Are you sure the patient has thyroiditis?
The term thyroiditis describes a group of acute and chronic inflammatory disorders affecting the thyroid gland. Drugs administered for many different medical conditions may also cause thyroiditis and those affected may present clinically in many different ways.
Infectious thyroiditis
Those most at risk from infections affecting the thyroid gland are children (most often due to a patent pyriform sinus) and the immunocompromised.
Patients are systemically ill and may present with signs of infection in structures anatomically close to the thyroid. Infectious thyroiditis leads to localised pain, swelling, erythema and localised warmth. Clinical management will involve administration of broad spectrum antimicrobial therapy. Once the organism responsible has been identified by a fine needle aspiration biopsy, further targeted specific treatment can be administered. Surgical intervention for drainage and removal of a sinus and or fistula are also sometimes required.
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Subacute thyroiditis
Also referred to as granulomatous or De Quervain’s thyroiditis, this is a more common inflammatory disease affecting the thyroid gland. Its cause is not clear, but it usually involves the gland symmetrically and may be associated with history of a recent upper respiratory tract infection. The thyroid is enlarged and tender on examination, and patients usually present with fever and an elevated erythrocyte sedimentation rate (ESR) level.
Recurrences may occur with diminishing severity over weeks or months. Although thyroid dysfunction is common, thyroid function usually returns to normal once the thyroiditis has resolved. Supportive management is usually required with non-steroidal anti-inflammatory drugs (NSAIDS) or aspirin, with glucocorticoids necessary in severe and protracted cases.
Riedel's thyroiditis
This exceedingly rare chronic sclerosing form of thyroiditis is a progressive process that can lead to complete destruction of the normal thyroid gland. It frequently causes cervical pressure symptoms and can involve immediate neighbouring structures within the neck. The cause is unknown, and treatment is limited to surgical release of neighbouring anatomical structures to relieve such symptoms as tracheal compression.
Drug-induced thyroiditis
Several drugs, given for a variety of medical conditions, may also cause thyroiditis. Please refer to the chapter, “Effects of Drugs on Thyroid Function Tests”.
Infectious thyroiditis
This condition is rare, as the thyroid gland is highly resistant to infection, due to its capsular containment and high vascularity. The gland also contains large amounts of iodine, as well as the ability to generate hydrogen peroxide used in the synthesis of thyroid hormone. All of these features act as natural protective mechanisms. However, in some individuals, including children, infections can be due to bacteria.
Other causal agents include mycobacteria and protozoa, with fungal infections occurring more often in immunocompromised individuals. Infectious thyroiditis may be acute, chronic, suppurative, non-suppurative, or septic. Rarely, infection causing infectious thyroiditis can occur in a cystic or degenerated nodule.
In children, a fistula may track from the pyriform sinus, thus anatomically resulting in the left lobe of the thyroid more susceptible to abscess formation. Fistula formation may also occur in adults due to a fourth branchial arch sinus. In immunocompromised patients (e.g. those receiving chemotherapy), the risk of infectious thyroiditis markedly increases.
An associated malignancy is also a cause of fistula formation. A thyroid abscess due to clostridium septicum is almost always associated with colonic carcinoma, and conditions such as metastatic breast carcinoma have been reported to present with acute thyroiditis. Infections can occur spontaneously as a result of fine needle aspiration (FNA) in susceptible individuals, and in those at risk, extreme care should be taken when performing this procedure.
Although this condition is rare, the prevalence is increasing due to the higher frequency of immunocompromised patients. Patients typically complain of pain in the anterior region of the neck and report difficulty with neck extension. They may also complain of painful dysphagia and referred pain to the ears or throat. There may be evidence of infection in structures adjacent to the thyroid within the neck. In severe cases, suppurative thyroiditis may spread to the chest, producing necrotising mediastinitis and pericarditis with gas formation.
Microscopically, acute inflammatory changes are seen within the thyroid gland. In bacterial infections, a polymorphonuclear and lymphocytic cellular infiltrate predominates, which can lead to necrosis and abscess formation. As healing occurs, fibrosis is prominent. FNA is important in identifying the infectious agent responsible. The appropriate stain (gram, acid fast or fungal) will help guide antibiotic therapy. However, in some cases, no source of infection will be found.
On clinical examination, the thyroid may show unilateral enlargement. A tender, warm mass may be palpated in a patient presenting with pyrexia, rigors, and lymphadenopathy. Clinical presentation in the autumn and winter months has also shown to predominate following upper respiratory tract infections.
Subacute thyroiditis
This spontaneous inflammatory condition (also called granulomatous or De Quervain’s thyroiditis) may last for weeks to months and can subsequently recur. It usually involves the entire thyroid gland and tends to follow an upper respiratory tract infection. It can occur in an epidemic form, and the aetiology remains incompletely understood. A viral cause has been postulated. In some cases, subacute thyroiditis has been associated with a history of mumps, parotitis, or orchitis. Elevated levels of mumps serologies have been found in those with subacute thyroiditis. The mumps virus has been cultured directly from thyroid tissue in some with subacute thyroiditis.
