▼Purpose: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. Materials and Methods: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US. In addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. Results: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21 %, 73 %, 86 %, 11 %, 0.8, respectively, for color Doppler US; 69 %, 75 %, 94 %, 30 %, 2.9, respectively, for SE-ES; 56 %, 81 %, 92 %, 32 %, 2.9, respectively, for SEstrain value; and 58 %, 78 %, 92 %, 30 %, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71 % for both strain value and strain ratio of nodules. Conclusion: SE as an additional ultrasound tool improves the value of ultrasound for the workup of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future. Zusammenfassung ▼Ziel: Viele Patienten mit Schilddrüsenknoten werden nicht nur therapeutisch, sondern auch zu diagnostischem Zweck operiert. Ziel von nicht-invasiven diagnostischen Verfahren ist es daher die Selektion von Patienten zur Operation zu optimieren. Strain Elastografie (SE) ermöglicht die Ultraschall-basierte Messung der Gewebeelastizität. Das Ziel der vorliegenden Studie war es den Stellenwert der SE in einer prospektiven Multizenter-Studie für die Differenzierung von Schilddrüsenknoten zu evaluieren. Material und Methoden: Die Studie wurde bei clinicaltrials.gov registriert und von den lokalen Ethikkommissionen der teilnehmenden Zentren genehmigt. Alle Patienten erhielten einen Ultraschall (US) der Schilddrüse inklusive Farbduplex-US. Zusätzlich wurden alle Knoten mittels SE (Hitachi Medical System) untersucht und eine Beurteilung der qualitativen Farbverteilung (SE-ES) und eine semiquantitative Messung der Elastizität mittels strain value und strain ratio durchgeführt. Ergebnisse: Insgesamt wurden 602 Patienten mit 657 Schilddrüsenknoten (567 benigne, 90 maligne) an 7 deutschen Zentren ausgewertet. Sensitivität, Spezifität, NPV, PPV, und +LR betrugen entsprechend 21 %, 73 %, 86 %, 11 %, 0,8 für den Duplex-US; 69 %, 75 %, 94 %, 30 %, 2,9 für SE-ES; 56 %, 81 %, 92 %, 32 %, 2,9 für SE-strain value; 58 %, 78 %, 92 %, 30 %, 2,6 für SE-strain ratio. Die diagnostische Genauigkeit betrug 71 % sowohl für SEstrain value, als auch SE-strain ratio. Schlussfo...

Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects.Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro.Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05).Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects.

Background: Common polymorphisms of the vitamin D receptor gene have been reported to affect the risk of breast, colon, prostate, and differentiated thyroid cancer (DTC), but polymorphisms within the genes of vitamin D metabolizing enzymes have not been studied in DTC. The aim of the present study was to investigate the genes for vitamin D enzymes in patients with DTC and healthy controls (HC) as well as the vitamin D (25hydroxyvitamin D 3 , and 1,25-hydroxyvitamin) status. Methods: German patients (n = 253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n = 302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1a-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]). Furthermore, the 25-hydroxyvitamin D 3 [25(OH)D 3 ] and 1,25-hydroxyvitamin [1,25(OH) 2 D 3 ] plasma levels were measured by a radioimmunoassay. Results: There was no difference in the genotypes; however, the CYP24A1 haplotype analysis showed that rs2248137C/rs2296241A (13.1% vs. 19.1%; corrected p [pc] = 0.04) was less frequent in the PTC, whereas the haplotypes rs2248137C/rs2296241G (56.0% vs. 41.9%; pc = 0.03), rs927650C/rs2296241G (22.5% vs. 8.4%; pc = 1.6 • 10-3), and rs927650C/rs2248137C/rs2296241G (21.1% vs. 7.3%; pc = 1.5 • 10-3) were more frequent in the FTC compared with HC. Furthermore, if patients and controls were grouped according to four 25(OH)D 3 categories (severely deficient, deficient, insufficient, and sufficient), then the patients with both DTC subtypes had significantly lower levels of circulating 1,25(OH) 2 D 3 , especially in the group with a deficient 25(OH)D 3 status compared with the controls. Although the polymorphisms showed no differences stratified for the four 25(OH)D 3 categories, the activation status by 1,25(OH) 2 D 3 differed significantly depending on the genotypes of the investigated CYP24A1 polymorphisms. Conclusions: A higher risk for DTC is conferred by haplotypes within the CYP24A1 gene, low circulating 25(OH)D 3 levels (deficiency), and a reduced conversion to 1,25(OH) 2 D 3. These results confirm and extend previous observations and also support a role of the vitamin D system in the pathogenesis of DTC. How deficient 25(OH)D 3 levels in combination with certain CYP24A1 haplotypes affect vitamin D activation is the subject of future studies.

No abstract

No abstract