Goiter index: an easily available ultrasonographic index for thyroid volume in autoimmune thyroid diseases

Abstract

This study aimed to confirm the applicability of the product of depth and width of the right thyroid lobe measured by ultrasonography, as an index of estimated thyroid volume in patients with Hashimoto thyroiditis. This study included 118 patients with Hashimoto thyroiditis and 163 patients with Graves’ disease. The product of depth and width of the right thyroid lobe ranged from 1.7 to 10.2 (median, 4.4) cm² for Hashimoto thyroiditis and 2.6 to 10.8 (median, 5.8) cm² for Graves’ disease. The estimated volume obtained by ellipsoidal approximation correlated well with the product of depth and width of the right thyroid lobe in Hashimoto thyroiditis (ρ = 0.820, p < 0.0001) and Graves’ disease (ρ = 0.928, p < 0.0001), respectively. However, the correlations were not identical. The comparison of 72 patients with Hashimoto thyroiditis and 72 patients with Graves’ disease who were matched for the product of depth and width revealed no significant difference in the estimated thyroid volume. These results show that the product of depth and width of the right thyroid lobe can be applied to indicate thyroid volume instead of the estimated volume obtained from ellipsoidal approximation in both Hashimoto thyroiditis and Graves’ disease within the range of volumes investigated in this study.

Graphical Abstract

Introduction

Diffuse goiter is one of the most common symptoms of autoimmune thyroid disease. The volume of enlarged thyroid glands is usually evaluated by palpation with inspection or ultrasonography. When evaluated using ultrasonography, an ellipsoidal approximation [1, 2] is commonly used for estimation; however, this method can be complicated, especially for general practitioners. Ultrasonography is an essential examination for patients with Hashimoto thyroiditis. It can reveal concomitant neoplastic diseases, such as primary thyroid lymphoma or thyroid cancers, in addition to evaluating thyroid volume. We previously reported a simple method for ultrasonographic volumetry using the product of the depth and width of the right thyroid lobe on the transverse plane (temporarily named the “goiter index”), which is applicable to patients with Graves’ disease [3]. The extent of thyroid gland enlargement should be recorded as an objective finding in patients. Therefore, there is a need for an easy volumetry method for evaluating the thyroid, which can be widely shared among physicians. As Hashimoto thyroiditis is more prevalent than Graves’ disease, we confirmed that this novel goiter index is also applicable to patients with Hashimoto thyroiditis and Graves’ disease in the current study.

Patients

Among the patients who underwent ultrasound thyroid examinations between April 2024 and June 2024, 118 patients with Hashimoto thyroiditis were enrolled in this study. Hashimoto thyroiditis was diagnosed based on the detection of anti-thyroglobulin and/or anti-thyroid peroxidase antibodies [4]. Patients with concomitant thyroid nodules were excluded from this study.

For comparison with Graves’ disease, 163 patients with Graves’ disease were also included in this study. We selected these from 193 participants in our previous study [3] based on goiter volume as estimated by ellipsoidal approximation to reduce the difference in the range of goiter size between Hashimoto thyroiditis and Graves’ disease. Graves’ disease was diagnosed according to guidelines published by the Japan Thyroid Association [5].

Methods

An ultrasound examination was performed in the sitting position with the patient’s neck extended. The depth and width of each thyroid lobe and isthmus were measured in the transverse plane with the maximum cross-section. The length of each lobe and isthmus was measured in the longitudinal plane. The estimated thyroid volume was defined as the sum of the volumes of both thyroid lobes and the isthmus. Each volume (mL) was calculated by ellipsoidal approximation according to the formula; 0.52 × depth (cm) × width (cm) × length (cm) (conventional volumetry). The product of depth (cm) and width (cm) of the right thyroid lobe (goiter index) was employed as an easy index for thyroid volume. The correlation between the estimated volume obtained by conventional volumetry and the product of the depth (cm) and width (cm) of the right thyroid lobe (goiter index) was investigated in each patient group. Furthermore, estimated volumes were compared between Hashimoto thyroiditis and Graves’ disease in patients who were matched according to the product of the depth (cm) and width (cm) of the right thyroid lobe (goiter index).

Ultrasound examinations were performed using an Aplio 500 (Canon Medical Systems Corporation, Ohtawara, Japan) and Philips iU 22 (Philips Japan Ltd., Tokyo, Japan). The levels of TSH were determined by a chemiluminescent immunoassay using a Roche Elecsys TSH (Roche Diagnostics, Basel, Switzerland). Anti-thyroglobulin and anti-thyroid peroxidase antibodies were measured using commercially available kits.

