Pilot study of ultrasound-guided microwave ablation for inactivating excess remnant thyroid after surgery in patients with differentiated thyroid cancer

Abstract

Objectives

To evaluate the safety and efficacy of ultrasound (US)-guided microwave ablation (MWA) for inactivating excess remnant thyroid (RT) after surgery in patients with differentiated thyroid cancer (DTC).

Methods

This study was registered in the Chinese Clinical Trial Registry under the identifier ChiCTR2200063200 on September 1, 2022. This study enrolled consecutive postsurgery DTC patients who were scheduled for radioactive iodine ablation (RAI) therapy. These patients exhibited excess RT, which was removed via MWA. Changes in RT volume/weight before and after MWA, as well as alterations in laboratory parameters, were assessed. Complications arising from MWA were documented and monitored.

Results

Twenty-three patients participated in the study. Following US-guided MWA, there was a statistically significant decrease in the volume/weight of RT, from [2.90 (1.78, 4.28)] mL/[2.66 (1.63, 3.92] g to (0.93 ± 0.43) mL/(0.83 ± 0.40) g (P < 0.001). Nineteen patients had an RT weight < 1 g post-MWA. An observed threshold effect between TSH levels and post-MWA follow-up time revealed an inflection point at 17.0 days, with TSH levels increasing by 2.5 mU/L per day from 0 to 17.0 days (P < 0.001), peaking above 30 mU/L on day 17.0. The TSH level subsequently decreased by 1.6 mU/L per day (P = 0.028) after 17.0 days. No serious complications were noted.

Conclusions

US-guided MWA is a relatively safe and effective method for inactivating excess RT after surgery and represents a potentially innovative minimally invasive approach. The relationship between TSH and follow-up time after MWA for inactivating excess RT reveals a threshold effect, aiding in determining the optimal timing for RAI therapy post-MWA, yet its universal applicability necessitates additional investigation.

Introduction

Thyroid cancer is a prevalent endocrine malignancy globally, with a rising global incidence over recent decades and a 20% increase in age-standardized incidence, driven by enhanced early tumor screening, a greater prevalence of personal risk factors, and increased exposure to environmental risks [1, 2]. The prevalent pathological types of thyroid cancer include papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), medullary carcinoma, and undifferentiated carcinoma. PTC and FTC, arising from thyroid follicular epithelial cells with superior cell differentiation ability, constitute differentiated thyroid cancer (DTC), which represents more than 95% of thyroid cancer cases [3]. Surgery is the primary treatment for DTC, with the follow-up and prognosis of DTC patients closely linked to the promptness and standardization of the initial surgical intervention [4, 5]. Guidelines from leading medical societies globally concur that the triad of surgery + radioactive iodine ablation (RAI) therapy + TSH suppression represents the optimal treatment strategy for DTC, with RAI for the removal of thyroid tissue (i.e., RAI remnant ablation), which has emerged as the key postoperative adjuvant therapy for DTC [4,5,6]. Notably, a crucial prerequisite for undertaking RAI remnant ablation is a thyroid stimulating hormone (TSH) level > 30 mU/L, a condition challenging to fulfill in cases of excess remnant thyroid (RT) [5, 7]. Certain patients may have a potential thorny problem prior to treatment with RAl: excess RT after incomplete/near-total thyroidectomy. Currently, there are two approaches for inactivating excess RT after initial DTC surgery: (1) Direct high-dose, multiple RAI remnant ablation: Guidelines advise against this approach for patients at increased risk of radiation exposure [4]. (2) Reoperation: In view of the disadvantages of direct high-dose, multiple RAI remnant ablation, major guidelines suggest that reoperation can be performed to remove excess RT, followed by RAI therapy [4,5,6]. While a viable alternative, reoperation following initial surgery is not without risks, including increased rates of complications such as nerve injuries, parathyroid gland damage, and incision infections [8,9,10,11,12]. Thus, shortcomings are evident in both high-dose RAI therapy and postreoperation RT removal. The safe and effective management of excess RT pre-RAI therapy poses a complex clinical challenge, necessitating the development of a novel treatment approach that addresses these limitations.

