Correlation of vascular endothelial growth factor and vascular endothelial growth factor receptor-1 levels in serum and thyroid nodules with histopathological and radiological variables.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) is a major cytokine in angiogenesis and has a role on aggressivity of various tumors. The expression of VEGF has been shown to increase in differential thyroid cancer. The aim of the study was to evaluate serum and intranodular VEGF (nVEGF) and VEGF receptor-1 (VEGFR-1) levels in patients with thyroid nodules and their relevance to ultrasonographic and pathological results. MATERIALS AND METHODS: A total of eighty patients were included in the study. Thyroid fine-needle aspiration biopsies were performed, and the levels of serum and nVEGF and VEGFR-1 were measured. Any possible correlations between serum and nVEGF, VEGFR-1, and biochemical/radiological variables were investigated. RESULTS: There were no significant differences between serum VEGF (sVEGF), nVEGF, sVEGFR-1, nVEGFR-1 levels, number of nodules, size of nodules, and benign and malignant ultrasonographic features. sVEGF and nVEGF were higher in malignant or suspicious nodules than that in benign nodules, but did not reach statistical significance (P > 0.05). sVEGFR-1 and nVEGFR-1 levels were higher in hyperthyroid patients than that in euthyroid patients (P < 0.05 and P = 0.003, respectively). nVEGFR-1 level was higher in hypothyroid patients than that in euthyroid patients (P = 0.016). sVEGF level was found to be higher in hyperactive nodules than that in others. Both sVEGFR-1 (P = 0.008) and nVEGF levels (P = 0.01) significantly increased with increasing age. nVEGFR-1 decreased with increasing body mass index (BMI) (P = 0.004). CONCLUSIONS: Our study showed the relationships of sVEGF, nVEGF, sVEGFR-1, and nVEGFR-1 levels with age, gender, BMI, and hyperthyroidism. To determine the role of VEGF/VEGFR-1 in thyroid nodules, further studies are required with a large number of patients.

The effect of type 2 diabetes on electrocardiographic markers of significant cardiac events.

BACKGROUND & OBJECTIVES: In diabetics, cardiac microvascular circulation disorder increases the risk of arrhythmia and sudden cardiac death. Tpeak-Tend (Tp-e) interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios measured by surface electrocardiogram (ECG) are new parameters used to evaluate ventricular arrhythmogenity. We aimed to compare QT dispersion (QTd), corrected QT dispersion (QTcd), P dispersion (Pd), Tp-e interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios in patients with type- 2 diabetes (T2D) with healthy population. METHODS: Electrocardiographic parameters of a total of 100 patients diagnosed with T2D were retrospectively analyzed and compared with the ECG results of 100 healthy age-, sex-, and body weight and height-matched controls. RESULTS: The Pd, QT interval, QTc interval, QTd, QTcd, Tp-e/QT, Tp-e/QT ratios were higher in the patients. A statistically significant correlation was found only between hemoglobin A1c and Tp-e dispersion, QTd, QTcd, Pd, Tp-e/QT and Tp-e/QTc parameters, in linear regression analysis. There was also a statistically significant positive correlation between the values of low-density lipoprotein, systolic blood pressure, and Tp-e dispersion. CONCLUSION: The risk of arrhythmia can be predicted by evaluating Tp-e interval, Tp-e dispersion, Tp-e/QT, and Tp-e/QTc ratio, suggesting heterogeneity of ventricular repolarization and P wave and Pd showing heterogeneity of atrial repolarization in diabetic patients.

Pituitary Apoplexy due to the Diagnostic Test in a Cushing"s Disease Patient.

Pituitary apoplexy is a medical condition that needs urgent diagnosis and treatment. It may occur spontaneously or may be precipitated by a variety of reasons including dynamic endocrine tests. Although pituitary apoplexy is usually seen in nonfunctional pituitary adenoma, it can also be seen in ACTH secreting macroadenomas. ACTH secreting adenomas present usually as microadenomas and in these patients apoplexy is rarely seen. In this paper we present a 30-year-old male patient with a history of Cushing"s disease who suffered from pituitary apoplexy after the 1 mg dexamethasone suppression test. He underwent endoscopic endonasal transsphenoidal surgery and his symptoms and signs were significantly improved.

