Advancements in ultrasound and other imaging techniques have increased the annual rate of detection for thyroid nodules (1). Thyroid nodules are detected in approximately 70% of the general population (1); fortunately, 80%–95% of the nodules are benign (2). Nonetheless, benign thyroid nodules (BTNs) require active treatment in the following scenarios: (i) when swelling/enlargement of the nodule affects aesthetic appearance; (ii) when patients experience pressure symptoms owing to the swelling; or (iii) when the patient experiences anxiety owing to the swelling (3). Although surgery is the main treatment modality for BTN (3), open surgery is highly invasive and can lead to medically-induced hypothyroidism (4, 5). Endoscopic thyroidectomy—a minimally invasive procedure—can be performed via areolar, axillary, and oral vestibular approaches (6). Despite the lack of neck scarring associated with the procedure, endoscopic thyroidectomy results insignificant trauma to the subcutaneous tissue along the lumpectomy path (6). Moreover, some patients refuse to undergo surgical treatment for reasons such as surgical anxiety and unwillingness to undergo general anesthesia, which is required for this procedure (7).

Microwave ablation (MWA)—a type of thermal ablation (TA)—is a promising treatment for BTN. Ultrasound-guided (US-guided) MWA has been recommended by several international guidelines owing to its relatively low rate of complications and confirmed efficacy (3, 8, 9). Hashimoto's thyroiditis (HT) (also known as chronic lymphocytic thyroiditis) is an autoimmune thyroid disease (10) whose incidence has increased rapidly over the past 30 years, having become one of the most common thyroid diseases at present, with an incidence rate of 0.3–1.5 cases/1,000 people (11, 12). Histopathological features of HT include enlarged thyroid volume, lymphoplasmacytic infiltration, presence of fibrotic tissue, and lymphoid follicle formation (10). There is a paucity of data on the difference in efficacy of MWA treatment for BTN with or without HT. A cohort study with a short-term (1-week) follow-up reported some differences in the effectiveness of US-guided radiofrequency ablation (RFA) for the treatment of papillary thyroid microcarcinoma (PTMC) between patients with and without HT (13). Previous studies have also indicated that thermal ablation may achieve better efficacy in the treatment of liver tumors individuals with comorbid liver cirrhosis (14). This phenomenon can be attributed to the low thermal conductivity of cirrhotic liver tissue, resulting in a higher temperature of the ablated area, known as the “oven effect” (15). We postulated that the unique histopathological characteristics of the thyroid gland in cases of HT may also result in a similar “oven effect”.Consequently, this study aimed to evaluate the effectiveness of US-guided MWA for BTN with HT vs. BTN without HT, based on changes in the volume reduction ratio (VRR) of BTNs in each group.

In the present study, we compared the effectiveness of ultrasound-guided MWA for the treatment of BTNs in patients with both BTNs and HT and those with BTNs and normal thyroid function, based on changes in the VRR. Our findings indicated that the relationship between VRR and follow-up time for US-guided MWA for BTN was nonlinear. An analysis of the threshold effect of follow-up time on VRR, indicated that the inflection points of the “BTN” and “BTN + HT” groups occurred at 2.1 months and 1.5 months after MWA, respectively.

Surgical procedures are currently the main clinical treatment for BTN (3). TA techniques such as RFA, MWA, and laser ablation (LA) have shown promise as alternatives to the surgical treatment of BTN. These techniques can all be performed by inserting ablation electrodes into the target tissues under the guidance of US and other imaging equipment. Although these procedures generate heat through different forms of physical energy, each is designed to induce coagulative necrosis of tissues at high temperatures, and the necrotic tissues are eventually cleared and absorbed by the body's immune system, resulting in physical local inactivation to achieve treatment success (21). Compared with that of RFA and LA, the effectiveness of MWA is not affected by tissue carbonization or current conduction and has the advantages of more uniform heat distribution, reduced heat loss, larger ablation range, and shorter ablation time (22). US-guided MWA has the advantages of high safety, precise efficacy, preservation of thyroid function, reproducibility, minimal trauma, and rapid recovery, and it can be performed on an outpatient basis under local anesthesia and has been established as a clinicallyvalid safe and effective method for the treatment of BTN (23).

HT is a slowly progressive disease with histopathological manifestations comprising gradual destruction and atrophy of normal thyroid follicles, lymphocytic infiltration and hyperplasia, and fibrous tissue hyperplasia forming vitelliform changes. In the mid to late stages of the disease, the fibrous tissue proliferates, the gland hardens, and single or multiple nodules are formed (10). Given that the histological features of the thyroid parenchyma in patients with HT differ from those of the normal thyroid gland, HT may affect the effectiveness of MWA for thyroid nodules. At present, there no studies have reported whether temporal trends in the VRR after MWA differ according to the presence of HT in patients with BTNs. To address this issue, we investigated changes in the VRR in these two groups of patients treated at our institution.

In the present study, the proportion of women was significantly higher in the “BTN + HT” group than in the “BTN” group (P = 0.027), which is consistent with the high female prevalence of HT of 5%–10% (24, 25). A previous report noted that nodules adjacent to the trachea and the recurrent laryngeal nerve may demonstrate incomplete ablation (26); in the present study, we observed no difference in the number of nodules adjacent to the “danger zone” between the groups. The above comparison results indicate that the baseline information of the two groups of patients was similar and comparable except for sex. The current findings indicated that the VRR of both groups gradually increased with time in both groups in a nonlinear fashion, and that the relationship exhibited a threshold effect. The inflection point in the “BTN + HT” group was observed at 1.5 months, which is slightly earlier than the inflection point of 2.1 months in the “BTN” group.

