Sonographic Features of Diffuse Hashimoto Thyroiditis: Determining Sensitivity of Features and Predictors of Malignancy

Subjects

Patients at a single U.S. medical center were included in this IRB-approved study. All patients underwent total or subtotal thyroidectomy between January 2011 and June 2015 and had a pre-operative diagnostic thyroid ultrasound examination within 1 year before surgery. Patient demographics were obtained from the radiology and/or pathology reports including age and gender.

Pathologic analysis

Patients who had undergone complete or partial thyroidectomy, most commonly for diffuse thyroid disease (20/101), nodule or mass (65/101), toxic and non-toxic nodular goiter (10/101), hyperparathyroidism (3/101), or other cervical findings suspicious for malignancy (3/101) were included in the study if there was histopathologic evidence of HT/chronic lymphocytic thyroiditis. Surgical histopathology reports were reviewed to determine the presence and extent of malignancy.

Sonographic analysis

Pre-operative ultrasound examinations were performed by sonographers on staff at a single tertiary level hospital using 10 MHz or higher linear probe (Logiq 9, GE, Waukesha, WI, USA). These examinations were retrospectively reviewed by a radiologist, and five predetermined sonographic features were analyzed for evaluation of diffuse form of HT. Specifically, the thyroid parenchyma was evaluated for the presence or absence of diffuse hypoechoic echogenicity (defined as diffuse decreased parenchymal echogenicity compared with adjacent strap muscles), parenchymal heterogeneity (defined as coarse echotexture with areas of mixed echogenicity involving >50% gland volume), echogenic septations (defined as diffuse or geographic regions of linear echogenic bands), hypoechoic micronodularity (defined as diffuse pattern of numerous hypoechoic nodules up to 6 mm), and hypervascularity (Figures 1-5). Color Doppler examination of whole gland vascularity was performed utilizing pulse repetition frequency and color Doppler gain levels optimized to minimize aliasing in carotid artery and internal jugular vein. Vascularity was assessed based on visual scale per classification described by Schulz et al. with types 1–3 representative of variable hypervascular state (Table 1).^[6] All examinations were peer reviewed by a second radiologist and a standardized interpretation was established to assess and minimize interobserver variability. Sonographically, the presence of HT was defined as the presence of one or more of the five sonographic characteristics. Final dictated radiology reports of the examinations were reviewed by an investigator blinded to the sonographic analysis to assess for diagnostic concordance.

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Figure 1

Parenchymal heterogeneity. A 37-year-old female with chronic lymphocytic (Hashimoto) thyroiditis presented with enlarging thyroid nodule. Sagittal gray scale ultrasound image of the thyroid gland demonstrates diffusely heterogeneous echotexture.

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Figure 2

Hypoechogenicity. A 35-year-old female with Hashimoto thyroiditis presented with thyroid mass. Transverse gray scale ultrasound image of the thyroid gland illustrates the parenchyma is iso- to hypoechoic to the adjacent strap musculature (*).

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Figure 3

Hypoechoic micronodularity. A 49-year-old female with Hashimoto thyroiditis presented with neck fullness. Sagittal gray scale ultrasound image of the thyroid gland with diffusely scattered hypoechoic micronodules.

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Figure 4

Echogenic septations. A 45-year-old female with Hashimoto thyroiditis presented for evaluation of hypothyroidism. Sagittal gray scale ultrasound image of the thyroid gland reveals scattered hyperechoic linear bands throughout the parenchyma (arrow).

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Figure 5

Hypervascularity. A 57-year-old female with Hashimoto thyroiditis presented for follow-up evaluation of indeterminate thyroid nodule. Transverse color Doppler ultrasound image of the thyroid gland demonstrates diffusely increased vascularity throughout the parenchyma. Common carotid artery and internal jugular vein are seen adjacent to the thyroid gland.

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Statistical analysis

Mann–Whitney test was used in comparison of continuous variables and the Fisher’s exact test for the comparison of categorical variables. Regression analysis performed with Spearman correlation coefficients. Values are provided either as mean ± standard deviation (range) or percentage (95% confidence interval). In all analyses, P < 0.05 was taken to indicate statistical significance.

