Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves' Disease from Destructive Thyroiditis in Thyrotoxic Patients

Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim, Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim

Abstract

Background: Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves' disease (GD) from destructive thyroiditis (DT).

Methods: This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen's kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173).

Results: The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method.

Conclusion: In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

Keywords: Blood flow velocity; Graves disease; Receptors, thyrotropin; Thyroiditis; Thyrotoxicosis; Ultrasonography, Doppler, color.

Conflict of interest statement

CONFLICTS OF INTEREST

This research was supported by research equipment from Samsung Medison Co., Ltd. (Seoul, Korea). The sponsor had no role in the writing of the manuscript or in the decision to submit the manuscript for publication.

Figures

Fig. 1.
Fig. 1.
Color Doppler patterns. (A) Pattern 0, normal blood flow; blood flow limited to the peripheral thyroid arteries, while parenchymal flow is absent. (B) Pattern 1, minimally increased thyroid blood flow; presence of mildly increased parenchymal flow. (C) Pattern 2, clearly increased blood flow with a diffuse homogenous distribution. (D) Pattern 3, markedly increased blood flow with a homogenous distribution, including the so-called “thyroid inferno.”
Fig. 2.
Fig. 2.
Doppler image and vascularity index (VI). (A) Color Doppler image at the right thyroid lobe. (B) Power Doppler image at the right thyroid lobe. (C) VI at the right thyroid lobe. (D) VI at the left thyroid lobe. VI displays the number of pixels, area, and ratio (%) measurements within the region of interest (ROI). To mark the ROI, we traced the thyroid structure manually with the exclusion of perithyroidal vascular structures.
Fig. 3.
Fig. 3.
Flow chart of enrolled study subjects. One hundred nine patients were screened and eight patients were excluded. Five patients had taken anti-thyroid drugs within 2 weeks. One patient had received thyroid isthmectomy for thyroid cancer. Two patients were diagnosed with toxic adenoma. Forty-six patients were diagnosed with Graves’ disease. Among the remaining 47 destructive thyroiditis patients, 18 with subacute thyroiditis, 22 with autoimmune thyroiditis, two with postpartum thyroiditis, and five with drug-induced thyroiditis were included.
Fig. 4.
Fig. 4.
(A) Comparison of microvascular ultrasonography vascularity index (MVUS-VI) values between destructive thyroiditis and Graves’ disease. Nine subjects who were false positives (high VI values without Graves’ disease) showed all had positive thyroid peroxidase or thyroglobulin antibodies. Six subjects were false negatives (low VI values with Graves’ disease). Three of them had ages older over 68 (two subjects) and history of corticosteroid treatment for a neurology problem (one subject). (B) Comparison of MVUS-VI values among subacute thyroiditis, autoimmune thyroiditis, and Graves’ disease patients. There might be a gray zone that overlaps between Graves’ disease and autoimmune thyroiditis. (C) Correlation of the MVUS-VI and thyrotropin receptor antibody (TSH-R-Ab). The MVUS-VI showed a positive correlation with TSH-R-Ab (r=0.544). (D) Correlation of MVUS-VI and thyroid stimulating immunoglobulin (TSI) bioassay. The MVUS-VI showed a strong positive correlation with TSI bioassay value (r=0.841).

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