T Rago

Azienda Ospedaliero-Universitaria Pisana, Pisa, Tuscany, Italy

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Publications (58)178.14 Total impact

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    ABSTRACT: Fine-needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains indeterminate for 12-18 % of nodules. BRAF V600E mutation has been reported to show a high specificity for malignant thyroid nodules and the use of this marker to refine indeterminate FNA cytology results may be a useful diagnostic adjunctive tool in the pre-operative evaluation of thyroid nodules. The aim of this study was to estimate the prevalence of BRAF exon 15 mutation (V600E) and its clinical value as a diagnostic tool in a series of thyroid nodules with indeterminate cytology from an area of borderline iodine deficiency.
    Journal of endocrinological investigation 09/2014; · 1.65 Impact Factor
  • Teresa Rago, Paolo Vitti
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    ABSTRACT: Among several ultrasound patterns, thyroid nodule hypoechogenicity, spot microcalcifications, and an absent halo sign are used for predicting increased risk of thyroid malignancy. The predictive value of ultrasound, however, increases at the expense of its sensitivity, and malignancy is predicted with high specificity only when multiple ultrasound features are simultaneously present. Ultrasound features are important in determining the strength of the indication for carrying out fine needle aspiration. To this end, a system for standardization of ultrasound features (Thyroid Imaging Reporting and Data System) aids in establishing risk of malignancy. Ultrasound elastosonography is a technique that assesses hardness as an indicator of malignancy risk. It has been carried out in selected studies of patients with thyroid nodules, and has been shown to have a high predictive value for malignancy, which is also maintained in cytologically indeterminate and non-diagnostic nodules. Although conventional ultrasound maintains its pivotal role in defining which nodules are candidates for ultrasound elastosonography characterization, the latter seems to have considerable potential in the diagnosis, or exclusion, of thyroid cancer. This especially concerns thyroid nodules with indeterminate cytology at fine-needle aspiration.
    Best practice & research. Clinical endocrinology & metabolism. 08/2014; 28(4):519-529.
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    ABSTRACT: Background. The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure. Patients. Two hundred consecutive patients were randomly assigned to a single LAT session (Group 1, 101 cases)) or to follow up (Group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume 6-17 ml, repeat benign cytological findings, normal thyroid function, no autoimmunity, no thyroid gland treatment. Methods. Group 1: LAT was performed in a single session with two optical fibers, a 1,064 nm Nd-YAG laser source, and an output power of 3 watts. Volume and local symptoms changes were evaluated 1, 6, 12, 24 and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: follow up with no treatment. Results. One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was -49±22%, -59±22%, -60±24%, and -57±25% at 6, 12, 24, and 36 months, respectively (p <0.001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (p<0.001). Local symptoms decreased from 38% to 8% of cases (p=0.002) and cosmetic signs from 72% to 16% of cases (p=0.001). Baseline size, presence of goiter, (p=0.55) or US findings (fluid component ≤20% (p=0.84), halo (p=0.46), vascularization (p=0.98), and calcifications (p=0.06) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In Group 2, nodule volume increased at 36 months (25±42% p=0.04). The efficacy and tolerability of the procedure were similar in different centers. Conclusions. A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.
    The Journal of clinical endocrinology and metabolism. 07/2014;
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    ABSTRACT: Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated.
    Cancer Cytopathology 06/2014; · 4.43 Impact Factor
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    ABSTRACT: Context: Clinical management of patients with thyroid nodules indeterminate at fine needle aspiration (FNA) cytology is still unsettled. Objective: To establish the clinical outcome of patients with thyroid nodules indeterminate at cytology and to identify the features associated with malignancy. Design: Retrospective evaluation. Patients: 1520 consecutive patients with indeterminate cytology among 100,065 patients who underwent FNA between January 2000 and December 2010. Results: 371/1520 (24.4 %) patients had thyroid cancer at histology, the follicular variant of papillary cancer being the most frequent histotype. 342 patients with cancer were free of disease after thyroidectomy and 131-I remnant ablation, while 29 needed further treatment because of persistent disease. Among them only 12 had persistence of disease at the end of follow-up. Atypias at cytology (p=0.001), blurred nodule margins (p=0.005) and spot microcalcifications (p=0.003) at thyroid ultrasound (US) were significantly associated with malignancy. A clinical score including cytology and US characteristics was calculated; the lowest value showed a high negative predictive value (83.9%) for the presence of malignancy and even higher (99.5%) for the presence of a more cumbersome cancer disease, only 4 out of the 29 patients who needed further treatment being included in the group with the lowest risk score. Conclusions: Patients with Thy 3 cytology and histology of thyroid cancer had an overall good prognosis. A clinical risk score including the results of cytology and US features is helpful in the management of patients with indeterminate thyroid nodules.
