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.

How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

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.

Intraosseous cavernous hemangioma of inferior turbinate: a rare case report.

Objectives. To investigate hemangiomas in the differential diagnosis of the nasal cavity neoplasms, even though it is an extremely rare mesenchymal tumor of the nasal cavity, and the world literature was reviewed. Case Report. A 57-year-old woman applied to our department with a 5-year history of left-sided nasal obstruction without history of epistaxis, nasal packaging, or facial trauma. Anterior rhinoscopic examination revealed a mass originating from inferior turbinate that completely obstructs the left nasal cavity. Paranasal computed tomography (CT) showed that the bony mass originated from the anterior part of the left inferior turbinate. Surrounding tissues were normal, and there was not any erosion or destruction. Mass was excised by the endoscopic approach. Histological diagnosis was reported as osseous cavernous hemangioma. Conclusion. Hemangiomas are a rare cause of intranasal masses. Its unusual site and masked presentation makes the differential diagnosis difficult. When a bony hard, well-shaped mass was seen in the nasal cavity, the possibility of intraosseous hemangioma must be remembered.

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.

CA 72-4 levels in patients with type 2 diabetes mellitus.

OBJECTIVE: CA 72-4 is one of the blood group carbohydrate antigens which can be used as a tumour marker in ovarian, pancreatic and gastrointestinal carcinomas. It can also be elevated in various benign conditions including pancreatitis. Diabetes mellitus is a chronic disorder related with the pancreas. In this study, we investigated CA 72-4 levels in patients with type 2 diabetes and its relation to the metabolic status. METHODS: Sixty-nine patients with type 2 diabetes mellitus (female/male = 40/29) and 60 healthy subjects (female/male = 35/25) participated in this study. The levels of serum CA 72-4 were measured and faecal occult blood tests (following 3 days of white diet were obtained for three consecutive days) were performed in all patients. Patients had a pathological finding for any of these two parameters were further investigated with upper gastrointestinal endoscopy, colonoscopy and computerised tomography. RESULTS: The mean levels of CA 72-4 was 1.89 +/- 2.61 U/ml in the study group and 1.4 +/- 0.98 U/ml in the control group (p > 0.05). There was no association between CA 72-4 levels and age and sex of the patients, duration of diabetes, body mass index, biochemical indicators of metabolic control (the levels of HbA(1c), fasting and postprandial glucose, serum lipids), the presence of microvascular complications (retinopathy, nephropathy, neuropathy) or treatment modalities. CONCLUSIONS: Elevated levels of CA 72-4 in diabetic patients are not related to diabetes and it should be interpreted as evaluated in a non-diabetic patient.

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.

Evaluation of Achilles tendon thickening in type 2 diabetes mellitus.

AIM: To investigate the effect of diabetes mellitus on the Achilles tendon, which may contribute to the long-term complications in the foot-ankle complex and to investigate the factors relating to its thickening. METHODS: The study group included 55 patients (26 female and 29 male) with type 2 DM, while the control group included 34 non-diabetic people (13 female and 21 male). We matched the female and male DM patients with their respective control groups in terms of age, BMI, height and body weight. Clinical and biochemical tests, as well as ultrasonographic evaluations of the internal carotid artery and the Achilles tendon, were carried out to evaluate the complications of diabetes mellitus, and to compare the Achilles tendon thickness (ATT) between the study and the control groups. RESULTS: In the female groups the Achilles tendon was significantly thicker in the diabetic patients than in their healthy controls (p<0.001). However, no difference was found in the ATT between the male diabetic patients and their male controls (p=0.74). The ATT correlated with the body mass index (BMI) (r=0.47, p=0.015) and body weight in diabetic female group (r=0.56, p=0.003). We also observed that the ATT values were higher in male DM patients with retinopathy (p=0.034) or neuropathy (p=0.019) compared to the male DM patients without these complications. CONCLUSIONS: The ATT in type 2 female diabetic patients was found to be higher than their non-diabetic controls, but no significant difference could be found between type 2 diabetic male patients and their non-diabetic controls by US. Our results might indicate a possible impact of diabetes on the ATT depending upon gender, but other mechanisms may also contribute to thickening of Achilles tendon.

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.

Evaluation of bone turnover in postmenopausal patients with type 2 diabetes mellitus using biochemical markers and bone mineral density measurements.

Although osteoporosis is reported as a potential complication of type 1 diabetes mellitus (DM), the effects of type 2 DM on bone mass are conflicting. Most of the studies conducted in recent years reveal that bone mineral density (BMD) values of type 2 DM patients are not decreased and even increased when compared with healthy control groups. In this study we evaluated bone turnover in 57 postmenopausal type 2 DM patients utilizing biochemical markers for bone formation and resorption, and BMD measurements. We found that BMD values in diabetic patients (0.91 +/- 0.11 g/cm(2) for lumbar region, 0.89 +/- 0.14 g/cm(2) for hip region) were higher than healthy postmenopausal control group (0.81 +/- 0.12 g/cm(2) for lumbar region, 0.76 +/- 0.10 g/cm(2) for hip region). Serum alkaline phosphatase values were similar to the control group, whereas serum osteocalcin and N-telopeptide/creatinine (NTx/Cr) values were significantly lower than the control group (osteocalcin: 8.82 +/- 4.03 ng/ml, NTx/Cr: 122.70 +/- 81.76 nMBCE/mMCr) in diabetic patients (osteocalcin: 4.44 +/- 3.53 ng/ml, NTx/Cr: 42.24 +/- 29.97 nMBCE/mMCr). Also a significant correlation was observed between body mass index and BMD values. Our findings suggested that the bone turnover rate is remarkably lower in type 2 DM patients compared to healthy postmenopausal patients.

Are you sure you forgot? Feeling of knowing in directed forgetting.

One significant issue in metamemory is how variables increasing memorability affect metamemory. Previous research has produced inconsistent results. The effect of directed forgetting on the magnitude and accuracy of feeling-of-knowing (FOK) judgments was investigated. Participants were presented with word pairs, some to be remembered and some to be forgotten, and then were asked to recall all target words regardless of initial instructions. For unrecalled items, they were asked to give FOK judgments about performance in a future memory task: a cued stem-completion task (Experiment 1) or a recognition test (Experiment 2). This encoding manipulation increased both the memory performance and the magnitude of FOK judgments. However, no such effect on the accuracy of FOK judgments was observed.