Thyroiditis encompasses many common thyroid disorders, each with multiple names, and this article discusses the diagnosis and treatment of the various types of thyroiditis.
Hashimoto’s thyroiditis, sporadic painless thyroiditis and postpartum painless thyroiditis all have an autoimmune background. In Hashimoto’s thyroiditis, activation of thyroid antigen-specific helper T cells causes an immune response against the thyroid gland. One theory suggests that this activation originates from a viral infection that has a protein similar to thyroid proteins, but direct evidence of viral origin is lacking. Another theory suggests that thyroid epithelial cells present proteins from their own cells to T cells, and there is evidence that autoimmune thyroiditis in women can be triggered by the accumulation of fetal cells in the maternal thyroid during pregnancy.
Once the helper T cells are activated, they induce B cells to secrete thyroid autoantibodies. In the United States, up to 10% of the population has elevated levels of thyroid autoantibodies in their sera, and up to 21% of women over the age of 60. The proportion of people with elevated levels of thyroid autoantibodies varies by race, with the Third National Health and Nutrition Examination Survey showing that 14.3% of people over the age of 12 have elevated levels of thyroid autoantibodies in whites, 10.9% in Mexicans, and only 5.3% in blacks. In a British study, 10% of postmenopausal women with elevated levels of thyroid autoantibodies had subclinical hypothyroidism and 0.5% had clinical hypothyroidism, and 2%-4% of normal thyroid functioners with elevated levels of thyroid autoantibodies progressed to clinical hypothyroidism each year. In a 10-year prospective study conducted in Switzerland, elevated thyroid peroxidase antibodies (TPO-Ab) predicted a tendency for subclinical hypothyroidism to progress to clinical hypothyroidism.
The most commonly detected thyroid autoantibodies are TPO-Ab, which is associated with significant thyroid abnormalities, and Tg-Ab, which tends to be positive for thyroid damage and lymphocytic inflammation, TPO-Ab, which binds to complement and exerts a direct cytotoxic effect on thyroid cells, and autoantibodies to the blocking TSH receptor (TR-Ab), which is seen in 10% of patients with Hashimoto’s thyroiditis. Tg-Ab is relatively uncommon and its role is unknown, and autoantibodies against glial antigens, thyroid hormone antigens, and sodium-iodine pump transport antigens are also present in patients with autoimmune thyroiditis.
The most common common pathology in all types of autoimmune thyroiditis is an infiltration of T and B cells in equal numbers. In patients with Hashimoto’s thyroiditis, thyroid cells express the Fas gene, a closely related group of tumor necrosis factor genes or supergene family, which is not expressed by normal thyroid cells. Apoptosis caused by the interaction of Fas genes with Fas gene ligands located on the surface of thyroid cells may be the cause of thyroid cell damage.
Genetic susceptibility
The inheritance of autoimmune thyroid disease is complex, with reported associations with HLA-DR3, HLA-DR4 and HLA-DR5 in white Hashimoto’s thyroiditis and painless postpartum thyroiditis, but other races associated with other loci. The cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene region may be associated with familial Hashimoto’s thyroiditis, but with painless postpartum thyroiditis The association was negative, and the incidence of subacute thyroiditis was increased in those with the HLA-Bw35 genotype.
Environmental factors
Patients with Hashimoto’s thyroiditis who smoke are more likely to develop hypothyroidism than nonsmokers, possibly because of exposure to thiocyanates in smokers, and there is an increased incidence of painless postpartum thyroiditis in smokers, and geographic differences in the development of Hashimoto’s thyroiditis, sporadic painless thyroiditis, and painless postpartum thyroiditis suggest that dietary iodine deficiency may have a protective effect against autoimmune thyroiditis .
Various forms of thyroiditis can cause hyperthyroidism, hypothyroidism, or a combination of both.
Painless sporadic thyroiditis, postpartum painless thyroiditis and painful subacute thyroiditis, inflammatory damage to the thyroid gland causes a transient increase in circulating thyroid hormone levels due to the release of already synthesized thyroid hormones, causing hyperthyroid symptoms. The earliest biochemical change in inflammatory thyroiditis before the onset of hyperthyroidism symptoms is an increase in serum thyroglobulin levels. As in other cases of hyperthyroidism, TSH levels are suppressed, total and free T3 and T4 levels are elevated, and serum T4 and T3 concentrations increase proportionally, reflecting the ratio of hormones stored in the thyroid gland (while T3 is more significantly elevated in Graves’ hyperthyroidism and toxic nodular goiter, the signs and symptoms of hyperthyroidism caused by thyroiditis are generally milder.
