Elevated Tg Research Articles

Papillary thyroid carcinoma risk factors in the Yunnan plateau of southwestern China

ObjectiveThis study investigated clinical and pathological characteristics and risk factors in papillary thyroid carcinoma (PTC) patients’ native to Yunnan plateau in southwestern China.MethodsClinical data from 1,198 patients diagnosed with PTC (n=578) and control subjects (n=620) with benign thyroid disease (ie, thyroid nodule disease, benign thyroid diseases [BTD]) in Yunnan province were analyzed retrospectively.ResultsThe mean patient age was lower for PTC than for BTD. Positive ratios of thyroid peroxidase antibody, thyroglobulin antibody (TGAb), and thyrotrophin receptor antibody (TRAb) were higher in PTC than in BTD patients. The ratio of PTC coexisting with Hashimoto’s thyroiditis (HT) or with lymphocytic thyroiditis was higher than that of BTD. The number of patients whose age at menarche was ≤13 years, who had given birth to less than or equal to two children, or who were in premenopause were higher in the PTC than in the BTD group. Multivariate conditional logistic regression analyses revealed that age >45 years, nodal size >1 cm, and elevated TG levels were protective factors against PTC. Abnormally elevated TGAb and TRAb levels were independent risk factors for PTC in females.ConclusionHT was not an independent risk factor for but was associated with PTC. TRAb is a risk factor for PTC in individuals living in the Yunnan plateau, but not for those in the plains region.

Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up.

Objective:Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC.Methods:The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl.Results:At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as “successful ablation”, a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis.Conclusion:Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up.

Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease.

Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD.

The application of 18F-FDG PET/CT in thyroid tumor

The clinical application of 18F-FDG PET/CT in thyroid tumor is primarily for restaging of patients with DTC but having a negative 131I whole-body scan in the presence of elevated serum Tg and TgAb levels. In parallel with the accumulation of clinical experience and increasing clinical utilization of 18F-FDG PET/CT, the application of 18F-FDG PET/CT in thyroid tumors is also broadened. This review aims at updating the application of 18F-FDG PET/CT in different types of thyroid tumors. Key words: Thyroid neoplasms; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose; Trends

Low postoperative nonstimulated thyroglobulin as a criterion for the indication of low radioiodine activity in patients with papillary thyroid cancer of intermediate risk 'with higher risk features'.

This study evaluated low-activity (131) I therapy in patients with papillary thyroid carcinoma (PTC) of intermediate risk 'with higher risk features' who had low nonstimulated thyroglobulin (Tg) after thyroidectomy. This was a prospective study including 102 patients with tumours >1 cm and aggressive histology; and/or >3 positive lymph node (LN) or LN >1·5 cm or exhibiting macroscopic extracapsular extension, and clinically apparent (cN1); and/or a combination of a tumour >4 cm, microscopic extrathyroidal extension and LN metastases (cN1). After thyroidectomy, all patients had nonstimulated Tg < 0·3 ng/ml and negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US). The patients were treated with a low activity of (131) I (1110 or 1850 MBq). Post-therapy whole-body scanning (RxWBS) showed ectopic uptake in four patients. When evaluated 12 months after (131) I therapy, nonstimulated Tg ≤ 0·2 ng/ml with negative TgAb and US, defined as excellent response to initial therapy, was achieved in 101 patients (99%). Only one patient with positive initial RxWBS had structural disease. During follow-up, four patients (4%) relapsed, including LN metastases in two, pulmonary metastases in one, and elevated Tg in one. The other 98 patients remained with nonstimulated Tg ≤ 0·2 ng/ml and negative TgAb and US. There was no case of death due to the tumour. We conclude that in intermediate-risk patients 'with higher risk features', low nonstimulated Tg measured with a second-generation assay can be used as criterion for the administration of low (131) I activities (1850 MBq or less).

Is 131I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

What is the role of florine-18 fluorodeoxyglucose/positron emission tomography/computed tomography imaging in well-differentiated thyroid cancers with negative iodine-131 scan high thyroglobulin and normal anti-thyroglobulin levels.

