Background

Acute suppurative thyroiditis (AST) is a rare condition with an incidence of 0.1% to 0.7 % among all thyroid disease. As the thyroid gland is resistant to infection due to protective factors, including high iodine content, high vascularity, extensive lymphatic drainage, and encapsulation, AST is extremely rare. Case reports therefore dominate the published literature, and there are no established guidelines or clinical trials regarding the diagnosis and management of patients with AST.

AST is a potentially life-threatening endocrine emergency that also can be associated with a high mortality rate in certain patients. Potential complications can occur pending abscess extension or rupture in patients with AST, leading to esophageal or tracheal fistula, jugular vein thrombophlebitis, descending necrotizing mediastinitis, or septicemia. A defining dogma is that early diagnosis and appropriate treatment are key factors toward achieving success in the management of patients with AST.

In many cases a predisposing factor to suppurative thyroiditis is identified, including having an immunocompromised state, pyriform sinus fistula (PSF), neck trauma, lymphatic or hemorrhagic spread (e.g., septic emboli), direct inoculation of thyroid gland (e.g., via fine needle aspiration [FNA] or central line placement), ruptured esophagus, or retropharyngeal abscess. ^, A wide spectrum of microbial pathogens has been reported in patients who suffer from suppurative thyroiditis, including both gram-positive and gram-negative bacteria, as well as fungus, Nocardia , and even mycobacteria.

Bacterial Infection

Most patients with acute suppurative thyroiditis are found to have a bacterial etiology, and present with signs and symptoms of infection including neck swelling, redness, warmth, tenderness, and fever. The most common bacterial pathogen of suppurative thyroiditis are gram-positive bacteria such as Staphylococcus and Streptococcus species. However, suppurative thyroiditis due to gram-negative organisms has been also reported. Separately, there are reports of suppurative thyroiditis due to Brucella infection, ^, as well as Escherichia coli infection due to hematogenous spread from urinary tract infection. Finally, Salmonella as a causative pathogen as well as and Porphyromonas bacteria have been implicated.

Fungal Infection

Infection of the thyroid gland via a fungal pathogen is uncommon, but ranks as the second most common cause of infectious thyroiditis. Fungal AST has been mainly reported in immunosuppressed patients. Specifically, fungal thyroiditis has been described due to Aspergillus , ^, Candida , Cryptococus , and Coccidioides immitis . ^,

Aspergillus is the most common reported fungal thyroiditis. It is most often seen in immunosuppressed patients with widespread disseminated Aspergillus infection. A thyroid function test can be variable in patients with Aspergillus suppurative thyroiditis. The most common presentation in this setting is acute neck pain and swelling accompanied by signs and symptoms of thyrotoxicosis. This can make such a diagnosis difficult to distinguish from subacute granulomatous thyroiditis, which is also painful. ^, A clinical presentation of Aspergillus thyroiditis presenting as an enlarging mass due to an abscess has been also reported. ^,

Granulomatous Infections

Granulomatous infectious thyroiditis is very rare, especially in the developed world. The two most common infectious pathogens causing granulomatous thyroid disease are Mycobacterium tuberculosis and Nocardia . Patients with tuberculous involvement of the thyroid gland usually present with an enlarging neck mass as part of widespread disseminated disease, though patients are usually euthyroid. Less common presentations of tuberculous thyroid involvement are an acute mycobacterial abscess and new onset hyperthyroidism, as well as hypothyroidism due to gland destruction. Patients with tuberculous thyroid involvement usually have subacute presentations similar to that of acute granulomatous thyroiditis (De Quervain’s thyroiditis). For this illness, the diagnosis must be made by histopathologic examination, acid-fast bacilli (AFB) staining, and microbiologic culture, usually in a patient with known disseminated M. tuberculous disease. ^,

Nocardiosis most commonly presents with pulmonary disease. However, extrapulmonary sites of Nocardia infection include the central nervous system and soft tissue. Thyroid involvement by Nocardia infection is extremely rare. The majority of patients with nocardiosis are immunosuppressed, often due to HIV infection or organ transplantation. The diagnosis is typically made based on the clinical picture in high-risk patients in whom Nocardia has already been identified, as Nocardia is an extremely difficult pathogen to grow in culture.

