Treatment of Goiter with Traditional Chinese Medicine Regimen Xing Qi Hua Ying Tang: A Clinical Study on 72 Patients with Multinodular and Diffuse Goiter

Abstract

Objective:

The present work aimed to further explore the therapeutic potential of Xing Qi Hua Ying Tang (XQHYT) by conducting a systemic clinical study in patients with goiter.

Design:

Seventy-two patients with either multinodular or diffuse goiter were enrolled and randomly assigned into treatment group receiving XQHYT (n = 36) and control group receiving Hai Zao Yu Hu Tang (n = 36).

Location:

Traditional Chinese Medicine Hospital of Shanxi.

Subjects:

Patients were diagnosed multinodular goiter or diffuse goiter resulting from Qi stagnation.

Intervention:

All patients took the extract twice a day (100 mL each time) for two courses of treatment, of which a single course lasted for 3 months. Before the treatment was commenced and after the completion of the treatment, general body checks, thyroid function test, and goiter size examination were performed.

Outcome measures:

Scoring of the clinical symptoms using Chinese medicine symptomatology was also done.

Results:

The symptom score of the treatment group was significantly lower than that of the control group (treatment group, 8.26 ± 2.62; control group, 10.02 ± 2.62; p < 0.05). Substantial reduction in goiter size was seen in 82.3% of XQHYT-treated patients, whereas in the control group only 67.7% of patients exhibited constricted goiter. When assessed by both the Chinese medicine criteria and goiter size, the overall effective rate of the treatment group was 91.2%, whereas that of the control group was only 67.7%. The difference was statistically significant (p < 0.05). XQHYT did not affect the normal functions of liver, kidney, and heart. For both groups of patients, their levels of thyroid-stimulating hormone, free T4 and free T3 were normal before the treatment, and were not affected by the treatment.

Conclusion:

XQHYT was shown to be a promising therapeutic regimen for the treatment of goiter. The herbal regimen ameliorated clinical symptoms of patients that were accompanied with reduction in the size of goiter.

Introduction

Goiter, which can be associated with hypo or hyperthyroidism, is a health problem affecting populations worldwide. Goiter with hypothyroidism can result from iodine deficiency and lack of selenium and iron intake, whereas that with hyperthyroidism can be associated with Graves' disease and thyroid neoplasms.¹ Currently, the use of thyroid hormone therapy and surgical intervention represent as the standard treatment for goiter. Their approaches yield some therapeutic benefits; however, a high rate of recurrence after the discontinuation of treatment was reported.^2,3 New therapies for goiter are therefore urgently needed.

Traditional Chinese Medicine (TCM) practitioners have been treating goiter for several centuries, and have accumulated extensive clinical experiences.⁴ Based on the theory of TCM, Qi is the vital energy important for physiological processes and activities. The deficiency of Qi of the spleen and stagnation of Qi from the liver can cause phlegm, eventually leading to the development of goiter.⁵ From this perspective of Chinese medicine, a herbal regimen that restores and enhances, the flowing of Qi holds promise as a potential therapeutic agent for the treatment of goiter. Traditional Chinese Medicine is a rich resource for novel drug candidates.⁶ The Chinese Medicine Hospital of Shaanxi has developed a Qi-promoting herbal regimen called Xing Qi Hua Ying Tang (XQHYT), of which the efficacy in treating goiter has been seen in the clinics. The present work was therefore aimed to examine the therapeutic efficacy of XQHYT in patients with either nodular or diffuse goiter. The findings would be important to the development of XQHYT as an effective therapeutic alternative to current standard treatments.

Patients and Methods

Patient characteristics

Seventy-two patients, 18 to 65 years of age, who were admitted to the Endocrinology Outpatient Clinic of the Chinese Medicine Hospital of Shaanxi between June 2011 and June 2013, were enrolled into this study. Patients were diagnosed with multinodular goiter or diffuse goiter resulting from Qi stagnation, and were randomly assigned into treatment (n = 36) and control (n = 36) groups. In the treatment group, there were 3 males and 33 females, 19 to 63 years of age (average age, 39.0 ± 12.6 years), who suffered from goiter for 2 months to 8 years and with the average size of goiter being 120 ± 60 mm. In the control group, there were 2 males and 34 females, 20 to 65 years of age (average age, 40.1 ± 13.1 years), who suffered from goiter for 2 months to 7 years and with the average size of goiter being 118 ± 57 mm. Between treatment and control groups, there were no significant differences in goiter size, clinical symptoms, course of disease, and patient characteristics (p > 0.05).