Correlations were analyzed using Spearman’s rank test. Differences between correlations were analyzed using an analysis of covariance. Differences in the distribution of continuous variables were analyzed using the Wilcoxon rank-sum test. Statistical analyses were performed using JMP (ver. 18, SAS Institute Inc., Cary, NC, USA). Data are presented as ranges with median values in parentheses.

This study was approved by the ethical committee of our hospital (approval number 051) and was conducted in accordance with the Declaration of Helsinki. The patients were given the right to opt out of the study.

Results

Patient demographics

The age and sex distributions of the patients are shown in Table 1. Among the 118 patients with Hashimoto thyroiditis, 54 were treated with levothyroxine. The levels of TSH were within the normal range in 91 patients, while TSH was >5.0 μU/mL in 19 patients and <0.5 μU/mL in another 8 patients. The titers of anti-thyroglobulin or anti-thyroid peroxidase antibodies are not shown because the assays vary according to the time of measurement.

Table 1. Patient demographics.

	Hashimoto thyroiditis	Graves’ disease
n	118	163
Age (years)	11–92 (65)	13–75 (35)
Female/Male	107/11	133/30
Estimated volume obtained by conventional volumetry (mL)*	15.0–82.6 (30.0)	15.8–84.0 (44.4)
Product of depth and width of right lobe (cm2)*	1.7–10.2 (4.4)	2.6–10.8 (5.8)

Data are shown as the range, with the median value in parentheses.

*Significant differences (p < 0.0001) were seen between Hashimoto thyroiditis and Graves’ disease.

The estimated thyroid volumes obtained by conventional volumetry of the patients with Hashimoto thyroiditis and Graves’ disease were 15.0–82.6 (30.0) mL and 15.8–84.0 (44.4) mL, respectively. The thyroid volumes in Graves’ disease were significantly (p < 0.0001) larger than those in Hashimoto thyroiditis. The product of depth and width of the right thyroid lobe were 1.7–10.2 (4.4) cm² for Hashimoto thyroiditis and 2.6–10.8 (5.8) cm² for Graves’ disease. The latter was significantly (p < 0.0001) larger than the former (Table 1).

Correlation between estimated volume obtained by conventional volumetry and the product of depth and width of the right thyroid lobe (goiter index) of Hashimoto thyroiditis and Graves’ disease

As shown in Fig. 1, a good correlation was observed between estimated thyroid volumes obtained by conventional volumetry and the product of depth and width of the right thyroid lobe (goiter index) in patients with Hashimoto thyroiditis (ρ = 0.820, p < 0.0001) and Graves’ disease (ρ = 0.928, p < 0.0001), respectively. However, a significant difference (p < 0.0001) was observed between the two correlations (Fig. 2).

Fig. 1. Correlation between estimated volume obtained by ellipsoidal approximation (conventional volumetry) and the product of depth and width of the right lobe.

A: Hashimoto thyroiditis; B: Graves’ disease. The regression equations derived for estimating the volume (in mL) based on the product of depth and width (in cm²) were as follows:

Hashimoto thyroiditis: Estimated volume (mL) = 6.76 × product of depth and width (cm²) + 0.07

Graves’ disease: Estimated volume (mL) = 9.14 × product of depth and width (cm²) – 8.32

Fig. 2. An analysis of covariance revealed a significant (p < 0.0001) difference between Hashimoto thyroiditis (red) and Graves’ disease (blue).

Estimated volume obtained by conventional volumetry of patients with Hashimoto thyroiditis and Graves’ disease after matching according to the product of depth and width of the right thyroid lobe (goiter index)

After matching the products of depth and width of the right thyroid lobe (goiter index) within the range of 2.9 to 9.6 (median, 5.1) cm², estimated thyroid volumes obtained by conventional volumetry of 72 patients with Hashimoto thyroiditis and 72 patients with Graves’ disease ranged from 15.2 to 72.1 (median, 35.1) mL and 18.0 to 82.3 (median, 36.7) mL, respectively. No significant difference was observed between Hashimoto thyroiditis and Graves’ disease (Fig. 3).

Fig. 3. After matching the distribution of the product of depth and width, no significant difference was observed in the volume estimated by conventional volumetry between the patients with Hashimoto thyroiditis and those with Graves’ disease. N.S.: not significant.

Discussion

Hashimoto thyroiditis is a common autoimmune disease. A recent meta-analysis revealed that the global prevalence of Hashimoto thyroiditis in adults is 7.5% [6]. Additionally, the positivity rate for anti-thyroglobulin autoantibodies and/or anti-thyroid peroxidase autoantibodies has been reported to range from 13.4% to 16.0% in the Japanese population [7]. Diffuse enlargement of the thyroid is a common sign in patients with Hashimoto thyroiditis. Infiltration of lymphocytes and fibrosis are characteristic histological findings of goitrous Hashimoto thyroiditis [8]. Elevated TSH levels induce thyroid enlargement. Significant reduction in the thyroid volume can be observed by the administration of levothyroxine [9, 10]. Therefore, the extent of enlargement was quite different among the patients.