This retrospective study aims to assess the cut-off value of thyroglobulin (Tg) levels in nux or metastatic well-differentiated thyroid cancers (DTCs) with normal anti-Tg levels using with fluorodeoxyglucose/positron emission tomography/computed tomography (FDG PET/CT). We reviewed FDG PET/CT images of 104 patients with well DTC (28 men, 76 women) whose: Iodine-131 (131 I) whole-body scanning was negative but had elevated Tg with normal anti-Tg levels. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of florine-18-FDG PET/CT findings were found to be 95.92%, 87.27%, 87.04%, 96.00%, and 91.35%, respectively. The best Tg cut-off value was found to be 10.4 ng/ml. In the Tg level <10.4 ng/ml group, the sensitivity, specificity, PPV, NPV, and accuracy of FDG PET/CT were found to be 94.1%, 91.30%, 88.8%, 95.4%, and 92.5%, respectively. In the other group, which Tg level ≥10.4 ng/ml, sensitivity, specificity, PPV, NPV, and accuracy of FDG PET/CT exams were found to be 96.8%, 84.3%, 86.1%, 96.4%, and 90.6%, respectively. FDG PET/CT imaging is a valuable imaging method in the evaluation of patients with elevated serum Tg levels and normal anti-Tg levels. Furthermore, it has potential utility in the dedifferentiation of active foci that are present, and in assessing optimal decision making during follow-up.

Insulin resistance, metabolic syndrome, and lipids in African women.

The metabolic syndrome is closely related to insulin resistance (IR) and cardiovascular disease. This study examined the prevalence of IR and metabolic syndrome as well as factors associated with IR among Nigerian women. Eighty-six women living in an urban area in Enugu, South-East Nigeria, were assessed. Demographic information included age, residence, physical activity, alcohol and tobacco intake and were collected with questionnaires. Blood pressure and anthropometric parameters were measured using standard methods. Fasting lipids, blood glucose, and insulin were measured. IR was calculated with homeostasis model assessment of IR formula. The ratios; triglyceride/high-density lipoprotein (TG/HDL), total cholesterol (TC)/HDL, and atherogenic index of plasma; log (TG/HDL) were calculated and compared with IR. Metabolic syndrome was sought for using both the WHO and the harmonized joint criteria. The mean age was 44.4 (13.1) years. Hypertension, obesity/overweight, and abdominal obesity were present in 31.5%, 81.1%, and 92.2%, respectively. There was elevated TC (62.2%), elevated low-density lipoprotein (45.6%), low HDL (40%), and elevated TG (14.4%) levels. IR was present in 39 (45.3%). Metabolic syndrome was present in 25 (29.1%) and 17 (19.8%) using the joint criteria and the WHO criteria, respectively. The sensitivity and specificity of the joint revised criteria in identifying IR individuals were 48.7% and 87.2%, respectively, and for the WHO criteria, were 38.5% and 95.7%, respectively. The only significant predictor of IR was the presence of diabetes; P = 0.03, odds ratio = 7.2 (95% confidence interval = 1.19-41.88). IR and metabolic syndrome were common. They were not related to any of the lipoprotein ratios. Metabolic syndrome had a low sensitivity in detecting IR.

Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients

Background/Aims: Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. Methods: A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² were considered CKD cases. Results: Hypertensive subjects with CKD had a higher prevalence of hyperuricemia and metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL-C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with ≤1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. Conclusion: Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD.

Analysis of BRAFV600E Mutation and Persistence of Papillary Thyroid Cancer after Total Thyroidectomy and Routine Central Neck Dissection

