Efficacy of radiofrequency ablation for treatment of toxic thyroid nodules-a narrative review.

Background and Objective: Radiofrequency ablation (RFA) has been used in the treatment of benign thyroid nodules for the past 20 years. The adaptation of RFA to benign autonomously functioning thyroid nodules (AFTNs) has been introduced into clinical practice with variable efficacy and outcomes published in the literature. To better understand international practices, we performed a literature search to better elucidate the efficacy and outcomes in the treatment of AFTNs with RFA. Methods: Comprehensive literature searches were independently conducted by two investigators on PubMed, EMBASE, and Scopus in October of 2022 to identify articles reporting AFTN treated by RFA using the terms "RFA", "radiofrequency ablation", "thyroid nodule", "toxic nodules", and "autonomous functioning thyroid nodule". Papers were selected by relevance of the title or abstract, and the date of publication. Key Content and Findings: In patients with toxic nodules, studies have shown 50% remission rate one year after single session of RFA, up to 71% after second dose. Adverse events are generally limited to postoperative pain lasting less than one day, however there are reports of self-limited voice changes, and self-limited hypothyroidism. RFA has been shown to be safe with no reported instances of post-procedure hypothyroidism or hypocalcemia when compared to radioactive iodine (RAI) and surgery. Conclusions: RFA is an acceptable alternative to surgical resection for the treatment of AFTNs in selective patients, however more studies on long-term hyperthyroidism remission rates and nodule regrowth are necessary for further applications.

Unexpected cure of a toxic nodule in a multinodular goiter induced by immune checkpoint inhibitors: a case report.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat cancers including metastatic melanomas and can induce endocrine side effects. The thyroid is frequently affected with classically transient thyrotoxicosis followed by hypothyroidism. The evolution of thyroid nodules and goiters under ICI therapy is poorly described. Case presentation: A 72-year-old male presenting with hyperthyroidism due to a toxic nodule in a multinodular goiter (MNG) started ICI therapy combining ipilimumab and nivolumab to treat metastatic melanoma. After an initial worsening of thyrotoxicosis, treated with carbimazole, he developed profound hypothyroidism, persisting after carbimazole discontinuation, needing a long-term levothyroxine supplementation. Ultrasound control performed 6 months after ICIs treatment initiation revealed diffuse thyroid atrophy with involution of all nodules. 123I-scintigraphy confirmed a destructive mechanism. Discussion: The evolution of MNG and toxic nodules is poorly described in patients treated with ICI since systematic US evaluations are lacking. We describe for the first time a toxic nodule cured by ICI therapy inducing destructive thyroiditis. Conclusion: Pre-existing nodules and MNG, even if toxic, are not a contraindication for ICI treatment provided the patients are carefully monitored.

Radioactive Iodine for the Treatment of Subclinical Thyrotoxicosis Grade 1 and 2: Outcome of up to 18-Year Follow Up.

Background: Subclinical thyrotoxicosis (SCT) is associated with significant morbidity and mortality, specifically increased risk of atrial fibrillation and cardiovascular death. The management is ill-defined due to the scarcity of randomised controlled studies. Some clinicians recommend radioiodine (RAI) treatment however its long-term outcome is unknown. Therefore, further data is needed to provide robust evidence-based guidelines. Methods: A prospective, single-protocol analysis of the outcome of SCT patients (Grade 1; 0.1-0.4 mIU/L and Grade 2; <0.1 mIU/L) treated with mean dose of 427 MBq of I131, followed up for up to 18 years. Thyroid function tests were measured at 4-6 weeks, 3-, 6-, and 12-months post-RAI, and annually thereafter. Cure was defined as achieving a euthyroid/hypothyroid state. Results: Seventy-eight patients with a median age of 68 years (range 36-84) and varying aetiology [55 toxic multinodular goitre (TMNG), 10 toxic nodule (TN) and 13 Graves' disease (GD)] were followed up for a median period of 7.5 years (range 1-18). The cure rate was 100%. The rates of hypothyroidism in TMNG, TN and GD were 23.6%, 30% and 38.5% respectively. The median time to hypothyroidism was 6 and 12 months in GD and TMNG/TN respectively. No differences in outcome between Grade 1 versus Grade 2 were observed. Conclusion: RAI using single mean dose of 427 MBq is effective and safe, irrespective of aetiology or grade of TSH suppression. GD patients become hypothyroid within the first year, whilst TMNG/TN for up to 9-years. Thus after 12 months of follow up, annual thyroid function monitoring is advised.

