Correlation between anti-thyroid peroxidase antibody levels and diffuse thyroid uptake of ¹⁸F-fluorodeoxyglucose in Hashimoto’s thyroiditis: a retrospective study

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) is a functional imaging technique known as FDG-PET that exploits the typically increased rate of glycolysis in specific cell types, such as malignant tumors and inflammatory tissue [1, 2]. Its use as a method of detecting malignant tumors and foci of infection has recently become more frequent.

With regard to the thyroid, a normal thyroid gland is not visible or shows only low-grade FDG uptake on FDG-PET [3, 4]. However, the increasing use of FDG-PET has led to incidental identification of patients with increased FDG uptake in the thyroid gland. FDG uptake in the thyroid predominantly conforms to one of two patterns: focal and diffuse. The prevalences of incidental focal and diffuse uptake in the thyroid reportedly vary from 0.1 to 4.8% and 0.1 to 4.5%, respectively [5]. Focal uptake in the thyroid suggests the possibility of a malignant tumor, such as papillary thyroid carcinoma, although most well-differentiated thyroid carcinomas are relatively slow-growing and can be FDG-negative [6, 7]. In contrast, diffuse FDG uptake is typically considered to be a result of benign conditions, such as Hashimoto’s thyroiditis or Graves’ disease, among others [8, 9]; however, there have been few reports of diffuse uptake. Furthermore, among patients with Hashimoto’s thyroiditis, not all patients exhibit diffuse uptake.

In the current study, we evaluated the factors associated with diffuse uptake by comparing Hashimoto’s thyroiditis patients with or without diffuse uptake in the thyroid.

In this study, we evaluated patients with Hashimoto’s thyroiditis, which was diagnosed based on the elevation of either anti-TPO titer or anti-Tg titer; Hashimoto’s thyroiditis patients with high titers of anti-thyroid antibodies were likely to exhibit intense diffuse FDG uptake in the thyroid. In contrast, the frequency of hypothyroidism was similar in patients with or without diffuse uptake in the thyroid.

Previous studies suggested that Hashimoto’s thyroiditis is the most frequent cause of diffuse FDG uptake in the thyroid. Yasuda et al. [10] reported that, in a sample of 36 patients with diffuse FDG uptake, there were seven with hypothyroidism and 27 who were positive for anti-TPO antibody. In a sample of 45 patients, Kim et al. [11] detected 10 patients with hypothyroidism and six with anti-TPO or anti-Tg antibodies. Karantanis et al. [12] evaluated 133 patients with diffuse uptake in the thyroid, in most of whom the indication for FDG-PET was oncology imaging, and reported that 63 (47.4%) had prior clinical diagnoses of hypothyroidism or autoimmune thyroiditis. This percentage was significantly higher than that of their control group (13/133; 9.8%). In an evaluation of 137 patients with diffuse uptake, Lee et al. [13] found that 76 (55.5%) were positive for anti-microsomal antibody. This frequency was higher than that of patients without diffuse uptake (64/1925; 3.3%).

The mechanisms underlying diffuse FDG uptake in the thyroid have not yet been clarified. Glucose utilization by normal thyrocytes appears to be dependent on TSH. However, in the current study, which evaluated only patients with Hashimoto’s thyroiditis, serum TSH and the frequency of hypothyroidism were similar regardless of diffuse FDG uptake. In fact, one patient in the present study required 100 μg levothyroxine despite low FDG uptake in the thyroid. However, Lee et al. [13] evaluated 2062 patients with or without diffuse uptake and found that TSH was significantly higher in patients with diffuse uptake. Therefore, the limited sample size in our study might underpower the results with respect to serum TSH and the frequency of hypothyroidism. Conversely, Yoshida et al. [14] evaluated 70 autopsied cases and reported that positive serum anti-thyroid antibodies in subjects without overt thyroid disease may indicate the existence of lymphocytic infiltration in the thyroid gland. In addition, inflammatory cells were shown to exhibit increased expression of glucose transporter isoforms when activated [15]. This indicates that thyroid FDG uptake may be associated with the degree of lymphocyte infiltration into the thyroid, rather than residual thyroid function, and higher SUVmax and high titers of anti-TPO antibody may indicate a higher degree of lymphocytic infiltration. Furthermore, in the current study, Hashimoto’s thyroiditis patients with high titers of anti-TPO antibody were more likely to exhibit diffusely swollen thyroids with a heterogeneous pattern on US. In a previous study, high anti-TPO titer was highly indicative of the degree of hypoechoic pattern in autoimmune thyroiditis [16]. That result is concordant with the results of the current study. Further studies are necessary to clarify the relationships between FDG uptake, the degree of chronic thyroiditis, and the degree of hypothyroidism.

Anti-TPO antibody was predictive of SUVmax in the present study. However, Karantanis et al. [12] studied 21 patients with diffuse uptake and no prior history of thyroid disease and reported no correlation between SUVmax and TSH or anti-TPO titer. The discrepancy between their results and those of the current study may be partially due to differing backgrounds of the subjects in the two studies. The present study only included patients with serologically diagnosed Hashimoto’s thyroiditis, while Karantanis et al. [12] included patients with other diseases. Several previous studies have evaluated clinical backgrounds in patients with diffuse uptake in the thyroid [10‐13], but the current study is unique in that only patients with Hashimoto’s thyroiditis were included. Additionally, in the clinical setting, diffuse FDG uptake may be observed in a patient without thyroid hormone replacement therapy, when his or her anti-TPO antibody titer is high.

The primary limitation of the present study was its small sample size. Notably, the relationship between higher SUVmax and high titers of anti-TPO antibody was observed in this study. However, additional studies with larger sample sizes are required to evaluate the relationship between TSH and diffuse FDG uptake. Another limitation of the present study was the method used for clinical diagnosis of Hashimoto’s thyroiditis. We evaluated only clinical symptoms and ultrasonographic findings but did not perform fine needle aspiration, to exclude the possibility of neoplastic diseases (e.g., thyroid lymphoma).

The results of the present study suggest that patients with Hashimoto’s thyroiditis and high titers of anti-thyroid antibodies are likely to exhibit intense diffuse FDG uptake in the thyroid. However, the frequency of hypothyroidism was similar in patients with or without diffuse uptake in the thyroid. Therefore, it should be borne in mind that thyroid function may be clearly impaired even in the presence of only mild FDG uptake in the thyroid.