ACTA ENDOCRINOLOGICA (BUC)

Background. Autoimmune thyroiditis, such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), is a complex, genetically linked condition. IL-8 and TNF-α play a crucial role in these pathologies. Methods. This research was conducted on Tunisian patients with autoimmune thyroiditis (AITD) to examine the link between genetic variations in the IL-8 and TNF-α genes, their protein expression, and the likelihood of developing GD or HT. A total of 319 healthy controls, 230 patients with HT, and 75 patients with GD underwent genotyping via PCR-RFLP for the TNF-α-238 G/A and IL-8+781C>T polymorphisms. Plasma levels of IL-1β and TNF-α were also quantified. Results. The IL-8-781 T/T genotype and the IL- 8-781 T allele were detected more frequently in HT and GD patients than in control participants. Patients with hypertension exhibited a higher frequency of the TNFA- 238 G/A genotype and the TNFA-238 A allele compared to control individuals. However, no significant variation was observed in IL-8 and TNFA protein expression between patients and controls. Conclusions. The strong association between the IL-8-781C/T and TNFA-238 G/A polymorphisms and HT and GD suggests that these polymorphisms may play a crucial role in susceptibility to AITD within the Tunisian population.

Background. Plasma level of ghrelin is possibly reduced in Helicobacter pylori infection and may account for the resultant failure to thrive. Objective. To investigate relationships between Helicobacter pylori infection, and plasma level of ghrelin, anthropometric measurements, appetite, educational and economical status of parents. Methods. Ninety-four children were screened for Helicobacter pylori infection with C-14 urea breath test. Anthropometric measurements were performed in Helicobacter pylori (+) and (-) groups. Plasma ghrelin was measured. Parents were asked to fill out the questionnaire prepared by the researcher on the number of family members, parents’ level of education, monthly income and children’s status for appetite. Results. Plasma ghrelin was lower in Helicobacter pylori (+) group (20.00 ± 22.10 ng/mL), compared to Helicobacter pylori (-) group (79.72 ± 78.13 ng/mL). The percentiles of measurements for height, weight and body mass index were higher in Helicobacter pylori (-) group. Results of C-14 urea breath test were negatively correlated with height, weight and body mass index; however, no correlation was detected between the results of C-14 urea breath test, and plasma ghrelin, number of family members, levels of parents’ education and income. A negative correlation was observed between the results of C-14 urea breath test and appetite. Conclusions. Helicobacter pylori infection is considered to play a restricting role in growth potential by decreasing ghrelin level in children. Moreover, the existence of a negative correlation between the results of C-14 UBT, and weight, height and body mass index suggests a possible link between Helicobacter pylori infection and poor growth.

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.

cancer has been continuously increasing, which is in line with the prevalent trend of obesity. Objective. This study aims to investigate the relationship between obesity and BRAFV600E mutation. Methods. The study collected clinical and demographic data of 140 patients with papillary thyroid carcinoma. Statistical analyses included independentsamples t-tests, chi-square tests, and univariate and multivariable logistic regression analyses, as well as receiver operating characteristic (ROC) curve analysis. Results. The mean BMI was significantly higher in the BRAFV600E-positive group than in the negative group (p<0.001). BMI was independently associated with BRAFV600E mutation in both univariate (p=0.007) and multivariate analyses (p=0.026). ROC analysis demonstrated that BMI had modest predictive value (p=0.003). Research has observed the existence of sex differences, with a higher proportion of males in the BRAFV600E-positive group (p=0.047). Among BRAFV600E-positive patients, males had higher BMI and were more frequently classified as overweight or obese (P < 0.001). However, sex was not identified as an independent predictor in multivariate analysis. No significant associations were found between BRAFV600E mutation and Hashimoto’s thyroiditis, diabetes, or fatty liver disease. Conclusion. This study demonstrates the association between higher BMI and BRAFV600E mutation in patients with PTC.

