Hyperglycemia is associated with lower levels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in wound fluid.

AIMS: Wounds in patients with hyperglycemia show impaired healing. Plasminogen activation is crucial in several overlapping phases of wound healing process. In this study, we aimed i) to compare acute wound fluid in patients with hyperglycemia and normoglycemia, ii) to focus on the elements of plasminogen activation in the wound fluid, and iii) to determine if the acute wound fluid characteristics are associated with surgical site infections. METHODS: In a cohort of 54 patients, a closed suction drain was placed in the wound above the anterior abdominal wall fascia under the skin in order to collect postoperative acute wound fluid samples for 3 following days after colorectal surgery. Patients were classified as normoglycemic (n=25) or hyperglycemic (n=29; 17 with type 2 diabetes and 12 with stress induced hyperglycemia). Surgical site infection was defined according to the Centers for Disease Control criteria. The levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAr), plasminogen activator inhibitor-1 (PAI-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and fibroblast growth factor-1 (FGF-1) were measured in the wound fluid. RESULTS: Compared to normoglycemic subjects, patients with hyperglycemia had significantly lower levels of uPA and uPAr in the wound fluid despite similar or even higher circulating levels. There was no significant difference in IL-1ß, TNF-α, PAI-1 and FGF-1 levels. In the whole study population, the wound fluid levels of uPA and uPAr were negatively correlated with circulating glucose levels. No difference was detected in the wound fluid characteristics of patients with and without surgical site infection. CONCLUSION: Patients with hyperglycemia exhibit decreased levels of uPA and uPAr in the wound fluid, suggesting a local failure in plasminogen activation at the wound site.

Insulin need in gestational diabetes is associated with a worse cardiovascular risk profile after pregnancy.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) treated with insulin are more likely to develop type 2 diabetes after pregnancy compared to mild GDM cases treated with medical nutrition treatment (MNT) alone. We aimed to compare levels of subclinical atherosclerosis markers in women with previous GDM treated with insulin and MNT alone. METHODS: Eighty-one women with previous GDM (45 treated with insulin, 36 treated with MNT) and 35 age-matched lean controls were included. Fasting glucose, insulin and lipids, circulating fibrinogen, CRP, PAI-1 and IL-6 levels were assayed. Carotid intima media thickness (IMT) was measured. RESULTS: Women with previous GDM treated with insulin in pregnancy had significantly higher fasting glucose, plasma PAI-1 levels and carotid IMT compared to women treated with MNT alone. In multiple regression analysis, insulin need in pregnancy was associated with increased carotid IMT and plasma PAI-1 levels (corrected for age, BMI, postpartum duration, fasting glucose and lipids; model r(2)=0.132; beta=0.297, p=0.014 for carotid IMT; model r(2)=0.198; beta=0.345, p=0.003 for PAI-1). CONCLUSION: Women with previous GDM treated with insulin in pregnancy had a worse cardiovascular risk profile compared to mild GDM patients. An intensive preventive approach for cardiovascular disorders is particularly essential for this subgroup of women.

Traditional and novel cardiovascular risk factors in non-functioning adrenal adenomas.

BACKGROUND: The majority of the incidentally discovered adrenal masses are non-functioning adrenal adenomas; however data regarding traditional and novel cardiovascular risk predictors in these subjects is lacking. The objective of our study was to investigate the levels of PAI-1, IL-6 and Apelin along with several traditional cardiovascular risk markers in subjects with non-functioning adrenal adenomas. METHODS: 38 subjects with non-functioning adrenal adenomas and 30, age, gender and BMI matched healthy controls were enrolled. Participants underwent hormonal evaluation including morning cortisol, adrenocorticotrophic hormone (ACTH), post dexamethasone suppression test (DST) cortisol, dehydroepiandrosterone sulfate (DHEAS) and urinary cortisol. Anthropometric and metabolic parameters, body composition, PAI-1, IL-6 and Apelin were measured. RESULTS: Subjects with non-functioning adrenal adenomas had significant elevations in systolic blood pressure, mean arterial pressure, waist circumference, uric acid, and post DST cortisol and had significantly reduced levels of DHEAS when compared to BMI matched controls. No significant difference was observed in terms of PAI-1, IL-6 and Apelin between groups. PAI-1 and IL-6 were significantly correlated with mean arterial pressure, BMI, uric acid, total and LDL-cholesterol. Linear regression analysis showed that morning cortisol and Apelin levels independently predicted HOMA levels in subjects with adrenal adenomas. CONCLUSION: Subjects with non-functioning adrenal adenomas feature several cardiovascular risk factors even when compared to BMI matched individuals. Subtle cortisol autonomy in adrenal adenomas may be associated with those findings.

