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CLASSIFICATION
The diagnostic term thyroiditis includes a group of inflammatory or inflammatory-like conditions. The terminology that has been employed is confusing, and no classification is ideal. We prefer the following nomenclature, which takes into account the cause when known.
1. Infectious thyroiditis, also referred to as either acute or chronic, and which in fact may be either, along with the qualifying term suppurative, nonsuppurative, or septic thyroiditis. It includes all forms of infection, other than viral, and is caused by invasion of the thyroid by bacteria, mycobacteria, fungi, protozoa, or flatworms. The disorder is rare.
2. DeQuervain's thyroiditis, commonly known as subacute thyroiditis but also termed subacute nonsuppurative thyroiditis, granulomatous, pseudotuberculous, pseudo-giant cell or giant cell thyroiditis, migratory or creeping thyroiditis, and struma granulomatosa. This condition, most likely of viral origin, lasts for a week to a few months, with a tendency to recur. The eponym was selected because of its uncertain cause.
3. Autoimmune thyroiditis, commonly referred to as chronic, Hashimoto's, or lymphocytic thyroiditis and also known as lymphadenoid goiter and struma lymphomatosa. This indolent disease usually persists for years and in the Western world is the principal cause of non-iatrogenic primary hypothyroidism. Nonspecific focal thyroiditis, characterised by local lymphoid cell infiltration without parenchymal changes, may be a variant of the autoimmune disease. The condition is covered in detail in Chapter 8. Another form of thyroiditis, also believed to be of autoimmune cause, has recently been described. It has been variably referred to as painless, silent, occult, subacute, subacute nonsuppurative, and atypical (silent) subacute thyroiditis, as well as hyperthyroiditis, transient thyrotoxicosis with low thyroidal RAIU and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism. There is no agreement on an inclusive name. The features of this disease entity overlap deQuervain's thyroiditis and Hashimoto's thyroiditis. The clinical course, with the exception of a the high erythrocyte sedimentation rate, is indistinguishable from deQuervain's thyroiditis. Yet, histologically, the condition cannot be differentiated from a milder form of Hashimoto's disease. This condition often occurs in the postpartum period and is also termed postpartum thyroiditis. All forms of autoimmune thyroiditis are considered in Chapter 8.
4. Riedel's thyroiditis is another disorder of unknown etiology. Synonyms include Riedel's struma, ligneous thyroiditis and invasive fibrous or chronic sclerosing thyroiditis. This condition is characterised by overgrowth of connective tissue which often extends into neighboring structures.
5. Miscellaneous varieties of thyroid inflammation or infiltration including local manifestations of a generalized disease processes. Among these are sarcoid and amyloid involvement of the thyroid. Radiation and direct trauma to the thyroid gland may also cause thyroiditis.
Infectious Thyroiditis.
The thyroid gland is remarkably resistant to infection. This has been attributed to its high vascularity, the presence of large amounts of iodine in the tissue, the fact that hydrogen peroxide is generated within the gland as a requirement for the synthesis of thyroid hormone and its normal encapsulated position away from external structures. However, in certain situations, particularly in children (1,2,2a), a persistent fistula from the pyriform sinus may make the left lobe of the thyroid particularly susceptible to abscess formation (3-7). Recurrent left-sided thyroid abcess has also been reported due to a fourth branchial arch sinus fistula8. In the immuno-compromised host, fungal infection may occur 9-12. Occasionally, acute bacterial supporative thyroiditis occurs in children receiving cancer chemotherapy13. Rarely, infection will occur in a cystic or degenerated nodule. As will be discussed, the principal differential diagnosis is generally between acute, meaning infectious, and subacute, meaning post-viral (non-infectious) inflammation of the gland.