Laboratory Testing and Diagnostic Imaging for Acute Suppurative Thyroiditis

When suspected, the initial laboratory evaluation in patients with possible AST should include measurement of a complete blood count (CBC) with differential, a comprehensive metabolic panel (CMP), serial thyroid function testing, an erythrocyte sedimentation rate (ESR) and a C-reactive protein (CRP), urine analysis, and urine culture, as well as blood and fungal cultures with antibiotic sensitivity. Serial thyroid function test is recommended because suppurative thyroiditis could be associated with acute thyrotoxicosis secondary to the release of preformed thyroxine and triiodothyronine given the acute destruction of thyroid follicles. ^{, , ,} Additional laboratory testing may be appropriate based on clinical and physical examination findings.

It is important to differentiate acute suppurative thyroiditis from other causes of acute neck swelling and pain (e.g., sternocleidomastoid abscess, parathyroid hemorrhage or abscess, lymph node suppuration, thyroglossal duct cyst infection, retropharyngeal abscess, subacute thyroiditis, aggressive thyroid cancer, thyroid nodule/cyst hemorrhage).

Ultrasonography (US) and computed tomography (CT) are two of the imaging modalities that can be used to facilitate the diagnosis of acute suppurative thyroiditis. However, a CT scan may be of limited utility in the early stages of thyroid inflammation, as the imaging findings on CT scan in early stages of AST are low-density areas and slight lobular swellings, both of which are nonspecific. Ultrasound is generally preferred as an imaging modality, and is more capable of diagnosing acute suppurative thyroiditis in the early stages. Ultrasound imaging findings at this stage include identification of hypoechoic areas within the thyroid gland, a finding of perithyroidal hypoechoic spaces, and effacement of the planes between perithyroid tissue and the thyroid gland.

Differentiating acute suppurative thyroiditis from subacute painful thyroiditis (De Quervain’s thyroiditis) in the early stage can be challenging and, given this, can result in the prescription of prednisone, which can effectively treat De Quervain’s thyroiditis but have an adverse impact and worsen clinical symptoms of acute suppurative disease. Subacute painful thyroiditis is relatively common, and it is associated with anterior neck discomfort overlying the gland, as well as an elevated white blood cell count, ESR, and CRP similar to acute suppurative thyroiditis. An iodine scintigraphy scan will not prove helpful to differentiate these two subtypes of thyroiditis in the setting of thyrotoxicosis, as both demonstrate low radioactive iodine uptake, typically less than 1%. Ultrasound and FNA of any mass or fluid collection is the most helpful method to differentiate between these two subtypes of thyroiditis. Thyroid US usually shows diffuse heterogenicity with low-intensity vascular flow in subacute painful thyroiditis. ^,

CT scan and US imaging findings during the acute, symptomatic stages of suppurative thyroiditis are more specific. In a study of 60 patients, CT scans performed during the acute stages demonstrated abscess formation, edema of the ipsilateral hypopharynx, and low density to the thyroid gland in 97%, 83%, and 76% of the patients, respectively. Swelling of the thyroid gland and thyroid shifting/deformity due to abscess formation were less common findings, being seen in 38% and 41% of patients, respectively. This study also examined the role of thyroid US during acute stages of disease. Abscess formation, hypoechoic areas in the thyroid gland, and perithyroidal hypoechoic spaces with effacement of the plane between the perithyroid tissue and thyroid gland were seen in 81%, 94%, and 88% of the patients, respectively.

Given the lack of sensitivity and specificity with other modalities, ultrasound-guided FNA and subsequent cytology/culture remains the best diagnostic method to clarify disease in patients with suspected AST.

Radionuclide imaging of the thyroid with I ¹²³ or TC ⁹⁹ are not helpful in diagnosing AST, as acute infection and thyroid cancer are both associated with focal decreased uptake in euthyroid patients, and diffuse decreased uptake in patients with hyperthyroidism due to destruction of the gland. The diagnostic utility of magnetic resonance imaging (MRI) in patients with AST is unknown due to limited data.

A PSF is a third and fourth pharyngeal pouch anomaly, usually occurring on the left side. PSF should be suspected in pediatric patients with recurrent AST or anterior neck abscess especially when on the left side. CT scan, US, direct laryngoscopy, and barium swallow are imaging modalities that can be used to help diagnose PSF, with barium swallow being the most sensitive method. The ability of imaging studies to detect PSF can vary with the stage of inflammation. One study by Masuoka et al. showed that a barium swallow can detect fistulas in 89% and 97% of cases during the acute and late inflammatory stages. The same study, however, showed that CT scans only detected fistulas in 20% and 54% of cases during these stages. ^{, ,}

Treatment of AST and Recommended Follow-up

AST is a life-threatening endocrine emergency with potential for high mortality. Patients with clinical suspicious of AST should be admitted to an inpatient hospital facility and a monitored setting. Stabilization of respiratory and cardiac function is necessary while the patient is undergoing diagnostic evaluation.

