Grey-scale analysis improves the ultrasonographic evaluation of thyroid nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03-0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4-74.5%), specificity of 72.0% (67.8-75.9%), positive likelihood ratio (LR) of 2.023 (1.434-2.852), and negative LR of 0.602 (0.398-0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59-7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69-105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7-90.1%), specificity of 46.8% (42.3-51.4%), positive LR of 1.442 (1.164-1.786), and negative LR of 0.498 (0.259-0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure

Thyroid autoantibodies and breast cancer

Dear Editor We read with interest the recent article by Shi and colleagues (2014) reporting a meta-analysis on the relationship between thyroid hormones, thyroid autoantibodies and breast cancer (BC). In the paper, the authors analyzed eight different studies, including 4,189 participants, and concluded that serum levels of free-triiodothyronine, thyroperoxidase and thyroglobulin autoantibodies are higher in patients affected by BC, compared with the control group. These findings are in agreement with the meta-analysis reported by Hardefeldt and colleagues, showing an increased risk of BC in patients with autoimmune thyroid disease, and with a recent article by our group in which the prevalence of BC in 3,921 female patients affected by both benign and malignant thyroid diseases was evaluated (Hardefeldt et al., 2012; Prinzi et al., 2014). In the latter, we showed that the prevalence of BC in patients affected by thyroid disease, as a whole, was significantly higher, compared to the general population (OR 3.3). Moreover, the age-matched analysis showed that the risk of BC was higher in younger patients (0–44 yr, OR 15.2), to decline with the increasing age. In the same study, when patients were dichotomized based on the presence or the absence of thyroglobulin and/or thyroperoxidase autoantibodies, both groups showed a higher risk of BC, compared to the general female population. When the two groups were compared to each other, however, the risk of BC was significantly lower in autoantibody positive patients. Thus, as clearly stated in our article, among patients affected by thyroid diseases, the presence of thyroid autoantibodies may have a protective role against BC (Prinzi et al., 2014). As a consequence, the sentence reported by Shi and colleagues in the Discussion section of their article stating that their findings are in disagreement with our data is not correct and should be, if at all possible, amended

Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p=0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p=0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk

Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT

International audienceBACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. METHODS: The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. RESULTS: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. CONCLUSIONS: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment

Gray-scale analysis nella valutazione del nodulo tiroideo

p 0.035).L’indice di disomogeneità del nodulo tiroideo risulta significativamente più alto nei noduli sospetti per malignità alla citologia (0,78 R.I. 0,58-1,44 vs 0,63 R.I. 0,47-0,87; p=0,02). Per validare la bontà del valore del coefficiente di variazione come misura di disomogeneità, si è confermato che esso è significativamente maggiore nel parenchima di pazienti con anti-TPO positivi rispetto ai negativi (mediana 0,38, R.I. 0,30-0,43 vs. 0,34, R.I. 0,29-0,41; Obiettivi dello studio: La gray-scale analysis è stata proposta per la caratterizzazione della patologia tiroidea diffusa (in particolare tiroidite autoimmune). Lo scopo dello studio è valutare se una tecnica basata sull’analisi dei livelli di grigio possa essere utilizzata per standardizzare la valutazione di ecogenicità ed ecostruttura del parenchima ed anche delle lesioni focali tiroidee.Materiali: Sono state esaminate le immagini ecografiche di 521 noduli solidi, candidati all’esecuzione di agoaspirato tiroideoecoassistito. Per ogni immagine, è stata selezionata un’area di interesse comprendente il nodulo. È stata inoltre considerataun’area di interesse delle stesse dimensioni e morfologia comprendente parenchima tiroideo normale ed una comprendente, per riferimento, i muscoli pretiroidei. Dati i valori di grigio medio e mediano e la deviazione standard dell’istogramma dei grigi del nodulo, del parenchima e del muscolo, sono stati calcolati: rapporto valore mediano di grigio nodulo/parenchima e parenchima/muscolo, coefficiente di variazione dei grigi sul parenchima e sul nodulo, come misura di disomogeneità ecostrutturale (indice di disomogeneità).Risultati: Il rapporto valore mediano di grigio nodulo/parenchima risulta significativamente più basso (come misura oggettiva di ipoecogenicità) nei noduli sospetti per malignità (categorie SIAPEC TIR4 e TIR5 oppure sospetti per carcinoma midollare) alla citologia (0,44 R.I. 0,38-0,60 vs 0,62 R.I. 0,43-0,93; p=0,003). Il dato è confermato sui noduli maligni confermati all’istologia definitiva rispetto ai benigni seguiti nel tempo (0,46 R.I. 0,39-0,75 vs 0,64 R.I. 0,43-0,93; p=0,03) e maligni all’istologia definitiva (0,73 R.I 0,52-1,21 vs 0,63 R.I.0.47-0,87; p=0,05).Conclusioni: La gray-scale analysis è una metodica a costo zero, facilmente applicabile da qualsiasi ecografista per la valutazione oggettiva delle caratteristiche ecografiche (ecogenicità ed anche ecostruttura) delle lesioni focali tiroidee, garantendo maggiore riproducibilità e minore variazione intra- ed interoperatore. I coefficienti ottenuti con questo metodo correlano con il rischio di malignità alla citologia ed all’istologia

