Alan P. Farwell
Subacute thyroiditis and acute infectious thyroiditis are two important causes of thyroid pain. The former is the most common cause of thyroid pain, while the latter is rare, but potentially life-threatening. Despite the common presentation of pain, two distinct clinical pictures evolve. Subacute thyroiditis is a relatively common disorder that has been attributed to a viral infection, although the evidence for a viral etiology is mostly circumstantial. In addition to pain, subacute thyroiditis causes transient thyrotoxicosis, followed by transient hypothyroidism and usually euthyroidism, and therapy is directed at thyroidal pain and dysfunction. In contrast, an infectious etiology is usually clear in the rare cases of acute infectious thyroiditis. Bacterial, fungal, and parasitic organisms all have been documented as etiologic agents, and therapy in acute thyroiditis is directed against the offending organism. In addition, acute thyroiditis is potentially life-threatening, and the prognosis is often dependent on the prompt recognition and treatment of this disorder.
DIFFERENTIAL DIAGNOSIS OF THE PAINFUL THYROID
In the patient who presents with neck pain, subacute and acute infectious thyroiditis must be differentiated from the other causes of anterior neck pain (Table 28.1). Essentially all of the nonthyroidal causes of neck pain are infectious in origin and present as discrete painful masses (1). Hemorrhage into either a thyroid cyst or a nodule usually presents with the sudden onset of unilateral neck pain associated with a marked increase in the size of a preexisting nodule. The pain associated with a rapidly enlarging carcinoma, usually anaplastic, is often more chronic in nature (2), as is painful Hashimoto's thyroiditis, which usually involves the entire gland, and antibodies directed against thyroglobulin (Tg) and thyroid peroxidase (TPO) are usually present in high titer (3). Radiation thyroiditis occurs in the setting of radioactive iodine treatment for hyperthyroidism or following supravoltage external radiation of the anterior neck for thyroid cancer or lymphoma. Amiodarone may cause thyroiditis, which may occasionally be painful (4,5). Globus hystericus, an anxiety reaction that is characterized by a constrictive feeling in the throat, is a diagnosis of exclusion.
TABLE 28.1. DIFFERENTIAL DIAGNOSIS OF THE PAINFUL ANTERIOR NECK MASS
Acute infectious thyroiditis
Hemorrhage into a cyst
Hemorrhage into a benign or malignant nodule
Rapidly enlarging thyroid carcinoma
Painful Hashimoto's thyroiditis
Painful amiodarone-induced thyroiditis
Infected thyroglossal duct cyst
Infected branchial cleft cyst
Infected cystic hygroma
Cellulitis of the anterior neck
From Farwell AP, Braverman LE. Inflammatory thyroid disorders. Otolaryngol Clin North Am 1996;29:541–556, with permission.
Because of the clinical presentation, frequency of occurrence, and differing etiology, subacute and acute infectious thyroiditis will be discussed separately.
Subacute thyroiditis is a spontaneous remitting inflammatory disorder of the thyroid that may last for weeks to months (6,7,8,9). This disorder has a number of eponyms, including de Quervain's thyroiditis, giant-cell thyroiditis, pseudogranulomatous thyroiditis, subacute painful thyroiditis, and subacute granulomatous thyroiditis (6). The first description of subacute thyroiditis was in 1895 by Mygind, who reported 18 cases of “thyroiditis akuta simplex” (10). The pathology of subacute thyroiditis was first described in 1904 by de Quervain, whose name is associated with the disorder, when he showed giant cells and granulomatous-type changes in the thyroids of affected patients (7). Subacute thyroiditis is the most common cause of the painful thyroid and may account for up to 5% of clinical thyroid abnormalities. As with other thyroid disorders, women are more frequently affected than men, with a peak incidence in the fourth and fifth decades (Table 28.2) (7,8,9). This disorder is rare in children (11) and the elderly (10).
