|Year : 2021 | Volume
| Issue : 3 | Page : 638-643
Changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation of thyroid nodules in patients with autoimmune thyroiditis
Xiaoyin Tang1, Ping Li2, Bo Zhai2, Xiaoli Zhu3
1 Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou; Department of Interventional Oncology, School of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, China
2 Department of Interventional Oncology, School of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, China
3 Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
|Date of Submission||24-Sep-2020|
|Date of Decision||29-Dec-2020|
|Date of Acceptance||05-Feb-2021|
|Date of Web Publication||9-Jul-2021|
Department of Interventional Oncology, School of Medicine, Renji Hospital, Shanghai Jiao-tong University, No. 160 Pujian Road, Pudong New District, Shanghai 200120
Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215000
Source of Support: None, Conflict of Interest: None
Settings and Design: The aim was to study the changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation (RFA) of thyroid nodules in patients with autoimmune thyroiditis.
Subjects and Methods: Patients (n = 135) with autoimmune thyroiditis and thyroid nodules were treated by RFA. The indices of thyroid function and thyroid antibody and T lymphocyte subsets were examined preoperation and on the 1st day and the 1st month after ablation. Any complications were recorded.
Statistical Analysis: The software SPSS 17.0.0 (version: 2008-8-23) running under Windows 8 was used for statistical analysis. The measurement data were expressed as x ± s, with P < 0.01 indicating a significant difference in the statistical data.
Results: Levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were in the normal range before ablation, and no significant changes occurred on the 1st day or in the 1st month after ablation. The change in the percentage of CD8+T cells and the absolute value of B cells were not statistically significant (P > 0.01), and the values were in the normal range. Compared with values recorded preoperation, the value of TG-Ab, TPO-Ab, CD4+/CD8+, the percentage of CD4+T cells, the absolute values of lymphocytes, T cells, CD4+T cells, and CD8+T cells decreased significantly at the 1st day after ablation (P < 0.01) and then recovered to preoperative levels during the first 30 days after ablation (P > 0.01). Within 1 month after ablation, none of the patients had complications such as active bleeding, infection, recurrent laryngeal nerve injury, parathyroid gland injury, skin scald, and so on.
Conclusions: After RFA of thyroid nodules in patients with autoimmune thyroiditis, thyroid function is not affected and no serious complications occurred. TG-Ab and TPO-Ab levels can be significantly decreased, and the distribution of T lymphocyte subsets can be changed in the short term after ablation.
Keywords: Autoimmune thyroiditis, radiofrequency ablation, thyroid antibody, thyroid nodule, T lymphocyte subsets
|How to cite this article:|
Tang X, Li P, Zhai B, Zhu X. Changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation of thyroid nodules in patients with autoimmune thyroiditis. J Can Res Ther 2021;17:638-43
|How to cite this URL:|
Tang X, Li P, Zhai B, Zhu X. Changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation of thyroid nodules in patients with autoimmune thyroiditis. J Can Res Ther [serial online] 2021 [cited 2021 Oct 19];17:638-43. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/638/321010
| > Introduction|| |
Autoimmune thyroiditis (autoimmune thyroid diseases [AITD]), such as Hashimoto's thyroiditis, is typical of T cell-mediated autoimmune diseases. The early clinical symptoms are not easily detected; the disease progresses slowly and easily reoccurs. The incidence rate in the general population is approximately 5%. AITD is characterized by diffuse goiter, as indicated by levels of serum thyroid peroxidase (TPO-Ab) and/or thyroglobulin antibody (TG-Ab); different degrees of change in thyroid function are seen and B and T lymphocytes can infiltrate inside the thyroid. Studies have shown that cellular and humoral immune responses increase the production of antibodies against thyroid tissue, eventually leading to the decline of thyroid function and a decrease in thyroid hormone synthesis. There is no effective medicine to cure this disease. Thyroid nodules have a high incidence in the general population.,,, In 2001, Dupuy et al. used radiofrequency ablation (RFA) for the first time in the treatment of local recurrent lesions in a case of differentiated thyroid cancer. In 2006, Kim et al. reported for the first time the application of RFA in the treatment of benign thyroid nodules (BTN). Since then, the study of RFA in BTN and recurrent thyroid carcinoma has gradually increased in China and in other countries, and the results have shown the efficacy and safety of this approach.,,,, Thyroid nodules are commonly seen in clinical cases of autoimmune thyroiditis. The changes in thyroid antibody and T lymphocyte subsets after RFA of thyroid nodules in patients with autoimmune thyroiditis have been rarely reported. In this study, we investigated the changes of thyroid antibody and T lymphocyte subsets after RFA of thyroid nodules in a group of patients with autoimmune thyroiditis.