Subacute thyroiditis has also been associated with other viruses, such as measles, infectious mononucleosis, myocarditis, cat scratch fever, Coxsackie, and Epstein Barr virus. A familial occurrence of subacute thyroiditis associated with HLA B35 has been shown. Up to 75% of those who present with subacute thyroiditis manifest HLA B35, which leads to a hypothesis that there could be a transmission of a viral infection in genetically predisposed individuals.
Other proposed causes include cytokines and new medical treatments that modify and manipulate the immune system, including interleukin 2, tumour necrosis factor, and interferon-alpha or -gamma. Use of these agents may cause immune alterations in those with subacute thyroiditis. Treatment for chronic hepatitis B and C with interferon-alpha can cause a destructive thyroiditis in up to 15% of those treated, with others demonstrating a mild increase in serum TSH levels. In contrast, in those receiving long term immunosupressive treatment, the rare finding of subacute thyroiditis suggests that autoimmunity might play only a minor role.
Histologically, subacute thyroiditis consists of a mixture of subacute, chronic, and granulomatous inflammatory changes associated with zones of parenchymal destruction and scar tissue. Early infiltration with polymorphonuclear leukocytes (PMNs) are replaced by lymphocytes and macrophages. Macroscopically, subacute thyroiditis can resemble cancer with pale, white lesions that are firm in consistency and which have poorly-defined margins encroaching irregularly on adjacent normal thyroid tissue.
Patients are usually women in the 3rd to 6th decade of life and who report severe anterior neck pain. Subacute thyroiditis is rare in children. On examination, the enlarged gland is usually smooth, firm, and uniformly enlarged bilaterally. Occasionally, the enlargement may be asymmetrical, with one lobe being much larger. The thyroid may be 2-3 times its normal size and exquisitely tender to palpation. A small minority of patients will experience painless or minimally painful subacute thyroiditis. Dysphagia and transient vocal cord paralysis may also be reported. As the entire thyroid gland can be affected with the generalised inflammatory response, pain may spread from one pole to another as a “creeping thyroiditis” and cause discomfort in the jaw or ears.
Patients may also complain of malaise, fatigue, myalgia, arthralgia, and a mild to moderate swinging fever. Symptoms usually peak within 3-4 days and completely disappear typically within weeks. Atypical features may include a more gradual onset over 1-2 weeks following a fluctuating course which lasts up to 6 weeks. Some reports have described patients who have suffered recurrences of diminishing intensity extending over many months.
In those with subacute thyroiditis, approximately one half of those affected will present in the acute phase with symptoms of thyrotoxicosis, such as palpitations, heat intolerance, and tremor caused by excessive release of thyroid hormone from the thyroid gland during the acute phase of the inflammatory process. Cases of thyroid storm in subacute thyroiditis have been described, with transient hypothyroidism occurring in up to a quarter of patients. Ultimately thyroid function will return to normal, and permanent hypothyroidism requiring long term treatment with thyroxine occurs in less than 10% of those affected.
Reidel's thyroiditis
This chronic sclerosing form of thyroiditis is exceedingly rare and occurs mostly in women during the 4th-7th decades. It is a progressive condition which leads to complete destruction and replacement of the thyroid gland by connective tissue. It results in variable pressure symptoms within the neck, which can often affect neighbouring structure.
The gland is replaced by dense fibrosis with scattered solitary follicular cells and occasional acini with small amounts of colloid. Histologically, there is marked tissue eosinophilia and extracellular deposition of eosinophil granule major basic proteins. This fibrosis binds the thyroid to the underlying trachea and strap muscles. Local pressure can lead to dyspnoea, dysphagia, hoarseness, and aphonia. If both recurrent laryngeal nerves are affected, stridor can result. Involvement of the parathyroid glands can cause hypoparathyroidism.
Similar fibrosclerotic processes in other areas of the body, including the lacrimal glands, orbits, parotid glands, mediastinum, lung, myocardium and retroperitoneal tissue (the syndrome of multifocal fibrosclerositis), can also be associated.
On examination, the thyroid may be normal in size or enlarged either symmetrically or unilaterally. It is usually non-tender and firm on palpation. Sometimes the disease is asymptomatic and may be discovered incidentally. If the process is advanced, then signs and symptoms of hypothyroidism may be evident.
Reidel’s thyroiditis has also been postulated to be associated with venous stasis, vascular damage, and hypercoagulability. Cerebral sinus thrombosis may be seen in those with the condition.
What else could the patient have?
