Chronic lymphocytic thyroiditis

Introduction to chronic lymphocytic thyroiditis Chronic lymphocytic thyroiditis (CLT), also known as autoimmune thyroiditis, is a chronic inflammatory autoimmune disease with its own thyroid tissue as an antigen. Japan's Kyushu University Hashimoto first (1912) reported four cases in the German medical journal and named Hashimoto (Hashimotosthyroiditis, HT), the most common thyroid inflammation in the clinic. In recent years, the incidence rate has increased rapidly. It has been reported that it has similar morbidity to hyperthyroidism. This disease is the most common cause of goiter and acquired hypothyroidism in children and adolescents. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific people Mode of infection: non-infectious Complications: Sjogren's syndrome Rheumatoid arthritis Anemia Systemic lupus erythematosus Hepatitis Edema

Causes of chronic lymphocytic thyroiditis

Genetic factors (45%):

It has become a consensus that CLT is produced by the interaction of genetic factors and non-genetic factors. The production of thyroid autoantibodies is related to autosomal dominant inheritance. In Europe and North America, HLA-B8 and DR3, DR5 are more common in CLT patients. The Japanese were more common with HLA-B35. Xu Chun et al. used PCR-SSCP to detect allele polymorphisms in HLA-DQA1 and DQB1 loci in 30 Han Chinese CLT patients, and found that the frequency of DQA1-0301 was significantly higher than that of normal controls. It is speculated that it may be a susceptibility gene in Chinese disease. A US research institute analyzed the genes of 56 Caucasian families with autoimmune thyroid disease and identified six genes associated with autoimmune thyroid disease. The AITD-1 gene located on chromosome 6 is associated with Graves disease and CLT; CLT-1 on chromosome 13 and CLT-2 on chromosome 12 are associated with the pathogenesis of CLT, after which they used Genomic screening method studied a Chinese American family with 27 family members and found that D1IS4191 and D9S175 are related to CLT, so it is believed that there are different genetic susceptibility to CLT among different races, Tomer et al. Studies have shown that an important decision thyroid autoantibodies gene located on chromosome 2q33, activation pathway essential co-stimulatory factor CTLA-4 gene is very likely that genes on chromosome thyroid antibodies 2q33.

Immunological factors (30%):

The mechanism by which immunological factors cause thyroid damage is not fully understood. At present, the following mechanisms are preferred:

(1) Defects in congenital immune surveillance: The number and quality of organ-specific inhibitory T lymphocytes are abnormal, and T lymphocytes can directly attack thyroid follicular cells.

(2) Humoral immune-mediated autoimmune mechanism: HK cells can attack thyroid follicular cells in synergy with anti-thyroid antibodies. When antigen-antibody binds, its complex exists in target cell target, activated HK cells and antibodies. The Fc fragment reacts to kill target cells. This antibody-dependent cytotoxicity of HK cells is activated by thyroglobulin-thyroglobulin antibody complex in CLT and kills with specific cytotoxicity. Thyroid follicular cells, in addition, TPOAb itself plays a cytotoxic role in thyroid tissue.

(3) The lytic effect of anti-thyroid antibodies bound to complement on follicular cells.

(4) Lymphocyte-mediated toxicity, anti-thyroid antibody triggers and activates it.

(5) CLT patients are often accompanied by other autoimmune diseases such as pernicious anemia, systemic lupus erythematosus, rheumatoid arthritis, type I diabetes, chronic active hepatitis, etc., which also prove the existence of autoimmune factors.

Environmental factors (15%):

Infection and dietary iodide are the two major environmental factors in the development of CLT. Wenzel et al. used western blotting to study the anti-Yersinia bacterial antibodies in serum of CLT patients. The frequency of this antibody was significantly higher than that of patients with non-autoimmune thyroid disease. In contrast to the normal control group, Yerinia bacteria in the small intestine and colon were associated with the development of CLT.

In areas with iodine deficiency or iodine-rich areas, the incidence of CLT increases, indicating that iodine plays an important role in the pathogenesis of CLT. In excess, genetically susceptible animals can develop thyroiditis, but if iodine is not depleted in the thyroid gland, Can prevent the development of severe thyroiditis, the mechanism has not yet been elucidated, Rose et al found that the addition of iodine in the diet, CLT thyroid damage significantly increased, the incidence of CLT increased, thyroglobulin iodization, T cell proliferation in CLT, the main Increased potency of the pathogenic antigen-Tg autoantigen and increased systemic immune response can lead to CLT.