| > Subjects and Methods|| |
From April 2015 to January 2020, 135 patients with autoimmune thyroiditis with merged thyroid nodules underwent ultrasound-guided percutaneous puncture and RFA in the Oncology Interventional Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University. The operations were approved by the hospital ethics committee. The patients were informed of the risks of anesthesia and surgery in detail, preoperatively, and each patient signed the consent form for anesthesia and radiofrequency therapy.
Inclusion criteria were
- Preoperative laboratory examination of the patient showed normal blood and coagulation function and normal thyroid function or adjustment to normal range after treatment by endocrinology department;
- Normal chest X-ray and electrocardiogram results;
- Preoperative ultrasonography indicated BTN (triads 3 and 4a), and pathology of tissue obtained by thyroid fine-needle puncture cytology biopsy clearly indicated benign tumors;
- The patient expressed a strong willingness to voluntarily undergo RFA;
- The foreign body sensation in the neck and the large volume of the nodules produces oppressive symptoms in the patient, who may fear a worsening of their condition and appearance;
- Both TPO-Ab and TG-Ab were positive.
Exclusion criteria were
- Patients with malignant thyroid tumors diagnosed by preoperative fine-needle aspiration cytology;
- Women who are pregnant or nursing;
- Cases of severe systemic diseases, such as severe blood coagulation dysfunction, myocardial infarction, stroke, cancer, connective tissue disease (scleroderma and systemic lupus erythematosus), systemic infection, and uncontrolled diabetes;
- Individuals with serious physical, neurological, or mental diseases.
Radiofrequency ablation preparation and procedures
All patients underwent preoperative thyroid high-frequency ultrasound examination and were assessed based on the following index parameters: thyroid nodule shape aspect ratio (rules/irregular), nodules (<1/≥1), nodal brim (clear/unclear), echo type (not a low echo/low echo), rear echo type (no/decay), echotexture (homogeneous/heterogeneous), internal blood flow (yes/no), microcalcification (absent/present), and neck lymph node metastasis (absent/present).
Ultrasound adopted Twice US system (Esaote, Italy), L522 and L523 probe, 7–10 MHz center frequency, with CEUS function. US contrast agent was SonoView (Sine Pharma, Italy). The RFA treatment system was Medsphere RF Generator S-500 (Medsphere, Shanghai, China).
Radiofrequency ablation procedures
The ablation was performed in the operating room. Tracheal intubation was conducted to deliver general anesthesia. After anesthesia was completed, the patient's shoulder and neck were placed on the shoulder pillow and neck pillow, and the cervical hyperextension position was adopted. Conventional sterile towels were used. The RFA power was adjusted to 20–40 W and the impedance mode was selected. We used ultrasound imaging along with color Doppler flow imaging to pinpoint the thyroid nodules and guide the needle position – preferably near the midline of the thyroid isthmus, after which the radiofrequency electrode penetrated into the bottom of the tumor. Once the RFA began, gasification was evident around the electrode until the tumor was completely covered by a strong echo. For large nodules, if the unit point ablation could not reach an effective ablation range, multiplanar puncture and multilevel melting methods were utilized, by adjusting the direction of the electrode and ablation plane, to carry out multiple ablations, until the tumors were completely covered in three-dimensional space by the strong echo. The thyroid nodule ablation was evaluated in real-time (using the ultrasonic imaging technology) such that some areas in the nodules received timely supplemental ablation, thus preventing residual nodules. After the ablation procedure, we used another ultrasound contrast agent to visualize the perfusion of the contrast in the thyroid nodules.
Peripheral blood was collected before surgery, 1 day after surgery, and 1 month after surgery, respectively. We measured the levels of free three iodine thyroid original glycine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), TG-Ab, TPO-Ab, and the lymphocyte subgroup as well as the absolute count (CD4+/CD8+, CD4+T cell percentage, the percentage of CD8+T cells, lymphocyte absolute value of B cells, T cells, absolute value of CD4+T cells, and CD8+T cells in absolute value). Any complications, such as active bleeding, infection, recurrent laryngeal nerve injury, parathyroid injury, skin scald, or other complications were recorded if they occurred within 1 month after the operation.