In contrast to subacute thyroiditis, the patient with infectious thyroiditis will appear septic and have more localised pain and tenderness that is more often in left lobe of the thyroid gland. They may also have an associated upper respiratory tract infection, present with associated lymphadenopathy, be immunocompromised, and may have evidence of localised erythema or abscess formation. Elevation of serum C-reactive protein or ESR levels can occur in both conditions, although an elevated leucocytosis with left shift would support an infective cause.
In those with subacute thyroiditis, the differential diagnosis of infectious thyroiditis needs to be considered. In Hashimoto’s thyroiditis, the thyroid may be slightly tender and painful, and serum thyroid antibodies will usually be elevated. Lymphocytic thyroiditis can follow the same clinical course of disease (initial stage of thyrotoxicosis, followed by hypothyroidism, then eventual normalisation of thyroid function). However, in these patients, the thyroid tends to be painless, non-tender, and the ESR level will be normal or only slightly elevated.
A retropharyngeal abscess may mimic the presentation of infectious thyroiditis. In these cases, the thyroid will be normal on ultrasound and radioiodine uptake scan. A computed tomography (CT) scan will be helpful in further characterizing the abscess.
Adults who present with a vague, slightly painful mass in the thyroid region without a fever should raise suspicion of a neoplastic lesion. Reidel’s thyroiditis may mimic the presentation of a thyroid carcinoma as a rapidly growing hard neck mass. A sarcoma may also need to be excluded.
Haemorrhage into a cyst within a nodular thyroid can be confused with subacute thyroiditis. However, when haemorrhage occurs suddenly, a fluctuant mass with a normal ESR level is present.
Generalised or systemic infiltrative or inflammatory diseases can involve the thyroid gland. Lesions of sarcoid can be found in the thyroid of those with systemic sarcoidosis. Amyloidosis can cause a goitre.
Radiation treatment for malignancy can induce a thyroiditis that may be painless, while I-131 treatment for thyrotoxicosis can cause inflammation that is occasionally painful and symptomatic. Thyroid irradiation may cause hypothyroidism requiring replacement levothyroxine.
Amiodarone induced hypothyroidism patients may exhibit a goitre. Those with AIT type-1 may have a diffuse goitre associated with Graves’ disease or multinodular goitre, those with type-2 usually will have no goitre.
Key laboratory and imaging tests
Patients with infectious thyroiditis are usually biochemically euthyroid unless the process is severe. Radioiodine uptake will typically be normal. Computerised tomography and ultrasonography can help identify a localised process. If an infection is suspected, FNA biopsy can be performed under ultrasound guidance. A barium swallow may help to identify a fistula that can be confirmed with a CT scan done while the patient blows into a syringe.
In patients with subacute thyroiditis, 50% will present with thyrotoxicosis, while transient hypothyroidism will be seen in around 25%. The characteristic finding of a raised ESR (sometimes >100mm/hr), raised levels of thyroid hormone (T4 andT3) and thyroglobulin, low radioactive iodine (RAI) uptake, and low or absent thyroid antibodies is virtually diagnostic. Color doppler ultrasound typically demonstrates absent hypervascularity in the acute phase.
In Reidel’s thyroiditis, thyroid function is usually normal, although one third become hypothyroid with progression of the disease. The ESR level is normal. Antithyroid antibodies are found in approximately two thirds of those with the condition.
Other tests that may prove helpful diagnostically
In patients with subacute thyroiditis, mild anaemia and hyperglobulinemia may be present. During the acute thyrotoxic phase, Tc-99m sestamibi will demonstrate increased perfusion, whereas Tc-99m pertechnate uptake will be markedly reduced. Ultrasound may demonstrate bilateral hypoechogenic areas within the thyroid and serve as a useful prognostic marker for the development of thyroid dysfunction. FNA may be required in helping to rule out malignancy.
Management and treatment of the disease
In infectious thyroiditis, FNA and drainage of any abscess is essential. Sometimes, further surgical exploration and drainage is required. Medical treatment with initial broad spectrum antibiotics (and more specific antimicrobial therapy when aspirate results are known) is indicated. Any sinus or fistula formation requires surgical removal of the fistula, sometimes to include partial thyroidectomy, to prevent recurrence. Surgery should be delayed until the inflammatory process is resolved. Few patients with infectious thyroiditis will develop hypothyroidism. Follow up with regular thyroid function testing is recommended.
In subacute thyroiditis, some patients require no specific treatment, while others may require supportive therapy, including analgesics, such as non-steroidal anti-inflammatory agents and aspirin. If these measures fail to control the symptoms, then 40mg prednisolone once daily may be started and tapered over 6 weeks. Pain relief with this approach is virtually diagnostic of subacute thyroiditis. If symptoms recur on a tapering dose of corticosteroids, then an increased dose is required.
