Halil Onder Ersoz

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.

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 enroled 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, β‐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.

Radioiodine treatment of hyperthyroidism: prognostic factors affecting outcome.

Objective: To assess the effectiveness of radioactive iodine (RAI) treatment in patients with hyperthyroidism and to evaluate prognostic factors affecting outcome.Research Design and Methods: Our cohort comprised 115 consecutive patients with hyperthyroidism treated with RAI at the Endocrinology Clinic at the Farabi Hospital, Trabzon, between 1994 and 2002. Data were retrieved from the endocrinology clinic database. Patients were categorized into three diagnostic groups: Graves’ disease (GD), toxic multinodular (TMN) hyperthyroidism, and toxic adenoma. Our policy, over the period of the study, was to offer a single fixed first dose (10 mCi) 131I to all patients with toxic nodular goiter (TNG) for the first time and to all patients with relapsed GD.Results: There was no significant difference in the cure rate between GD and TNG, but Graves’ patients had a significantly higher incidence of hypothyroidism (p<0.001). In contrast, incidence of euthyroidism was significantly increased in TNG than those of the patients with GD (p<0.05). The incidences of hyperthyroidism, euthyroidism, cure rate, and persistent hyperthyroidism did not vary significantly between females and males. Age at onset of hyperthyroidsim at diagnosis was not associated with outcome of RAI therapy. The incidence of hypothyroidism in patients who had nonpalpable goiter was higher than those in patients who had medium or large goiter (p<0.05). The means of serum FT3 and TT4 at presentation were correlated with the development of hypothyroidism after RAI therapy. Logistic regression analysis showed serum FT3 concentration at presentation to be significant contributing factor to failure to respond to a single dose of RAI. Patients who had higher FT3 concentrations at diagnosis were more likely to fail to respond to RAI therapy.Conclusions: The results of the present study of a cohort of patients with hyperthyroidism demonstrate that a single fixed dose of 10 mCi of RAI is highly effective in curing GD as well as toxic nodular hyperthyroidism. Therefore, treatment potocols for these groups should be identical. The most important factors that determine efficacy of RAI treatment are serum FT3 concentrations at diagnosis before the initiation of treatment and goiter size. Therefore, these factors should be taken into consideration when planning treatment. If such factors are present, the initial dose of RAI should be increased.

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.

Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus.

OBJECTIVE The objective of this study was to evaluate and compare the effects of gliclazide-modified release (gliclazide-MR), metformine (MET) and pioglitazone (PIO) monotherapies on glycemic control and conventional/non-conventional cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS A single center, randomized, 52-wk comparator-controlled clinical study was carried out in patients with newly diagnosed uncontrolled T2DM. A total of 57 patients were randomized into gliclazide-MR, metformin and pioglitazone groups. Drugs were administered for 12 months. Anthropometric measurements, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin, HOMA-IR, lipid parameters, the markers of coagulation/fibrinolysis, inflammation and endothelial dysfunction were measured at baseline and at months 3, 6, and 12. RESULTS In the gliclazide-MR group, HC, FPG, HbA1c, insulin, HOMA-IR, TC, trigylcerides, Lp (a), E-selectin and Hcy were significantly decreased after treatment compared to baseline. In the MET group, BMI, WC, FPG, PPG, HbA1c, ICAM-1 and Hcy significantly decreased after treatment compared to baseline. In PIO group, WC, HC, FPG, PPG, HbA1c, C-peptid, HOMA-IR, trigylcerides, vWF, IL-6, ICAM-1, E-selectin and Hcy significantly decreased after treatment compared to baseline, whereas, HDL-C increased. At the end of the month 12, the decreases in insulin and HOMA-IR score were more pronounced with PIO compared to gliclazide. CONCLUSIONS Gliclazide-MR, MET and PIO monotherapies, were equally effective in proving glycemic control in patients with newly diagnosed, oral antidiabetic (OAD)-naive T2DM. But, improvements in conventional/non-conventional cardiovascular risk factors were more pronounced in patients on PIO therapy compared to gliclazide and MET therapies. Also, all of the 3 drugs represent effective and safe first-line pharmacological treatment options in these patients.

The Significance Of Galectin-3 Expression in the Immunocytochemical Evaluation of Thyroid Fine Needle Aspiration Cytology

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.

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.

Acromegaly presenting with diabetic ketoacidosis, associated with retinitis pigmentosa and octreotide-induced bradycardia: a case report and a review of the literature.

Carbohyrate intolerance is a common feature of acromegaly. Frank diabetes mellitus is seen in about 10–20% of patients. There is no report of acromegaly presenting with diabetic ketoacidosis (DKA), associated with retinitis pigmentosa (RP), in the literature. We report the occurrence of DKA and RP in a patient with acromegaly. A 39-year-old Turkish man was admitted to the emergency ward with a 1-mo history of thirst, polyuria, weight loss of 10 kg, and loss of consciousness for 2 d. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. At ophthalmological examination, funduscopy showed RP. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma. During the medical treatment with octreotide, symptomatic sinusoidal bradycardia was developed (pulse rate 45 bpm, and blood pressure 70/40 mmHg). Octreotide therapy was stopped. Pituitary adenoma was removed surgically. For treatment of DKA, insulin need was very high in the first days after the onset of ketoacidosis, but decreased after initiation of treatment with octreotide and after successful operation. Insulin was stopped 7 d after surgery. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only six other cases of DKA associated with acromegaly and only three other cases of RP associated with acromegaly were found in the medical literature. In conclusion, to our knowledge, the present case is a first report of DKA and RP in patient with acromegaly.

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 Cushin’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 mm-Hg. 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 μg/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 131Iodine-metaiodobenzylguanidine (131I-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.

Epinephrine-secreting cystic pheochromocytoma presenting with an incidental adrenal mass

Cystic adrenal masses are a relatively rare condition, and are usually nonfunctioning and asymptomatic. Differential diagnosis includes pheochromocytoma (PHEO) and adrenal carcinoma; 8–10% of patients with PHEO may be completely asymptomatic. Moreover, fewer than 10% of PHEOs secrete pure epinephrine. We report a case of a E-secreting pure cystic PHEO presenting with an incidental adrenal mass. A 49-year-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal cystic mass with a thick wall that was incidentally discovered by abdominal ultrasonography during examination for nausea, vomiting, headache, and angina-like chest pain in another hospital. On admission, her blood pressure was 100/60 mmHg. Tension Holter monitoring revealed paroximal hypertension (178/136 mmHg) and hypotension (78/54 mmHg) attacks. Of urinary catecholamines and its metabolites, only urine metanephrine was markedly increased, despite a urine epinephrine level near the upper limit of normal ranges. Abdominal computed tomography and magnetic resonance imaging studies revealed a cystic round tumor approx 5 cm in diameter, located in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed pure cystic PHEO. Postoperatively, the urine metanephrine level returned to normal range and urine epinephrine level was decreased approx 60%. In conclusion, a diagnosis of E-secreting PHEO should be considered in patients with nonspecific symptoms, presenting with an incidental cystic adrenal mass, even in the absence of hypertension.