Pierpaolo Trimboli

Ultrasound Sensitivity for Thyroid Malignancy Is Increased by Real-Time Elastography: A Prospective Multicenter Study

CONTEXT Thyroid nodules are selected for biopsy on the basis of clinical and ultrasound (US) findings. Ultrasonography detects nodules at risk of malignancy, but its diagnostic accuracy does not rule out with certainty the possibility of cancer in lesions without suspicious findings. OBJECTIVE The objective of the study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in thyroid nodules and to assess the improvement provided by combination of RTE, B-mode US, and color flow Doppler (CFD). DESIGN This was a prospective multicenter study. PATIENTS A consecutive series of 498 thyroid nodules was blindly evaluated by US, CFD, and RTE before biopsy or surgery. Nodules were classified at RTE by four-class color scale. Patients with benign cytology underwent follow-up over 12 months, whereas patients with indeterminate, suspicious, or malignant cytology were surgically treated. RESULTS At follow-up, 126 nodules were malignant and 372 benign. RTE classes III-IV showed 81% sensitivity and 62% specificity. The presence of at least one US risk factor (hypoechogenicity, microcalcifications, irregular margins, intranodular vascularization, and taller than wide shape) had 85% sensitivity and 91% negative predictive value. When RTE was combined with US, the presence of at least one of the six parameters had 97% sensitivity and 97% negative predictive value, with an odds ratio of 15.8 (95% confidence interval 5.7-43.8). CONCLUSIONS RTE is a valuable tool for detecting malignant thyroid lesions with a sensitivity similar to traditional US and CFD features. By adding RTE evaluation, the sensitivity for malignancy of US findings is markedly increased and the selection of nodules that do not need cytology is made more reliable.

Unstimulated Highly Sensitive Thyroglobulin in Follow-up of Differentiated Thyroid Cancer Patients: A Meta-Analysis

CONTEXT Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse. OBJECTIVE Our objective was to conduct a meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up. DATA SOURCES We performed a comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013. STUDY SELECTION Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were 1) articles not within the field of interest; 2) reviews, letters, or conference proceedings; 3) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5) insufficient data to reassess diagnostic performance of basal serum hsTg. DATA EXTRACTION Information was collected concerning basic study data, patient characteristics, and technical aspects. For each study, the number of true-positive, false-positive, true-negative, and false-negative findings for basal hsTg, considering stimulated Tg measurement as a reference standard, were recorded. DATA SYNTHESIS Pooled data demonstrated that the negative predictive value of hsTg was 97% and 99% considering a stimulated Tg measurement >1 ng/mL and >2 ng/mL as cutoffs for positivity, respectively. Despite the high pooled sensitivity of basal hsTg, the pooled specificity, accuracy, and positive predictive value were insufficient to completely substitute for a stimulated Tg measurement. CONCLUSIONS Basal hsTg measurement has a very high negative predictive value but an insufficient positive predictive value for monitoring DTC patients. Therefore, a Tg stimulation test can be avoided in patients with an undetectable basal hsTg, whereas a stimulated Tg measurement should be considered when hsTg levels are detectable.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta‐analysis

The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine‐needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta‐analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates.

The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration

BackgroundThe reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer.MethodsSeventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA.ResultsFive patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%). In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the FNA group were not initially diagnosed because of false negative (N = 1), indeterminate (N = 2) or not adequate (N = 1) samples.ConclusionsCNB can reduce the false negative and inconclusive results of conventional FNA and should be considered a first-line method in assessing solid thyroid nodules at high risk of malignancy.

Medullary thyroid cancer diagnosis: An appraisal

Since its first description in 1951, a timely diagnosis of medullary thyroid carcinoma (MTC) may represent a diagnostic challenge in clinical practice. Several contributions have been addressed to the treatment and follow‐up of MTC, but review articles focused on the diagnostic problems of this cancer in clinical practice are sparse. As a delayed diagnosis and an inadequate initial treatment may severely affect the prognosis of this thyroid malignancy, the appropriate use and the correct interpretation of the available diagnostic tools for MTC are of crucial importance. The purpose of the present article is to provide an easy‐to‐use guide reviewing the main issues of MTC diagnosis: (1) basal serum calcitonin; (2) stimulated serum calcitonin; (3) additional serum markers for MTC; (4) ultrasound and other imaging techniques; (5) fine‐needle aspiration (FNA) cytology; (6) calcitonin measurement on FNA washout; (7) rearranged during transfection (RET) mutations; and (8) scope of the problem.

Comparison of Malignancy Rate in Thyroid Nodules with Cytology of Indeterminate Follicular or Indeterminate Hürthle Cell Neoplasm

