Validity of multiplex biomarker model of 6 genes for the differential diagnosis of thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Currently the cytological examination of fine needle aspiration (FNA) biopsies is the standard technique for the pre-operative differential diagnosis of thyroid nodules. However, the results may be non-informative in ~20% of cases due to an inadequate sampling and the lack of highly specific, measurable cytological criteria, therefore ancillary biomarkers that could aid in these cases are clearly needed. The aim of our study was to evaluate the mRNA expression levels of 8 candidate marker genes as the diagnostic biomarkers for the discrimination of benign and malignant thyroid nodules and to find a combination of biomarkers with the highest diagnostic value.</p> <p>Materials and methods</p> <p>mRNA expression levels of eight candidate marker genes - <it>BIRC5, CCND1, CDH1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3 </it>was measured by real-time RT-PCR in paired nodular and surrounding normal thyroid tissue specimens of 105 consecutive patients undergoing thyroid surgery and compared between different types of thyroid lesions.</p> <p>Results</p> <p>Significant differences in the mRNA expression levels between the normal and malignant thyroid tissues and between benign and malignant nodules were found for <it>BIRC5, CCND1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3</it>, but not <it>CDH1</it>. On a single gene basis, relative quantity (RQ) of <it>LGALS3 </it>had the highest diagnostic value for the discrimination of malignant and benign thyroid nodules (AUC = 0.832, P < 0.0001 and 90.9% sensitivity and 65.6% specificity at the optimal cut-off on ROC curve). The only two-marker set that outperformed <it>LGALS3 </it>was RQ sum of <it>LGALS3 </it>and <it>BIRC5 </it>(AUC = 0.841, P < 0.0001). An application of multivariate logistic regression analysis resulted in the generation of a multiplex biomarker model based on <it>LGALS3, BIRC5, TFF3, CCND1, MET </it>and <it>CITED1 </it>that had considerably higher specificity than a single marker or two marker gene-based models (AUC = 0.895, P < 0.0001, 70.5% sensitivity and 93.4% specificity).</p> <p>Conclusions</p> <p>This study confirmed that mRNA expression levels of 7 out of 8 candidate genes analysed have a diagnostic value for the distinction of benign and malignant thyroid nodules. The multiplex biomarker model based on 6 genes outperformed a single marker or two marker-based models and warrants feasibility studies on FNA biopsies and the validation in a larger cohort of patients.</p

The Latvian School of Internal Medicine as a Model for Succession of Ideas

Pārrāvums ideju pēctecībā ir viena no mūsdienu pasaules pamatproblēmām. Ievada vietā vēlos pastāstīt par savām pārdomām, kas radās kādās saviesīgās vakariņās, sēžot pie viena galda ar dažādu Eiropas valstu pārstāvjiem. Sarunas ievirzījās par Eiropas, un ne tikai Eiropas, ekonomiskās krīzes cēloņiem. Itāliešu viedoklis bija, ka Eiropa ir zaudējusi savu kultūru un nokļuvusi neizglītotu barbaru politiķu un biznesmeņu rokās, bet angļi un vācieši iebilda, ka nevis kultūras zudums, bet gan pārmērīgs savtīgums un turīgo cilvēku vēlēšanās ar dažādiem juridiskiem trikiem izvairīties no nodokļu maksāšanas un pārmērīga uzticēšanās baņķieru solījumiem iegūt naudu bez reāla darba ir visu ekonomisko nelaimju pamatā

Hypercalcemia and CYP24A1 Gene Mutation Diagnosed in the 2nd Trimester of a Twin Pregnancy : A Case Report

Publisher Copyright: © Am J Case Rep, 2021.Objective: Rare disease Background: Loss-of-function mutations of the CYP24A1 gene cause a deficiency of the CYP24A1 enzyme, which is involved in the catabolism of 1,25-dihydroxyvitamin D3. Patients who are CYP24A1 enzyme deficient are at increased risk of developing hypercalcemia during pregnancy and should avoid additional vitamin D supplementation. This case report provides additional information for managing and diagnosing patients with a CYP24A1 gene mutation. Case Report: A primipara woman with a twin pregnancy was admitted to our hospital for frequent hypertensive crises. She had no history of hypercalcemia-associated signs and symptoms except nephrocalcinosis, and reported no oth-er abnormalities or discomfort at presentation. Laboratory tests revealed that the parathyroid hormone level was suppressed and the serum calcium level was markedly increased. The 25-hydroxyvitamin D level was at the upper limit of the reference range while the 1,25-dihydroxyvitamin D3 level was elevated, suggesting a vitamin D catabolism disorder. A genetic test was performed and a homozygous likely pathogenic variant (based on the American College of Medical Genetics and Genomics guidelines) c.964G>A (p.Glu322Lys) was detected in the CYP24A1 gene (NM_000782.5). A cesarean section delivery was performed due to a single intrauterine demise at 33 weeks of gestation. The preterm newborn was diagnosed with transitional hypercalcemia and hyperphosphatemia; however, he was not treated, as he was asymptomatic. Conclusions: Patients with a CYP24A1 gene mutation are at increased risk of hypercalcemia and fetal demise; therefore, 25-hy-droxyvitamin D and calcium levels should be monitored in routine blood tests during pregnancy. Hypercalcemia in a newborn should be carefully evaluated and treated, as hypercalciuria can lead to nephrocalcinosis.Peer reviewe

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration

Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration

OBJECTIVE: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. DESIGN: Register-based cross-sectional study. METHODS: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. RESULTS: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. CONCLUSIONS: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe

Ensuring Effective Prevention of Iodine Deficiency Disorders.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pagePrograms initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention.Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency.Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.EUthyroid info:eu-repo/grantAgreement/EC/FP7/63445