Plasma thrombin-activatable fibrinolysis inhibitor levels are not associated with glucose intolerance and subclinical atherosclerosis in women with previous gestational diabetes.

We aimed to determine plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in women with previous gestational diabetes mellitus (GDM) and to evaluate the possible association of plasma TAFI with glucose intolerance and markers of subclinical atherosclerosis. This cross-sectional study was performed in 111 women with previous GDM and 60 controls. Glucose intolerance was evaluated. Homeostasis model assessment score was calculated. Circulating lipids, interleukin-6, matrix metalloproteinase-1, fibrinogen, plasminogen activator inhibitor-1, and TAFI antigen levels were assayed. Carotid intima media thickness (IMT) was measured. Women with previous GDM had increased levels of atherosclerosis markers and carotid IMT. On the other hand, plasma TAFI antigen levels were similar (P = .395). Thrombin-activatable fibrinolysis inhibitor was not associated with the indices of insulin resistance, glucose intolerance, markers of atherosclerosis, and carotid IMT. Our data demonstrated that plasma TAFI was not altered in women with previous GDM. TAFI was not associated with glucose intolerance and subclinical atherosclerosis.

Acute phase reactants predict the risk of amputation in diabetic foot infection.

BACKGROUND: prediction of amputation would aid clinicians in the management of diabetic foot infections. We aimed to assess the predictive value of baseline and post-treatment levels of acute phase reactants in the outcome of patients with diabetic foot infections. METHODS: we collected data prospectively during minimum follow-up of 6 months in patients with infected diabetic foot ulcers hospitalized in Dokuz Eylul University Hospital between January 1, 2003, and January 1, 2008. After excluding patients who did not attend the hospital for follow-up visits regularly (n = 36), we analyzed data from 165 foot ulcer episodes. RESULTS: limb ischemia and osteomyelitis were much more frequent in patients who underwent amputation. Wagner grade, which assesses ulcer depth and the presence of osteomyelitis or gangrene, was higher in patients who needed amputation. Ulcer size was slightly larger in the amputation group. Baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, white blood cell counts, and platelet counts were significantly elevated in patients who underwent amputation. Albumin levels were significantly suppressed in the amputation group. Univariate analysis showed that a 1-SD increase in baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, and white blood cell counts and a 1-SD decrease in post-treatment albumin levels were significantly associated with increased risk of amputation. Post-treatment C-reactive protein level was strongly associated with amputation risk. CONCLUSIONS: circulating levels of acute phase reactants were associated with amputation risk in diabetic foot infections.

Effect of levothyroxine suppression therapy on plasma thrombin activatable fibrinolysis inhibitor antigen levels in benign thyroid nodules.

OBJECTIVE: The aim of this prospective study was to investigate the effect of LT4 suppression therapy on plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen and plasminogen activator inhibitor-1 (PAI-1) levels in benign thyroid nodules. We also compared hyperthyroid patients and healthy controls. SUBJECTS AND METHODS: Twenty premenopausal women with benign thyroid nodules were given LT4 suppression therapy for 1 year. Plasma TAFI and PAI-1 antigen levels were measured at baseline and after LT4 suppression treatment. The endogenous hyperthyroid group was composed of 19 premenopausal females with newly diagnosed endogenous hyperthyroidism. Eighteen age-matched euthyroid healthy premenopausal women were enrolled as the control group. RESULTS: TAFI antigen levels decreased after LT4 suppression treatment; however, the difference was not statistically significant (p = 0.057). LT4 treatment resulted in a nonsignificant increase in PAI-1 levels. Patients with endogenous hyperthyroidism had decreased levels of TAFI antigen and increased levels of PAI-1 antigen (p < 0.05). There was a negative correlation between the FT(4) and TAFI antigen levels. Serum TSH was positively correlated with the plasma levels of TAFI antigen. CONCLUSION: LT4 suppression therapy for benign thyroid nodules did not result in a significant decrease in TAFI antigen levels in premenopausal women, but endogenous hyperthyroidism was associated with significantly decreased levels of TAFI antigen.