TABLE 28.2. COMPARISON BETWEEN SUBACUTE AND ACUTE INFECTIOUS THYROIDITIS
Acute Infectious Thyroiditis
Age of onset (yr)
20–60 (80% 40–50)
Sex ratio (F:M)
Bacterial, fungal, parasitic, mycobacterial organisms
Moderate, HLA Bw-35
Pyriform sinus fistula
Giant cells, granulomas
Suppuration, offending organism
Positive for offending organism
Upper respiratory illness
Fever and malaise
Thyrotoxicosis, hypothyroidism, or both
Thyroid peroxidase antibodies
Low titer/absent, transient
Low titer/absent, transient
Common if patent pyriform sinus fistula
ESR, erythrocyte sedimentation rate; HLA, histocompatibility antigen; RAIU, radioactive iodine uptake.
Farwell AP, Braverman LE. Inflammatory thyroid disorders. Otolaryngol Clin North Am 1996;29:541–556; Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646–2655; and Fatourechi V, Aniszewski JP, Fatourechi GZ, et al. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab 2003;88:2100–2105, with permission.
A viral etiology has most often been implicated in subacute thyroiditis (12,13,14,15). However, the evidence supporting this association is largely indirect. Only mumps virus (12) and an unidentified cytopathic virus (13) have been directly isolated from affected thyroids, while electron microscopy, an electromagnetic imaging study, demonstrated viral particles in thyroid tissue from a single patient with subacute thyroiditis (16).
Subacute thyroiditis often follows an upper respiratory tract infection and occasionally includes a prodromal phase of muscular aches and pains, fever, and malaise (10). In deed, cases of subacute thyroiditis tend to be seasonal and geographical, coinciding with seasonal enterovirus infections (9). Subacute thyroiditis has been associated with infections by adenovirus, coxsackie, Epstein-Barr, and influenza viruses (10,13), and has been reported after hepatitis B vaccination (17) and during both interferon (18,19) and combination interferon and ribavirin therapy (20) for chronic hepatitis C. In 1967, Volpe et al (14) reported rising antibody titers to mumps virus, echovirus, adenovirus, and enterovirus in convalescent serum of 32 patients with subacute thyroiditis (Fig. 28.1). However, an additional 26 patients had viral antibody titers that did not change (14), and in another study, serum, stool, and fine-needle thyroid aspirations in 27 consecutive patients with subacute thyroiditis revealed no evidence of enteroviral infection (21). A single report has described a fourfold rise in serum coxsackie antibody titers after a documented case of subacute thyroiditis (22). Recently, 10 patients presented with postviral thyroiditis that followed a similar course to subacute thyroiditis but was painless (23). In addition, there have been reports of painless subacute thyroiditis diagnosed by fine-needle aspiration biopsy.
FIGURE 28.1. Viral antibody titers in subacute thyroiditis. A survey of 72 patients with subacute thyroiditis identified 32 with antibodies to common viruses that changed sufficiently in titer to suggest that they may play an etiologic role in the disorder. (From Volpe R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab 1967;27:1275–1284, with permission.)
Thyroid autoimmunity may be present during the acute phase of the disease, as indicated by the presence of antibodies against TPO, Tg, and the thyrotropin (TSH) receptor (6,26) and by sensitization of T lymphocytes against thyroid antigen (27). However, this is often transient and is most likely due to release of antigen during inflammation rather than a primary event. Several reports have suggested that subacute thyroiditis may trigger the production of TSH receptor antibodies (28), contributing to a prolonged hypothyroid phase (29) and occasionally leading to the development of Graves' disease (30), although this was not observed in the most recent epidemiological survey (9).
There is an apparent genetic predisposition to subacute thyroiditis, with histocompatibility antigen (HLA)–Bw35 reported in all ethnic groups (10), including approximately two-thirds of Caucasian and Chinese patients (31). The relative risk of HLA-Bw35 in subacute thyroiditis is high, ranging from 8.0 to 56.6 (10). Additional evidence for genetic susceptibility is the simultaneous development of subacute thyroiditis in identical twins heterozygous for the HLA-Bw35 haplotype (32). However, an epidemic of “atypical” subacute thyroiditis was described in a town in the Netherlands in which a painful goiter was present in only 2 of 12 patients (33). HLA-B15/62 was found in 5 of 11 patients tested, while only 1 patient tested positive for HLA-Bw35. Lastly, a weak association of subacute thyroiditis with HLA-DRw8 has been reported in Japanese patients (34).
