Thyroid Disease : Hashimoto's thyroiditis (chronic lymphocytic thyroiditis)

Home of Kyle J. Norton for The Better of Living & Living Health  Thyroid is one of the largest endocrine glands found in the neck, below the Adam’s Apple with the function of regulating the body use of energy, make of proteins by producing its hormones as a result of the stimulation of thyroid-stimulating hormone (TSH) produced by the anterior pituitary.
Thyroid disease is defined as a condition of malfunction of thyroid. Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones. Hypothyroidism is a condition in which the thyroid gland is under active and produces very little thyroid hormones. Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis)
Hashimoto’s thyroiditis is an autoimmune disease in which the immune system attacks the thyroid gland of that mostly often leads to an underactive thyroid gland (hypothyroidism). According to the study by the University of Pisa, Women with Hashimoto’s thyroiditis (HT)  suffer from a high symptom load independently from hypothyroidism, which results just a contributing factor to the development of the clinical syndrome. In agreement with these results, we recently reported on the presence of symptoms and signs consistent with fibromyalgia (FM) in patients with HT regardless thyroid dysfunction, focusing to the weight of anti-thyroid autoimmunity in the HT-associated clinical syndrome(a).

A. Symptoms
1. Dysphagia, shortness of breath, voice changes, and odynophagia
In the study to review the data of patients who underwent thyroidectomy from 2005 through 2009, by the Medical University of South Carolina, showed that in three hundred thirty-three patients were identified. The mean age was 51 years, and 82% were female. Fifty-two percent (n=172) of patients experienced compressive symptoms preoperatively, including dysphagia (n=131) and shortness of breath (n=83). Twenty-six percent (n=86) of patients presented with voice changes, and 8% (n=27) complained of odynophagia(1).

2. Anxiety, negative mood, depression, dry skin, cold intolerance, puffy eyes, muscle cramps and fatigue, deep voice, constipation, slow thinking and poor memory.
Hashimoto’s thyroiditis is a common auto-immune disorder. The most common presenting symptoms may include anxiety, negative mood, depression, dry skin, cold intolerance, puffy eyes, muscle cramps and fatigue, deep voice, constipation, slow thinking and poor memory, according to the study by the Leiden University Medical Center(2).

3. General health and overall quality of life
Women with Hashimoto’s thyroiditis (HT) also with positive anti-TPO titer are experience to a significantly higher prevalence of general health symptoms as compared to those without HT. Besides the histological thyroiditis grade, anti-TPO levels were positively correlated with the symptom score(2a).

4. Other symptoms
There is a report of a case of an 11 years old girl who presented with history of swelling in front of the neck along with constipation, anorexia, weight gain and increasing pallor over a period of six months. Additionally she had an episodic history of joint pains and abdominal pain with no specific relation to diet, time, other gastrointestinal or genitourinary symptom. Hypothyroid goiter (Autoimmune thyroiditis, Hashimoto’s thyroidits) was diagnosed by raised thyroid stimulating hormone (TSH), low T4 and presence of thyroid specific antibodies in blood(2b).

B.  Causes and Risk factors
B.1 Causes
1. Autoimmune disorder
In the study to summarize the current knowledge on Hashimoto’s thyroiditis and its pathogenesis and to introduce the readers to the basic concept of autoimmune thyroid disease, found that Hashimoto’s thyroiditis and Graves’ disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient. During this response, cytotoxic autoantibodies, stimulatory autoantibodies, blocking autoantibodies, or cell-mediated autoimmunity may be observed. Persons with classic Hashimoto’s thyroiditis have serum antibodies reacting with thyroglobulin and thyroid peroxidase. These antibodies (particularly antibodies against thyroid peroxidase) are complement-fixing immunoglobulins and may be cytotoxic. In addition, many patients have cell-mediated immunity directed against thyroid antigens. Cell mediated-immunity is also a feature of experimental thyroiditis induced in animals by injection of thyroid antigen with adjuvants. Hashimoto’s thyroiditis is predominantly the clinical expression of cell-mediated immunity leading to destruction of thyroid cells, which in its severest form causes thyroid failure(3a).
 