Objective. To study the correlation between neck circumference(NC) and umbilical artery blood flow in physiologic pregnancies. Methods. One hundred and one healthy pregnant woman in the third trimester were enrolled. Anthropometric measurements and ultrasonic testing were done. Results. The women with NC ≥34.7cm had a more elevated umbilical artery pulsatility index(PI) and systolic/diastolic ratio (S/D) than the women with NC <34.7cm (P<0.01). NC were positively correlated with PI(r=0.224,P=0.024) and S/D ratio(r=0.415,P=0.0001). In multivariate analysis, NC was independently associated with PI (β=0.026, P=0.016) and S/D ratio (β=0.132, P=0.0001). Conclusions. Obesity has an adverse impact on feto-placetal vessels, and NC was superior to body mass index.

Objective. ARMC5 mutations are responsible for the development of primary bilateral macronodular adrenal hyperplasia (PBMAH). In this study, we aimed to report a novel ARMC5 germline variant in a PBMAH patient family. Method. CT examination and dexamethasone suppression test (DST) were used in the diagnosis of PBMAH. Sanger sequencing was used to validate the familial heredity. For the novel variant, protein predictive analysis was performed to study the changes of secondary and tertiary structures and hydrophobicity. Results. A 45 years old male (proband, III-1) was diagnosed as PBMAH. Whole-exome sequencing (WES) was performed, finding one mutation: c.719_ 724dup, p Arg240_ Pro241dup. Sanger sequencing showed the II-2, III-1, IV-1 with heterozygous gene, confirming the familial heredity. For protein predictive analysis, the predicted secondary structure of variants has one alpha–helix structure incomplete compared with normal ARMC5. The tertiary structure could draw the same conclusion, that hydrophobicity decreases after mutation. Conclusion. We reported a new-found ARMC5 germline variant in PBMAH using WES and protein predictive analysis. With the help of WES, early diagnosis of PBMAH could help variant carriers to prevent the occurrence of cancer by lifetime follow-up.

Context. It is well known that thyroid hormones are important, being involved in affects the metabolism of carbohydrate, protein, lipids. The relationship between thyroid hormones and lipid metabolism is the focus of recent research. Objective. To investigate the relationship between subclinical hypothyroidism and lipid metabolism in women. Design. We conducted an epidemiological survey of thyroid diseases among women in Northeast China from September 2014 to December 2014. Subjects and Methods. A total of 1397 women underwent physical examinations and laboratory tests for thyroid function and lipid metabolism. Results. We found that the detection rate of subclinical hypothyroidism was 13.03%. Patients with subclinical hypothyroidism showed significantly higher levels of triglyceride (1.69±1.9 vs. 1.45±1.4) and the risk of hyper triglyceridemia in women with thyroid stimulating hormone (TSH) levels ≥10mIU/L was 4.96-fold higher compared with that in the normal population (P<0.01). Conclusion. Disorders of lipid metabolism in women with subclinical hypothyroidism show a direct correlation with the level of TSH, and the risk of hyper triglyceridemia is significantly increased when the level of TSH ≥10mIU/L.

Purpose. Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Materials and Methods. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. Results. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). Conclusion. SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Background. Thyroid-associated ophthalmopathy (TAO), one of the most common orbital diseases in adults, seriously reduces patients’ quality of life. Although human tear proteomics identified many abnormal expressed proteins and proposed several pathogeneses of TAO, most of these studies focused on the active stage or mixed types in TAO. In this study we identified significantly changed proteins and preliminary revealed the potential signalling pathways and mechanisms of TAO with the late, inactive stage. Patients and Methods. Tears from TAO patients (n=6) with a CAS score < 3 and 6 control healthy subject were collected. The pooled tears were further fractionated using high pH reversed-phase chromatography, then submitted to LC-MS/MS and subsequent bioinformatic analysis. Results. Proteomic profiling identified 107 significantly changed proteins between the inactive stage of TAO patients and healthy cases. Among these proteins, 62 were upregulated, and 45 were downregulated in TAO cases compared to healthy individuals. Enrichment analysis revealed that the immune system, cell cycle, metabolism (carbohydrate metabolism and metabolism of cofactors and vitamins), protein synthesis and degradation might play a vital role in the progress of inactive TAO. The present investigation represents the first proteomic tear study of TAO patients in the inactive stage. Conclusion. The results shed light on the differences between inactive TAO patients and healthy cases, thus enabling us to understand better the molecular mechanisms and potential targets for the treatment of inactive TAO.