Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

PURPOSE: Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. METHOD: A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. RESULTS: Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). CONCLUSION: Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Clinical research of insulin glargine U300 in type 1 diabetes mellitus patients with frequent hypoglycaemia: real-world experience.

INTRODUCTION: We aimed to see whether insulin glargine U300 can provide better blood glucose control while reducing hypoglycaemia in a more homogeneous population compared to previous studies. MATERIAL AND METHODS: The retrospective study included type 1 diabetes mellitus (T1DM) patients with frequent hypoglycaemia. For evaluation of fasting blood glucose, haemoglobin glycated (HbA1c) and weight at 6 months and 12 months (final), observation windows of 120-240 days (4-8 months) and 240-480 days (9-16 months) after insulin glargine U300 initiation, respectively, were permitted. Mean follow-up time was 12 months. Hypoglycaemia was defined as blood glucose level < 70 mg/dl, either symptomatic or asymptomatic, measured in hospital or at home. RESULTS: Forty-four patients were included in the study, and 35 patients completed the study - 20 (57.1%) females and 15 (42.9%) males, with a mean age of 24.1 ±6.6 years. Mean body mass index was 24.4 ±7.4 kg/m2. A significant decrease was not found between baseline and HbA1c values at 6 months (p = 0.199), but a significant decrease was found in the final period (between 9-16 months) (p = 0.025). Hypoglycaemic events occurred in all patients (100%) before using insulin glargine U300, while the incidence of hypoglycaemic events gradually decreased to 74.3%, 68.6%, and 68.6% between months 1-3, 3-6, and 6-9, respectively. Of the 26 patients who declared their level of satisfaction, 23 (88.5%) were satisfied, 2 (7.7%) indicated that there was no significant difference, and 1 (3.8%) patient was unsatisfied. CONCLUSIONS: Over 9-16 months of follow-up, insulin glargine U300 led to a significant reduction not only of HbA1c levels but also of the frequency of hypoglycaemia, and also yielded high satisfaction rates.

Clinical research of insulin glargine U300 basal-bolus therapy and insulin degludec/aspart co-formulation in type 2 diabetes mellitus: A real world experience.

AIMS: Insulin degludec/aspart (IDegAsp) and insulin glargine U300 (IGlarU300) have recently emerged as popular new-generation insulin analogues. The aim of this real-life study was to investigate the patient profiles in which IGlarU300 and IDegAsp were preferred and the insulin combinations after which each of them were mostly used and also to analyse the effect of these two insulin analogues on blood glucose regulation and hypoglycaemia. MATERIALS AND METHODS: The retrospective study included 174 patients that were switched from basal insulin, basal-bolus insulin, or premixed insulin to IGlarU300 or IDegAsp due to uncontrolled blood glucose levels or history of hypoglycaemia. Hypoglycaemia, body weight, body mass index (BMI), fasting plasma glucose (FPG) and HbA1c levels over 3-month periods were evaluated for each patient. RESULTS: There were 84 and 90 patients in the IGlarU300 and IDegAsp groups, respectively. Body weight was similar in both groups. Baseline FPG and HbA1c levels in the IGlarU300 and IDegAsp groups were 9.0%, 175.5 mg/dL and 9.4%, 193.5 mg/dL, respectively. A significant decrease was found in FPG and HbA1c levels in both groups (138.5, 7.8 vs 141.5, 8.2; P < .001 for all). Moreover, a significant weight gain was observed in both groups (P < .05 for both). The prevalence of hypoglycaemia in both groups decreased significantly and consistently between months 1 and 9 (P < .001). At month 12, although this decrease continued in the IGlarU300 group (P = .013), no significant decrease was observed in the IDegAsp group (P = .057). CONCLUSION: Both twice-daily IDegAsp ± bolus insulin and IGlarU300 basal bolus insulin therapies are effective and safe treatment modalities.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus.

BACKGROUND: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. OBJECTIVE: To investigate the relationship between PSW and MPI in type 2 diabetic patients. METHOD: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. RESULTS: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). CONCLUSION: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus / Onda Pressistólica Associada à Disfunção Ventricular Esquerda Subclínica e Avaliada com Base no Índice de Performance Miocárdica em Pacientes com Diabetes Mellitus Tipo 2