The software SPSS 17.0.0 (ver 1; IBM, Armonk, New York, USA) running under Windows 8 was used for statistical analysis. The measurement data were expressed as x ± s, with P < 0.01 indicating a significant difference in the statistical data.
| > Results|| |
In total, 135 patients were enrolled in this study: 8 males and 127 females; male: female = 1:15.9. The average age was 47 ± 14 years. The preoperative thyroid function of the patients was normal or adjusted to normal after endocrine department treatment. Both TPO-Ab and TG-Ab were positive before surgery [Table 1].
In all cases, the ablation process went smoothly. FT3, FT4, and TSH levels were in the normal range before surgery, the 1st day after surgery, and the 1st month after surgery, and no thyroid dysfunction was observed. Levels of TG-Ab and TPO-Ab compared with levels measured preoperatively, decreased significantly on the 1st day after surgery (P < 0.01) and then recovered to preoperative level after the 1st month after surgery (P > 0.01) [Figure 1]. All patients were discharged successfully on the 1st day after surgery.
None of the patients showed any complications, such as active bleeding, infection, recurrent laryngeal nerve injury, parathyroid gland injury, and skin scald.
|Figure 1: Changes over time in thyroglobulin antibody and thyroid peroxidase antibody|
Click here to view
The percentage of CD8+T cells and the absolute value of B cells were not statistically significant (P > 0.01), and the values were in the normal range. CD4+/CD8+, the percentage of CD4+T cells, and the absolute values of lymphocytes, T cells, CD4+T cells, and CD8+T cells were significantly decreased on the 1st day after surgery (P < 0.01), after which they recovered to preoperative levels at the first month after surgery (P > 0.01) [Table 2] and [Figure 2].
|Figure 2: Changes over time in T lymphocyte subsets. (a) Absolute value of T lymphocytes, CD4+T lymphocytes, CD8+T lymphocytes, and B lymphocytes; (b) changes in CD4+T (%) and CD8+T (%); (c) change in CD4/CD8; (d) Change over time of the absolute value of lymphocytes|
Click here to view
| > Discussion|| |
Because both autoimmune thyroiditis and thyroid nodules are common thyroid diseases, the occurrence of autoimmune thyroiditis combined with thyroid nodules is common in clinical practice. Due to the continuous stimulation of thyroid nodules by inflammation, patients are at risk of thyroid cancer, which poses a great threat to the patient's life and makes treatment more necessary. Until recently, surgery has been the traditional treatment of BTN. RFA, as a new minimally invasive treatment technology, has been increasingly applied, with success, in the treatment of BTN or recurrent thyroid cancer.,,,,,,,,,,,,,,,,,, In recent years, our department has applied RFA technology in the treatment of patients with autoimmune thyroiditis complicated with thyroid nodules, and all postoperative thyroid nodules have been effectively treated. However, the effect of RFA on thyroid antibodies and T lymphocyte subsets in patients with autoimmune thyroiditis is still unclear, and there are few relevant in China or other countries.
It has been reported in the literature that RFA can change the immune function of patients with malignant tumors. The mechanism of action can be considered as follows: (1) various cytokines (such as heat shock protein and anti-inflammatory cytokine interleukin-10.) stimulated by RFA treatment and various tumor antigens released by tumor necrosis after RFA treatment stimulate the immune system to produce antitumor immune response dominated by Thl cells.,, (2) After the tumor cells have been killed by RFA, the tissue becomes coagulated and necrotic, which significantly reduces the load of tumor cells, greatly reduces the production of immunosuppressive factors, and finally, improves the immune function. (3) Decomposition products that are generated after the necrosis of tumor cells can stimulate an antitumor immune response. In the present study, the effects of RFA on immune function in patients with autoimmune thyroiditis complicated with thyroid nodules were assessed by detecting thyroid antibodies and T lymphocyte subsets.