Microwave ablation (MWA) is a form of thermal ablation. Ultrasound (US)-guided MWA can inactivate thyroid nodules and has a similar effect on normal thyroid tissues. By employing MWA, outcomes akin to those of surgical resection can be achieved through precise thermal tissue destruction (Fig. 1). Currently, reports on the use of MWA to inactivate excess RT after initial surgery for DTC are lacking. This study aimed to assess the safety and efficacy of US-guided MWA in patients with excess RT following DTC surgery who are receiving RAI therapy.

Fig. 1

Schematic diagram illustrating US-guided MWA for a thyroid nodule (A) and inactivation of excess RT (B)

The dashed shading in Figure A indicates the extent of nodal ablation; Figure B demonstrates that glands in the dashed-shaded portion should be inactivated as much as possible, except for glands adjacent to the recurrent laryngeal nerve (the “danger triangle”), which may be preserved in limited amounts

Materials and methods

Patients

Sequential patients with DTC admitted to Shenzhen Second People’s Hospital between January 2018 and January 2023, after surgery and intended for RAI therapy, were enrolled. These patients exhibited excess RT before RAI therapy, which was removed via MWA. This study design followed the international regulations of the Helsinki Declaration. Our research was approved by the Ethics Committee of Shenzhen Second People’s Hospital (20220518002–FS01) and registered in the Chinese Clinical Trial Registry (ChiCTR2200063200). Written informed consent was obtained from all participants. Inclusion criteria: (1) patients with DTC at intermediate risk of recurrence; (2) low-risk DTC patients willing and suitable for long-term follow-up and tumor recurrence monitoring; (3) patients who have had subtotal thyroidectomy requiring postoperative assessment to complement total resection and are unwilling or unsuitable for reoperation. Exclusion criteria: (1) pregnancy, lactation, or intent of pregnancy within six months; (2) severe cardiac, hepatic, or renal insufficiency; (3) severe coagulation abnormalities; (4) vocal cord dysfunction opposite residual thyroid tissues; and (5) inability to cooperate during MWA under local anesthesia (e.g., severe cough, asthma, ergotism). The conceptual framework of the study is illustrated in Fig. 2.

Fig. 2

Conceptual framework of the study

Equipment and instruments

This study utilized the following equipment: (1) a MyLab Twice US diagnostic instrument (Esaote, Italy) with an LA533 probe (4–13 MHz) and an LA332E probe (3–11 MHz); (2) an MTI-5 A MWA therapy instrument (Nanjing Changcheng Medical Equipment Company Limited, Nanjing, China) including a microwave generator (2450 MHz), a microwave cable, and an XR-A1610W liquid-cooled circulation MWA needle (16 G, 10 cm); and (3) a US contrast agent (Sonovue, Bracco Suisse SA, Italy) mixed with 5 ml of 0.9% saline to prepare a suspension for application.

MWA process of inactivating excess RT

Pre-MWA assessment

The patient’s age, sex, and personal and treatment history were documented, with a focus on initial surgical admission medical records, imaging, laboratory reports, surgical records, and pathological findings. Standard preoperative assessments, including liver and kidney function, coagulation studies, complete blood count, and electrocardiogram, should be performed, and laryngoscopy should be conducted to assess bilateral vocal cord function, particularly on the side opposite the RT. Preoperative thyroid function tests should include TSH, total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), and parathyroid hormone (PTH). Prior to MWA, US can measure the three diameters of RT for volume and weight calculations via the following formulas:

Volume of RT (mL) = transverse diameter (cm) × vertical diameter (cm) × anteroposterior diameter (cm) × 0.5244 [13].

Weight of RT (g) = transverse diameter (cm) × vertical diameter (cm) × anteroposterior diameter (cm) ×0.479 [14].

