ACTA ENDOCRINOLOGICA (BUC)

Background. Thyroid nodules stiffness may predict thyroid malignancy. Objectives. The purpose of the study was to investigate the diagnostic value, interobserver agreement and reliability of real time ultrasound elastography (USE) when assessing solid thyroid nodules. Design. A prospective, observational study in a tertiary center. Subjects and Methods. In 49 patients scheduled for thyroidectomy, a senior radiologist and two radiologists in training independently assessed 81 solid thyroid nodules with USE using a 6600 Hitachi machine. Pathology results were used as a reference standard. Nodule stiffness was evaluated using the Asteria scoring system. The diagnostic ability of the elastography scores for the assessment of the thyroid solid nodules was evaluated using AUROC (area under the receiver operating characteristic curve) analysis. The Cohen’s kappa (k) values were used for interobserver agreement evaluation and interclass correlation coefficient (ICC) was used as a measure of reliability. Results. Pathology results revealed 20 papillary carcinomas and 61 benign nodules. The elastography identification of malignant nodules by the senior radiologist was performed with an AUROC of 0.84 [95% Confidence interval (CI) 0.74-0.91], with Sensitivity= 100%, and Specificity= 68.85%. When performed by ultrasound operators in training, the diagnostic performance slightly decreased. With no statistically significant difference between the diagnostic performance of the three readers, USE demonstrated good inter-observer agreement and good reliability (ICC= 0.81). Conclusion. USE may be an accurate tool of assessment for solid thyroid nodules, identifying with high sensitivity the malignant ones, particularly micronodules. USE is reproducible and reliable when used both by experienced operators and medical professionals in training.

Background. Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely “myofibroblasts” (MFBs) have been linked to HT. Aim. Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT. Material and Methods. Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM). Results. Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43μm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01). Conclusion. Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.

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Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH.

Context. The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. Objective. The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. Design. The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3β-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. Methods. Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. Results. All the inhibitors attenuated the hCGinduced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. Conclusion. hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.

Context. Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective. The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design. Cross-sectional Subjects and Methods. By targeted metabolomics we analyzed serum samples of 70 women using ultrahighperformance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results. Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions. By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.

Context. Childhood cancer survival has increased substantially over the past few decades. However, long-term side effects associated with cancer treatment have also risen. Especially thyroid gland disorders are common. Objective and Design. The present retrospective cross-sectional study aimed to investigate risk factors of long-term TD in survivors of leukemia-lymphoma. Subjects and Methods. The study included 44 acute lymphoblastic leukemia (ALL) and 26 Hodgkin lymphoma survivors (HL). Abnormal laboratory and pathological ultrasonographic findings of the thyroid gland were accepted as a thyroid disorder. The possible causes of thyroid disorders were investigated. Results. Long-term thyroid disorder was found in 40% of the patients. This rate was higher in HL patients than in ALL (65% vs. 25%). Thyroid disorder was significantly more common in patients who received radiotherapy to the neck (57% vs. 17%). Radiotherapy to the neck area was the only significant determinant for thyroid disorders in the regression models [OR 33.17, 95% CI (2.76-398.9) p = 0.006]. However, HL remained significantly associated with TD in the logistic model performed using cancer type [OR 19.25, 95% CI (2.39-155.3) p = 0.006]. Conclusions. The study showed that radiotherapy applied to the neck was an essential risk factor for long-term TD in the average 6-year follow-up of cancer survivors. However, we recommend that childhood cancer survivors should be followed closely for a long time since long-term endocrine side effects were reported during longer than six years follow-up periods.

Background. An increasing number of studies suggest that hypothyroidism may lead to hepatorenal toxicity. This study examined whether thymoquinone (TQ), the main active Nigella sativa constituent, could prevent the detrimental influences of hepatorenal toxicity of hypothyroidism during the juvenile period in rats. Methods. The male rats were randomly divided into four groups (n = 7), including control, propylthiouracil (PTU), PTU-TQ 5 mg/kg, and PTU-TQ 10 mg/kg. PTU was dissolved in drinking water at a concentration of 0.05% and administered for six weeks. In the PTU-TQ5 and PTU-TQ10 groups, animals received PTU plus 5 mg/kg and 10 mg/kg of the TQ (i.p.) for six weeks, respectively. The rats were evaluated after TQ treatment by measuring serum markers of liver and kidney function tests as well as oxidative stress biomarkers in liver and kidney tissues. Results. Administration of TQ (5 and 10 mg/ kg) decreased oxidative stress damage in liver and kidney tissue in hypothyroidism rats with improvement in activities of antioxidant enzymes and a decrease in MDA in both liver and kidney homogenates. Furthermore, TQ treatment significantly inhibited the elevation of serum biochemical markers of liver and kidney function associated with this hepatorenal toxicity. Conclusion. These results suggest that the protective effect of TQ in hypothyroidism-induced hepatorenal toxicity in rats is attributed to its ability to reduce oxidative stress in hepatic and renal tissues. However, more studies are recommended to investigate the exact mechanism (s) for the effect of TQ on hepatorenal outcomes of hypothyroidism in human subjects.