Non-surgical management of RG
When surgery is not indicated or it is not feasible because of the patient’s general status, frailty, or comorbidities, a wait-and-see approach or medical treatment of RG may be proposed5,21. In the most recent literature, no new studies regarding levothyroxine supplementation or radioiodine treatment have been published. For both options many drawbacks are present (missed malignancy, risk of thyrotoxicosis or of an increase airway obstruction) and only with the advantage of a slow and modest size reduction at best21. Instead minimal-invasive techniques such as transcervical microwave ablation (TcMA), transcervical radiofrequency ablation (TcRfA), or selective embolization of the thyroid arteries (SETA), whose preliminary reports date back to the 2000s, are being further explored.
Ultrasound-guided microwave TCA of RG combined with ethanol injection was reported as an effective and safe treatment for solitary nodular RG, especially for patients who are ineligible or unwilling to receive surgical treatment 46,47. A first preliminary experience was presented by Cui et al in 2018 on 10 patients a mean volume reduction ratio (VRR) of around 67% was reported after one month, while no local (pain, hematoma, etc.) or functional (thyrotoxicosis crisis, changes in TSH, etc.) adverse events were reported46. In a subsequent prospective study from the same hospital involving 72 patients (mean age 47.8 years) and with a mean follow-up of 23.9 months, TCA yielded a mean VRR of 83.12 ± 12.74 % (range: 52.01–100%) after one year; 57 patients (79.2%) showed a total regression of the intrathoracic extension (by CT scan) while 8 patients (11.1%) needed a second procedure because of “regrowth of unsatisfactory reduction”. 4.2% (3/72). Two patients complained of temporary neck pain/discomfort, while there was a case of postprocedural dysphonia, which resolved spontaneously after 1 month, for an overall complication rate of 4.2%47.
It should be noticed that in both studies, a significant reduction in terms of RG-associated signs and symptoms (i.e. , neck circumference and a VAS scale measuring pain, shortness of breath, positional dyspnea, dysphagia, and dysphonia) was obtained, despite the fact that the procedure focused only on the largest retrosternal nodule46,47.
TcRfA is another option and Chiang et al. recently showed a VRR of 75.5% (p<0.001) in a series of 16 RGs48. In this series, only 4 (25%) patients showed complete regression of the substernal portion of the goiter, while there was a case of temporary hoarseness and a case of subcutaneous/focal mediastinal hematoma, which was managed conservatively (complication rate 12.5%). Nonetheless, all the patients reported significantly lower cosmetic and symptom scores on the VAS scale at 6 months48.
Regarding the SETA procedure, a small Italian series of 10 patients reported complete success in reducing the thyroid function and RG dimensions but no formal endpoints were used, and follow-up time was not reported. In addition, all patients developed transient thyrotoxicosis requiring corticosteroids, antibiotics, and methimazole, while one patient (10%) had right vocal cord fixation lasting around 6 months49. Yilmaz and coworkers instead presented their experience with SETA in 56 goiters, and among them 47 were considered “intrathoracic”50. The procedure was conducted successfully in 145 out of the 146 thyroid arteries and complications occurred in 27 patients (48%), but if we eliminate a case of intraoperative blurry vision, one case of groin hematoma, and 23 cases of hyperthyroidism (since it is a predictable effect because of the necrosis of the gland), only 3 (5%) patients developed temporary hoarseness. Notably, after 6 months, the mean thyroid volume was reduced from 147.0 mL to 62.6 mL, while the mean retrosternal extension was reduced from 31.7 mm to 15.9 mm (P < .001). Quality of life was measured by the popular ThyPRO tool and the mean scores improved from 155.4 to 70.4 (P < .001)50. These authors also reported that one patient died of myocardial infarction two weeks after SETA, and a possible causative effect cannot be excluded. Despite the absence of a comparative study, SETA is reported to be applicable irrespective of the goiter dimensions but this does not fit the preprocedural reported mean dimensions of the nodules (80.2 ± 46.7 mL for SETA50, versus 76.10 ± 50.56 mL for TcMA47).
In summary, all these non-surgical approaches have many advantages (no reported risk of iatrogenic hypothyroidism or hypoparathyroidism; they are a day or one-day procedures for ablation and SETA, respectively; they can be performed even in very fragile patients, etc.) but they retain the fundamental limit of not permitting any histological evaluation of the RG, even though at least one50, or two47 consecutive non-malignant (up to Bethesda category 3) fine-needle core biopsies were required as an inclusion criterion. The clinical experience remains however limited and, most importantly, the lack of a head-to-head comparison between standard surgical resection and these techniques remains their central limit.