Current domestic and international guidelines, as well as the literature, do not define specific quantitative criteria for “excess RT” [4, 5]. This study assumes that RAI therapy is predicated on total or near-total thyroidectomy. Near-total thyroidectomy involves inactivating nearly all visible thyroid tissue, leaving < 1 g of nontumorigenic tissue behind [4]; >1 g constitutes excess RT. An experienced interventional sonographer conducted pre-MWA US assessments to evaluate RT characteristics comprehensively, including location, size, morphology, borders, adjacent structures, and blood flow, particularly in proximity to vital anatomical landmarks such as the common carotid artery, trachea, and recurrent laryngeal nerve. A tailored MWA protocol was designed to effectively deactivate RT. Patients underwent a low-iodine diet regimen before MWA; levothyroxine was discontinued temporarily for individuals not receiving TSH suppression therapy and for three weeks for those receiving such therapy.

MWA procedure

The patient was placed in a supine position with the neck hyperextended. Cardiac and oxygen saturation monitoring equipment was confirmed to function normally. Venous access was established, and the neck skin was disinfected with an aseptic towel. Preablation contrast-enhanced ultrasound (CEUS) was conducted to elucidate the RT boundaries, extent of the active zone, and blood flow distribution and to redefine the ablation scope. Layered anesthesia of the skin puncture site, thyroid envelope, and adjacent tissues was performed under US guidance via the use of 2% lidocaine hydrochloride. “Liquid isolation” involves injecting 0.9% sodium chloride solution under US guidance into specific areas to create a protective barrier around critical tissues near the thyroid gland. Depending on the effectiveness of fluid isolation, the precise MWA margin ranged from 3 mm to 5 mm from the esophagotracheal groove or the region of the recurrent laryngeal nerve. In cases of adequate fluid isolation, a 3 mm margin was maintained, whereas a 5 mm margin was maintained under conditions of inadequate fluid isolation, such as severe adhesions or insufficient fluid stagnation time. The MWA instrument was set to 30 W [15], and under US guidance, the MWA electrode was percutaneously inserted into the RT for gradual ablation via a “mobile ablation” technique. Color Doppler blood flow imaging (CDFI) confirmed the absence of blood flow signals in glandular tissue. Continuous patient communication during ablation was maintained to monitor for complications, especially when deep glandular tissue near the recurrent laryngeal nerve was treated, prompting vocalization tests for hoarseness detection. Postablation, CEUS reassessment was performed to evaluate ablation success. Additional ablation targeted any residual perfusion areas, ensuring complete inactivation of nonessential tissues while sparing structures such as the laryngeal recurrent nerve. Gauze dressing was applied to the neck puncture site, and intermittent ice pack application was advised for six hours to prevent bleeding and thermal complications.

Post-MWA assessment

Safety assessment

Patient data were documented for procedural duration, hemorrhage, incision length, length of hospital stay, and adverse events. Adverse events were assessed in accordance with the grading system for adverse events established by the Society of Interventional Radiology (SIR) [16]. This system categorizes adverse events into three levels on the basis of their severity: adverse reactions, minor complications, and severe complications. Adverse reactions involve substantial pain and discomfort that resolve spontaneously without medical intervention, potentially leading to disability or mortality as severe complications, whereas other issues are classified as minor complications.

Effectiveness assessment

MWA was clinically effective in inactivating excess RT: no serious adverse events occurred; the weight of RT after ablation was < 1 g, or the TSH level was > 30 mU/L during the 1-month follow-up period after MWA. CEUS was employed for a quantitative evaluation of the volume/weight of RT post-MWA. The formula used was as follows: volume/weight of RT post-MWA = volume/weight of RT pre-MWA - volume/weight of CEUS-perfused defective glands, or the volume/weight of the perfused region after MWA was directly measured as the volume/weight of RT post-MWA.

Statistical analysis

The statistical software used included SPSS (version 20.0; SPSS, Chicago, IL, USA), R (http://www.R-project.org), and EmpowerStats software (www.empowerstats.com, X&Y solutions, Inc. Boston MA). Categorical variables were assessed via the chi-square test. The measurement data are presented as the means ± standard deviations. For normally distributed data with comparable variances, t tests were employed. Nonnormally distributed data were analyzed via the Mann–Whitney U test. A generalized additive mixed model was utilized to examine the temporal trends of each variable (e.g., TSH), along with generating fitted plots to identify potential threshold effects concerning follow-up time. Threshold effects were explored to determine the inflection point of each variable over time, utilizing fitted curves and the likelihood ratio test to validate the nonlinear relationship between variables and follow-up time. A piecewise linear regression model was subsequently applied to determine the threshold values [17, 18]. Statistical significance was set at p < 0.05.