Increased osteoprotegerin levels in women with previous gestational diabetes developing metabolic syndrome.

Osteoprotegerin (OPG), a novel soluble member of tumour necrosis factor receptor superfamily, has been shown to link cardiovascular disorders. The aim of this study is to investigate the potential relationship between serum OPG levels, cardiovascular risk factors and metabolic syndrome in a relatively large group of women with previous GDM. In this cross-sectional case-control study, 128 women with previous GDM and 67 age-matched controls were enrolled. Subjects were evaluated for the diagnosis of metabolic syndrome according to the criteria of the American Heart Association (AHA). Fasting glucose, insulin, serum lipids, CRP and OPG were assayed. HOMA score was calculated. Carotid intima media thickness (IMT) was measured. There was no significant increase in OPG levels in women with previous GDM when compared to controls. On the other hand, women with previous GDM developing metabolic syndrome had higher OPG levels than those without metabolic syndrome and healthy controls. Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT. Serum OPG is related to cardiovascular risk factors and metabolic syndrome, and might be involved in the development of cardiovascular disorders in women with previous GDM.

Evaluation of postpartum carbohydrate intolerance and cardiovascular risk factors in women with gestational diabetes.

We aimed to evaluate the predictors of subsequent development of postpartum carbohydrate intolerance, metabolic syndrome and cardiovascular risk factors in women with previous GDM. Two hundred fifty-two consecutive women with GDM were enrolled. After exclusion of women who did not attend to the hospital for follow-up visits for minimum 1 year, data of 195 patients were evaluated. Seventy-one lean women with negative screening for GDM were included as a control group. The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose and metabolic syndrome was significantly higher in women with previous GDM than healthy controls. Women with previous GDM were more insulin resistant, had an atherogenic lipid profile and increased carotid IMT. The most important predictors of postpartum diabetes were the need for insulin treatment during index pregnancy and glucose values on antepartum OGTT. Among women with previous GDM, the development of postpartum diabetes and metabolic syndrome was associated with increased carotid IMT. Our data show that women with previous GDM are at high risk for developing carbohydrate intolerance, metabolic syndrome and atherosclerosis. Antepartum prediction of high risk subjects for the subsequent development of postpartum carbohydrate intolerance and metabolic syndrome seems to be vital to prevent cardiovascular outcomes.

The levels of soluble CD40 ligand and C-reactive protein in normal weight, overweight and obese people.

OBJECTIVE: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration. METHODS: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m(2); Group 2 (overweight), BMI 25 kg/m(2) to 29.9 kg/m(2); and Group 3 (obese), BMI>or=30 kg/m(2). RESULTS: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. CONCLUSION: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

Management of gestational diabetes by physicians in Turkey.

AIMS: We sought to investigate the practice patterns of clinicians (family physicians, internists and obstetricians) in Turkey in screening for gestational diabetes mellitus (GDM), management and monitoring of hyperglycaemia in pregnant women with GDM, and assessment of glucose tolerance in the postpartum state. METHODS: Between January and December 2007, current practices of Turkish physicians (n=434) were assessed by a questionnaire which was concerned with physician demographics and clinical practice including screening and diagnostic methods for GDM, management of GDM during pregnancy and postpartum assessment of glucose tolerance. The questionnaire was developed in respect to the recommendation of the Fifth International Workshop-Conference on GDM and the standards of the American Diabetes Association (ADA). RESULTS: Although most of the physicians stated that they performed screening for GDM and postpartum screening for glucose intolerance in women with GDM, their screening practices vary. The proportion of women who were provided with a nutrition counselling by a registered dietician and a patient education by a trained nurse was low, especially in women treated by the family physicians. Home glucose monitoring was widely used in the management of GDM, however, postprandial glucose assays were used occasionally. Regular and NPH insulin preparations were the most preferred drugs to treat GDM. Internists were more likely to use insulin analogues. On the other hand, a significant number of physicians stated that they used oral antidiabetics (OADs). A considerable number of family physicians used OADs which have not been proved to be safe in pregnancy. CONCLUSIONS: Our results suggest that there is considerable variation in the clinical practice patterns of physicians. An education program to enhance the clinical aptitude of physicians, particularly family physicians, in the medical management of GDM should be designed throughout the country.

The effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers.

