Endocrinology and Metabolism

Original Article

Clinical Study
Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis: Cheng-Chun Yang, Yung Hsu, Jyun-Yan Liou; Endocrinol Metab. 2021;36(1):81-95. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.833

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Background
Ultrasound-guided minimally invasive procedures are widely used to treat thyroid diseases. The objective of this study was to assess the efficacy and safety of ethanol ablation (EA) in comparison with other non-surgical options in the treatment of benign thyroid cystic nodules.
Methods
We conducted a systematic search of studies on EA for thyroid cystic nodules, mainly in the Ovid-MEDLINE and Embase, Web of Science, and Cochrane databases. The standardized mean difference (SMD) of the volume reduction ratio (VRR) after EA versus other non-surgical treatments comprised the primary outcome, whereas the odds ratio (OR) of therapeutic success rates between the two groups comprised the secondary outcome.
Results
The meta-analysis included 19 studies (four randomized controlled trials and 15 non-randomized studies) with 1,514 participants. The cumulative VRR of EA was 83.908% (95% confidence interval [CI], 79.358% to 88.457%). EA had a significantly higher pooled VRR (SMD, 0.381; 95% CI, 0.028 to 0.734; P=0.030), but not a significantly higher pooled therapeutic success rate (OR, 0.867; 95% CI, 0.132 to 5.689; P=0.880), than other forms of non-surgical management including radiofrequency ablation (RFA), polidocanol sclerotherapy, and simple aspiration with or without saline flush. However, the VRR and therapeutic success rate were not significantly different between EA and RFA. Major complications were recorded only in six patients (0.53%) with self-limiting dysphonia.
Conclusion
The role of EA as the first-line treatment for benign thyroid cysts and predominantly cystic nodules is supported by its high effectiveness and good safety profile compared to other currently available non-surgical options.

Citations

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Review Article

Thyroid
Management of Low-Risk Papillary Thyroid Cancer: Nicole M. Iñiguez-Ariza, Juan P. Brito; Endocrinol Metab. 2018;33(2):185-194. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.185

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The incidence of thyroid cancer has increased, mainly due to the incidental finding of low-risk papillary thyroid cancers (PTC). These malignancies grow slowly, and are unlikely to cause morbidity and mortality. New understanding about the prognosis of tumor features has led to reclassification of many tumors within the low-risk thyroid category, and to the development of a new one “very low-risk tumors.” Alternative less aggressive approaches to therapy are now available including active surveillance and minimally invasive interventions. In this narrative review, we have summarized the available evidence for the management of low-risk PTC.

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Original Articles

Percutaneous Ethanol Injection in Autonomous Functioning Thyroid Nodules and Complex Cysts: Five Years' Experience.: Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn; J Korean Endocr Soc. 2002;17(1):57-68. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection therapy (PEI) performed with ultrasonography guidance has recently been used in cases of autonomous functioning thyroid nodules (AFTN) and benign complex cysts. We performed this study to analyze the effects of PEI on AFTN and benign complex cysts. METHEODS: From September 1995 to September 2000, we performed PEI on 456 outpatients (47 men and 409 women, mean age 42.4+/-11.8 years) with AFTN or benign complex cysts. All cases were subjected to fine needle aspirations (FNA) by ultrasonography-guidance if necessary. FNA was performed at least twice with results of colloid nodule in cases of complex cysts. For AFTN, cases with FNA results of follicular neoplasm were also included. After PEI on AFTN, patients were classified into three response groups: complete response as judged by our new criteria (CR, normalization of TSH and free T4, disappearance of hot nodule on thyroid scan) along with the old criteria of previous studies (normalization of TSH and free T4, recovery of suppressed extranodular tissue on thyroid scan), partial response (PR, normalized free T4 but suppressed TSH, persistent hot nodule despite recovery in suppressed extranodular tissue) and no response (no change of hot nodule). Complex cysts were classified into three groups in accordance with volume reduction after PEI: complete response (CR, above 90% of volume reduction), partial response (PR, 50~89%) and no response (below 50%). RESULTS: Overall pre-treatment volumes were 15.3+/-12.1 mL and post-treatment volumes were 2.8+/-2.9 mL, with 66.4+/-19.9% of volume reductions in AFTN and complex cysts. Volume reductions were 71.5+/-18.0% in AFTN, and 66.1+/-15.0% in complex cysts. In 24 cases of AFTN, responses satisfying the previous criteria were 14 (58.3%) of CR, 6 (25.0%) of PR, and 4 (16.7%) of no response. However, by the new criteria there were 1 (4.2%) of CR, 10 (41.6%) of PR, and 13 (54.2%) of no response. In 432 cases of complex cysts, CR was observed in 82 (19.0%), PR in 261 (60.4%) and no response in 89 (20.6%). The volume reductions in complex cysts with pre-treatment volume larger than 15 mL were higher than those of groups with smaller volumes (p<0.001). Pre-treatment volumes were not correlated with post-treatment volumes, nor with volume reductions. Volume reductions were not correlated with the amounts of injected ethanol. Mild and transient complications were observed in 41 cases (9.0%) during PEI, consisting of transient neck pain (n=36, 7.9%), transient unilateral vocal cord palsy (n=3, 0.7%), intracavitary hemorrhage (n=1, 0.2%), and transient hypotension (n=1, 0.2%). CONCLUSION: Our data suggest that the efficacy of PEI on AFTN is temporary and does not usually induce long-term complete remissions. In complex cysts, however, PEI may have potential as an additive treatment modality to thyroid hormone suppressive therapy