We found that the percentage of CD4+/CD8+ and CD4+T cells, and the absolute value of lymphocytes, T cells, CD4+T cells, and CD8+T cells decreased significantly on the 1st day after the operation (P < 0.01). The preoperative level was restored 1 month after operation (P < 0.01). There were no statistically significant differences in the percentage of CD8+T cells and the absolute value of B cells before surgery compared with the 1st day and the 1st month after surgery (P < 0.01), and the indices were in the normal range. The results suggest that the thyroid function of patients with autoimmune thyroiditis complicated with a thyroid nodule is not affected after RFA. TG-Ab and TPO-Ab were significantly decreased in a short period after the operation. At the same time, the percentage of CD4+/CD8 + and CD4+T cells and the absolute value of lymphocytes, T cells, CD4+T cells, and andCD8+T cells can also be significantly reduced.
In this study, TG-Ab and TPO-Ab in patients with autoimmune thyroiditis complicated with thyroid nodule were significantly reduced in a short period after receiving RFA. The reason may be that CD4+/CD8+, the percentage of CD4+T cells, the absolute value of lymphocytes, the absolute value of T cells, the absolute value of CD4+T cells, and the absolute value of CD8+T cells decreased significantly in the short term after RFA, leading to the decrease in the number and activity of CD4+T cells and CD8+T cells, thus weakening the attack on thyroid tissue. Even if the absolute value of B cells did not change significantly, the synthesis of TG-Ab and TPO-Ab was eventually reduced due to the reduced presentation of relevant antigens.
In summary, although there is currently no effective cure for autoimmune thyroiditis, patients with autoimmune thyroiditis combined with merged thyroid nodule line who are treated with RFA do not experience negative changes in thyroid function; i.e., severe complications. In fact, RFA treatment can significantly reduce the level of TG-Ab and TPO-Ab shortly after the RFA and change the distribution of T lymphocyte subsets. Further research on this phenomenon may uncover important aspects of the mechanism and treatment of autoimmune thyroiditis. However, because the etiology of autoimmune thyroiditis is relatively complex, RFA treatment as it relates to the immune function of the human body has not been completely assessed. Our study is from a clinical perspective. The specific mechanisms remain to be discovered, and such research would advance our understanding of AITD and contribute to clinical prevention, diagnosis, and treatment.
| > Conclusions|| |
After RFA of thyroid nodules in patients with autoimmune thyroiditis, thyroid function is not affected and no serious complications occurred. TG-Ab and TPO-Ab levels can be significantly decreased, and the distribution of T lymphocyte subsets can be changed in the short term after ablation.
Xiaoyin Tang and Ping Li designed the study, collected and analyzed the data, and drafted the manuscript. Xiaoli Zhu and Bo Zhai conceived and coordinated the overall study and revised the manuscript. All authors read and approved the final manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Klecha AJ, Barreiro Arcos ML, Frick L, Genaro AM, Cremaschi G. Immune-endocrine interactions in autoimmune thyroid diseases. Neuroimmunomodulation 2008;15:68-75.
Topliss DJ. Clinical update in aspects of the management of autoimmune thyroid diseases. Endocrinol Metab (Seoul) 2016;31:493-9.
Ajjan RA, Weetman AP. The pathogenesis of Hashimoto's thyroiditis: Further developments in our understanding. Horm Metab Res 2015;47:702-10.
Singer PA, Cooper DS, Daniels GH, Ladenson PW, Greenspan FS, Levy EG, et al
. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association. Arch Intern Med 1996;156:2165-72.
Tan GH, Gharib H. Thyroid incidentalomas: Management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226-31.
Smith-Bindman R, Miglioretti DL, Johnson E, Lee C, Feigelson HS, Flynn M, et al
. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA 2012;307:2400-9.
Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009;39:699-706.
Dupuy DE, Monchik JM, Decrea C, Pisharodi L. Radiofrequency ablation of regional recurrence from well-differentiated thyroid malignancy. Surgery 2001;130:971-7.
Kim YS, Rhim H, Tae K, Park DW, Kim ST. Radiofrequency ablation of benign cold thyroid nodules: initial clinical experience. Thyroid 2006;16:361-7.
Cesareo R, Pasqualini V, Simeoni C, Sacchi M, Saralli E, Campagna G, et al
. Prospective study of effectiveness of ultrasound-guided radiofrequency ablation versus control group in patients affected by benign thyroid nodules. J Clin Endocrinol Metab 2015;100:460-6.
Ugurlu MU, Uprak K, Akpinar IN, Attaallah W, Yegen C, Gulluoglu BM. Radiofrequency ablation of benign symptomatic thyroid nodules: Prospective safety and efficacy study. World J Surg 2015;39:961-8.