Purpose The aim of this study is to investigate the predictive value of BRAF V600E mutation for the persistence of papillary thyroid cancer (PTC) after total thyroidectomy and routine central neck dissection. Patients and Methods We collect the clinicopathological data of 288 PTC patients with total thyroidectomy (TT) and routine central neck dissection (CND), and analyzed the relationship between BRAFV600E mutation status and the rate of elevated non-stimulated thyroglobulin (NSTg) value. And we also collect the clinicopathological data of 370 PTC patients who needed radio iodine ablation(RIA) after TT and routine CND, and analyzed the relationship between BRAFV600E mutation status and the rate of elevated stimulated Tg (STg)value before RIA. The clinicopathological data included gender, age at diagnosis, multifocality, bilaterality, tumor size, extrathyroidal invasion, and lymph node status of these patients. All the patents were diagnosis as PTC before operation by the combination with ultrasonograph and FNA (fine needle asperation). Results BRAFV600E mutation is not associated with the elevated rate of elevated Tg value after TT and routine CND. Conclusions BRAF V600E mutation is not an independent predictive factor for the persistence of papillary thyroid cancer (PTC) after TT and routine CND.

Prévalence de la dyslipidémie dans la population rurale de Guéoul (Sénégal)

IntroductionThe cardiovascular risk factors are clearly increasing in developing countries. Among these factors, dyslipidemia is often found, this due to the change in behavioral and dietary habits (OMS, 2006). Dyslipidemia is a “primary or secondary pathological changes in serum lipids”. It is a chronic and metabolic abnormality, characterized by persistently elevated TG, LDL-c, and a decrease in HDL (Attias et al., 2013–2014). The objective of this study is to determine the prevalence of dyslipidemia, and give the lipid profile of the population in Gueoul. Patients and methodsWe performed a comprehensive observational study, cross-sectional descriptive on Senegalese aged 35 or over, living in Gueoul for at least 6 months. Lipid profile (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol) was systematically after 12hours of fasting. ResultsDyslipidemia was found in 61.3 % of cases with 50 % pure hypercholesterolemia (n=705). Only 20 subjects (2.3 %) knew they had dyslipidemia. The detection rate was 59.8 % (n=844). The type most represented was hypoHDLemia (45.6 %) followed by hyperLDLemia (28.8 %). Triglycerides were increased in only 2.8 % of cases. ConclusionThe prevalence of dyslipidemia is very high in our regions. It is often associated with female gender, hypertension, diabetes, and obesity. Its main causes are physical inactivity, change in lifestyle and eating habits. It is often misunderstood and its management is limited in most cases to low-calorie diet.

Clinical Usefulness of F-18 FDG PET/CT in Papillary Thyroid Cancer with Negative Radioiodine Scan and Elevated Thyroglobulin Level or Positive Anti-thyroglobulin Antibody.

Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P < 0.001, HR = 1.13; 95% CI, 1.061-1.208). The cut-off level of Tg was 21.5ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64%, 94%, 86%, 81%, and 83%. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64%, 94%, 88%, 81% and 83%. Those under TSH suppression were 67%, 92%, 80%, 85% and 83%. F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.

Abstract 3468: Impact of histology on serum thyroglobulin as a biomarker for nonmedullary thyroid cancer recurrence