    The Journal of clinical endocrinology and metabolism 04/2014; · 6.50 Impact Factor
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    ABSTRACT: Context:The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown.Objective:To correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis.Setting:General community living in an Italian village.Main Outcome Measures:Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg.Results:Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 μ g/L vs 86.5 μ g/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047).Conclusions:Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.
    The Journal of clinical endocrinology and metabolism 09/2013; · 6.50 Impact Factor
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    ABSTRACT: Context: Iodine deficiency disorders are a major public health problem, and programs have been implemented to improve iodine nutrition. Objective: The objective of the study was to verify the effects of voluntary iodine prophylaxis in a small rural community (Pescopagano, Italy). Design: The design of the study was the evaluation of the prevalence of thyroid disorders 15 years after a previous survey conducted before iodine prophylaxis. Setting: The setting for this study was a general community survey. Participants: One thousand one hundred forty-eight residents were examined in 2010 and 1411 in 1995. Results: In 2010, 757 of 1148 subjects (65.9%) routinely used iodized salt, urinary iodine excretion being significantly higher than in 1955 (median 98.0 μg/L, vs 55.0 μg/L, P < .0001). The prevalence of goiter was lower in 2010 than in 1995 (25.8% vs 46.1%, P < .0001), mainly due to the reduction of diffuse goiter (10.3% vs 34.0%, P < .0001). In 2010 vs 1995, thyroid autonomy in subjects younger than 45 years old (3 of 579, 0.5% vs 25 of 1010, 2.5% P = .004) and nonautoimmune hyperthyroidism in subjects older than 45 years old (8 of 569, 1.4% vs 18 of 401, 4.5%, P = .03) were less frequent. The prevalence of hypothyroidism was higher in 2010 vs 1995 (5.0% vs 2.8%, P = .005), mainly because of an increased frequency of subclinical hypothyroidism in subjects younger than 15 years old (7 of 83, 8.4% vs 0 of 419, 0.0%, P < .0001). Accordingly, serum thyroid autoantibodies (19.5% vs 12.6%; P < .0001) and Hashimoto's thyroiditis (14.5% vs 3.5%; P < .0001) were more frequent in 2010 than in 1995. Conclusions: In the present work, the role of voluntary iodine prophylaxis was assessed in a small rural community relatively segregated, in which genetic and other environmental factors have not substantially changed between the 2 surveys. Iodine intake strongly affected the pattern of thyroid diseases, but the benefits of correcting iodine deficiency (decreased prevalence of goiter and thyroid autonomy in younger subjects and reduced frequency of nonautoimmune hyperthyroidism in older subjects) far outweighs the risk of development of thyroid autoimmunity and mild hypothyroidism in youngsters.
    The Journal of clinical endocrinology and metabolism 03/2013; 98(3):1031-9. · 6.50 Impact Factor
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    ABSTRACT: Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n = 114), papillary classical variant (cPTC) (n = 34) and papillary tall cell variant (TcPTC) (n = 14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.
    PLoS ONE 01/2013; 8(9):e72911. · 3.73 Impact Factor
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    ABSTRACT: Background Graves' Orbitopathy (GO) is thought to be related to one or more autoantigens present in the thyroid and in orbital tissues. Although this may not imply a quantitative relation between thyroid antigens and degree of GO, which in turn is a risk factor for a more pronounced GO, we postulated that the severity of GO may parallel the amount of thyroid tissue, namely the size of the thyroid gland. This hypothesis is also based on the observation that patients with Graves' disease presenting with large goiters tend to have more severe hyperthyroidism, Thus, we evaluated retrospectively whether there is a correlation between the degree of GO at its first observation and, among other parameters, the thyroid volume. Methods Eighty-six consecutive patients with untreated GO lasting for no longer than 24 months underwent an endocrinological and an ophthalmological evaluation, the latter including: exophthalmometry, eyelid width, clinical activity score (CAS), diplopia and visual acuity. The overall degree of GO was ranked using the NO SPECS score as well as a modification of the NO SPECS score. The following parameters were considered for correlations: time since GO appearance, time since detection of hyperthyroidism, FT3, anti-TSH receptor antibodies, thyroid volume and cigarette-years. Results Thyroid volume, but not the other parameters, correlated significantly by simple regression with exophthalmometry (P=0.02) and CAS (P=0.02). The standard NO SPECS score correlated with FT3 (P=0.05), thyroid volume (P=0.02), and cigarette-years (P=0.03), by simple, but not by multiple regression analysis. The modified NO SPECS score correlated with thyroid volume (P=0.007) and cigarette-years (P=0.04) by simple regression, and with thyroid volume also by multiple regression analysis (P=0.05). Conclusions Thyroid volume correlates with the severity of GO at its first observation, especially with exophthalmometry and CAS. The finding is in line with a possible pathogenetic role of antigens shared by the thyroid and orbital tissues. Nevertheless, other mechanisms may explain this observation, including an overall more reactive immune system in patients with a large goiter, resulting in more severe thyroid and eye disease, regardless of the nature of the autoantigen, or whether it is shared by the thyroid and the orbit.