Results

Baseline data

Twenty-six patients with DTC who had excess RT postsurgery and pre-RAI therapy underwent US-guided MWA. One patient stopped taking levothyroxine for 3 weeks prior to MWA, with a TSH level > 30 mU/L, and two patients did not adhere to the levothyroxine cessation requirement. The study included a total of twenty-three patients (Table 1).

Table 1 Baseline data

Volume/weight changes in RT before and after MWA

The extent of RT inactivation was determined by CEUS to assess the efficacy of MWA. Table 2 indicates a significant reduction in the volume/weight of RT post-MWA compared with pre-MWA (P < 0.001). Among the twenty-three patients in the study, nineteen had an RT weight of < 1 g following MWA, resulting in a clinical effectiveness rate of approximately 82.61% on the basis of the criteria established in this study.

Table 2 Volume/weight changes in RT before and after MWA

Laboratory parameters pre- and post-MWA

Thyroid-related hormones

Table 3 presents the number of cases with follow-up data and the quantification of changes in thyroid-related hormones due to irregular patient follow-up data. The TSH level was [30.65 (8.94, 80.01)] mU/L at 0.5 months post-MWA, which was significantly greater than the preablation level (P = 0.012). At 1 month postablation, the TSH level was lower than that at 0.5 months but higher than that pre-MWA, with the difference from pre-MWA not being significant (P = 0.114). TT3, TT4, FT3, FT4, and Tg were lower at 0.5 months post-MWA, with FT3 and FT4 significantly lower than pre-MWA levels; other laboratory parameters did not significantly differ. PTH levels were slightly elevated but not significantly different (P = 0.523). No statistically significant differences were observed in the above laboratory parameters 1 month after MWA (P value > 0.05).

Table 3 Laboratory parameters pre- and post-MWA

Threshold effect analysis of TSH and follow-up time

The generalized additive mixed model was applied to assess the TSH trend over time, as depicted in Fig. 3. A generalized additive mixed model was used to analyze the inverted “U”-shaped trend of TSH after MWA. The solid line in the center of the figure represents the fitted line, whereas the dashed lines flanking it indicate the 95% confidence intervals. Figure 3 shows a nonlinear relationship between TSH and follow-up duration, with an initial increase followed by a subsequent decrease, indicating a threshold effect. Analysis of TSH as the dependent variable and follow-up time as the independent variable revealed two threshold effects, as detailed in Table 4. The log-likelihood ratio test with P < 0.05 confirmed the absence of a simple linear relationship, leading to the selection of Model II over Model I. Model II employed piecewise linear regression to pinpoint the time inflection at 17.0 days. At the 17.0-day threshold, TSH increased by 2.5 mU/L daily within the 0– to 17.0–day period (P < 0.001), and after 17.0 days, TSH decreased by 1.6 mU/L daily (P = 0.028).

Fig. 3

TSH levels over time following MWA

Table 4 Threshold effect for the relationship of follow-up time with TSH

Complications

There were no serious complications as defined by the SIR. One patient experienced an adverse reaction characterized by neck pain radiating to the teeth and behind the ears, which spontaneously resolved within 2 days. Additionally, three patients developed hoarseness post-MWA, which resolved within 1 month following hormonal treatment.