Diagnosis and inclusion criteria

Multinodular and diffuse goiters were diagnosed as per the guidelines published by the Ministry of Health of People's Republic of China, namely “Traditional Chinese Medicine New Guiding Principles for Clinical Medicine” and “Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine,” in conjunction with the standard criteria of goiter of western medicine.⁷ The study enrolled only patients who fulfilled the criteria, and excluded patients inflicted with other diseases or serious complications, and those with dysfunctions in cardiovascular system, liver, and kidney. Informed consent was obtained from patients. The study was approved by the Ethics Committee of the Chinese Medicine Hospital of Shaanxi.

Treatment regimen and schedule

Patients of the treatment group were administered XQHYT, which consists of astragalus (30 g), white peony root (15 g), bupleurum (9 g), Citrus aurantium (15 g), chuanxiong (10 g), tangerine peel (10 g), wide wood incense (9 g), dried rind of unripe mikan (9 g), Prunella vulgaris (15 g), Fritillaria thunbergii (12 g), Fructus trichosanthis (15 g), calcined oyster shell (30 g), and honey-fried Glycyrrhiza uralensis (6 g). Patients of the control group were given Hai Zao Yu Hu Tang, which is another Qi-promoting herbal regimen consisting of components different from that of XQHYT, namely Sargassum (30 g), Ecklonia kurome (15 g), Fritillary (15 g), Pinellia ternate (10 g), Vatica mangachapoi (6 g), Angelica sinensis (15 g), Ligusticum chuanxiong Hort (10 g), Forsythia suspense (10 g), and G. uralensis (6 g). Both XQHYT and Hai Zao Yu Hu Tang were prepared as an extract (200 mL) by the pharmacy of the Chinese Medicine Hospital of Shaanxi. The extract was divided equally into two portions.

All patients took the extract twice a day (100 mL each time) for 6 months. In view of the long treatment length, patients were first treated for 3 months, and were examined for any adverse effects. If patients did not show any adverse effects, they received treatment for another 3 months. There was no break between the two courses of treatment. During the entire course of treatment, patients with symptoms, who were continuously followed up by phone interview (once a week), were following the abovementioned guidelines. All patients were also advised to avoid any intake of irritating foods (e.g., processed foods containing a lot of artificial ingredients such as flavoring and preservatives).

Patient examination

Before the treatment was commenced and after the completion of the treatment, body examination was performed in all the enrolled patients to ensure no adverse effects were associated with the herbal treatment. The examination included general body check-up, blood routine, urine test, stool analysis, liver function test (i.e., ALT), kidney function test (creatinine in blood [Cr] and blood urea nitrogen), and electrocardiogram. The therapeutic efficacy of the herbal treatment was assessed by B-mode transverse ultrasonography, thyroid function test measuring thyroid-stimulating hormone, free T4, and free T3, and cytopathology studying abnormal cell proliferation and other pathological features. Patients were also examined as per the guidelines published by the Ministry of Health of People's Republic of China, namely “Traditional Chinese Medicine New Guiding Principles for Clinical Medicine” and “Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine.”

Statistical analysis

Ranked data were analyzed using Wilcoxon rank-sum test, with measurement data examined using chi-square test. Correlation between symptoms, thyroid size, and other efficacy endpoints were also evaluated. All tests were performed using SPSS version 13.0. Statistical significance was indicated by p value <0.05.

Results

Treatment with XQHYT appeared to ameliorate clinical symptoms of goiter

In the treatment group a total of 34 patients completed the treatment course, while in the control group there were 31 patients. The clinical symptoms of goiter of these patients were scored and analyzed (Table 1). Results showed that for patients of both groups the scores decreased after treatment with TMC. Of note, the score of the treatment group was significantly lower than that of the control group (treatment group, 8.26 ± 2.62; control group, 10.02 ± 2.62; p < 0.05).

Table 1.

Scores of Chinese Medicine Symptomatology Before and After the Intake of Herbal Regimen of the Treatment and Control Groups

Group	N	Before	After
Treatment	34	12.18 ± 3.64	8.26 ± 2.62^a,b
Control	31	12.06 ± 3.41	10.02 ± 3.16

p < 0.05 compared with before treatment.

p < 0.05 compared with the control group.

The number of effective cases, which was assessed by the criteria of Traditional Chinese Medicine, of the two groups were also compared (Table 2). Significant improvement after the completion of treatment was seen in 12 and 6 patients of the treatment and control groups, respectively. The difference was statistically significant (p < 0.05). The overall effective rate of the treatment group was 94.1%, whereas that of the control group was only 77.4%.

Table 2.

Improvement in Chinese Medicine Symptomatology After Treatment with Herbal Regimen in the Treatment and Control Groups

Group	N	Significant improvement	Improvement	No improvement	Overall effective rate (%)
Treatment	34	12^a	20	2	32/34 (94.1)
Control	31	6	18	7	24/31 (77.4)

p < 0.05 compared with the control group.