Radioiodine Imaging and Treatment in Thyroid Disorders.

Thyroid hormones T3 and T4 are crucial for development and differentiation of various cells in the body. They are also essential for regulating metabolism in nearly all tissues. Iodine is an integral element in the synthesis of thyroid hormone and is actively transported into the thyroid by a Na+/I- symporter. The thyroid can take up radioactive iodine just like it would take iodine and hence can be used to evaluate and treat several thyroid diseases. Radioactive iodine is one of the first radioisotopes to be used in medicine.

Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy of Radioactive Iodine Monotherapy versus Radioactive Iodine Therapy and Adjunctive Lithium for the Treatment of Hyperthyroidism.

Background: The objective of this article is to evaluate the outcomes in patients undergoing radioactive iodine (RAI) with adjunctive lithium (Li) therapy versus (vs.) RAI therapy alone for the treatment of hyperthyroidism.Methods: A systematic review of the literature was undertaken to analyze clinical trials comparing RAI with adjunctive Li therapy vs. RAI therapy alone for the treatment of hyperthyroidism.Results: Six randomized-controlled trials (RCT) involving 755 patients were analyzed. RAI with adjunctive Li was associated with a significantly higher cure rate for hyperthyroidism when compared to RAI alone. Furthermore, a significantly higher cure rate for hyperthyroidism at 12 months was achieved with RAI and adjunctive Li. Adjuvant Li with RAI for ≤ 7 days showed significantly higher cure rate compared to RAI alone, whereas > 7 days of adjuvant Li with RAI did not show any difference in cure rate compared to RAI alone. RAI with adjunctive Li was associated with a significantly higher cure rate for patients with Graves' disease compared to RAI alone. There was no significant difference between RAI with adjunctive Li and RAI alone for toxic nodular thyroid disorder (toxic nodule and toxic multinodular goiter) and thyroid volume >40 grams and ≤40 grams.Conclusions: RAI with adjunctive Li therapy demonstrated superiority over RAI therapy alone with regards to both curing hyperthyroidism and, reduced time till cure, with a limited side effect profile. A large multicenter RCT is required, and if this confirms the data from these smaller trials, then this could change current practice.

A synchronous papillary and follicular thyroid carcinoma presenting as a large toxic nodule in a female adolescent.

CASE PRESENTATION: We report for the first time a synchronous papillary and follicular thyroid carcinoma in a 12-year-old girl presenting with a large (5 cm diameter) left thyroid nodule, an increased left and right upper pole technetium tracer uptake at scintigraphy and hyperthyroidism. The uptake at the right lobe was explained by the crossing of the left nodule to the right site of the neck at Computed Tomography (CT) scanning. BACKGROUND: Although thyroid nodules are less common in children than in adults, there is more vigilance required in children because of the higher risk of malignancy. According to literature, about 5% of the thyroid nodules in adults are malignant versus 20-26% in children. The characteristics of 9 other pediatric cases with a differentiated thyroid carcinoma presenting with a toxic nodule, which have been reported during the last 20 years, are summarized. A nodular size of more than 3.5 cm and female predominance was a common finding. CONCLUSIONS: The presence of hyperthyroidism in association with a hyperfunctioning thyroid nodule does not rule out thyroid cancer and warrants careful evaluation, even in the absence of cervical lymph node invasion.

Monopolar Radiofrequency Ablation of Thyroid Nodules: A Prospective Austrian Single-Center Study.