Etiology
<SMALL>Virtually any bacterium can infect the thyroid. Streptococcus, staphylococcus, pneumococcus, salmonella 14,15, 15a, bacteroides, t. pallidum, pasteurella spp 16 and m. tuberculosis 17-19 have all been described. The subject has been extensively reviewed 10,20,21. In addition, certain fungi, including coccidioides immitis, aspergillus, actinomycosis, and candida albicans (22), nocardia(23), acinobacter baumanii(24) and cryptococcus (24a) have also been associated with thyroiditis. In the latter cases, the hosts have often been immuno-compromised, either due to malignancy or to AIDS (25). Malignancy may also be associated with thyroid abscess due to a fistulous connection (26).</SMALL>
Most commonly, however, especially in children, infection of the thyroid gland is a result of direct extension from an internal fistula from the pyriform sinus (3-,5,21,27). This tract is thought to represent the course of migration of the ultimo branchial body from the site of its embryonic origin in the fifth pharyngeal pouch (5a). Careful histopathological studies of these fistulae have demonstrated that they are lined by squamous columnar or ciliated epithelium and occasionally form branches in the thyroid lobe (3,5). In addition, occasional cells positive for calcitonin have been found in the fistulae and increased numbers of C-cells were noted in the thyroid lobe at the point of termination of the tract. The predominance of acute thyroiditis in the left lobe of the thyroid gland, particularly in infants and children, is explained by the fact that the right ultimo branchial body is often atrophic and does not develop in the human (as well as in other species such as reptiles). The reason for this phenomenon is not known. Acute thyroiditis may involve a normal gland, or arise in a multinodular goiter. At times, no source of infection can be demonstrated. The possibility of a persistent thyroglossal duct should be considered for patients with midline infections (9).
Pathology
Pathological examination reveals characteristic changes of acute inflammation. With bacterial infections, heavy polymorphonuclear and lymphocytic cellular infiltrate is found in the initial phase, often with necrosis and abscess formation. Fibrosis is prominent as healing occurs. In material obtained by fine needle aspiration, the infectious agent may be seen on a gram, acid fast or appropriate fungal stains. Fungal thyroiditis was clearly demonstrated in a patient with candida albicans (4).
Clinical Manifestations
Acute thyroiditis is quite rare with no more than one to two patients per year observed in a large tertiary care hospital. As the number of immunocompromised patients increase, cases of suppurative thyroiditis are increasing. It may be somewhat more common in the pediatric age group, although it is still quite unusual. The proper treatment of an acute thyroiditis in children generally requires the surgical removal of the fistula. (3-5) This almost always leads to a permanent cure of the condition.
The dominant clinical symptom is pain in the region of the thyroid gland which may subsequently enlarge and become hot and tender. The patient is unable to extend the neck and often sits with the neck flexed in order to avoid pressure on the thyroid gland. Swallowing is painful. There are usually signs of infection in structures adjacent to the thyroid, local lymphadenopathy as well as temperature elevation and, if bacteremia occurs, chills. Gas formation has been noted with suppurative thyroiditis (25a). Symptoms are generally more obvious in children than in adults. Adults may present with a vague slightly painful mass in the thyroid region without fever, which may raise the possibility of a malignancy. It may occur more commonly in the fall and winter following upper respiratory tract infections.
In general, there are no signs or symptoms of hyper- or hypothyroidism. However, exceptions to both have been reported particularly if the thyroiditis is generalized, such as occurs with fungal processes (24a) or mycobacterial infections. At times, even in patients with bacterial thyroiditis, destruction of the thyroid gland is sufficient to release thyroid hormone in amounts sufficient to cause symptomatic hyperthyroidism (17). The adult thyroid gland contains approximately 600 ug of T4/g (28). Given a typical 15 to 20 g gland, sufficient hormone can be released to cause transient thyrotoxicosis.
Diagnosis
Pain in the anterior neck will usually lead to a consideration of the possibility of thyroiditis. Since the major differential diagnosis will lie between acute suppurative thyroiditis and subacute thyroiditis, it is critical to compare the history, physical, and particularly laboratory data in these two conditions (see Table 19-1). In general, the patient with acute thyroiditis appears septic, has greater and more localized pain in the thyroid gland, may have an associated upper respiratory infection, has lymphadenopathy and may be immuno-compromised. Localization of the tenderness to the left lobe should suggest the possibility of an infection as should any erythema or apparent abscess formation. The presence of an elevated white blood count with a shift to the left would argue for infection, however, elevations in sedimentation rate are common in both acute and subacute thyroiditis. As mentioned, patients with bacterial thyroiditis are not hyperthyroid, but exceptions do occur. This is more common, but, by no means universal in patients with subacute thyroiditis.