1. Primary hyperparathyroidism (PHPT)
In the study to investigate and determine the prevalence of patients having both HT and PHPT, and the possible relation between these two diseases including 45,231 patients, which were referred by their general practitioner or endocrinologist, under suspicion of having thyroid and/or parathyroid disease., indicated that all 2,267 patients had normal or slightly elevated TSH levels. In conclusion, although the reported rate of prevalence of PHPT in the general population is about 0.3%, our results indicated a 1.89% occurrence of PHPT in 2267 patients with HT in central Serbia. This may be due to the autoimmune inflammatory process in HT supporting PHPT to PTH or calcium supporting HT or to common genetical predisposition of both entities(3).

2. Cerebellar ataxia
Both hypothyroidism and Hashimoto’s thyroiditis (HT) can rarely be associated with cerebellar ataxia.
There is a report of a  report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT(4).

B.2. Risk factors
1. Childhood weight gain and childhood overweight
Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women, according to the study by the Medical Research Council Unit for Lifelong Health and Ageing(5).

2. Genetic factors
In the study to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients, showed that CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients(6).

3. Female
In the study to investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes, showed that patients with thyroid antibodies were significantly older (P < 0.001), had a longer duration of diabetes (P < 0.001), and developed diabetes later in life (P < 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P < 0.001)(7).

4. Other risk factors
According to the study by the Kaunas University of Medicine, pregnancy, drugs, age, sex, infection, and irradiation may be associated to the risk factors of Hashimoto’s thyroiditis (HT)(8).

C. Complications and diseases associated to Hashimoto’s thyroiditis
C.1. Complication
1. Goiter
The most frequent cause of goiter in children is a deficit of iodine, leading to endemia of goiter in the regions with insufficient supplementation of this element. Goiter occurs also in the course of autoimmunological diseases of the thyroid gland (Hashimoto disease, Graves’ disease),  According to the theory of goiter pathogenesis, excessive enlargement of the thyroid gland is due to adaptation of follicle cells of the gland aiming at neutralizing the impaired synthesis of the thyroid hormones caused by various intrathyroid, environmental and genetic factors/agents, according to the study by(9).

2. Coronary heart disease
Risk of subsequent coronary heart disease in patients with Hashimoto’s thyroiditis, according to the study by the Lund University/Region Skåne(10).

3. Selective memory deficit 
There is a report of a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years, according to the study by the 1st University Department of Neurology(11).

4. Myxedema coma
There is a report of a case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto‘s thyroiditis(12).

5. Impaired fertility and miscarriage
Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto’s thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the increased thyroid hormone requirement., according to Bereich Forschung und Lehre des Zentrallabors, Universitätsklinikum Essen(13).

 
C.2. Diseases associated to Hashimoto’s thyroiditis
1. Hashimoto’s encephalopathy (HE)
Hashimoto’s encephalopathy (HE) is a rarely recognized neurocognitive syndrome that is associated with thyroid autoimmunity. It is more common in women(14).

2. Neurofibromatosis Type 1 
Hashimoto’s thyroiditis is a common form of chronic autoimmune thyroid disease (AITD) and often coexists with other autoimmune diseases, but Hashimoto’s thyroiditis associated with an autosomal dominant neurofibromatosis type 1 is exceedingly rare.  There is a report of a case of a 30-year-old Bengali woman presented to the OPD with complaints of aching pain and tingling sensation in her hands and feet. Physical examination revealed dysmorphic facies, nodular swelling in the neck, cafe-au-lait spots, and neurofibromas covering the entire surface of her body. Her thyroid hormones were within normal limits. Thyroid ultrasound revealed a cystic area in the left lobe of the gland, and ultrasound-guided fine needle aspiration cytology revealed lymphocytic infiltration of the gland, suggesting Hashimoto’s thyroiditis. High levels of autoimmune antibodies such as antithyroglobulin and antimicrosomal antibodies confirmed the diagnosis(15).

