Diagnostic Role of Conventional Ultrasonography and Shearwave Elastography in Asymptomatic Patients with Diffuse Thyroid Disease: Initial Experience with 57 Patients

Thyroid ultrasonography (US) is a useful diagnostic tool in the evaluation of thyroid disease including thyroid nodules and diffuse thyroid disease (DTD).1-9 Hashimoto thyroiditis (HT) and Graves disease (GD) are included in DTD, and known US features of DTD are decreased or increased diffuse heterogeneous parenchymal echogenicity, a coarse echotexture, micronodulation, and scattered microcalcifications.4, 6, 7, 10, 11 US can provide valuable information on the course of subclinical hypothyroidism (SCH) and is also being used in the evaluation of DTD in patients with thyroid functional abnormality with thyroid autoantibodies such as thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb).5, 12, 13 Rosário, et al. analyzed 117 patients with SCH, and reported that both diffuse hypoechogenicity on US and the presence of TPOAb increase the risk of SCH developing into overt hypothyroidism.13

US elastography is a newly developed dynamic technique that provides information about tissue hardness by using a degree of distortion under the application of an external force or by using shear acoustic waves remotely induced by a focused ultrasonic beam.14-16 This method has been applied in the differentiation of benign and malignant thyroid lesions.14-17 Previous studies have demonstrated the diagnostic role of US used in DTD diagnosis.5, 7 However, to the best of our knowledge, no reports have shown the interobserver agreement of US or the diagnostic performances of shearwave elastography in DTD diagnosis. In this study, we investigated the role of conventional US and shearwave elastography in the diagnosis of asymptomatic patients with DTD.

Of the 57 patients, DTD was diagnosed in 22 patients using serum TPOAb or TBII. The mean age (50.1±11.6 years) of patients with DTD was older than that (49.7±10.4 years) of patients without DTD (p=0.887). Gender was not associated with DTD (p=0.639).

Reproducibility of conventional US observations was assessed between three observers who analyzed the same images. If only patients diagnosed with heterogeneous echogenicity by all three radiologists were considered, the generalized kappa value was 0.27, which means a fair degree of agreement.

The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the three radiologists were 18.2-59.1%, 57.1-94.3%, 57.9-66.7%, 44.4-71.4% and 62.5-69.0%, respectively, on conventional US for the identification of DTD. The A_zs were 0.52-0.585 on conventional US by three radiologists. Also, the A_zs were not statistically different between the three radiologists (p=0.387) (Table 1).

Table 1
Comparison of Diagnostic Performances for the Identification of Diffuse Thyroid Disease

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In the 35 (61.4%) patients consisting of the normal serology group, mean elasticity value was 23.4±10.8 kPa (range, 9.0 kPa to 54.5 kPa), and mean maximum elasticity value was 33.7±12.4 kPa (range, 11.0 kPa to 61.4 kPa). In the 22 (38.6%) patients of the DTD group, mean elasticity value was 24.1±10.0 kPa (range, 9.3 kPa to 53.6 kPa), and mean maximum elasticity value was 36.4±13.3 kPa (range, 15.1 kPa to 70.6 kPa) (Fig. 3). Although the mean values of mean and maximum elasticity were higher in patients with DTD than those in the normal group, there were no statistically significant differences between the two groups (p=0.802 and p=0.452).

Fig. 3
Box plots show elasticity values of normal and diffuse thyroid disease group. The central line of each box indicates the median and the asterisk (^*) indicates the mean elasticity value of each group, respectively. In the box plots of mean elasticity values (A) and maximum elasticity values (B), mean values of both mean and maximum elasticity were higher in patients with diffuse thyroid disease than those in the normal group. However, there were no statistically significant differences between the two groups (p=0.802 and p=0.452). DTD, diffuse thyroid disease; Mean, mean elasticity value; Maximum, maximum elasticity value.

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The cutoff values of shearwave elastography in DTD diagnosis were 27.6 kPa and 41.3 kPa using the mean and maximum elasticity, respectively. When using the mean elasticity value as a diagnostic criterion for DTD, the sensitivity and specificity were 40.9% and 82.9%, respectively. And when the maximun elasticity value was used as a diagnostic criterion for DTD, the sensitivity and specificity were 40.9% and 77.1%, respectively. Using the mean and maximum elasticity values as a diagnostic criteria for DTD, A_z values were 0.619 and 0.59, respectively (Table 1).

