Efficacy,of,Xiaojin,Capsules,Combined,with,Selenium,Yeast,Capsules,on,120,Cases,of,Hashimoto’s,Thyroiditis,with,Abnormal,Thyroid,Function

Zeyuan SHI, Daoxin WANG, Jianxin HE, Zijie SU

1. School of Clinical Medicine, Henan University, Kaifeng 475004, China; 2. School of Nursing and Health, Henan University, Kaifeng 475004, China; 3. The First Affiliated Hospital of Henan University, Kaifeng 475004, China; 4. Henan Provincial People’s Hospital, Zhengzhou 475003, China

Abstract [Objectives] To explore the efficacy of Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of Hashimoto’s thyroiditis (HT) with abnormal thyroid function. [Methods] A total of 180 HT patients who were treated in the First Affiliated Hospital of Henan University and Henan Provincial People’s Hospital from December 2020 to December 2021 were selected as the research subjects and randomly divided into the observation group (n=120) and the control group (n=60) in at a tratio of 2∶1 ratio according to their visiting time. The observation group was treated with Xiaojin Capsules (oral, 5 capsules each time, twice a day for 12 weeks) and Selenium Yeast Capsules (oral, 1 capsule each time, twice a day for 12 weeks). The control group was treated with only Selenium Yeast Capsules (oral, 1 capsule each time, twice a day for 12 weeks). [Results] The difference in the levels of thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TGAb), serum free triiodothyronine (FT3), serum free thyroxine (FT4), and thyroid stimulating hormone (TSH) between the observation group and control group was statistically significant (P<0.05). The diameters of thyroid between the observation group and the control group before, during and after treatment were significantly different (P<0.05). The total effective rate of the observation group was 82.5% (99/120), which was significantly higher than 56.67% (34/60) in the control group, and the difference was statistically significant (P<0.05). The cure rate (22.50%) in the observation group was significantly higher than the control group (3.33%), and the difference was statistically significant (P<0.01). The ineffective rate of the observation group was 17.50%, which was significantly lower than that of the control group (40.00%), and the difference was statistically significant (P<0.01). The markedly effective rate of the observation group was 40.83%, which was significantly higher than that of the control group (31.67%), and the difference was statistically significant (P<0.05). The effective rate in the observation group was 191%, and the effective rate in the control group was 21.67%, and the difference was not statistically significant (P>0.05). [Conclusions] Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of HT can eliminate or alleviate the clinical symptoms and signs, significantly reduce the levels of TPO-Ab and TGAb in serum, restore thyroid function, improve thyroid shape and structure in the treatment of HT, and the clinical effect is satisfactory.

Key words Xiaojin Capsules, Selenium Yeast Capsules, Hashimoto’s thyroiditis, Abnormal thyroid function, Observation of efficacy

Hashimoto’s thyroiditis (HT) is chronic lymphocytic thyroiditis. Its etiology is not clear yet, and there is still a lack of accepted and satisfactory treatment methods. Its disease progresses slowly and cannot heal itself. With the progression of the disease, thyroid function will be reduced, and there may be goiter, thyroid nodules and even a few nodules may become cancerous. Studies have found that HT is closely related to the occurrence, development, recurrence and metastasis of thyroid cancer[1]. In this study, from December 2020 to December 2021, we used Selenium Yeast Capsules combined with Xiaojin Capsules in the treatment of HT with abnormal thyroid function and obtained satisfactory effects.

2.1 General dataWe selected a total of 180 HT patients who were treated in the First Affiliated Hospital of Henan University and Henan Provincial People’s Hospital from December 2020 to December 2021 as the research subjects and randomly divided them into the observation group (n=120) and the control group (n=60) in at a tratio of 2∶1 ratio according to their visiting time. The observation group included 31 males and 89 females, aged 16-61 years, with average age of (35.13±3.28) years, disease duration of 6-36 months, and average duration of (12±3) months. The control group included 17 males and 43 females, aged 14-64 years, with average age of (34.13±2.26) years, disease duration of 6-36 months, and average duration of (12±3) months. We statistically analyzed the general data of the two groups and the difference was not statistically significant (P>0.05), which was comparable. This study was approved by the Ethics Committee of the First Affiliated Hospital of Henan University (ethical approval number: HUSOM2020-042).

2.2 Diagnostic criteria(i) Diffuse thyroid damage and enlargement in imaging examination; (ii) significant increase in serum thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TGAb); (iii) confirmed by fine needle aspiration biopsy cytology.

2.3 Inclusion criteria(i) Meeting the diagnostic criteria for HT; (ii) abnormal thyroid function; (iii) the patients have voluntarily signed the informed consent.