Pathogenesis

Pathological changes

(1) Macroscopic view: In typical cases, bilateral thyroid diffuse enlargement, in some cases, the enlargement of one leaf gland is obvious, the gland enlargement is about 2 to 5 times of normal, the surface is smooth or fine nodular, and the capsule Complete, thickened, with little adhesion to the surrounding tissue, the cut surface is slightly raised, the texture is tough like rubber, showing obvious or inconspicuous lobulated, gray or grayish yellow, lack of luster due to less gelatin content, similar to hyperplastic lymph nodes There is no bleeding, calcification or necrosis. In the middle and late stages, it may be nodular due to extensive fibrosis, and the texture is hard. Some cases adhere to the surrounding tissues.

(2) Microscopic examination: The main histological features are thyroid follicular destruction, atrophy, decreased glial content in the lumen, follicular epithelial eosinophilia and interstitial lymphocytes, plasma cell infiltration, and prominent germinal center lymph Follicular formation and varying degrees of fibrosis.

The infiltration of lymphocytes is distributed in the lobules, and there are more between the follicles and the lobes, and there are fewer between the lobes. The lymphocytes between the follicles often form lymphoid follicles or diffuse distribution with germinal centers. The lymphoid follicles are mainly composed of small lymphocytes. It is composed of lymphocytes transformed at various levels in the germinal center, while the diffusely distributed lymphocytes mainly surround the degenerated epithelium, sometimes a small amount of lymphocytes invade into the follicles, between the epithelial cells and the basement membrane, and even invade In the follicular cavity, in addition to small lymphocytes, there are also many different plasma cells, tissue cells, immunoblasts and multinucleated giant cells, and the ratio of lymphoid tissue to thyroid tissue varies, usually around 1/3.

Chronic lymphocytic thyroiditis prevention

It is an autoimmune disease with no special precautions. Long-term use of thyroxine after surgery can reduce the incidence of hypothyroidism, and at the same time continue to treat Hashimoto's disease, especially in patients who have more thyroid tissue removed during surgery. This group of patients are given oral replacement therapy with levothyroxine tablets after surgery. 50mg / d as the starting dose, according to the review of FT3, FT4, TSH results gradually adjust the amount of thyroxine tablets until the maintenance amount, and as long as possible to take the medication time or lifelong medication, the group has complete follow-up data, follow-up for more than 3 years of thyroid hormone The average level of water control was within the normal range, and no hypothyroidism occurred.

Chronic lymphocytic thyroiditis complications Complications Sjogren's syndrome rheumatoid arthritis anemia systemic lupus erythematosus hepatitis edema

Patients with chronic inflammation often have other autoimmune diseases such as Sjogren's syndrome, rheumatoid arthritis, diabetes, diabetes, systemic lupus erythematosus, adrenal insufficiency, idiopathic ovarian dysfunction and chronic active hepatitis. Etc., if the disease progresses, the hypothyroidism may occur after a few years, manifested as thyroid atrophy, mucinous edema, slow heart rate, body aches, fatigue, lack of activity, thick skin and so on.

Chronic lymphocytic thyroid symptoms common symptoms thyroid enlargement, fatigue, neck lymphadenopathy, dysphagia, inability to goiter

History and symptoms:

More common in women aged 30 to 50, the onset of insidious, slow development of the disease, the main manifestations of thyroid enlargement, mostly diffuse, a few can be limited, part of the face, swelling of the limbs onset.

Clinical manifestations of typical cases:

1. Slow development, long course of disease, early asymptomatic, when the goiter occurs, the course of disease has reached an average of 2 to 4 years.

2. Common symptoms are general malaise, many patients do not have throat discomfort, 10% to 20% of patients have local pressure or thyroid gland pain, and occasionally tender tenderness.

3. The thyroid is mostly bilateral symmetry, diffuse enlargement, isthmus and conical leaves often increase at the same time, but also unilateral enlargement, the thyroid often increases with the progression of the disease, but rarely presses the neck Breathing and difficulty swallowing, when palpation, the thyroid texture is tough, the surface can be smooth or fine sand-like, and can also be nodular in shape, generally no adhesion to the surrounding tissue, can move up and down during swallowing movement.

4. The cervical lymph nodes are generally not swollen, and a few cases may also be associated with cervical lymphadenopathy, but the quality is soft.

Examination of chronic lymphocytic thyroiditis

Laboratory inspection:

Thyroid function test

Serum T3, T4, FT3, and FT4 are generally normal or low. Even in patients with hyperthyroidism, T3 and T4 levels are often normal.