3. Chronic hepatitis C
In the study to investigate the relation of thyroid function with hashimoto thyroiditis (HT, an autoimmune disease of unknown etiology also known as chronic lymphocytic thyroiditis) in patients with chronic hepatitis C (CHC), showed that he incidence of thyroid dysfunction is significantly higher among CHC patients with HT than among CHC patients without HT. If suspected, these patients should be carefully monitored because the clinical symptoms of thyroid dysfunction are not obvious and the drug therapy(16).

4. Reactive thrombocytosis
According to our literature review, this is the first reported case of reactive thrombocytosis due to Hashimoto’s thyroiditis and/or subclinical hypothyroidism. A 31-year-old man without any complaint was admitted to the Hematology Department for thrombocytosis which was detected in his routine follow-up. He had been using thyroid hormone replacement for 2 years because of hypothyroidism as Hashimoto’s thyroiditis was earlier diagnosed. Due to miscommunication, he stopped his medication levothyroxine 0.1 mg/day 2 weeks in advance and he was still off-drug on admission. Platelet count was 715 × 10/l in the first admission center. Subclinical hypothyroidism diagnosis was made with the present findings and thyroid hormone replacement therapy was again commenced gradually. Platelet counts and thyroid-stimulating hormone value were normal 6 weeks later(17).

5. Thyroid papillary carcinoma
In a retrospective study of patients undergoing partial or total thyroidectomy for PTC between 2007 and 2009, a total of 41 cases, found that there is a rate of 26.8% of patients with association between TH and CPT, but without differences in relation to tumor size(18). 

D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
Fine-needle aspiration (FNA) cytology in the evaluation of thyroid lesions with diagnostic accuracy of 98.6% with 100% sensitivity, 98.6% specificity, 80% positive predictive value, and 100% negative predictive value. FNA is extremely valuable in the initial evaluation of thyroid swelling in children(19).
1. Overlapping thyroid follicular lesions coexisting with Hashimoto’s thyroiditis
In the study the types and incidence of thyroid follicular lesions coexisting with Hashimoto’s thyroiditis (HT). showed that FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained(20).

2. Follicular neoplasm or colloid nodule
An association between papillary thyroid carcinoma (PTC) and Hashimoto’s thyroiditis (HT) is well recognized. Both entities may often display overlapping morphologic features. In the study to evaluate the accuracy of fine needle aspiration (FNA) of concomitant PTC and HT, showed that the remaining cases (13 cases) showed diagnostic features of PTC in 2 cases (interpretation errors), some features of PTC in 8 cases (insufficient diagnostic features), features of only HT in 2 cases, and 1 case was acellular (sampling errors). Originally, 10 cases with features of PTC were diagnosed as either follicular neoplasm or colloid nodule with or without HT. Histologically, 1 of 13 cases was a cystic variant and 7 of 13 cases were follicular variants of papillary carcinoma. It is important to be aware of the coexistence of PTC and HT. Deliberate search for evidences of PTC in every case of HT may be necessary to improve diagnostic accuracy of the FNA(21).

3. Hürthle cell adenomas, follicular adenoma, nodular goiter, macrofollicular adenoma and malignant lymphoma
In the study to determine the accuracy of cytologic interpretation in the diagnosis of Hashimoto’s thyroiditis (HT), indicated that in 27 (69%) aspirates, HT was diagnosed on both the FNAB and surgical specimens. In 10 of 27 FNABs an associated lesion was not sampled by FNAB. In four of these 10 aspirates some of the cellular features of HT were misinterpreted, and the possibility of an associated neoplasm could not be ruled out. This resulted in four false positive diagnoses. In 12 (31%) FNABs from nine patients, the cytologic diagnosis of HT was not confirmed histologically. These cases included five Hürthle cell adenomas and one case each of follicular adenoma, nodular goiter, macrofollicular adenoma and malignant lymphoma. This resulted in five false negative diagnoses(22).