Most published studies exploring MWA for BTN have used fixed time points for follow up, commonly recording changes in volume and VRR at 1, 3, 6, and 12 months after ablation (23, 27, 28). However, in actual clinical practice, follow-up times are influenced by poor patient compliance and insufficient knowledge of the disease. Moreover, considering the influence of the COVID-19 pandemic and our epidemic prevention policy (29), a significant proportion of patients in this retrospective study were unable to visit our healthcare facility for follow-up at the prescribed time points. Nevertheless, in this study, using the data from clinical practice, we dutifully recorded the MWA follow-up times, the nodule volumes, and VRR data for the included patients.

We used a piece-wise linear regression model to analyze the threshold effect and determine the inflection point for VRR in each group. The inflection point reflects achange in the acceleration of changes in nodule size. Prior to the inflection point, rates of change are rapid. After the inflection point, the rate begins to decrease, although changes in size can still be observed. As mentioned previously, the inflection point occurred earlier in the “BTN + HT” group than in the “BTN” group. We suspect that histological changes in the thyroid parenchyma caused by HT influenced the efficacy of MWA for BTN, given that patients with HT concomitant with BTN exhibited earlier and faster nodule shrinkage in the early post-MWA period. Specifically, these differences may be related to differences in the thermal conductivity of the thyroid tissue between the two groups. Liu et al. (15) found that the thermal conductivity of background tissue is important for tumor heating based on in vitro models. When the environmental thermal conductivity around the tumor is low, the heat of ablation will be concentrated inside the tumor. In essence, the sclerotic tissue surrounding the tumor may act as an insulator, increasing the heat inside the tumor and preventing heat loss to the outside, which is known as the “oven effect” (15). An in vitro study also observed that heat is more likely to be deposited inside liver tumors surrounded by cirrhosis (14). Histopathologically, HT is characterized by the destruction of normal thyroid follicular cells due to lymphocytic infiltration, which is responsible for HT-induced hypothyroidism (10). Simultaneously, fibrous tissue hyperplasia causes gland atrophy, fibrosis, and hardening. Given these pathological changes, the thyroid tissue of HT may create an “oven effect” similar to that produced by cirrhotic tissue in the liver. During MWA treatment, heat may therefore accumulate within BTNs, leading to rapid coagulation necrosis. Owing to the diffuse chronic inflammatory cells present in the thyroid gland in patients with HT, the autoimmune system is activated more quickly, and necrotic substances are phagocytosed and eliminated (30). This may explain the faster rate of shrinkage for nodules in the “BTN + HT” group.

In clinical practice, we often encounter patients with HT who ask whether they can receive MWA treatment for their BTNs, and the corresponding evidence was previously unavailable to inform our answers to this question. To the best of our knowledge, few studies have investigated potential differences in the effectiveness of MWA for BTN between patientswith and without HT. However, some studies have investigated the effectiveness of RFA for PTMC in patients with or without HT (13, 31). Interestingly, these two studies reached inconsistent conclusions and had certain limitations. Zhang et al. (31) analyzed data for 30 patients with PTMC and 30 patients PTMC + HT.The authors concluded that RFA was effective in patients with PTMC + HT, and that its efficacy and safety were similar to those for patients with PTMC without HT through 1–18 months of follow-up. While the sample size in this study was considerably small, the follow-up time was adequate. The other study was a large cohort study of 797 nodules (573 vs. 224 nodules in the “PTMC” group vs. “PTMC + HT” group) that focused on the effect of RFA for early-stage PTMC on the extent of the ablation zone in those with HT (13). After 1 week of RFA treatment, the size of PTMCs was smaller in patients with HT than in thosewith a healthy thyroid. Despite thelarge size of the cohort, a 1-week follow-up is too short for evaluating the effect of RFA for PTMC, as the ablation area may change after the inflammatory edema period has elapsed. Given the lack of evidence in this area, we conducted the current retrospective study to investigate whether the effects of MWA differ between patients with BTN and those with BTN + HT. The preliminary finding that the inflection point occurred 15 days earlier in the BTN + HT group without increases in the rate or severity of adverse events may help to allay patient concerns.

In terms of adverse events, two patients experienced temporary hoarseness owing to thermal damage of the recurrent laryngeal nerve, and this may be attributed to the close proximity of the nerve to the nodules and to the loss of isolation fluid during the ablation process without timely replenishment. During MWA, radiating pain in the face, ears, and teeth may occur due to heat transfer during ablation of the nodular envelope near the superficial thyroid gland, although this pain generally resolves spontaneously at the end of the ablation procedure (32). Overall, there was no difference or specificity in the incidence of complications between the two groups in the current study.

The present study had some limitations. First, this was a retrospective study with unavoidable patient selection bias, and the greater frequency of female patients in the “BTN + HT” group may have had certain effects on the results. Second, this study used a fixed ablation power of 30 W. We were unable to compare treatment effects and thresholds for different ablation powers, which can cause differences in the degree of carbonation, which in turn affects the VRR. Third, HT is a chronic progressive disease, and the histopathology of thyroid glands varies at different time periods. Therefore, future large-scale studies should aim to compare differences in the effectiveness of on MWA for BTN concomitant with HT at different time periods, are warranted.

The VRR exhibits a nonlinear relationship with follow-up time during US-guided MWA for BTNs, for which a threshold effect can be observed. The current results indicated that the VRR in both groups increased before and after the inflection point, although the rate of change was greater before than after the inflection point. The earlier inflection point observed in the “BTN + HT” group may be related to the “oven effect” of affected tissue in patients with HT; however, additional studies are required to determine the exact mechanism underlying these differences.