patients with hyperthyroidism. Therefore, the main purpose of this study was to evaluate the profile of coagulation and fibrinolytic parameters including TAFI and TFPI in patients with hyperthyroidism. We also investigated the relationships between serum thyroid hormones and hemostatic parameters in these patients. Thirty patients with untreated hyperthyroidism and 25 age- and sex-matched healthy controls were included in the study. Factor V (FV), protein C, protein S, TFPI, and TAFI were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with the control subjects, TAFI Ag levels were increased significantly in patients with hyperthyroidism [mean ± SD (ranges)] [177.03 ± 20.37 (131-206%) versus 145.9 ± 23.0 (89-169%)] (P < 0.001), whereas FV [89.8 ± 21.02 (49-124%) versus 116.1 ± 31.4 (56.4-200%)], protein C [72.8 ± 46.22 (2-149%) versus 144.0 ± 26.3 (74-158%)] and protein S [60.06 ± 42.82 (9-156%) versus 151 ± 33 (76-231%)] activities and TFPI Ag levels [69.56 ± 17.63 (39-140 ng/ml) versus 87.5 ± 15.9 (64-121 ng/ml)] were decreased significantly (P < 0.001 for all of them). We did not find a significant difference between Graves' disease and toxic nodular goiter for hemostatic parameters. In patients with Graves' disease, serum-free T₃ levels were inversely correlated with TFPI Ag levels (r: -0.57, P < 0.05). In conclusion, we found some important differences in the hemostatic parameters between the patients with hyperthyroidism and healthy controls. Increased TAFI and decreased FV, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system may contribute to the excess mortality due to cardiovascular disease seen in patients with hyperthyroidism.
Endocrine 10/2009; 36(3):473-8. · 1.42 Impact Factor
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ABSTRACT: Ischemia-modified albumin (IMA) is a novel marker of tissue ischemia. Nowadays, IMA is accepted as a marker of oxidative stress. In this study, we aimed at establishing an association between IMA and hyperglycemia, blood pressure, lipid parameters, microvascular complications, hsCRP, and microalbuminuria in type 2 diabetes patients without overt macrovascular disease and acute ischemia. Fifty type 2 diabetes mellitus patients without a history of macrovascular disease or end-stage renal disease were enrolled into the study. Age-matched 30 healthy individuals were also included in the study as a control group. Plasma IMA (0.329 ± 0.046 and 0.265 ± 0.045 AbsU; P < 0.0001) and hsCRP levels (0.51 ± 0.36 and 0.32 ± 0.17 mg/dl; P < 0.0001) were significantly higher in the diabetic group compared to healthy controls. IMA level was significantly correlated with hsCRP (r = 0.76; P < 0.0001), HbA1c (r = 0.72; P < 0.0001), microalbuminuria (r = 0.40; P = 0.004), systolic blood pressure (r = 0.28; P = 0.049), diastolic blood pressure (r = 0.44; P = 0.005), and HOMA-IR (r = 0.42; P = 0.005) levels in the entire diabetic subjects. In the diabetic patients group, presence of microalbuminuria was associated with a higher plasma IMA level (0.355 ± 0.035 and 0.265 ± 0.0045 AbsU; P < 0.0001, patients with microalbuminuria and control subjects, respectively). In the type 2 diabetes patients with nephropathy, IMA level (0.355 ± 0.035 and 0.311 ± 0.046 AbsU; P = 0.002) was determined higher compared to the diabetes patients without nephropathy. Diabetic patients without an overt cardiovascular disease still have a higher serum IMA level compared to healthy controls. The correlation of high plasma IMA levels with high hsCRP and microalbuminuria levels in diabetic subjects indicates the presence of a chronic ischemic process. Therefore, elevated IMA levels may indicate an underlying subclinical vascular disease in type 2 diabetes mellitus patients.
Endocrine 09/2009; 36(3):425-32. · 1.42 Impact Factor
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ABSTRACT: Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 +/- 1.74 and 8.98 +/- 1.91 micromol/l; P < 0.0001) and microalbuminuria levels (73.40 +/- 98.15 and 29.53 +/- 5.08 mg/day; P = 0.021) were significantly higher in the group with MTHFR gene mutation while creatinine clearance levels (101.1 +/- 42.6 and 136.21 +/- 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of the patients with diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy.