Shin, et al.5 indicated that thyroid US in SCH has a significant predictive value in treatment outcome, which was comparable to other well-known prognostic parameters such as TPOAb or high TSH levels. Recently, Kim, et al.7 prospectively evaluated the efficacy of thyroid US in the identification of asymptomatic DTD, and concluded that real-time thyroid US is useful in differentiating DTD from normal thyroid parenchyma in asymptomatic patients.

However, US is very subjective and dependent on the performer, which causes interobserver variability between examiners.22, 23 There are several reports on the interobserver agreement in US assessment of thyroid nodules.22-25 These reports conclude that if US is performed by experienced radiologists, relatively good agreement can be expected.22-24 However, there were no reports on the interobserver variability of US in the evaluation of echogenicity of the underlying thyroid gland. In this study, fair agreement with a kappa value of 0.26 was observed on the heterogeneous echogenicity on conventional US by three radiologists. This result showed that in diagnosing DTD, conventional US had poor reproducibility even when all images were simultaneously reviewed by three experienced radiologists. Also, diagnostic performances were variable among the observers. The sensitivity, specificity, accuracy, PPV, and NPV of three radiologists were 18.2-59.1%, 57.1-94.3%, 57.9-66.7%, 44.4-71.4% and 62.5-69.0% on conventional US when identifying DTD (Table 1). These results are different from those of other studies.7, 26 We speculate that the reasons for the differences7, 26 are different gold standards, patient populations, and interobserver variability among radiologists and pathologists. Especially, lymphocytic thyroiditis, of which the pathologic hallmark is lymphocytic infiltration, can show a certain pathologic spectrum, ranging from lymphocytic thyroiditis only to atrophic and eosinophilic change of thyroid cells with fibrosis.27 Depending on which stage of lymphocytic thyroiditis is being observed, there will be variations in diagnostic performances that will, in turn, affect the results. Therefore, the pathologic stage of disease is thought to be a important factor that decides what kinds of results US elastography obtains.

US elastography is based on the deformity formed by external compression,17 and the diagnostic performances of US elastography in general greatly depend on the quality of the freehand compression applied.28 Shearwave elastography is a technique which characterizes tissue structure by using shear acoustic waves remotely induced by a focused ultrasonic beam.29 Because shearwave elastography produces the radiation force in the probe, this may be more reproducible than conventional elastography, in which radiating force is produced by repetitive external compression by an operator.16 Furthermore, shearwave elastography shows quantitative tissue elasticity within a given region of interest.30 This reproducibility and quantitative information are very useful advantages of shearwave elastography. In the present study, we performed a quantitative measurement of thyroid tissue stiffness employing shearwave elastography, using mean and maximum elasticity values, and found that the mean values of mean and maximum elasticity in patients with DTD were not significantly different from those in the normal group (mean 24.1±10 kPa versus 23.4±10.8 kPa and maximum 36.4±13.3 kPa versus 33.7±12.4 kPa, respectively, p=0.802 and p=0.452) (Table 1). The specificity was higher when the mean elasticity value was used instead of the maximum elasticity value, however, the sensitivities of shearwave elastography were same when both indices were used in diagnosing DTD.

Our study has some limitations. First, the number of patients included in our study was relatively small to generalize reproducibility of conventional US and diagnostic performance of shearwave elastography. Future studies with larger populations are needed. Second, final diagnosis of the patients included in this study was based on the serologic levels of autoantibodies. False-negative and false-positive serologic results might have an effect on our results, nevertheless, they were not considered. Third, this study was a retrospective analysis to evaluate a reproducibility of conventional US between three observers using only static captured images. To resolve and validate our result, real time US might be helpful in further studies. Lastly, this study did not evaluate diagnostic performances of US and elastography according to pathologic spectrum of DTD. For example, hepatitis has variable US results, depending on liver fibrosis stage, because stiffness changes by stage.31 Thus, for a more insight, studies are needed on how US elastography results vary by pathologic stages of DTD to understand the full potential of its practical use. In conslusion, conventional US did not show a reliable interobserver agreement in the diagnosis of DTD. Although not statistically significant, shearwave elastography may provide additional information for the diagnosis of DTD. Therefore, larger prospective studies are needed to define the values of shearwave elastography in diagnosing DTD.