The primary events in the pathology of subacute thyroiditis are destruction of the follicular epithelium and loss of follicular integrity; however, the histopathological changes are distinct from those found with Hashimoto's thyroiditis (35,36). Although the evaluation of subacute thyroiditis rarely requires histological examination, the diagnosis has been made on the basis of FNAB (37). The lesions are patchy in distribution and are of varying stages of development, with infiltration of mononuclear cells in affected regions and partial or complete loss of colloid and fragmentation and duplication of the basement membrane (Fig. 28.2) (10). The characteristic follicular lesion is a central core of colloid surrounded by multinucleate giant cells (35,38). These follicular lesions progress to form granulomas. Carcinoembryonic antigen has been reported at the center of granulomas in acute-stage subacute thyroiditis, while carcinoma antigen 19–9 expression has been reported in the lesions in the later stages of the disease, suggesting a histiocytic or follicular cell origin for the giant cells (39). Caseation, hemorrhage, and calcification do not occur, and the pathological changes revert to normal, with minimal residual fibrosis, once the disease subsides.
FIGURE 28.2. Histopathologic findings in subacute thyroiditis. Thyroid follicles are destroyed, and there is a mixed inflammatory infiltrate, desquamated thyroid epithelial cells, edema, and colloid undergoing phagocytosis by histiocytes (foreign body–type giant cells, arrow). (Hematoxylin and eosin, 40× magnification.) (From Lazarus JH. Silent thyroiditis and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. The thyroid. Philadelphia: Lippincott-Raven Publishers, 1996:577–591, with permission.)
The characteristic feature of subacute thyroiditis is pain in the region of the thyroid, either gradual or sudden in onset (Table 28.3) (7).
The pain is usually constant and often severe, involving the entire thyroid in many patients. Occasionally, one side is initially affected and is followed in days to weeks by involvement of the contralateral side. The pain is often aggravated by turning the head or swallowing and may radiate to the jaw, ear, or occiput on the ipsilateral side. Rarely, subacute thyroiditis may present as a nontender solitary nodule. In these cases, the diagnosis has been made after FNAB (37).
TABLE 28.3. COMMON CLINICAL FEATURES OF SUBACUTE THYROIDITISa
Pain in neck or thyroid
Tender, firm thyroid
Constant, dull pain
High serum thyroid hormones
High serum thyroglobulin
High C-reactive protein
24-h RAIU < 5%
ESR, erythrocyte sedimentation rate; RAIU, radioactive iodine uptake.
a The clinical features have been reported in < 50% of patients with subacute thyroiditis.
From Fatourechi V, Aniszewski JP, Fatourechi GZ, et al. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab 2003;88: 2100–2105; Lazarus JH. Silent thyroiditis and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. The thyroid. Philadelphia: Lippincott-Raven Publishers, 1996:577–591; Pearce EN, Bogazzi F, Martino E, et al. The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease. Thyroid 2003;13:643–648; and Szabo SM, Allen DB. Thyroiditis: differentiation of acute suppurative and subacute thyroiditis. Case report and review of the literature [review]. Clin Pediatr (Phila) 1989;28:171–174, with permission.
Patients may report a viral prodrome, including myalgia, low-grade fever, lassitude (which may be debilitating), pharyngitis, and dysphagia. Symptoms of thyrotoxicosis are present in the majority of patients (6,9), due to follicular destruction and leakage of preformed hormone from the gland. Rarely, subacute thyroiditis may mimic temporal arteritis (40).
Palpation usually reveals an exquisitely tender, hard, ill-defined nodular thyroid (Table 28.3). The tender region may encompass an entire lobe, and mild tenderness may be present in the contralateral lobe. The overlying skin is occasionally warm and erythematous. Cervical lymphadenopathy is rarely present. While the vast majority of patients are only mildly to moderately ill, subacute thyroiditis may have a dramatic presentation, with marked fever, severe thyrotoxicosis, and obstructive symptoms due to pronounced thyroid inflammation and edema.