BACKGROUND: Monopolar radiofrequency ablation is currently deemed an exotic treatment option for benign thyroid nodules in many central European countries. The aim of this study was to evaluate prospectively the safety and efficacy of this method in a large patient cohort following its introduction in Austria. METHODS: Peri- and post-interventional complications were analyzed for 277 patients. Efficacy was determined for 300 and 154 nodules at 3 and 12 months post treatment, respectively. All treatments were performed with an internally cooled 18G radiofrequency electrode using a free-hand, "moving-shot" technique following subcutaneous and local perithyroidal anesthesia. RESULTS: Mean patient age (SD) was 52 ± 12.9 years (75% female), and overall mean baseline nodule volume (SD) was 13.8 ± 15.9 mL. Nodules were visible in 62.8% of patients, 40% had a symptom score ≥4 on a 10-point visual analogue scale, and 14.4% had hyperthyroidism. Mean overall nodule volume reduction rates (VRR) at 3 and 12 months were 68 ± 16% and 82 ± 13%, respectively (p < 0.001). At 12 months, 81% of nodules exhibited a VRR of ≥70%, with 10%, 6%, and 2% of nodules showing VRRs of 60-70%, 50-60%, and ≤50%, respectively. Subgroup analysis according to baseline nodule size (≤10 mL to >30 mL) or baseline nodule composition (solid, mixed, cystic) revealed significantly higher VRRs for smaller and cystic nodules. Moreover, nodule shrinkage was accompanied by significantly improved symptom and cosmetic scores after 3 and 12 months (p < 0.001). Of 32 hyperthyroid patients, 27 (84%) were euthyroid, four had subclinical hyperthyroidism, and one had subclinical hypothyroidism at last follow-up. Post-procedural complications were absent in 83% of patients, minimal in 12.9%, moderate and reversible in 3.2% (1.8% voice change, 0.7% hyperthyroidism, 0.3% wound infection treated with antibiotics, 0.3% epifascial hematoma), and irreversible in 0.7% (one case with hypothyroidism and one with a wound infection treated by surgery). CONCLUSIONS: It is concluded that a single treatment course with monopolar radiofrequency ablation is both safe and highly effective in terms of nodule volume reduction, relief of local symptoms, and (in patients with hyperthyroidism) restoration of euthyroid function. In no case was a prescription of thyroid medication required among those patients who were euthyroid at baseline.

Intrathoracic toxic thyroid nodule causing hyperthyroidism with a multinodular normal functional cervical thyroid gland.

Radionuclide scintigraphy with I-131 and Tc-99m pertechnetate ((99)mTc04) has been widely used in detecting toxic nodules. Intrathoracic goiter usually presents as an anterior mediastinal mass. Mostly the connection between intrathoracic mass and the cervical thyroid gland is clearly and easily identified occurring as a result of inferior extension of thyroid tissue in the neck, which is called as secondary intrathoracic goiter. Completely separated, aberrant or in other words primary intrathoracic goiters arise as a result of abnormal embryologic migration of ectopic thyroid closely associated with aortic sac and descend into the mediastinum. Intrathoracic goiters are generally nontoxic nodules existing with mass effect without causing hyperthyroidism. However, mostly reported cases had enlarged thyroid glands in the neck. This report demonstrates the usefulness of I-131 and (99)mTc04 scintigraphy for detecting intrathoracic goiter causing hyperthyroidism with a normal functioned cervical thyroid gland.

Comparison of ultrasonography features and malignancy rate of toxic and nontoxic autonomous nodules: a preliminary study.

