Blood coagulation and fibrinolysis in male patients with hypogonadotropic hypogonadism: plasma factor V and factor X activities increase in hypogonadotropic hypogonadism.

BACKGROUND AND OBJECTIVES: In men, androgens have both pro- and anti-thrombotic effects. Androgen deficiency in men is associated with an increased incidence of cardiovascular disease (CVD). However, the influence of hypogonadism on hemostasis is controversial. Little is known about hemostatic features of male patients with idiopathic hypogonadotropic hypogonadism (IHH). Thus, the aim of the present study was to evaluate the markers of endogenous coagulation and fibrinolysis, and to investigate the relationships between endogenous sex hormones and hemostatic parameters and serum lipid profile in men with IHH. DESIGN AND METHODS: Seventeen patients with IHH and 20 age-matched healthy controls were included in the study. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors (F) V, VII, VIII, IX, and X activities, von Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA), and tissue plasminogen activator inhibitor (PAI-1), as well as common lipid variables, were measured. The relationships between serum sex hormones and these hemostatic parameters were examined. RESULTS: Compared with the control subjects, platelet count, FV, FX, and protein C activities were significantly increased in patients with IHH (p<0.01, p<0.05, p<0.01, and p<0.05, respectively), whereas AT III was decreased (p<0.05). Fibrinogen, FVIII, vWF, t-PA, PAI-1, and the other coagulation/fibrinolysis parameters and lipid profile in patients with IHH were not different from the controls. In patients with IHH, we showed that serum LH level was negatively correlated with fibrinogen (r: -0.78, p<0.01) and protein C (r: -0.55, p<0.05) and positively correlated with t-PA (r: 0.53, p<0.05). Serum FSH levels inversely correlated with fibrinogen (r: -0.75, p<0.01). INTERPRETATION AND CONCLUSIONS: We found some differences in the hemostatic parameters between the patients with IHH and healthy controls. Increased platelet count, FV and FX activities and decreased AT III levels in patients with IHH represent a potential hypercoagulable state, which might augment the risk for atherosclerotic and atherothrombotic complications. Therefore, IHH may be associated with an increased risk of CVD. However, sex hormones may play a role at different levels of the complex hemostatic system in patients with IHH.

Blood coagulation, fibrinolysis and lipid profile in patients with primary hyperparathyroidism: increased plasma factor VII and X activities and D-Dimer levels.

BACKGROUND AND OBJECTIVES: Primary hyperparathyroidism (PHPT) is associated with an increased cardiovascular mortality and morbidity rate. However, the exact role of PTH and/or calcium in the development of cardiovascular disease (CVD) is still controversial. The influence of PHPT on hemostasis is yet unknown. Therefore, the main purpose of this study was to investigate the markers of endogenous coagulation/fibrinolysis and to evaluate the relationships between these hemostatic parameters, serum lipid profile and serum calcium and PTH in patients with PHPT. DESIGN AND METHODS: Twenty-three patients with PHPT and 20 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) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipoprotein variables, were measured. The relationships between biochemical parameters and these hemostatic parameters were examinated. RESULTS: Compared with the control subjects, platelet count, FVII, FX activities, and D-Dimer levels were significantly increased in patients with PHPT (p<0.001, p<0.05, p<0.001, and p<0.05, respectively). Among the lipids, the levels of TC, TG and LDL-C were significantly increased in patients with PHPT (p<0.01, p<0.001, p<0.001, respectively) than those in controls. In patients with PHPT, we showed a positive correlation between urinary phosphorus excretion and factors VIII, IX, and X (r: 0.572, p<0.01; r: 0.543, p<0.01; r: 0.532, p<0.01, respectively). F IX activity was positively correlated with TC (r: 0.463, p<0.05) and LDL-C (r: 0.549, p<0.01) There was a positive correlation between serum ALP and PAI-1 levels (r: 0.451, p<0.05). ApoB was positively correlated with D-Dimer (r: 0.421, p<0.05). We did not find any significant correlation between iPTH and serum calcium and the hemostatic parameters that we measured. INTERPRETATION AND CONCLUSIONS: In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased platelet count, F VII and FX activities and D-Dimer levels in patients with PHPT represent a potential hypercoagulable state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality rate due to CVD in patients with PHPT.