4. Solitary thyroid nodule
There is a rerort of a a 56-year-old female with solitary thyroid nodule diagnosed as Hurthle cell neoplasm on FNAC, but subsequent histopathological diagnosis following resection revealed Hashimoto’s thyroiditis with marked Hurthle cell change(22a).

D.2. Diagnosis
After recording the past and present history and completing a physical exam, including assessing symptoms and complaints commonly seen in hypothyroidism and neck esamination. The tests which your doctor orders may include
1. Blood test
The aim of the test is to determine the level of thyroid function. Underactive thyroid gland is presented with the low level of thyroid hormone is low with elevated TSH as your pituitary gland tries to stimulate your thyroid gland to produce more thyroid hormone.

2. An antibody test
The aim of the test is to check for the presence of  antibodies against thyroid peroxidase, the an enzyme which plays an important role in the production of thyroid hormones.

 3. Thyroid scan
In the study to  review the experience over the past 5 years of 32 thyroid scans in Hashimoto’s thyroiditis, showed that  wide variety of images were obtained, the most common finding being that of an enlarged gland with diffusely increased tracer uptake, a pattern identical to that found in Graves’ disease (eight patients). Of the remainder, four scans were normal, four showed an enlarged gland with normal tracer uptake, five a multinodular gland with normal tracer uptake, five a multinodular gland with high tracer uptake, five a single non-functioning nodule and in one patient there was low tracer uptake by the gland. It is apparent that the thyroid scan in Hashimoto’s thyroiditis can mimic a wide range of thyroid disorders(23).

4. Fine needle aspiration cytology
FNAC plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost. It can accurately diagnose Hashimoto’s thyroidits in most patients. However, a small percentage of cases may be missed due to the inherent limitations of this procedure and the varied cytomorphology of this lesion. Therefore thorough cytological evaluation and an integrated approach are necessary to pick up correct diagnosis and to avoid unnecessary surgery(24).

E. Preventions
E.1. Diet to prevent and treat Hashimoto’s thyroiditis 
1.  Brazil Nuts and Sunflower Seeds
In the study to investigate Selenium and thyroidal function; the role of immunoassays, showed that that dietary intake of about 300 micro g of selenium daily may have a toxic effect on growth hormone and insulin like growth factor-1 metabolism, as well as in the synthesis of thyroid hormones. Main adverse effects may be anorexia, diarrhea, depression, hemorrhage, liver and kidney necrosis, blindness, ataxia and respiratory disturbances. Dermatitis and CNS deficiency have also been described. It is concluded that selenium plays an important role in regulating thyroid function, as well as in the homeostasis of thyroid hormones through the action of selenoproteins, in which it incorporates as selenocystein(1). Others suggested that a different pattern of response to Se supplementation in HT relative to baseline TPOab titers, and this, if confirmed, could be used to identify which patients would benefit most from treatment. An improvement in thyroid function and morphology should be demonstrated before Se routine supplementation can be recommended in the treatment of HT(25).

2.  Sea buckthorn 
Sea buckthorn (Hippophae rhamnoides L.) constitutes thorny nitrogen fixing deciduous shrub. Sea buckthorn(SBT) is primarily valued for its very rich vitamins A, B(1), B(12), C, E, K, and P; flavonoids, lycopene, carotenoids, and phytosterols. and therapeutically important since it is rich with potent antioxidants. Scientifically evaluated pharmacological actions of SBT are like inflammation inhibited by reduced permeability, loss of follicular aggregation of lymphocytes from the inflamed synovium and suppress lymphocyte proliferation(26).

3. Balanced diet
Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes(27).

E.2. Phytochemicals and Antioxidants to prevent and treat Hashimoto’s thyroiditis

In the study to investigate prooxidant-antioxidant status only in Hashimoto’s thyroiditis (HT) patients with subclinical (sHT) and overt hypothyroidism (oHT), found that there were significant increases in oxidative stress parameters in serum and LDL-fraction in oHT patients. However, oxidative stress was detected to stimulate partly in serum, but not LDL fraction in sHT patients(28).