Depending on the age and clinical circumstances, one may wish to proceed with invasive or non-invasive studies. The most discriminating tests for recognizing a difference between the two conditions are either an iodine uptake or scan showing a very low value in subacute thyroiditis with a normal value found in the patient with localized bacterial thyroiditis (21). If a thyroid ultrasound shows a localized process, a needle aspiration can be performed. This will be definitive. A CT scan may be useful in identifying the location of the abscess, but this is required only in unusual situations (29). Gallium scans are sometimes performed in the course of an evaluation for a fever of unknown origin. Localization of gallium to the thyroid gland is a very useful finding confirming thyroid inflammation as the source of the problem (22). If an infectious process is identified, particularly of the left lobe of a younger individual, then a barium swallow should be performed with attention to the possibility of a fistulous tract located on the left side between the pyriform sinus and the thyroid gland. In general bacterial infections tend to be localized whereas the post viral subacute thyroiditis is more often generalized, although intermediate conditions can certainly exist.
Occasionally, pain from an infectious process elsewhere in the neck will present as anterior neck tenderness. For example, a retropharyngeal abscess may present with typical symptoms of acute thyroiditis. The thyroid gland, however, will have a normal uptake, be normal on scan, and only on CT scan will the retropharyngeal abscess be recognized. The tendency for the pain of thyroid inflammation to be referred to the throat or ears should be kept in mind, although recognition of the anatomic source of the problem is usually not such a difficult issue in patients with acute thyroiditis due to their localized symptoms.
Treatment
The diagnosis and choice of antibiotic therapy are often aided by microscopic examination and appropriate staining of a fine needle aspirate. The procedure is best done under ultrasound guidance so that the source of the specimen is identified. It may also serve as a mechanism for drainage of an abscess and can be repeated to facilitate healing. Some abscesses will require surgical exploration and drainage. The choice of therapy will also depend on the immune status of the patient. Systemic antibiotics are required for severe infections. Candida albicans thyroiditis can be treated with amphotericin B and 5 fluconazol 100 mg daily. While patients with tuberculosis or parasitic infections tend to have a more indolent course, these infections can present with acute symptoms and this possibility should be considered if the epidemiology is consistent. For example, thyroidal echinococcosis occurs in countries in which this parasite is endemic (30). Trypanosomiasis of the thyroid has also been reported (21).
Prognosis
In some patients with thyroiditis, the destruction may be sufficiently severe that hypothyroidism results. Thus, patients with a particularly diffuse thyroiditis should have follow-up thyroid function studies performed to determine that this has not occurred. Surgical removal of a fistula or branchial pouch sinus (30a) is required to prevent recurrence when this is present.
The diagnostic term thyroiditis includes a group of inflammatory or inflammatory-like conditions. The terminology that has been employed is confusing, and no classification is ideal. We prefer the following nomenclature, which takes into account the cause when known.
1. Infectious thyroiditis, also referred to as either acute or chronic, and which in fact may be either, along with the qualifying term suppurative, nonsuppurative, or septic thyroiditis. It includes all forms of infection, other than viral, and is caused by invasion of the thyroid by bacteria, mycobacteria, fungi, protozoa, or flatworms. The disorder is rare.
2. DeQuervain's thyroiditis, commonly known as subacute thyroiditis but also termed subacute nonsuppurative thyroiditis, granulomatous, pseudotuberculous, pseudo-giant cell or giant cell thyroiditis, migratory or creeping thyroiditis, and struma granulomatosa. This condition, most likely of viral origin, lasts for a week to a few months, with a tendency to recur. The eponym was selected because of its uncertain cause.
3. Autoimmune thyroiditis, commonly referred to as chronic, Hashimoto's, or lymphocytic thyroiditis and also known as lymphadenoid goiter and struma lymphomatosa. This indolent disease usually persists for years and in the Western world is the principal cause of non-iatrogenic primary hypothyroidism. Nonspecific focal thyroiditis, characterised by local lymphoid cell infiltration without parenchymal changes, may be a variant of the autoimmune disease. The condition is covered in detail in Chapter 8. Another form of thyroiditis, also believed to be of autoimmune cause, has recently been described. It has been variably referred to as painless, silent, occult, subacute, subacute nonsuppurative, and atypical (silent) subacute thyroiditis, as well as hyperthyroiditis, transient thyrotoxicosis with low thyroidal RAIU and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism. There is no agreement on an inclusive name. The features of this disease entity overlap deQuervain's thyroiditis and Hashimoto's thyroiditis. The clinical course, with the exception of a the high erythrocyte sedimentation rate, is indistinguishable from deQuervain's thyroiditis. Yet, histologically, the condition cannot be differentiated from a milder form of Hashimoto's disease. This condition often occurs in the postpartum period and is also termed postpartum thyroiditis. All forms of autoimmune thyroiditis are considered in Chapter 8.