Case presentation

A 35-year-old female was diagnosed with PTC through fine needle aspiration biopsy of a nodule in the right thyroid lobe (measuring 1.0 cm × 0.8 cm × 0.7 cm) in August 2020. She underwent surgery at our hospital, involving resection of the right lobe, isthmus, partial left lobe, and lymph node dissection in the VI neck area. Postsurgery pathology revealed multifocal PTC in the right lobe (largest diameter of 1.1 cm), with 6 out of 8 lymph nodes in the VI area showing metastases (0.2 cm to 0.5 cm in diameter) and a BRAF^V600E mutation. The patient’s postoperative recurrence risk was classified as intermediate according to the 2015 ATA guidelines for DTC recurrence risk stratification [5] by the Department of Nuclear Medicine, necessitating RAI therapy. However, incomplete thyroid resection during the initial surgery and excess RT (measuring approximately 4.1 cm × 1.3 cm × 1.3 cm, with a volume of approximately 3.63 mL and weight of approximately 3.32 g) indicated the ineffectiveness of direct RAI therapy due to potential serious side effects. It was recommended that patients undergo reoperation or US-guided MWA to remove excess RT before receiving RAI therapy. In October 2020, the patient opted for US-guided MWA to inactivate excess RT (Fig. 4). The volume of RT inactivated through MWA was approximately 2.63 mL, and approximately 2.40 g was weighed, as assessed by CEUS. Post-MWA, the RT volume was approximately 1.00 mL, weighing approximately 0.92 g, successfully achieving the objective of inactivating excess RT. The patient’s TSH level was 15.06 mU/L before MWA and increased to 87.80 mU/L (greater than 30 mU/L) 15 days post-MWA, satisfying the criteria for suitable RAI therapy according to guidelines, with no adverse events.

Fig. 4

US-guided MWA to inactivate excess RT

(A) CDFI revealed abundant blood flow signals in the RT, which were mainly concentrated in the left lobe before MWA. (B) CEUS revealed uneven hyperenhancement of the RT pre-MWA. (C) Two-dimensional US demonstrated thermal damage to the RT during MWA, with a widespread hyperechoic vaporization zone observed within the RT. (D) Post-MWA CEUS revealed a perfusion defect pattern in the RT, indicating successful inactivation of the RT

Discussion

RAI therapy is a crucial postoperative intervention for DTC, with guidelines advocating RAI for all DTC patients postsurgery, except for those with “micropapillary thyroid cancer without local or distant metastases” [4, 5]. Excess RT significantly impairs the efficacy of RAI therapy [5, 7, 14]. Following total bilateral lobectomy of the thyroid, visible glandular tissue is removed, yet complete excision of all thyroid tissue remains challenging; however, RT in patients undergoing total/near-total thyroidectomy is microscopic postoperatively, necessitating prior total/near-total thyroidectomy for RAI therapy [4, 5]. Nevertheless, some patients skip total/near-total thyroidectomy before RAI due to various factors, such as inadequate preoperative assessment, conflicting guidelines on surgical resection extent, hospital-specific surgical practices, and patient preferences against extensive thyroidectomy. Guidelines recommend reoperation to eliminate excess RT before RAI therapy for such cases [5, 7], although reoperation is invasive and may be declined by certain patients. This study investigated the safety and efficacy of US-guided MWA in inactivating excess RT to address the challenge of excessive RT pre-RAI therapy in DTC patients.

The volume/weight of RT decreased significantly after MWA from 2.90 mL/2.66 g to 0.93 mL/0.83 g (P < 0.001), demonstrating the effectiveness of MWA in inactivating excess RT. MWA, a form of thermal ablation, is primarily used for treating thyroid nodules in patients with thyroid disorders. It induces coagulative necrosis in nodules, allowing for phagocytosis and absorption of necrotic tissue by the body’s immune system to achieve therapeutic outcomes. MWA for RT removal represents an extension of thermal ablation technology in thyroid diseases, transitioning from local deactivation to widespread thermal destruction. MWA is electrode-free and features a high ablation frequency, deep tissue penetration, minimal tissue carbonization effects, and advantages such as rapid heat generation, low heat dissipation, short ablation duration, and a large treatment area [19]. MWA offers advantages such as rapid heat generation and low heat loss, making it suitable for ablating a broader range of residual thyroid tissue. Among methods for inactivating excess RT, RAI primarily utilizes ionizing radiation to induce necrosis in the thyroid follicular cells of RT, resembling “bloodless” RT surgery. Surgical approaches involve direct RT removal for elimination. MWA inactivates RT through thermal destruction, categorizing it as a form of “physiological removal.” Although inactivated, RT persists in the body but loses its normal physiological functions, achieving effects akin to those of physical removal observed in surgical procedures. The included patients have a high thyroid volume and significant RT size, which is fully consistent with the criteria of excess RT prior to RAI treatment. The reasons for choosing MWA over reoperation are as follows: (1) Clinical decision-making context: primary surgical adhesions lead to a significantly higher risk of reoperation, especially within a short period of time [8, 9]. (2) Characterization of the distribution of the RT: the RT in the patients had a focal distribution, i.e., one side of the gland lobes, and were not diffusely enlarged in patients with hyperthyroidism, which would be suitable for a more precise ablation. (3) Strong willingness of patients: the majority of patients assessed for RAI therapy post-surgery were informed about excess RT and the requirement of prompt reoperation, a less favored option among patients. Meanwhile, minimally invasive MWA is gaining acceptance, and all the included patients signed an informed consent form and explicitly chose the minimally invasive MWA. At the same time, we will thoroughly inform about the advantages and disadvantages of MWA, rigorously assess indications in clinical practice, and avoid excessive substitution for surgery.