Intrinsic factors affecting adequacy of thyroid nodule fine-needle aspiration cytology

Objective To evaluate intrinsic nodule features predictive of an inadequate report in fine-needle aspiration cytology (FNAC). Design Single-centre cross-sectional study. Methods Between May 2005 and April 2011, 3279 ultrasonography-assisted FNACs were carried out and features of nodules recorded prospectively. Univariate logistic regression analyses were performed to estimate the association between nondiagnostic cytology and variables such as age, gender, single nodule, maximum nodule diameter and estimated volume. Results Inadequate or nondiagnostic samples were reported in 1195 FNACs. All diameters were found to be predictors of nondiagnostic cytology; estimated nodule volume, on the other hand, was not. Nodules with a diameter <10 mm were more frequently nondiagnostic (OR 1.65, 95% CI 1.401.94, P < 0.001). Neither micro- nor macrocalcification increased the risk of inadequacy. On the contrary, mixed lesions were more frequently diagnostic (OR 0.68, 95% CI 0.850.80, P < 0.001). Solid nodule aspiration was performed more easily on isoechogenic nodules (OR 0.64, 95% CI 0.540.77, P < 0.001); the same procedure was more cumbersome on hypoechogenic lesions (OR 1.87, 95% CI 1.622.16, P < 0.001). Increased vascularization did not cause a significant increase in the nondiagnostic results. Blurred margins increased the inadequacy rate (OR 1.45, 95% CI 1.241.69, P < 0.001), while presence of a hypoechogenic halo decreased it (OR 0.67, 95% CI 0.540.82, P < 0.001). Conclusions Some ultrasonographic features suggestive of malignancy may be predictive of inadequate cytology. Patients must be notified that the FNA report may be nondiagnostic and that this represents a limitation of the technique related to the structure of lesions

Grey-scale analysis in the ultrasonographic evaluation of thyroid nodules

Objective: Subjective analysis of ultrasonography (US) images is the first-line method to assess thyroid nodules, although it is limited by inter-observer variability and experience. The purpose of this study is to perform a quantitative measurement of echogenicity and echo-pattern, obtaining an objective estimate of the degree of hypoechogenicity and homogeneity, associated with risk of malignancy. Methods: From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided FNA. In a single US image, three regions of interest (ROIs) were drawn: the first including the nodule; the second included a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, obtaining the median, mean and SD of the pixels comprising each ROI. Echogenicity was expressed as a ratio: the nodule/parenchyma and parenchyma/muscle median grey ratios were calculated. The heterogeneity index was calculated as the coefficient of variation of grey histogram for each of the three ROIs. Results or Case Presentation: Nodule/parenchyma median grey ratio was significantly lower (more hypoechoic) in nodules found to be suspicious for cancer, according to the cytology report (p=0.006) and in confirmed malignant nodules (p=0.02). A nodule/parenchyma median grey ratio <0.46 has a sensitivity of 53.6% and specificity of 71.1% in predicting malignancy (OR 2.84; p=0.01). It can also be used as a continuous measure of hypoechogenicity and risk of malignancy (OR 0.20; p=0.02). Discussion: US is a widely available and harmless method. It nonetheless is operator-dependent. The inter-observer agreement seems to be relatively good; however, a merely slight agreement was reported for echogenicity and echotexture. We developed a method to perform a quantitative measurement of thyroid echogenicity, avoiding the need for fixed US operating conditions. Conclusion: Evaluation of nodule echogenicity according to the nodule/parenchyma median grey ratio allows for an objective stratification of thyroid nodule structure and risk of malignancy.Objective: Subjective analysis of ultrasonography (US) images is the first-line method to assess thyroid nodules, although it is limited by inter-observer variability and experience. The purpose of this study is to perform a quantitative measurement of echogenicity and echo-pattern, obtaining an objective estimate of the degree of hypoechogenicity and homogeneity, associated with risk of malignancy. Methods: From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided FNA. In a single US image, three regions of interest (ROIs) were drawn: the first including the nodule; the second included a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, obtaining the median, mean and SD of the pixels comprising each ROI. Echogenicity was expressed as a ratio: the nodule/parenchyma and parenchyma/muscle median grey ratios were calculated. The heterogeneity index was calculated as the coefficient of variation