Neurofibromatosis type 1 associated with pheochromocytoma: a case report and a review of the literature.

Pheochromocytoma (PHEO) occurs in 0.1-5.7% of patients with neurofibromatosis type 1 (NF1). We report a case of adrenal PHEO in a patient with NF1. A 30-yr-old Turkish man was admitted to our hospital for further examinations of a right adrenal mass, that was incidentally discovered by abdominal ultrasonography during examinations for acute hepatitis B infection in another hospital. In his past medical history, the patient had only had one palpitation, sweating and headache episode 4 yr before. On admission, his blood pressure was 110/70 mmHg. Physical examination revealed signs of NF1. He had multiple neurofibromas over the entire skin, café-au-lait spots on the trunk and extremities and skinfold freckling. Bilateral opthalmic examination revealed multiple Lisch nodules. The 24-h ambulatory blood pressure monitoring revealed paroximal hypertension attacks (190/148 mmHg). Urinary catecholamines were markedly increased. Magnetic resonance imaging (MRI) revealed a solid round tumor approximately 5 cm in diameter, located in right adrenal gland. A 131Iodine-metaiodobenzylguanidine (131I-MIBG) scan showed uptake in the right adrenal gland. The pre-operative treatment with an alpha-blocker (phenoxybenzamine) was performed. Right adrenalectomy was performed; the surgical specimen revealed PHEO. Urine catecholamines and their metabolites returned to normal ranges on post-operative day 7. In conclusion, an adrenal mass can be incidentally discovered in any patient. After diagnosis of NF1, patients who have episodes of hypertension, sweating, headache and palpitation should be evaluated for PHEO.

Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients.

In this prospective, randomised, open trial, we wanted to evaluate the efficacy and safety of hourly subcutaneous (SC) insulin lispro administration in the treatment of diabetic ketoacidosis (DKA) in comparison with intravenous (IV) regular insulin treatment. Twenty patients were enrolled in the study. The patients were randomly assigned into two groups. Following a bolus injection of 0.15 U/kg IV regular insulin, group L received half of this dose as hourly SC insulin lispro while group R was treated conventionally with IV regular insulin infusion. At the end of treatment period, time that needed for normalisation of serum glucose, beta-hydroxybutyrate, blood pH and urine ketone levels were not different in groups L and R. There was no mortality or serious side effects in both groups. In this study, we revealed that treatment of mild and moderate DKA with SC insulin lispro is equally effective and safe in comparison with IV regular insulin.

Pheochromocytoma combined with pre-clinical Cushing's syndrome in the same adrenal gland.

Pheochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. In most of them, ectopic adrenocorticotropic hormone (ACTH) produced by PHEO resulted in bilateral adrenocortical hyperplasia. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report on a patient and discuss the peculiar diagnostic aspects of this entity. A 52-yr-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal mass that was incidentally discovered by abdominal ultrasonography during examinations for abdominal bloating and "gas" in other hospital. The patient had a history of palpitations, nervousness, sweating and heat intolerance. On admission, her blood pressure was 140/90 mmHg. A physical examination revealed no signs of an excessive production of adrenocortical steroids such as in CS. Tension Holter monitoring revealed paroximal hypertension attacks (183/105 mmHg). Urinary catecholamines were markedly increased. Her serum cortisol concentrations ranged from 5 to 17 microg/dl, whereas ACTH levels were undetectable. Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-day low-dose dexamethasone suppression test (DST). Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approximately 4 cm in diameter, located in the right adrenal gland. A 131 lodine-metaiodobenzylguanidine (131 I-MIBG) scan revealed uptake within tumor in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed PHEO and adrenocortical hyperplasia. To our knowledge, the present report is a rare case of PHEO combined with PCS in the same adrenal gland.

Sphenoid sinus brown tumor, a mass lesion of occipital bone and hypercalcemia: an unusual presentation of primary hyperparathyroidism.

