Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.

PURPOSE: The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly. METHODS: This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA. RESULTS: The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness. CONCLUSION: This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.

Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome.

PURPOSE: Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role. METHODS: We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined. RESULTS: Serum betatrophin level was significantly higher in women with PCOS than the control group [1.10 (0.20-4.20) vs 0.70 (0.20-3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40) pg/ml, p = 0.13]. Serum betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R2 = 0.22, F = 2.56, p = 0.03). CONCLUSIONS: Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.

THYROID MALIGNANCY RISK OF INCIDENTAL THYROID NODULES IN PATIENTS WITH NON-THYROID CANCER.

CONTEXT: Thyroid incidentaloma is a common disorder in endocrinology practice. Current literature regarding the risk of thyroid cancer in incidentalomas found in patients with non-thyroid cancer is limited. OBJECTIVE: The aim of the present study was to investigate the frequency of thyroid malignancy in thyroid incidentalomas detected in patients with non-thyroid cancer. DESIGN: Case control study. SUBJECTS AND METHODS: The database of 287 thyroid nodules from 161 patients with a history of non-thyroid cancer followed between 2008 and 2014 were retrospectively evaluated. RESULTS: From 287 thyroid nodules, 69.7 % had a benign final cytology. Thyroid cancer detected in one nodule while follicular neoplasia detected in 4 nodules, atypia of unknown significance (AUS) detected in 10 nodules, Hurthle cell neoplasia detected in 5 nodules and suspicious for malignancy detected in 6 nodules according to fine needle aspiration biopsy results. Metastasis of the non-thyroid cancer to the thyroid gland was detected in 4 nodules. Twenty seven nodules from 15 patients were removed with surgery. There were 3 malignant nodules found after surgery (1 papillary, 1 follicular and 1 medullary cancer). In addition to these three thyroid cancers, two patients with benign nodules had co-incidental thyroid cancer detected after surgery. Finally, 11.1 % of thyroid nodules which underwent thyroid surgery had malignant histopathology except for co-incidental and metastatic cancers. CONCLUSIONS: The frequency of thyroid malignancy seems not to be substantially increased in incidental thyroid nodules detected in patients with non-thyroid cancer when these patients were evaluated in nodule-based approach.

Association of polymorphisms in the IL-18 and IL-12 genes with susceptibility to Type 1 diabetes in Turkish patients.

BACKGROUND: Recent studies have indicated that polymorphisms of the interleukin-18 (IL-18) and interleukin- 12 (IL-12) genes are associated with the development of Type 1 diabetes mellitus (T1DM) in some populations, but not all. AIM: The present study was designed to examine the roles of polymorphisms in the IL-18 promoter and IL-12p40 with respect to susceptibility to T1DM in Turkish patients. SUBJECTS AND METHODS: Ninety-one patients with T1DM and 87 unrelated healthy subjects were included in the study. The IL-18 polymorphisms at positions -607 and -137 were detected by a sequence-specific PCR method. The single nucleotide polymorphism in the IL-12p40 3' untranslated region (3'-UTR) at position +1188 was analyzed by the PCR-restriction fragment length polymorphism (RFPL) method. RESULTS: The allelic and genotypic frequencies of the IL-18 and IL-12p40 polymorphisms did not differ significantly between subjects with T1DM and the controls (p>0.05). However, diabetic patients with the -137 (CC) genotype showed a younger onset age compared to patients with the -137 (GG) genotype (p=0.02). In addition, patients with the -607 (CC) genotype had higher levels of glycated hemoglobin (HbA1c) than patients with the -607 (AC) genotype (p=0.004). Furthermore, patients with the IL-12p40 (AC) genotype had higher HbA(1c) levels than patients with the IL-12p40 (AA) genotype (p=0.01). CONCLUSIONS: The results of the present study show that the IL- 18 and IL-12p40 polymorphisms may have some effect on the onset age and deterioration of glycemic control in Turkish patients with T1DM.

Plasma visfatin concentrations in subjects with type 1 diabetes mellitus.

BACKGROUND/AIMS: Visfatin is a recently discovered adipokine, and its circulating concentrations have not been adequately studied in type 1 diabetes mellitus (DM). Therefore, this study was designed to examine plasma visfatin levels in type 1 diabetic patients and to determine the relationships between visfatin and duration of diabetes, body mass index, glycemic control, insulin dosage and lipid profile. METHODS: Forty-eight patients with type 1 DM and 26 healthy controls were investigated. RESULTS: Type 1 diabetic patients had significantly low visfatin levels compared with controls (18.8 +/- 1.7 vs. 20.2 +/- 0.3 ng/ml; p < 0.0001). Visfatin levels were comparable between patients with a short duration of diabetes (<10 years) and patients with a long duration of diabetes (>or=10 years) (18.9 +/- 1.7 vs. 18.2 +/- 2.0 ng/ml; p > 0.05). There was a significant correlation between visfatin and hemoglobin A1c (HbA1c) even after the adjustment for age, sex, body mass index and duration of diabetes (r = -0.48, p = 0.005) in the patient group. Multivariate analysis showed that significant determinants of visfatin concentrations were HbA1c and duration of diabetes (r(2) = 0.27). CONCLUSION: These data emphasize that plasma visfatin concentrations are lower in patients with type 1 DM and related to glycemic control reflected by HbA1c.

Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes.

AIMS: Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low-density lipoprotein (LDL) size and all seven subclasses, as well as the 'atherogenic-lipoprotein phenotype'[ALP, e.g. concomitant presence of elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol and increased small, dense LDL]. METHODS: In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation. RESULTS: Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL-I (P = 0.0074) and increased LDL-IVA (P = 0.0146) and -IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL-I and positively with LDL-IVA and -IVB (all P < 0.05). ALP due to high HDL-cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107). CONCLUSIONS: Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end-points in these women remains to be determined by future prospective studies.

Visfatin concentration is decreased in women with gestational diabetes mellitus in the third trimester.

Our aim is to investigate visfatin concentration and its relationship to glycated hemoglobin (HbA1c), insulin resistance, lipid parameters, and neonatal birth weight in women with gestational diabetes mellitus (GDM). In our study group, there were 47 women with GDM and 31 women with normal glucose tolerance (NGT) between 33-39 weeks of gestation. Plasma visfatin levels were significantly decreased in pregnant women with GDM compared to those with NGT (p=0.001). Homeostasis model assessment-insulin resistance (HOMA-IR) levels were higher in the GDM group than in the NGT group (p=0.006). In all subjects, plasma visfatin levels were negatively correlated with HOMA-IR, post-prandial blood glucose, triglycerides, and VLDL cholesterol (p<0.05). We did not observe any statistically significant correlation between the plasma visfatin levels and the selected parameters in the GDM group, but in the NGT group plasma visfatin levels were negatively correlated with HOMA-IR (r=-0.36, p=0.04). There was no correlation between visfatin concentrations and fetal birth weight in either group (p>0.05). By regression analysis, having GDM was found to be the only significant determinant (t=3.5, p=0.001) of visfatin concentration (R=0.39, r2=0.15). We conclude that women with GDM have significantly decreased visfatin concentrations in the third trimester. Future studies are required to establish the exact role of visfatin in the pathogenesis of GDM.

The association of neurofibromatosis, bilateral pheochromocytoma and primary hyperparathyroidism.

Neurofibromatosis (NF) is a hereditary disease and carries increased risk of both benign and malignant tumor development. Pheochromocytoma or hyperparathyroidism have been reported to be associated with NF type 1 (NF1). However, the coexistance of pheochromocytoma and parathyroid adenoma in a patient with NF1 is very rare. We report a case of a 37-year-old male with NF1, bilateral pheochromocytoma and parathyroid adenoma. This association sould be kept in mind in patients with NF1 in initial evaluation as well as during follow-up.

Effect of cisplatin on skin metastasis in breast cancer patients.

BACKGROUND: Metastatic breast cancer is a common clinical entity, and its treatment is still a major clinical problem in modern oncology. Both cisplatin (CDDP) and 5-fluorouracil (5-FU) are effective agents. PATIENTS AND METHODS: In this retrospective study, the therapeutic efficacy and tolerability of CDDP and continuous infusion of 5-FU were evaluated in patients with pretreated metastatic breast cancer. 16 patients were surveyed. All of them were pretreated with anthracyclines in an adjuvant and/or therapeutic setting. Eight of them also received taxanes after the failure of anthracyclines. CDDP at 80 mg/m(2) for 1 day and 5-FU at 1,000 mg/m(2) as a continuous 24-hour infusion for 5 consecutive days were administrated every 3 weeks. RESULTS: 13 patients were included in response analysis. Because of severe toxicity, chemotherapy protocols of 3 patients were stopped after the first cycle. The objective response rate (partial response) was 46%. No complete response was observed. The median response duration was 5 (3.5-7) months in the response group. Favorable objective responses were observed more frequently in cases with skin metastasis. Five out of 6 patients who attained partial remission had skin metastasis. Response rates were similar in patients pretreated with taxanes and in those not pretreated with taxanes (75 vs. 80%). The most serious toxicity was myelosuppression (25%). CONCLUSIONS: Although this study is based on only a limited number of patients, the combination of CDDP and 5-FU can be recommended in patients refractory to both anthracyclines and taxanes and especially in cases of skin metastasis with a good performance status.