Graves disease
Introduction
Introduction to Graves disease Toxic diffuse goiter is an autoimmune disease. The clinical manifestations are not limited to the thyroid gland, but a multi-system syndrome, including: high metabolic syndrome, diffuse goiter, eye signs, skin lesions and thyroid limbs. End disease, because most patients have high metabolic syndrome and thyroid enlargement, it is called toxic diffuse goiter, also known as Graves disease. In addition to thyroid, invasive endocrine exophthalmos can exist alone without hypermetabolism. . basic knowledge The proportion of illness: 0.02% Susceptible people: good for women aged 20-40 Mode of infection: non-infectious Complications: leukemia thyroid cancer hyperthyroidism
Cause
Cause of Graves disease
The disease has been confirmed to be an autoimmune disease, but its pathogenesis has not yet been fully elucidated. One of its characteristics is the presence of autoantibodies in the serum that can react or stimulate the thyroid tissue. This antibody can stimulate rodents. The thyroid gland, which enhances its function and causes tissue hyperplasia, but its action is slow and long-lasting, so it was originally called the long-acting thyroid stimulating kiss (LATS). Later, due to different methods, there may be other names such as human thyroid stimulating hormone. (HTS), LATS protectant (LATSP), TSH replacement active (TDA), thyroid stimulating immunoglobulin (TSI) or thyroid stimulating antibody (TSAb), collectively referred to as TSH receptor antibody (TSAb), is the lymph node of this disease The IgG secreted by the cell, whose corresponding antigen is the TSH receptor or the part adjacent to the serosal surface of the thyroid cell. When TSI binds to the thyroid cell, the TSH receptor is activated, so that the function of the thyroid is stimulated, causing hyperthyroidism and goiter. Its role is similar to that of TSH. It is believed that the production of autoantibodies is mainly related to the inhibitory T lymphocyte (Ts) function associated with the underlying defects. Low, Ts function deficiency leads to inappropriate sensitization of helper T cells, and B cells produce anti-self thyroid antibodies with the participation of interleukin-1 and interleukin 2, in addition, the leukocyte cell migration inhibition test for thyroid tissue is positive in this disease. The reaction, thyroid and post-balloon tissue have obvious lymphocytic infiltration, indicating that cell-mediated immunity is involved.
Individual immunological monitoring defects, can not explain some specific immune diseases, but also need to be linked to the idiotype cascade mechanism, the variable regions of heavy and light chains in immunoglobulin molecules have antigenic determinants, according to the region The sequence of the amino acid determines the specificity of the antibody, and the variable of different specificity has different antigenic determinants or genotype determinants. For example, rabbits are immunized with monoclonal human myeloma protein, and the obtained antiserum can be combined with myeloma immunoglobulin. The structure of the variable region of the protein is specifically bound. These structures are called genotypes. The application of the idiotype/antiidiotype principle can be extended to explain the formation of receptor antibodies in diseases such as Graves disease and myasthenia gravis. For example, in myasthenia gravis, the ligand (acetylcholine) binds to the cell surface receptor and its corresponding antibody (anti-acetylcholine, ie genotype), and thus the receptor and antibody have the same structure that can bind to the ligand, In addition, Farid et al. immunized rabbits with anti-human TSH antibodies to obtain anti-genotype antibodies, which in the thyroid culture cells can bind to TSH receptors. It can stimulate the synthesis of cAMP, which acts as if it is Graves' disease LATS or TSAb.
The self-anti-TSH receptor antibody (TRAb) in Graves disease is a group of polyclonal antibodies acting at different binding sites of TSH receptors. TRAb can be divided into excitatory and closed type, and one type of excitatory type and THS receptor. After binding, it promotes the synthesis and release of thyroxine into the blood, and the thyroid cells are also stimulated and proliferated, called TSAb, which is the main autoantibody in Graves' disease. The other type, when combined with TSH receptor, only promotes thyroid cell enlargement, but Does not cause the synthesis and release of hormones, called thyroid cell enlargement, but does not cause the synthesis and release of hormones, called thyroid growth immunoglobulin (TGI), blocking autoantibodies and TSH after full binding, blocking and inhibition Thyroid function, called thyroid function inhibitory antibody (TFIAb) and thyroid growth blocking antibody (TGRAb), a small number of patients with Graves disease have obvious hypermetabolic disease, but the goiter is very mild, probably due to excitatory antibodies in vivo, TRAb predominates Caused.
The autoimmune monitoring defects are controlled by genetic genes. The disease has obvious family aggregation. The agreement between the same egg and the hyperthyroidism is 50%. The occurrence of this disease is related to some histocompatibility complex (MHC). For example, DR4 antigen or HLA-B8, B46, etc., mental factors, such as trauma, anger is an important predisposing factor, which can lead to decompensation of Ts cell population and also promote cytotoxicity.