The optimal timing for RAI therapy after US-guided MWA to remove excess RT remains unreported. This study, for the first time, computed that the threshold TSH value post-MWA was correlated with follow-up time via the threshold effect analysis method at 17.0 days after MWA, suggesting that this value is the potential optimal juncture for RAI therapy. The generalized additive mixed model revealed an inverted “U”-shaped TSH trend after MWA, with a continuous increase from 0 to 17.0 days attributed to reduced thyroid hormone secretion feedback after excess RT removal. The subsequent decline in TSH beyond day 17.0 may be linked to sustained TSH elevation via the hypothalamic‒pituitary‒thyroid axis and its subsequent reduction. As TSH continues to increase, the hypothalamus‒pituitary‒thyroid axis governs the release of thyroid hormones from residual unaltered RT after MWA, leading to a negative feedback loop and a decrease in the TSH level. As TSH levels rise, the hypothalamus‒pituitary‒thyroid axis regulates the body, prompting the release of thyroid hormones from residual untreated RT, leading to a subsequent decrease in TSH due to negative feedback. Research has revealed a positive correlation between a shorter interval after DTC surgery and RAI treatment (particularly within 3 months), with higher RAI treatment success rates [20]. This association may stem from the acute stress state of RT immediately after surgery, a lack of pathological alterations such as fibrosis or scarring, heightened sensitivity to external iodine stimuli, and increased iodine absorption capacity. Patients should discontinue levothyroxine usage during the waiting period for RAI treatment postsurgery, as prolonged drug withdrawal can induce severe adverse effects on patients’ endocrine, psychoneurological, and cardiovascular systems. Therefore, after surgery, patients should receive RAI promptly upon wound healing from prior to surgery, with low residual RT levels and TSH > 30 mU/L [7]. TSH levels peaked on day 17.0 after MWA for RT removal, coinciding with healed puncture wounds and meeting guideline criteria, indicating the optimal timing for RAI therapy initiation and offering crucial guidance for nuclear medicine practitioners in devising RAI treatment strategies.

Based on the relevant literature, we believe that the elevated levels of Tg after MWA may be associated with the following factors: (1) Short-term Tg elevation: Thermal ablation disrupts thyroid tissue through heat effects, leading to the release of cell contents (including Tg) into the bloodstream. This may result in a transient rise in Tg levels postoperatively (1–3 months), which is linked to acute necrosis of cells in the ablation zone and inflammatory reactions [21]. It is noteworthy that Tg levels tend to stabilize or decrease in the long term. During long-term follow-up (more than 6 months), Tg levels post-ablation may gradually decrease but typically remain higher than levels following total thyroidectomy, indicating fibrosis in the ablation zone and reduced residual thyroid tissue. However, the follow-up duration in this study was relatively short, all within one month, aligning with the study’s objectives. The patients included in this study underwent RAI therapy promptly after deactivating excessive residual thyroglobulin to prevent the negative impact of thyroid fibrosis on RAI treatment. (2) Residual tissue at the ablation zone periphery: This study preserved RT 5 mm away from the recurrent laryngeal nerve during MWA, and the remaining thyroid tissue retained its Tg-secreting function. (3) Microscopic residual foci: Some patients may have tiny foci that are not visible on imaging. However, in this study, patients underwent subsequent RAI therapy after MWA, which could help eliminate hidden foci. Therefore, we posit that the changes in Tg levels after thermal ablation such as thyroid MWA or radiofrequency ablation vary depending on treatment objectives, nature of the pathology, and postoperative timing. In this study, Tg levels not only simply reflect DTC residual or recurrence risks but are primarily associated with acute responses post-ablation, residual normal thyroid tissue, or lesions. Monitoring the trend of Tg levels dynamically rather than focusing solely on absolute values may aid in better interpreting clinical phenomena.