1. Resveratrol
In the study of resveratrol, the main ingredient found in skin and seed of grape and its impact on aging and thyroid function, showed that resveratrol is believed to regulate several biological processes, mainly metabolism and aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both papillary and follicular thyroid cancer by activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway as well as increase of p53 and its phosphorylation. Finally, resveratrol also influences thyroid function by enhancing iodide trapping and, by increasing TSH secretion via activation of sirtuins and the phosphatidylinositol- 4-phosphate 5 kinase γ (PIP5Kγ) pathway, positively affects metabolism(29)

2. Polyphenolic flavonoids
In the comparison of the efficacy of polyphenolic flavonoids found in black and green tea in thyroid function, showed that green tea extract at 2.5 g% and 5.0 g% doses and black tea extract only at 5.0 g% dose have the potential to alter the thyroid gland physiology and architecture, that is, enlargement of thyroid gland as well as hypertrophy and/or hyperplasia of the thyroid follicles and inhibition of the activity of thyroid peroxidase and 5(‘)-deiodinase I with elevated thyroidal Na+, K+-ATPase activity along with significant decrease in serum T3 and T4, and a parallel increase in serum thyroid stimulating hormone (TSH)(30)

3. Selenium
According to the study by the Hôpital du Cluzeau, in patients with Hashimoto’s disease and in pregnant women with anti-TPO antibodies, selenium supplementation decreases anti-thyroid antibody levels and improves the ultrasound structure of the thyroid gland. Although clinical applications still need to be defined for Hashimoto’s disease, they are very interesting for pregnant women given that supplementation significantly decreases the percentage of postpartum thyroiditis and definitive hypothyroidism(31).

2. Vitamin D
In the study to investigate vitamin D status in children with Hashimoto thyroiditis, showed that the higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children(32).
 
F. Treatments
A. In conventional Medicine
1. Levothyroxine therapy
In the study to evaluate the clinical course of Hashimoto‘s thyroiditis (HT) in children and adolescents and the effects of levothyroxine therapy on the clinical course and laboratory findings, showed that thyroid functions of the patients with HT should be monitored periodically for hypothyroidism. Levothyroxine therapy may positively affect the clinical course of the disease and the antibody titers(33).

2. Combination of liothyronine (T3) and levothyroxine
In a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine, found thatnine controlled clinical trials were identified that compared treatment with levothyroxine alone and treatment with combinations of levothyroxine plus liothyronine and included a sufficient number of adult hypothyroid patients to yield meaningful results. In only one study did the combined therapy appear to have beneficial effects on the mood, quality of life, and psychometric performance of the patients over levothyroxine alone. These results have not been confirmed by later studies using either T₃ substitution protocols or approaches with fixed combinations of levothyroxine plus liothyronine, including those based on the physiological proportion in which T₃ and T₄ are secreted by the human thyroid. However, in some of these studies the patients preferred levothyroxine plus liothyronine combinations, for reasons not explained by changes in the psychological and psychometric tests employed. Yet patients’ preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine, even in the small doses used in these studies. Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism(34).

B.  In traditional Chinese Medicine
1. Aconite cake-separated moxibustion and option the better therapeutic program
In the study to explore the effects on thyroid function in patients of Hashimoto‘s thyroiditis treated with aconite cake-separated moxibustion and option the better therapeutic program with eighty-five cases randomly divided into a moxibustion group (42 cases) and a western medication group (43 cases). The moxibustion group was treated by aconite cake-separated moxibustion therapy with acupoints of two groups [(1) Danzhong (CV 17), Zhongwan (CV 12), Guanyuan (CV 4); (2) Dazhui (GV 14), Shenshu (BL 23), Mingmen (GV 4)] alternatively and oral administration of 25 microg Euthyrox everyday. The western medication group was oral administration of 25 microg Euthyrox everyday, showed that aconite cake-separated moxibustion at Guanyuan (CV 4) and Mingmen (GV 4) combined with oral administration of Euthyrox can improve clinical symptoms and thyroid function in patients of Hashimoto‘s thyroiditis, which is better than simple oral administration of Euthyrox (levothyroxine)(35).