Once the steroids have been discontinued, symptoms will recur in up to 20% of patients. TSH suppression with levothyroxine therapy may help reduce thyroid stimulation, but may prolong the inflammatory process. In 90% of patients, there will be a complete and spontaneous recovery with a return to normal thyroid function. Ten percent of the patients will require longterm levothyroxine replacement for permanent hypothyroidism.
There is no specific treatment for Reidel’s thyroiditis, with the recommended management dependent on clinical presentation. Levothyroxine treatment is not usually required and does not influence the course of the disease. Corticosteroid therapy can be effective in some who have active inflammation. In those who relapse, tamoxifen, which aims to inhibit fibroblast proliferation, can be used. In some, combination therapy of these two agents may be effective. In patients with compressive symptoms, surgery may be required to release the trachea, and tracheostomy may be indicated. Surgery can be technically difficult if the fibrosis is adherent to the surrounding structures.
What’s the Evidence?/References
Fatourechi, V, Aniszewski, JP, Fatourechi, GZ, Atkinson, EJ, Jaconsen, SJ. “Clinical features and outcomes of subacute thyroiditis in an incidence cohort: Olmstead County, Minnesota study”. J Clin Endocrinol Metab. vol. 88. 2003. pp. 2100-5. (This longitudinal study looks at the occurrence of subacute thyroiditis in one area over a 37 year period. The incidence, symptoms, and treatment are reviewed.)
Hennessey, JV. “Reidel's thyroiditis: A clinical review”. J Clin Endocrinol Metab. vol. 96. 2011. pp. 3031-41. (This helpful, comprehensive article reviews Reidel's thyroiditis. The clinical recognition, pathophysiology and clinical course of the condition are reviewed.)
Mizukoshi, T, Noguchi, S, Murakami, T, Futata, T, Yamashita, H. “Evaluation of recurrence in 36 subacute thyroiditis patients managed with prednisolone”. Intern Med. vol. 40. 2001. pp. 292-5. (A study investigating the treatment of subacute thyroiditis with corticosteroids in a small cohort. Patients are closely followed with reducing doses of steroids and the recurrence rate as well as baseline laboratory data is evaluated.)
Paes, JE, Burman, KD, Cohen, J, Franklyn, J, McHenry, CR. “Acute bacterial suppurative thyroiditis; a clinical review and expert opinion”. Thyroid. vol. 20. 2010. pp. 247(This useful review of recently available literature looks at the favourable outcome of less invasive treatment approaches in acute suppurative thyroiditis. It suggests the use of a clinical algorithm as a useful guide in the management of this condition.)
Shah, SS, Baum, SG. “Diagnosis and management of infectious thyroiditis”. Curr Infect Dis Rep. vol. 2. 2000. pp. 147-53. (Comprehensive review of the background, clinical diagnosis as well as pathogenesis of infectious thyroiditis. Management of this condition in children and adults is also described as comparisons with other thyroid inflammatory disorders.)
Additional references
Few, J, Thompson, NW, Angelos, P, Simeone, D, Giordano, T. “Reidel's thyroiditis; treatment with tamoxifen”. 1996.
Lucaya, J, Berdon, WE, Enriquez, G, Regas, J, Carreno, JC. “Congenital pyriform sinus fistula: a cause of acute left sided suppurative thyroiditis and neck abscess in children”. Pediatric Radiol. vol. 21. 1990. pp. 27-9.
Nishihara, E, Miyauchi, A, Matsuzuda, F, Sasaki, I, Ohye, H. “Acute suppurative thyroiditis after fine needle aspiration causing thyrotoxicosis”. Thyroid. vol. 15. 2005. pp. 1183-7.
Parana, R, Cruz, M, Lyra, L, Cruz, T. “Subacute thyroiditis during treatment with combination therapy (interferon plus ribavirin) for hepatitis C virus”. J Viral Hepat. vol. 7. 2000. pp. 393-5.
Parmar, RC, Bavedekar, SB, Sahu, DR, Warkw, S, Kamat, JR. “Thyroiditis as a presenting feature of mumps”. Pediatr Infect Dis J. vol. 20. 2001. pp. 637-8.
Schwartzentruber, DJ, White, DE, Zweig, MH, Weintrub, BD, Rosenberg, SA. “Thyroid dysfunction associated with immunotherapy for patients with cancer”. Cancer. vol. 68. 1991. pp. 2384
Volpe, R, Row, VV, Ezrin, C. “Circulating viral and thyroid antibodies in subacute thyroiditis”. J Clin Endocrinol Metab. vol. 27. 1967. pp. 1275-84.
Volpe, R. “The management of subacute (de Quervain's) thyroiditis”. Thyroid. vol. 5. 1993. pp. 253-5.
Zimmermann-Belsing, T, Feldt-Rasmussen, U. “Reidel's thyroiditis: an autoimmune or primary fibrotic disease?”. J Intern Med. vol. 235. 1994. pp. 271-4.
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