Abstract Purpose Thyroid cancer is one of the most common cancer diagnoses amongst cancer survivors given the overall good prognosis. Thyroglobulin (Tg) is a thyroid but not tumor specific marker. Serum Tg levels less or equal to 0.1 ng/ml in patients without Tg autoantibodies (TgAbs) indicate cure following total thyroid ablation. The major limitations of Tg are false low interferences by TgAbs and a lack of established reference ranges for cured patients with thyroid remnants. Additionally, it is unknown if thyroid histology impacts on its utility as a biomarker for disease recurrence. This retrospective study investigates the relationship between the various histological subtypes of non-medullary thyroid cancers and TG levels to determine whether TG levels are an effective predictor of disease recurrence for all subtypes of differentiated thyroid cancers (DTC). Methods: We retrospectively examined all patients with DTC seen at the National Cancer Centre Singapore between January 1, 2004 and March 31, 2014. 745 DTC cases were identified and patient records were examined. Diagnosis of DTC and subtype determination was based on histological analysis of thyroid tissues during fine-needle-aspiration-biopsy(FNAB) or from tissue samples during surgery. DTC recurrence was confirmed by histology or by CT/PET scan. Each patient had blood drawn before Iodine-131 treatments and regular follow up surveillance CT/PET scans as well as following biochemical tests: TSH, free thyroxine, thyroglobulin and TGAb. To avoid interference from the presence of thyroglobulin antibody (TGAb), only patients with TGAb levels below 40IU/ML at baseline were included for the analysis. The association of the histological subtypes with failure of TG levels to rise secondary to recurrence was determined by a Fisher's test. Results: 463 patients met the inclusion criteria above and were available for analysis of TG as a biomarker for DTC recurrence. The histologies included: 61 (13%) follicular thyroid cancer (FTC), 369 (80%) papillary thyroid cancer (PTC) and 33 others (7%). 52 patients with recurrent DTC was identified with either histological or radiological evidence of disease. An elevated serum TG was found in 94% (49/52) of patients with a recurrence of DTC, of which 81% (42/52) were PTC, 12% (6/52) were FTC. FTC was overrepresented in the 3 patients whereby TG was not predictive of recurrence accounting for 2 of the 3 cases (66% vs 33% PTC; P = 0.06). Conclusions: Rise in serum TG is predictive for DTC recurrence in the absence of TgAB interference. Our data suggests that FTCs may be overrepresented in the group where serum TG was not predictive of recuurence. A bigger sample size will be needed to determine if the utility of serum TG is affected by histological subtype. Citation Format: Logesh Raki, Rehena Ganguly, Joanne Ngeow. Impact of histology on serum thyroglobulin as a biomarker for nonmedullary thyroid cancer recurrence. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3468. doi:10.1158/1538-7445.AM2015-3468

Metabolic Syndrome without Diabetes or Hypertension Still Necessitates Early Screening for Chronic Kidney Disease: Information from a Chinese National Cross-Sectional Study.

Metabolic syndrome (MS) is prevalent, with an increasing contribution to the incidence of chronic kidney disease (CKD). The study of the relationship between them is important. The CKD survey, a national cross-sectional study, provided a large database to accomplish this study. The study population were 41 131 adults from this survey between 2008 and 2009. CKD was defined as estimate glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 or the presence of albuminuria. MS was diagnosed by National Cholesterol Education Program—Adult Treatment Panel III (ATPIII), ATPIII-modified or International Diabetes Federation (IDF) criteria. Logistic regression model was applied to study the impact of MS or its components on CKD or its components. The age and sex standardized prevalence of MS by ATPIII, ATPIII-modified and IDF criteria was 11.77% (11.13%–12.40%), 21.51% (20.69%–22.34%) and 16.67% (15.92–17.42)% respectively. Multivariate logistic regression models showed that MS and its components were associated with higher CKD prevalence. The risk for CKD and its components increased with the number of MS components. After adjusting for hypertension and diabetes, the odds ratios of MS for CKD decreased, but remained significantly more than 1 between 1.16(95%CI 1.07–1.26) and 1.37 (95% CI 1.25–1.50) across the different models. Similar results were found with albuminuria, while for decreased eGFR, after adjusting for hypertension and diabetes, the odds ratios of MS and MS components (except elevated TG) became insignificant. In conclusion, MS is prevalent and associated with a higher prevalence of CKD. Different MS components are associated with different risks for CKD, even after adjusting for hypertension and diabetes, which may mainly be contributed more by the increased risk for albuminuria than that for decreased eGFR. More attention must be paid to the population with MS, including those with elevated blood pressure and serum glucose.

Complementary effect of combination of statins with coenzyme q10 and omega-3 fatty acids in patients with combined dyslipidemia