Endocrine 07/2009; 36(2):255-61. · 1.42 Impact Factor
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ABSTRACT: Type 2 diabetes mellitus is the leading cause of macrovascular diseases and related death. Additionally, diabetes mellitus is frequently complicated by other cardiovascular risk factors, such as hypercholesterolemia, hypertension, obesity, hypercoagulability, and inflammation. We wanted to evaluate and compare the effects of treating with a one-year course of atorvastatin or simvastatin on inflammatory markers such as high sensitive C-reactive protein (hsCRP), fibrinogen, and ferritin in uncontrolled type 2 diabetic patients. Also, we planned to investigate the correlation between inflammatory markers and metabolic parameters. Fifty type 2 diabetic patients (30 women, 20 men; mean age: 49.9 +/- 8.5 years) were enrolled into the study. Twenty healthy subjects, matched on body mass index and age, were also included in the study as a control group. Diabetic patients were divided into two groups and received simvastatin or atorvastatin (Group S and A, respectively). After 1 year of statin treatment (Group A), there were significant decreases in total cholesterol (217.3 +/- 46.5-173.8 +/- 37.2 mg/dl; P < 0.0001), LDL-cholesterol (146.7 +/- 50.3-102.3 +/- 31.1 mg/dl, P < 0.0001), hsCRP (0.88 +/- 0.62-0.35 +/- 0.18 mg/dl, P < 0.0001), fibrinogen (258.2 +/- 16.9-215.5 +/- 10.6 mg/l; P < 0.0001), and ferritin (118.2 +/- 73.9-81.2 +/- 72.5 ng/ml, P < 0.0001) levels compared to basal values. In the S group, there were significant decreases in total cholesterol (224.4 +/- 61.2-175.0 +/- 47.8 mg/dl; P < 0.0001), LDL-cholesterol (140.9 +/- 56.7-110.9 +/- 42.2 mg/dl, P < 0.0001), hsCRP (0.98 +/- 1.3-0.46 +/- 0.25 mg/dl, P < 0.0001), fibrinogen (265.7 +/- 26.8-222.1 +/- 20.6 mg/l; P < 0.0001), and ferritin (136.7 +/- 101.1-85.6 +/- 32.1 ng/ml, P < 0.0001) levels compared to basal values. At the end of the study, hsCRP, fibrinogen, and ferritin levels were correlated with LDL (r = 0.42; P = 0.005, with hsCRP), (r = 0.40; P = 0.008, with fibrinogen), (r = 0.46; P = 0.002, with ferritin) and HDL (r = -0.50; P < 0.0001, with hsCRP), (r = -0.32; p = 0.042, with fibrinogen), (r = -0.48; P < 0.0001, with ferritin) cholesterol levels. Atorvastatin and simvastatin treatments were found to be effective for the control of hypercholesterolemia and resulted in a significant decrease in acute phase reactants in uncontrolled type 2 diabetic patients.
Endocrine 03/2009; 35(3):380-8. · 1.42 Impact Factor
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Endocrine 02/2009; · 1.42 Impact Factor
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ABSTRACT: Diagnosis of polycystic ovary syndrome (PCOS) is very difficult in women with ovulatory cycles. We assessed the diagnostic value of prostate-specific antigen (PSA) and free prostate-specific antigen (fPSA) in women with ovulatory or anovulatory PCOS. Study group consisted of 62 women with PCOS and 35 healthy female controls. PCOS group was divided into two subgroups as anovulatory (n = 42; 68%, Group A) and ovulatory group (n = 20; 32%, Group B). A cut-off level of PSA and fPSA was established for the sensitivity, specificity, positive likelihood ratio, area under curve, diagnostic accuracy, and positive and negative predictive values of diagnosis of PCOS. In group A, a PSA level of greater than 10 pg/ml yielded a sensitivity of 73.2%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 88.2% and a negative predictive value of 59.3%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 71.2%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 87.2% and a negative predictive value of 58.4%. In group B, a PSA level of greater than 10 pg/ml yielded a sensitivity of 65%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 76.5% and a negative predictive value of 69.6%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 65.4%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 75.5% and a negative predictive value of 68.4%. Circulating androgens and hirsutism are independently associated with the degrees of PSA and fPSA in PCOS women. Increased plasma levels of PSA (>10 pg/ml) and fPSA (>2.1 pg/ml) could be helpful as a diagnostic tool for women with ovulatory or anovulatory PCOS.
