Value of the New Elastography Technique using Acoustic Radiation Force Impulse in Differentiation between Hashimoto’s Thyroiditis and Graves’ Disease

INTRODUCTION

Both Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are autoimmune diseases of thyroid gland.^[1] GD is a genetic disorder and is the most common cause of hyperthyroidism and characterized by circulating thyroid-stimulating hormone receptor autoantibodies with thyroid-stimulating activity.^[2] On the other hand, HT is the most common cause of hypothyroidism.^[3,4] Pathologically, the disease is characterized by marked lymphocytic infiltration of the thyroid.^[5]

Differentiation of GD from HT may sometimes be difficult on the basis of clinical and laboratory findings.^[1]. Ultrasonography is a well-established technique in the diagnosis of thyroid diseases.^[6] However, recently, Pishdad et al.^[7] reported low sensitivity of sonography in differentiation between GD and HT and he concluded that ultrasound alone cannot differentiate between the two diseases due to marked overlapping in sonographic picture.

It was reported in the literature that increased arterial flow in the thyroid was not only seen in GD with hyperthyroidism but was also seen in HT with hypothyroidism.^[8] Thyroid gland hypervascularity is seen whatever the functional state and the level of thyroid hormones.^[9-12] Hence, color Doppler ultrasound may fail to differentiate between the two diseases with confidence.

Elastography is a relatively new technique measuring tissue stiffness and elasticity.^[13,14] Strain elastography and shear wave elastography (SWE) are the two basic types of elastography. Strain elastography uses external force for the prediction of tissue stiffness.^[15] SWE utilizes acoustic radiation force impulse (ARFI) imaging to measure the shear wave velocity (SWV) of the target area, which is considered quantitative operator independent. The SWV is calculated bythe production of small (1–10 mm) localized tissue displacements using short duration acoustic pulse; this tissue displacement results in shear wave dissemination, which is tracked and measured as SWV (m/s).^[16] Virtual touch tissue imaging quantification (VTIQ) (VTQ) is the name given to the new technique that quantifies tissue elasticity by calculating the SWV.^[17]

In the current study, we evaluated the role and accuracy of SWE in the differentiation between GD and HT, in comparison with the B-mode ultrasound and color Doppler ultrasound.

MATERIALS AND METHODS

RESULTS

In total, 130 patients (18 male, 112 female; mean age: 37 years; age range: 18–52 years) were included in the study. Sixty-five patients with HT (mean age, 41 years), 35 patients with GD (mean age, 33 years), and 30 healthy controls (median age, 29 years) were examined. The groups were similar in terms of age and sex. No significant difference in the mean age between the different groups (P = 0.61). The GD group included 22 patients was non treated and 13 patients received previous treatment. The HT group was divided into early disease (18 patients) and chronic disease (47 patients) (based on history, clinical examination, and laboratory findings).

Shear wave elastography

The mean SWV was 2.61 ± 0.32 m/s in the GD group (range: 2.1–3.21 m/s), 2.85 ± 0.52 m/s in the HT group (range: 2.31–3.82 m/s), and 1.75 ± 0.37 m/s in the control group (range: 1.24–2.36 m/s) [Tables 5 and 6]. The mean SWVs in the GD and HT groups were significantly higher than that in the control group (P < 0.001). The mean SWV in the HT group was higher than that in the GD group (P = 0.03) [Figures 1-5].

Table 5 Results of shear wave elastography.

	Control	HT	GD	P value between normal and the two groups	P value between HT and GD
SWV (m/s)				<0.001	0.03
Mean	1.75±0.37	2.85±0.52	2.61±0.32
Range	1.24–2.36	2.3–3.8	2.1–3.21
Elastograpram				0.15	0.025
Pattern I	19 (63.3%)	9 (13.8%)	9 (25.7%)
Pattern II	11 (36.7%)	25 (38.4%)	16 (45.7%)
Pattern III		31 (47.7%)	10 (25.6%)
Pattern IV			-

HT: Hashimoto’s thyroiditis, GD: Graves’ disease

Table 6 Shear wave velocity between different groups subgroups (m/s).

SWV (m/s)	HT		GD
	Early HT (n=18)	Chronic HT (n=47)	Non-treated (n=22)	Treated (n=13)
Mean	2.31±0.24	2.63±0.56	2.31±0.23	2.49±0.41
Range	2.3–2.7	2.34–3.8	2.1–2.6	2.3–3.21

Statistically significant difference between chronic HT and early HT (P<0.01) and non-treated GD (P<0.01), and no significant difference between treated and untreated GD and early HT (P=0.72 and 0.34, respectively). There was a significant difference between treated and non-treated GDs (P=0.01). HT: Hashimoto’s thyroiditis, GD: Graves’ disease, SWV: Shear wave velocity

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Figure 1

Patient with normal thyroid gland: (a) Grayscale ultrasound showing smooth homogenous isoechoic echopattern. (b) Color Doppler: Type I pattern. (c) Shear wave velocity 1.67 m/s (depth 1.5 cm).