s / Atherosclerosis 241 (2015) e149ee229 e207 EAS-0936. COMPLEMENTARY EFFECT OF COMBINATION OF STATINS WITH COENZYME Q10 AND OMEGA-3 FATTY ACIDS IN PATIENTS WITH COMBINED DYSLIPIDEMIA S. T oth, M. Sajty, T. Pek arov a, J. Feda cko, K. Spi s akov a, D. Pella. 1st Department of Internal Medicine, avol Jozef Saf arik University in Ko sice Faculty of Medicine, Kosice, Slovakia * Corresponding author. Introduction: Several studies have described a positive effect of statins and omega-3 PUFA or CoQ10 on cardiovascular system. The aim of this study was to determine the effect of this triple combination on various parameters associated with the progression of cardiovascular disorders. Material and methods: 90 patients taking statins at a dose, which allowed target LDL levels, but with remained elevated TG levels (1.5-4.5 mmol/L) were randomized into three groups (each N1⁄430). In the placebocontrol group we indicated continued administration of statins. In the groups with additive treatment patients continued use of statins in combination with omega-3 PUFA 3 g/day respectively omega-3 PUFA 3 g/ day and 200 mg CoQ10/day during three months. After 3 months (± 1 week), we performed a final examination and collection of samples. We observed the lipid profile (total cholesterol, HDL, LDL, TG), hsCRP levels, activity SOD and GPx and presence of negative pleiotropic effects of statins. Results: Combination of statins with omega-3 PUFA significantly reduced TG and increased HDL levels. Significant reduction of hsCRP and increse of GTx and SOD was detected as well. Triple combination significantly decreased LDL and increased HDL in compare to control and dual combination. hsCRP significantly decreased in compare to control and dual combination group. SOD significantly increased in compare to control and dual combination group and GPx in compare to control. Conclusion: According to our study we suggest positive and complementary effect of combined therapy on lipid parameters, endothelial function and some negative pleiotropic effects of statins. EAS-0948. STATINS IMPACT IN A PORTUGUESE PRIMARY CARE UNIT J. Frutuoso. Internal Medicine, Hospital Jos e Joaquim Fernandes, Beja,

Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic Excess Iodine Intake

Acute iodine excess in newborns can cause hypothyroidism, but there are limited data on the effects of iodine excess on thyroid function in older infants. The aim of this study was to measure the effects of chronic excess iodine intake on thyroid function in 6-24-month-old infants. In this cross-sectional study, infants (n=696) in eastern Nepal were studied. Spot urine samples, venous blood samples, and household salt samples were collected, and urinary iodine concentration (UIC), serum free thyroxine (fT4), thyrotropin (TSH), thyroglobulin (Tg), and titrated household salt iodine concentration (SIC) were measured. Daily iodine intake was calculated from UIC based on estimates of urine volume at this age. Median (25th-75th percentile) household SIC was 89 (70-149) ppm, while national legislation stipulates a fortification level of 50 ppm. Median UIC was 407 (312-491) μg/L; 76% of infants had a UIC >300 μg/L, suggesting iodine excess. Calculated mean iodine intake in 12-24-month-old infants was 220 μg/day, exceeding the recommended safe upper limit for iodine at this age (200 μg/day). Among the infants, 15.8% had an elevated Tg, 7.4% had subclinical hypothyroidism, but <1% had overt hypothyroidism. UIC was not a significant predictor of thyroid function, thyroid hormones, or Tg. In 6-24-month-old infants exposed to excessive iodine intake, ∼7% have subclinical hypothyroidism but <1% have overt hypothyroidism. These findings suggest the thyroid in late infancy is already able to adapt to high iodine intakes and, in most cases, maintain euthyroidism.

Abstract 337: Berberine Attenuates Hyperlipidemia in Mice by a Novel Underlying Mechanism Involving Trib1

