Pan Liwen（潘立文）, Wang Xiaoming（王晓明）, Yang Xianzhen（杨先振）, and Li Guangfu（李光富）

Chuxiong Medical College, Yunnan Province, Chuxiong 675000, China

Analysis of the features of TCM and western medicine in the diagnosis and treatment of subclinical hypothyroidism characteristics

Pan Liwen（潘立文）＊, Wang Xiaoming（王晓明）, Yang Xianzhen（杨先振）, and Li Guangfu（李光富）

Chuxiong Medical College, Yunnan Province, Chuxiong 675000, China

The diagnosis and treatment of subclinical hypothyroidism are summarized by reviewing the related English and Chinese literature, the comparative analysis of traditional Chinese medicine (TCM) and western medicine in the understanding of subclinical hypothyroidism, the epidemiology, etiology, pathogenesis, the patterns and the clinical manifestation in addition to the therapeutic principle and drugs of subclinical hypothyroidism, with a prospect of providing insight in the clinical treatment of the disease.

Exploration; Analysis; TCM; Modern medicine; Subclinical hypothyroidism; Theory

The subclinical hypothyroidism（SCH）is a kind of disease which can be diagnosed mainly by the result of the laboratory examination. This view is actually supposed by Basteine A11and other scholars. These scholars give the original def i nition of this disease, and the original narriation of the clinical manifestation of the patients who are suffering from this disease. First of all, those patients with SCH don’t have the typical manifestation of clinical hypothyroidism, and don’t belong to any crew of clinical hypothyroidism. But they really have some indexes not normal. This abnormality manifests not only on the Throid-Stimulating Hormone index but also on the symptoms and signs of them. This abnormality mainly ref l exes on the weakened capability of thyroid organ which causes that the index of sTSH is always above the normal level. Meanwhile, the level of FT4 (Free Thyroid Hormone) and the antibodies of the thyroid organ on those patients are usually normal. Generally speaking, this subclinical hypothyroidism state (if I am permitted to name this disease just a kind of state or abnormal state) just happens in the natural pathegenosis process of Hashimoto thyroiditis. This state can also be found among the patients who have accepted the operation which was done for healing hyperthyroidism what they were suf f ering from subclinical hypothyroidism can also be found among the patients who have accepted the radioactive iodine therapy too.

Now the academic circle has many quite different views about this disease. Some scholars2insist that this state doesn’t need special therapy, and the really important thing is that doctors should try to heal the primary pathogeny. Such as those patients whose diseases are caused by Hashimoto Thyroiditis, if they can recover from this thyroiditis, their subclinical hypothyroidism will be cured soon. So, these schlars’ real thought is if you can’t cure the thyroiditis, the patients who are suf f ering from subclinical hypothyroidism won’t have the possibility to be cured. And these scholars believe, even if the disease hasn’t been cured, the subclinical hypothyroidism state won’t give the patients’ bodies too much damages3. But some of other scholars insist that those patients with subclinical hypothyroidism should receive the therapy, because this state will bring them many bad af f ects including the hyperlipidemia and cardiovascular disease risks. According to my recent research, I find if those subclinical hypothyroidism patients don’t receive the proper therapy, they may have the rather high possibilities to get sick of the hyperlipdemia and cardiovascular diseases. So, I believe that the academic circle really should explore and discuss the epidemiology, diagnosis, antidiastole,complications and western and TCM therapies of this disease. In a word, they should give much more concern to this disease. Herein this article is just one which is written for exploring and discussing the epidemiology, diagnosis, antidiastole, complications and western and TCM therapies of SCH.

THE EPIDEMIOLOGY OF SCH

An epidemiological study with a large sample shows that subclinical hypothyroidy’s mobidity reaches 3%～8%4,5.This means subclinical hypothyroid is a very common disease in the crowd. Actually, another epidemiological study with a large sample shows that this disease’s mobidity reaches 5%～13.2% and the women’s mobidity is above two times of the men’s. However when detecting these patients’ surum TSH, they found that their surum TSH level increased just a little. Another feature on them is their antibodies of thyroid organ’s level increased a lot.

From the data showed above, we can find out that the subclinical hypothyroidism really has a very high mobidity in the ordinary and the mobidity really has a very big dif f erence between different genders. The epidemiology study also shows that many patients’s SCH may be caused by the Autoimmunological Thyroiditis.