Abstract Background: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. Objective: To investigate the relationship between PSW and MPI in type 2 diabetic patients. Method: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. Results: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). Conclusion: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Resumo Fundamento: O índice de performance miocárdica (IPM) avalia as funções sistólica e diastólica do ventrículo esquerdo. A onda pressistólica (OPS) é geralmente detectada no exame Doppler da via de saída do ventrículo esquerdo e seus possíveis mecanismos são complacência prejudicada e rigidez do ventrículo esquerdo. Objetivo: Investigar a relação entre OPS e IPM em pacientes com diabetes tipo 2. Método: 129 pacientes com diabetes tipo 2 foram incluídos no estudo. Os sujeitos foram alocados em dois grupos, com base na presença de OPS no exame ecocardiográfico com Doppler. Foram incluídos 90 pacientes (38 homens, idade média 57,77 ± 10,91 anos) no grupo OPS-positiva e 39 pacientes (13 homens; idade média 55,31 ± 11,29 anos) no grupo OPS-negativa. Valor de p < 0,05 foi considerado para significância estatística. Resultados: O IPM foi mais alto no grupo OPS-positiva (0,63 ± 0,17 vs 0,52 ± 0,13, p < 0,001). Além disso, a disfunção ventricular esquerda subclínica (DVE) foi maior no grupo OPS-positiva (p = 0,029). Análise univariada mostrou associação de OPS com IPM anormal (p = 0,031), assim como o coeficiente de correlação de Pearson mostrou correlação entre velocidade de OPS e IPM (r: 0,286, p = 0,006). Conclusão: Presença de OPS na ecocardiografia com Doppler foi associada à DVE subclínica em pacientes com diabetes tipo 2. Esse exame ecocardiográfico de fácil execução pode ser relacionado à DVE subclínica entre pacientes com diabetes tipo 2.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus / Onda Pressistólica Associada à Disfunção Ventricular Esquerda Subclínica e Avaliada com Base no Índice de Performance Miocárdica em Pacientes com Diabetes Mellitus Tipo 2

Abstract Background: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. Objective: To investigate the relationship between PSW and MPI in type 2 diabetic patients. Method: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. Results: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). Conclusion: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Resumo Fundamento: O índice de performance miocárdica (IPM) avalia as funções sistólica e diastólica do ventrículo esquerdo. A onda pressistólica (OPS) é geralmente detectada no exame Doppler da via de saída do ventrículo esquerdo e seus possíveis mecanismos são complacência prejudicada e rigidez do ventrículo esquerdo. Objetivo: Investigar a relação entre OPS e IPM em pacientes com diabetes tipo 2. Método: 129 pacientes com diabetes tipo 2 foram incluídos no estudo. Os sujeitos foram alocados em dois grupos, com base na presença de OPS no exame ecocardiográfico com Doppler. Foram incluídos 90 pacientes (38 homens, idade média 57,77 ± 10,91 anos) no grupo OPS-positiva e 39 pacientes (13 homens; idade média 55,31 ± 11,29 anos) no grupo OPS-negativa. Valor de p < 0,05 foi considerado para significância estatística. Resultados: O IPM foi mais alto no grupo OPS-positiva (0,63 ± 0,17 vs 0,52 ± 0,13, p < 0,001). Além disso, a disfunção ventricular esquerda subclínica (DVE) foi maior no grupo OPS-positiva (p = 0,029). Análise univariada mostrou associação de OPS com IPM anormal (p = 0,031), assim como o coeficiente de correlação de Pearson mostrou correlação entre velocidade de OPS e IPM (r: 0,286, p = 0,006). Conclusão: Presença de OPS na ecocardiografia com Doppler foi associada à DVE subclínica em pacientes com diabetes tipo 2. Esse exame ecocardiográfico de fácil execução pode ser relacionado à DVE subclínica entre pacientes com diabetes tipo 2.

Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma.

OBJECTIVE: Although the strong association between hyperprolactinaemia and platelet aggregation is well recognized, there are no studies on changes in coagulation and fibrinolytic status in patients with prolactinoma. To our knowledge, tissue plasminogen activator inhibitor-1 (PAI-1), 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 prolactin (PRL) and these haemostatic parameters and serum lipid profile in patients with prolactinoma. RESEARCH METHODS AND PROCEDURES: Twenty-two patients with untreated, newly diagnosed prolactinoma and 20 age-matched healthy controls were included in the study. Platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time, fibrinogen, factors V, VII, VIII, IX and X activities, von Willebrand factor, antithrombin III (AT-III), protein C, protein S, tissue plasminogen activator (t-PA), PAI-1, TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum PRL and these haemostatic parameters were evaluated. RESULTS: Compared with the control subjects, total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, platelet count, fibrinogen, AT-III, PAI-1 and PAI-1/t-PA ratio were significantly increased in patients with prolactinoma (P < 0.0001, P < 0.001, P < 0.05, P < 0.05, P < 0.0001, P < 0.05, P < 0.0001 and P < 0.0001, respectively), whereas TFPI levels were significantly decreased (P < 0.01). Plasma TAFI Ag levels were not significantly different in patients with prolactinoma compared with the controls. In patients with prolactinoma, serum PRL was positively correlated with plasma FVII levels and apo B (r: 0.679, P < 0.05; r: 0.548, P < 0.05, respectively). CONCLUSION: We found some important differences in the haemostatic parameters between the patients with prolactinoma and healthy controls. Increased platelet count, fibrinogen, PAI-1 and decreased TFPI in patients with prolactinoma may represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the haemostatic system and dyslipidaemia may lead to the excess mortality in patients with prolactinoma.