Recent genome wide association studies have identified tribbles homolog 1 (Trib1) as a risk factor in Myocardial Infarction. Trib1 has been shown to regulate VLDL production and hepatic lipogenesis in mice. Liver-specific overexpression of Trib1 reduced hepatic VLDL production and knockdown of Trib1 elevated plasma TG and cholesterol due to the increased VLDL production. However, currently little is known about the regulation of endogenous Trib1 expression and the relationship with plasma lipid homeostasis. In this study, we demonstrate that treating hyperlipidemic mice with 200 mg/kg of berberine (BBR), a natural lipid lowering compounds for 2 weeks reduced plasma total cholesterol by 24% and VLDL-cholesterol by 73% as compared to control mice. Hepatic gene expression analysis revealed that LDLR mRNA levels were not changed by BBR treatment. However, Trib1 mRNA levels were 70% (p&lt;0.01) higher in BBR-treated group than that of control group. The elevation of hepatic Trib1 mRNA levels was also observed in BBR-treated mice fed a regular diet. To further characterize the LDLR-independent mechanism responsible for plasma TG lowering, BBR (150 mg/kg) was orally administered to LDLR knockout mice and we observed a 47% (p&lt;0.05) reduction of serum TG levels after 6-days of BBR treatment while serum TC levels were not reduced. Importantly, the reduction of serum TG in LDLR KO mice by BBR treatment was accompanied by approximately 2-fold (p&lt;0.05) increase in hepatic Trib1 mRNA levels in BBR-treated group as compared to control group. Furthermore, upregulation of Trib1 mRNA expression by BBR was inversely associated with the expression of key lipogenic genes (ACC1, SCD1, C/EBPα, GPAT1, MLXIPL and DGAT1) and measures of lipogenesis. By using HepG2 in vitro model system, we show BBR treatment also significantly increases Trib1 mRNA expression and reduces mRNA and protein expression of lipogenic genes. Taken together, our studies demonstrate for the first time that hepatic expression of Trib1 is upregulated by the natural lipid lowering compound BBR and that Trib1 plays an important role in the hypolipidemic effect of BBR independent of LDLR.

Abstract 28: Mechanistic Studies of HDL Mimetic Peptide ATI-5261 Reveal Aspects of Class A Alpha-helix Structure that Induce Cytotoxicity and Hypertriglyceridemia in vivo: Design of Safe Analogs with Potent Anti-atherosclerosis and Anti-diabetic Actions

HDL mimetic peptides hold promise for the treatment of cardio-metabolic diseases. Transient increases in plasma TG and/or safety concerns may limit their therapeutic applications however, particularly in high risk patients with hypertriglyceridemia and diabetes. Presently, we sought to identify peptide structural features responsible for these adverse effects. The single helix peptide ATI-5261 was used as a model, since it forms a class A α-helix like many HDL mimetic peptides and has exceptional secondary structure and solubility. High dose ip injection (300 mg/kg) of ATI-5261 induced muscle toxicity in C57Bl/6 mice vs. vehicle (serum CPK@4 h = 32,314±2359 vs 143±44 IU/L), increased ALT and AST activities (233±10 &amp; 4595±933 vs 26±6 &amp; 84±21 IU/L) and elevated plasma TG (1951±77 vs 37±7 mg/dl). A majority (~90%) of the cytotoxicity and TG increase was eliminated by removing phenylalanine residues from the apolar face of ATI-5261. Similar results were obtained by removing cationic arginine residues from the lipid-water interface. Thus both features were necessary, but each not sufficient, to induce cytotoxicity and TG elevations. Based on this, a peptide (CS6253) was created that was non-toxic (no adverse effect level &gt;500 mg/kg; t1/2 =7.0±0.6 h in rats), retained secondary structure (75±5% α-helicity), high solubility and ability to stimulate ABCA1-dependent cholesterol efflux efficiently (Km=0.80±0.40 vs. 0.86±0.25 μg/ml ATI-5261). In vivo CS6253 was TG neutral, promoted macrophage RCT, and reduced (32%) substantial atherosclerosis in apoE KO mice fed western diet 10 wks (lesion area = 22±4 vs. 15±2% with 30 mg CS6253/kg, ip injection every 48 h for 6 wks, p&lt;0.01) and improved glucose - and insulin- tolerance tests with lowering of HbA1c levels in C57Bl/6 mice fed high-fat diet (DIO model). In summary, the cytotoxic and TG elevating effects of high-dose ATI-5261 were dependent on class A α-helix structure. CS6253 with its improved safety margin represents a novel ABCA1 ligand peptide with potential to treat diabetes and associated cardiovascular disease.