Reduced creatinine clearance is related to an increased risk for diabetic foot ulcer development. Wound healing has been reported to be worse in diabetic patients with impaired kidney functions than general diabetic population. This study aimed to investigate the effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers. Data from 147 neuropathic diabetic foot ulcer episodes were included in this observational study. Patients were admitted to Dokuz Eylul University Hospital between January 2003 and June 2008. Patients were excluded if they had limb ischemia. Diabetic nephropathy was investigated by 24h urinary albumin excretion and serum creatinine levels. Creatinine clearance was calculated according to Cockcroft-Gault formula. Foot ulcers were followed up for 6 months to determine the outcome. Our short-term follow-up revealed that neuropathic diabetic ulcers healed worse in patients with decreased creatinine clearance than in those who had normal creatinine clearance. Amputation rates were also found to be higher. Our results suggest that creatinine clearance is an important factor affecting wound healing in patients with neuropathic diabetic foot ulcers.

Incidence of thyroid dysfunction and thyroid cancer in renal transplant recipients: a single center experience.

BACKGROUND: The prevalence of thyroid cancer in renal transplant population has not been widely studied, and there is no consensus on the management of thyroid cancer in transplant patients. The aim of this study was to evaluate changes in thyroid hormone levels and investigate the incidence of the thyroid cancer after renal transplantation. MATERIALS AND METHODS: From October 1989 to April 2007, 122 renal allograft recipients that were being followed underwent thyroid ultrasonography to determine nodules together with thyroid hormone levels. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was performed to the nodules > 10 mm or those with 8-10 mm diameter but with calcifications. RESULTS: One hundred and eight patients (88.5%) had normal thyroid function. None of the patients had overt hypothyroidism, 2 had subclinical hypothyroidism, 10 subclinical thyrotoxicosis, and 2 low T3 syndrome. Mean thyroid volume was 14.2 +/- 7.2 ml. In all, 91.8% was diagnosed with goiter (n = 112). Seventy-two thyroid nodules were detected in 49 kidney allograft recipients (single nodule in 30, multiple in 19 patients). Eighty-four biopsy samples were reported as benign (n = 21, 87.5%), 8 as suspicious (n = 2, 8.3%), and 4 as inadequate (n = 1, 4.1%). After surgery, one of the patients (0.8%) with suspicious FNAB was reported as papillary thyroid carcinoma. CONCLUSION: Because of the high incidence of thyroid dysfunction in transplant patients, screening of thyroid function should be a part of follow-up. Our results suggest that although frequency of nodules is increased in kidney transplant patients, prevalence of thyroid cancer is slightly, but not significantly, higher than that of the normal population.

Adrenal incidentaloma, clinical, metabolic, follow-up aspects: single centre experience.

To investigate clinical characteristics, metabolic parameters and follow-up findings of subjects with incidentally discovered adrenal tumors. 376 consecutive subjects who have been evaluated since 2002 were included. Initial radiological examination was CT. Hormonal evaluation included 8.00 a.m. cortisol, DHEA-S, ACTH and in hypertensive subjects, plasma renin activity, and serum aldosterone. Urinary free cortisol (UFC), urinary normetanephrine, and metanephrine were measured. Overnight 1 mg dexamethasone suppression test was performed. Radiological evaluation was performed at 6th and 12th months and annually in subsequent visits. Hormonal evaluation was performed 6 months after the initial visit and annually in subsequent visits. Additionally, patients were evaluated for the development of Type 2 diabetes mellitus, hypertension, hyperlipidemia, and metabolic syndrome in 6-month intervals. Mean age of the participants was 54.7 ± 13.1. Female subjects were more commonly affected (70%). CT was the most frequent radiological intervention that discovered adrenal masses (57%). The vast majority of the participants (85.6%) had benign adrenal adenomas. Primary adrenocortical malignancy was detected in 4 subjects (1.1%). Subjects with adrenal adenomas had significantly smaller tumor diameters (P ≤ 0.001 vs. other tumors). Sensitivity and specificity of 40 mm as a cut-off value in the differentiation of adrenal gland malignancies from benign tumors was 73.3 and 54.8%, respectively. Most of the adrenal adenomas were non-functioning (73.5%). Subclinical Cushing syndrome (sCS) was detected in 12.5%. The overall prevalence of Type 2 diabetes mellitus, hypertension, hyperlipidemia, and metabolic syndrome was 18.4, 54.9, 59.6, and 48.1%, respectively. They were significantly more common in middle-aged and elderly subjects. During 24 months follow-up 10.2% of adenomas featured increase in tumor diameter and 2.06% developed sCS. Young subjects featured more stable tumor diameter and hormonal status. Most of the incidentally discovered adrenal tumors were non-functioning adrenal adenomas. Clinically overt hormone hypersecretion syndromes were mainly shown in young subjects, while adrenal gland malignancies and sCS were more common in older ages. Mass enlargement and development of subclinical cortisol secretion were not rare and observed especially in middle-aged and elderly subjects. Metabolic derangements were common; however, a possible independent association between adrenal adenoma and metabolic problems need to be elucidated with prospective studies.