THE DIAGNOSIS, CLINICAL MANIFESTATION AND PATHOGENY OF SCH IN WESTERN AND CHINESE TRADITIONAL MEDICINE

From the definition of SCH, we may easily conclude that SCH is very easy to be diagnosed. It seems that if only the patients’ TSH level increases and sFT3, FT4’s level are still normal, the doctors can easily diagnose SCH for them. But herein I must specially emphasize the SCH patients’ clinical manifestation again. Because some clinical doctors think even if the patients are just in a SCH state, they will certainly manifest some typical symptoms or signs of hypothyroidism6,7. But I think this is not a so right point. Certainly, I must admit that some patients really have typical manifestation like hypothyroidism, but actually there are still a lot of patients don’t have typical symptoms or signs like hypothyroidism. Even if some patients have the symptoms, the symptoms are only very slight such as slight tiredness, weakness, trichomadesis, aversion to cold, mucous edema, constipation and abdominal distention, etc. So, I think the doctors can’t diagnose SCH only depending on the clinical manifestation. They should diagnose this disease mainly depending on the laboratory examination. Now, many scholars usually mention another important view8that maybe those patients who have normal sTSH and FT4 are still in the state of SCH, if their sTSH’s level have high sensitive reaction to TRH. In a word, no matter what kind of view about SCH’s definition, this disease’s diagnosis will mainly depend on the high serum TSH level and the normal sFT3, sFT4 level.

There are so many pathogenies which can cause the SCH state. I have concluded the main pathogenies as follws (the rank order is based on their occurrence probability):

1.Chronic antoimmunological thyroiditis.

2.Received the opertation of partial thyroidectomy or radioiodine therapy.

3.Caused by other diseases.

4.Physiological variation of thyroid function.

5.Using amiodarone, iodine substance and lithium salt.

6.Subacute thyroiditis.

7.Postpartum thyroiditis.

8.Inaccurate test results.

9.Haven’t received adequate therapy in the treatment of hypothyroidism.

10. Excessive dosage in the treatment of hyperthyroidism.

From the state mentioned above, we can easily fi nd that subclinical hypothyroidism is relatively easy to be diagnosed, but the doctors should seriously fi nd out the real pathogeny of this disease so that doctors can easily distinguish who are the real subclinical hypothyroidism patients, who are not.

Now many scholars start to concentrate on the SCH’s TCM diagnosis and antidiastole. By researching the ancient and modern documents and combining with personal experience, I think the SCH’s clinical manifestation is consistent with the diagnosis of Xulao or Yingbing disease in TCM. Xulao means comsuptive diseases and Yingbing means diseases of thyroid in TCM. Based on the basic features and principles of TCM, many scholars consider that it is rather important for TCM clinical doctors to give the treatment of each disease based on the syndromes differentiation of those patients. So, even if treating the same disease, the doctors still need to divide the patients into dif f erent situations or patterns. For SCH, the doctors should divide it into two dif f erent patterns. One is the damp abundance due to splenic asthenia pattern and anotherone is asdthenic splenonephro-yang pattern. The reason is about their manifestations. SCH’s main clinical manifestations are slight tiredness, weakness, trichomadesis, aversion to cold, mucous edema, constipation and abdominal distention, etc. The pathogeny that the patients will manifest those symptoms is due to the abundant damp beacuse of splenic asthenia or asdthenic splenonephro-yang. Because in the basical theory of TCM, spleen has the function of transporting the water into different organs and tissues and keeping the body have the normal dryness degree. And the kidney governs the whole body’s water system. So, when the spleen or spleen and kidney’s Yangqi are insufficient, the patients’ body will manifest many symptoms or signs like tiredness, weakness, trichomadesis, aversion to cold, and mucous edema. Another important function of spleen is to help the gastrointestine to digest the food and absorb the nutrition. So, when the patient’s spleen doesn’t have enough Yangqi, its gastrointestinal motility will become weak and the patients will probably manifest the symptoms like constipation and abdominal distention, etc.