Familial lipoprotein lipase deficiency – neonatal presentation

A baby girl, born by normal spontaneous vaginal delivery with birth weight 3.845kg, was admitted for neonatal jaundice on day 2 of life. Her mother had maternal gestational diabetes on diet control. Her father was newly diagnosed with hyperlipidaemia on health screen and was put on diet control. There was no consanguinity. Her serum bilirubin level on admission was 186mmol/L with normal liver function test. However, the serum was noted to be very lipaemic when checking with bedside bilirubin machine and it persisted for few blood samples. The baby girl was on exclusive breastfeeding. In view of lipaemic serum, random lipid profile was checked and showed hypertriglyceridemia (TG) 10.6mmol/L (<1.7mmol/L) and cholesterol (TC) 3.1mmol/L (<5.2mmol/L). Repeated fasting sample showed persistent elevated triglyceride level 8.5mmol/L. Other blood parameters including amylase and liver enzymes were unremarkable. Physical examination showed no dysmorphic features. There was no hepatosplenomegaly or xanthoma. Ophthalmologically examination did not show any lipaedmia retinalis. In view of elevated serum triglyceride, further workup included lipoprotein electrophoresis and genetic analysis for lipoprotein lipase (LPL) gene were performed. Dietitian was consulted and the baby girl was given a therapeutic trial with commercially available special milk formula, Monogen (85% medium-chain triglyceride oil). The pretreatment lipid profile were TG 8.5mmol/L, TC 4.8mmol/L and HDL 0.6mmol/L (>1.3mmol/L) while TG 6.0mmol/L, TC 3.9mmol/L and HDL 0.6mmol/L after 2 weeks of special milk. She otherwise tolerated the special formula well. Parents’ fasting lipid profiles were also checked. Mother showed hypertriglyceridemia 3.0mmol/L, and father had elevated TG 3.57mmol/L, TC 7.14mmol/L and LDL 4.65mmol/L ( G and heterozygous LPL {type:entrez-nucleotide,attrs:{text:NM_000237.2,term_id:145275217,term_text:NM_000237.2}}NM_000237.2:.836T>G mutations. Parental screening showed father carried a heterozygous LPL {type:entrez-nucleotide,attrs:{text:NM_000237.2,term_id:145275217,term_text:NM_000237.2}}NM_000237.2:c.835C>G mutation while mother carried heterozygous LPL {type:entrez-nucleotide,attrs:{text:NM_000237.2,term_id:145275217,term_text:NM_000237.2}}NM_000237.2:c.836T>G mutation. The patient was confirmed to be compound heterozygous lipoprotein lipase deficiency. On monthly follow-up evaluations 10 months after hospital admission, the patient remained asymptomatic, maintained adequate growth, and had triglyceride levels gradually on downward trend 4.7mmol/l.

Association of Human Adenovirus-36 With Dyslipidemia in Tehranian Children and Adolescent; TLGS

Background: The human adenovirus-36 (Adv36) has been associated with obesity and lipid disorders in some countries. The primary dyslipidemia related to obesity is characterized by increased TG, decreased HDL levels and abnormal LDL composition. Childhood obesity is a major public health problem in most developing countries. Objectives: The aim of this study was to investigate the association between Adv36 and lipid disorders in Tehranian youth. Patients and Methods: In a cross-section/observational study, anthropometric, blood pressure and biochemical measurements were examined in 54 youth, aged below 19 years, selected randomly from participants of Tehran Lipid and Glucose Study (TLGS) of Iran. Human Adv36 antibody of serum was determined using ELISA method. Results: Of 54 youth, with a mean age of 14.78 ± 2.62 years, 85.2% were Adv36 seropositive (N = 46) and 14.8% were seronegative (N = 8). Subjects with Adv36 seropositive had higher mean of age, weight, TC, LDL-C, TG and SBP and lower level of HDL-C, waist, FBS and DBP. The unadjusted OR for elevated TG increased in participants who were Adv36 seropositive (OR 3.062, 95% CI: 0.344-27.293). Although the unadjusted OR for other lipid variables, such as elevated TC and LDL-C or decreased HDL-C, tended to increase in participants who were Adv36 seropositive (OR 1.028, 95% CI: 0.996 - 1.060; OR 1.057, 95% CI: 0.107 - 10.481; OR 1.125, 95% CI: 0.238 - 5.325, respectively), the results were not significant. Conclusions: It seems that seropositive Adv36 has a strong association with lipid disorders, especially elevated TG level in Tehranian children and adolescent.