Most patients with bacterial AST are acutely ill and require empiric broad-spectrum antibiotic treatment while diagnostic evaluations, including blood culture, abscess culture, and tissue sampling, are being completed. Most patients with bacterial suppurative thyroiditis require an open surgical procedure including excision or drainage, in addition to antibiotic treatment. There are case reports of successful conservative treatments following only ultrasound-guided drainage of abscesses. But as abscesses are most often complex and loculated, needle drainage is often not a definitive treatment in most cases, and surgical drainage is necessary. Although exceedingly rare, patients with comprised airways require urgent transcutaneous or open-surgical drainage, and conservative diagnostic and therapeutic US-FNA is not appropriate in these patients.

As noted earlier, the rapid initiation of broad-spectrum antibacterial therapy should be initiated promptly with the goals of covering opportunistic infections. Such coverage should be empirically broadened further when treating an immunocompromised host.

The treatment of fungal suppurative thyroiditis includes systemic antifungal therapy, along with aggressive surgical debridement when indicated. In patients with M. tuberculosis thyroid involvement, treatment with quadruple antituberculous therapy (e.g., rifampicin, isoniazid, pyrazinamide, and ethambutol) is usually sufficient and has been shown to lead to full resolution involving nonresistant strains. However, occasionally surgery or drainage of an abscess must occur in addition to antituberculous treatment. ^,

Surgical thyroidectomy (near-total or hemithyroidectomy) should be considered only when there is evidence of persistent or progressive (nonresponsive to treatment) thyroidal infection despite abscess drainage and medical therapy. ^, Patients with multiple, poorly defined, less discrete abscesses with evidence of persistent or progression of disease despite appropriate antibiotic treatment should also undergo thyroidectomy. However, clinicians should consider the higher risks and rates of potential complications following thyroidectomy in these settings given the presence of inflammation which complicates the identification of the recurrent laryngeal nerves and parathyroid glands. In such settings, abscess drainage and medical therapy followed by elective thyroidectomy after the acute inflammatory process has been resolved could be considered.

Unique to AST due to pyriform sinus suppurative thyroiditis is abscess incision and drainage, antimicrobial treatment, and surgical removal of the PSF with or without partial thyroidectomy. ^, Endoscopic electrocauterization of the tract is an acceptable alternative to surgery. However, this is a new procedure with limited data regarding long-term outcomes. ^,

Rarely, acute suppurative thyroiditis can be associated with thyroid malignancy. Otani et al. reported a case of an adult female who presented with signs and symptoms of AST and responded to antimicrobial agents. Initial FNA did not show any overt evidence of papillary thyroid carcinoma (PTC); however, her thyroid inflammatory area decreased from 47 mm to 27 mm following antimicrobial treatment. At that point a more recognizable thyroid nodule was identified in the tissue and the patient underwent repeat FNA due to worrisome ultrasound features. At this point, FNA cytology was positive for PTC, and confirmed with surgical pathology. Puthanpurayil et al. also reported a case of 17-year-old patient with AST who responded to antibiotic therapy, and where a thyroid inflammatory area reduced from 3 cm to 1.5 cm, and was confirmed as a discrete nodule. The patient underwent repeat FNA outside of the setting of acute inflammation. FNA cytology of the second biopsy was suspicious for PTC and malignancy was confirmed with histopathology.

In summary, acute suppurative thyroiditis is a very rare yet dangerous condition. Host factors that predispose to this entity include pyriform sinus tract formation or other manipulation or exposure of the sterile thyroid to the outside environment, such as skin or oral mucosa. Although bacterial pathogens are most commonly causative, many other infectious agents have been described including M. tuberculosis . Prompt treatment is mandated given the risk of systemic infection, and the proximity of any abscess or mass to the vital neck structures. Most often when abscess formation is confirmed, drainage or surgical treatment is required. When detected early, AST can be effective treated, but in other more advanced settings, AST can be deadly.