Based on what is mentioned, we can find that SCH’s diagnosis is not so hard for clinical doctors. This disease can be diagnosed by its laboratory examination results, which mainly depended on the abnormally increased sTSH level and FT3, FT4 level. The main pathogeny of SCH is the antoimmunological thyroiditis, and the rest pathogenies include the operation of thyroid or radioidodine therapy and some other pathogenies. SCH is called Xulao or Yingbing in TCM, and its TCM patterns are damp abundance due to splenic asthenia pattern and asdthenic splenonephro-yang pattern.

THE COMPLICATIONS OF SCH

Clinical Hypothyroidism(CH)

Frankly speaking, SCH could be seen as a very important independent and main pathogeny of CH. And furtherly speaking, SCH could be seen as a mainest pathogeny of CH. There are a very high-quarlity research9showing that SCH actually is a very important risk factor for promoting the formation of hypothyroidism. Besides that, the level of increased s-TSH level, the old age, female, and anti-thyroid antibody are other very important risk factors for promoting SCH to become into CH. In the survey of Wickham, he found that those women whose anti-thyroid antibodies were positive, s-TSH level were over 6mU/liter and aged over 50, would have about 57% probability to become into CH patients in 20 years9.

From the point of TCM, I think this situation usually ref l ects on those patients’ spleen Yang’s damage degree which have become more serious. Some people’s damage of spleen Yang have even affected the kidney Yang and form the pattern of asdthenic splenonephro-yang. Because when you observe those paitients, you will fi nd their clinical manifestations like tiredness, weakness, trichomadesis, aversion to cold, mucous edema, constipation and abdominal distention, etc will become more serious or obvious, and these more serious sypotoms or signs reflect on the furtherly weakened Yang of spleen or spleen and kidney. The clear narriation of the mechanism of this has been stated in the second part of this article, so here the article will delete the state of this.

Cardiovascular diseases

Now many important surveys or researches have showed or proved that SCH is a rather important and independent risk factor for cardiovascular disease10,13. In many researches, the researchers found SCH really had very close relationship with hyperlipidemia, especially with the over increased serum cholesterol, triglyceride, low-density lipoprotein and over decreased high-density lipoprotein. In Colorado state of US, some American scholars had finished an epidemiological survey with very big samples, which covered about 22842 healthy people, 2336 SCH and 114 CH patients. After comparing the healthy people and those patients, the researchers found that the patients’ hyperlipidemia’s morbidity were much higher than the healthy ones (P＜0.001)14. Because of the abnormally increased sLDL, sTC and sTG, many patients’ blood vessel endothelium system will gradually become damaged, which mainly embodied in the endothelial dysfunction and abnormal hemodynamic indexes15. Because there is a kind of material called Nitric Oxide (NO) in the vascular endothelium and this material will diffuse into the vascular smooth muscle cells, which can lead to the relaxation of the vascular smooth muscle. So, when the endothelium has been damaged and the synthesis mechanism of that material has already been destroyed, the patients’ peripheral vascular resistance (SVR) will be increased, the atherosclerosis will be accelerated and the potential risk to be sick of coronary heart disease will increase too.

Another point which is valuable to be emphasized is evenon those people whose sTSH are only near the upper limit, there are still some evidences for the damage of their vascular endothelium15. Some researches16,17pointed out that as for those patients whose thyroid function were only slightly functionally declined, their blood vessels still had the signs of atherosclerosis. Those cardiovascular diseases like coronary heart disease and etc will attack those patients.

From the perspective of TCM, the weakened spleen and kidney Yangqi would affect the patients function of transporting the water and dampness. So, in the patients’inner part of bodies, the superf l uous water and dampness will become a kind of pathogeny which will result in a lot of spittle stored in the patients. When the spittle in the blood vessels become more and more, people will gradually suffer from atherosclerosis and other kinds of cardiovaschlar diseases. This situation in TCM is in accordance with the phlegm turbidity pattern’s standard. This pattern approximates to hyperlimidemia in western medicine. The main manifestations of this pattern of SCH patients are numbness of limbs, chest tightness, chest pain, dizziness, headache, trapped heavy body and excessive phlegm. When the phlegm turbidity blocks the thoracic Yang, the body will manifest the symptoms like chest pain, chest tightness, etc. If the phlegm blocks the blood vessels, the patients will manifest the symptoms like numbness of limbs and headache. The dampness and phlegm which are in the bodies will make people have the feeling that they are just like a trapped heavy body.