Brown tumor is a focal lesion of the bone caused by primary or, less commonly, secondary or tertiary hyperparathyroidism (HPT). While the mandible is the most frequently involved bone in the head and neck region, atypical involvement of the cranium in the area of the sphenoid sinus is exceedingly rare. In the literature, a unique case of brown tumor of the sphenoid sinus was reported in a patient with primary HPT. We present a case of sphenoid sinus and occipital bone brown tumor associated with primary HPT. A 47-yr-old woman presented a 2-yr history of headaches, dizziness, diffuse body and articular pain, fatigue, and a 6-month history of intermittent nausea and vomiting, polydipsia, and polyuria. Magnetic resonance imaging (MRI) demonstrated an expansive mass lesion in the sphenoid sinus with erosion of the sellar floor and medial wall of the right orbit, and expansion in the medulla of bone. Examination of biopsy specimens obtained from sphenoid sinus mass confirmed the diagnosis of brown tumor. The biochemical laboratory studies showed elevation of parathyroid hormone and confirmed the diagnosis of primary HPT. Excision of a parathyroid adenoma affected the metabolic status into normalizing. At the follow-up of 12 months postoperatively, the size of sphenoid sinus brown tumor decreased and the mass of occipital bone disappeared. In conclusion, this is a first report of primary HPT masquerading as a destructive fibrous sphenoid sinus brown tumor associated with a mass lesion of occipital bone and hypercalcemia in the literature.

Effect of low-dose metoprolol in combination with sibutramine therapy in normotensive obese patients: a randomized controlled study.

OBJECTIVE: Sibutramine is an effective appetite suppresser agent, but treatment is often complicated with side effects, including palpitations and hypertension. In this study, we aimed to assess the effect of low-dose cardio-selective beta blocker combination with sibutramine treatment. METHODS: In total, 57 obese subjects were enrolled in the study and separated into two groups in order to receive sibutramine 10 mg/day plus placebo (group P) or sibutramine 10 mg/day plus metoprolol 25 mg/day (group M). Patients were evaluated in the beginning and at the end of the third month with anthropometric measurements, biochemical analysis, peripheral insulin resistance, and ambulatory 24 h blood pressure monitoring. Side effects were evaluated with a visual analog scale. RESULTS: During the study period, the drop-out rate was significantly higher in group P compared with group M (55 and 21%, respectively, P=0.014). Palpitations and headache were prominent symptoms in group P. Diastolic blood pressure (78.6+/-11.6 and 70.6+/-4.8 mmHg, respectively, P=0.013) and mean heart rate (84.3+/-6.1 and 75.8+/-8.4 beats/min, respectively, P=0.003) were significantly higher in group P compared with group M at the end of the third month. Weight loss was similar between the two groups (100.9+/-11.5 to 91.8+/-12.8 kg for group P, P<0.0001 and 97.9+/-13.2 to 88.9+/-13.8 kg for group M, P<0.0001). We did not find any deleterious effect of metoprolol on metabolic parameters. CONCLUSION: Addition of low-dose metoprolol to sibutramine therapy increased patient compliance to the treatment, and decreased the frequency and severity of side effects including hypertension and palpitations, without decreasing the drug efficacy or causing significant deleterious changes in metabolic parameters.

Blood coagulation and fibrinolytic activity in hypothyroidism.

The influence of hypothyroidism on haemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. Hypothyroidism has been associated with atherosclerosis; a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. The aim of the present study was to investigate the markers of endogenous coagulation and vascular endothelial cell function and to evaluate the relationship between serum lipid profile, thyroid hormones and haemostatic parameters in hypothyroid patients. We investigated various haemostatic parameters in 20 patients with hypothyroidism and compared them with 20 euthyroid controls. The relationship between serum thyroid hormones and the haemostatic parameters was examined. The plasma levels of fibrinogen, AT III and PAI-1 were significantly increased in hypothyroid patients compared with the control group, whereas factors VIII and X activity was decreased. We showed that free T3 levels correlated with factor IX activity. Free T4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. aPTT correlated inversely with t-PA activity and positively with protein C activity. Anti-Tg correlated inversely with FV. There was a positive correlation between triglycerides and protein C. Protein S correlated inversely with high density lipoprotein cholesterol. We found a hypofibrinolytic state in patients with hypothyroidism. Our results suggest that the risk of developing thrombosis and ultimately myocardial infarction via high PAI-1 levels may be increased in patients with hypothyroidism, a result in line with recent epidemiological data. However, thyroid hormones may play a role at different levels of the complex haemostatic system.

Blood coagulation and fibrinolysis in patients with hyperthyroidism.

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=-0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=-0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=-0.45, p<0.05; r=-64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves'disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.