Prevention
Graves disease prevention
1. No disease prevention first: emotional factors play an important role in the pathogenesis of hyperthyroidism. "Ji Shengfang. The treatment of tumors" said: "The tumors are mostly irritated and overwhelmed. "Because, prevention of hyperthyroidism, we should first maintain a happy spirit in our daily life. Comfortable mood, followed by a reasonable diet to avoid irritating food, is also an important preventive measure; at the same time, living regulations, do not work hard; help the spleen and stomach, enhance Physical fitness is important for improving your own immunity and disease resistance.
2. Disease prevention and prevention: prevention of disease is the most ideal prevention, but if hyperthyroidism has occurred, it should be diagnosed early and treated early to prevent the disease from changing, that is, to prevent the development of the disease and the occurrence of complications. "Su Wen. Jade machine true Tibetan articles" cloud: "The five internal organs are connected, the movements are all secondary, the five internal organs are sick, then each pass its victory," Therefore, according to the law of the occurrence of complications of hyperthyroidism, take preventive measures To prevent the occurrence of complications and control the transformation of the disease.
3. After the anti-recurrence: As the saying goes: "The disease is like a mountain, the disease is like a silk," the analogy of the image after the disease has a state to be restored, there is a recovery of the fluid loss of the liquid. Be cautious, the original condition may be delayed and re-integrated. Therefore, in the initial stage, drugs, diet, spiritual medicated diet, etc. should be comprehensively conditioned, and regular inspections and careful monitoring are important measures to prevent recurrence after illness.
Complication
Graves disease complications Complications leukemia thyroid cancer hyperthyroidism
1. Hypothyroidism: This is a prominent and flattening after 131 iodine treatment. According to a series of foreign studies, the constant group, that is, the rate of hypothyroidism in the first year after treatment of 131 iodine 3.7 MBq per gram of thyroid gland (100 Ci) 5% to 10%, after which the annual increase of 2% to 3% to more than 10 years after treatment can reach 30% to 70%. In recent years, the long-term domestic follow-up data, the incidence of hypothyroidism is also significantly improved, because After the serum TSH radioimmunoassay was carried out, the sensitivity of the diagnosis of hypothyroidism was improved. According to our hospital's follow-up of 64 cases between 958 and 1980, the incidence of hypothyroidism in the late stage of 131 iodine treatment was 25% for 2 to 5 years, 6 to 10 years. It was 50%, 83.5% in 16-20 years, and the overall rate of hypothyroidism was 52.08%.
There are three kinds of speculations about the possible causes of hypothyroidism: First, the dose of 131 iodine is too large, and the thyroid tissue is destroyed too much. The second speculation may be that ionizing radiation damages the nucleus, so that it cannot be regenerated. The longer the thyroid function, the more thyroid function Decreased, the third is believed to be due to an autoimmune response.
2. Carcinogenicity: Clinical application of this therapy for more than 30 years, the incidence of leukemia and thyroid and thyroid cancer is not higher than the natural incidence of the two diseases, some people analyzed the incidence of thyroid cancer in three treatments, 131 iodine treatment group (22714 cases) was 0.1%, surgical group (11732 cases) was 0.5%, antithyroid drugs (1238 cases) was 3%, and another group reported 131 iodine treatment of 60 000 cases of 18 cases of leukemia Occurred, this figure is no higher than the natural incidence of leukemia in the general population. There are about 50,000 cases of domestic 131 iodine treatment for hyperthyroidism. Only 2 cases of leukemia have been reported, and the incidence rate is not higher than the natural incidence of general residents. And both cases occurred in about 1 year after 131 iodine treatment, the onset time is short, whether it is directly related to 131 iodine treatment, there are still doubts, because young patients are sensitive to radiation, some people report infant and childhood In patients with X-ray treatment of the neck, the incidence of thyroid cancer is high, so for the sake of caution, adolescent patients under the age of 25 should choose other treatments.
3. Genetic effects: the fertility of hyperthyroidism patients after 131 iodine treatment is not affected, the congenital malformation of the offspring of birth, the incidence of stillbirth and premature infants has not increased, the incidence of infertility is not significantly different from normal residents, domestic According to the data, many 131 iodine-treated patients have given birth to healthy children. Even some female patients have had endocrine disorders due to hyperthyroidism. Those who have been infertile have given birth to their children. Of course, 131 iodine treatment has been observed. The post-chromosome has a mutation, but it can gradually return to normal. Therefore, the biological significance and clinical significance of chromosomal variation after 131 iodine treatment remains to be further explored, although it is currently considered that from the genetic point of view, 131 iodine treatment increases gene mutations and chromosomes. The risk of distortion is small, but considering the long-term effects of ionizing radiation, genetic effects also require long-term follow-up observations to arrive at a correct conclusion. To protect the health of the next generation and the children of the next generation, the pregnancy is classified as 131 iodine. The contraindications for treatment are reasonable.