2. Brown seaweed Sargassum 
For nearly 2000 years Sargassum spp., a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including thyroid disease (e.g. goitre). In the study to assess the scientific evidence for therapeutic claims made for Sargassum spp. in TCM and to identify future research needs, showed that the bioactive compounds in Sargassum spp. appear to play a role as immunomodulators and could be useful in the treatment of thyroid related diseases such as Hashimoto’s thyroiditis. Further research is required to determine both the preventative and therapeutic role of Sargassum spp. in thyroid health(36).

3. Syndromes of TCM
In the study to analyse the thyroid and immune functions of the patients, and their relationship with the syndromes of TCM. The results showed that, in the patients with Yin deficiency syndrome, the contents of total T4, T3 were higher than normal and TSH lower than normal, while in Yang deficient patients, the contents of total T4, T3 were lower than normal and TSH higher than normal. This results suggested that the states of thyroid functions were closely related to the TCM syndromes. It was also found that the percentage of OKT 4+ cells and the self-recognizing ability of lymphocytes were lower than normal in patients with hyperthyroidism and Yin deficiency. While in patients with hypothyroidism and Yang deficiency, they were higher than normal. These meant that the abilities of lymphocyte autoreaction in Yin deficient patients were in contrary tendency with those in Yang deficient patients. The former had the manifestation of over-inhibition while the latter, hyperaction. Besides, the contents of auto-antibodies were higher than normal in both the patients with hyperthyroidism and hypothyroidism, which manifested itself as a common character of autoimmune thyroid diseases. The results indicated that there were common characters as well as individual characters of thyroid and immune functions between hyperthyroid patients and hypothyroid patients, and these characters might well be the material bases of various syndromes in TCM(37).

C. In Herbal Medicine
1. Alkaloid tetrandrine 
Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms.According to the study by the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, TTetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects(38).

2. Salvia miltiorrhiza, Tripterygium wilfordi, Tanacetum parthenium and Curcuma longa
In the study to to be investigate erbal medicine for their efficacy in treating human diseases, showed that
anumber of herbal products are in use for their immunosuppressive effects. This capacity of herbs may have useful applications in immune-mediated disorders including autoimmune diseases and organ transplant rejection. Plants such as Salvia miltiorrhiza and Tripterygium wilfordii has been shown to reduce inflammatory cytokines and mediators, indicating their value in the treatment of acute graft rejections and autoimmunity. Tanacetum parthenium inhibits the release of pro-inflammatory mediators from macrophages and lymphocytes and Curcuma longa down regulates the expression of cytokines and chemokines as well as the transcription factor NF-kappaB(39).

3. Radix Bupleuri
Radix Bupleuri, is one of the most frequently prescribed crude herbs in the prescriptions of traditional Chinese medicine for the treatment of inflammatory diseases and auto-immune diseases. In the study to determine whether the crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium, had beneficial effects on autoimmune disease, indicated that treatment with BPs 15 or 30 mg kg(-1) day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. BPs 30 mg kg(-1) day(-1) improved weight loss and spleen swelling when compared with vehicle-treated group(40).

4. Polygonum multiflorum and Artemisia scoparia
According to the study by the National Taiwan University, emodin and scoparone, the active principles isolated from Polygonum multiflorum and Artemisia scoparia, respectively, both exhibit vasorelaxant and immunosuppressive effects. Emodin (10(-6)-3 x 10(-5) M) and scoparone (10(-6)-3 x 10(-5) M) dose dependently relaxed rat thoracic aortic rings precontracted with phenylephrine. Emodin (3 x 10(-7)-10(-4) M) and scoparone (10(-6)-3 x 10(-4) M) also dose dependently suppressed the responses of human mononuclear cells to phytohemagglutinin and mixed lymphocyte reaction. These compounds may be useful as new templates for the development of better immunosuppressive agents with vasorelaxant actions for use against transplantation rejection and autoimmune disease(41).

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