    Thyroid: official journal of the American Thyroid Association 10/2012; · 2.60 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules. In this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA. The prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed. Using data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules. The expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method.
    European Journal of Endocrinology 06/2012; 167(3):393-400. · 3.14 Impact Factor
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    ABSTRACT: Background: the most important side effect of radioiodine (131I) therapy is sialoadenitis and xerostomy. Aim: to evaluate by ultrasound (US) parotid and submandibular glands after 131I therapy for differentiated thyroid cancer (DTC). Patients: 76 subjects thyroidectomised for DTC submitted to salivary glands US examination. Forty3 of them had been previously treated with 131I: 22 with 1.11 GBq (30 mCi) for remnant ablation, and 21 with higher doses (up to 44.4 GBq - 1200 mCi) for metastases. 33 subjects were studied before 131I therapy, and were the controls. Parotid and submandibular volume, homogeneity and echogenicity were determined. 131I treated patients filled a questionnaire about sialoadenitis symptoms. Results: Parotid gland volume was significantly higher in treated patients (28.3 ± 16.2 ml) than in untreated patients (20.7 ± 10.4 ml p = 0.0154) and related to the time from last 131I therapy. 3 had parotid volume <1.5 ml and complained severe xerostomy. Submandibular gland volume was similar in treated (11.2 ± 7.6 ml) and untreated patients (8.6 ± 4.2 ml, p = 0.0602). Homogeneity and echogenicity were similar in treated and untreated patients. Sialoadenitis symptoms were reported in 26% and were related to the 131I cumulative dose. Symptoms were not related to gland volume. Hypoechogenicity and inhomogeneity of the parotids were more frequent in patients with salivary stickiness. Conclusion: parotid, but not submandibular, volume is increased after 131I treatment depending on the received activity and the time from irradiation, but not on sialoadenitis symptoms. Xerostomy is associated to gland atrophy at US.
    Journal of endocrinological investigation 04/2012; · 1.65 Impact Factor
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    ABSTRACT: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.
    Journal of endocrinological investigation 10/2011; 35(8):754-9. · 1.65 Impact Factor
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    ABSTRACT: The possible association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a still debated issue. We analyzed the frequency of PTC, TSH levels and thyroid autoantibodies (TAb) in 13 738 patients (9824 untreated and 3914 under l-thyroxine, l-T(4)). Patients with nodular-HT (n=1593) had high titer of TAb and/or hypothyroidism. Patients with nodular goiter (NG) were subdivided in TAb-NG (n=8812) with undetectable TAb and TAb+NG (n=3395) with positive TAb. Among untreated patients, those with nodular-HT showed higher frequency of PTC (9.4%) compared with both TAb-NG (6.4%; P=0.002) and TAb+NG (6.5%; P=0.009) and presented also higher serum TSH (median 1.30 vs 0.71 μU/ml, P<0.001 and 0.70 μU/ml, P<0.001 respectively). Independently of clinical diagnosis, patients with high titer of TAb showed a higher frequency of PTC (9.3%) compared to patients with low titer (6.8%, P<0.001) or negative TAb (6.3%, P<0.001) and presented also higher serum TSH (median 1.16 vs 0.75 μU/ml, P<0.001 and 0.72 μU/ml, P<0.001 respectively). PTC frequency was strongly related with serum TSH (odds ratio (OR)=1.111), slightly related with anti-thyroglobulin antibodies (OR=1.001), and unrelated with anti-thyroperoxidase antibodies. In the l-T(4)-treated group, when only patients with serum TSH levels below the median value (0.90 μU/ml) were considered, no significant difference in PTC frequency was found between nodular-HT, TAb-NG and TAb+NG. In conclusion, the frequency of PTC is significantly higher in nodular-HT than in NG and is associated with increased levels of serum TSH. Treatment with l-T(4) reduces TSH levels and decreases the occurrence of clinically detectable PTC.
    Endocrine Related Cancer 05/2011; 18(4):429-37. · 5.26 Impact Factor
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    ABSTRACT: Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology. The study included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3 (low). In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%. USE may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.