BACKGROUND Thyroid nodules that are read on cytology as follicular or Hürthle cell neoplasms (FN and HN, respectively) and indeterminate for malignancy require surgery to differentiate benign from malignant nodules. We analyzed FN and HN with indeterminate cytology to determine if there were differences in the rate and types of thyroid malignancy and if the rate of thyroid malignancy was influenced by age or sex. METHODS We analyzed 463 nodules with an indeterminate cytological diagnosis of FN and 140 nodules with an indeterminate cytological diagnosis of HN. The histopathological diagnosis after thyroidectomy was the method for establishing the diagnosis and type of malignancy. RESULTS For the entire series of 603 patients there were 106 (17.6%) with thyroid cancer; 80 of these had a cytology reading of FN and 26 had HN. Extrathyroidal invasion in the grouped HN and FN patients who had papillary thyroid carcinoma (PTC) was more common in females than in males (62% vs. 25 %, p < 0.05). The rate of thyroid cancer was similar in FN (17.3%) and HN (18.6%). The rate of Hürthle cell thyroid cancer was significantly higher in HN than in FN (5.0% vs. 0.7%, p < 0.01) and the rate of the oncocytic variant of PTC was also significantly greater in HN compared to FN nodules (23.1% vs. 1.7%, p < 0.05). The rate of follicular thyroid carcinoma was almost identical in patients with HN and FN (19.2% vs. 18.8 %). CONCLUSIONS There is little difference in the rate of malignancy between thyroid nodules with a cytological reading of FN indeterminate for malignancy and HN indeterminate for malignancy but there is a difference in the types of thyroid cancers in these groups. Hürthle cell thyroid cancer and the oncocytic variant of PTC is more common in nodules with an HN indeterminate for malignancy cytology reading than in nodules with a FN indeterminate for malignancy cytology reading. Since Hürthle cell thyroid cancer and the oncocytic variant of PTC are more aggressive than other thyroid cancers, it is likely that patients with an HN indeterminate for malignancy cytology will, as a group, have more aggressive thyroid cancers than those with an FN indeterminate for malignancy cytology.

Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study

Only few studies analysed the capability of cytology in detecting medullary thyroid cancer (MTC), and they reported a low accuracy of this diagnostic technique. Recently, calcitonin (CT) measurement in aspiration needle washout (FNA‐CT) of thyroid and neck lesions has been reported as a sensitive tool for MTC. The aim of this study is to compare the sensitivity of FNA‐CT and cytology in detecting MTC and to assess a cut‐off value of FNA‐CT for clinical practice.

Diagnostic value of thyroglobulin assay in cervical lymph node fine-needle aspirations for metastatic differentiated thyroid cancer.

Purpose of review Differentiated thyroid cancers (DTCs) have generally an indolent behavior. However, in a minority of these patients cervical metastasis at diagnosis or recurrence during follow-up may occur. Then, in suspicious neck lymph nodes fine-needle aspiration (FNA) is warranted. Thyroglobulin measurement in needle washout fluids (FNA-Tg) since its first description has been reported to increase the diagnostic accuracy of cytology in neck lymph nodes suspicious for metastatic DTC. Recent findings Recent literature suggests that FNA-Tg can substitute conventional cytology and, in turn, simplifies clinical management of DTC patients. However, because of the large difference between these clinical studies, the data are sparse. Thus, neither procedures nor assay method for FNA-Tg have been standardized. Summary FNA-Tg measurement is the more accurate tool to detect neck recurrences and metastases from DTC. Providing strict standardization of preanalytical and analytical phase, FNA-Tg may suffice to confirm or exclude neck DTC recurrence in patients with concurrent well differentiated papillary cancer type, suspicious neck ultrasound findings and increased serum thyroglobulin after thyroidectomy. On the contrary, FNA-Tg accuracy increases by adding cytological examination when FNA is performed before thyroidectomy, in patients with more aggressive histological types, and if low-undetectable serum thyroglobulin and/or positive serum antithyroglobulin antibodies occur.

Analysis of clinical, ultrasound and colour flow‐Doppler characteristics in predicting malignancy in follicular thyroid neoplasms

Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool in the evaluation of thyroid nodules because of its high sensitivity, specificity and accuracy. However, while FNAC is very reliable in detecting papillary thyroid carcinomas (PTC) and anaplastic thyroid carcinomas, follicular neoplasms (FN) represent the grey zone in which cytology cannot discriminate malignant from benign tumours. 1 Consequently, in presence of nodules cytologically classified as FN, thyroidectomy is usually required and the histological evaluation reveals that about 80% are benign lesions. Thus, identification of parameters associated with malignancy is needed. In this context, several studies have focused on clinical, ultrasonographic and cytological aspects, with controversial results. 2,3

Liquid and softgel levothyroxine use in clinical practice: state of the art.

Levothyroxine is recognized as the treatment of choice for hypothyroidism. So far, the tablet levothyroxine has been the formulation almost exclusively used, even though an optimal daily dose of levothyroxine has been unsuccessfully sought and a consensus not achieved. Due to progressive use of a more individually tailored levothyroxine dose, increasing evidence has instead displayed that many gastrointestinal disorders, polypharmacy, and food interference may raise the daily levothyroxine requirement. In recent years, alternative levothyroxine formulations have become available and have rapidly gained attention because of their pharmacokinetic properties. This study aims to provide an overview regarding the use of softgel capsule and/or liquid levothyroxine solution while performing a review of published studies about such topic. A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Google Scholar databases has been conducted to find published articles on this topic. The search algorithm was based on the combinations of the following terms: “oral solution” or “soft gel” or “liquid”, and “levothyroxine”. The computer search resulted in 75 articles; through a critical review of such titles and abstracts and a screening of their references lists, the review included 18 original articles relating to 800 patients treated with alternative formulations. Despite some limits, the results obtained using softgel and liquid levothyroxine were consistent with each other. In selected categories of levothyroxine-treated patients (pediatric, suffering from hypo-achlorhydria, polypharmacy, undergone bariatric surgery, fed through enteric tube) these new formulations have shown promising attributes in improving a treatment that needs to be individually tailored.