2. Determination of serum TSH concentration

Serum TSH level can reflect the metabolic state of patients. Generally, TSH is normal in normal thyroid function, but it is elevated in hypothyroidism. However, some patients with normal T3 and T4 may have elevated TSH, which may be due to thyroid dysfunction. Sexual TSH is elevated to maintain normal thyroid function. CLT should be highly suspected when TSH is more than twice normal. In recent years, there have been more and more reports of subclinical hypothyroidism. The indicator for subclinical hypothyroidism is TSH. Gao, it has been reported that after 20 years of follow-up observation, 55% of subclinical hypothyroidism CLT women can develop clinical hypothyroidism, the initial thyroid antibody positive, the rate of progression to hypothyroidism is 2.6% (33%) per year. The initial rate of hypothyroidism in patients with elevated TSH was 2.1% (27%) per year. It was also reported that if CLT was associated with subclinical hypothyroidism, and TSH was >20 nU/ml, 25% could progress annually. To the clinical type of hypothyroidism, and those with a slight increase in TSH can return to normal.

3.131I absorption rate check

Can be lower than normal, but also higher than normal, most patients are at normal levels.

4. Anti-thyroid antibody assay

Anti-thyroglobulin antibody (TGAb) and anti-thyroid microsomal antibody (TMAb) assays are helpful in the diagnosis of CLT. In recent years, TPO (peroxidase) has been proven to be the antigen of TMAb, which can fix complement and has "cytotoxicity". "The role, and confirmed that TPOAb causes thyroid follicular cell damage through activation of complement, antibody-dependent cell-mediated cytotoxicity and sensitized T cell killing. TPO-Ab can directly bind to TPO and inhibit TPO activity. TPO is a key enzyme in the synthesis of thyroxine. TPOAb has replaced TMAb for the diagnosis of CLT. The positive rate of TGAb and TPOAb combined detection is over 90%. For single detection, TPOAb determination is superior to TGAb in the diagnosis of CLT. According to reports in the literature, 80% of CLT patients tested positive for TGAb, while 97% of patients tested positive for TPOAb, but it was also reported that the positive rate of TGAb and TPOAb in CLT patients was less than 50%, the first affiliated hospital of Zhongshan University of Guangzhou concluded Of the 335 cases of CLT confirmed by postoperative pathology, only about half of the cases were positive for TGAb and TPOAb.

5. The potassium perchlorate excretion test is positive, and the iodine release rate is >10%.

6. Cytological examination

Fine needle aspiration cytology (FNAC) and tissue cryosection histological examination have a decisive role in the diagnosis of CLT. CLT can be diffuse parenchymal atrophy, lymphocytic infiltration and fibrosis, and thyroid cells slightly enlarged. Eosinophilic staining, ie Hurthle cells.

7. Other inspections

ESR increased, the flocculation test was positive, gamma globulin IgG increased, blood beta lipoprotein increased, and lymphocyte count increased.

Film degree exam:

1.B ultra-checking the sound image as:

(1) The diffuse enlargement of the two thyroid glands is generally symmetrical, and may also be mainly swollen on one side and thickened in the isthmus.

(2) The surface is uneven, forming a nodular surface, the shape is stiff, the edge becomes dull, and the probe is pressed with a hard object.

(3) The gland is uneven and low echo, see suspicious nodule-like echo, but the boundary is unclear, can not be repeated on multiple cut surfaces, sometimes only shows partial echo reduction, and some visible fine line-like strong echo formation irregularity The network looks like a change.

(4) There may be small cystic changes inside.

2. Color Doppler sound image performance: blood flow in the thyroid is rich, sometimes almost fire sign, the upper thyroid artery flow rate is high, the inner diameter is thicker, but the arterial flow rate and resistance index are significantly lower than hyperthyroidism, and the frequency bandwidth, diastolic The amplitude of the period is increased, and there is no symptoms of hyperthyroidism, which can be identified.

3. Thyroid nuclides scan: showing thyroid enlargement but reduced iodine intake, uneven distribution, if there is a large nodular shape can be cold nodule performance.

4. Positron emission tomography (PET): PET examination with 18-fluoro-deoxyglucose (18F-FDG), non-invasive examination of tissue glucose metabolism, can be used for diagnosis A variety of tumors, diffuse 18F-FDG absorption in thyroid examination may suggest thyroiditis, activation of the lymphoid tissue of the thyroid may be the cause of 18F-FDG absorption, but should be distinguished from thyroid cancer because of 18F-FDG/PET identification Thyroid malignancy and CLT are still difficult and should be identified in combination with other clinical tests.