    The Journal of clinical endocrinology and metabolism 12/2010; 95(12):5274-80. · 6.50 Impact Factor
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    ABSTRACT: Bariatric surgery allows stable body weight reduction in morbidly obese patients. In presurgical evaluation, obesity-related co-morbidities must be considered, and a multidisciplinary approach is recommended. Precise guidelines concerning the endocrinological evaluation to be performed before surgery are not available. The aim of this study was to evaluate the prevalence of common endocrine diseases in a series of obese patients scheduled for bariatric surgery. We examined 783 consecutive obese subjects (174 males and 609 females) aged 18-65 years, who turned to the obesity centre of our department from January 2004 to December 2007 for evaluation before bariatric surgery. Thyroid, parathyroid, adrenal and pituitary function was evaluated by measurement of serum hormones. Specific imaging or supplementary diagnostic tests were performed when indicated. The overall prevalence of endocrine diseases, not including type 2 diabetes mellitus, was 47.4%. The prevalence of primary hypothyroidism was 18.1%; pituitary disease was observed in 1.9%, Cushing syndrome in 0.8%, while other diseases were found in less than 1% of subjects. Remarkably, the prevalence of newly diagnosed endocrine disorders was 16.3%. A careful endocrinological evaluation of obese subjects scheduled for bariatric surgery may reveal undiagnosed dysfunctions that require specific therapy and/or contraindicate the surgical treatment in a substantial proportion of patients. These results may help to define the extent of the endocrinological screening to be performed in obese patients undergoing bariatric surgery.
    Obesity Surgery 10/2010; 21(1):54-60. · 3.10 Impact Factor
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    ABSTRACT: To evaluate the risk of papillary thyroid carcinoma (PTC) at fine-needle aspiration (FNA) cytology in 34 120 patients. False positive and false negative rates of FNA cytology were 1.2 and 1.8% in comparison with the histology in 3406 nodules from 3004 patients who underwent surgery. PTC (901 cases) was more frequent in solitary nodule (SN; 446/13 549, 3.3%) than in multinodular goiter (MNG; 411/19 923, 2%, chi(2)=48.8; P<0.0001), and in males (209/6382, 3.3%) than in females (648/26 945, 2.40%, chi(2)=15.58; P<0.0001). PTC prevalence in Graves' disease (GD; 13/286, 4.5%) and Hashimoto's thyroiditis (HT; 31/508, 6.1%) was higher than in SN, this difference being significant in HT (chi(2)=8.7; P=0.003), but not in GD (chi(2)=1.6; P=0.2). Using the multiple logistic regression analysis, independent risk predictors of PTC were determined, which were younger age (odds ratio (OR)=0.97, confidence interval (CI) 0.964-0.974; P<0.0001), male gender (OR=1.44, CI 1.231-1.683; P<0.0001), and SN versus MNG (OR=0.63, CI 0.547-0.717; P<0.0001). The individual risk predictivity was highly improved by including serum TSH in the prediction model, which was measured at FNA in 11 919 patients. A cytology suspicious or indicative of PTC was associated with younger age, male gender, and solitary versus multiple nodularity. These clinical parameters, together with serum TSH, may allow formulation of an algorithm that could be usefully applied to predict the risk of PTC in individual patients when cytology does not give a diagnostic result.
    European Journal of Endocrinology 04/2010; 162(4):763-70. · 3.14 Impact Factor
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    ABSTRACT: The risk of papillary thyroid cancer (PTC) is related to serum TSH, and the development of thyroid autonomy by reducing TSH levels decreases the frequency of PTC in patients with nodular goiter. Our aim was to investigate the effect of L-thyroxine (LT(4)) on the frequency of PTC diagnosed by cytology in a large series of patients with nodular goiter untreated (n=20 055) or treated with L-T(4) (n=7859). L-T(4)-treated patients with respect to untreated patients presented significantly lower serum TSH (median, interquartile range: 0.30 muU/ml, 0.08-0.62 microU/ml versus 0.70 muU/ml, 0.38-1.14 muU/ml; P<0.0001) and prevalence of PTC (3.2 vs 5.1%; P<0.0001). The frequency of PTC was closely related to serum TSH, with it being lowest in patients with TSH below the normal range (<0.4 muU/ml; 189/10 059, 1.9%) and highest in patients with TSH above the normal range (>3.4 muU/ml; 21/127, 16.5%), also showing a progressive increase from the lower to the upper quartile of normal range. A significantly higher proportion of L-T(4)-treated patients (6650/7859, 84.6%) had serum TSH below the median (0.90 muU/ml) with respect to untreated patients (12,599/20,055, 62.8%; chi(2) P value <0.0001), with it being included in the range of TSH associated with a lower frequency of PTC. The relationship between serum TSH and frequency of PTC was unrelated to the type of nodularity (solitary versus multinodular) and was not age dependent. In conclusion, patients with nodular goiter, treatment with L-T(4) is responsible for the reduction of serum TSH and is associated with a decreased frequency of PTC.
