Safety and Efficacy of Radiofrequency Ablation of Thyroid Nodules

Expanding Treatment Options in the United States

Iram Hussain; Fizza Zulfiqar; Xilong Li; Shahzad Ahmad; Jules Aljammal

Disclosures

J Endo Soc. 2021;5(8) 

In This Article

Results

A total of 58 thyroid nodules in 53 patients (50 female, 3 male) were treated with RFA. The patients were predominantly Caucasian (51 Caucasian, 1 African American, and 1 Asian patient). The median age was 45 years (range, 30–77 years) (Table 1). Eleven patients did not return for follow-up (10 female and 1 male, all Caucasian). The remaining 42 patients had a total of 23 NFTNs and 24 AFTNs that were analyzed after RFA. Thirty-nine nodules were predominantly solid (defined as more than 75% solid) and 8 were mixed solid-cystic nodules (defined as 25%-75% solid), of which 6 were >50% solid, and 2 were ~25% solid and 75% cystic. Baseline characteristics of the cohort are described in Table 1.

On initial post-RFA evaluation, the median reduction in volume was 70.8% (range, 32.1%-96.3%) after a median follow-up period of 109 days (range, 31–654 days) (Figures 2 and 3). Twenty-five patients had contralateral thyroid nodules that were not treated with RFA. The volume reduction in RFA treated nodules was significant compared to those that were not treated (P value <0.0001). Nodules that did not undergo RFA did not significantly change during the same follow-up period (Figure 4).

Figure 2.

Change in volume over time in nonfunctioning thyroid nodules (NFTN) after radiofrequency ablation (RFA). Each line represents an individual nodule; Time 0 days indicates the day of the RFA procedure, with the length of the line representing length of follow-up period. Each circle represents a point in time where volume of the nodule was measured by ultrasonography, and the points are connected by lines to give an approximate rate of volume reduction. A, Change in volume of NFTNs with initial volumes of less than 20 mL. B, Change in volume of NFTNs with initial volumes of more than 20 mL.

Figure 3.

Change in volume over time in autonomously functioning thyroid nodules (AFTN) after radiofrequency ablation (RFA). Each line represents an individual nodule; Time 0 days indicates the day of the RFA procedure, with the length of the line representing length of follow-up. Each circle represents a point in time where volume of the nodule was measured by ultrasonography, and the points are connected by lines to give an approximate rate of volume reduction. A, Change in volume of AFTNs with initial volumes of less than 20 mL. B, Change in volume of AFTNs with initial volumes of more than 20 mL.

Figure 4.

Change in volume over time of incidental thyroid nodules that did not undergo radiofrequency ablation (RFA). Each line represents an individual nodule; Time 0 days indicates the day RFA was performed on the contralateral nodule, with the length of the line representing length of follow-up. Each circle represents a point in time where volume of the nodule was measured by ultrasonography, and the points are connected by lines to give an approximate rate of volume reduction. A, Change in volume of incidental thyroid nodules in patients who underwent RFA of nodules with initial volume <20 mL. B, Change in volume of incidental thyroid nodules in patients who underwent RFA of nodules with initial volume >20 mL.

Volume reduction percentage (VRP) had an inverse relationship with the size of the nodule (P = 0.0266); with median VRP of 75.9% (range, 32.1%-96.3%) in nodules less than 10 mL in volume (n = 27 nodules); 61.6% (range, 40%-89.6%) in nodules 10 to 20 mL (n = 10); and 50.4% (range, 32.1%-92.9%) in nodules more than 20 mL (n = 10), respectively (Table 2). Overall, 38 out of 47 nodules (~80.9%) had a volume reduction of more than 50% during the total follow-up period (Figures 2 and 3). A volume reduction of more than 50% within the first 6 months of the ablation could only be confirmed in 30 nodules, as post-RFA ultrasonography was performed after 6 months in some patients.

The median VRP in predominantly solid nodules was 69% (range, 32.1%-96.3%), while the median VRP of mixed solid-cystic nodules was 77% (range, 47.4%-92.9%); however, this difference was not statistically significant (P = 0.249).

The initial median volume of NFTNs (n = 23) was 10.4 mL (range, 1.95–54.9 mL), which decreased to a median of 2.09 mL (range, 0.57–31.6 mL) after RFA, representing a median VRP of 69% (range, 32.1–86.1%) over a median follow-up period of 116 days (range, 40–654 days) (Figure 2). The initial median volume of AFTNs (n = 24) was 5.4 mL (range, 0.4–53.9 mL), which decreased to a median of 1.8 mL (range, 0.08–36.4 mL) after RFA, representing a median VRP of 71.1% (range, 31.7%-96.3%) over a median follow-up period of 87 days (range, 31–613 days) (Figure 3). There was a trend toward higher energy use resulting in smaller volume reduction (P = 0.1); however, there was no significant association between energy applied and volume reduction when adjusted for the initial volume of the nodule (P = 0.43). Both NFTNs and AFTNs showed similar volume reductions, and there was no statistical difference between the groups when adjusted for initial volume and energy applied.