Diagnosis and diagnosis of chronic lymphocytic thyroiditis

diagnosis

At present, the diagnostic criteria for CLT have not been unified. In 1975, Fisher proposed five diagnostic protocols, namely, 1 diffuse thyroid enlargement, toughness, uneven surface or nodules, 2TGAb, TMAb positive; 3 elevated blood TSH, 4 thyroid Scanning has irregular concentration or sparseness, 5 perchlorate potassium excretion test is positive, 2 out of 5 can be diagnosed as CLT, 4 can be diagnosed, generally in clinical as long as typical CLT clinical manifestations, serum TGAb TPOAb positive can be clinically diagnosed as CLT. For patients with atypical clinical manifestations, high titer anti-thyroid antibody assay is needed to diagnose. For these patients, if serum TGAb and TPOAb are positive, necessary imaging examination should be given. Co-diagnosis, and given thyroxine diagnostic treatment, if necessary, should be confirmed by FNAC or frozen section histological examination.

Atypical performance:

It is worth noting that the clinical manifestations of CLT are often not typical, or combined with other thyroid diseases or autoimmune diseases, the main atypical manifestations are:

(1) Hashimoto's hyperthyroidism: Graves disease and CLT are combined and can be transformed into each other. Patients may have clinical manifestations of hyperthyroidism, high titers of TGAb and TPOAb, and may have TSAb positive, 131I absorption rate of thyroid is increased, and no Inhibited by T4, pathology has both GD and CLT characteristic changes.

(2) exophthalmia type: mainly invasive exophthalmos, may be associated with goiter, normal thyroid function, TGAb, TPOAb positive, some patients can detect TSAb (thyroid stimulating antibody) and pro-ocular immunoglobulin.

(3) subacute thyroid type: clinical manifestations similar to subacute thyroiditis, acute onset, rapid thyroid enlargement and pain, 131I absorption rate is normal, T3, T4 normal, TGAb, TPOAb high titer positive.

(4) Adolescent type: CLT accounts for about 40% of adolescent goiter. Adolescent CLT has normal thyroid function, TGAb, TPOAb titer is low, clinical diagnosis is difficult, and some patients have slower goiter, called adolescent hyperplasia. Type, thyroid tissue lacks eosinophils, often without systemic and other local symptoms, patients with hypothyroidism can affect growth and development.

(5) associated with thyroid tumor type: often manifested as solitary nodules, hard, TGAb, TPOAb titer is higher, the nodules may be part of thyroid tumor or thyroid cancer, the surrounding part is CLT, CLT combined with thyroid cancer The rate was 0.5% to 26.0%. The First Affiliated Hospital of Sun Yat-sen University of Guangzhou (1998) reported that 13% (9/69) of a group of CLTs had thyroid cancer, and Gyory (1999) reported that CLT combined tumors accounted for 11.8% (14/118). Therefore, when the following conditions are encountered in the clinic, the possibility of combining tumors should be considered, FNAC or excisional biopsy should be performed: 1 thyroid pain is obvious, thyroxine treatment is ineffective, 2 glandular thyroid hormone treatment does not shrink but increases, 3 goiter enlargement The neck lymph nodes are swollen and have compression symptoms. There are a single cold nodule in the gland, which is asymmetrical and hard.

(6) fibrotic type (atrophic type): patients with a longer course of disease may have extensive or partial fibrosis of the thyroid gland, manifested as thyroid atrophy, hard texture, TGAb and TPOAb may be destroyed by thyroid, fibrosis is not high, thyroid function Also reduced, tissue sections showed the same as CLT, often misdiagnosed as primary hypothyroidism or thyroid cancer, which is one of the main causes of mucinous edema in adults.

(7) Complicated with other autoimmune diseases: manifested as multiple autoimmune diseases, such as CLT with Addisons disease, diabetes, pernicious anemia, idiopathic hypoparathyroidism, myasthenia gravis, systemic lupus erythematosus and other diseases Some people also call "autoimmune polyglandular failure syndrome" or "polygranulomatous failure syndrome", such as multiple endocrine neoplasia syndrome type II (Addison disease, AITD, type I diabetes, hypogonadism) One of the performances.