Endocrine 12/2008; 35(1):123-9. · 1.42 Impact Factor
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ABSTRACT: Various abnormalities of coagulation-fibrinolytic system have been reported in patients with thyroid dysfunction. Several studies indicate that coagulation and fibrinolytic system is disturbed in the patients with hypothyroidism. Also, the influence of hypothyroidism on hemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. The levels of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and tissue factor pathway inhibitor (TFPI) have been investigated only once in patients with hypothyroidism. Therefore, the main purpose of this study was to evaluate the profile of coagulation and fibrinolytic parameters including TAFI and TFPI in patients with hypothyroidism. Fifteen patients with untreated hypothyroidism and 15 age-matched healthy controls were included in the study. Factors V(FV), VII (FVII), VIII (FVIII) activities, von Willebrand factor (vWF), protein C, protein S, thrombomodulin (TM), TFPI, and TAFI were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with the control subjects, FVII activity, and TM Ag and TAFI Ag levels were significantly increased in patients with hypothyroidism, whereas FV, FVIII, vWF, protein C and protein S activities, and TFPI Ag levels were significantly decreased. We did not find any significant correlation between serum thyroid hormones and the hemostatic parameters that we measured. In conclusion, we found some important differences in the hemostatic parameters between the patients with hypothyroidism and healthy controls. Increased FVII, TM, and TAFI and decreased FV, FVIII, vWF, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system may contribute to the excess mortality due to cardiovascular disease seen in patients with hypothyroidism.
Endocrine 11/2008; 35(1):75-80. · 1.42 Impact Factor
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ABSTRACT: Growth hormone/insulin-like growth factor-1(GH/IGF-1) hypersecretion may influence risk factors contributing to the increased cardiovascular morbidity and mortality associated with acromegaly However, so far little is known about the impact of GH/IGF-1 on coagulation and fibrinolysis in acromegalic patients as possible risk factors for cardiovascular disease (CVD). To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between GH/IGF-1 and these hemostatic parameters and serum lipid profile in patients with acromegaly.
A total of 22 patients with active acromegaly and 22 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX, and X activities, von-Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-I (PAI-1), TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum GH/IGF-1 and these hemostatic parameters were evaluated.
Compared with the control subjects, fibrinogen, AT III, t-PA, and PAI-1 were increased significantly in patients with acromegaly (P < 0.0001, P < 0.05, P < 0.01, and P < 0.0001, respectively), whereas protein S activity and TFPI levels were decreased significantly (P < 0.05 and P < 0.01, respectively). Plasma TAFI Ag levels did not significantly change in patients with acromegaly compared with the controls. In patients with acromegaly, serum GH levels were inversely correlated with TFPI and apo AI levels (r: -0.514, P: 0.029 and r: -0.602, P: 0.014, respectively). There was also a negative correlation between insulin-like growth factor-1 (IGF-1) and PAI-1 (r: -0.455, P: 0.045).
We found some important differences in the hemostatic parameters between the patients with acromegaly and healthy controls. Increased fibrinogen, t-PA, PAI-1 and decreased protein S and TFPI in acromegalic patients may represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system and dyslipidemia may contribute to the excess mortality due to CVD seen in patients with acromegaly.
Endocrine 11/2008; 33(3):270-6. · 1.42 Impact Factor
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ABSTRACT: The aim of this study is to evaluate the significance of immunohistochemical expression of Galectin-3 in the differential diagnosis of benign and malignant thyroid nodules. We studied the fine needle aspiration specimens of 38 patients who had evaluated for nodular goiter and undergone a thyroid surgery between 2004-2005. Slides had been stained immunocytochemically with Galectin-3. The cytoplasmic staining of Galectin-3 was analyzed. Three cases of five follicular carcinomas had positive staining for Galectin-3, while two had not. Two cases with follicular adenomas were negative for Galectin-3. Five cases of six papillary carcinomas had positive staining for Galectin-3, while one case (the case with a papillary microcarcinoma) had not. The single cases with medullary and anaplastic carcinomas were negative for Galectin-3. None of the cases with a benign thyroid pathology had positive staining for Galectin-3. Galectin-3 immunocytochemical staining, had a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3% for thyroid malignancies. For the evaluation of follicular neoplasm, Galectin-3 immunocytochemical staining had a sensitivity of 60%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Galectin-3 expression in thyrocytes is a strong indicator of a malignant proliferative lesion especially for papillary and to an extent in follicular thyroid neoplasms. Galectin-3 could be used as a supplementary marker for cytological diagnosis.
Pathology & Oncology Research 05/2008; 14(4):457-60. · 1.37 Impact Factor