Allergic reactions to human insulin: a review of current knowledge and treatment options.

Although the incidence of insulin allergy decreased after the introduction of recombinant human insulin preparations, it is still a major problem which may be life-threatening in some cases. In this article, we attempted to review current knowledge concerning allergic reactions to human insulin and discuss the available treatment options of insulin allergy.

Prediction of developing metabolic syndrome after gestational diabetes mellitus.

OBJECTIVE: To determine the predictors of subsequent development of metabolic syndrome (MS) in women with previous gestational diabetes mellitus (GDM). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): One hundred sixty-four consecutive women with previous GDM were evaluated after a mean follow-up of 40.54 months from index pregnancy. Sixty-five lean women with negative screening for GDM were included as a control group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Subjects were evaluated for diagnosis of MS according to criteria of the National Cholesterol Education Program and the International Diabetes Federation. Tests were performed including a 75-g oral glucose tolerance test (OGTT), fasting insulin, lipids, plasma fibrinogen, blood pressure, and body measurements. The homeostasis model assessment score was calculated. RESULT(S): The MS prevalence was higher in women with previous GDM, according to both definitions. Univariate analysis showed that prepregnancy obesity, weight gain during follow-up, and fasting glucose level at the OGTT of the index pregnancy were predictors of developing MS. Multivariate analysis showed that fasting glucose level >100 mg/dL at the OGTT of the index pregnancy was an independent predictor of the MS development. CONCLUSION(S): We suggest that early prediction of women with previous GDM who are at high risk for developing MS is possible, and it is vital to prevent MS-related complications.

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome.

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.

Effect of levothyroxine replacement therapy on paraoxonase-1 and carotid intima-media thickness in subclinical hypothyroidism.

BACKGROUND: Paraoxonase-1 (PON-1) may play an important role in atherosclerosis. Atherosclerosis is an inflammatory disease and C-reactive protein is a marker for inflammation. The aim of this study was to determine serum PON-1 activity and high-sensitivity C-reactive protein (hs-CRP) levels and assess carotid intima-media thickness, a marker of early atherosclerotic changes, in patients with subclinical hypothyroidism. MATERIAL/METHODS: hs-CRP concentrations and PON-1 activity with respect to carotid intima-media thickness were evaluated in 38 subclinical hypothyroidism patients (normolipidemic, mean age: 49.79+/-10.04 years) before and after 3 months of stable euthyroidism and compared with those of 19 euthyroid normolipidemic healthy individuals (mean age: 49.95+/-8.12 years). RESULTS: At baseline, the patients with subclinical hypothyroidism had similar levels of PON-1 activity and hs-CRP and a similar lipid profile as the controls; however, the carotid intima-media thickness was greater than in the controls. Levothyroxine treatment had no effect on serum PON-1 activity and hs-CRP level, but it resulted in a significant reduction in carotid intima-media thickness in the subclinical hypothyroidism patients. CONCLUSIONS: PON-1 activity and hs-CRP levels did not significantly differ between subclinical hypothyroid patients and controls. Although levothyroxine treatment might have the potential to reverse the progression of atherosclerosis in subclinical hypothyroid patients, PON-1 activity and hs-CRP levels were not affected by this treatment. The reduction in carotid intima-media thickness was independent of the decrease in serum lipid profile or other variables.

Hypercalcemia due to Graves' disease in a patient with thyroid hemiagenesis.