4. Exacerbation of exophthalmia: only seen in a small number of patients, most patients have different degrees of relief after treatment and improved.
Symptom
Graves disease symptoms common symptoms goiter, anorexia, hyperhidrosis, weight loss, irritability, goiter, cold, fear of hot blood vessel murmur
The diagnosis of typical cases is generally not difficult. The clinical manifestations of mild patients, or elderly and children, are less typical and the diagnosis often requires laboratory tests.
Diagnostic clinical manifestations pay special attention to heat, sweating, agitation, sputum with weight loss, resting heart rate, special eye signs, goiter, etc., such as vascular murmurs found in the thyroid, tremor, more Diagnostic significance.
Examine
Graves disease check
1. Determination of total thyroxine (total T4). In the normal case of thyroid hormone-binding globulin (TBG), the increase of T4 (over 12 ng/dl) suggests hyperthyroidism. If TBG is suspected to be abnormal, I125 should be determined. -T3 binding ratio (normally 0.99 ± 0.1, hyperthyroidism is 0.74 ± 0.12) and multiplied by T4 value to correct the abnormality of TBG, calculate the free thyroid index (FT4I), the patient's results increased, as normal, should Try to make further inspections.
2. The total blood T3 normal value is 100 ~ 150mg / dl, the disease is increased, the amplitude is often greater than the total T4.
3. Determination of anti-T3 (rT3), the normal mean value of blood rT3 was 50 ng.dl, and the hyperthyroidism was significantly increased.
4. Free T4 (FT4) and free T3 (FT3) The results of FT4 and FT3 are not affected by the above-mentioned TBG, and can reflect the T4 functional state more accurately than the total T4 and T3 results. The normal value: FT4 is 10.3~ 25.7pmol / L, FT3 was 2.2 ~ 6.8pmol / L, the results of hyperthyroidism patients were significantly higher than the normal high limit.
5. 131I rate of thyroid, such as increased iodine rate, 3 hours greater than 25%, or 24 hours greater than 45% (close-range method), peak advance can be consistent with the disease, but should be used for T3 inhibition test to distinguish between simpleness Goiter.
6. T3 inhibition test: The method is as described above. The rate of 131I in the second and normal goiter is significantly decreased, reaching more than 50%. In patients with this disease and invasive exophthalmos, the stimulation of thyroid by TSH has been replaced by TSAb. It is not inhibited by T3 and T4. Therefore, after a week of T320g for 8 hours, the second dose of 131I is not inhibited or less than 50%. This method should not be used for elderly patients with coronary heart disease, so as to avoid heart rhythm. Disorder or angina.
7. Thyroid stimulating hormone releasing hormone (TRH) stimulation test: patients with excitatory reactions are normal, such as TSH close to zero, or immunometric asay results with higher sensitivity, TSH is lower than normal, and is not excited by TRH It can be suggested that hyperthyroidism (including T3 hyperthyroidism), the significance of this test is similar to the T3 inhibition test, and can avoid the disadvantages of ingestion of T3 affecting the heart, aggravating symptoms, etc., but the supply of reagents has not yet become popular.
8. TSAb or TSI The positive rate of patients with this disease is about 80% to 90%. After the treatment of the disease, the activity of TSAb is obviously decreased or turned normal, which is beneficial to follow-up efficacy and identification of recurrence after treatment. Clinically, this is often used to estimate the resistance. The thyroid medication is stopped for a suitable period of time.
9. Anti-thyroglobulin antibody (TGA) and anti-thyroid microsomal antibody (MCA): TGA and MCA can be positive in this disease, but its titer is far less than Hashimoto's thyroiditis.
Diagnosis
Diagnosis and diagnosis of Graves disease
diagnosis
Diagnosis can be based on medical history, clinical symptoms, and laboratory tests.
Differential diagnosis
In the differential diagnosis, we must consider: 1 simple goiter, except for goiter, there is no such symptoms and signs, although sometimes the 131I uptake rate is increased, most of the T3 inhibition test shows inhibition, serum T3, rT3 are normal, 2 nerves Functional dysfunction, 3 autonomic hyperfunctional thyroid nodules, radioactivity concentrated at the nodules during scanning: repeated scans after TSH stimulation, showing increased nodule radioactivity, 4 other, tuberculosis and rheumatism often have low fever, hyperhidrosis Speed, etc., diarrhea as the main manifestation is often misdiagnosed as chronic colitis, the performance of senile hyperthyroidism is atypical, often apathy, anorexia, obvious weight loss, easy to be misdiagnosed as cancer, unilateral invasive exophthalmia need to Identification of intraorbital and cranial low tumors, hyperthyroidism with muscle disease, need to be identified with familial cycle paralysis and myasthenia gravis.