During the active phase of subacute thyroiditis, the erythrocyte sedimentation rate (ESR) is usually markedly elevated (Table 28.3) (7). In fact, a normal ESR essentially rules out subacute thyroiditis as a tenable diagnosis. C-reactive protein is another inflammatory marker that appears to be selectively elevated in subacute thyroiditis (41). The white blood count is normal to mildly increased, and there is often a normochromic, normocytic anemia.
Biochemical thyrotoxicosis is present in approximately 50% of patients in the acute phase of subacute thyroiditis (6,9). The serum thyroxine (T4) concentration is disproportionately elevated relative to the serum triiedothyronine T3 concentration, reflecting the intrathyroidal T4-to-T3 ratio (42). In addition, the acute illness decreases the peripheral deiodination of T4 to T3, resulting in lower T3 concentrations than expected (43). Serum TSH concentrations are low to undetectable. Consistent with follicular destruction, serum Tg concentrations are elevated (44,45). Antibodies directed against Tg and TPO are either absent or present in low titer.
The radioactive iodine uptake (RAIU) is low, most often < 2% at 24 hours. Thus, subacute thyroiditis falls into the category of “low RAIU thyrotoxicosis” (46). As with the ESR discussed earlier, a normal RAIU essentially rules out subacute thyroiditis as a tenable diagnosis. Similarly, low uptake has been reported with technetium (Tc99) pertechnetate, while Tc99-sestamibi uptake may be elevated early in subacute thyroiditis (47). Ultrasound has been suggested as playing a useful supporting role in the diagnosis of subacute thyroiditis (48), particularly color-flow Doppler ultrasonography, in which the gland appears hypoechoic with low to normal vascularity (49). There has been a single report of increased radiogallium uptake in the thyroid in a patient with subacute thyroiditis (50).
Salicylates and other nonsteroidal anti-inflammatory drugs are often adequate to decrease thyroidal pain in mild to moderate cases (6,9). In more severe cases, oral glucocorticoids (prednisone up to 40 mg/day) may provide dramatic relief of pain and swelling, often within a few hours of administration and in most cases within 24 to 48 hours (6,7). In fact, if thyroidal/neck pain fails to improve after 72 hours of prednisone corticosteroid therapy, the diagnosis of subacute thyroiditis should be questioned. Despite the clinical response, the underlying inflammatory process may persist, and symptoms may recur if the dose is tapered too rapidly. Up to 20% of patients will have a recurrence of thyroidal pain upon discontinuation of prednisone, which responds to restarting treatment (9,10,51,52). In general, full-doses prednisone are given for a week, followed by tapering the dose over 2 to 4 weeks. The use of steroid prednisone appears to have no effect on the development of transient hypothyroidism, but may be associated with a higher incidence of permanent hypothyroidism (9).
There appears to be no predictive differences between patients who have recurrent pain when prednisone is tapered and those whose pain has resolved (52). However, determination of the RAIU before discontinuing prednisone may be helpful in identifying those patients at the highest risk for early relapse (7). If the RAIU is still low, the inflammatory process is ongoing, and therapy should not be discontinued.
Patients with recurrent prednisone symptoms after withdrawal of corticosteroids usually respond to reinstitution or continuation of therapy for an additional month (10). While subacute thyroiditis is a self-limited disease and the vast majority of patients respond to the measures discussed above, there are occasional patients who suffer from repeated exacerbations of pain and inflammation (6). In these patients, therapy with T4 has been helpful in preventing exacerbations, suggesting that endogenous TSH may contribute to their occurrence (6,10). Rarely, thyroidectomy or thyroid ablation with radioactive iodine when the uptake is normal may be indicated for management of patients with protracted courses of severe neck pain and malaise (6,10).
If clinical thyrotoxicosis is present, beta-adrenergic blocking drugs such as propranolol are useful. Antithyroid drugs have no role in the therapy of subacute thyroiditis, as the gland is not hyperfunctioning (46). The oral cholecystographic agents sodium iopanoate (1,000 mg daily) and sodium ipodate (500 mg daily) have been utilized to achieve rapid control of severe thyrotoxicosis in patients with subacute thyroiditis (53,54); however, both drugs are no longer available in the United States.