Effectiveness of Percutaneous Ethanol Injection in Benign Cold Thyroid Nodules: Five Years' Experience.: Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn; J Korean Endocr Soc. 2001;16(2):210-220. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection therapy (PEI) which is performed with the guidance of ultrasonography has recently been used in patient who had benign cold thyroid nodules. We performed this study to analyze the long-term effects of PEI on benign cold thyroid nodules. METHOD: From September 1995 to September 2000, we treated 198 outpatients (12 men and 186 women, who had a mean age of 40.8 years, with a range of 15-71) who had benign cold thyroid nodules at the Asan Medical Center. The PEI was performed on 141 patients who had solitary nodules (SN) and on 57 patients who had prominent nodules or Questionable or typing error? multiple nodules (MN). All patients had fine needle aspirations (FNAs) at least twice which resulted in a diagnosis of the presence of a colloid nodule. Thyroid hormone was given to all patients along with TSH measurements. The thyroid hormone dose was titrated to correspond to TSH level of a low normal range. These patients were followed up for mean period of 37.6 months (range 18-60). Patients who were treated with PEI were classified into three groups according to their volume reduction: a complete response (CR, which was above 90% in volume reduction), a partial response (PR, which was a 50-89%) reduction and No Response (which was below 50% or an increased size) groups. RESULTS: The overall pre-treatment volumes of the nodules were 15.7+/-19.8 mL. The overall post-treatment volumes were 2.4+/-2.6 mL and consisted of volume reductions of 70.1+/-17.1%. The results of PEI for all of the patients were: a complete reduction (CR) in 34 cases (17.2%), a partial reduction (PR) in 142 cases (71.7%) and No Response in 22 patients (11.1%). In 141 patients in the SN group, in which there was a mean follow-up duration of 36.7+/-11.2 months, the volume reductions were 68.3+/-18.8%. CR was observed in 20 patients (14.2%), PR in 103 (73.0%) and No Response in 18 (12.8%). In twenty-two of the SN patients (22/141, 15.6%) we were able to discontinue the thyroid hormone suppressive therapy because those nodules had markedly decreased in volume after PEI without any further increase of nodule size during the follow-up period. In 57 patients in the MN group, over a mean follow-up durations of 37.1+/-11.4 months, the volume reductions were 74.3+/-12.1%. CR was observed in 14 patients (24.6%), PR in 39 (68.4%) and No Response occurred in 4 (7.0%). During the follow-up period after PEI, further volume reductions were observed for 36 months after thyroid hormone suppressive therapy in the Response Group. Differences in volume reductions between the SN and MN groups were not statistically significant but the volume reductions in patients who had a pre-treatment volume larger than 15 mL were higher than those in the smaller group (p<0.001). In the cases of the SN and MN groups, volume reductions did not correlate with either the amount of injected ethanol or the pre-treatment volumes, but the pre-treatment volumes correlated with post-treatment volumes in the patients who had SN (p<0.001, r=0.411) and MN (p<0.001, r=0.729). We observed mild, but transient complications in 32 patients (16.2%) during PEI which included a transient neck pain (n=27, 13.6%), a transient unilateral vocal cord palsy (n=4, 2.0%), and an abscess formation (n=1, 0.5%) which was cured. CONCLUSION: These results suggest that PEI is a feasible adjunctive therapy to use in thyroid hormone suppressive therapy for benign cold thyroid nodules

Percutaneous Ethanol Injection in Benigh Thyroid Nodules.: Hong Kyu Kim, Il Min Ahn, Eun Joo Lee, Jin Yub Kim, Mi Heon Lee, Sung Jin Lee, Ho Kyu Lee; J Korean Endocr Soc. 1998;13(3):373-383. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection(PEI) performed in guidance of ultrasonography has been used in cases of thyroid cyst and autonomous functiong thyroid nodule(AFTN). We performed this study to determine the feasibility of PEI on the various type of benign cold nodules(solid, pure cyst, complex cyst) and AFTN. METHOD: Ninety patients(age 41+12 years; 83 women and 7 men) with hot and cold nodule were included in this study. All cases were subjected to FNAB, and sono-guided in cases of complex cyst, at least twice with results of colloid nodule. T4 suppression treatment was done for cold solid nodules for at least 6 months and cases which had partial response(50% or more volume reduction but no further volume decrease on T4 suppression) were included in this study. After PEI, we classified AFTN into three different response groups; complete response (normali- zation of TFT and thyroid scan finding), partial response(normalized freeT4 but suppressed TSH or persistently suppressed scan), or failure group. Each subtypes(solid, pure cyst, complex cyst) of cold nodules were also classified into three groups in accordance with volume reduction; complete response(above 90% of volume reduction), partial response(50-90%), and failure(below 50% or increase in size) group. RESULTS: Overall responses rate of PEI for benign thyroid nodule were complete; 70(78%), partial; 18(20%), and failure; 2(2%). In 27 cold solid nodules, complete response was observed in 23(85%) and partial response in 4(15%). In 11 pure cysts, complete response was observed in 7(64%), partial response in 3(27%), and 1 case(9%) of failure was lost after 1 trial of PEI. In 45 cases of complex cyst, complete response was observed in 36(80%), partial response in 8 (18%), and 1 case(2%) of failure was subjected to operation with pathology report of Hiirthle cell adenoma. In 7 cases of AFTN, complete response was observed in 4(57%) and partial response in 3(43%). We observed complications during PEI therapy such as transient neck pain(n=10), transient unilateral vocal cord palsy(n=l), and intracavitary hemorrhage(n=2), transient hypotension during ethanol injection(n 1). CONCLUSION: Our data suggest that efficacy of PEI(57%) in AFTN is inferior to conventional therapies like surgery and radioiodine, but still can be an alternative therapeutic modality in selected cases. In cold nodules, especially of solid type and complex cyst, PEI may have feasibility as a therapeutic modality in restricted cases. Further studies of prolonged follow-up for the possibility of neglecting occult malignancy are warranted.

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