4. Riedel's thyroiditis is another disorder of unknown etiology. Synonyms include Riedel's struma, ligneous thyroiditis and invasive fibrous or chronic sclerosing thyroiditis. This condition is characterised by overgrowth of connective tissue which often extends into neighboring structures.
5. Miscellaneous varieties of thyroid inflammation or infiltration including local manifestations of a generalized disease processes. Among these are sarcoid and amyloid involvement of the thyroid. Radiation and direct trauma to the thyroid gland may also cause thyroiditis.
Infectious Thyroiditis.
The thyroid gland is remarkably resistant to infection. This has been attributed to its high vascularity, the presence of large amounts of iodine in the tissue, the fact that hydrogen peroxide is generated within the gland as a requirement for the synthesis of thyroid hormone and its normal encapsulated position away from external structures. However, in certain situations, particularly in children (1,2,2a), a persistent fistula from the pyriform sinus may make the left lobe of the thyroid particularly susceptible to abscess formation (3-7). Recurrent left-sided thyroid abcess has also been reported due to a fourth branchial arch sinus fistula8. In the immuno-compromised host, fungal infection may occur 9-12. Occasionally, acute bacterial supporative thyroiditis occurs in children receiving cancer chemotherapy13. Rarely, infection will occur in a cystic or degenerated nodule. As will be discussed, the principal differential diagnosis is generally between acute, meaning infectious, and subacute, meaning post-viral (non-infectious) inflammation of the gland.
Etiology
<SMALL>Virtually any bacterium can infect the thyroid. Streptococcus, staphylococcus, pneumococcus, salmonella 14,15, 15a, bacteroides, t. pallidum, pasteurella spp 16 and m. tuberculosis 17-19 have all been described. The subject has been extensively reviewed 10,20,21. In addition, certain fungi, including coccidioides immitis, aspergillus, actinomycosis, and candida albicans (22), nocardia(23), acinobacter baumanii(24) and cryptococcus (24a) have also been associated with thyroiditis. In the latter cases, the hosts have often been immuno-compromised, either due to malignancy or to AIDS (25). Malignancy may also be associated with thyroid abscess due to a fistulous connection (26).</SMALL>
Most commonly, however, especially in children, infection of the thyroid gland is a result of direct extension from an internal fistula from the pyriform sinus (3-,5,21,27). This tract is thought to represent the course of migration of the ultimo branchial body from the site of its embryonic origin in the fifth pharyngeal pouch (5a). Careful histopathological studies of these fistulae have demonstrated that they are lined by squamous columnar or ciliated epithelium and occasionally form branches in the thyroid lobe (3,5). In addition, occasional cells positive for calcitonin have been found in the fistulae and increased numbers of C-cells were noted in the thyroid lobe at the point of termination of the tract. The predominance of acute thyroiditis in the left lobe of the thyroid gland, particularly in infants and children, is explained by the fact that the right ultimo branchial body is often atrophic and does not develop in the human (as well as in other species such as reptiles). The reason for this phenomenon is not known. Acute thyroiditis may involve a normal gland, or arise in a multinodular goiter. At times, no source of infection can be demonstrated. The possibility of a persistent thyroglossal duct should be considered for patients with midline infections (9).
Pathology
Pathological examination reveals characteristic changes of acute inflammation. With bacterial infections, heavy polymorphonuclear and lymphocytic cellular infiltrate is found in the initial phase, often with necrosis and abscess formation. Fibrosis is prominent as healing occurs. In material obtained by fine needle aspiration, the infectious agent may be seen on a gram, acid fast or appropriate fungal stains. Fungal thyroiditis was clearly demonstrated in a patient with candida albicans (4).
Clinical Manifestations
Acute thyroiditis is quite rare with no more than one to two patients per year observed in a large tertiary care hospital. As the number of immunocompromised patients increase, cases of suppurative thyroiditis are increasing. It may be somewhat more common in the pediatric age group, although it is still quite unusual. The proper treatment of an acute thyroiditis in children generally requires the surgical removal of the fistula. (3-5) This almost always leads to a permanent cure of the condition.