The clinical course of subacute thyroiditis is self-limited, comprising four phases (Fig. 28.3) (6,7,8). The acute phase, consisting of thyroidal pain and thyrotoxicosis, usually lasts 3 to 6 weeks, but may last longer. A period of transient asymptomatic euthyroidism follows. Transient hypothyroidism occurs after several more weeks in 30% to 50% of patients (9,55) and may last for several months. The final recovery phase follows, when all aspects of thyroid function return to normal in 4 to 6 months, including morphology (48). While permanent hypothyroidism has been reported to be relatively rare, occurring in up to 5% of patients (55), recent studies suggest this incidence may be higher. A small study from France reported an incidence of permanent hypothyroidism of 31% (56), while a larger series from the Mayo Clinic reported an incidence of 15% (9).
FIGURE 28.3. Clinical course of subacute thyroiditis. (From Pearce EV, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646–55, with permission.)
Relapse of subacute thyroiditis is rare, occurring in up to 4% of patients (9,57). However, some patients with a history of subacute thyroiditis were found to be particularly sensitive to the inhibitory effects of exogenously administered iodide, suggesting a persistent thyroid abnormality (58).
In addition, there have been case reports of Graves' disease occurring after subacute thyroiditis (30,59). Thus, long-term follow-up of patients after an episode of subacute thyroiditis is suggested.
ACUTE INFECTIOUS THYROIDITIS
Acute infectious thyroiditis, also known as acute suppurative thyroiditis, infectious thyroiditis, bacterial thyroiditis, and pyogenic thyroiditis, is a rare disorder, with ~300 cases having been reported in the adult literature (15,60,61,62) and ~100 cases reported in the pediatric literature (63,64). However, bacterial infections of the thyroid are potentially life-threatening, often with an explosive onset, and the prognosis is often dependent on the prompt recognition and treatment. Immunosuppressed patients, such as those with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), as well as organ-transplant patients on pharmacologic immunosuppression, are particularly at risk for infectious thyroiditis. In these cases, opportunistic infections of the thyroid are more often chronic and insidious in onset.
In contrast to most other organs in the body, the thyroid gland is remarkably resistant to infection. Protective mechanisms contributing to the relative resistance of the thyroid to infection include (a) the rich blood supply to and lymphatic drainage from the thyroid; (b) the high glandular content of iodine, which may be bactericidal; and (c) the separation of the thyroid from other structures of the neck by fascial planes and the complete, protective fibrous capsule surrounding the gland. Indeed, experimental models of infectious thyroiditis are difficult to develop, as shown by the observation that direct injection of either staphylococci or streptococci into the carotid arteries of dogs rarely resulted in thyroidal infection (65). Thyroidal infections are most commonly bacterial in origin, with fungi, parasitic organisms, and mycobacteria being isolated much less frequently (Table 28.4) (15,60,61,62,63,64). The most common predisposing factor to infections of the thyroid appears to be preexisting thyroid disease; simple goiter, nodular goiter, Hashimoto's thyroiditis, or thyroid carcinoma has been present in up to two thirds of women and one half of men with infectious thyroiditis (60,66,67,68).
TABLE 28.4. PATHOGENESIS OF INFECTIOUS THYROIDITIS, 1900–1980
From Farwell AP, Braverman LE. Inflammatory thyroid disorders. Otolaryngol Clin North Am 1996;29:541–556; and Berger SA, Zonszein J, Villamena P, et al. Infectious diseases of the thyroid gland [Review]. Rev Infect Dis 1983;5:108–122, with permission.
The thyroid appears relatively resistant to direct inoculation of bacteria. Only one case of infectious thyroiditis has been reported as a complication of thyroid surgery (67), despite an incidence of wound infections of 0.5% to 1% (69). While the route of infection was rarely documented in the early literature, it is now apparent that transmission of infective organisms via a pyriform sinus fistula is the most common route of thyroidal infection, especially in children (Fig. 28.4). The first cases of infectious thyroiditis due to a fistula originating from the left pyriform sinus were reported in 1979 (70). Additional reports identified infected embryonic cysts of the third and fourth branchial pouches as routes of thyroidal infection (71,72,73,74,75,76). Subsequently, studies of over 100 patients with infectious thyroiditis have identified pyriform sinus fistulae, primarily left-sided, in up to 90% of these patients, especially in those with recurrent episodes (63,64,67,74,77,78,79). Infectious thyroiditis is often preceded by an upper respiratory infection, which may induce inflammation of the fistula and promote the transmission of pathogens to the thyroid. Consistent with these observations, infectious thyroiditis is more common in the late fall and late spring months (63,67,77).