The procedure involves minimally invasive 16 G MWA needle insertion under local anesthesia, leading to reduced trauma and faster recovery. None of the patients experienced severe complications, such as life-threatening events or disabilities, and any adverse reactions or mild complications were reversible posttreatment, demonstrating the overall safety of MWA for RT removal. The incidence of temporary hoarseness in this study (13.04%, 3/23) exceeded previously reported rates of thermal ablation for thyroid nodules (ranging from 0.75 to 4.35%) [22]. Previous research has indicated a heightened risk of nerve injury within a 2 mm radius of the ablation zone [23]. While US imaging can clearly depict the path of the inferior thyroid artery trunk of the recurrent laryngeal nerve and its branches near the inferior pole of the thyroid gland, the nerve often exhibits variations in positioning, branching patterns, and external structure. Notably, the recurrent laryngeal nerve may emit two to three “dendritic” branches within the thyroid region, making nerve injury a prevalent complication of thermal ablation therapy for thyroid nodules, primarily stemming from transient heat-induced damage [23]. MWA for excess RT involves extensive glandular tissue ablation. In patients with a history of surgery, tissue adhesion can complicate the separation of RT in the posterior interstitial space via “liquid isolation”. Consequently, there is an increased likelihood of injury to the recurrent laryngeal nerve. Ablation of the glands adjacent to the recurrent laryngeal nerve poses a risk of nerve injury. Neck pain radiating to the teeth and ears, experienced by one patient, is a common adverse effect of thermal ablation. This discomfort may result from heat-induced stimulation of sensitive nerve cells in the thyroid, which typically resolve without specific intervention [15]. The majority of patients assessed for RAI therapy post-surgery were informed about excess RT and the requirement of prompt reoperation, a less favored option among patients. Meanwhile, minimally invasive MWA is gaining acceptance. However, patients should be thoroughly educated on the advantages and disadvantages of MWA for inactivating excess RT.

The innovative aspects of this study are as follows: (1) MWA technology was utilized for excess RT removal. US-guided MWA offers clear minimally invasive benefits and enhanced precision, presenting a novel alternative for patients who are experiencing reoperation and are at high risk for general anesthesia. (2) To our knowledge, this is the first instance of implementing the threshold effect analysis method to determine the TSH threshold value and post-MWA follow-up time. This finding implies a potential optimal period for conducting RAI therapy, offering crucial insights for nuclear medicine practitioners. The limitations of the study are as follows: (1) Given the variations in patients’ conditions and doses of RAI therapy, the efficacy of RAI therapy after RT removal was not assessed, warranting further investigation. (2) Owing to patient adherence to follow-up and the impact of the COVID-19 pandemic, some individuals have deviated from the prescribed follow-up schedule. To address this issue, the study documented actual follow-up dates and utilized a generalized additive mixed model for data fitting and analysis, mitigating this limitation. (3) Given the pilot nature of this study with a limited sample size, there could be constraints in the effectiveness of applying a generalized additive mixed model. To mitigate this limitation, expanding the study across multiple centers to increase the sample size is recommended.

Conclusions

US-guided MWA is a relatively safe and effective method for inactivating excess RT after surgery and represents a potentially innovative minimally invasive approach. The relationship between TSH and follow-up time after MWA for inactivating excess RT reveals a threshold effect, aiding in determining the optimal timing for RAI therapy post-MWA, yet its universal applicability necessitates additional investigation.