Gray-scale analysis nella valutazione del nodulo tiroideo

Obiettivi dello studio: La gray-scale analysis è stata proposta per la caratterizzazione della patologia tiroidea diffusa. Lo scopo dello studio è validare una tecnica ecografica basata sull’analisi dei livelli di grigio al fine di standardizzare la valutazione di ecogenicità ed ecostruttura di parenchima e lesioni focali tiroidee. Metodi: Sono stati esaminate le immagini ecografiche di 521 noduli solidi, candidati all’esecuzione di agoaspirato. Per ogni immagine, è stata selezionata un’area di interesse comprendente il nodulo. E’ stata inoltre considerata un’area di interesse delle stesse dimensioni e morfologia comprendente parenchima tiroideo normale ed una comprendente, per riferimento, i muscoli pretiroidei. Dati i valori di grigio medio e mediano e la deviazione standard dell’istogramma dei grigi del nodulo, del parenchima e del muscolo, sono stati calcolati: rapporto valore mediano di grigio nodulo/parenchima e parenchima/muscolo, coefficiente di variazione dei grigi sul parenchima e sul nodulo, come misura di disomogeneità ecostrutturale (indice di disomogeneità). Risultati: Il rapporto valore mediano di grigio nodulo/parenchima risulta significativamente più basso (come misura oggettiva di ipoecogenicità) nei noduli sospetti per malignità (categorie SIAPEC TIR4/TIR5 o sospetti per carcinoma midollare) alla citologia (p=0.006). Il dato è confermato sui noduli maligni confermati all’istologia definitiva rispetto ai benigni seguiti nel tempo (p=0.02). Un rapporto del valore mediano di grigio nodulo/parenchima <0.46, ottenuto mediante analisi della curva ROC, ha una sensibilità del 53.6% e una specificità del 71.1% nel predire la malignità (OR 2.84; p=0.01). A differenza della descrizione qualitativa, può inoltre essere utilizzato come una misura continua di ipoecogenicità e rischio di malignità (OR 0.20; p=0.02). Per validare la bontà del valore del coefficiente di variazione come misura di disomogeneità, si è confermato che esso è significativamente maggiore nel parenchima di pazienti con anti-TPO positivi rispetto ai negativi (p=0.035), mentre non è risultato essere un predittore significativo di malignità dei noduli. Conclusioni: La gray-scale analysis è una metodica a basso costo, facilmente applicabile per la valutazione oggettiva delle caratteristiche ecografiche, in particolare dell’ecogenicità, delle lesioni focali tiroidee, fornendone una stima quantitativa. I coefficienti ottenuti con questo metodo correlano con il rischio di malignità alla citologia ed all’istologia

A comprehensive score to diagnose Hashimoto's thyroiditis: a proposal

The heterogeneity of diagnostic criteria of Hashimoto’s thyroiditis leads to overdiagnosis and prevents strong conclusions from being drawn in clinical studies. The aim of this study is to propose a comprehensive scoring system. A case–control study compared a set of presurgical features of patients with lymphocytic infiltration of the thyroid (Hashimoto’s thyroiditis) and controls, in order to design a multi-criteria scoring system. Given a dichotomous outcome (lymphocytic infiltration of the thyroid), a set of covariates was analyzed in 180 patients after total thyroidectomy. A different validation cohort of 1,171 patients was reviewed and classified according to the score. Variables associated with the diagnosis of Hashimoto’s thyroiditis were first assessed by univariate analysis. Analysis showed that TPOAb (area under the ROC curve (AUC), 0.67; 95 % CI 0.57–0.77) and TgAb (0.63; 95 % CI 0.54–0.74) were univariate predictors of the diagnosis of HT, which is largely recognized. Combined covariates were then tested using stepwise logistic regression analysis. The final regression model included TPOAb, TgAb, and thyroid vascularity (AUC 0.72; 95 % CI 0.62–0.81). A scoring system was developed, which has a sensitivity of 45.5 % and a specificity of 89.0 %, with a cutoff of 1.7. The likelihood of incident hypothyroidism was higher (OR 2.30; p = 0.004) in the positive (≥1.7) score group. A scoring system has a better performance than any single predictor and is able to identify the subgroup of individuals at higher risk to develop subsequent hypothyroidism