Ji Hong M, Baek JH, Choi YJ, Lee JH, Lim HK, Shong YK, et al
. Radiofrequency ablation is a thyroid function-preserving treatment for patients with bilateral benign thyroid nodules. J Vasc Interv Radiol 2015;26:55-61.
Lim HK, Baek JH, Lee JH, Kim WB, Kim TY, Shong YK, et al
. Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer. Eur Radiol 2015;25:163-70.
Hu K, Wu J, Dong Y, Yan Z, Lu Z, Liu L. Comparison between ultrasound-guided percutaneous radiofrequency and microwave ablation in benign thyroid nodules. J Cancer Res Ther 2019;15:1535-40.
Chauhan VK, Manchanda RK, Narang A, Marwaha RK, Arora S, Nagpal L, et al
. Efficacy of homeopathic intervention in subclinical hypothyroidism with or without autoimmune thyroiditis in children: An exploratory randomized control study. Homeopathy 2014;103:224-31.
Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: Autoimmune thyroid disease: Old and new players. Eur J Endocrinol 2014;170:R241-52.
Fietta AM, Morosini M, Passadore I, Cascina A, Draghi P, Dore R, et al
. Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer. Hum Immunol 2009;70:477-86.
Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al
. Selenium and the course of mild Graves' orbitopathy. N Engl J Med 2011;364:1920-31.
Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 2007;92:1263-8.
Na DG, Lee JH, Jung SL, Kim JH, Sung JY, Shin JH, et al
. Radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: Consensus statement and recommendations. Korean J Radiol 2012;13:117-25.
Andersen SL, Olsen J, Wu CS, Laurberg P. Smoking reduces the risk of hypothyroidism and increases the risk of hyperthyroidism: Evidence from 450,842 mothers giving birth in Denmark. Clin Endocrinol (Oxf) 2014;80:307-14.
D'Aurizio F, Villalta D, Metus P, Doretto P, Tozzoli R. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? Autoimmun Rev 2015;14:363-9.
Arena S, Latina A, Baratta R, Burgio G, Gullo D, Benvenga S. Chronic lymphocytic thyroiditis: could it be influenced by a petrochemical complex? Data from a cytological study in South-Eastern Sicily. Eur J Endocrinol 2015;172:383-9.
Radetti G. Clinical aspects of Hashimoto's thyroiditis. Endocr Dev 2014;26:158-70.
Cosmi L, Santarlasci V, Maggi L, Liotta F, Annunziato F. Th17 plasticity: Pathophysiology and treatment of chronic inflammatory disorders. Curr Opin Pharmacol 2014;17:12-6.
Glick AB, Wodzinski A, Fu P, Levine AD, Wald DN. Impairment of regulatory T-cell function in autoimmune thyroid disease. Thyroid 2013;23:871-8.
Bai X, Sun J, Wang W, Shan Z, Zheng H, Li Y, et al
. Increased differentiation of Th22 cells in Hashimoto's thyroiditis. Endocr J 2014;61:1181-90.
Ryu HS, Park YS, Park HJ, Chung YR, Yom CK, Ahn SH, et al
. Expression of indoleamine 2,3-dioxygenase and infiltration of FOXP3+regulatory T cells are associated with aggressive features of papillary thyroid microcarcinoma. Thyroid 2014;24:1232-40.
Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ, et al
. Radiofrequency ablation of benign thyroid nodules: Safety and imaging follow-up in 236 patients. Eur Radiol 2008;18:1244-50.
Baek JH, Kim YS, Lee D, Huh JY, Lee JH. Benign predominantly solid thyroid nodules: Prospective study of efficacy of sonographically guided radiofrequency ablation versus control condition. AJR Am J Roentgenol 2010;194:1137-42.
Monchik JM, Donatini G, Iannuccilli J, Dupuy DE. Radiofrequency ablation and percutaneous ethanol injection treatment for recurrent local and distant well-differentiated thyroid carcinoma. Ann Surg 2006;244:296-304.
Schueller G, Kettenbach J, Sedivy R, Stift A, Friedl J, Gnant M, et al
. Heat shock protein expression indSuced by percutaneous radiofrequency ablation of hepatocellular carcinoma in vivo
. Int J Oncol 2004;24:609-13.
Kudo M. Radiofrequency ablation for hepatocellular carcinoma: Updated review in 2010. Oncology 2010;78 Suppl 1:113-24.
Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol 2011;29:235-71.
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[Table 1], [Table 2]