Sonographic features of diffuse HT

Well-recognized sonographic features of diffuse HT include a hypoechoic and enlarged thyroid gland with heterogeneous parenchyma containing echogenic septations and micronodules.^[8] Overall, the present study demonstrated 84% sensitivity in detection of HT sonographically. Parenchymal heterogeneity was found to be most sensitive finding in HT followed by hypoechoic micronodularity and diffuse hypoechogenicity. These findings are in agreement with previously published studies with diffusely hypoechoic appearance of the thyroid gland as an indicator of hypothyroidism with a positive predictive value (PPV) up to 88%.^[10] Hypoechoic micronodularity is also recognized as a key diagnostic feature with a PPV up to 95%.^[8,11] These two features are believed to represent manifestations of the diffuse lymphocytic infiltration of the thyroid gland over time. Parenchymal heterogeneity and diffuse hypoechogenicity are not only suggestive of HT but also are postulated to be correlated with the degree of immune-mediated changes and extent of hypothyroidism.^[10]

In addition, the other sonographic features, despite lacking strong predictive values, also serve as markers of disease. In the present study, hypervascularity was the least commonly observed feature as it was present in only 18% of HT patients. This may reflect a greater proportion of patients with chronic (burned out) disease. Hypervascularity exists on a continuum related to the stage of autoimmune thyroid disease with most marked vascularity during the initial inflammatory stage which tapers off in the later fibrotic stage.^[12,13] The hypervascularity during the initial inflammatory stage heralds the development of varying degrees of hypothyroidism as blood flow is recruited by elevated TSH levels in response to countless cycles of follicular damage and scarring, which eventually lead to a chronic avascular state.^[8,12] Overall, it is understood that the co-occurrence of several sonographic features of HT improves sensitivity and accuracy in diagnosis.^[14] Review of the radiology reports demonstrated diagnostic confidence was best when three or more sonographic features were present.

HT and coexisting thyroid malignancy

Malignancy can occur in patients with HT, with some authors reporting a significant increased risk above the average population. For example, a nationwide cohort study conducted in Taiwan demonstrated a 1.68-fold greater risk of developing malignancy in patients with HT.^[15] Specifically, primary thyroid lymphoma has been classically associated with HT; however, it is rare relative to PTC.^[5] Although not confirmed, a number of pathophysiological mechanisms have been proposed to explain these observations including TSH and immunologic driven malignant degeneration of chronic thyroiditis and increased expression of oncogenes in HT patients.^[16] Furthermore, increased risk of colon, lung, and breast cancer has been reported in HT patients, related to underlying autoimmune processes.^[15] The present study compared the occurrence of thyroid malignancy in patients who had histologically confirmed HT with and without sonographically evident HT. Malignancy occurred in slightly higher proportion in patients with sonographic evidence of HT compared to those without the sonographic features of HT, although this was not statistically significant. Conversely, about 87% of patients with PTC (the most commonly observed malignancy) also had sonographic evidence of HT. There was no significant trend among patient demographic factors and the incidence of malignancy although other studies have noted malignancy more frequently occurred in the young and middle age groups with female predominance.^[13,15]

Although the risk of malignancy in HT is increasingly scrutinized in the literature, relatively few studies have investigated the specific sonographic features of HT that are correlative with malignancy. This was one of the goals of the present study. While none of the sonographic features reached statistical significance, parenchymal heterogeneity was the most sensitive feature, while hypoechoic micronodularity demonstrated the greatest PPV for malignancy (Table 5). This may be linked to the aforementioned concept that these two sonographic features are associated with a more advanced stage of HT. It has been shown that nodular form of HT is more frequently encountered in the thyroid gland demonstrating a background of diffuse HT than without diffuse HT.^[17] It can be postulated that this combination of nodular pattern, parenchymal heterogeneity and hypoechoic micronodularity may be interlinked and associated with an advanced disease stage and theoretically an increased risk of malignancy.

In concordance with previous work, nodal metastases were more common in patients without sonographic findings of HT, occurring in about 83%. This corroborates the general understanding in the literature that patients with thyroid malignancy and HT have lower rates of capsular invasion and extrathyroidal extension and therefore a more favorable prognosis.^[18] This finding suggests that patients without sonographic evidence of HT may have an earlier and less sonographically evident stage of thyroid disease and thus are not yet afforded this protective effect.

The limitations of this study include the modest sample size which comprised patients from a single institution, which may not be entirely representative of the general population and limit the statistical power to analyze significant differences between the subgroups. In addition, there is potential selection bias as our patients were recruited from a pool of patients with clinically evident thyroid abnormalities which were ultimately treated surgically. Therefore, our cohort likely included patients with more advanced stages of thyroid disease.