FIGURE 28.4. Thyroid abscess due to pyriform sinus fistula (shaded). Fistulous tract extends from apex of the left pyriform sinus to the abscess either adjacent to or within the left lobe of the thyroid. A: Frontal view. B: Lateral view. (From Har-el G, Sasaki CT, Prager D, Krespi YP. Acute suppurative thyroiditis and the branchial apparatus. Am J Otolaryngol 1991;12:6–11, with permission.)
Infectious thyroiditis has also been reported to occur as a result of direct spread of pathogenic organisms via patent thyroglossal duct fistulae (80). Infections of the retropharyngeal space (pharyngitis and tonsillitis) or the lateral pharyngeal spaces (pharyngitis, tonsillitis, parotitis, otitis, and mastoiditis) may rarely spread down posterior and lateral fascial planes into the neck and communicate with the structures in the pretracheal space (1). Infection may also arise directly from the pretracheal space through perforations in the esophagus (60).
As with any organ, infective organisms may reach the thyroid via spread from a distant focus through the blood stream or lymphatics. Case reports of hematogenous spread from infections of the skin (81), lower respiratory tract, urinary tract, and gastrointestinal tract have been described (60). This occurs more often in adults than children, usually in the presence of other underlying illnesses (68,82,83), and acute suppurative thyroiditis has been reported in association with aggressive treatment of acute myelogenous leukemia in children (84).
Over 90% of patients with acute bacterial thyroiditis present with thyroidal pain, tenderness, fever, and local compression, resulting in dysphagia and dysphonia (Table 28.5) (68,77). The pain may radiate to the ear or mandible on the side of the infection (85). Signs and symptoms of systemic toxicity may be present. The thyroid is tender to palpation, with unilateral or bilateral lobar enlargement, and is associated with erythema and warmth of the skin. Abscess formation is indicated by fluctuance; a firm nodule may progress to fluctuance in the course of 1 to 3 days, so repeated physical examinations may be necessary. Cervical lymphadenopathy may be present but is not a prominent feature unless there is a predisposing pharyngitis.
TABLE 28.5. SIGNS AND SYMPTOMS OF ACUTE BACTERIAL THYROIDITIS
High ESR/C-reactive protein
Antecedent upper respiratory illness
Left lobe involvement
ESR, erythrocyte sedimentation rate.
From Berger SA, Zonszein J, Villamena P, et al. Infectious diseases of the thyroid gland [review]. Rev Infect Dis 1983;5:108–122; Rich EJ, Mendelman PM. Acute suppurative thyroiditis in pediatric patients [review]. Pediatr Infect Dis J 1987;6:936–940; Chi H, Lee YJ, Chiu NC, et al. Acute suppurative thyroiditis in children. Pediatr Infect Dis J2002;21:384–387; and Szabo SM, Allen DB. Thyroiditis. Differentiation of acute suppurative and subacute thyroiditis. Case report and review of the literature [review]. Clin Pediatr (Phila) 1989;28:171–174, with permission.
The laboratory evaluation of the painful thyroid should include determination of serum TSH as a reasonable initial thyroid function test. Normal thyroid function tests are seen in over two thirds of patients with acute suppurative thyroiditis (60,63,77), although thyrotoxicosis and hypothyroidism have been reported (77,86,87). Leukocytosis and an elevated ESR and C-reactive protein level are commonly observed in both subacute thyroiditis and infectious thyroiditis; thus these tests are not discriminatory. Radionuclide imaging, preferably with radioiodine, is useful in the case of a solitary painful nodule, and the RAIU will provide information on the overall function of the gland, which should be normal (88). The presence of soft-tissue gas on radiograph of the neck indicates infection with anaerobic, gas-forming organisms. Magnetic resonance imaging (MRI), ultrasonography, and computed tomography (CT) are most helpful in the identification of pyriform sinus fistulae or parathyroidal abscesses (89,90,91,92,93,94). These imaging studies, as well as other radionuclide studies, are best reserved for patients in whom the diagnosis is unclear (80,95).