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Figure 2

Patient with Hashimoto’s thyroiditis: (a) Grayscale ultrasound showing hypoechoic heterogeneous echopattern. (b) Color Doppler: Type II pattern. (c) Elstogram reveals type III pattern. (d) Shear wave velocity 2.81 m/s (depth 1.9 cm).

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Figure 3

Patient with Hashimoto’s thyroiditis: (a) Grayscale ultrasound showing hypoechoic heterogeneous echopattern with miconodularity. (b) Color Doppler: Hypervascularity with Type II pattern. (c) Shear wave velocity 3.28 m/s (depth 1.3 cm).

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Figure 4

Patient with Graves’ disease: (a) Grayscale ultrasound showing hypoechoic echopattern. (b) Color Doppler: Type III pattern (thyroid inferno). (c) Elstogram reveals type II pattern. (d) Shear wave velocity 2.36 m/s (depth 1.5 cm).

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Figure 5

Patient with Graves’ disease: (a): Hypoechoic parenchyma with marked hypervascularity. (b): Shear wave velocity = 3.16 m/s (depth = 1.6 cm).

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In the GD group, the mean SWV of patients who were and were not undergoing antithyroid therapy was 2.31 ± 23 m/s and 2.49 ± 41 m/s, respectively (P < 0.01). Patients who were undergoing antithyroid therapy showed a significantly higher SWV than patients who were not undergoing antithyroid therapy.

In the HT group, the mean SWV of patients with early disease and chronic disease was 2.31 ± 0.24 m/s and 2.63 ± 0.56 m/s, respectively. The difference was statistically significant (P < 0.01).

There was no significant difference between treated and untreated GD and early HT (P = 0.72 and 0.34, respectively).

Real-time elastography was studied in the current study. No lobes showed Pattern IV. Patter III was seen in 47.7% of patients with HT and 25.6% of patients with GD (P = 0.025).

Furthermore, we tried to correlate the SWV and the different sonographic and color Doppler parameters [Table 7]. High velocities were seen in lobes with coarse echotexture, nodularity, and fine septations (P < 0.05, < 0.01, and < 0.01, respectively), which would probably correlate with the degree of fibrosis.

Table 7 Correlation between sonogaphic findings and SWV.

Ultrasound	SWV	P value between HT and GD groups
Echogenicty
Iso/mildly hypoechoic	2.42±0.72	0.43
Markedly hypoechoic	2.62±0.61
Echotecture		<0.05
Fine	1.98±0.52
Coarse	2.82±0.61
Size		0.38
<1 cm	2.32±0.22
1–2 cm	2.02±0.41
>2 cm	2.58±0.52
Echogenic septations		<0.01
Yes	2.87±0.32
No	2.31±0.51
Nodularity		<0.01
Yes	2.98±0.47
No	2.62±0.61
Color flow pattern		0.34
Hypervascular (Patterns II and III)	2.68±0.41
Non hypervascular (Patterns 0 and I)	2.52±0.23

GD: Graves’ disease, SWV: Shear wave velocity, HT: Hashimoto’s thyroiditis

DISCUSSION

This study confirms that the SWV of the thyroid glands with autoimmune thyroiditis (both GD and HT) is higher than normal glands, and the SWV increases with the degree of fibrosis. Although the SWV differs between the GD and the HT, there is overlap in velocities between the two groups.

The ARFI is an emerging technique providing information about tissue stiffness. It contains two modes, VTI and VTQ. They provide the information about tissue elasticity qualitatively and quantitatively, respectively.^[20]

Stiffness or elasticity is an important physical parameter of biological tissue; in GD, elasticity is increased due to diffuse hypertrophy and hyperplasia of follicular cells, colloid depletion, and lymphoid infiltration as well as hypervascularity.^[21] On the other hand, lymphocytic infiltration and fibrosis occurring in the thyroid gland of HT increase the stiffness of the thyroid tissue.^[15] Correspondingly, in the current study, the mean SWVs in the GD and HT groups were significantly higher than that in the control group (P < 0.001); this objective index might make the sonographer more confident in making developmental trauma disorder diagnosis. Nevertheless, our findings showed that although there was statistically significant difference between the SWVs in both HT and GD, there was marked overlapping between the two groups, making differentiation between the two groups unreliable.