OBJECTIVE: When a scintigraphically autonomous nodule does not produce thyroid hormones enough to suppress serum thyrotrophin, it is generally defined as nontoxic autonomous nodule. In this study, we aimed to compare clinical and ultrasonographical (US) features and cytological and histopathological results of toxic and nontoxic autonomous nodules. METHODS: Patients who underwent thyroidectomy and were evaluated with technetium-99m-pertechnetate scintigraphy preoperatively in our institution between May 2008 and December 2014 were identified from medical records. Among these, treatment naïve patients with scintigraphically autonomous thyroid nodules were chosen and classified into toxic (hyperthyroid) and nontoxic (euthyroid) groups. The demographic data, preoperative US features of the nodules, fine needle aspiration biopsy and histopathological results were analyzed. RESULTS: There were 170 (89.0%) patients with toxic and 21 (11.0%) patients with nontoxic autonomous nodules. A total of 258 scintigraphically autonomous nodules were analyzed among which 227 were clinically functional (toxic) and 31 were clinically euthyroid (nontoxic). Echogenity, texture, marginal irregularity, presence of halo and macrocalcification were similar in toxic and nontoxic autonomous nodules. Toxic autonomous nodules were significantly bigger and had a significantly higher rate of microcalcification compared to nontoxic ones (p = 0.001 and p = 0.025, respectively). There was no significant difference in terms of cytological diagnosis between toxic and nontoxic autonomous nodules (p = 0.052). Atypia of undetermined significance/follicular lesion of undetermined significance cytology was significantly higher in nontoxic group (p = 0.01). 20 (8.8%) of 227 toxic and 2 (6.5%) of 31 nontoxic autonomous nodules were malignant (p = 0.59). Considering all nodules regardless of the thyroid function, 8.5% of autonomous nodules was malignant. CONCLUSION: US features and malignancy potential of nontoxic autonomous nodules resemble toxic autonomous nodules. Lower diameter suggests that they can represent a preliminary stage of toxic ones and have potential of toxicity when get bigger in size. There is still a considerable risk of malignancy risk in autonomous nodules whether toxic or not.

An experimental comparison of two different technetium source activities which can imitate thyroid scintigraphy in case of thyroid toxic nodule.

PURPOSE: In cases of thyroid toxic autonomous nodule, anterior projection of Tc-99m pertechnetate image shows a hot nodule that occupies most, or the entire thyroid lobe with near-total or total suppression of the contra lateral lobe. In this case is very difficult to distinguish toxic nodule from lobe agenesis. Our interest was to estimate and determinate the rate of radioactivity when the source with high activity can make total suppression of the second source with low activity in same conditions with thyroid scintigraphy procedures. MATERIAL AND METHODOLOGY: Thyroid scintigraphy was performed with Technetium 99 meta stable pertechnetate. A parallel high resolution low energy collimator was used as an energy setting of 140 KeV photo peak for T-99m. Images are acquired at 200 Kilo Counts in the anterior projection with the collimator positioned as close as the patient's extended neck (approximately in distance of 18 cm). The scintigraphy of thyroid gland was performed 15 minutes after intravenous administration of 1.5 mCi Tc-99m pertechnetate. Technetium 99 meta stable radioactive sources with different activity were used for two scintigraphies studies, performed in same thyroid scintigraphy acquisition procedures. In the first study, were compared the standard source with high activity A=11.2 mCi with sources with variable activities B=1.33 mCi; 1.03 mCi; 0.7 mCi; 0.36 mCi; and 0.16mCi) in distance of 1.5cm from each other sources, which is approximately same with distance between two thyroid lobes. In the second study were compared the sources with low activity in proportion 70:1(source A = 1.5 mCi and source B=0.021mCi). As clinical studies we preferred two different patents with different thyroid disorders. There were one patient with thyroid toxic nodule in the right lobe, therefore the second patient was with left thyroid nodule agenesis. RESULTS: During our examination, we accurately determined that two radioactive sources in proportion 70:1 will be displayed as only one source with complete suppression of other source with low radioactivity. Also we found that covering of toxic nodules with lead cover (plaque), can allow visualization of activity in suppressed lobe. CONCLUSION: Our study concluded that total lobe suppression, in cases of patients with thyroid toxic nodule, will happened for sure, if toxic nodule had accumulated seventy times more radioactivity than normal lobe. Also we concluded that covering of the toxic nodule with lead plaque, may permit the presentation of radioactivity in suppressed nodule.

Anaplastic carcinoma and toxic multinodular goiter: an unusual presentation.

A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far.