FNAB is the best single laboratory test in the evaluation of infectious thyroiditis and will be diagnostic in most cases (15,60,61,62,63,64,96,97), especially when the tenderness is limited to a solitary nodule or a localized area and subacute thyroiditis has been ruled out. In addition to obtaining samples for cytology and gram stain and culture, provision should be made to obtain samples for special studies in the appropriate setting, such as Gomori's silver methenamine stain to identify Pneumocystis carinii in an immunocompromised patient (98,99).
Acute infectious thyroiditis is usually bacterial in origin (Table 28.4) (15,60,61,62,63,64,77). In adults, Staphylococcus aureus and Streptococcus pyogenes are the offending pathogens in >80% of patients and are the sole pathogen in over 70% of cases (Table 28.6) (60). In children, alpha- and beta-hemolytic Streptococcus and a variety of anaerobes account for 70% of cases, while mixed pathogens are identified in over 50% of cases (Table 28.6) (15,63,64). Other bacterial pathogens that have been shown to cause infectious thyroiditis include Salmonella typhii, brandenberg, and enteriditis (60,100,101,102), Actinomyces naeslundi (60), Actinobacillus actinomycetemcomitans (60), Brucella melitensis (103,104), Clostridium septicum (60), Eikenella corrodens (63,105), Enterobacter (63), Escherichia coli, Haemophilus influenzae (60), Klebsiella sp. (63), Pseudomonas aeruginosa (60), Serratia marcescens (106), and Staphylococcus nonaureus (60,63).
TABLE 28.6. CULTURE RESULTS IN ACUTE BACTERIAL THYROIDITIS
From Berger SA, Zonszein J, Villamena P, et al. Infectious diseases of the thyroid gland [Review]. Rev Infect Dis 1983;5:108–122; and Rich EJ, Mendelman PM. Acute suppurative thyroiditis in pediatric patients [Review]. Pediatr Infect Dis J 1987;6:936–940, with permission.
Treatment of acute bacterial thyroiditis requires admission to the hospital, drainage of any abscess, and parenteral antimicrobial therapy aimed at the causative agent. Gram stain and culture of the fine-needle aspirate will reveal the causative organism in over 90% of cases. If no organisms are seen on the gram stain, nafcillin and gentamycin, or a third-generation cephalosporin, are appropriate initial therapy in adults, while a second-generation cephalosporin or clindamycin is reasonable in children. Since a pyriform sinus fistula is the most common route of infection in bacterial thyroiditis (63,67,74), a barium swallow (73), CT (90,91,94), or MRI (93) of the neck should be performed to look for a communicating fistula in most patients with the first episode and all patients with recurrent episodes. Such fistulae must be surgically excised for definitive cure and prevention of recurrent infection (67,74,76,78,107,108).
Mortality from acute bacterial thyroiditis has markedly improved from the 20% to 25% reported in the early 1900s, with the extensive review by Berger et al estimating an overall mortality of 8.6% (60). However, more recent reviews, including over than 100 patients, failed to list mortality as a complication of acute bacterial thyroiditis, possibly due to a higher index of suspicion and earlier therapy (63,64,67,68). Mortality still may occur if the diagnosis is delayed and antimicrobial therapy is not initiated (60). In survivors, complete recovery is the rule, although there have been reports of transient hypothyroidism, vocal cord paralysis (which may also be transient) (67,109), and recurrence of infection as sequelae of acute bacterial thyroiditis (60,63,67,68,110).
Fungal infection of the thyroid, while rare, is the second most common cause of infectious thyroiditis (Table 28.4). Over 30 cases of fungal thyroiditis have been reported in the world's literature, with at least 26 cases caused by Aspergillus species (60,111,112). Virtually all of the affected patients were immunocompromised, with the most common underlying conditions being glucocorticoid therapy, leukemia, and lymphoma. Disseminated aspergillosis was present, and most of the diagnoses were made postmortem. The pathology was consistent with hematogenous spread, with focal abscesses, hemorrhagic lesions surrounding blood vessels, or diffuse necrotizing thyroiditis. In one patient with disseminated aspergillosis, suppurative thyroiditis was suspected on an In-111 white-blood-cell scan and confirmed by biopsy (95). Case reports of fungal infections of the thyroid have included Coccidioides immitis (113) and Histoplasma capsulatum (114,115) in endemic regions and Candida albicans (116), Allescheria boydii (117), and Nocardia asteroides (118) as sporadic infections.