Primary thyroid paraganglioma presenting with double thyroid nodule: a case report.

Paragangliomas (PGs) are exceptionally rare tumors. Only 24 cases have previously been reported. Both preoperative and postoperative differential diagnosis is very difficult. Due to interesting nature in diagnosis and differential diagnosis, we describe the case 58-year-old euthyroid woman with a thyroid PG. The patient had presented with euthyroid multinodular goiter to a secondary hospital. The patient was treated with right lobectomy, isthmectomy, and left partial lobectomy without any imaging procedures. No complication had been developed during and following the operation. Initial pathological examination suggested medullar thyroid carcinoma (MTC) in a nodule of 4.5 cm in diameter on right thyroid lobe and a nodule of 2.5 cm in diameter on the left thyroid lobe without amyloid stroma and referred to our third-stage hospital. Repeated pathological examination involving immunohistochemistry revealed that the tumor was stained positively to neuron-specific enolase, chromogranin A, synaptophysin, and S-100 protein. No immunoreactivity was detected against thyroglobulin, calcitonin, parathormone, carcino-embryonic antigen, thyroid transcription factor-1, and cytokeratin. A diagnosis of thyroid PG was finally made. Laboratory analyses and imaging procedures excluded any neck or extracervical tissues metastasis or multiple endocrine neoplasia. In conclusion, thyroid PG is an elusive tumor. We present this interesting nature thyroid PG case to highlight importance of careful evaluation of clinical and pathological findings to correctly identify paragangliomas which anatomically mimic MTCs. This report is the first case of thyroid PG presenting with multinodular goiter in the literature.

Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism.

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.

Adrenal ganglioneuroma: report of a new case.

Although adrenal ganglioneuroma (GN) is a rare tumor originating from the neural crest tissue of the sympathetic nervous system, detection of this tumor has increased, as imaging procedures such as ultrasonography (US) and computed tomography (CT) have become prevalent. The clinical presentation for most patients is asymptomatic, and most of those tumors are hormone silent. We describe a case of adrenal GN incidentally diagnosed in a 68-year-old female patient. Physical examination, routine laboratory studies, and hormonal tests were within normal ranges. Abdominal CT and magnetic resonance imaging showed a solid oval tumor approximately 6 x 4 cm in the left adrenal gland without remarkable signs of malignancy. Left adrenalectomy was performed for treatment purposes. Histological diagnosis of the tumor was a ganglioneuroma originating from the adrenal medulla. Adrenal GN occurs rarely in adults and preoperative diagnosis is difficult, especially in asymptomatic cases. It needs careful evaluation and surgical treatment. According to our knowledge, this is the fifth case of adrenal GN in an adult patient from Turkey in English literature.

Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism.

BACKGROUND AND OBJECTIVES: Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality and morbidity. Little is known about hemostatic features of patients with PHPT. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patints 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 serum calcium and PTH and these hemostatic parameters in patients with PHPT. DESIGN AND METHODS: Twenty-four patients with PHPT and 20 age-, sex-, and-weight-matched healthy controls were included in the study. Tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-1 (PAI-1), TFPI, and TAFI were measured. The relationships between serum calcium, phosphorus, and PTH and these hemostatic parameters were examinated. RESULTS: Compared with the control subjects, t-PA, PAI-1, and PAI-1/t-PA ratios were significantly increased in patients with PHPT (P<0.0001), whereas TFPI levels were significantly decreased (P<0.0001). Plasma TAFI Ag levels did not significantly change in patients with PHPT compared with the controls. In patients with PHPT, serum phosphorus was negatively correlated with plasma PAI-1 Ag levels and PAI-1/t-PA ratio (r: -0.453, P<0.05; r: -0.580, P<0.01 respectively). There was a positive correlation between Cl/P ratio and plasma PAI-1 levels and PAI-1/t-PA ratio (r: 0.434, P<0.05; r: 0.528, P<0.05 respectively). iPTH was positively correlated with plasma PAI-1/t-PA ratio (r: 0.429, P<0.05). INTERPRETATION AND CONCLUSIONS: In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased PAI-1, PAI-1/t-PA ratios and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality due to cardiovascular disease seen in patients with PHPT.

Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hypothyroidism.

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.

Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI.

OBJECTIVE: 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. RESEARCH METHODS AND PROCEDURES: 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. RESULTS: 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). DISCUSSION: 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.