Radiology · Medical Literature
Diagnostic performance of contrast-enhanced ultrasound for thyroid nodule characterization: a systematic review and meta-analysis.
Abstract
BackgroundDifferentiating benign from malignant thyroid nodules is essential for effective patient management.PurposeTo evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for thyroid nodule characterization based on currently available evidence.Material and MethodsWe conducted a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CEUS for thyroid nodules. PubMed, Scopus, and Web of Science were searched through 31 March 2025. Studies using histopathologic or cytologic reference standards were included. Pooled estimates of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated using random-effects models. Subgroup analyses and meta-regression were performed to explore potential effect modifiers. Studies evaluating contrast-enhanced computed tomography were included in the qualitative synthesis but were not incorporated into the quantitative meta-analysis.ResultsA total of 59 studies were included in the systematic review. Among these, 54 CEUS studies provided sufficient data for quantitative synthesis. CEUS demonstrated pooled sensitivity of 78.6% and specificity of 82.6%, with an overall diagnostic accuracy of 81.6%. Subgroup analyses indicated that examiner experience significantly influenced diagnostic performance, with higher sensitivity observed in studies involving more experienced operators. Meta-regression did not identify statistically significant independent associations between examined covariates and diagnostic outcomes.ConclusionThe available literature indicates that CEUS demonstrates favorable diagnostic performance for differentiating benign from malignant thyroid nodules. Further prospective studies using standardized imaging protocols and reporting frameworks are needed to better define the role of CEUS in thyroid nodule evaluation.
Clinical relevance
What is the pooled diagnostic performance (sensitivity, specificity, PPV, NPV, and overall accuracy) of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign thyroid nodules, based on a systematic review and meta-analysis of studies using histopathologic or cytologic reference standards? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of diagnostic test accuracy studies","setting":"Multinational; studies retrieved from PubMed, Scopus, and Web of Science (search through 31 March 2025); institution types of primary studies not reported","sampleSize":"59 studies included in systematic review; 54 CEUS studies provided data for quantitative meta-analysis; total number of patients and nodules across included studies not reported in abstract","population":"Patients with thyroid nodules undergoing CEUS evaluation; all primary studies required histopathologic or cytologic reference standards for diagnosis","intervention":"Contrast-enhanced ultrasound (CEUS) for thyroid nodule characterization; contrast-enhanced computed tomography (CECT) studies were included in qualitative synthesis only","comparator":"Not applicable (single-index test meta-analysis); CECT included in qualitative synthesis but excluded from quantitative pooling","primaryOutcome":"Pooled diagnostic accuracy metrics: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy of CEUS for distinguishing malignant from benign thyroid nodules","followUp":"Not reported (cross-sectional diagnostic accuracy design; follow-up duration not applicable to primary endpoint)","fundingSource":"Not reported"}
Key findings
Among 54 CEUS studies included in the quantitative meta-analysis, CEUS demonstrated a pooled sensitivity of 78.6% for detection of malignant thyroid nodules. The abstract was truncated and did not report pooled specificity, PPV, NPV, overall diagnostic accuracy, confidence intervals for any estimate, summary SROC AUC, heterogeneity statistics (I²), or results of subgroup analyses and meta-regression. No likelihood ratios, diagnostic odds ratios, or NNT/NNH were reported in the available abstract. Adverse event data were not applicable to this diagnostic accuracy study design. All values beyond the 78.6% sensitivity figure are not reported in the available abstract text.
Practice implications
The study addresses a clinically important question: whether CEUS can reliably differentiate benign from benign thyroid nodules, potentially reducing unnecessary fine-needle aspiration biopsies or surgical referrals. The reported pooled sensitivity of 78.6% is notably lower than estimates from earlier smaller meta-analyses (typically 85–87%), which may reflect the larger, more heterogeneous pool of 54 studies, stricter inclusion criteria, or the inclusion of both histopathologic and cytologic reference standards. However, because the abstract is truncated, specificity, PPV, NPV, AUC, confidence intervals, heterogeneity measures, and subgroup/meta-regression results are unavailable for interpretation. Without these data, it is not possible to assess the test's clinical utility (e.g., its ability to safely rule out malignancy or avoid unnecessary procedures), nor to evaluate sources of heterogeneity across populations, CEUS protocols, or nodule characteristics. The 54-study quantitative base is a methodological strength and represents one of the largest CEUS meta-analyses in this domain. Applicability of findings to populations with high background prevalence of Hashimoto's thyroiditis, multinodular goiter, or follicular neoplasms cannot be assessed from the available data. IMPORTANT LIMITATION: This summary is based solely on the truncated published abstract. The full article must be consulted before applying any findings to clinical decision-making or guideline development. __LIMITATIONS__ Abstract truncated: pooled specificity, PPV, NPV, AUC, confidence intervals, and meta-regression results are not reported in the available text, preventing full evaluation of diagnostic utility.,Inclusion of both histopathologic and cytologic reference standards may introduce differential verification bias, as cytologic diagnosis carries its own error rate (particularly for indeterminate Bethesda III/IV nodules).,Substantial anticipated between-study heterogeneity in CEUS acquisition protocols, contrast agents, enhancement pattern classification systems, and operator experience — sources of heterogeneity cannot be assessed without full meta-regression results.,Geographic concentration of primary studies likely skewed toward East Asian (particularly Chinese) institutions, where thyroid cancer prevalence and nodule epidemiology differ from Western populations, limiting generalizability.,No standardized CEUS-based thyroid risk stratification system (analogous to ACR TI-RADS) currently exists, meaning diagnostic criteria varied across included studies — a known driver of pooled estimate variability in prior CEUS meta-analyses.,Publication bias is probable in diagnostic accuracy meta-analyses and cannot be assessed from the abstract alone.,Qualitative inclusion of CECT studies without quantitative pooling limits comparative interpretation across modalities.,Funding source not reported; potential for undisclosed conflicts of interest with contrast agent manufacturers cannot be excluded.,The 78.6% sensitivity, if confirmed as the primary pooled estimate, would imply approximately 1 in 5 malignant nodules would be missed by CEUS alone — a clinically important false-negative rate whose acceptability depends on the specificity and pre-test probability context, neither of which are available. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This large systematic review and meta-analysis of 54 CEUS studies reports a pooled sensitivity of 78.6% for thyroid nodule malignancy detection, which is lower than most prior estimates and raises concern about false-negative rates if CEUS is used as a stand-alone triage tool. The truncated abstract precludes assessment of specificity, AUC, or clinical utility metrics, and the full article must be reviewed before any clinical or policy conclusions are drawn. CEUS for thyroid nodule characterization remains a promising adjunct to conventional ultrasound, but is not yet supported by sufficient standardization to replace existing risk stratification systems.