The dominant clinical symptom is pain in the region of the thyroid gland which may subsequently enlarge and become hot and tender. The patient is unable to extend the neck and often sits with the neck flexed in order to avoid pressure on the thyroid gland. Swallowing is painful. There are usually signs of infection in structures adjacent to the thyroid, local lymphadenopathy as well as temperature elevation and, if bacteremia occurs, chills. Gas formation has been noted with suppurative thyroiditis (25a). Symptoms are generally more obvious in children than in adults. Adults may present with a vague slightly painful mass in the thyroid region without fever, which may raise the possibility of a malignancy. It may occur more commonly in the fall and winter following upper respiratory tract infections.
In general, there are no signs or symptoms of hyper- or hypothyroidism. However, exceptions to both have been reported particularly if the thyroiditis is generalized, such as occurs with fungal processes (24a) or mycobacterial infections. At times, even in patients with bacterial thyroiditis, destruction of the thyroid gland is sufficient to release thyroid hormone in amounts sufficient to cause symptomatic hyperthyroidism (17). The adult thyroid gland contains approximately 600 ug of T4/g (28). Given a typical 15 to 20 g gland, sufficient hormone can be released to cause transient thyrotoxicosis.
Diagnosis
Pain in the anterior neck will usually lead to a consideration of the possibility of thyroiditis. Since the major differential diagnosis will lie between acute suppurative thyroiditis and subacute thyroiditis, it is critical to compare the history, physical, and particularly laboratory data in these two conditions (see Table 19-1). In general, the patient with acute thyroiditis appears septic, has greater and more localized pain in the thyroid gland, may have an associated upper respiratory infection, has lymphadenopathy and may be immuno-compromised. Localization of the tenderness to the left lobe should suggest the possibility of an infection as should any erythema or apparent abscess formation. The presence of an elevated white blood count with a shift to the left would argue for infection, however, elevations in sedimentation rate are common in both acute and subacute thyroiditis. As mentioned, patients with bacterial thyroiditis are not hyperthyroid, but exceptions do occur. This is more common, but, by no means universal in patients with subacute thyroiditis.
Depending on the age and clinical circumstances, one may wish to proceed with invasive or non-invasive studies. The most discriminating tests for recognizing a difference between the two conditions are either an iodine uptake or scan showing a very low value in subacute thyroiditis with a normal value found in the patient with localized bacterial thyroiditis (21). If a thyroid ultrasound shows a localized process, a needle aspiration can be performed. This will be definitive. A CT scan may be useful in identifying the location of the abscess, but this is required only in unusual situations (29). Gallium scans are sometimes performed in the course of an evaluation for a fever of unknown origin. Localization of gallium to the thyroid gland is a very useful finding confirming thyroid inflammation as the source of the problem (22). If an infectious process is identified, particularly of the left lobe of a younger individual, then a barium swallow should be performed with attention to the possibility of a fistulous tract located on the left side between the pyriform sinus and the thyroid gland. In general bacterial infections tend to be localized whereas the post viral subacute thyroiditis is more often generalized, although intermediate conditions can certainly exist.
Occasionally, pain from an infectious process elsewhere in the neck will present as anterior neck tenderness. For example, a retropharyngeal abscess may present with typical symptoms of acute thyroiditis. The thyroid gland, however, will have a normal uptake, be normal on scan, and only on CT scan will the retropharyngeal abscess be recognized. The tendency for the pain of thyroid inflammation to be referred to the throat or ears should be kept in mind, although recognition of the anatomic source of the problem is usually not such a difficult issue in patients with acute thyroiditis due to their localized symptoms.
Treatment
The diagnosis and choice of antibiotic therapy are often aided by microscopic examination and appropriate staining of a fine needle aspirate. The procedure is best done under ultrasound guidance so that the source of the specimen is identified. It may also serve as a mechanism for drainage of an abscess and can be repeated to facilitate healing. Some abscesses will require surgical exploration and drainage. The choice of therapy will also depend on the immune status of the patient. Systemic antibiotics are required for severe infections. Candida albicans thyroiditis can be treated with amphotericin B and 5 fluconazol 100 mg daily. While patients with tuberculosis or parasitic infections tend to have a more indolent course, these infections can present with acute symptoms and this possibility should be considered if the epidemiology is consistent. For example, thyroidal echinococcosis occurs in countries in which this parasite is endemic (30). Trypanosomiasis of the thyroid has also been reported (21).
Prognosis
In some patients with thyroiditis, the destruction may be sufficiently severe that hypothyroidism results. Thus, patients with a particularly diffuse thyroiditis should have follow-up thyroid function studies performed to determine that this has not occurred. Surgical removal of a fistula or branchial pouch sinus (30a) is required to prevent recurrence when this is present.