(8) Hashimoto encephalopathy: severe and rare. Since the first case was reported in 1966, only about 50 cases have been reported in the world. The etiology and pathogenesis are unclear. The clinical manifestations can be:

1 vasculitis type: characterized by repeated episodes of stroke-like episodes.

2 diffuse progression: there may be disturbance of consciousness, confusion, lethargy or coma, abnormal cerebrospinal fluid examination, increased protein content, increased monocytes, positive thyroid antibodies, especially TPOAb titers, thyroid hormone levels are generally normal Or low, EEG can be abnormal, the treatment of this disease with corticosteroids, thyroxine also has a good effect, chronic lymphocytic thyroiditis (CLT), also known as autoimmune thyroiditis, is A chronic inflammatory autoimmune disease with its own thyroid tissue as an antigen. Hashimoto of Kyushu University, Japan (1912) first reported 4 cases in the German medical journal and named Hashimoto thyroiditis (HT). It is the most common thyroid inflammation in the clinic. In recent years, the incidence rate has increased rapidly. It has been reported that it has similar morbidity to hyperthyroidism. This disease is the most common cause of goiter and acquired hypothyroidism in children and adolescents.

Physical examination found:

The thyroid gland is diffuse or localized, with a hard texture and a sense of elasticity. The boundary is clear, no tenderness, and the surface is smooth. Some of the thyroid gland may be nodular, the cervical lymph nodes are not swollen, and some may have mucus of the extremities. Edema.

Auxiliary inspection:

(1) Early thyroid function can be normal, and the thyroid function of Hashimoto's hyperthyroidism is slightly elevated. As the disease progresses, T3 and T4 may decrease, TSH increases, TMAb and TGAb are positive, and (2) thyroid radionuclide imaging has Irregular concentration or sparse area, a few showed "cold nodules", (3) positive potassium perchlorate release test, (4) serum gamma globulin increased, albumin decreased, (5) thyroid puncture showed a large number of lymphocytic infiltration .

Differential diagnosis

Nodular goiter

A small number of CLT patients may have thyroid nodular changes, and even multiple nodules, but the thyroid autoantibody titers in patients with nodular goiter are reduced or normal, thyroid function is usually normal, and clinical hypothyroidism is rare.

2. Adolescent goiter

During puberty, persistent thyroid enlargement is a compensatory hyperplasia in which the thyroid hormone temporarily increases in thyroid hormone requirements. The thyroid function is generally normal, and the thyroid autoantibody titer is mostly normal.

3.Graves disease

The enlarged thyroid texture is usually soft, and the anti-thyroid antibody titer is low, but there are also high titers. It is difficult to distinguish between the two, especially when the CLT is combined with hyperthyroidism, the thyroid function can also be increased. If necessary, fine needle aspiration can be performed. Cytological examination.

4. Thyroid malignancy

CLT can be combined with thyroid malignant tumors, such as papillary thyroid carcinoma and lymphoma. When CLT has nodular changes, such as nodule isolation, when the texture is hard, it is difficult to distinguish it from thyroid cancer. Some cases of bilobal thyroid cancer may appear. Bilateral thyroid enlargement, hard or combined with bilateral neck lymphadenopathy, is also difficult to identify with CLT, anti-thyroid antibodies should be tested, antibody titers in thyroid cancer cases are generally normal, thyroid function is also normal, such as clinically difficult to diagnose The thyroid hormone can be given experimental treatment. If the gland is obviously reduced or softened after taking the drug, CLT can be considered; if there is still no obvious change, FNAC or surgical biopsy should be performed to confirm the diagnosis.

5. Chronic invasive fibrous thyroiditis

In 1896, Riedel first reported 2 cases, so it was called Riedel thyroiditis. Because the thyroid texture of the lesion is hard as wood, it is also called woody thyroiditis. The lesion often exceeds the thyroid gland and invades surrounding tissues such as muscles, blood vessels, nerves and even trachea. The symptoms of compression of adjacent organs, such as difficulty in swallowing, difficulty in breathing, hoarseness, etc., the contour of the thyroid gland can be normal, the quality is as hard as stone, no pain, adhesion to the skin, no swallowing activity, no surrounding lymph nodes, normal thyroid function, Hypothyroidism may occur after thyroid tissue is completely replaced by fibrous tissue, accompanied by fibrosis in other parts, such as mediastinum, retroperitoneum, lacrimal gland, gallbladder, etc., anti-thyroid antibody titer is reduced or normal, feasible fine needle biopsy, such as test results Unsatisfactory, feasible thyroid tissue biopsy.

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