Hypothyroidism
The hypothyroid phase of thyroiditis is due to the gradual depletion of stored thyroid hormones. All types of thyroiditis can progress to persistent hypothyroidism, which seems to be seen more often in patients with markedly elevated thyroid autoantibodies in the serum or in patients with more severe hypothyroidism. With the gradual decline in thyroid function, TSH levels gradually increase, and elevated serum TSH levels with normal free T4 and T3 levels are called subclinical hypothyroidism, or mild thyroid failure. With the progression of thyroid failure, serum T4 concentrations gradually decrease, and elevated serum TSH accompanied by decreased T4 levels is called clinical hypothyroidism, and because elevated TSH levels stimulate the thyroid gland to release T3, unless thyroid disease is very severe, total and free T3 and T4 levels generally do not decrease, and in most cases, once patients experience a decrease in T3 levels below normal levels, patients often present with typical hypothyroid signs and symptoms [6].
Types of thyroiditis
Hashimoto’s thyroiditis
Patients with Hashimoto’s thyroiditis are the most common type of thyroiditis and present with elevated thyroid autoantibodies in the serum and an enlarged thyroid gland. In the United States and other countries with adequate dietary iodine intake (median urinary iodine levels >100 mcg/L), Hashimoto’s thyroiditis is the most common cause of hypothyroidism and goiter. Sometimes patients present with alternating hyperthyroidism and hypothyroidism, most likely due to alternating thyroid stimulating and blocking antibodies.
The presentation of Hashimoto’s thyroiditis is often initially a symmetrical enlargement of the thyroid gland that is painless, hard and uneven. .
In patients with Hashimoto’s thyroiditis, once hypothyroidism is present, levothyroxine may be given. For subclinical hypothyroidism, since progression to clinical hypothyroidism is common and predisposes to abnormal lipid metabolism and atherosclerotic heart disease, thyroid hormone replacement therapy has been advocated, with the goal of treatment being to restore TSH levels to normal.
In patients with Hashimoto’s thyroiditis with significant enlargement of the thyroid gland, levothyroxine sodium may be given as a TSH inhibitor for a short period of time (e.g., 6 months) to shrink the enlarged thyroid gland. Most patients with Hashimoto’s thyroiditis (regardless of whether the thyroid gland is normal or hypothyroid) have their thyroid gland shrink by 30% within 6 months after giving levothyroxine sodium treatment, and if the thyroid gland does not shrink in size, adjustment of the dosage should be considered. Because treatment with levothyroxine sodium does not reduce thyroid autoantibody concentrations unless accompanied by hypothyroidism, it is no longer necessary to test thyroid autoantibody concentrations once the diagnosis of Hashimoto’s thyroiditis is clear.
Although thyroid lymphoma is very rare, it has a 67-fold increased risk in patients with Hashimoto’s thyroiditis. Patients with significant thyroid nodules with Hashimoto’s thyroiditis should have a fine needle aspiration biopsy of the thyroid to rule out lymphoma and thyroid cancer, and patients with thyroid cancer in combination with Hashimoto’s thyroiditis or other lymphocytic infiltrations have a better prognosis than patients without lymphocytic infiltrations.
Painless postpartum thyroiditis
Patients with painless postpartum thyroiditis develop lymphocytic inflammation in the thyroid gland within a few months after delivery. Its incidence is estimated to be as high as 10% in the United States, and it is more common in women with elevated TPO-Ab in early pregnancy or after delivery, the presence of other autoimmune diseases (such as type 1 diabetes), and a family history of autoimmune thyroid disease.
Only 1/3 of patients with postpartum painless thyroiditis present with the typical three phases of hyperthyroidism, which typically occurs 1-6 months postpartum and lasts 1-2 months, followed by hypothyroidism, which typically occurs 4-8 months postpartum and lasts 4-6 months. 80% of women return to normal thyroid function within 1 year. However, a group of follow-up studies showed that persistent hypothyroidism occurred in 50% after 7 years, and persistent hypothyroidism was more common in women with multiple births and in patients with spontaneous abortions, and after the first painless postpartum thyroiditis, it recurred in 70% after another pregnancy [7 8].
Most patients with postpartum painless thyroiditis have a small, hard, non-tender thyroid gland, elevated TPO-Ab or TG-Ab or both, normal sedimentation, and a 24-h iodine uptake rate that distinguishes postpartum painless thyroiditis from postpartum Graves’ hyperthyroidism, which has a low iodine uptake rate (<5%) and is elevated in postpartum Graves' hyperthyroidism, and for the presence of thyrotoxic signs without Since radioactive iodine can be excreted through breast milk and 123I has a half-life of 13 hours, breast milk should be aspirated and discarded at least 2 days after the test in lactating women.