Among the patients with NFTNs, 7 were already on levothyroxine for hypothyroidism prior to RFA, which was continued after the procedure. One of these patients did have an elevated TSH (9.6 mIU/L) after RFA while free T4 remained normal (1.2 ng/dL); however, this was attributed to the patient taking her levothyroxine inconsistently. None of the patients who were not on levothyroxine prior to RFA treatment developed thyroid dysfunction after the procedure. These patients had a median TSH of 1.3 mIU/L both before (range, 0.75–3.75 mIU/L), and after (range, 0.9–2.7 mIU/L) RFA; and a median free T4 of 0.94 ng/dL (range, 0.8–1.3 ng/dL) before RFA and 0.89 ng/dL (range, 0.74–1.1 ng/dL) after RFA. There was no significant difference between the pre- and post-RFA TSH (P = 0.09); however, the difference between the pre- and post-RFA free T4 was significant (P = 0.02). Of the 15 patients not on levothyroxine prior to RFA, 6 patients had TPO Ab checked, and 3 of these patients had elevated TPO Ab levels. Only 3 of the 7 patients already on levothyroxine had their TPO Ab checked, and all had elevated levels.

Patients with AFTNs had predominantly subclinical hyperthyroidism, with only 1 patient out of 20 with overt hyperthyroidism, and 1 patient who had normal thyroid function tests with AFTN diagnosed on radioactive iodine uptake and scan. Eight patients were on methimazole prior to RFA; it was continued in 6 patients immediately after the procedure and discontinued in 2 patients. Of the 6 patients who continued methimazole, 3 patients had discontinued it after 1 month, 6 months, and 7 months, respectively, and 3 patients were on a lower dose (2.5–5 mg by mouth daily) at the last follow-up appointment. Of note, out of the 8 patients on methimazole prior to RFA, 5 patients had TPO Ab checked; 2 patients had elevated levels, whereas 3 patients did not have TPO Ab. Of the 3 patients who were on methimazole at the last follow-up, only 1 had positive TPO Ab. Thyroid-stimulating immunoglobulin and thyroglobulin antibodies were not checked.

Thyroid function tests significantly improved after RFA of AFTNs in patients not on methimazole, with a median TSH of 0.1 mIU/L (range, 0.01–0.32 mIU/L) before the procedure, compared with a median TSH of 0.63 mIU/L (range, 0.01–1.2 mIU/L) after RFA (P = 0.0015); and a median free T4 of 1.15 ng/dL (range, 0.9–1.9 ng/dL) before RFA and 0.9 ng/dL (range, 0.7–1.8 ng/dL) after the procedure (P = 0.01). All patients had normal free T4 levels (normal range, 0.7–1.8 ng/dL) after RFA; and 15 of 20 patients (75%) had their TSH normalize (normal range, 0.4–4.5 mIU/L) within 12 months of the procedure; however, 3 of the 15 patients were still on methimazole. These 3 patients chose to continue methimazole rather than get definitive therapy with radioactive iodine or surgery.

The patient with normal thyroid function tests in the presence of a confirmed AFTN reported resolution of symptoms after the procedure and her TSH remained normal. One patient had 2 RFA procedures on the same AFTN 1 year apart and only the first ablation was used in the volume reduction calculations. She had a volume reduction of 76.3% after her first ablation; however, her TSH remained suppressed so she elected to have a second RFA, with a further volume reduction of 29.6% over 58 days. Her TSH did normalize after the second procedure; the level was 0.76 mIU/L with the patient off methimazole at the last follow-up. Her cosmetic score improved from 4 to 2 after the first RFA and from 2 to 1 after the second.

The median cosmetic score before RFA was 4 (range, 0–4), and this improved significantly to a median of 2 (range, 0–4) after the procedure (P < 0.0001). NFTNs caused more cosmetic concern with a median cosmetic score of 4 (range, 3–4) before RFA, whereas patients with AFTNs had a median cosmetic score of 3.5 (range, 0–4). After RFA, the median cosmetic score decreased significantly to 2 (range, 0–4) and 1 (range, 0–3) in NFTNs and AFTNs, respectively. One patient with a NFTN and pretreatment cosmetic score of 4 was not seen physically in clinic so posttreatment cosmetic score was not assessed. Compressive symptoms (if present prior to RFA) improved in all patients. The response to RFA is summarized in Table 3.

No major complications were noted after RFA. Among minor complications, 1 patient developed a hematoma that resolved spontaneously within a day; and 1 patient developed hoarseness of voice during the procedure and 10 mL of cold dextrose 5% in water was injected in the tracheoesophageal groove with partial improvement in symptoms at the time. She did not have any predisposing factors for hoarseness of voice (nonsmoker, not a singer, and no vocal polyps confirmed on laryngoscopy). Her voice returned to normal in 6 months. Vocal cord recovery was documented by laryngoscopy and ultrasonography. The total complication rate was 4.2%.

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