2.4 Exclusion criteria(i) Accompanied or suspected of coexisting with other thyroid diseases (primary thyroid antibody, thyroid nodules, thyroid cancer,etc.); (ii) received radioactive iodine therapy; (iii) history of thyroid surgery; (iv) clearly diagnosed with other autoimmune diseases; (v) pregnant and lactating women; (vi) allergic constitution and frequent allergic reactions; (vii) currently participating in other clinical trials or the completion time of other clinical trials is less than 6 months; (vii) received immunomodulatory drugs, selenium preparations, and traditional Chinese medicine (TCM) treatment within 3 months.

2.5 Dropout and rejection criteria(i) Failure to take medicines and follow-up visits as prescribed; (ii) incomplete information; (iii) voluntary withdrawal.

2.6 Treatment methodsThe observation group was treated with Xiaojin Capsules (Jianmin Pharmaceutical Group Co., Ltd., SFDA Approval No.: Z10970132; oral, 5 capsules each time, twice a day for 12 weeks) and Selenium Yeast Capsules (Wuhu Huaxin Bio-Pharmaceutical Co., Ltd., SFDA Approval No.: H20052532; oral, 1 capsule each time, twice a day for 12 weeks). The control group was treated with only Selenium Yeast Capsules and the method and dose were the same as the observation group.

2.7 Observation indicatorsChanges of serum TPO-Ab and TGAb in the two groups of patients before and after treatment; imaging changes of thyroid morphology and size; changes in serum free triiodothyronine (FT3), serum free thyroxine (FT4) and thyroid stimulating hormone (TSH).

2.8 Efficacy evaluation criteriaCured: clinical symptoms disappear, serum TPO-Ab and TGAb return to normal levels, imaging (color Doppler ultrasonic examination preferred) shows normal thyroid texture, shape and size; markedly effective: clinical symptoms disappear, serum TPO-Ab and TGA values after treatment are less than half of those before treatment, and color Doppler ultrasonic examination shows that the diameter of the enlarged thyroid is reduced by ≥50%; effective: clinical symptoms disappear or significantly relieve, serum TPO-Ab and TGAb decrease and ≤ 30%; color Doppler ultrasonic examination shows that the diameter of goiter is reduced by ≥ 30%; ineffective: the clinical symptoms, serology, and imaging indicators failure to meet the above criteria.

3.1 Changes in serological indicatorsBefore treatment, there was no significant difference in thyroid antibodies TPO-Ab and TGAb between the observation group and the control group (P>0.05). After 6 weeks of treatment, the difference in thyroid antibodies TPO-Ab and TGAb between two groups was statistically significant (P<0.05). After 12 weeks of treatment, the difference in thyroid antibody TPO-Ab and TGAb between two groups was statistically significant (P<0.01), as shown in Table 1.

Table 1 Comparison of TPO-Ab and TGAb between two groups before, and after 6 and 12 weeks of treatment IU/mL)

3.2 Imaging changes in thyroidWe compared the changes in the left lobe, right lobe and isthmus of each thyroid diameter (by color Doppler ultrasonic examination, mm) before, during and after treatment between the two groups of patients. We found that before treatment, there was no significant difference in the data of left lobe, right lobe and isthmus (P>0.05); after 6 weeks and 12 weeks of treatment, the differences in left lobe, right lobe and isthmus were statistically significant (allP<0.05), as indicated in Table 2.

Table 2 Comparison of thyroid meridians before, 6 weeks, and 12 weeks after treatment in the two groups mm)

3.3 Comparison of efficacyAfter 12 weeks of treatment in the two groups, the total effective rate of the observation group was 82.5%, which was significantly higher than 56.67% in the control group, and the difference was statistically significant (P<0.05). The cure rate 22.50% in the observation group was significantly higher than 3.33% in the control group, and the difference was statistically significant (P<0.01). The ineffective rate of the observation group (17.50%) was significantly lower than that of the control group (40.00%), and the difference was statistically significant (P<0.01). The markedly effective rate in the observation group was 40.83%, which was significantly higher than that in the control group (31.67%), and the difference was statistically significant (P<0.05). The effective rate in the observation group was 191% in the control group, it was 21.67%, and the difference was not statistically significant, as shown in Table 3.

Table 3 Comparison of clinical efficacy between the two groups of patients [cases (%)]

3.4 Changes in thyroid functions FT3, FT4and TSHBefore treatment, there was no significant difference in FT3, FT4and TSH values between the observation group and control group (allP>0.05). After 6 weeks of treatment, there was no significant difference in the FT3and FT4values between the two groups (allP>0.05), and the difference in TSH value between two groups was significantly different (P<0.05). After 12 weeks of treatment, the difference in FT3, FT4and TSH values between the two groups was statistically significant (allP<0.01). After 12 weeks of treatment, the thyroid function of 78 cases in the observation group returned to normal, accounting for 65.00%, and the thyroid function of 11 cases in the control group returned to normal, accounting for 18.33%. The efficacy of the observation group was better than that of the control group, and the difference was statistically significant (P<0.01), as shown in Table 4.