The af f ection on the Neuromuscular system

A report18pointed out that the abnormality of the neuromuscular system among the patients with SCH was a very common phenomena, and that this abnormality could be reversed by L-T4 replacement therapy. And this report also pointed out that the pregnant women with subclinical hypothyroidism might delay the development of the intelligence of their children, whose thyroid function is normal. Some reports pointed out that SCH patients’ exercising muscle metabolic function would be obviously weakened by this disease. In addition, the exercising tolerance of patients with SCH, maximum oxygen carrying capacity, and the maximum power output were significantly lower than the normal ones, while the respiratory quotient was signif i cantly higher than the normal group’s people19.

In TCM, those neuromuscular system manifestations are caused by asdthenic splenonephro-Yang, excessive dampness and phlegm. Because in TCM theory, the brain is the house of intelligence, if the spleen and kidney’s Yang are weak which will make the lucid yang can’t warm the house of intelligence, the patients will manifest a lot of neuromuscular system’s symptoms or signs like slow reaction, the memory capacity weakened, or the motor and sensory function decline, etc. If the excessive dampness and phlegm affect the house of intelligence, these symptoms or signs will manifest more obviously. Generally speaking, the effect of SCH on the neuromuscular system is very obvious, and its related forming mechanism still need to be researched furthermore.

THE THERAPY OF SCH

The therapy of SCH by western medicine

In western medicine, the main therapeutic drug for this disease is L-T4. There are three RCTs20,22researched on the curative ef f ect of L-T4 which focuses on the general symptoms of subclinical hypothyroidism. Two of them confirmed that the general symptom scores and the levels of sTSH of the SCH patients who received L-T4 treatment were signif i cantly improved rather than those patients in blank group who received just placebo treatment. This reflects that L-T4 replacing treatment is ef f ective for the SCH patients to improve their symptoms and sTSH level. There was another randomized double-blind controlled trial done by Dr.Cooper21. In this trail, Dr. Cooper found there were higher incidence rates on all the 33 patients whose tests’ statistics were performed according to the Bilevicz’s clinical hypothyroidism symptom scale. After receiving one year’s therapy of L-T4, those patients’ symptom scores had significant improvement and the same situation happened to those patients’ sTSH level.

Among those complications of SCH patients, the most dangerous and important one is the cardiovascular disease. So, the therapeutic effect for this complication by L-T4 is very important for the clinical researchers. In a randomized double-blind controlled trial done by Monzani23, the researcher found that those SCH patients whose ages were below 55 had a very signif i cant change in their thickness of carotid intimamedia layer (TCIM). After receiving the therapy of L-T4, those patients’ TCIM had been declined signif i cant, and this index’s decline had very close relationship with the level of sTSH and sTC. This evidence shows a very strong sign that L-T4 has arather important function in reducing the risk of SCH patients’cardiovascular complications by reducing the level of sTC, sTSH and the atherosclerosis.

Generally speaking, the therapeutic effect of L-T4 for SCH is rather signif i cant, especially in improving the clinical symptoms and reducing the level of sTSH. This drug can also reduce the risk of cardiovascular diseases and make the excessively high lipoprotein level normal. In a word, L-T4 is rather useful for changing the pathological state of SCH patients. However, some patients maybe cannot get benefits from this western medicine drug, and still have some serious symptoms of SCH. Sometimes, although some patients’ sTSH level have been reduced to a rather low level, they still have obvious symptoms of SCH. This is the reason why those people had better take the TCM or other substitute therapy.

The therapy of SCH by TCM

From what is mentioned above, it is known that SCH belongs to Xulao or Yingbing diseases in TCM, and its main patterns are as follows: 1. Damp abundance due to splenic asthenia pattern; 2. Asdthenic splenonephro-yang pattern. In traditional TCM theory, all the basic clinical manifestations of SCH are the reflection of insufficient kidney and spleen Yangqi. So, it becomes rather important for clinical TCM doctors to pay attention to the Yangqi’s function and treat those SCH patients from the perspective of weakened Yangqi of spleen and kidney. In clinical practice, the TCM doctors should adopt the basic therapeutic methods of tonifying the spleen and kidney Yangqi and removing excessive water and dampness. Based on the documents24,27collected from CNIK and WIKI database combined with the anthor's clinical personal experience, the author summarizes some basic prescriptions and TCM herbs which are used for SCH. The high-frequently quoted related articles shows that Jisheng Shenqi pills, Yougui pills, Buzhong Yiqi decoction, Guipi pills, Zhenwu decoction, Fuzi Lizhong decoction, and Linggui Zhugan decoction are the main prescriptions that the clinical doctors adopt to treat SCH in those medical reports. The high-frequently used TCM herbs are monkshood, cinnamon, ginger, cassia twig, astragalus membranaceus, red ginseng and white atractylodes rhizome etc. From the total clinical therapeutic effects of those TCM prescriptions and herbs reported in these articles, the author fi nds that using TCM or combined with western medicine will be a good choice for healing SCH.