    Endocrine Related Cancer 01/2010; 17(1):231-9. · 5.26 Impact Factor
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    ABSTRACT: SUMMARY BACKGROUND Thyroid nodular disease is common, especially in iodine-deficient areas, whereas the incidence of thyroid cancer, while steadily increasing in the past three decades, is relatively low, comprising approximately 1% of all new malignancies . The risk is quite low that a solitary thyroid nodule or multiple nodules within a goiter harbor clinically evident malignancies . Still, the risk of malignancy is higher in patients who have thyroid surgery for compressive symptoms, hyperthyroidism, or Graves' disease, during which occult thyroid cancers are often discovered by serendipity . Fine- needle aspiration biopsy (FNAB) of thyroid nodules has become the main source of distinguishing malignant from benign nodules . While FNAB has reduced surgical intervention by 25% and has increased the yield of cancer in surgical specimens to more than 30%, approximately 20 to 25% of FNAB cytology specimens are nondiagnostic or indeterminate, and a few (5%) have false positive or false negative cytology results . Thus, some patients still may undergo unnecessary surgery on the basis of FNAB . The objective of this study was to evaluate the risk of papillary thyroid carcinoma (PTC) in FNAB cytology in a cohort of 34,120 patients .
    01/2010;
  • T Rago, P Vitti
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    ABSTRACT: A firm or hard consistency is associated with an increased risk of malignancy in thyroid nodules. Ultrasound (US) elastosonography is a new powerful diagnostic technique that assesses hardness as indicator of malignancy that was recently applied in the diagnostic approach of nodular thyroid disease. The basic principle of elastosonography is that tissue compression produces strain (displacement), that is less in hard than in soft tissues and is scored measuring the degree of distortion of US beam under the application of an external force, during the examination. The US elastogram is displayed over the B-mode image in a colour scale that corresponds to tissue elasticity. The US elastosonography performed on selected series of patients has displayed a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 98%. The predictivity of US elastographic measurement was independent from the nodule size, high sensitivity and specificity being observed also in nodules <1 cm. These data were also confirmed by other authors in smaller cytological series. Available data suggest that predictivity of US elastosonography is maintained in indeterminate lesions. Conventional US maintains a pivotal importance to define which nodules are suitable for elastographic characterization. Indeed, nodules in which US reveals the presence of calcified shell and cystic nodules have to be excluded from the US elastographic evaluation. Another limitation is that the nodule to be examined must be clearly distinguishable from other nodules present in the thyroid. Thus, multinodular goiters with coalescent nodules are not suitable for this analysis. US elastosonography seems to have a great potential as a new tool for the diagnosis of thyroid cancer, especially in nodules with indeterminate cytology.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 10/2009; 53(5):455-64. · 1.92 Impact Factor
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    ABSTRACT: Higher TSH values, even within normal ranges, have been associated with a greater risk of thyroid malignancy. The relationship between TSH and papillary thyroid cancer (PTC) has been analyzed in 10 178 patients submitted to fine needle aspiration of thyroid nodules with a cytology of PTC (n=497) or benign thyroid nodular disease (BTND, n=9681). In 942 patients, submitted to surgery (521 from BTND and 421 from PTC), the histological diagnosis confirmed an elevated specificity (99.6%) and sensitivity (98.1%) of cytology. TSH levels were significantly higher in PTC than in BTND both in the cytological and histological series and also in patients with a clinical diagnosis of multinodular goiter (MNG) and single/isolate nodule (S/I). A significant age-dependent development of thyroid autonomy (TSH <0.4 microU/ml) was observed in patients with benign thyroid disease, but not in those with PTC, diagnosed both on cytology and histology. In patients with MNG, the frequency of thyroid autonomy was higher and the risk of PTC was lower compared to those with S/I. In all patients, the presence of thyroid auto-antibodies (TAb) was associated with a significant increase of TSH. However, both in TAb positive and TAb negative patients TSH levels were significantly higher in PTC than in BTND. Our data confirm a direct relationship between TSH levels and risk of PTC in patients with nodular thyroid diseases. Thyroid autonomy conceivably protects against the risk of PTC, while thyroid autoimmunity does not play a significant role.
    Endocrine Related Cancer 07/2009; 16(4):1251-60. · 5.26 Impact Factor