Ultrasonography is essential in the management of Hashimoto thyroiditis. It is an effective tool for differentiating primary thyroid lymphoma and diffuse sclerosing subtype of papillary thyroid carcinoma from Hashimoto thyroiditis [11, 12]. Pederson et al. [13] reported that echogenicity of the thyroid correlates well with lymphocyte infiltration, titers of anti-thyroid autoantibodies, and levels of TSH. In addition, volumetry can be easily performed using ultrasonography. It has been reported that 63–72% of patients with Hashimoto thyroiditis have compressive symptoms [14, 15]. It has also been reported that the thyroid volume of patients with compressive symptoms is larger than that of patients without symptoms [15]. Although Watt et al. [16] reported that the QOL of patients with Hashimoto thyroiditis is independent of the thyroid volume, diffuse goiter and its extent are important issues for patients with Hashimoto thyroiditis.

A simple method for the evaluation and description of the extent of diffuse goiter that can be widely shared among general practitioners and endocrinologists in daily clinical settings is desirable. Our previous study revealed that the product of depth and width of the right thyroid lobe (goiter index), as well as estimated volume by ellipsoidal approximation, is well correlated with the weight of the thyroid obtained from operative records in patients with Graves’ disease [3]. Because the thyroid volume of patients with Hashimoto thyroiditis was not evaluated in our previous study, we investigated the applicability of the goiter index for Hashimoto thyroiditis in the current study.

To investigate whether the novel goiter index has equivalent usefulness among the patients with Hashimoto thyroiditis and those with Graves’ disease, we compared the relationship of the goiter index and the estimated volume obtained by ellipsoidal approximation, which is an established method for estimating the thyroid volume, between Hashimoto thyroiditis and Graves’ disease. Because resected specimens from patients with Hashimoto thyroiditis are usually unavailable for the measurement of thyroid volumes, we had no alternative but to evaluate the correlation between the estimated volumes and the product of depth and width of the right thyroid lobe (goiter index) in this study. This is one of the limitations of this study. Further we could not compare the results of our easy volumetry method and measurements performed using CT [17, 18] because we have no CT volumetry data for our patients.

The relationship of the goiter index and the estimated volume by conventional volumetry was equivalent between Hashimoto thyroiditis and Graves’ disease in most ranges of thyroid volume investigated in this study (Graphical Abstract). In addition, there was no significant difference in the volumes obtained by conventional volumetry between patients with Hashimoto thyroiditis and Graves’ disease matched by the product of depth and width (goiter index). Therefore, the goiter index can be applied to Hashimoto thyroiditis and Graves’ disease, at least within the range of volumes investigated in this study, which is in line with the range of most cases of Hashimoto thyroiditis reported by Dayan and Daniels [8]. Although it is unclear whether the goiter index is applicable to thyroid glands larger than those investigated in the present study, we speculate that considerable variation will occur in glands larger than those evaluated in this study.

Graphical Abstract.

When the goiter index was identical, the estimated volume of Hashimoto thyroiditis was slightly, but not significantly, smaller than that of Graves’ disease. Although we could not determine the reason for this difference in the current study, Kara et al. [19] demonstrated that the shear wave velocity (SWV) of Hashimoto thyroiditis is higher than that of healthy controls. They also revealed a positive correlation between SWV and anti-thyroglobulin antibody levels or gland volume and a negative correlation between SWV and echogenicity of the thyroid in patients with Hashimoto thyroiditis [19]. These results show that the elasticity of the thyroid in Hashimoto thyroiditis is diminished with the progression of inflammatory changes in the thyroid. Diminished elasticity is suggested to play a role in lowering the estimated volume by conventional volumetry, because ultrasound examinations are performed with the patient’s neck extended.

Careful assessment is required for patients with asymmetric diffuse goiters. In addition, it is unknown whether the goiter index is applicable to thyroid glands larger than those investigated in the present study. These are additional limitations of the goiter index. Nevertheless, it was concluded that this novel goiter index will enable convenient and semi-quantitative evaluation of the extent of diffuse goiter in patients with autoimmune thyroid diseases in daily clinical settings.

Disclosures

The authors declare no conflicts of interest in association with the present study. No funding was received for this study. Tsukasa Murakami is a member of the Editorial Board of Endocrine Journal.

Authors’ Contribution

Conceptualization: TM

Data curation and discussion: TM, ME, NH, YN, JT, and HN

Statistical analysis: TM

Writing: TM