Thyroid hemiagenesis is a rare anomaly due to failure of development of one thyroid lobe during embryological life. A lot of thyroid disorders may accompany thyroid hemiagenesis. In this report, we present a case of thyroid hemiagenesis, who had moderate hypercalcemia due to Graves' disease. A 43-year-old woman presented with weight loss of more than 5 kg within one month, heat intolerance, and increased sweating. For the past month, she had been troubled by intermittent symptoms of vomiting, thirst, and constipation. On examination, she had tachycardia with no signs of dehydration. Pulse rate was 110 per minute. She had fine tremor, proximal muscle weakness, and asymmetric smooth goiter and hyperplasia in the right thyroid gland. Thyroid function tests confirmed the diagnosis of hyperthyroidism. Although hypercalcemia may be detected in patients with thyrotoxicosis, to the best of our knowledge, this is the first case report of thyroid hemiagenesis accompanying hypercalcemia due to thyrotoxicosis.

Soluble CD40 ligand, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor-1-antigen in normotensive type 2 diabetic subjects without diabetic complications. Effects of metformin and rosiglitazone.

OBJECTIVE: To evaluate subclinical inflammation and fibrinolysis in low-risk type 2 diabetic subjects and to assess the efficacy of metformin and rosiglitazone in this group. SUBJECTS AND METHODS: Sixty-one normotensive, normoalbuminuric type 2 diabetic subjects without diabetes-related complications were included in a 4-week standardization period with glimepiride. After the standardization period, 21 subjects were excluded and the remaining 40 were randomly divided into two groups matched for age, gender, body mass index and disease duration. The first group (n = 20) received metformin (1,700 mg/day), the second group (n = 20) rosiglitazone (4 mg/day) for 12 weeks. Patients with low-density lipoprotein-cholesterol higher than 130 mg/dl at the beginning of the randomization period were treated with simvastatin (maximum dose 20 mg/day). Twenty-three healthy controls were also recruited. Cytokine measurements were performed with ELISA kits. RESULTS: Baseline plasma plasminogen activator inhibitor-1 (PAI-1) level of type 2 diabetic subjects was significantly elevated (p = 0.038), but baseline levels of soluble CD40 ligand (sCD40L) and thrombin-activatable fibrinolysis inhibitor-1 (TAFI) antigen did not differ from healthy controls. Twelve weeks of metformin or rosiglitazone therapy did not cause significant changes in sCD40L, PAI-1 and TAFI antigen levels. In simvastatin-treated subjects (n = 9) significant reductions of PAI-1 were achieved (p = 0.028), while sCD40L and TAFI-Ag did not differ from baseline values. CONCLUSION: Our results showed that nonobese diabetic patients at low cardiovascular risk had similar levels of subclinical markers of inflammation and fibrinolysis as matched healthy controls. Neither metformin nor rosiglitazone caused marked changes in sCD40L, PAI-1 and TAFI antigen levels. A subset of patients who received simvastatin showed a modest decrease in PAI-1 level and could contribute to beneficial vasculoprotective effect of the drug in type 2 diabetics.

Natural course of benign adrenal incidentalomas in subjects with extra-adrenal malignancy.

Patients with extra-adrenal malignancies are diagnosed increasingly with benign adrenal tumors, as well as non-oncology subjects. We aimed to demonstrate the natural course of adrenal adenomas in terms of mass size and hormonal status in oncology and non-oncology subjects. We also compared the characteristics and behavior of adrenal adenomas with adrenal malignancies. In our registry of adrenal tumors (n = 335), we prospectively evaluated 29 oncology subjects (EAM+) and age, gender, and follow-up duration matched 110 non-oncology subjects (EAM-) with adrenal adenomas. Median follow-up was 24 months. We also included 16 subjects with adrenal malignancies (primary; 3 and metastasis; 13). Tumor size was followed-up with CT or MRI at 6th and 12th months and annually in subsequent visits. Hormonal assessment was repeated at the 6th month after the initial visit and annually in subsequent visits. Initial tumor size, mean increase in tumor size, and number of subjects who showed mass enlargement or developed subclinical Cushing Syndrome were comparable (P > 0.05) between EAM+ and EAM- groups. Subjects with malignant adrenal tumors were older (P = 0.06), had larger tumors at presentation (P < 0.001), and showed mass enlargement during a shorter follow-up duration (P < 0.001). Oncology subjects with adrenal adenomas featured similar baseline and follow-up parameters in terms of mass enlargement and development of subclinical Cushing Syndrome when compared with non-oncology subjects. Malignant adrenal tumors were characterized with large, rapidly growing tumors of older ages. Conservative approach can be suggested to oncology subjects for adrenal adenomas unless clinical and radiological suspicion of adrenal malignancy is present.