Mild hyperthyroidism rarely requires treatment, but for severe cases beta-blockers can be given. Since thyroid hormone production does not increase, the application of antithyroid drugs is prohibited. The hypothyroid phase usually does not require treatment, but if hypothyroidism lasts for a long time or if hypothyroid symptoms are present, thyroid hormone therapy can be given and discontinued after 6-9 months to observe whether thyroid function returns to normal.
Painless sporadic thyroiditis
Painless thyroiditis in the postpartum period cannot be distinguished from painless sporadic thyroiditis, except in relation to pregnancy, and the latter is more difficult to study because of its dissemination, which may be a subacute onset of Hashimoto’s thyroiditis. The clinical course of painless sporadic thyroiditis, in which hyperthyroidism may account for 1% of hyperthyroidism, is the same as that of painless postpartum thyroiditis, and although most people with abnormal thyroid function eventually return to normal, 20% of patients eventually develop persistent hypothyroidism. The symptoms are generally mild, with 50% of patients having diffuse mild enlargement of the thyroid gland and a hard texture. 50% of patients have a higher than normal TPO-Ab, but the titer is less than that of patients with Hashimoto’s thyroiditis, and the 24h iodine uptake rate is low or even undetectable. The exact recurrence rate is not known.
Painful subacute thyroiditis
Painful subacute thyroiditis is a self-limiting inflammatory disease and is the most common cause of thyroid pain, accounting for 5% of clinical thyroid disorders. It often follows an acute upper respiratory infection, with a peak incidence in summer, consistent with the peak occurrence of enteroviruses, and therefore subacute thyroiditis is presumed to be caused by enteroviruses, but direct evidence is still lacking.
Subacute thyroiditis starts with generalized myalgia, pharyngitis, hypothermia and fatigue, followed by fever and severe neck pain and swelling. 50% of patients have thyrotoxicosis, which usually returns to normal thyroid function after a few weeks, followed by a period of hypothyroidism lasting 4-6 weeks, consistent with postpartum painless thyroiditis and painless sporadic thyroiditis. Although thyroid function returns to normal on its own after 6-12 months in 95% of patients, hypothyroidism persists in 5% of patients and recurs in only 2% of patients with painful subacute thyroiditis.
The hallmarks of painful subacute thyroiditis are a markedly accelerated blood sedimentation, elevated C-reactive protein, normal or mildly elevated white blood cell count, elevated peripheral blood thyroid hormone levels, a T4/T3 ratio above 20, reflecting the proportion of hormones stored in the thyroid gland, lower than normal or undetectable TSH levels, generally normal TPO-Ab, and a 24h iodine uptake rate in the thyroid gland during the hyperthyroid phase of subacute thyroiditis. The 24h iodine uptake rate of the thyroid is reduced in the hyperthyroid phase of subacute thyroiditis (<5%), which is distinguished from Graves' disease. Color Doppler ultrasound also helps to differentiate between increased thyroid vascularity in Graves' hyperthyroidism and hypoechoic thyroid with reduced or normal blood flow in subacute thyroiditis.
Treatment of painful subacute thyroiditis is simply symptom relief. NSAIDs or salicylates are sufficient to control mild thyroid pain. For severe neck pain, high-dose steroid hormones (e.g. prednisone 40 mg/d) provide immediate pain relief and should be tapered over 4-6 weeks. Steroid hormones should be discontinued when iodine uptake returns to normal levels. β-blockers can control The symptoms of hyperthyroidism, the hypothyroid phase is generally mild and of short duration, and there is generally no need to apply levothyroxine sodium therapy, but it can be applied for symptomatic patients.
Septic thyroiditis
Septic thyroiditis is often caused by bacterial infections, but can also be caused by fungal, mycobacterial and parasitic infections. In general, the thyroid gland is not susceptible to infection because of its envelope, high iodine concentration, abundant blood flow and wide lymphatic drainage. Septic thyroiditis is rare and occurs most often in patients with pre-existing thyroid disease (thyroid cancer, Hashimoto’s thyroiditis or multinodular goiter, congenital anomalies such as pyriform sinus fistula are the most common in children). Pneumocystis carinii and other opportunistic infections have been reported in the thyroid gland.
Patients with septic bacterial thyroiditis often have an acute onset with fever, dysphagia and speech disturbances, pain and erythema in the anterior neck and tenderness of the neck swelling, which may be preceded by symptoms of upper respiratory tract infection. Thyroiditis caused by fungal, mycobacterial and parasitic infections and opportunistic bacterial infections in AIDS patients often presents as chronic and insidious.
Thyroid function is usually normal, but hyper- and hypothyroidism have been reported. White blood cell counts and sedimentation are elevated, and areas of suppuration are usually cold nodules, with fine needle aspiration biopsy for Gram’s stain and culture as diagnostic tests. Treatment includes appropriate antibiotics and abscess excision and drainage, and the disease can be fatal if diagnosis and treatment are delayed.