Table 4 Comparison of FT3, FT4 and TSH before, 6 weeks and 12 weeks after treatment between the two groups

3.5 Incidence of adverse drug reactionsDuring the treatment period, there were no abnormal vital signs, abnormal liver and kidney function, abnormal cardiac function, abnormal digestive tract ulcer and bleeding tendency in the two groups of patients. During the treatment period in the observation group, there were 9 cases of upper respiratory tract infection, 5 cases of nausea, 3 cases of mild anemia, 3 cases of constipation, 3 cases of diarrhea, and 2 cases of palpitations, and the total incidence of adverse drug reactions was 17.1%. In the control group, there were 5 cases of upper respiratory tract infection, 3 cases of nausea, 2 cases of palpitations, 2 cases of constipation, 2 cases of diarrhea, and 1 case of mild anemia during the treatment period, and the total incidence of adverse drug reactions was 16.7%. The above adverse events did not affect the treatment of this disease.

According to pathological studies, HT is caused by the interaction of genetic factors, environmental factors,etc.The reduced function of suppressor T lymphocytes in the thyroid tissue and enhanced effect of helper T lymphocytes cause the B lymphocytes in the thyroid tissue to differentiate and produce a large number of anti-thyroid antibodies, and then antibody-dependent and natural killer T cell-mediated cytotoxicity leads to thyroid dysfunction due to destruction of thyroid cells[2]. In the early stage of HT, the thyroid function is slightly hyperactive or normal, and the treatment effect at this stage is relatively good. However, at this stage, the symptoms of patients are not obvious, and it is not easy to be found by patients, so it is easy to miss the best treatment period. As the disease further progresses, hypothyroidism, goiter, thyroid nodules, and even cancerous nodules may appear. Therefore, the treatment of HT should focus on two points: (i) adjusting the pituitary gland and thyroid endocrine axis to restore it to normal; (ii) correcting the disorder of the immune system.

The prescription of Xiaojin Capsules is derived from the classic prescription Xiaojindan inSurgicalTreatmentoftheWholeSyndromeofHealthSetwritten by Wang Hongxu in the Qing Dynasty. In the prescription, Moschus, Aconiti Kusnezoffii Radix, Olibanum, Myrrha, Pheretima, Angelicae Sinensis Radix, Momordicae Semen, Liquidambaris Resina, Wulingzhi, Motan are matched, which have the effects of soothing the liver, regulating qi and resolving phlegm, dredging collaterals and activating blood, reducing swelling and resolving mass, conforming to the syndrome differentiation and treatment of Chinese medicine according to its pathogenesis of "liver depression and spleen deficiency, spleen and kidney yang deficiency"[2]. Studies have shown that Xiaojin Capsules can counteract the inflammatory response caused by xylene and carrageenan, and have a certain regulatory effect on the immune system[3], and reduce the level of thyroid autoantibodies and can restore thyroid function to normal through regulating the balance of helper T cell subsets 1 (Th1) and 2 (Th2).

Selenium Yeast Capsules are a combination of selenium and yeast, and selenium exists in thyroid tissue cells and acts as selenoprotein. Studies have found that the occurrence of HT is related to selenium deficiency, and glutathione peroxidase (GSH-Px) in selenoproteins has antioxidant effects, and can not only remove oxygen free radicals in the body tissue cells, but also protect the integrity of the thyroid cell membrane. Selenium can maintain thyroid hormone synthesis and metabolism, and regulate immune function. Selenium deficiency will reduce the antioxidant capacity of GSH-PX, leading to the damage of thyroid cells by peroxidative substances, accordingly leading to disease[4-8]. Studies have shown that selenium yeast can treat tumors and liver diseases through increasing the activity of GSH-Px, and the efficacy is definite[9-10]. In this study, we used Selenium Yeast Capsules to effectively reduce the level of thyroid autoantibodies and oxidative stress, regulate human immune function, and improve thyroid function.

During the treatment of the patients in this study, the incidence of adverse drug reactions in the observation group and the control group were 17.1% and 16.7%, respectively. Through the analysis of adverse drug reactions, we found that in addition to the drug use factors in this study, environment, diet, complications,etc.were all related to the occurrence of adverse drug reactions. There is no conclusive evidence that all adverse events are drug-induced. In this study, we found that for Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of HT, the efficacy of 12 weeks of treatment was significantly better than 6 weeks, and after 12 weeks of treatment, the total effective rate of the observation group could reach 82.5.%. In conclusion, Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of HT can eliminate or relieve clinical symptoms and signs, significantly reduce the serum TPO-Ab and TGAb levels, restore thyroid function, and improve thyroid morphology and structure. This study indicates that Xiaojin Capsules combined with Selenium Yeast Capsules have a satisfactory clinical effect in the treatment of Hashimoto’s thyroiditis.