The true incidence of infection of the thyroid with Mycobacterium tuberculosis is difficult to determine, as the pathology of lymphocytic infiltration and granuloma formation is nonspecific in the absence of demonstrable acid-fast bacilli. Using strict pathological criteria, only 19 cases have been reported in the literature (60). Thyroidal tuberculosis is associated with disseminated or miliary disease, and symptoms are usually present for months (119,120,121). Pain, tenderness, and fever are much less common than in cases of bacterial thyroiditis. While at least three of the reported patients with tuberculous thyroiditis died (60), resolution without sequelae usually follows appropriate antituberculous therapy. However, recurrent laryngeal nerve paralysis has been described (122).
Infections with atypical mycobacteria, including M. chelonei and M. intracellulare, have also been described (60). Thyroidal infection with M. avian-intracellulare has been reported in patients with AIDS in the setting of widely disseminated disease (123). While acid-fast organisms have been found in the thyroid of individuals with disseminated M. leprae (124), symptomatic thyroid infection has not been described.
Parasitic thyroidal infection is extremely rare. Only nine reports of echinococcal (tapeworm) thyroiditis have been reported in the United States, located in sheep- and cattle-farming regions (60). Symptoms, primarily in the form of a goiter, are usually present for years, and the diagnosis is often made at the time of surgery. If echinococcal infection is suspected, biopsy of the lesion is contraindicated due to risk of spillage and rupture of the cyst contents. Surgical removal is the preferred mode of treatment, with antiparasitic agents useful as adjunctive therapy and for inoperable cases.
Strongyloides stercoralis, or roundworm, is widely disseminated in tropical climates, including the southeastern United States. Involvement of the thyroid has been described only in the setting of disseminated disease in immunocompromised patients (125). Therapy is aimed at the disseminated infection, with thiabendazole an effective drug. Mortality with disseminated Strongyloides infection is high due to both the infection and the immunocompromised status of the patient. A single patient with cysticercosis of the thyroid, acquired from ingestion of the eggs of the pork tapeworm Taenia solium, has been described (126).
Only seven cases of syphilitic infection of the thyroid have been reported in the world's literature (60). These infections most often presented as painless nodules. Other symptoms included local compression and occasionally hypothyroidism and ulceration of the skin.
Thyroidal Infections in Immunocompromised Patients
With the increasing incidence of infection by HIV leading to AIDS, as well as the increased use of immunosuppressive agents, several novel opportunistic pathogens have involved the thyroid. The most common infectious organism found in the thyroid at postmortem examination in patients with AIDS is cytomegalovirus (CMV), occurring in the setting of disseminated CMV infection (127,128). However, symptomatic thyroidal infection with CMV has not been reported. As mentioned above, thyroidal involvement with M. avian-intracellulare has been reported in the setting of widely disseminated disease (123).
The thyroid is a site of extrapulmonary infection with Pneumocystis carinii, a fungal organism based on RNA sequencing (129). In fact, asymptomatic infection of the thyroid was found in up to 20% of patients with disseminated Pneumocystis infection at autopsy (127). Extrapulmonary Pneumocystis infection occurs most often in patients receiving prophylaxis with aerosolized pentamidine. Symptomatic thyroidal infection, presenting as a painless nodule, was first reported in 1988 (130), followed by numerous other case reports. The diagnosis of Pneumocystis carinii infection is made by performing Gomori's silver methenamine stain on specimens obtained by biopsy. Since this is not a routine staining procedure, it must be requested when performing a biopsy on immunocompromised patients. Treatment with parenteral trimethoprim-sulfamethoxazole followed by prolonged oral administration (up to 2 months) is curative and may result in the restoration of normal thyroid function in regions that were previously “cold” by radioiodine scanning (98).
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