Percutaneous ethanol injection therapy in benign solitary solid cold thyroid nodules: A randomized trial comparing one injection with three injections

The aim of the present study was to evaluate the efficacy of percutaneous e thanol injection therapy (PEIT) with special reference to dose response and symptom score and to describe side effects in a parallel-group randomized clinical trial with 6 months of follow-up, comparing 2 different treatment strategies. Sixty euthyroid outpatients with a benign solid and scintigraph ically solitary cold thyroid nodule causing local discomfort were assigned to 1 session with a single intranodular injection of sterile 98% ethanol (P EIT-1, n = 30) or 3 weekly sessions with 1 injection of sterile 98% ethanol (PEIT-3, n = 30). In the PEIT-1 group, the pretreatment nodule volume was 9.9 +/- 5.7 mL (mean +/- SD). It decreased to 7.0 +/- 4.7 mL after 1 month, and 5.6 +/- 5.9 mL after 6 months (p = 3.2 x 10(-6)), and the ethanol dose given was 24.7% +/- 7.5% of the pretreatment nodule volume, The overall re duction in nodule volume was 46%. In the PEIT-3 group the pretreatment nodu le volume was 9.4 +/- 4.2 mL. It decreased to 5.9 +/- 3.5 mL 1 month after the last session, and 4.6 +/- 2.6 mL after 6 months (p = 4.0 x 10(-10)), an d the cumulative ethanol dose given was 47.9% +/- 21.3% of the pretreatment nodule volume. The overall reduction in nodule volume was 51%, and the dif ference between the 2 treatment regimens was 5.3% +/- 5.5% (mean +/- SE of difference, p = 0.3). A satisfactory treatment dose, defined as a total int ranodular spread of ethanol visualized on the monitor screen, was achieved in only 50%-60% of the sessions. This was due to pain that necessitated pre mature discontinuation of the injection and was apparently severe enough in 3 patients in the PEIT-3 group that they refused additional treatment. Twe nty-two of 30 (73%) patients in the PEIT-1 group and 19 of 30 (63%) in the PEIT-3 group had a marked effect on symptoms at 6-month follow-up (p = 0.6) . Side effects comprised transient thyrotoxicosis in 2 patients, permanent ipsilateral facial dysesthesia and increased flow of tears in 1 patient, pa ranodular fibrosis impeding subsequent surgery in 1 case and various degree s of pain and tenderness related to PEIT in nearly all. Major side effects were dose dependent. We conclude that PEIT is effective in inducing necrosi s and reducing the volume of benign solid cold thyroid nodules. The additiv e effect of 2 additional doses compared with 1 dose is insignificant. The o ptimum management strategy has yet to be clarified. Limitations relate to t he procedure being quite painful despite local anesthesia and the fact that side effects are in no way negligible, and therefore, a word of caution in routine use is advisable.