In the current study, the mean SWV was 2.61 ± 0.32 m/s in the GD group (range: 2.1–3.21 m/s), 2.85 ± 0.52 m/s in the HT group (range: 2.31–3.82 m/s), and 1.75 ± 0.37 m/s in the control group (range: 1.24–2.36 m/s). The higher elasticity in diffuse thyroid disease is in agreement with previous studies. Two studies using strain ratios done by Ruchala et al.^[22] and Menzilcioglu et al.^[23] found higher strain ratios in diffuse thyroid disease than control group and were compatible with our study. Hekimoglu et al.^[14] found SWV in control group (1.63 ± 0.12 m/s) which is close to our results (1.75 ± 0.37 m/s) and they found significantly higher velocity in the group of chronic autoimmune thyroiditis than the control group. Furthermore, Fukuhara et al.^[24] compared SWVs between patients with CAT and a healthy control group using SWE by ARFI.^[11] They found that the mean SWV in patients with CAT was 2.47 ± 0.57 m/s, which was significantly higher than that in the control group (1.59 ± 0.41 m/s). All these studies were in agreement with the current study that the SWV of the patient group (HT + GD) is significantly higher than that of the control group.

The higher SWV in HT than GD is not in agreement with two previous reports. Sporea et al.^[25] compared the SWV among 29 patients with GD, 22 patients with CAT, and 23 control subjects and found a significantly higher SWV in the GD than in the CAT group (2.82 ± 0.47 vs. 2.49 ± 0.48 m/s, respectively). Furthermore, Rahatli et al.^[26] in a study included 30 patients with HT and 22 patients with GD found patients with GD had significantly higher shear wave velocities than those with HT (P < 0.001). The difference between the results of current study and these two studies may be due to difference in number of the patients, and the fact that most of patients with HT included in the study was in chronic stage. On the other hand, our study is in agreement with previous study by Du et al.,^[27] who in a study included 74 patients with diffuse thyroid disease and 30 normal controls found higher SWV in HT than GD groups (2.72 ± 1.52 m/s, vs. 2.14 ± 0.31 m/s), but they reported the difference as statistically insignificant.

Liu et al.^[28] recently reported that the SWV is not suitable for differentiation between chronic thyroiditis and GD, and this assumption was confirmed by our study due to marked overlapping between the two groups. In the current study, the SWV was higher in treated GD than non-treated GD and there was a significant difference between chronic HT and early HT. The cause of the marked overlapping observed in our study probably related to the presence of cases with non-treated GD and early HT, both of them have similar SWV.

Kim et al.^[29] in a prospective study found that real-time thyroid US is useful in differentiating diffuse thyroid disease from normal thyroid parenchyma. In the current study, grayscale ultrasound proved accurate in differentiation between normal thyroid tissue and patients with HT or GD. However, regarding differentiation between HT and GD, there was a significant overlap between the sonographic pictures, with only coarse texture and nodularity were significantly more common in HT than GD. In the current study, we studied each ultrasound sign separately for the differentiation between HT and GD and found that most specific sign for diagnosing HT was nodularity (97.87%) and the most sensitive sign was coarse echotexture (81.54%). No sign had high sensitivity and specificity. These results are similar to the study by Pishdad et al.^[7] who reported that sonography had a high specificity (90.6%) but low sensitivity (47.1% and 45.2%) in the diagnosis and differentiation of GD and HT. Furthermore, Tabur et al. found that sonography has high specificity (90%) and low sensitivity (35%) in the diagnosis of thyroiditis.^[30] Furthermore, in the current study, coarse echotexture as a sign of HT had a sensitivity of 81.54%, a result similar to those of Patel et al., who found that diffuse heterogeneity had a sensitivity of 88.2% in the diagnosis of HT.^[31]

Furthermore, we tried to correlate the SWV and the different sonographic signs. High velocities were seen in lobes with coarse echotexture, nodularity, and fine septations (P < 0.05, < 0.01, and < 0.01, respectively). The presence of these signs may correlate with the degree of fibrosis. Our results are similar to those of Kandemirli et al.^[32] who in a study included that 85 patients found high elasticity values in that thyroid glands with marked hypoechoic, septations, and pseudonodular appearance.

In the current study, the color Doppler ultrasound showed a sensitivity of 91.8% and a specificity of 56.92% in the differentiation between HT and GD. The low specificity is due to the fact that 28 patients (43.1%) with HT showed hypervascularity (Pattern II), but the Pattern III was seen only in patients with GD. Increased vascularity in HT was previously reported.^[33,34] Ceylan et al.^[35] reported hypervascularity in 85% of their patients with HT. The presence of HT with hypervascularity leads to the low specificity of CDF in differentiation between HT and GD.

A limitation of this study is that biopsy and/or pathological specimens were not available for all patients; we relied mainly on the clinical and laboratory findings. The HT group and GD were unequal, with a larger number of early and chronic HT. No inter- and intra-observer data were tried. The last to mention is that only the GD and HT patients were involved. Other types of diffuse thyroid disease were not included in the study.

CONCLUSION

Quantitative and qualitative SWE is useful for diagnosing diffuse thyroid disease and evaluate the degree of fibrosis in autoimmune thyroiditis. However, ARFI techniques cannot alone differentiate between HT and GD reliably, but the addition of the technique to the conventional ultrasound and color Doppler ultrasound may facilitate the differentiation between the two diseases.