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p<0.001, p=0.009). A positive correlation was determined between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative correlation between the osteocalcin and thyroid stimulating hormone (TSH) (p<0.05); a positive correlation between the osteocalcin and thyroid hormones (FT3,FT4) (p<0.001); and a positive correlation between the deoxypyridinoline and hydroxyproline (p<0.001). No correlation was determined between sclerostin and TSH,FT3,FT4 (p>0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

The Clinical Values of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Levels in Blood and Thyroid Nodules.

AIM: Insulin-like growth factor-1 (IGF-1) is a potent mitogen for many cells. IGF-1 plays a role in the pathogenesis of various tumors with its mutagenic and antiapoptotic properties. The aim of this study was to determine both the serum and intranodular levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with nodular thyroid diseases. MATERIALS AND METHODS: In this study, 80 subjects who performed fine-needle aspiration biopsy (FNAB) were required in order to investigate the effects of serum and intranodular IGF-1 and IGFBP-3 in the pathogenesis of nodules. After performing FNAB, IGF-1 and IGFBP-3 levels were determined in blood and aspiration samples. RESULTS: The serum levels of IGF-1 (232.8 ± 12.9 ng/ml) and IGFBP-3 (4.8 µg/ml) were found significantly higher than that of the intranodular IGF-1 (39.1 ng/ml) and intranodular IGFBP-3 levels (0.173 µg/ml) (p < 0.01). Intranodular levels of IGF-1 and IGFBP-3 were higher in subjects with multinodular thyroid gland than those of subjects with solitary nodules (p = 0.043). A positive correlation between the nodule size and the serum IGFBP-3 levels was detected (p = 0.042, r = 0.23). CONCLUSION: This study demonstrated the possible role of both IGF-1 and IGFBP-3 in the growth and the formation of multinodularity of thyroid nodules.

Increased Serum Levels of IL-28 and IL-29 and the Protective Effect of IL28B rs8099917 Polymorphism in Patients with Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is thought to result from decreased T helper type 2 (Th2) responses, leading to the progressive destruction of thyrocytes. IFN-λ1, -λ2, and -λ3 (also known as IL-29, IL-28A, and IL-28B, respectively) are recently described members of the IFN-λ family and have been shown to decrease the production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in HT remain unknown. The purpose of this study was to examine whether IL29 and IL28B gene polymorphisms are susceptibility genes for the development of HT. Also, we investigated the effects of IL-29 and IL-28 serum levels in the pathogenesis of HT. Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, single-nucleotide polymorphisms (SNPs) of IL28B rs8099917 (IL28 G/T) and IL29 rs30461 (IL29 T/C) were studied in 99 patients with HT and 100 healthy controls. Considering the allelic distribution of the IL28 G/T polymorphism, a higher frequency of the G allele was observed in the control group versus the HT group. Thus, it was suggested that the G allele may be protective against HT pathogenesis (OR = 0.388, 95% CI = 0.217-0.693; p = 0.001). Our findings also demonstrated that there was a statistically significant difference in serum IL-28 and IL-29 levels between case and control groups (p < 0.001). Increased serum levels of IL-28 and IL-29 were found in patients with HT. However, we did not find a relationship between the IL29 gene polymorphism and HT. In conclusion, the IL28B gene polymorphism and serum IL-28 and IL-29 levels seem to play a role in the pathogenesis of HT.

Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease.

Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (p < 0.05). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (p = 0.001). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, r (2) = 0.54, p < 0.001). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules.

Focused parathyroidectomy without intra-operative parathormone monitoring: The value of PTH assay in preoperative ultrasound guided fine needle aspiration washout.