The recent scientif i c research on SCH’s therapy in TCM

Luli and Teng Weiping.et al. found28the spatial learning ability and spatial memory ability of the female rats decreased after they had been modeled into SCH pathological model. And they found that the mechanism of this situation is probably related with the less expression of BDNF gene and excessive expression of RAP1 gene. Liao Hong29had found that among SCH rats, most of them had increased sTSH and sTC, sTG level and those abnormalities can be cured by the TCM herbs which had the function of tonifying the spleen and kidney Yangqi. Those modern scientif i c researches shows that SCH’s TCM essence maybe is close to the state of asdthenic splenonephro-yang.

CONCLUSION AND DISCUSSION

SCH is becoming more and more common in the ordinary people, especially in those patients who have the autoimunological thyroiditis or suf f ered from the thyroid operations or radioiodine therapy. Now the mainstream opinion holds that the diagnosis of SCH mainly relies on the laboratory test. If the patients’ sTSH is higher than the normal level and the sFT3 and sFT4’s level are lower than the normal level, the clinical doctors can diagnose SCH. The main clinical manifestation of SCH are slight tiredness, weakness, trichomadesis, aversion to cold, mucous edema, constipation and abdominal distention, etc. These symptoms or signs have very close relationship with the patients’ weakened thyroid function. TCM holds that these symptoms and signs are caused by asdthenic splenonephroyang. Because all the tissues, organs and other parts of people’s bodies are warmed and promoted by the Yangqi of kidney. So, if the Yangqi of kidney are weak, the patients will be suffer from the symptoms and signs stated above. If SCH can’t be controlled, the patients may be suf f er from many complications like clinical hypothyroidism, cardiovascular and pathological changes of neuromuscular system, etc. In western medicine, the mainstream scholar circle adopts L-T4 as the main therapeutic drug for SCH now. This drug can rather effectively control the SCH state and make the abnormal sTSH’s level become normal. This drug can also relieve some patients’ complications of cardiovascular diseases and hypolipidemia improved, but the total ef f ect is not very satisfactory and the symptoms and signs can not be relieved significantly. Adopting the TCMtherapeutic methods can easily improve the patients’ SCH state especially relieving some complications and the typical symptoms. The main principle that the clinical TCM doctors should emphasize on is TCM’s treating methods must be based on the patients’ dif f erent patterns. Based on many ancient and modern docments and the author's personal clinical experience, theoretical analysis, the author concludes that SCH’s main patterns are 1.Damp abundance due to splenic asthenia pattern; 2.Asdthenic splenonephro-yang pattern. Based on the highfrequently quoted articles, the main therapeutic prescriptions are Jisheng Shenqi pills, Yougui pills, Buzhong Yiqi decoction, Guipi pills, Zhenwu decoction, Fuzi Lizhong decoction, and Linggui Zhugan decoction. The high-frequently used TCM hurbs are monkshood, cinnamon, ginger, cassia twig, astragalus membranaceus, red ginseng and white atractylodes rhizome, etc. The therapeutic ef f ect of TCM for SCH is very good. In the future, if the clinical doctors could adopt the integrated therapy which combines the western and traditional Chinese medicine, the therapeutic ef f ect will become better and we can gradually fi nd out the main mechanism of TCM and the integrated medicine therapy.

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（Accepted: May 17, 2016）

Funding：The experimental research and clinical applicaitions of Wenshen decoction to treat subclinical hypothyroidism (Project No: [2008]614), supported by the scientif i c research fund of Health Department of Hubei Province.

*Correspondence author:E-mail: astronomypan@163.com; Mobile phone: +86-18087875780