Blood routine, urine test, stool analysis, liver function test, kidney function test, and electrocardiogram of all enrolled patients were normal before the study, and were not affected significantly by the treatment, suggesting both XQHYT and Hai Zao Yu Hu Tang were safe in patients with goiter.

Treatment with XQHYT decreased the size of goiter

Whether the treatment with Tang would decrease the size of goiter was also addressed (Table 3). The size of goiter was determined before and after the treatment with Tang using ultrasonography. In the treatment group, there were 10 patients showing significant reduction in goiter size, whereas in the control group, there were only 6 patients exhibiting comparable outcome. The difference was statistically significant (p < 0.05). The overall effective rate of the treatment group was 82.3%, whereas that of the control group was only 67.7% (p < 0.05).

Table 3.

Reduction in Goiter Size After Treatment with Herbal Regimen in the Treatment and Control Groups

Group	N	Significant reduction	Reduction	No reduction	Overall effective rate (%)
Treatment	34	10	18	6	28/34 (82.3)^a
Control	31	6	15	11	21/31 (67.7)

p < 0.05 compared with the control group.

Outcome analysis by the combined use of Chinese medicine criteria and goiter size

The treatment outcome of patients was also assessed by the combined use of Chinese medicine criteria and goiter size (Table 4). Significant improvement after the completion of treatment was seen in 12 and 5 patients of the treatment and control groups, respectively. The difference was statistically significant (p < 0.05). The overall effective rate of the treatment group was 91.2%, whereas that of the control group was only 67.6% (p < 0.05). Thyroid function tests of all enrolled patients before the study were normal, and were affected neither in treatment nor control groups. Between treatment and control groups there was no significant difference in thyroid function tests before and after the treatment.

Table 4.

Outcome Analysis by the Combined Use of Chinese Medicine Criteria and Goiter Size

Group	N	Significant reduction	Reduction	No reduction	Overall effective rate (%)
Treatment	34	12	19	3	31/34 (91.2)^a
Control	31	5	16	10	21/31 (67.7)

p < 0.05 compared with the control group.

Discussion

Goiter is a commonly seen endocrine disorder, affecting 4% to 10% of population worldwide.⁸ Treatment options for patients with goiter have remained limited. The recurrence rate of surgical intervention is also unacceptably high.³ It is therefore imperative to develop a new therapeutic approach for the treatment of goiter. Chinese medicine practitioners have been treating goiter for centuries, and have accumulated extensive knowledge and clinical experiences.⁴

Based on the theory of TCM, tumor, including goiter, result from the disrupted flowing of Qi. XQHYT is an herbal regimen known for its Qi-promoting effect, and so has been believed to be a potential therapeutic for treatment of goiter. The use of XQHYT in the treatment of patients with goiter may have yielded satisfactory results. In this context, the present work was aimed to further explore the therapeutic potential of XQHYT by conducting a systemic evaluation using both diagnostic criteria of Traditional Chinese and modern medicines.

The present study demonstrated that treatment with XQHYT contributed to significant constriction in goiter size, which was accompanied with amelioration in the clinical symptoms. Outcome analysis by the combined use of Chinese symptomatology and goiter size showed that the overall effective rate of the treatment group was 91.2%, whereas that of the control group was only 67.7% (p < 0.05). With the clinical symptoms relieved, the quality of life of patients should have also improved. Treatment with XQHYT was associated with shrinkage of goiter, enabling surgical resection in patients, whose tumors are originally too large for surgery. The reduced goiter size would also improve the long-term clinical outcome after surgery.⁹ Importantly, XQHYT did not present any undesirable effects even when it has been administered for 6 months. In fact, XQHYT consists of herbs, of which the therapeutic effect in goiter treatment has been reported. Astragalus, which is one of the major components of XQHYT, was reported as able to alleviate clinical symptoms of patients with Graves' disease.¹⁰ Another component C. aurantium was shown to have protective effects on thyroid.^11,12 Of note, extract of P. vulgaris was demonstrated to reduce goiter size in clinical patients.¹³

To summarize, the present work provided evidences supporting XQHYT as a promising regimen for the treatment of goiter. Nevertheless, the number of patients enrolled in this study was limited, and more importantly, most patients were female. The formulation, safety, and pharmacokinetic properties of the herbal regimen will be further investigated in a larger cohort. The combined use of Traditional Chinese Medicine with surgical intervention and antithyroid therapy is worth studying as well.

Footnotes

Acknowledgment

This study was supported by the Project of Administration of Traditional Chinese Medicine of Shanxi Province (No. 1C47).

Author Disclosure Statement

No competing financial interests exist.

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