BACKGROUND: The accurate identification of hyperfunctioning parathyroid (HP) gland is the only issue for definitive surgical treatment in primary hyperparathyroidism (pHPT). Various imaging and operative techniques have been proposed to confirm the localization of the diseased gland. Nevertheless, none of these methods proved to be the gold standard. The presented study aimed to assess the value of parathyroid hormone assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation for focused parathyroidectomy without intra-operative PTH monitoring. MATERIAL AND METHODS: The retrospective analysis of 57 patients with pHPT who underwent FNA-PTH was conducted from a prospective database. Biochemical assessment together with radiological (ultrasonography) and nuclear (MIBI scan) imaging was reviewed. Associations between FNA-PTH washout values and localization technics were evaluated and compared in terms of operative findings. RESULTS: Focused parathyroidectomy without intraoperative PTH monitoring was performed to 45 patients with high FNA-PTH values. The median largest diameter of the target parathyroid lesion identified by ultrasonography was 13 mm (range, 6 to 36). The median serum PTH level was 190 pg/mL (range, 78 to 1709; reference range, 15 to 65) whereas the median washout PTH was 2500 pg/mL (range, 480 to 3389). According to operative findings high FNA-PTH levels correctly identified parathyroid adenoma in 40 cases (89% of sensitivity and 100% of specificity and positive predictive value) whereas MIBI scan localized the lesion in 36 of these cases (80% of sensitivity). CONCLUSIONS: The higher level of PTH in preoperative ultrasound guided FNA washout is a considerable data to predict the correct localization of HP, particularly in circumstances of greater values than the serum PTH level. However, although its specificity is high, in cases of coexisting nodular thyroid disease, associated additional HP might be missed at focused parathyroidectomy without PTH monitoring, leading to recurrent disease.

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly.

BACKGROUND: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly. METHODS: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined. RESULTS: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively). CONCLUSIONS: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.

Assessment of Mean Platelet Volume and its Effect on Disease Control in Patients with Acromegaly.

BACKGROUND: Morbidity and mortality rates due to cardiovascular diseases are more common in acromegalic patients than the healthy population. Platelets play a significant role in both the onset and progression of clotting which then cause the development of atherosclerotic plaques. Increased mean platelet volume (MPV) is an indicator of platelet activation and known as an independent risk factor for atherosclerotic processes. The aim of this study was to compare MPV levels between acromegalic and non-acromegalic patients. METHODS: The data of 56 acromegalic patients and 72 controls matched for age, gender, and the presence of diabetes were retrospectively reviewed. RESULTS: MPV levels were found to be higher in acromegalic patients compared to controls (8.82 ± 1.17 fL and 7.74 ± 0.87 fL, respectively, p < 0.001). Acromegalic patients were also classified according to their status of remission (a total of 27 patients were in remission and 29 patients were not in remission). Both age and gender were similar between the groups (p = 0.145 and p = 0.616, respectively). MPV levels at the time of diagnosis and after six months of treatment (p = 0.555 and p = 0.917, respectively) were not statistically significant. CONCLUSIONS: Our results suggest that MPV levels are higher in acromegalic patients than the controls until the early stages of treatment, independent of diabetes. Therefore, MPV levels may be an important determinant of acromegalic patients.

Increased serum tumor necrosis factor receptor-associated factor-6 expression in patients with non-metastatic triple-negative breast cancer.

Obesity appears to be associated with an increased risk of breast cancer (BC) and an inferior oncological outcome at the time of diagnosis, with poor outcomes most prominent in cases of triple-negative BC (TNBC). The present study analyzed serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and TNF receptor associated factor-6 (TRAF) protein expression levels in 48 patients with non-metastatic BC and 26 obese control patients (without BC). The mean age of the cohort was 52.5 years (range, 35-78 years) and the patients had a median body mass index of 33.5 kg/m2 (range, 30-47 kg/m2). In the study population, 27.1% of BC patients were triple negative and 70.8% were hormone receptor (HR)-positive. Median serum TRAF6 expression was 0.90 ng/ml (range, 0.55-1.53 ng/ml) in the 13 TNBC patients and 0.63 ng/ml (range, 0.49-1.22 ng/ml) in the 35 HR-positive BC patients; thus, TRAF6 expression was significantly higher in the TNBC patients compared with the obese control group (0.90 vs. 0.73 ng/ml; P=0.033). Furthermore, median serum TRAF6 expression levels were significantly higher in HR-negative patients compared with HR-positive patients (0.83 vs. 0.62 ng/ml; P=0.002). The present study demonstrated that serum TRAF6 expression levels were increased in TNBC and HR-negative patients with non-metastatic BC compared with HR- and human epidermal growth factor receptor 2-positive cases or the obese healthy control group. Therefore, elevated TRAF6 expression may be a poor prognostic factor in non-metastatic BC. In addition, we propose that progesterone (PR) negativity may be a more useful poor prognosis factor than estrogen receptor (ER) negativity, as TRAF6 expression levels were higher in the PR-negative patients compared with the ER-negative patients.