Kubilay Ukinc

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.

Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications.

Objectives: To investigate the markers of endogenous coagulation/fibrinolysis and vascular endothelial cell function, and to assess the relationships between hemostatic parameters and diabetic vascular complications in type 2 diabetic patients. Materials and Methods: Coagulation and fibrinolysis parameters were measured in 92 type 2 diabetic patients (43 male, 49 female, mean age 50.1 ± 13.4 years) with (n = 44) and without (n = 48) vascular diabetic complications, and in 40 nondiabetic healthy subjects (20 male, 20 female, mean age 49.8 ± 15.1 years). Common lipid parameters were also measured. Results: The plasma levels of fibrinogen, antithrombin III (AT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) activity and prothrombin time were found to be significantly increased in the type 2 diabetic patients compared with the healthy subjects. Glycosylated hemoglobin lc was inversely correlated with plasma protein S and activated prothrombin time. Protein C and S activities were positively correlated with plasma vWF activity, and were negatively correlated with plasma t-PA levels. vWF activity was negatively correlated with plasma t-PA levels. AT III levels were positively correlated with plasma total cholesterol levels, plasma low density lipoprotein cholesterol levels, plasma triglycerides and D-dimer levels. Plasma PAI-1 levels and factor V activity in diabetic patients with microvascular complications were significantly higher than those of the diabetic patients without microvascular complications. The plasma PAI-1 and platelet count were increased in patients with diabetic retinopathy compared with the diabetic patients without retinopathy. Plasma PAI-1 levels and factor VII activity were significantly higher in the diabetic patients with nephropathy than in diabetic patients without nephropathy. Plasma concentrations of fibrinogen and PAI-1 were significantly higher in the diabetic patients with neuropathy than the diabetic patients without neuropathy. Conclusions: The data demonstrated that patients with type 2 diabetes mellitus had a hypercoagulable state and hypofibrinolysis, thereby indicating that activation of coagulation with a reduced fibrinolytic activity may contribute to the increased risk of vascular disease in type 2 diabetic patients.

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.

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.

Large volume donor plasmapheresis in inherited thrombophilia implicated in arterial thrombosis

BACKGROUND Life-threatening complications following apheresis are rare, and include venous thrombosis. Arterial thrombosis following apheresis has not been reported. CASE REPORT A 48 year old donor had cerebral infarction following large volume plasma donation. The outcome was fatal. He was found to be heterozygous for both methylene tetrahydrofolate reductase (MTHFR) 677C-T mutation and Prothrombin 20210G-A allele. CONCLUSION This case suggests that large volume plasma donation may trigger arterial thrombotic events in inherited thrombophilia. Therefore, the effects of plasmapheresis on coagulation system should be studied thoroughly.

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 α-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.

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.

Renal Failure due to Bardet-Biedl Syndrome

Objective: To describe a case of Bardet-Biedl syndrome involving renal failure and retinal dystrophy. Case Presentation and Intervention: A 50-year-old female patient presented to the emergency service with uremic symptoms and metabolic acidosis. Polydactyly, retinitis pigmentosa, obesity, strabismus, nistagmus and renal failure were found. Because she had end-stage renal failure, hemodialysis therapy was started. She has been well for 18 months, without any complication on hemodialysis. Conclusion: Bardet-Biedl syndrome should be considered in patients with polydactyly, retinitis pigmentosa and renal failure.

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.