Drug-related thyroiditis
Many drugs can affect thyroid function or thyroid function test results, and only a few have been found to stimulate autoimmune or destructive thyroid inflammation.
Amiodarone
High dose anti-thyroid medication – potassium perchlorate or iopantothenic acid may be applied before thyroidectomy
High dose steroid hormone, iopantothenic acid
Sodium levothyroxine
Hypothyroidism caused by amiodarone is due to iodine excess, which occurs in up to 20% of iodine-sufficient areas. Patients with pre-existing autoimmune thyroid disease are at increased risk of developing amiodarone, and hypothyroid patients can be treated with levothyroxine sodium, and can continue to be treated with amiodarone, which reduces T3 production by decreasing 5’deiodinase activity in peripheral tissues. Therefore a higher dose of levothyroxine sodium is needed than is normally required to restore TSH levels to normal.
Amiodarone induced hyperthyroidism occurs in up to 23% of cases and is more common in iodine deficient areas. Amiodarone induced type I hyperthyroidism refers to the synthesis and release of excess thyroid hormones from the thyroid gland, caused by excess iodine, but is more likely to occur in patients with pre-existing subclinical thyroid disease, especially in patients with nodular goiter. The distinction between the two is difficult, with some patients having both types, and in iodine-sufficient areas, patients with both types often have lower than normal iodine uptake rates and increased blood flow in type I hyperthyroidism on color Doppler ultrasonography and decreased blood flow in type II hyperthyroidism [9].
Amiodarone induced type I hyperthyroidism is best treated with high doses of antithyroid drugs (tabazol or propylthioxypyrimethamine), sometimes with potassium perchlorate to prevent further iodine uptake by the thyroid, and lithium has also been suggested for type I. Amiodarone induced type II hyperthyroidism is effective with high doses of steroid hormone therapy, and recently iopantothenic acid has been found to be effective for type II, although slightly less effective than steroid hormones, and for type I Type I is also effective in those requiring surgical treatment.
Careful examination of the thyroid gland, screening for basal thyroid function, and checking for thyroid autoantibodies TPO-Ab and TG-Ab should be performed prior to amiodarone treatment, and thyroid function should be monitored after a 6-month interval once treatment has been initiated.
Lithium
In patients with a thyroid autoimmune base, lithium therapy increases serum concentrations of thyroid autoantibodies, causing subclinical hypothyroidism to become clinical hypothyroidism. It is estimated that up to 10-33% of patients have elevated thyroid autoantibodies after long-term lithium therapy. Hyperthyroidism has also been reported with long-term lithium treatment, possibly due to direct toxic effects of lithium on thyroid cells or painless sporadic thyroiditis caused by lithium.
Interferon alpha and interferon 2
Up to 15% of patients without a thyroid autoimmune background treated with interferon alfa will develop elevated TPO-Ab or abnormal thyroid function, possibly due to subclinical or clinical hyperthyroidism or hypothyroidism. A thyroid iodine uptake test can help distinguish drug-induced Graves’ hyperthyroidism, which has increased iodine uptake, from drug-induced thyroiditis, which has decreased.
Patients with Graves’ hyperthyroidism that develops after treatment with interferon alpha should be given antithyroid medication. While continuing interferon alpha or interferon 2, beta-blockers and, if necessary, nonsteroidal anti-inflammatory drugs or steroid hormone therapy may be given for inflammatory hyperthyroidism, and levothyroxine sodium for hypothyroidism. Although thyroid function often returns to normal after discontinuation of interferon, there is an increased risk of subsequent autoimmune thyroid disease. Screening for thyroid function, thyroid autoantibodies TPO-Ab and TG-Ab should be performed before and every 6 months after starting treatment with interferon alpha or interferon 2.
Riedel’s thyroiditis
Riedel’s thyroiditis is a local feature of a systemic fibrotic process that manifests as progressive fibrosis of the thyroid gland with involvement of surrounding tissues and accounts for 0.05% of thyroid disorders requiring surgery. The cause is unknown and thyroid autoantibody levels are elevated in up to 67% of patients, but it is not clear whether this is a cause or a consequence of thyroid fibrous degeneration and destruction.
The patient’s thyroid gland is painlessly enlarged, hard and fixed, and compression of the trachea and esophagus may cause symptoms, and invasion of the surrounding parathyroid glands by fibrous changes may cause hypoparathyroidism. Most patients have normal thyroid function at the time of presentation, but once a large portion of normal thyroid tissue is involved, they will present with hypothyroidism. Surgical open biopsy is diagnostic, and although early application of steroids, methotrexate and tamoxifen have been reported to be effective, surgical treatment is usually required.
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